US2006258702A1PendingUtilityA1
Stabilization of hypoxia inducible factor (HIF) alpha
Est. expiryDec 6, 2021(expired)· nominal 20-yr term from priority
Inventors:Volkmar Guenzler-PukallThomas B. NeffQingjian WangMichael P. ArendLee A. FlippinAlex Melekhov
A61P 9/12A61P 43/00A61P 9/08A61P 7/00A61P 9/10A61P 9/04A61P 39/00A61P 37/04A61P 7/06A61P 9/00A61P 3/10A61P 37/00A61P 31/00A61P 29/00A61P 25/28A61P 25/14A61P 25/08A61P 25/00A61P 25/16A61P 35/00A61P 11/00A61P 1/04A61P 13/12A61P 17/02A61P 1/16A61K 31/472A61K 31/4418A61K 31/17A61K 31/44C07K 14/505A61K 31/496A61K 31/4738A61K 31/63G01N 33/746A61K 31/4375A61K 31/00C07K 14/4702A61K 31/4745A61K 38/1709A61K 31/47
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Claims
Abstract
The present invention relates to methods of stabilizing the alpha subunit of hypoxia inducible factor (HIF). The invention further relates to methods of preventing, pretreating, or treating conditions associated with HIF, including ischemic and hypoxic conditions. Compounds for use in these methods are also provided.
Claims
exact text as granted — not AI-modified1 . A method for stabilizing the alpha subunit of hypoxia inducible factor (HIF-α) in a subject, the method comprising administering to the subject an amount of a compound of Formula Ib effective for inhibiting hydroxylation of HIF-α
wherein
A is 1,2-arylidene, 1,3-arylidene, 1,4-arylidene; or (C 1 -C 4 )-alkylene, optionally substituted by one or two halogen, cyano, nitro, trifluoromethyl, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-hydroxyalkyl, (C 1 -C 6 )-alkoxy, —O—[CH 2 ] x —C f H (2f+1−g) Hal g , (C 1 -C 6 )-fluoroalkoxy, (C 1 -C 8 )-fluoroalkenyloxy, (C 1 -C 8 )-fluoroalkynyloxy, —OCF 2 Cl, —O—CF 2 —CHFCl; (C 1 -C 6 )-alkylmercapto, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 6 )-alkoxycarbonyl, carbamoyl, N—(C 1 -C 4 )-alkylcarbamoyl, N,N-di-(C 1 -C 4 )-alkylcarbamoyl, (C 1 -C 6 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkyl, phenyl, benzyl, phenoxy, benzyloxy, anilino, N-methylanilino, phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N—(C 1 -C 4 )-alkylsulfamoyl, N,N-di-(C 1 -C 4 )-alkylsulfamoyl; or by a substituted (C 6 -C 12 )-aryloxy, (C 7 -C 11 )-aralkyloxy, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl radical, which carries in the aryl moiety one to five identical or different substituents selected from halogen, cyano, nitro, trifluoromethyl, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, —O—[CH 2 ] x —C f H (2f+1−g) Hal g , —OCF 2 Cl, —O—CF 2 —CHFCl, (C 1 -C 6 )-alkylmercapto, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 6 )-alkoxycarbonyl, carbamoyl, N—(C 1 -C 4 )-alkylcarbamoyl, N,N-di-(C 1 -C 4 )-alkylcarbamoyl, (C 1 -C 6 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkyl, sulfamoyl, N—(C 1 -C 4 )-alkylsulfamoyl, N,N-di-(C 1 -C 4 )-alkylsulfamoyl;
or where A is —CR 5 R 6 and R 5 and R 6 are each independently selected from hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, aryl, or a substituent of the α-carbon atom of an α-amino acid, where the amino acid is a natural L-amino acid or its D-isomer;
B is —CO 2 H, —NH 2 , —NHSO 2 CF 3 , tetrazolyl, imidazolyl, 3-hydroxyisoxazolyl, —CONHCOR′″, —CONHSOR′″, CONHSO 2 R′″, where R′″ is aryl, heteroaryl, (C 3 -C 7 )-cycloalkyl, or (C 1 -C 4 )-alkyl, optionally monosubstituted by (C 6 -C 12 )-aryl, heteroaryl, OH, SH, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-thioalkyl, (C 1 -C 4 )-sulfinyl, (C 1 -C 4 )-sulfonyl, CF 3 , Cl, Br, F, I, NO 2 , —COOH, (C 2 -C 5 )-alkoxycarbonyl, NH 2 , mono-(C 1 -C 4 -alkyl)-amino, di-(C 1 -C 4 -alkyl)-amino, or (C 1 -C 4 )-perfluoroalkyl; or where B is a CO 2 -G carboxyl radical, where G is a radical of an alcohol G-OH in which G is selected from (C 1 -C 20 )-alkyl radical, (C 3 -C 8 ) cycloalkyl radical, (C 2 -C 20 )-alkenyl radical, (C 3 -C 8 )-cycloalkenyl radical, retinyl radical, (C 2 -C 20 )-alkynyl radical, (C 4 -C 20 )-alkenynyl radical, where the alkenyl, cycloalkenyl, alkynyl, and alkenynyl radicals contain one or more multiple bonds; (C 6 -CO 6 )-carbocyclic aryl radical, (C 7 -CO 6 )-carbocyclic aralkyl radical, heteroaryl radical, or heteroaralkyl radical, where a heteroaryl radical or heteroaryl moiety of a heteroaralkyl radical contains 5 or 6 ring atoms; and where radicals defined for G are substituted by one or more hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 5 -C 8 )-cycloalkenyl, (C 6 -CO 2 )-aryl, (C 7 -C 16 )-aralkyl, (C 2 -C 12 )-alkenyl, (C 2 -C 12 )-alkynyl, (C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 1 -C 8 )-hydroxyalkyl, —O—[CH 2 ] x —C f H (2f+1−g) —F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, cinnamoyl, (C 2 -C 12 )-alkenylcarbonyl, (C 2 -C 12 )-alkynylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -CO 2 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkynyloxycarbonyl, acyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 ) aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkyl-carbamoyl, N—(C 6 -C 16 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -CO 6 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 102 )-aryloxy-(C 1 -C 10 )alkyl)-carbamoyl, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 2 -C 12 )-alkenylamino, (C 2 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C-C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino, (C 3 -C 8 )-cycloalkylcarbonylamino, (C 6 -C 12 ) arylcarbonylamino, (C 7 -C 16 )-aralkylcarbonylamino, (C 1 -C 12 )-alkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-arylcarbonyl-N—(C 1 -C 10 )alkylamino, (C 7 -C 11 )-aralkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkylcarbonylamino-(C 1 -C 8 )alkyl, (C 6 -C 12 )-arylcarbonylamino-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkylcarbonylamino(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 ) alkylamino-(C 1 -C 10 )-alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 6 )-arylmercapto, (C 6 -C 16 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, (C 7 -C 16 )-aralkylsulfonyl, sulfamoyl, N—(C 1 -C 10 )-alkylsulfamoyl, N,N-di(C 1 -C 10 )-alkylsulfamoyl, (C 3 -C 8 )-cycloalkylsulfamoyl, N—(C 6 -C 12 )-alkylsulfamoyl, N—(C 7 -C 16 )-aralkylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylsulfamoyl, (C 1 -C 10 )-alkylsulfonamido, N—((C 1 -C 10 )-alkyl)-(C 1 -C 10 )-alkylsulfonamido, (C 7 -C 16 )-aralkylsulfonamido, or N—((C 1 -C 10 )-alkyl-(C 7 -C 16 )-aralkylsulfonamido; where radicals which are aryl or contain an aryl moiety, may be substituted on the aryl by one to five identical or different hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )alkoxy, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 1 -C 8 )-hydroxyalkyl, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkyl-carbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 ) aralkylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkynyloxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di-(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di —(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkylaralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino, (C 3 -C 8 )-cycloalkylcarbonylamino, (C 6 -C 12 )-arylcarbonylamino, (C 7 -C 16 )-alkylcarbonylamino, (C 1 -C 12 )-alkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-arylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkylcarbonylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-arylcarbonylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkylcarbonylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 12 )-arylmercapto, (C 6 -C 12 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 6 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, or (C 7 -C 16 )-aralkylsulfonyl;
X is O or S;
Q is O, S, NR′, or a bond; where,
if Q is a bond, R 4 is halogen, nitrile, or trifluoromethyl; or where,
if Q is O, S, or NR′, R 4 is hydrogen, (C 1 -C 10 )-alkyl radical, (C 2 -C 10 )-alkenyl radical, (C 2 -C 10 )-alkynyl radical, where alkenyl or alkynyl radical contains one or two C—C multiple bonds; unsubstituted fluoroalkyl radical of the formula —[CH 2 ] x —C f H (2f+1−g) —F g , (C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl radical, (C 1 -C 6 )-alkoxy-(C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl radical, aryl radical, heteroaryl radical, (C 7 -C 11 )-aralkyl radical, or a radical of the formula Z
—[CH 2 ] v —[O] w —[CH 2 ] t -E (Z)
wherein
E is a heteroaryl radical, a (C 3 -C 8 )-cycloalkyl radical, or a phenyl radical of the formula F
v is 0-6,
w is 0 or 1,
t is 0-3, and
R 7 , R 8 , R 9 , R 10 , and R 11 are identical or different and are hydrogen, halogen, cyano, nitro, trifluoromethyl, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 6 )-alkoxy, —O —[CH 2 ] x —C f H (2f+1−g) —F g , —OCF 2 —Cl, —O—CF 2 —CHFCl, (C 1 -C 6 )-alkylmercapto, (C 1 -C 6 )-hydroxyalkyl, (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 8 )-alkoxycarbonyl, carbamoyl, N—(C 1 -C 8 )-alkylcarbamoyl, N,N-di-(C 1 -C 8 )-alkylcarbamoyl, or (C 7 -C 11 )-aralkylcarbamoyl, optionally substituted by fluorine, chlorine, bromine, trifluoromethyl, (C 1 -C 6 )-alkoxy, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylcarbamoyl, (C 1 -C 6 )-alkylcarbonyloxy, phenyl, benzyl, phenoxy, benzyloxy, NR Y R Z where R y and R z are independently selected from hydrogen, (C 1 -C 12 )-alkyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 3 -C 12 )-alkenyl, (C 3 -C 12 )-alkynyl, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 12 )-alkoxy, (C 7 -C 12 )aralkoxy, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 ) arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl; or further where R y and R z together are —[CH 2 ] h , in which a CH 2 group can be replaced by O, S, N—(C 1 -C 4 )-alkylcarbonylimino, or N—(C 1 -C 4 )-alkoxycarbonylimino; phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N—(C 1 -C 8 )-alkylsulfamoyl, or N,N-di-(C 1 -C 8 )-alkylsulfamoyl;
or alternatively R 7 and R 8 , R 8 and R 9 , R 9 and R 10 , or R 10 and R 11 , together are a chain selected from —[CH 2 ] n — or —CH═CH—CH═CH—, where a CH 2 group of the chain is optionally replaced by O, S, SO, SO 2 , or NR Y ; and n is 3, 4, or 5; and if E is a heteroaryl radical, said radical can carry 1-3 substituents selected from those defined for R 7 , R 8 , R 9 , R 10 , and R 11 , or if E is a cycloalkyl radical, the radical can carry one substituent selected from those defined for R 7 , R 8 , R 9 , R 10 , and
or where, if Q is NR′, R 4 is alternatively R″, where R′ and R″ are identical or different and are hydrogen, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 8 )-alkyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 1 -C 10 )-alkylcarbonyl, optionally substituted (C 7 -C 16 )-aralkylcarbonyl, or optionally substituted C 6 -C 12 )-arylcarbonyl; or R′ and R″ together are —[CH 2 ] h , in which a CH 2 group can be replaced by O, S, N-acylimino, or N—(C 1 -C 10 )-alkoxycarbonylimino, and h is 3 to 7;
R 3 , R 16 , R 17 and R 19 are identical or different and are hydrogen, hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C 20 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )cycloalkyl-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl-(C 1 -C 6 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkoxy, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 7 -C 16 )-aralkenyl, (C 7 -C 16 )-aralkynyl, (C 2 -C 20 )-alkenyl, (C 2 -C 20 )-alkynyl, (C 1 -C 20 )-alkoxy, (C 2 -C 20 )-alkenyloxy, (C 2 -C 20 )-alkynyloxy, retinyloxy, (C 1 -C 20 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxy, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 16 )-hydroxyalkyl, (C 6 -C 16 )-aryloxy-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 7 -C 12 )-aralkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 2 -C 20 )-alkenyloxy-(C 1 -C 6 )-alkyl, (C 2 -C 20 )-alkynyloxy-(C 1 -C 6 )-alkyl, retinyloxy-(C 1 -C 6 )-alkyl, —O—[CH 2 ] x C f H (2f+1−g) F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 20 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, cinnamoyl, (C 2 -C 20 )-alkenylcarbonyl, (C 2 -C 20 )-alkynylcarbonyl, (C 1 -C 20 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 20 )-alkenyloxycarbonyl, retinyloxycarbonyl, (C 2 -C 20 )-alkynyloxycarbonyl, (C 6 -C) 2 )-aryloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di-(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N,N-dicyclo-(C 3 -C 8 )-alkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)-carbamoyl, N—(C 1 -C 6 )-alkyl-N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)-carbamoyl, N-(+)-dehydroabietylcarbamoyl, N—(C 1 -C 6 )-alkyl-N-(+)-dehydroabietylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 18 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N-((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl; CON(CH 2 ) h , in which a CH 2 group can be replaced by O, S, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; a carbamoyl radical of the formula R
in which R x and R v are each independently selected from hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, aryl, or the substituent of an α-carbon of an α-amino acid, to which the L- and D-amino acids belong, s is 1-5, T is OH, or NR*R**, and R*, R** and R*** are identical or different and are selected from hydrogen, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkyl, (+)-dehydroabietyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 1 -C 10 )-alkanoyl, optionally substituted (C 7 -C 16 )-aralkanoyl, optionally substituted (C 6 -C 12 )-aroyl; or R* and R** together are —[CH 2 ] h , in which a CH 2 group can be replaced by O, S, SO, SO 2 , N-acylamino, N—(C 1 -C 10 )-alkoxycarbonylimino, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -c 16)-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-arbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxyamino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino, (C 3 -C 8 )-cycloalkanoylamino, (C 6 -C 12 )-aroylamino, (C 7 -C 16 )-aralkanoylamino, (C 1 -C 12 )-alkanoyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkanoyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-aroyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkanoyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkanoylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aroylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkanoylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino(C 1 -C 10 )-alkyl, (C 1 -C 20 )-alkylmercapto, (C 1 -C 20 )-alkylsulfinyl, (C 1 -C 20 )-alkylsulfonyl, (C 6 -C 12 )-arylmercapto, (C 6 -C 12 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, (C 7 -C 16 )-aralkylsulfonyl, (C 1 -C 12 )-alkylmercapto-(C 1 -C 6 )-alkyl, (C 1 -C 12 )-alkylsulfinyl-(C 1 -C 6 )-alkyl, (C 1 -C 12 )-alkylsulfonyl-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylmercapto-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylsulfinyl-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylsulfonyl-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylmercapto-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylsulfinyl-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylsulfonyl-(C 1 -C 6 )-alkyl, sulfamoyl, N—(C 1 -C 10 )-alkylsulfamoyl, N,N-di-(C 1 -C 10 )-alkylsulfamoyl, (C 3 -C 8 )-cycloalkylsulfamoyl, N—(C 6 -C 12 )-arylsulfamoyl, N—(C 7 -C 6 )-aralkylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylsulfamoyl, (C 1 -C 10 )-alkylsulfonamido, N—((C 1 -C 10 )-alkyl)-(C 1 -C 10 )-alkylsulfonamido, (C 7 -C 16 )-aralkylsulfonamido, and N—((C 1 -C 10 )-alkyl-(C 7 -C 16 )-aralkylsulfonamido; where an aryl radical may be substituted by 1 to 5 substituents selected from hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 2 -C 16 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl-(C 1 -C 6 )-alkoxy, (C 3 -C 8 )-cycloalkyl(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkoxy, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 2 -C 16 )-alkenyl, (C 2 -C 12 )-alkynyl, (C 1 -C 16 )-alkoxy, (C 1 -C 16 )-alkenyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxy, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 8 )-hydroxyalkyl, (C 6 -C 16 )-aryloxy-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 7 -C 12 )-aralkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, —O—[CH 2 ] x C f H (2f+1−g) F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 6 )-aralkylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkynyloxycarbonyl, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-Cycloalkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C— 2 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N,N-dicyclo-(C 3 -C 8 )-alkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)carbamoyl, N—(C 1 -C 6 )-alkyl-N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)carbamoyl, N-(+)-dehydroabietylcarbamoyl, N—(C 1 -C 6 )-alkyl-N-(+)-dehydroabietylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 16 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyl, N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyl, N-((C 7 -C 16 )-aralkyloxy-(C 1 -C 11 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, CON(CH 2 ) h , in which a CH 2 group can be replaced by, O, S, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 16 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C so)-alkyl)carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 6 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 11 )-alkyl)carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino, (C 3 -C 8 )-cycloalkanoylamino, (C 6 -C 12 )-aroylamino, (C 7 -C 16 )-aralkanoylamino, (C 1 -C 12 )-alkanoyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkanoyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-aroyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkanoyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkanoylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aroylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkanoylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 16 )-arylmercapto, (C 6 -C 16 )-arylsulfinyl, (C 6 -C 16 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, or (C 7 -C 16 )-aralkylsulfonyl;
R 18 is hydrogen, hydroxyl, chloro, fluoro, iodo, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C 20 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )cycloalkyl-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl-(C 1 -C 6 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkoxy, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 7 -C 16 )-aralkenyl, (C 7 -C 16 )-aralkynyl, (C 2 -C 20 )-alkenyl, (C 2 -C 20 )-alkynyl, (C 1 -C 20 )-alkoxy, (C 2 -C 20 )-alkenyloxy, (C 2 -C 20 )-alkynyloxy, retinyloxy, (C 1 -C 20 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxy, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 16 )-hydroxyalkyl, (C 6 -C 16 )-aryloxy-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 7 -C 12 )-aralkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 2 -C 20 )-alkenyloxy-(C 1 -C 6 )-alkyl, (C 2 -C 20 )-alkynyloxy-(C 1 -C 6 )-alkyl, retinyloxy-(C 1 -C 6 )-alkyl, —O—[CH 2 ] x C f H (2f+1−g) F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 20 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, cinnamoyl, (C 2 -C 20 )-alkenylcarbonyl, (C 2 -C 20 )-alkynylcarbonyl, (C 1 -C 20 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 20 )-alkenyloxycarbonyl, retinyloxycarbonyl, (C 2 -C 20 )-alkynyloxycarbonyl, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di-(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N,N-dicyclo-(C 3 -C 8 )-alkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)-carbamoyl, N—(C 1 -C 6 )-alkyl-N-((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)-carbamoyl, N-(+)-dehydroabietylcarbamoyl, N—(C 1 -C 6 )-alkyl-N-(+)-dehydroabietylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 18 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl; CON(CH 2 ) h , in which a CH 2 group can be replaced by O, S, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; a carbamoyl radical of the formula R
in which R x and R v are each independently selected from hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, aryl, or the substituent of an α-carbon of an α-amino acid, to which the L- and D-amino acids belong, s is 1-5, T is OH, or NR*R**, and R*, R** and R*** are identical or different and are selected from hydrogen, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkyl, (+)-dehydroabietyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 1 -C 10 )-alkanoyl, optionally substituted (C 7 -C 16 )-aralkanoyl, optionally substituted (C 6 -C 12 )-aroyl; or R* and R** together are —[CH2] h , in which a CH 2 group can be replaced by O, S, SO, SO 2 , N-acylamino, N—(C 1 -C 10 )-alkoxycarbonylimino, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -c] 6 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxyamino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino, (C 3 -C 8 )-cycloalkanoylamino, (C 6 -C 12 )-aroylamino, (C 7 -C 16 )-aralkanoylamino, (C 1 -C 12 )-alkanoyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkanoyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-aroyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkanoyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkanoylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aroylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkanoylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino(C 1 -C 10 )-alkyl, (C 1 -C 20 )-alkylmercapto, (C 1 -C 20 )-alkylsulfinyl, (C 1 -C 20 )-alkylsulfonyl, (C 6 -C 12 )-arylmercapto, (C 6 -C 12 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, (C 7 -C 16 )-aralkylsulfonyl, (C 1 -C 12 )-alkylmercapto-(C 1 -C 6 )-alkyl, (C 1 -C 12 )-alkylsulfinyl-(C 1 -C 6 )-alkyl, (C 1 -C 12 )-alkylsulfonyl-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylmercapto-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylsulfinyl-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylsulfonyl-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylmercapto-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylsulfinyl-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylsulfonyl-(C 1 -C 6 )-alkyl, sulfamoyl, N—(C 1 -C 10 )-alkylsulfamoyl, N,N-di-(C 1 -C 10 )-alkylsulfamoyl, (C 3 -C 8 )-cycloalkylsulfamoyl, N—(C 6 -C 12 )-arylsulfamoyl, N—(C 7 -C 16 )-aralkylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylsulfamoyl, (C 1 -C 10 )-alkylsulfonamido, N—((C 1 -C 10 )-alkyl)-(C 1 -C 10 )-alkylsulfonamido, (C 7 -C 16 )-aralkylsulfonamido, and N—((C 1 -C 10 )-alkyl-(C 7 -C 16 )-aralkylsulfonamido; where an aryl radical may be substituted by 1 to 5 substituents selected from hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 2 -C 16 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl-(C 1 -C 6 )-alkoxy, (C 3 -C 8 )-cycloalkyl(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkoxy, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 2 -C 16 )-alkenyl, (C 2 -C 12 )-alkynyl, (C 1 -C 16 )-alkoxy, (C 1 -C 16 )-alkenyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxy, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 8 )-hydroxyalkyl, (C 6 -C 16 )-aryloxy-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 7 -C 12 )-aralkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, —O—[CH 2 ] x C f H (2f+1−g) F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkynyloxycarbonyl, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N,N-dicyclo-(C 3 -C 8 )-alkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)carbamoyl, N—(C 1 -C 6 )-alkyl-N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)carbamoyl, N-(+)-dehydroabietylcarbamoyl, N—(C 1 -C 6 )-alkyl-N-(+)-dehydroabietylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 16 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyl, N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyl, N-((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, CON(CH 2 ) h , in which a CH 2 group can be replaced by, O, S, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 16 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino, (C 3 -C 8 )-cycloalkanoylamino, (C 6 -C 12 )-aroylamino, (C 7 -C 16 )-aralkanoylamino, (C 1 -C 12 )-alkanoyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkanoyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-aroyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkanoyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkanoylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aroylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkanoylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 16 )-arylmercapto, (C 6 -C 16 )-arylsulfinyl, (C 6 -C 16 )-arylsulfonyl, (C 7 -C 6 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, or (C 7 -C 16 )-aralkylsulfonyl;
f is 1 to 8;
g is 0 or 1 to (2f+1); and
x is 0 to 3;
or a physiologically active salt or prodrug derived therefrom.
2 . The method of claim 1 , wherein
A is —CH 2 —; B is —CO 2 H or —COO—CH 3 ; X is —O—; Q is —O—; R 3 is halogen; R 4 and R 16 are hydrogen; R 17 and R 18 are identical or different and are selected from the group consisting of hydrogen, (C 1 -C 20 )-alkoxy, and (C 7 -C 16 )-aralkyloxy; and R 19 is hydrogen or halogen; or a physiologically active salt or prodrug derived therefrom.
3 . The method of claim 1 , wherein
A is —CH 2 —; B is —CO 2 H; X is O; Q is O; R 3 is chlorine; R 4 is hydrogen; R 16 is hydrogen; R 17 is hydrogen, methoxy, 2-propyloxy, or benzyloxy; R 18 is hydrogen, methoxy, butyloxy, 2-propyloxy, or benzyloxy; and R 19 is hydrogen or chlorine; or a physiologically active salt or prodrug derived therefrom.
4 . The method of claim 1 , wherein the compound is selected from the group consisting of: N-((1-chloro-4-hydroxy-7-(2-propyloxy) isoquinolin-3-yl)-carbonyl)-glycine, N-((1-chloro-4-hydroxy-6-(2-propyloxy) isoquinolin-3-yl)-carbonyl)-glycine, N-((1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino)-acetic acid, N-((1-chloro-4-hydroxy-7-methoxyisoquinolin-3-yl)-carbonyl)-glycine, N-((1-chloro-4-hydroxy-6-methoxyisoquinolin-3-yl)-carbonyl)-glycine, N-((7-butyloxy)-1-chloro-4-hydroxyisoquinolin-3-yl)-carbonyl)-glycine, N-((6-benzyloxy-1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino)-acetic acid, ((7-benzyloxy-1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino)-acetic acid methyl ester, N-((7-benzyloxy-1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino)-acetic acid, N-((8-chloro-4-hydroxyisoquinolin-3-yl)-carbonyl)-glycine, and N-((7-butoxy-4-hydroxy-isoquinoline-3-carbonyl)-amino)-acetic acid.
5 . The method of claim 1 , wherein the compound is N-((1-chloro-4-hydroxy-7-(2-propyloxy) isoquinolin-3-yl)-carbonyl)-glycine.
6 . The method of claim 1 , wherein the compound is N-((1-chloro-4-hydroxy-6-(2-propyloxy) isoquinolin-3-yl)-carbonyl)-glycine.
7 . The method of claim 1 , wherein the compound is N-((1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino)-acetic acid.
8 . The method of claim 1 , wherein the compound is N-((1-chloro-4-hydroxy-7-methoxyisoquinolin-3-yl)-carbonyl)-glycine.
9 . The method of claim 1 , wherein the compound is N-((1-chloro-4-hydroxy-6-methoxyisoquinolin-3-yl)-carbonyl)-glycine.
10 . The method of claim 1 , wherein the compound is N-((7-butyloxy)-1-chloro-4-hydroxyisoquinolin-3-yl)-carbonyl)-glycine.
11 . The method of claim 1 , wherein the compound is N-((6-benzyloxy-1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino)-acetic acid.
12 . The method of claim 1 , wherein the compound is ((7-benzyloxy-1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino)-acetic acid methyl ester.
13 . The method of claim 1 , wherein the compound is N-((7-benzyloxy-1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino)-acetic acid.
14 . The method of claim 1 , wherein the compound is N-((8-chloro-4-hydroxyisoquinolin-3-yl)-carbonyl)-glycine.
15 . The method of claim 1 , wherein the compound is N-((7-butoxy-4-hydroxy-isoquinoline-3-carbonyl)-amino)-acetic acid.
16 . The method of claim 1 , wherein the subject is an organ for transplant.
17 . The method of claim 1 , wherein the subject is a mammalian subject.
18 . The method of claim 1 , wherein the subject is a human subject.
19 . The method of claim 1 , wherein the compound is administered orally.
20 . The method of claim 1 , wherein the compound is administered transdermally.
21 . The method of claim 1 , wherein the compound is administered systemically.
22 . The method of claim 1 , wherein the compound is administered by injection.
23 . The method of claim 1 , wherein the compound is administered intravenously.
24 . The method of claim 1 , wherein administration of the compound inhibits HIF hydroxylase enzyme activity.
25 . The method of claim 1 , wherein the subject has or is at risk for having a HIF-associated condition.
26 . The method of claim 25 , wherein the HIF-associated condition is selected from the group consisting of a renal disorder, a pulmonary disorder, a cardiac disorder, a neurological disorder, and a disorder associated with hypoxia or ischemia.
27 . The method of claim 1 , wherein the method further comprises administering a second therapeutic agent to the subject.
28 . The method of claim 27 , wherein the second therapeutic agent is selected from the group consisting of an angiotensin converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), a diuretic, a statin, and carnitine.
29 . A pharmaceutical composition for the treatment of a HIF-associated condition comprising a compound of Formula Ib
wherein
A is 1,2-arylidene, 1,3-arylidene, 1,4-arylidene; or (C 1 -C 4 )-alkylene, optionally substituted by one or two halogen, cyano, nitro, trifluoromethyl, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-hydroxyalkyl, (C 1 -C 6 )-alkoxy, —O—[CH 2 ] x —C f H (2f+1−g) Hal g , (C 1 -C 6 )-fluoroalkoxy, (C 1 -C 8 )-fluoroalkenyloxy, (C 1 -C 8 )-fluoroalkynyloxy, —OCF 2 Cl, —O—CF 2 —CHFCl; (C 1 -C 6 )-alkylmercapto, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 6 )-alkoxycarbonyl, carbamoyl, N—(C 1 -C 4 )-alkylcarbamoyl, N,N-di-(C 1 -C 4 )-alkylcarbamoyl, (C 1 -C 6 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkyl, phenyl, benzyl, phenoxy, benzyloxy, anilino, N-methylanilino, phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N—(C 1 -C 4 )-alkylsulfamoyl, N,N-di-(C 1 -C 4 )-alkylsulfamoyl; or by a substituted (C 6 -C 12 )-aryloxy, (C 7 -C 11 )-aralkyloxy, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl radical, which carries in the aryl moiety one to five identical or different substituents selected from halogen, cyano, nitro, trifluoromethyl, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, —O—[CH 2 ] x —C f H (2f+g−1) Hal g , —OCF 2 Cl, —O—CF 2 —CHFCl, (C 1 -C 6 )-alkylmercapto, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 6 )-alkoxycarbonyl, carbamoyl, N—(C 1 -C 4 )-alkylcarbamoyl, N,N-di-(C 1 -C 4 )-alkylcarbamoyl, (C 1 -C 6 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkyl, sulfamoyl, N—(C 1 -C 4 )-alkylsulfamoyl, N,N-di-(C 1 -C 4 )-alkylsulfamoyl;
or where A is —CR 5 R 6 and R 5 and R 6 are each independently selected from hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-Cycloalkyl, aryl, or a substituent of the α-carbon atom of an α-amino acid, where the amino acid is a natural L-amino acid or its D-isomer;
B is —CO 2 H, —NH 2 , —NHSO 2 CF 3 , tetrazolyl, imidazolyl, 3-hydroxyisoxazolyl, —CONHCOR′″, —CONHSOR′″, CONHSO 2 R′″, where R′″ is aryl, heteroaryl, (C 3 -C 7 )-cycloalkyl, or (C 1 -C 4 )-alkyl, optionally monosubstituted by (C 6 -C 12 )-aryl, heteroaryl, OH, SH, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-thioalkyl, (C 1 -C 4 )-sulfinyl, (C 1 -C 4 )-sulfonyl, CF 3 , Cl, Br, F, I, NO 2 , —COOH, (C 2 -C 5 )-alkoxycarbonyl, NH 2 , mono-(C 1 -C 4 -alkyl)-amino, di-(C 1 -C 4 -alkyl)-amino, or (C 1 -C 4 )-perfluoroalkyl; or where B is a CO 2 -G carboxyl radical, where G is a radical of an alcohol G-OH in which G is selected from (C 1 -C 20 )-alkyl radical, (C 3 -C 8 ) cycloalkyl radical, (C 2 -C 20 )-alkenyl radical, (C 3 -C 8 )-cycloalkenyl radical, retinyl radical, (C 2 -C 20 )-alkynyl radical, (C 4 -C 20 )-alkenynyl radical, where the alkenyl, cycloalkenyl, alkynyl, and alkenynyl radicals contain one or more multiple bonds; (C 6 -C 16 )-carbocyclic aryl radical, (C 7 -C 16 )-carbocyclic aralkyl radical, heteroaryl radical, or heteroaralkyl radical, where a heteroaryl radical or heteroaryl moiety of a heteroaralkyl radical contains 5 or 6 ring atoms; and where radicals defined for G are substituted by one or more hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C) 2 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 5 -C 8 )-cycloalkenyl, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 2 -C 12 )-alkenyl, (C 2 -C 12 )-alkynyl, (C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 1 -C 8 )-hydroxyalkyl, —O—[CH 2 ] x —C f H (2f+1−g) —F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, cinnamoyl, (C 2 -C 12 )-alkenylcarbonyl, (C 2 -C 12 )-alkynylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkynyloxycarbonyl, acyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 ) aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkyl-carbamoyl, N—(C 6 -C 16 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )alkyl)-carbamoyl, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -C 6 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 2 -C 12 )-alkenylamino, (C 2 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C-C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino, (C 3 -C 8 )-cycloalkylcarbonylamino, (C 6 -C 12 ) arylcarbonylamino, (C 7 -C 16 )-aralkylcarbonylamino, (C 1 -C 12 )-alkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-arylcarbonyl-N—(C 1 -C 10 )alkylamino, (C 7 -C 11 )-aralkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkylcarbonylamino-(C 1 -C 8 )alkyl, (C 6 -C 12 )-arylcarbonylamino-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkylcarbonylamino(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 ) alkylamino-(C 1 -C 10 )-alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 16 )-arylmercapto, (C 6 -C 16 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 6 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, (C 7 -C 16 )-aralkylsulfonyl, sulfamoyl, N—(C 1 -C 10 )-alkylsulfamoyl, N,N-di(C 1 -C 10 )-alkylsulfamoyl, (C 3 -C 8 )-cycloalkylsulfamoyl, N—(C 6 -C 12 )-alkylsulfamoyl, N—(C 7 -C 16 )-aralkylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylsulfamoyl, (C 1 -C 10 )-alkylsulfonamido, N—((C 1 -C 10 )-alkyl)-(C 1 -C 10 )-alkylsulfonamido, (C 7 -C 16 )-aralkylsulfonamido, or N—((C 1 -C 10 )-alkyl-(C 7 -C 16 )-aralkylsulfonamido; where radicals which are aryl or contain an aryl moiety, may be substituted on the aryl by one to five identical or different hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )alkoxy, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 1 -C 8 )-hydroxyalkyl, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkyl-carbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 ) aralkylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-Cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkynyloxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-Cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di-(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 1 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkylaralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino, (C 3 -C 8 )-cycloalkylcarbonylamino, (C 6 -C 12 )-arylcarbonylamino, (C 7 -C 16 )-alkylcarbonylamino, (C 1 -C 12 )-alkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-arylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkylcarbonyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkylcarbonylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkylcarbonylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-arylcarbonylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkylcarbonylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 12 )-arylmercapto, (C 6 -C 12 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, or (C 7 -C 16 )-aralkylsulfonyl;
X is O or S;
Q is O, S, NR′, or a bond; where,
if Q is a bond, R 4 is halogen, nitrile, or trifluoromethyl; or where,
if Q is O, S, or NR′, R 4 is hydrogen, (C 1 -C 10 )-alkyl radical, (C 2 -C 10 )-alkenyl radical, (C 2 -C 10 )-alkynyl radical, where alkenyl or alkynyl radical contains one or two C—C multiple bonds; unsubstituted fluoroalkyl radical of the formula —[CH 2 ] x —C f H (2f+1−g) —F g , (C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl radical, (C 1 -C 6 )-alkoxy-(C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl radical, aryl radical, heteroaryl radical, (C 7 -C 11 )-aralkyl radical, or a radical of the formula Z
—[CH 2 ] v —[O] w —[CH 2 ] t -E (Z)
wherein
E is a heteroaryl radical, a (C 3 -C 8 )-cycloalkyl radical, or a phenyl radical of the formula F
v is 0-6,
w is 0 or 1,
t is 0-3, and
R 7 , R 8 , R 9 , R 10 , and R 11 are identical or different and are hydrogen, halogen, cyano, nitro, trifluoromethyl, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 6 )-alkoxy, —O —[CH 2 ] x —C f H (2f+1−g) —F g , —OCF 2 —Cl, —O—CF 2 —CHFCl, (C 1 -C 6 )-alkylmercapto, (C 1 -C 6 )-hydroxyalkyl, (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkoxy-(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 8 )-alkoxycarbonyl, carbamoyl, N—(C 1 -C 8 )-alkylcarbamoyl, N,N-di-(C 1 -C 8 )-alkylcarbamoyl, or (C 7 -C 11 )-aralkylcarbamoyl, optionally substituted by fluorine, chlorine, bromine, trifluoromethyl, (C 1 -C 6 )-alkoxy, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylcarbamoyl, (C 1 -C 6 )-alkylcarbonyloxy, phenyl, benzyl, phenoxy, benzyloxy, NR Y R Z where R y and R z are independently selected from hydrogen, (C 1 -C 12 )-alkyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 3 -C 10 )-cycloalkyl, (C 3 -C 12 )-alkenyl, (C 3 -C 12 )-alkynyl, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 12 )-alkoxy, (C 7 -C 12 )aralkoxy, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 ) arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl; or further where R y and R z together are —[CH2] h , in which a CH 2 group can be replaced by O, S, N—(C 1 -C 4 )-alkylcarbonylimino, or N—(C 1 -C 4 )-alkoxycarbonylimino; phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N—(C 1 -C 8 )-alkylsulfamoyl, or N,N-di-(C 1 -C 8 )-alkylsulfamoyl;
or alternatively R 7 and R 8 , R 8 and R 9 , R 9 and R 10 , or R 10 and R 11 , together are a chain selected from —[CH 2 ] n — or —CH═CH—CH═CH—, where a CH 2 group of the chain is optionally replaced by O, S, SO, SO 2 , or NR Y ; and n is 3, 4, or 5; and if E is a heteroaryl radical, said radical can carry 1-3 substituents selected from those defined for R 7 , R 8 , R 9 , R 10 , and R 11 , or if E is a cycloalkyl radical, the radical can carry one substituent selected from those defined for R 7 , R 8 , R 9 , R 10 , and
or where, if Q is NR′, R 4 is alternatively R″, where R′ and R″ are identical or different and are hydrogen, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 8 )-alkyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 1 -C 10 )-alkylcarbonyl, optionally substituted (C 7 -C 16 )-aralkylcarbonyl, or optionally substituted C 6 -C 12 )-arylcarbonyl; or R′ and R″ together are —[CH 2 ] h , in which a CH 2 group can be replaced by O, S, N-acylimino, or N—(C 1 -C 10 )-alkoxycarbonylimino, and h is 3 to 7;
R 18 is hydrogen, hydroxyl, chloro, fluoro, iodo, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C 20 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )cycloalkyl-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl-(C 1 -C 6 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkoxy, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 7 -C 16 )-aralkenyl, (C 7 -C 16 )-aralkynyl, (C 2 -C 20 )-alkenyl, (C 2 -C 20 )-alkynyl, (C 1 -C 20 )-alkoxy, (C 2 -C 20 )-alkenyloxy, (C 2 -C 20 )-alkynyloxy, retinyloxy, (C 1 -C 20 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxy, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 16 )-hydroxyalkyl, (C 6 -C 16 )-aryloxy-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 7 -C 12 )-aralkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 2 -C 20 )-alkenyloxy-(C 1 -C 6 )-alkyl, (C 2 -C 20 )-alkynyloxy-(C 1 -C 6 )-alkyl, retinyloxy-(C 1 -C 6 )-alkyl, —O—[CH 2 ] x C f H (2f+1−g) F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 20 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, cinnamoyl, (C 2 -C 20 )-alkenylcarbonyl, (C 2 -C 20 )-alkynylcarbonyl, (C 1 -C 20 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 20 )-alkenyloxycarbonyl, retinyloxycarbonyl, (C 2 -C 20 )-alkynyloxycarbonyl, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di-(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N,N-dicyclo-(C 3 -C 8 )-alkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)-carbamoyl, N—(C 1 -C 6 )-alkyl-N-((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)-carbamoyl, N-(+)-dehydroabietylcarbamoyl, N—(C 1 -C 6 )-alkyl-N-(+)-dehydroabietylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 6 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 18 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl; CON(CH 2 ) h , in which a CH 2 group can be replaced by O, S, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; a carbamoyl radical of the formula R
in which R x and R v are each independently selected from hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, aryl, or the substituent of an α-carbon of an α-amino acid, to which the L- and D-amino acids belong, s is 1-5, T is OH, or NR*R**, and R*, R** and R*** are identical or different and are selected from hydrogen, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkyl, (+)-dehydroabietyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 1 -C 10 )-alkanoyl, optionally substituted (C 7 -C 16 )-aralkanoyl, optionally substituted (C 6 -C 12 )-aroyl; or R* and R** together are —[CH 2 ] h , in which a CH 2 group can be replaced by O, S, SO, SO 2 , N-acylamino, N—(C 1 -C 10 )-alkoxycarbonylimino, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -c 16)-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxyamino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino, (C 3 -C 8 )-cycloalkanoylamino, (C 6 -C 12 )-aroylamino, (C 7 -C 16 )-aralkanoylamino, (C 1 -C 12 )-alkanoyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkanoyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-aroyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkanoyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkanoylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aroylamino-(C 1 -C 8 )-alkyl, (C 7 -C 6 )-aralkanoylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino(C 1 -C 10 )-alkyl, (C 1 -C 20 )-alkylmercapto, (C 1 -C 20 )-alkylsulfinyl, (C 1 -C 20 )-alkylsulfonyl, (C 6 -C 12 )-arylmercapto, (C 6 -C 12 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, (C 7 -C 16 )-aralkylsulfonyl, (C 1 -C 12 )-alkylmercapto-(C 1 -C 6 )-alkyl, (C 1 -C 12 )-alkylsulfinyl-(C 1 -C 6 )-alkyl, (C 1 -C 12 )-alkylsulfonyl-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylmercapto-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylsulfinyl-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylsulfonyl-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylmercapto-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylsulfinyl-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylsulfonyl-(C 1 -C 6 )-alkyl, sulfamoyl, N—(C 1 -C 10 )-alkylsulfamoyl, N,N-di-(C 1 -C 10 )-alkylsulfamoyl, (C 3 -C 8 )-cycloalkylsulfamoyl, N—(C 6 -C 12 )-arylsulfamoyl, N—(C 7 -C 16 )-aralkylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylsulfamoyl, (C 1 -C 10 )-alkylsulfonamido, N—((C 1 -C 10 )-alkyl)-(C 1 -C 10 )-alkylsulfonamido, (C 7 -C 16 )-aralkylsulfonamido, and N—((C 1 -C 10 )-alkyl-(C 7 -C 16 )-aralkylsulfonamido; where an aryl radical may be substituted by 1 to 5 substituents selected from hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 2 -C 16 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl-(C 1 -C 6 )-alkoxy, (C 3 -C 8 )-cycloalkyl(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkoxy, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 2 -C 16 )-alkenyl, (C 2 -C 12 )-alkynyl, (C 1 -C 16 )-alkoxy, (C 1 -C 16 )-alkenyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxy, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 8 )-hydroxyalkyl, (C 6 -C 16 )-aryloxy-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 7 -C 12 )-aralkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, —O—[CH 2 ] x C f H (2f+1−g) F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkynyloxycarbonyl, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N,N-dicyclo-(C 3 -C 8 )-alkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)carbamoyl, N—(C 1 -C 6 )-alkyl-N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)carbamoyl, N-(+)-dehydroabietylcarbamoyl, N—(C 1 -C 6 )-alkyl-N-(+)-debydroabietylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 16 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyl, N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyl, N-((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, CON(CH 2 ) h , in which a CH 2 group can be replaced by, O, S, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 6 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino, (C 3 -C 8 )-cycloalkanoylamino, (C 6 -C 12 )-aroylamino, (C 7 -C 16 )-aralkanoylamino, (C 1 -C 12 )-alkanoyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkanoyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-aroyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkanoyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkanoylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aroylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkanoylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 16 )-arylmercapto, (C 6 -C 16 )-arylsulfinyl, (C 6 -C 16 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, or (C 7 -C 16 )-aralkylsulfonyl;
R 3 , R 16 , R 17 and R 19 are identical or different and are hydrogen, hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 1 -C 20 )-alkyl, (C 3 -C 8 )-Cycloalkyl, (C 3 -C 8 )cycloalkyl-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl-(C 1 -C 6 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkoxy, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 7 -C 16 )-aralkenyl, (C 7 -C 16 )-aralkynyl, (C 2 -C 20 )-alkenyl, (C 2 -C 20 )-alkynyl, (C 1 -C 20 )-alkoxy, (C 2 -C 20 )-alkenyloxy, (C 2 -C 20 )-alkynyloxy, retinyloxy, (C 1 -C 20 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxy, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 16 )-hydroxyalkyl, (C 6 -C 16 )-aryloxy-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 7 -C 12 )-aralkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 2 -C 20 )-alkenyloxy-(C 1 -C 6 )-alkyl, (C 2 -C 20 )-alkynyloxy-(C 1 -C 6 )-alkyl, retinyloxy-(C 1 -C 6 )-alkyl, —O—[CH 2 ] x C f H (2f+1−g) F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 20 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, cinnamoyl, (C 2 -C 20 )-alkenylcarbonyl, (C 2 -C 20 )-alkynylcarbonyl, (C 1 -C 20 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 20 )-alkenyloxycarbonyl, retinyloxycarbonyl, (C 2 -C 20 )-alkynyloxycarbonyl, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di-(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N,N-dicyclo-(C 3 -C 8 )-alkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—((C 3 -C 8 )-Cycloalkyl-(C 1 -C 6 )-alkyl)-carbamoyl, N—(C 1 -C 6 )-alkyl-N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)-carbamoyl, N-(+)-dehydroabietylcarbamoyl, N—(C 1 -C 6 )-alkyl-N-(+)-dehydroabietylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 18 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N-((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl; CON(CH 2 ) h , in which a CH 2 group can be replaced by O, S, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; a carbamoyl radical of the formula R
in which R x and R v are each independently selected from hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, aryl, or the substituent of an α-carbon of an α-amino acid, to which the L- and D-amino acids belong, s is 1-5, T is OH, or NR*R**, and R*, R** and R*** are identical or different and are selected from hydrogen, (C 6 -C 12 )-aryl, (C 7 -C 11 )-aralkyl, (C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkyl, (+)-dehydroabietyl, (C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 7 -C 12 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkyl, (C 1 -C 10 )-alkanoyl, optionally substituted (C 7 -C 16 )-aralkanoyl, optionally substituted (C 6 -C 12 )-aroyl; or R* and R** together are —[CH 2 ] h , in which a CH 2 group can be replaced by O, S, SO, SO 2 , N-acylamino, N—(C 1 -C 10 )-alkoxycarbonylimino, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 7 -c 6)-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)-carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyloxyamino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino, (C 3 -C 8 )-cycloalkanoylamino, (C 6 -C 12 )-aroylamino, (C 7 -C 16 )-aralkanoylamino, (C 1 -C 12 )-alkanoyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkanoyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-aroyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkanoyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkanoylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aroylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkanoylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino(C 1 -C 10 )-alkyl, (C 1 -C 20 )-alkylmercapto, (C 1 -C 20 )-alkylsulfinyl, (C 1 -C 20 )-alkylsulfonyl, (C 6 -C 12 )-arylmercapto, (C 6 -C 12 )-arylsulfinyl, (C 6 -C 12 )-arylsulfonyl, (C 7 -C 16 )-aralkylmercapto, (C 7 -C 16 )-aralkylsulfinyl, (C 7 -C 16 )-aralkylsulfonyl, (C 1 -C 12 )-alkylmercapto-(C 1 -C 6 )-alkyl, (C 1 -C 12 )-alkylsulfinyl-(C 1 -C 6 )-alkyl, (C 1 -C 12 )-alkylsulfonyl-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylmercapto-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylsulfinyl-(C 1 -C 6 )-alkyl, (C 6 -C 12 )-arylsulfonyl-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylmercapto-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylsulfinyl-(C 1 -C 6 )-alkyl, (C 7 -C 16 )-aralkylsulfonyl-(C 1 -C 6 )-alkyl, sulfamoyl, N—(C 1 -C 10 )-alkylsulfamoyl, N,N-di-(C 1 -C 10 )-alkylsulfamoyl, (C 3 -C 8 )-cycloalkylsulfamoyl, N—(C 6 -C 12 )-arylsulfamoyl, N—(C 7 -C 16 )-aralkylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylsulfamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylsulfamoyl, (C 1 -C 10 )-alkylsulfonamido, N—((C 1 -C 10 )-alkyl)-(C 1 -C 10 )-alkylsulfonamido, (C 7 -C 16 )-aralkylsulfonamido, and N—((C 1 -C 10 )-alkyl-(C 7 -C 16 )-aralkylsulfonamido; where an aryl radical may be substituted by 1 to 5 substituents selected from hydroxyl, halogen, cyano, trifluoromethyl, nitro, carboxyl, (C 2 -C 16 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-Cycloalkyloxy-(C 1 -C 12 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 12 )-alkoxy, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl-(C 1 -C 6 )-alkoxy, (C 3 -C 8 )-cycloalkyl(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkoxy, (C 6 -C 12 )-aryl, (C 7 -C 16 )-aralkyl, (C 2 -C 16 )-alkenyl, (C 2 -C 12 )-alkynyl, (C 1 -C 16 )-alkoxy, (C 1 -C 16 )-alkenyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxy, (C 1 -C 12 )-alkoxy(C 1 -C 8 )-alkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy, (C 7 -C 16 )-aralkyloxy, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxy, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxy, (C 1 -C 8 )-hydroxyalkyl, (C 6 -C 16 )-aryloxy-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aryloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, (C 7 -C 12 )-aralkyloxy-(C 1 -C 8 )-alkoxy-(C 1 -C 6 )-alkyl, —O—[CH 2 ] x C f H (2f+1−g) F g , —OCF 2 Cl, —OCF 2 —CHFCl, (C 1 -C 12 )-alkylcarbonyl, (C 3 -C 8 )-cycloalkylcarbonyl, (C 6 -C 12 )-arylcarbonyl, (C 7 -C 16 )-aralkylcarbonyl, (C 1 -C 12 )-alkoxycarbonyl, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyl, (C 6 -C 12 )-aryloxycarbonyl, (C 7 -C 16 )-aralkoxycarbonyl, (C 3 -C 8 )-cycloalkoxycarbonyl, (C 2 -C 12 )-alkenyloxycarbonyl, (C 2 -C 12 )-alkynyloxycarbonyl, (C 6 -C 12 )-aryloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 7 -C 16 )-aralkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkoxycarbonyl, (C 3 -C 8 )-cycloalkoxy-(C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 12 )-alkylcarbonyloxy, (C 3 -C 8 )-cycloalkylcarbonyloxy, (C 6 -C 12 )-arylcarbonyloxy, (C 7 -C 16 )-aralkylcarbonyloxy, cinnamoyloxy, (C 2 -C 12 )-alkenylcarbonyloxy, (C 2 -C 12 )-alkynylcarbonyloxy, (C 1 -C 12 )-alkoxycarbonyloxy, (C 1 -C 12 )-alkoxy-(C 1 -C 12 )-alkoxycarbonyloxy, (C 6 -C 12 )-aryloxycarbonyloxy, (C 7 -C 16 )-aralkyloxycarbonyloxy, (C 3 -C 8 )-cycloalkoxycarbonyloxy, (C 2 -C 12 )-alkenyloxycarbonyloxy, (C 2 -C 12 )-alkynyloxycarbonyloxy, carbamoyl, N—(C 1 -C 12 )-alkylcarbamoyl, N,N-di(C 1 -C 12 )-alkylcarbamoyl, N—(C 3 -C 8 )-cycloalkylcarbamoyl, N,N-dicyclo-(C 3 -C 8 )-alkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 3 -C 8 )-cycloalkylcarbamoyl, N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)carbamoyl, N—(C 1 -C 6 )-alkyl-N—((C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl)carbamoyl, N-(+)-dehydroabietylcarbamoyl, N—(C 1 -C 6 )-alkyl-N-(+)-dehydroabietylcarbamoyl, N—(C 6 -C 12 )-arylcarbamoyl, N—(C 7 -C 16 )-aralkylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 16 )-arylcarbamoyl, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyl, N—((C 1 -C 16 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyl, N—((C 6 -C 16 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyl, N-((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyl, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)-carbamoyl, CON(CH 2 ) h , in which a CH 2 group can be replaced by, O, S, N—(C 1 -C 8 )-alkylimino, N—(C 3 -C 8 )-cycloalkylimino, N—(C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkylimino, N—(C 6 -C 12 )-arylimino, N—(C 7 -C 16 )-aralkylimino, N—(C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylimino, and h is from 3 to 7; carbamoyloxy, N—(C 1 -C 12 )-alkylcarbamoyloxy, N,N-di-(C 1 -C 12 )-alkylcarbamoyloxy, N—(C 3 -C 8 )-cycloalkylcarbamoyloxy, N—(C 6 -C 16 )-arylcarbamoyloxy, N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 6 -C 12 )-arylcarbamoyloxy, N—(C 1 -C 10 )-alkyl-N—(C 7 -C 16 )-aralkylcarbamoyloxy, N—((C 1 -C 10 )-alkyl)carbamoyloxy, N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 1 -C 10 )-alkoxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 6 -C 12 )-aryloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, N—(C 1 -C 10 )-alkyl-N—((C 7 -C 16 )-aralkyloxy-(C 1 -C 10 )-alkyl)carbamoyloxy, amino, (C 1 -C 12 )-alkylamino, di-(C 1 -C 12 )-alkylamino, (C 3 -C 8 )-cycloalkylamino, (C 3 -C 12 )-alkenylamino, (C 3 -C 12 )-alkynylamino, N—(C 6 -C 12 )-arylamino, N—(C 7 -C 11 )-aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C 1 -C 12 )-alkoxyamino, (C 1 -C 12 )-alkoxy-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino, (C 3 -C 8 )-cycloalkanoylamino, (C 6 -C 12 )-aroylamino, (C 7 -C 16 )-aralkanoylamino, (C 1 -C 12 )-alkanoyl-N—(C 1 -C 10 )-alkylamino, (C 3 -C 8 )-cycloalkanoyl-N—(C 1 -C 10 )-alkylamino, (C 6 -C 12 )-aroyl-N—(C 1 -C 10 )-alkylamino, (C 7 -C 11 )-aralkanoyl-N—(C 1 -C 10 )-alkylamino, (C 1 -C 12 )-alkanoylamino-(C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkanoylamino-(C 1 -C 8 )-alkyl, (C 6 -C 12 )-aroylamino-(C 1 -C 8 )-alkyl, (C 7 -C 16 )-aralkanoylamino-(C 1 -C 8 )-alkyl, amino-(C 1 -C 10 )-alkyl, N—(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, N,N-di-(C 1 -C 10 )-alkylamino-(C 1 -C 10 )-alkyl, (C 3 -C 8 )-cycloalkylamino-(C 1 -C 10 )-alkyl, (C 1 -C 12 )-alkylmercapto, (C 1 -C 12 )-alkylsulfinyl, (C 1 -C 12 )-alkylsulfonyl, (C 6 -C 16 )-arylmercapto, (C 6 -C 16 )-arylsulfinyl, (C 6 -C 16 )-arylsulfonyl, (C 7 -C 6 )-aralkylmercapto, (C 7 -C 6 )-aralkylsulfinyl, or (C 7 -C 16 )-aralkylsulfonyl;
f is 1 to 8;
g is 0 or 1 to (2f+1); and
x is 0 to 3;
or a physiologically active salt or prodrug derived therefrom.Join the waitlist — get patent alerts
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