US 7,741,324 B2Granted

Imidazotriazines as protein kinase inhibitors

AssigneeOSI Pharmaceuticals, Inc.

InventorsAndrew Philip Crew, Mark Joseph Mulvihill, Douglas Scott Werner

Life of this patent

Estimating the term…

Abstract

Compounds of the formula and pharmaceuticaly acceptable salts thereof, wherein Q1 and R1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of various diseases and conditions that respond to treatment by inhibition of tyrosine kinases.

Claims12

Dependent claims

A compound represented by Formula I:

or a pharmaceuticaly acceptable salt thereof, wherein:
Q1 is phenyl substituted by —(X1)0-1—(Y1)0-1—R4 wherein X1 is 3-(O)—, 4-(O)—, 3-(NH)—, or 4-(NH)—;
and Y1 is —CH2— or —(SO2)—;
R4 is C0-10alkyl, C2-10alkenyl, C2-10alkynyl, aryl, heteroaryl, cycloC3-10alkyl, heterocyclyl, cycloC3-10alkenyl, or heterocycloalkenyl, any of which is optionaly substituted by one or more independent G41 substituents;
R1 is C0-10alkyl, cycloC3-10alkyl, bicycloC5-10alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, or heterobicycloC5-10alkyl, any of which is optionaly substituted by one or more independent G1l substituents;
each G11 is independently —OR21, —NR21R31, —CO2R21, —C(O)R21, —CONR21R31, —NR21C(═O)R31, —NR21C(═O)OR31, —NR21C(═O)NR31R21a, —NR21S(O)j3R31, —OC(═O)OR21, —OC(═O)NR21R31, C0-10alkyl, cycloC3-8alkyl, cycloC3-8alkenyl, heterocyclyl-C0-10alkyl, or heterocyclyl-C2-10alkenyl, any of which is optionaly substituted with one or more independent halo, oxo, —CF3, —OCF3, —OR2221, —NR2221R3331(R2221a)j3a, —C(O)R2221, —CO2R2221, —CONR2221R3331, —NO2, —CN, —S(O)j3aR2221, —SO2NR2221R3331, —NR2221C(═O)R3331, —NR2221C(═O)OR3331, —NR2221C(═O)NR3331R2221a, —NR2221S(O)j3aR3331, —C(═S)OR2221, —C(═O)SR2221, —NR2221C(═NR3331)NR2221aR3331a, —NR2221C(═NR3331)OR2221a, —NR2221C(═NR3331)SR2221a, —OC(═O )OR2221, —OC(═O )NR2221R3331, —OC(═O )SR2221, —SC(═O )OR2221, or —SC(═O )NR2221R3331;
each G41 is independently halo, oxo, —CF3, —OCF3, —OR2, —NR2R3(R2a)j1, —C(O)R2, —CO2R2, —CONR2R3, —NO2, —CN, —S(O)j1R2, —SO2NR2R3, —NR2C(═O)R3, —NR2C(═O)O R3, —NR2C(═O )NR3R2a, —NR2S(O)j1R3, —C(═S)O R2, —C(═O )SR2, —NR2C(═NR3)NR2aR3a, —NR2C(═NR3)OR2a, —NR2C(═NR3)SR2a, —OC(═O)O R2, —OC(═O)NR2R3, —OC(═O )SR2, —SC(═O)OR2, —SC(═O)NR2R3, C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, or heterocyclyl-C2-10alkynyl, any of which is optionaly substituted with one or more independent halo, oxo, —CF3, —OCF3, —OR222, —NR222R333(R222a)j1a, —C(O)R222, —CO2R222, —CONR222R333, —NO2, —CN, —S(O)j1aR222, —SO2NR222R333, —NR222C(═O)R333, —NR222C(═O)OR333, —NR222C(═O)NR333R222a, —NR222S(O)j1aR333, —C(═S)OR222, —C(═)SR222, —NR222C(═NR333)NR222aR333a, —NR222C(═NR333)OR222a, —NR222C(═C NR333)SR222a, —OC(═O )OR222, —OC(═O)NR222R333, —OC(═O)SR222, —SC(═O)OR222, or —SC(═O)NR222R333 substituents;
or G41 can be independently aryl-C0-10alkyl, aryl-C2-10alkenyl, aryl-C2-10alkynyl, hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl- C2-10alkynyl, any of which is optionaly substituted with one or more independent halo, —CF3, —OCF3, —OR222, —NR222R333(R222a)j2a, —C(O)R222, —CO2R222, —CONR222R333, —NO2, —CN, —S(O)j2aR222, —SO2NR222R333, —NR222C(═O )R333, —NR222C(═O)OR333, —NR222C(═O)NR333R222a, —NR222S(O)j2aR333, —C(═S)OR222, —C(═O )SR222,—NR222C(═NR333)NR222aR333a, —NR222C(═NR333)OR222a, —NR222C(═NR333)SR222a, —OC(═O)OR222, —OC(═O )NR222R333, —OC(═O)SR222, —SC(═O)OR222, or —SC(═O)NR222R333 substituents;
R2, R2a, R3, R3a, R222, R222a, R333, R333a, R21, R21a, R31, R2221, R2221a, R3331, and R3331a are each independently C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10alkynyl, aryl-C0-10alkyl, aryl-C2-10alkenyl, aryl- C2-10alkynyl, hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl-C2-10alkynyl, any of which is optionaly substituted by one or more independent G13 substituents;
or in the case of —NR2R3(R2a)j1or —NR21R31(R21a)j3 or —NR222R333(R222a)j1a or —NR222R333(R222a)j2a or —NR2221R3331(R2221a)j3a R2 and R3, or R21and R31, or R222 and R333, or R3331, or R2221and R3331, respectfuly, are optionaly taken together with the nitrogen atom to which they are attached to form a 3-10 membered saturated or unsaturated ring, wherein said ring is optionaly substituted by one or more independent G14 substituents and wherein said ring optionaly includes one or more independent heteroatoms other than the nitrogen to which R2 and R3, or R222 and R333, or R222 and R3331, are attached;
G13 and G14 are each independently a C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10alkynyl, aryl-C0-10alkyl, aryl-C2-10alkenyl, aryl-C2-10alkynyl, hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl-C2-10alkynyl, any of which is optionaly substituted with one or more independent halo, —CF3, —OCF3, —OR77, —NR77R87, —C(O)R77, —CO2R77, —CONR77R87, —NO2, —CN, —S(O),j5aR77, —SO2NR77R87, —NR77C(═O)R87, —NR77C(═O)OR87, —NR77C(═O)NR87R77a, —NR77S(O),j5aR87, —C(═S)OR77, —C(═O)SR77, —NR77C(═NR87)NR77aR87a, —NR77C(═NR87)OR77a, —NR77C(═NR87)SR77a, —OC(═O )OR77, —OC(═O)NR77R87, —OC(═O )SR77, —SC(═O)OR77, —P(O)OR77OR87, or —SC(═O)NR77R87 substituents;
R41, R51, R77, R77a, R87, R87a, R778, and R888 are each independently C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC2-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl- C2-10alkynyl, C1-10alkylcarbonyl, C2-10alkenylcarbonyl, C2-10alkynylcarbonyl, C1-10alkoxycarbonyl, C1-10alkoxycarbonylC1-10alkyl, monoC1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl, C1-10alkyl(aryl)aminocarbonyl, monohetarylaminocarbonyl, dihetarylaminocarbonyl, or alkylhetarylaminocarbonyl, any of which is optionaly substituted with one or more independent halo, cyano, hydroxy, nitro, C1-10alkoxy, —SO2N(C0-4alkyl)(C0-4alkyl), or —N(C0-4alkyl)(C0-4alkyl) substituents;
or R77, R77a, R87, and R87a are each independently aryl-C0-10alkyl, aryl-C2-10alkenyl aryl-C2-10alkynyl, hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, hetaryl-C2-10alkynyl, mono(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl, mono(aryl)aminoC1-6alkyl, di(aryl)aminoC1-6alkyl, monohetarylaminoalkyl, dihetarylaminoalkyl, or —N(C1-6alkyl)-C1-6alkyl-aryl, any of which is optionaly substituted with one or more independent halo, cyano, nitro, —O(C0-4alkyl), C1-10alkyl, C2-10alkenyl, C2-10alkynyl, haloC1-10alkyl, haloC2-10alkenyl, haloC2-10alkynyl, —COOH, C1-4alkoxycarbonyl, —CON(C0-4alkyl)(C0-4alkyl), —SO2N(C0-4alkyl)(C0-4alkyl), or —N(C0-4alkyl)(C0-4alkyl) substituents;
and
j1, j1a, j2a, j3, j3a, and j5a are each independently 0, 1, or 2.

12 more elements

A compound selected from:

5-(3-benzyloxy-2-fluoro-phenyl)-7-cyclobutyl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-cyclobutyl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclobutanone,
3-[4-Amino-5-(3 -benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-y]-cyclobutanol,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-1-methyl-cyclobutanol,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-1ethyl-cyclobutanol,
5-(3-Benzyloxy-phenyl)-7-(3-methylamino-cyclobutyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(3-dimethylamino-cyclobutyl)-imidazo[5,1f][1,2,4]triazin-4-ylamine,
7-(3-Azetidin-1-yl-cyclobutyl)-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(3-piperidin-1-yl-cyclobutyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
N-{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclobutyl}-acetamide,
{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclobutyl}-carbamic acid methyl ester,
1-{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclobutyl}-3-methyl-urea,
N-{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclobutyl}-methanesulfonamide,
7-Azetidin-3-yl-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
1-{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-azetidin-1-yl}-ethanone,
{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclobutyl}-methanol,
5-(3-Benzyloxy-phenyl)-7-(3-dimethylaminomethyl-cyclobutyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(3-diethylaminomethyl-cyclobutyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
7-(3-Azetidin-1-ylmethyl-cyclobutyl)-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(3-piperidin-1-ylmethyl-cyclobutyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclobutanecarboxylic acid amide,
5-(3-Benzyloxy-phenyl)-7-cyclohexyl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclohexanone,
4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclohexanol,
4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-1-methyl-cyclohexanol,
4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-1-ethyl-cyclohexanol,
4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclohexanecarboxylic acid methyl ester,
4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclohexanecarboxylic acid amide,
4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclohexanecarboxylic acid methylamide,
{4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclohexyl}-methanol,
7-(4-Aminomethyl-cyclohexyl)-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(4-dimethylaminomethyl-cyclohexyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
7-(4-Azetidin-1-ylmethyl-cyclohexyl)-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(4-pyrrolidin-1-ylmethyl-cyclohexyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(4-piperidin-1-ylmethyl-cyclohexyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-piperidin-4-yl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
1-{4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-piperidin-1-yl}-ethanone,
5-(3-Benzyloxy-phenyl)-7-cyclopentyl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclopentanecarboxylic acid methyl ester,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclopentanecarboxylic acid amide,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclopentanecarboxylic acid methylamide,
{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclopentyl}-methanol,
7-(3-Aminomethyl-cyclopentyl)-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5(3-Benzyloxy-phenyl)-7-(3-dimethylaminomethyl-cyclopentyl)-imidazo [5,1-f][1,2,4]triazin-4-ylamine,
7-(3-Azetidin-1-ylmethyl-cyclopentyl)-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5(3-Benzyloxy-phenyl)-7-(3-pyrrolidin-1-ylmethyl-cyclopentyl)-imidazo [5,1-f][1,2,4]triazin-4-ylamine,
5(3-Benzyloxy-phenyl)-7-(3-piperidin-1-ylmethyl-cyclopentyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
N-{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclopentylmethyl}-acetamide,
{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclopentylmethyl}-carbamic acid methyl ester,
1-{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo [5,1-f][1,2,4]triazin-7-yl]-cyclopentylmethyl}-3-methyl-urea,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclopentanone,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclopentanol,
7-(3-Amino-cyclopentyl)-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5(3-Benzyloxy-phenyl)-7-(3-dimethylamino-cyclopentyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
7-(3-Azetidin-1-yl-cyclopentyl)-5-(3-benzyloxy-phenyl)-imidazo [5,1-f][1,2,4]triazin-4-ylamine,
5(3-Benzyloxy-phenyl)-7-(3-pyrrolidin-1-yl-cyclopentyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(3-piperidin-1-yl-cyclopentyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-phenyl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzoic acid methyl ester,
4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzamide,
4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-N-methyl-benzamide,
{4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-phenyl}-methanol,
7-(4-Aminomethyl-phenyl)-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(4-dimethylaminomethyl-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
N-{4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzyl}-acetamide,
{4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzyl}-carbamic acid methyl ester,
1-{4-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzyl}-3-methyl-urea,
5-(3-Benzyloxy-phenyl)-7-(4-dimethylaminomethyl-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
7-(4-Azetidin-1-ylmethyl-phenyl)-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(4-pyrrolidin-1-ylmethyl-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(4-piperidin-1-ylmethyl-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzoic acid methyl ester,
3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzamide,
3-[4-Amino -5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-N-methyl-benzamide,
{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-phenyl}-methanol,
7-(3-Aminomethyl-phenyl)-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
N-{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzyl}-acetamide,
{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzyl}-carbamic acid methyl ester,
1-{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzyl}-3-methyl-urea,
N-{3-[4-Amino-5-(3-benzyloxy-phenyl)-imidazo[5,1-f][1,2,4]triazin-7-yl]-benzyl}-methanesulfonamide,
5-(3-Benzyloxy-phenyl)-7-(3-dimethylaminomethyl-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3 -Benzyloxy-phenyl)-7-(3-diethylaminomethyl-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
7-(3-Azetidin-1-ylmethyl-phenyl)-5-(3-benzyloxy-phenyl)-imidazo [5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(3-pyrrolidin-1-ylmethyl-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(3-piperidin-1-ylmethyl-phenyl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-pyridin-4-yl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-oxazol-2-yl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-thiophen-3-yl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-thiophen-2-yl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-thiazol-5-yl-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-thiazol-2-yl-imidazo [5,1-f][1,2,4]triazin-4-ylamine,
5-(3-Benzyloxy-phenyl)-7-(1H-imidazol-2-yl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine, or 5-(3-Benzyloxy-phenyl)-7-(1H-imidazol-4-yl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine,
or a pharmaceutically acceptable salt thereof.

91 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/185,599Filed 20 Jul 2005 · us provisional application
Priority: 20 Jul 2004
Published: US 2006/0019957 A126 Jan 2006
Granted: 22 Jun 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification24 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 5/14
Drugs for disorders of the endocrine system: of the thyroid hormones, e.g. T3, T4

Family

Application60/589,514Us provisional application · filed 20 Jul 2004
US 2006/0019957 A1Pre-grant publication · published 26 Jan 2006
US 7,741,324 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Citations

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Abstract

A compound represented by Formula I:

or a pharmaceuticaly acceptable salt thereof, wherein:
Q1 is phenyl substituted by —(X1)0-1—(Y1)0-1—R4 wherein X1 is 3-(O)—, 4-(O)—, 3-(NH)—, or 4-(NH)—;
and Y1 is —CH2— or —(SO2)—;
R4 is C0-10alkyl, C2-10alkenyl, C2-10alkynyl, aryl, heteroaryl, cycloC3-10alkyl, heterocyclyl, cycloC3-10alkenyl, or heterocycloalkenyl, any of which is optionaly substituted by one or more independent G41 substituents;
R1 is C0-10alkyl, cycloC3-10alkyl, bicycloC5-10alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, or heterobicycloC5-10alkyl, any of which is optionaly substituted by one or more independent G1l substituents;
each G11 is independently —OR21, —NR21R31, —CO2R21, —C(O)R21, —CONR21R31, —NR21C(═O)R31, —NR21C(═O)OR31, —NR21C(═O)NR31R21a, —NR21S(O)j3R31, —OC(═O)OR21, —OC(═O)NR21R31, C0-10alkyl, cycloC3-8alkyl, cycloC3-8alkenyl, heterocyclyl-C0-10alkyl, or heterocyclyl-C2-10alkenyl, any of which is optionaly substituted with one or more independent halo, oxo, —CF3, —OCF3, —OR2221, —NR2221R3331(R2221a)j3a, —C(O)R2221, —CO2R2221, —CONR2221R3331, —NO2, —CN, —S(O)j3aR2221, —SO2NR2221R3331, —NR2221C(═O)R3331, —NR2221C(═O)OR3331, —NR2221C(═O)NR3331R2221a, —NR2221S(O)j3aR3331, —C(═S)OR2221, —C(═O)SR2221, —NR2221C(═NR3331)NR2221aR3331a, —NR2221C(═NR3331)OR2221a, —NR2221C(═NR3331)SR2221a, —OC(═O )OR2221, —OC(═O )NR2221R3331, —OC(═O )SR2221, —SC(═O )OR2221, or —SC(═O )NR2221R3331;
each G41 is independently halo, oxo, —CF3, —OCF3, —OR2, —NR2R3(R2a)j1, —C(O)R2, —CO2R2, —CONR2R3, —NO2, —CN, —S(O)j1R2, —SO2NR2R3, —NR2C(═O)R3, —NR2C(═O)O R3, —NR2C(═O )NR3R2a, —NR2S(O)j1R3, —C(═S)O R2, —C(═O )SR2, —NR2C(═NR3)NR2aR3a, —NR2C(═NR3)OR2a, —NR2C(═NR3)SR2a, —OC(═O)O R2, —OC(═O)NR2R3, —OC(═O )SR2, —SC(═O)OR2, —SC(═O)NR2R3, C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, or heterocyclyl-C2-10alkynyl, any of which is optionaly substituted with one or more independent halo, oxo, —CF3, —OCF3, —OR222, —NR222R333(R222a)j1a, —C(O)R222, —CO2R222, —CONR222R333, —NO2, —CN, —S(O)j1aR222, —SO2NR222R333, —NR222C(═O)R333, —NR222C(═O)OR333, —NR222C(═O)NR333R222a, —NR222S(O)j1aR333, —C(═S)OR222, —C(═)SR222, —NR222C(═NR333)NR222aR333a, —NR222C(═NR333)OR222a, —NR222C(═C NR333)SR222a, —OC(═O )OR222, —OC(═O)NR222R333, —OC(═O)SR222, —SC(═O)OR222, or —SC(═O)NR222R333 substituents;
or G41 can be independently aryl-C0-10alkyl, aryl-C2-10alkenyl, aryl-C2-10alkynyl, hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl- C2-10alkynyl, any of which is optionaly substituted with one or more independent halo, —CF3, —OCF3, —OR222, —NR222R333(R222a)j2a, —C(O)R222, —CO2R222, —CONR222R333, —NO2, —CN, —S(O)j2aR222, —SO2NR222R333, —NR222C(═O )R333, —NR222C(═O)OR333, —NR222C(═O)NR333R222a, —NR222S(O)j2aR333, —C(═S)OR222, —C(═O )SR222,—NR222C(═NR333)NR222aR333a, —NR222C(═NR333)OR222a, —NR222C(═NR333)SR222a, —OC(═O)OR222, —OC(═O )NR222R333, —OC(═O)SR222, —SC(═O)OR222, or —SC(═O)NR222R333 substituents;
R2, R2a, R3, R3a, R222, R222a, R333, R333a, R21, R21a, R31, R2221, R2221a, R3331, and R3331a are each independently C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10alkynyl, aryl-C0-10alkyl, aryl-C2-10alkenyl, aryl- C2-10alkynyl, hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl-C2-10alkynyl, any of which is optionaly substituted by one or more independent G13 substituents;
or in the case of —NR2R3(R2a)j1or —NR21R31(R21a)j3 or —NR222R333(R222a)j1a or —NR222R333(R222a)j2a or —NR2221R3331(R2221a)j3a R2 and R3, or R21and R31, or R222 and R333, or R3331, or R2221and R3331, respectfuly, are optionaly taken together with the nitrogen atom to which they are attached to form a 3-10 membered saturated or unsaturated ring, wherein said ring is optionaly substituted by one or more independent G14 substituents and wherein said ring optionaly includes one or more independent heteroatoms other than the nitrogen to which R2 and R3, or R222 and R333, or R222 and R3331, are attached;
G13 and G14 are each independently a C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10alkynyl, aryl-C0-10alkyl, aryl-C2-10alkenyl, aryl-C2-10alkynyl, hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl-C2-10alkynyl, any of which is optionaly substituted with one or more independent halo, —CF3, —OCF3, —OR77, —NR77R87, —C(O)R77, —CO2R77, —CONR77R87, —NO2, —CN, —S(O),j5aR77, —SO2NR77R87, —NR77C(═O)R87, —NR77C(═O)OR87, —NR77C(═O)NR87R77a, —NR77S(O),j5aR87, —C(═S)OR77, —C(═O)SR77, —NR77C(═NR87)NR77aR87a, —NR77C(═NR87)OR77a, —NR77C(═NR87)SR77a, —OC(═O )OR77, —OC(═O)NR77R87, —OC(═O )SR77, —SC(═O)OR77, —P(O)OR77OR87, or —SC(═O)NR77R87 substituents;
R41, R51, R77, R77a, R87, R87a, R778, and R888 are each independently C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC2-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl- C2-10alkynyl, C1-10alkylcarbonyl, C2-10alkenylcarbonyl, C2-10alkynylcarbonyl, C1-10alkoxycarbonyl, C1-10alkoxycarbonylC1-10alkyl, monoC1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl, C1-10alkyl(aryl)aminocarbonyl, monohetarylaminocarbonyl, dihetarylaminocarbonyl, or alkylhetarylaminocarbonyl, any of which is optionaly substituted with one or more independent halo, cyano, hydroxy, nitro, C1-10alkoxy, —SO2N(C0-4alkyl)(C0-4alkyl), or —N(C0-4alkyl)(C0-4alkyl) substituents;
or R77, R77a, R87, and R87a are each independently aryl-C0-10alkyl, aryl-C2-10alkenyl aryl-C2-10alkynyl, hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, hetaryl-C2-10alkynyl, mono(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl, mono(aryl)aminoC1-6alkyl, di(aryl)aminoC1-6alkyl, monohetarylaminoalkyl, dihetarylaminoalkyl, or —N(C1-6alkyl)-C1-6alkyl-aryl, any of which is optionaly substituted with one or more independent halo, cyano, nitro, —O(C0-4alkyl), C1-10alkyl, C2-10alkenyl, C2-10alkynyl, haloC1-10alkyl, haloC2-10alkenyl, haloC2-10alkynyl, —COOH, C1-4alkoxycarbonyl, —CON(C0-4alkyl)(C0-4alkyl), —SO2N(C0-4alkyl)(C0-4alkyl), or —N(C0-4alkyl)(C0-4alkyl) substituents;
and
j1, j1a, j2a, j3, j3a, and j5a are each independently 0, 1, or 2.

12 more elements

Facts

Application

11/185,599Filed 20 Jul 2005 · us provisional application

Priority

20 Jul 2004

Published

US 2006/0019957 A126 Jan 2006

Granted

22 Jun 2010

Term ends

Not estimatedThe source records don’t support an estimate.

Classification24 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 5/14
Drugs for disorders of the endocrine system: of the thyroid hormones, e.g. T3, T4