US2010137401A1PendingUtilityA1
2-methylprop anamides and their use as pharmaceuticals
Est. expiryJun 24, 2024(expired)· nominal 20-yr term from priority
A61P 9/00A61P 43/00A61P 7/02A61P 3/06A61P 9/10A61P 9/04A61P 3/10A61P 9/12A61P 3/04A61P 29/00A61P 25/28A61P 27/06A61P 19/10C07C 2601/08C07C 2602/10C07C 2602/08C07C 233/22C07C 233/11C07C 235/22C07D 307/22A61P 13/12C07C 233/13C07C 2601/14C07C 323/60C07D 319/20C07D 209/14C07C 233/23C07C 2602/28C07D 209/16C07C 2602/42C07C 233/19C07C 2601/02
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Claims
Abstract
The present invention relates to inhibitors of 11-β hydroxyl steroid dehydrogenase type 1, antagonists of the mineralocorticoid receptor (MR), and pharmaceutical compositions thereof. The compounds of the invention can be useful in the treatment of various diseases associated with expression or activity of 11-β hydroxyl steroid dehydrogenase type 1 and/or diseases associated with aldosterone excess.
Claims
exact text as granted — not AI-modified1 . A compound of Formula I:
or pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 is phenyl, Cy 1 -(CH 2 ) m —O— or Cy 1 -(CH 2 ) m —S—, wherein said phenyl is optionally substituted by 1, 2, 3, 4 or 5 R 1a ;
R 2 is —(CR 4 R 5 ) n Cy 2 , —(CR 4 R 5 ) t Cy 3 , or Cy 4 ;
R 3 is H, C 1-6 alkyl or C 3-6 cycloalkyl;
R 4 and R 5 are each, independently, H, halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more R 4a ;
R 6 is H or C 1-6 alkyl optionally substituted by one or more OH;
R 1a and R 1b are independently halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R 1c is halo, OH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, phenyl, benzyl, C(O)OR g or OR g ;
R 4a is halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Cy 1 is aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 —W—X—Y—Z;
Cy 2 is:
Cy 3 is phenyl optionally substituted by one or more R 1a ;
Cy 4 is:
U is CH 2 , NH or O;
W, W′ and W″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is each optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
X, X′ and X″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Y, Y′ and Y″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Z, Z′ and Z″ are each, independently, H, halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
wherein two —W—X—Y—Z together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
or wherein two —W—X—Y—Z together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with the atom to which they are both attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
or wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein —W—X—Y—Z is other than H;
wherein —W′—X′—Y′—Z′ is other than H;
wherein —W″—X″—Y″—Z″ is other than H;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R e and R f are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R e and R f together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R g is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl or cycloalkylalkyl;
j is 0, 1, 2, or 3;
m is 0, 1, or 2;
n is 0, 1, 2, or 3;
q1 is 0, 1, 2, 3 or 4;
q2 is 0, 1, 2 or 3;
q3 is 1, 2, 3, 4 or 5;
q is 0, 1, 2, 3, 4 or 5;
r is 1 or 2; and
t is 2 or 3;
with the provisos:
a) when R 1 is phenyl optionally substituted by 1, 2, 3, 4 or 5 R 1a and R 2 is (CR 4 R 5 ) t Cy 3 , at least one of R 4 and R 5 is other than H;
b) when R 1 is phenyl optionally substituted by 1, 2, 3, 4 or 5 R 1a and R 2 is Cy 2 , Cy 2 is other than 1-[3-(2-methoxyphenoxy)benzyl]-piperidine-4-yl, 1-[3-(2-methoxyphenoxy)-benzyl]-pyrrolidin-3-yl, 1,2,2,6,6-pentamethyl-piperidin-4-yl or cyclohexyl substituted by one NR c R d ; and
c) when R 2 is cyclohexyl, R 1 is other than 3,5-di-tert-butyl-4-hydroxyphenyl.
2 . The compound of claim 1 having the structure of formula II:
or pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 is phenyl optionally substituted by 1, 2, 3, 4 or 5 R 1a ;
R 3 is H, C 1-6 alkyl or C 3-6 cycloalkyl;
R 4 and R 5 are each, independently, H, halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more R 4a ;
R 6 is H or C 1-6 alkyl optionally substituted by one or more OH;
R 1a and R 1b are independently halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R 4a is halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Cy 2 is:
U is CH 2 , NH or O;
W′ and W″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
X′ and X″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-6 dialkylamino;
Y′ and Y″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Z′ and Z″ are each, independently, H, halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
wherein two —W′—X′—Y′—Z′ together with the atom to which they are both attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
or wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein —W′—X′—Y′—Z′ is other than H;
wherein —W″—X″—Y″—Z″ is other than H;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R e and R f are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R e and R f together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
n is 0, 1, 2, or 3;
q1 is 0, 1, 2, 3 or 4;
q2 is 0, 1, 2 or 3;
q3 is 1, 2, 3, 4 or 5;
q is 0, 1, 2, 3, 4 or 5; and
r is 1 or 2;
with the provisos:
a) when n is 0, Cy 2 is other than 1-[3-(2-methoxyphenoxy)benzyl]-piperidine-4-yl, 1-[3-(2-methoxyphenoxy)benzyl]-pyrrolidin-3-yl, 1,2,2,6,6-pentamethyl-piperidin-4-yl or cyclohexyl substituted by one NR c R d ; and
b) when n is 0 and Cy 2 is cyclohexyl, R 1 is other than 3,5-di-tert-butyl-4-hydroxyphenyl.
3 . The compound of claim 2 having the structure of formula IIa:
wherein:
R 1 is phenyl optionally substituted by 1, 2, 3, 4 or 5 R 1a ;
R 6 is H or C 1-6 alkyl optionally substituted by one or more OH;
R 7 is halo, CN, NO 2 , OH, OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , S(O) 2 NR c R d , C 1-4 alkoxy, C 1-6 alkyl, C 2-6 , alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkyl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkyl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
Cy 2 is:
R 1a is halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
W′ and W″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
X′ and X″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Y′ and Y″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Z′ and Z″ are each, independently, H, halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
wherein two —W′—X′—Y′—Z′ together with the atom to which they are both attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
or wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein —W′—X′—Y′—Z′ is other than H;
wherein —W″—X″—Y″—Z″ is other than H;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R e and R f are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R e and R f together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
q is 0, 1, 2, 3, 4 or 5;
r is 1 or 2;
t is 2 or 3; and
v is 2, 3, 4 or 5;
with the proviso that when Cy 2 is cyclohexyl, R 1 is other than 3,5-di-tert-butyl-4-hydroxyphenyl.
4 . The compound of claim 2 having the structure of Formula IIaa:
wherein:
R 6 is H or C 1-6 alkyl optionally substituted by one or more OH;
R 7 is halo, CN, NO 2 , OH, OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , S(O) 2 NR c R d , C 1-4 alkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkyl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkyl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
Cy 2 is:
R 1a is halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R c , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
W′ and W″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
X′ and X″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Y′ and Y″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 1-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Z′ and Z″ are each, independently, H, halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
wherein two —W′—X′—Y′—Z′ together with the atom to which they are both attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
or wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein —W′—X′—Y′—Z′ is other than H;
wherein —W″—X″—Y″—Z″ is other than H;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R e and R f are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R e and R f together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
q is 0, 1, 2, 3, 4 or 5;
r is 1 or 2;
v is 2, 3, 4 or 5; and
u1 is 0, 1, 2, 3 or 4.
5 . The compound of claim 2 having the structure of Formula IIb:
wherein:
R 4 and R 5 are each, independently, H, halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more R 4a ;
R 6 is H or C 1-6 alkyl optionally substituted by one or more OH;
R 1a and R 1b are independently halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R 4a is halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Cy 2 is:
U is CH 2 , NH or O;
W′ and W″ are each, independently, absent, C 1-6 alkylenyl, C 2-4 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
X′ and X″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Y′ and Y″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 1-6 alkynylenyl are each optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 , haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Z′ and Z″ are each, independently, H, halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 2-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
wherein two —W′—X′—Y′—Z′ together with the atom to which they are both attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
or wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein —W′—X′—Y′—Z′ is other than H;
wherein —W″—X″—Y″—Z″ is other than H;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R e and R f are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R e and R f together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
n is 1, 2 or 3;
q1 is 0, 1, 2, 3 or 4;
q2 is 0, 1, 2 or 3;
q3 is 1, 2 or 3;
q is 0, 1, 2, 3, 4 or 5;
r is 1 or 2; and
u is 0, 1, 2, 3, 4 or 5.
6 . The compound of claim 1 having the structure of Formula III:
or pharmaceutically acceptable salt or prodrug thereof, wherein:
R 3 is H, C 1-6 alkyl or C 3-6 cycloalkyl;
R 4 and R 5 are each, independently, H, halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more R 4a ;
R 1a is each independently, halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R 4a is halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R e and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
t is 2 or 3; and
u is 0, 1, 2, 3, 4 or 5;
with the proviso that at least one of R 4 and R 5 is other than H.
7 . The compound of claim 3 having the structure of Formula IIIa:
or pharmaceutically acceptable salt or prodrug thereof, wherein:
R 4 and R 5 are each, independently, H, halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more R 4a ;
R 4′ is halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, or C 1-4 haloalkoxy;
R 5′ is H, halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more R 4a ;
R 1a is independently, halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R 4a is halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
t1 is 1 or 2; and
u is 0, 1, 2, 3, 4 or 5.
8 . The compound of claim 1 having the structure of formula IV:
or pharmaceutically acceptable salt or prodrug thereof, wherein:
R 3 is H, C 1-6 alkyl or C 3-6 cycloalkyl;
R 6 is H or C 1-6 alkyl optionally substituted by one or more OH;
R 1a is halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R 1c is halo, OH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, phenyl, benzyl, C(O)OR g or OR g ;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R g is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl or cycloalkylalkyl;
u is 0, 1, 2, 3, 4 or 5; and
j is 0, 1, 2 or 3.
9 . The compound of claim 1 having the structure of Formula V:
or pharmaceutically acceptable salt or prodrug thereof, wherein:
R 2 is (CR 4 R 5 ) n Cy 2 , (CR 4 R 5 ) t Cy 3 , or Cy 4 ;
R 3 is H, C 1-6 alkyl or C 3-6 cycloalkyl;
R 4 and R 5 are each, independently, H, halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more R 4a ;
R 6 is H, C 1-6 alkyl optionally substituted by one or more OH;
R 1a and R 1b are each, independently, halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R 1c is halo, OH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, phenyl, benzyl, C(O)OR g or OR g ;
R 4a is halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Cy 1 is aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 —W—X—Y—Z;
Cy 2 is:
Cy 3 is phenyl optionally substituted by one or more R a ;
Cy 4 is:
U is CH 2 , NH or O;
W, W′ and W″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-6 dialkylamino;
X, X′ and X″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Y, Y′ and Y″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-4 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Z, Z′ and Z″ are each, independently, H, halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-6 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkyl, C 1-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
wherein two —W—X—Y—Z together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″; or wherein two —W—X—Y—Z together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with the atom to which they are both attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″; or wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein —W—X—Y—Z is other than H;
wherein —W′—X′—Y′—Z′ is other than H;
wherein —W″—X″—Y″—Z″ is other than H;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R e and R f are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl; or R e and R f together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R g is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl or cycloalkylalkyl;
m is 0, 1, or 2;
n is 0, 1, 2, or 3;
t is 2 or 3;
q1 is 0, 1, 2, 3 or 4;
q2 is 0, 1, 2 or 3;
q3 is 1, 2 or 3;
q is 0, 1, 2, 3, 4 or 5;
r is 1 or 2; and
j is 0, 1, 2, or 3.
10 . The compound of claim 1 wherein R 1 is phenyl optionally substituted by 1, 2, 3, 4 or 5 halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl.
11 . The compound of claim 1 wherein R 1 is phenyl substituted by 1, 2 or 3 halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-6 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl.
12 . The compound of claim 1 wherein R 1 is phenyl substituted by 1, 2 or 3 halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2 , dialkylamino, C 1-6 alkyl, or C 1-6 haloalkyl.
13 . The compound of claim 1 wherein R 1 is 4-chlorophenyl optionally substituted by 1 or 2 halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, or C 1-6 haloalkyl.
14 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; and Cy 2 is:
R 6 is H.
15 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; Cy 2 is:
R 1b is halo, CN, NO 2 , OH, C 1-4 alkoxy optionally substituted by one or more OH, C 1-4 haloalkoxy, or C 1-6 alkyl optionally substituted by 1, 2, or 3 OH, C 1-4 alkoxy, halo, CN or NO 2 ; and
q3 is 1, 2 or 3.
16 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; and Cy 2 is
R 8 is C 2-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein C 2-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted by one or more halo or OH; and
q1 is 0, 1, 2, 3 or 4.
17 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; R 6 is H; R 8 is C 2-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein C 2-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted by one or more halo or OH; Cy 2 is
—W′—X′—Y′—Z′ is independently halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 2-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group; and
q1 is 0, 1, 2, 3 or 4.
18 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; Cy 2 is:
R 6 is H.
19 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; Cy 2 is:
—W′—X′—Y′—Z′ is independently halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl; and
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group.
20 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; Cy 2 is:
—W′—X′—Y′—Z′ is independently halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted by 1, 2 or 3 halo, C 2-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR e R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R e and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group; and
v is 2, 3, 4 or 5.
21 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; Cy 2 is:
R 7 is halo, CN, NO 2 , OH, OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , S(O) 2 NR c R d , C 1-4 alkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein said C 1-4 alkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl; and
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
with the proviso that when n is 0 and Cy 2 is cyclohexyl, R 1 is other than 3,5-di-tert-butyl-4-hydroxyphenyl.
22 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; Cy 2 is:
q is 2, 3, 4 or 5; and
two —W′—X′—Y′—Z′ together with the atom to which they are both attached to form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″.
23 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; Cy 2 is:
q is 2, 3, 4 or 5; and
two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a fused 5- or 6-membered aryl or fused 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″.
24 . The compound of claim 1 wherein:
R 2 is (CR 4 R 5 ) n Cy 2 ; R 6 is H or C 1-6 alkyl optionally substituted by one or more OH; Cy 2 is:
r is 1 or 2;
—W′—X′—Y′—Z′ and —W″—X″—Y″—Z″ are each halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
q4 is 0, 1, 2 or 3; and
q5 is 0, 1, 2 or 3.
25 . The compound of claim 1 wherein R 2 is (CR 4 R 5 ) n Cy 2 , and n is 1, 2 or 3.
26 . The compound of claim 1 wherein R 2 is (CR 4 R 5 ) t Cy 3 and t is 2.
27 . The compound of claim 1 wherein R 2 is (CR 4 R 5 ) t Cy 3 and t is 3.
28 . The compound of claim 1 wherein:
R 2 is (CR 4′ R 5′ )(CR 4 R 5 ) t1 Cy 3 ; R 4′ is halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, or C 1-4 haloalkoxy; R 5′ is, H, halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino; and t1 is 1 or 2.
29 . The compound of claim 1 wherein R 2 is:
R 6 is H or C 1-6 alkyl.
30 . The compound of claim 1 wherein:
R 2 is:
R 1c is halo, OH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, phenyl, or benzyl; and
j is 0, 1 or 2.
31 . A compound selected from:
2-(4-chlorophenyl)-N-cyclohexyl-2-methylpropanamide; 2-(4-chlorophenyl)-2-methyl-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]propanamide; 2-(4-chlorophenyl)-2-methyl-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]propanamide; 2-(4-chlorophenyl)-N-[(1R,2R)-2-(benzyloxy)cyclohexyl]-2-methylpropanamide; 2-(4-chlorophenyl)-2-methyl-N-(tetrahydrofuran-3-yl)propanamide; 2-(4-chlorophenyl)-2-methyl-N-(2-phenylcyclopropyl)propanamide; 2-(4-chlorophenyl)-N-[(1S)-1-cyclohexylethyl]-2-methylpropanamide; 2-(4-chlorophenyl)-N-(1-methyl-3-phenylpropyl)-2-methylpropanamide; 2-(4-chlorophenyl)-N-[1-(3-hydroxy-4-methylbenzyl)propyl]-2-methylpropanamide; 2-(4-chlorophenyl)-N-(1,1-dimethyl-2-phenylethyl)-2-methylpropanamide; 2-(4-chlorophenyl)-N-[1-(hydroxymethyl)cyclopentyl]-2-methylpropanamide; 2-(4-chlorophenyl)-N-(3-hydroxy-2,2-dimethylpropyl)-2-methylpropanamide; N-[(1R)-1-benzyl-2-hydroxyethyl]-2-(4-chlorophenyl)-2-methylpropanamide; 2-(4-chlorophenyl)-N-[3-(hydroxymethyl)bicyclo[2.2.1]hept-2-yl]-2-methylpropanamide; 2-(4-chlorophenyl)-N-{[(trans)-2-hydroxycyclohexyl]methyl}-2-methylpropanamide; 2-(4-chlorophenyl)-N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-2-methylpropanamide; 2-(4-chlorophenyl)-N-[(1S,2R)-2-hydroxy-1-methyl-2-phenylethyl]-2-methylpropanamide; N-[(1S)-1-benzyl-2-methoxyethyl]-2-(4-chlorophenyl)-2-methylpropanamide; 2-(4-chlorophenyl)-N-[(1S)-2-hydroxy-1-(1H-indol-3-ylmethyl)ethyl]-2-methyl propanamide; 2-(4-chlorophenyl)-N-[2-(4-chlorophenyl)-1-methylethyl]-2-methyl-2-propanamide; and 2-(4-chlorophenyl)-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-2-methylpropanamide; and 2-(4-chlorophenyl)-N-cyclopentyl-N-cyclopropyl-2-methylpropanamide, or pharmaceutically acceptable salt thereof.
32 . A compound of claim 1 selected from:
N-Cyclohexyl-2-methyl-2-(phenylthio)propanamide; 2-methyl-2-(phenylthio)-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]propanamide; 2-methyl-2-(phenylthio)-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]propanamide; N-[(1R,2R)-2-(benzyloxy)cyclohexyl]-2-methyl-2-(phenylthio)propanamide; 2-methyl-2-(phenylthio)-N-(tetrahydrofuran-3-yl)propanamide; 2-methyl-N-(2-phenylcyclopropyl)-2-(phenylthio)propanamide; N-[(1S)-1-cyclohexylethyl]-2-methyl-2-(phenylthio)propanamide; N-(1-methyl-3-phenylpropyl)-2-methyl-2-(phenylthio)propanamide; N-[1-(3-hydroxy-4-methylbenzyl)propyl]-2-methyl-2-(phenylthio)propanamide; N-(1,1-dimethyl-2-phenylethyl)-2-methyl-2-(phenylthio)propanamide; N-[1-(hydroxymethyl)cyclopentyl]-2-methyl-2-(phenylthio)propanamide; N-[(1R)-1-benzyl-2-hydroxyethyl]-2-methyl-2-(phenylthio)propanamide; N-[3-(hydroxymethyl)bicyclo [2.2.1]hept-2-yl]-2-methyl-2-(phenylthio)propanamide; N-{[(trans)-2-hydroxycyclohexyl]methyl}-2-methyl-2-(phenylthio)propanamide; N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-2-methyl-2-(phenylthio)-propanamide; N-[(1S,2R)-2-hydroxy-1-methyl-2-phenylethyl]-2-methyl-2-(phenylthio)propanamide; N-[(1S)-1-benzyl-2-methoxyethyl]-2-methyl-2-(phenylthio)propanamide; N-[(1S)-2-hydroxy-1-(1H-indol-3-ylmethyl)ethyl]-2-methyl-2-(phenylthio)propanamide; N-[2-(4-chlorophenyl)-1-methylethyl]-2-methyl-2-(phenylthio)propanamide; N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-2-methyl-2-(phenylthio)propanamide; 2-[(2-chlorobenzyl)thio]-N-Cyclohexyl-2-methylpropanamide; 2-{[4-(benzyloxy)phenyl]thio}-N-cyclohexyl-2-methylpropanamide; N-cyclohexyl-2-[(4-hydroxyphenyl)thio]-2-methylpropanamide; 2-{[4-(cyanomethoxy)phenyl]thio}-N-cyclohexyl-2-methylpropanamide; N-cyclohexyl-2-[(4-ethoxyphenyl)thio]-2-methylpropanamide; 2-{[4-(allyloxy)phenyl]thio}-N-cyclohexyl-2-methylpropanamide; N-cyclohexyl-2-methyl-2-{[4-(2,2,2-trifluoroethoxy)phenyl]thio}propanamide; ethyl (4-{[2-(cyclohexylamino)-1,1-dimethyl-2-oxoethyl]thio}phenoxy)acetate; (4-{[2-(cyclohexylamino)-1,1-dimethyl-2-oxoethyl]thio}phenoxy)acetic acid; N-cyclohexyl-2-{[4-(3-hydroxypropoxy)phenyl]thio}-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-2-methyl-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]propanamide; 2-[(2-chlorobenzyl)thio]-2-methyl-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-propanamide; 2-[(2-chlorobenzyl)thio]-N-[(1R,2R)-2-(benzyloxy)cyclohexyl]-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-2-methyl-N-(tetrahydrofuran-3-yl)propanamide; 2-[(2-chlorobenzyl)thio]-2-methyl-N-(2-phenylcyclopropyl)propanamide; 2-[(2-chlorobenzyl)thio]-N-[(1S)-1-cyclohexylethyl]-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-N-(1-methyl-3-phenylpropyl)-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-N-[1-(3-hydroxy-4-methylbenzyl)propyl]-2-methyl-propanamide; 2-[(2-chlorobenzyl)thio]-N-(1,1-dimethyl-2-phenylethyl)-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-N-[1-(hydroxymethyl)cyclopentyl]-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-N-(3-hydroxy-2,2-dimethylpropyl)-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-N-(3-hydroxy-2,2-dimethylpropyl)-2-methylpropanamide; N-[(1R)-1-benzyl-2-hydroxyethyl]-2-[(2-chlorobenzyl)thio]-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-N-[3-(hydroxymethyl)bicyclo[2.2.1]hept-2-yl]-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-N-{[(trans)-2-hydroxycyclohexyl]methyl}-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-N-[(1S,2R)-2-hydroxy-1-methyl-2-phenylethyl]-2-methylpropanamide; N-[(1S)-1-benzyl-2-methoxyethyl]-2-[(2-chlorobenzyl)thio]-2-methylpropanamide; 2-[(2-chlorobenzyl)thio]-N-[(1S)-2-hydroxy-1-(1H-indol-3-ylmethyl)ethyl]-2-methyl propanamide; 2-[(2-chlorobenzyl)thio]-N-[2-(4-chlorophenyl)-1-methylethyl]-2-methyl-2-propanamide; and 2-[(2-chlorobenzyl)thio]-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-2-methylpropanamide; and 2-(4-chlorophenoxy)-N-cyclohexyl-2-methylpropanamide, or pharmaceutically acceptable salt thereof.
33 . A composition comprising a compound of claim 1 , 31 , or 32 and a pharmaceutically acceptable carrier.
34 . A method of modulating 11βHSD1 or MR comprising contacting said 11βHSD1 or MR with a compound of Formula I:
or pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 is phenyl, Cy 1 -(CH 2 ) m —O— or Cy 1 -(CH 2 ) m —S—, wherein said phenyl is optionally substituted by 1, 2, 3, 4 or 5 R 1a ;
R 2 is (CR 4 R 5 ) n Cy 2 , (CR 4 R 5 ) t Cy 3 , or Cy 4 ;
R 3 is H, C 1-6 alkyl or C 3-6 cycloalkyl;
R 4 and R 5 are each, independently, H, halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more R 4 ;
R 6 is H or C 1-6 alkyl optionally substituted by one or more OH;
R 1a and R 1b are, each independently, halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R 1c is halo, OH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, phenyl, benzyl, C(O)OR g or OR g ;
R 4a is halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-6 dialkylamino;
Cy 1 is aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 —W—X—Y—Z;
Cy 2 is:
Cy 3 is phenyl optionally substituted by one or more R 1a ;
Cy 4 is:
U is CH 2 , NH or O;
W, W′ and W″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is each optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
X, X′ and X″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Y, Y′ and Y″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Z, Z′ and Z″ are each, independently, H, halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 2-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
wherein two —W—X—Y—Z together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
or wherein two —W—X—Y—Z together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with the atom to which they are both attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″; or wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein —W—X—Y—Z is other than H;
wherein —W′—X′—Y′—Z′ is other than H;
wherein —W″—X″—Y″—Z″ is other than H;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R e and R f are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R e and R f together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R g is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl or cycloalkylalkyl;
m is 0, 1, or 2;
n is 0, 1, 2, or 3;
t is 2 or 3;
q1 is 0, 1, 2, 3 or 4;
q2 is 0, 1, 2 or 3;
q3 is 1, 2, 3, 4 or 5;
q is 0, 1, 2, 3, 4 or 5;
r is 1 or 2;
j is 0, 1, 2, or 3.
35 . The method of claim 34 wherein said modulating is inhibiting.
36 . A method of treating a disease in a patient, wherein said disease is associated with expression or activity of 11βHSD1 or MR, comprising administering to said patient a therapeutically effective amount of a compound of Formula I:
or pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 is phenyl, Cy 1 -(CH 2 ) m —O— or Cy 1 -(CH 2 ) m —S—, wherein said phenyl is optionally substituted by 1, 2, 3, 4 or 5 R 1a ;
R 2 is (CR 4 R 5 ) n Cy 2 , (CR 4 R 5 ) t Cy 3 , or Cy 4 ;
R 3 is H, C 1-6 alkyl or C 3-6 cycloalkyl;
R 4 and R 5 are each, independently, H, halo, OH, CN, C 1-4 alkyl, C 1-4 alkoxy, wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted with one or more R 4a ;
R 6 is H or C 1-6 alkyl optionally substituted by one or more OH;
R 1a and R 1b are, each independently, halo, CN, NO 2 , OR a , C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C 2-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
R 1c is halo, OH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, phenyl, benzyl, C(O)OR g or OR g ;
R 4a is halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Cy 1 is aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 —W—X—Y—Z;
Cy 2 is:
Cy 3 is phenyl optionally substituted by one or more R a1 ;
Cy 4 is:
U is CH 2 , NH or O;
W, W′ and W″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is each optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
X, X′ and X″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-4 alkynylenyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Y, Y′ and Y″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, COO, CONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl or C 2-6 alkynylenyl is optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;
Z, Z′ and Z″ are each, independently, H, halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;
wherein two —W—X—Y—Z together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
or wherein two —W—X—Y—Z together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with the atom to which they are both attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 3-20 membered cycloalkyl group or 3-20 membered heterocycloalkyl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
or wherein two —W′—X′—Y′—Z′ together with two adjacent atoms to which they are attached optionally form a 5- or 6-membered aryl or 5- or 6-membered heteroaryl group, each optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;
wherein —W—X—Y—Z is other than H;
wherein —W′—X′—Y′—Z′ is other than H;
wherein —W′—X′—Y′—Z′ is other than H;
R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;
R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R e and R f are each, independently, H, C 2-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;
or R e and R f together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
R g is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl or cycloalkylalkyl;
m is 0, 1, or 2;
n is 0, 1, 2, or 3;
t is 2 or 3;
q1 is 0, 1, 2, 3 or 4;
q2 is 0, 1, 2 or 3;
q3 is 1, 2, 3, 4 or 5;
q is 0, 1, 2, 3, 4 or 5;
r is 1 or 2;
j is 0, 1, 2, or 3.
37 . The method of claim 36 wherein said disease is obesity, diabetes, glucose intolerance, hyperglycemia, hyperlipidemia, lipodystrophy, cognitive impairment, dementia, glaucoma, hypertension, cardiovascular disorders, osteoporosis, hypertension, a cardiovascular, renal or inflammatory disease, heart failure, atherosclerosis, arteriosclerosis, coronary artery disease, thrombosis, angina, peripheral vascular disease, vascular wall damage, stroke, dyslipidemia, hyperlipoproteinaemia, diabetic dyslipidemia, mixed dyslipidemia, hypercholesterolemia, hypertriglyceridemia, type 1 diabetes, type 2 diabetes, obesity, metabolic syndrome, insulin resistance or general aldosterone-related target organ damage.Join the waitlist — get patent alerts
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