US2005272786A1PendingUtilityA1
Naphthyl benzoxazoles and benzisoxazoles as estrogenic agents
Est. expiryDec 13, 2021(expired)· nominal 20-yr term from priority
C07D 231/56C07D 261/20C07D 263/57
54
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Claims
Abstract
This invention provides estrogen receptor modulators of formula 1, having the structure wherein, A is wherein R 1 , R 2 , R 3 , and R 4 , and X as defined in the specification, or a pharmaceutically acceptable salt thereof.
Claims
exact text as granted — not AI-modified1 - 7 . (canceled)
8 . A method of treating or inhibiting prostatitis or interstitial cystitis in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkyl of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
9 . A method of treating or inhibiting inflammatory bowel disease, Crohn's disease, ulcerative proctitis, or colitis in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
10 . A method of treating or inhibiting prostatic hypertrophy, uterine leiomyomas, breast cancer, endometrial cancer, polycystic ovary syndrome, endometrial polyps, benign breast disease, adenomyosis, ovarian cancer, melanoma, prostrate cancer, colon cancer, glioma or astioblastomia in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, faranyl, thienyl —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
11 . A method of lowering cholesterol, triglycerides, Lp(a), or LDL levels; inhibiting or treating hypercholesteremia; hyperlipidemia; cardiovascular disease; atherosclerosis; hypertension; peripheral vascular disease; restenosis, or vasospasm; or inhibiting vascular wall damage from cellular events leading toward immune mediated vascular damage in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R, NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
12 . A method of providing cognition enhancement or neuroprotection; or treating or inhibiting senile dementias, Alzheimer's disease, cognitive decline, stroke, anxiety, or neurodegenerative disorders in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
13 . A method of treating or inhibiting free radical induced disease states in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
14 . A method of treating or inhibiting vaginal or vulvar atrophy; atrophic vaginitis; vaginal dryness; pruritus; dyspareunia; dysuria; frequent urination; urinary incontinence; urinary tract infections in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
15 . A method of treating or inhibiting vasomotor symptoms in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O;
or a pharmaceutically acceptable salt thereof.
16 . A method of inhibiting conception in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof
17 . A method of treating or inhibiting arthritis in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 O, CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
18 . The method according to claim 17 , wherein the arthritis is rheumatoid arthritis, osteoarthritis, or spondyloarthropathies.
19 . A method of treating or inhibiting joint swelling or erosion; or treating or inhibiting joint damage secondary to arthroscopic or surgical procedures in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
20 . A method of treating or inhibiting psoriasis or dermatitis in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
21 . A method of treating or inhibiting ischemia, reperfusion injury, asthma, pleurisy, multiple sclerosis, systemic lupus erythematosis, uveitis, sepsis, hemmorhagic shock, macular degeneration or type II diabetes in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
22 . A method of treating or inhibiting endometriosis in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl, thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof.
23 . A pharmaceutical composition which comprises a compound of formula I, having the structure
wherein,
A is
R 1 , R 3 , and R 4 are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 2 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, triflouroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, furanyl thienyl, —NO 2 , —NR 5 R 6 , —N(R 5 )COR 6 , —CN, —CHFCN, —CF 2 CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl, trifluoroalkoxy, —COR 5 , —CO 2 R 5 , —NO 2 , CONR 5 R 6 , NR 5 R 6 or N(R 5 )COR 6 ;
R 5 and R 6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, aryl of 6-10 carbon atoms, —CN, —CHFCN, or —CF 2 CN; wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluroalkyl of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, —COR 7 , —CO 2 R 7 , —NO 2 , CONR 7 R 8 , NR 7 R 8 or N(R 7 )COR 8 ;
R 7 and R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or aryl of 6-10 carbon atoms;
X is O, S;
or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier.Join the waitlist — get patent alerts
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