COMPOUNDS AND COMPOSITIONS AS HEDGEHOG PATHWAY MODULATORS
First Claim
Patent Images
1. A compound of Formula I:
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in which;
Y1 and Y2 are independently selected from N and CR10;
wherein R10 is selected from hydrogen, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy and —
OXNR10aR10b;
wherein R10a and R10b are independently selected from hydrogen and C1-6alkyl;
R1 is selected from cyano, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy, C6-10aryl, dimethyl-amino, C1-6alkyl-sulfanyl and C3-8heterocycloalkyl optionally substituted with up to 2 C1-6alkyl radicals;
R2 and R5 are independently selected from hydrogen, cyano, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy and dimethylamino;
R3 and R4 are independently selected from hydrogen, halo, cyano, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy and halosubstituted-C1-6alkoxy;
or either R1 and R2 or R1 and R5 together with the phenyl to which they are both attached form C5-10heteroaryl;
R6 and R7 are independently selected from hydrogen, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy and halosubstituted-C1-6alkoxy;
with the proviso that R6 and R7 are not both hydrogen;
R8 is selected from hydrogen, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy and halosubstituted-C1-6alkoxy;
R9 is selected from —
S(O)2R11, —
C(O)R11, —
NR12aR12b and —
R11;
wherein R11 is selected from aryl, heteroaryl, cycloalkyl and heterocycloalkyl;
R12a and R12b are independently selected from C1-6alkyl and hydroxy-substituted-C1-6alkyl;
wherein said aryl, heteroaryl, cycloalkyl and heterocycloalkyl of R9 can be optionally substituted with 1 to 3 radicals independently selected from C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy, C6-10aryl-C0-4alkyl, C5-10heteroaryl-C0-4alkyl, C3-12cycloalkyl and C3-8heterocycloalkyl;
wherein said aryl-alkyl substituent of R9 is optionally substituted with 1 to 3 radicals independently selected from halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy and methyl-piperazinyl;
and the pharmaceutically acceptable salts, hydrates, solvates and isomers thereof.
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Abstract
The invention provides a method for modulating the activity of the hedgehog signaling pathway. In particular, the invention provides a method for inhibiting aberrant growth states resulting from phenotypes such as Ptc loss-of-function, hedgehog gain-of-function, smoothened gain-of-function or Gli gain-of-function, comprising contacting a cell with a sufficient amount of a compound of Formula I.
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Citations
12 Claims
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1. A compound of Formula I:
in which; Y1 and Y2 are independently selected from N and CR10;
wherein R10 is selected from hydrogen, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy and —
OXNR10aR10b;
wherein R10a and R10b are independently selected from hydrogen and C1-6alkyl;R1 is selected from cyano, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy, C6-10aryl, dimethyl-amino, C1-6alkyl-sulfanyl and C3-8heterocycloalkyl optionally substituted with up to 2 C1-6alkyl radicals; R2 and R5 are independently selected from hydrogen, cyano, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy and dimethylamino; R3 and R4 are independently selected from hydrogen, halo, cyano, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy and halosubstituted-C1-6alkoxy;
or either R1 and R2 or R1 and R5 together with the phenyl to which they are both attached form C5-10heteroaryl;R6 and R7 are independently selected from hydrogen, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy and halosubstituted-C1-6alkoxy;
with the proviso that R6 and R7 are not both hydrogen;R8 is selected from hydrogen, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy and halosubstituted-C1-6alkoxy; R9 is selected from —
S(O)2R11, —
C(O)R11, —
NR12aR12b and —
R11;
wherein R11 is selected from aryl, heteroaryl, cycloalkyl and heterocycloalkyl;
R12a and R12b are independently selected from C1-6alkyl and hydroxy-substituted-C1-6alkyl;wherein said aryl, heteroaryl, cycloalkyl and heterocycloalkyl of R9 can be optionally substituted with 1 to 3 radicals independently selected from C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy, C6-10aryl-C0-4alkyl, C5-10heteroaryl-C0-4alkyl, C3-12cycloalkyl and C3-8heterocycloalkyl; wherein said aryl-alkyl substituent of R9 is optionally substituted with 1 to 3 radicals independently selected from halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy and methyl-piperazinyl; and the pharmaceutically acceptable salts, hydrates, solvates and isomers thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
Specification
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Current AssigneeSun Pharmaceutical Industries Limited
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Original AssigneeIRM LLC
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InventorsPan, Shifeng, Wu, Xu, Wan, Yongqin, Cheng, Dai, Jiang, Jiqing, Han, Dong, Gao, Wenqi
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Granted Patent
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Time in Patent OfficeDays
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Field of Search
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US Class Current514/211.150
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CPC Class CodesA61P 1/18 for pancreatic disorders, e...A61P 13/08 of the prostateA61P 35/00 Antineoplastic agentsA61P 43/00 Drugs for specific purposes...C07C 235/56 having the nitrogen atom of...C07C 237/40 having the nitrogen atom of...C07C 255/57 containing cyano groups and...C07C 2601/14 The ring being saturatedC07D 413/04 directly linked by a ring-m...
