Claims for Patent: 8,148,401

Summary for Patent: 8,148,401

Title:	Benzimidazole derivatives
Abstract:	The present invention relates to a compound of the Formula I or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3A, R3B, R4, R5, X, m, and n are as defined herein. Such novel benzamidazole derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.
Inventor(s):	Michael J. Munchhof, Lawrence A. Reiter, Susan D. La Greca, Christopher S. Jones, Qifang Li
Assignee:	Pfizer Corp SRL
Application Number:	US12/142,119
Patent Claims:	1. A compound of Formula II(a), wherein: each R1 is independently halo, (C1-C6)alkyl, (C1-C6)alkoxy, —CF3, —CN, or —NR16R17; R2 is hydrogen or (C1-C6)alkyl; R3B is hydrogen, (C1-C6)alkyl, —(CH2)t(C6-C12)aryl, or —(CH2)t(C3-C12)carbocyclyl; R4 is hydrogen or (C1-C6)alkyl; R10 is —(CH2)t(C6-C12)aryl or —(CH2)t(4 to 14 membered heterocyclyl), wherein each of said (C6-C12)aryl and (4 to 14 membered heterocyclyl) is optionally substituted with from 1 to 5 substituents each of which is independently selected from (C1-C6)alkyl, —CN, halo, —CF3, —OCF3, —NR16R17, (C1-C6)alkoxy, —NO2, —(CH2)t(C6-C12)aryl, —C(O)(C1-C6 alkyl), —C(O)CF3, azido, (4 to 12 membered heterocyclyl), and —S((C1-C6)alkyl); each R16 and R17 is independently selected from hydrogen and (C1-C6)alkyl; n is 0, 1, 2, 3, or 4; and each t is independently 0, 1, or 2; or a pharmaceutically acceptable salt thereof. 2. A compound according to claim 1, wherein: each R1 is independently F, Cl, Br, —CH3, —OCH3, —CF3, —CN, or —NR16R17; R2 is hydrogen; R3B is hydrogen, —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —CH2CH2CH2CH3, —CH2CH(CH3)2, or —CH2(phenyl); R4 is hydrogen; and R10 is phenyl, pyridyl, or 2,3-dihydro-1,4-benzodioxinyl, wherein each of said phenyl, pyridyl, and 2,3-dihydro-1,4-benzodioxinyl is optionally substituted with from 1 to 5 substituents each of which is independently selected from (C1-C6)alkyl, —CN, halo, —CF3, —OCF3, —NR16R17, (C1-C6)alkoxy, —NO2, —(CH2)t(C6-C12)aryl, —C(O)(C1-C6 alkyl), —C(O)CF3, azido, (4 to 12 membered heterocyclyl), and —S((C1-C6)alkyl); or a pharmaceutically acceptable salt thereof. 3. A compound according to claim 2, wherein: each R1 is independently F, Cl, —CH3, —OCH3, —CF3, —CN, or —N(CH3)2; R3B is —CH3; and R10 is phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, or 2,3-dihydro-1,4-benzodioxin-6-yl, wherein each of said phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, and 2,3-dihydro-1,4-benzodioxin-6-yl is optionally substituted with from 1 to 5 substituents each of which is independently selected from (C1-C6)alkyl, —CN, halo, —CF3, —OCF3, —NR16R17, (C1-C6)alkoxy, —NO2, —(CH2)t(C6-C12)aryl, —C(O)(C1-C6 alkyl), —C(O)CF3, azido, (4 to 12 membered heterocyclyl), and —S((C1-C6)alkyl); or a pharmaceutically acceptable salt thereof. 4. A compound according to claim 3, wherein R10 is phenyl, 3-pyridyl, or 2,3-dihydro-1,4-benzodioxin-6-yl, wherein each of said phenyl, 3-pyridyl, and 2,3-dihydro-1,4-benzodioxin-6-yl is optionally substituted with from 1 to 5 substituents each of which is independently selected from (C1-C6)alkyl, —CN, halo, —CF3, —OCF3, —NR16R17, (C1-C6)alkoxy, —NO2, —(CH2)t(C6-C12)aryl, —C(O)(C1-C6 alkyl), —C(O)CF3, azido, (4 to 12 membered heterocyclyl), and —S((C1-C6)alkyl); or a pharmaceutically acceptable salt thereof. 5. A compound according to claim 4, wherein R10 is phenyl optionally substituted with from 1 to 5 substituents each of which is independently selected from (C1-C6)alkyl, —CN, halo, —CF3, —OCF3, —NR16R17, (C1-C6)alkoxy, —NO2, —(CH2)t(C6-C12)aryl, —C(O)(C1-C6 alkyl), —C(O)CF3, azido, (4 to 12 membered heterocyclyl), and —S((C1-C6)alkyl); or a pharmaceutically acceptable salt thereof. 6. A compound according to claim 5, wherein R10 is phenyl optionally substituted with from 1 to 5 substituents each of which is independently selected from —CH3, —CN, —F, —Cl, —Br, —CF3, —OCF3, —NR16R17, —OCH3, and —NO2; or a pharmaceutically acceptable salt thereof. 7. A compound of Formula III(a), wherein: each R1 is independently halo, (C1-C6)alkyl, (C1-C6)alkoxy, —CF3, —CN, or —NR16R17; R2 is hydrogen or (C1-C6)alkyl; R3B is hydrogen, (C1-C6)alkyl, —(CH2)t(C6-C12)aryl, or —(CH2)t(C3-C12)carbocyclyl; R4 is hydrogen or (C1-C6)alkyl; R11 is —(CH2)t(C6-C12)aryl or —(CH2)t(4 to 14 membered heterocyclyl), wherein each of said (C6-C12)aryl and (4 to 14 membered heterocyclyl) is optionally substituted with from 1 to 5 substituents each of which is independently selected from (C1-C6)alkyl, —CN, halo, —CF3, —OCF3, —NR16R17, (C1-C6)alkoxy, —NO2, —(CH2)t(C6-C12)aryl, —C(O)(C1-C6 alkyl), —C(O)CF3, azido, (4 to 12 membered heterocyclyl), and —S((C1-C6)alkyl); each R16 and R17 is independently selected from hydrogen and (C1-C6)alkyl; n is 0, 1, 2, 3, or 4; and each t is independently 0, 1, or 2; or a pharmaceutically acceptable salt thereof. 8. A compound of Formula IV(a) wherein: each R1 is independently halo, (C1-C6)alkyl, (C1-C6)alkoxy, —CF3, —CN, or —NR16R17; R2 is hydrogen or (C1-C6)alkyl; R3B is hydrogen, (C1-C6)alkyl, —(CH2)t(C6-C12)aryl, or —(CH2)t(C3-C12)carbocyclyl; R4 is hydrogen or (C1-C6)alkyl; each R12 is independently selected from —(CH2)t(C6-C12)aryl, —(CH2)t(4 to 14 membered heterocyclyl), (C1-C6)alkyl, —CN, halo, —CF3, —OCF3, —NR16R17, (C1-C6)alkoxy, —NO2, —(CH2)t(C6-C12)aryl, —C(O)(C1-C6 alkyl), —C(O)CF3, azido, (4 to 12 membered heterocyclyl), and —S((C1-C6)alkyl); each R16 and R17 is independently selected from hydrogen and (C1-C6)alkyl; n is 0, 1, 2, 3, or 4; each t is independently 0, 1, or 2; and z is 0, 1, 2, 3, 4, or 5; or a pharmaceutically acceptable salt thereof. 9. A compound according to claim 8, wherein: R2 is hydrogen; R3B is —CH3; R4 is hydrogen; and each R12 is independently selected from —CN, —F, —Cl, —Br, —CF3, —OCF3, —NR16R17, —OCH3, and —NO2; or a pharmaceutically acceptable salt thereof. 10. A compound according to claim 9, wherein: each R1 is independently halo, —CH3, —OCH3, —CF3, —CN, or —N(CH3)2; R12 is —CN, —F, —Cl, —Br, —CF3, —OCF3, —OCH3, or —NO2; and z is 1; or a pharmaceutically acceptable salt thereof. 11. A compound according to claim 10, wherein: R12 is —CN, —F, —Cl, —Br, or —CF3; and n is 0; or a pharmaceutically acceptable salt thereof. 12. A compound according to claim 11, wherein R12 is —CN, or a pharmaceutically acceptable salt thereof. 13. A compound selected from: 1-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-3-(4-cyanophenyl)urea; 1-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-3-(4-chlorophenyl)urea; 1-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-3-(6-fluoropyridin-3-yl)urea; N-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]chromane-6-carboxamide; N-[(2R,4R)-2-(6-chloro-1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-2,3-dihydro-1,4-benzodioxine-6-carboxamide; 1-{(2R,4R)-1-methyl-2-[5-(trifluoromethyl)-1H-benzimidazol-2-yl]piperidin-4-yl}-3-[6-(trifluoromethyl)pyridin-3-yl]urea; 1-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-3-(4-methoxyphenyl)urea; N-[(2R,4R)-2-(6-methoxy-1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-2,3-dihydro-1,4-benzodioxine-6-carboxamide; 1-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-isobutylpiperidin-4-yl]-3-(4-cyanophenyl)urea; and 1-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-3-(6-fluoro-5-methylpyridin-3-yl)urea; or a pharmaceutically acceptable salt thereof. 14. A compound which is or a pharmaceutically acceptable salt thereof. 15. A compound which is or a pharmaceutically acceptable salt thereof. 16. A compound which is or a pharmaceutically acceptable salt thereof. 17. A pharmaceutical composition, comprising an effective amount of at least one compound according to claim 1, and a pharmaceutically acceptable carrier.