Pyrrolo [2,3-D] pyrimidine compounds
View Patent ↗A compound of the formula wherein R 1 , R 2 and R 3 are as defined above, which are inhibitors of the enzyme protein tyrosine kinases such as Janus Kinase 3 and as such are useful therapy as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases.
1. A compound of the formula
or the pharmaceutically acceptable salt thereof; wherein
R 1 is OR 9 , S(O) q R 9 , or a group of the formula
R 2 and R 3 are each independently of hydrogen, deuterium, amino, halo, hydoxy, nitro, carboxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkyl, or (C 1 -C 6 )alkoxy wherein the alkyl or alkoxy groups are optionally substittued by one to three groups selected from halo, hydroxy, carboxy, amino(C 1 -C 6 )alkylthio, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl) 2 amino, (C 5 -C 9 )heteroaryl, (C 2 -C 9 )heterocycloalkyl, (C 3 -C 9 )cycloalkyl or (C 6 -C 10 )aryl;
or R 2 and R 3 are each independently (C 7 -C 10 )cycloalkyl, (C 7 -C 10 )cycloalkoxy, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl) 2 amino, (C 6 -C 10 )arylamino, (C 1 -C 6 )alkylthio, (C 6 -C 10 )arylthio, (C 1 -C 6 )alkylsulfinyl, (C 6 -C 10 )arylsulfinyl, (C 1 -C 6 )alkylsulfonyl, (C 6 -C 10 )arylsulfonyl, (C 1 -C 6 )acyl, (C 1 -C 6 )alkoxy-CO—NH—, (C 1 -C 6 )alkylamino-CO—, (C 5 -C 9 )heteroaryl, (C 2 -C 9 )heterocycloalkyl or (C 6 -C 10 )aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-CO—NH—, (C 1 -C 6 )alkoxy-CO—NH—, (C 1 -C 6 )alkyl-CO—NH—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy-CO—NH—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy-CO—NH—(C 1 -C 6 )alkoxy, carboxy, carboxy(C 1 -C 6 )alkyl, carboxy(C 1 -C 6 )alkoxy, benzyloxycarbonyl(C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkoxy, (C 6 -C 10 )aryl, amino, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxycarbonylamino, (C 6 -C 10 )aryl(C 1 -C 6 )alkoxycarbonylamino, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl) 2 amino, (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )alkyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkyl, cyanoamino-CO—NH—, (C 1 -C 6 )alkylamino-CO—NH—, ((C 1 -C 6 )alkyl) 2 amino-CO—NH—, (C 6 -C 10 )arylamino-CO—NH—, (C 5 -C 9 )heteroarylamino-CO—NH—, (C 1 -C 6 )alkylamino-CO—NH—(C 1 -C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amino-CO—NH—(C 1 -C 6 )alkyl, (C 6 -C 10 )arylamino-CO—NH—(C 1 -C 6 )alkyl, (C 5 -C 9 )heteroarylamino-CO—NH—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfonyl, (C 1 -C 6 )alkylsulfonylamino, (C 1 -C 6 )alkylsulfonylamino(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfonyl, (C 6 -C 10 )arylsulfonylamino, (C 6 -C 10 )arylsulfonylamino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfonylamino, (C 1 -C 6 )alkylsulfonylamino(C 1 -C 6 )alkyl, (C 5 -C 9 )heteroaryl or (C 2 -C 9 )heterocycloalkyl;
R 4 is hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, or (C 2 -C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C 1 -C 4 )alkoxy, (C 1 -C 6 )acyloxy, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl) 2 amino, cyano, nitro, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl or (C 1 -C 6 )acylamino;
or R 4 is (C 7 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C 1 -C 6 )acyloxy, (C 1 -C 6 )acylamino, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl) 2 amino, cyano, cyano(C 1 -C 6 )alkyl, trifluoromethyl(C 1 -C 6 )alkyl, nitro, nitro(C 1 -C 6 )alkyl or (C 1 -C 6 )acylamino;
R 5 is trifluoromethyl(C 1 -C 6 )alkyl, (C 1 -C 3 )alkyl(difluoromethylene)(C 1 -C 3 )alkyl, or (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five carboxy, cyano, amino, deuterium, hydroxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo, (C 1 -C 6 )acyl, (C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy-CO—NH, (C 1 -C 6 )alkylamino-CO—, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl, nitro, cyano(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, nitro(C 1 -C 6 )alkyl, trifluoromethyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamino, (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino, amino(C 1 -C 6 )acyl, amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl, ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl, R 15 R 16 N—CO—O—, R 15 R 16 N—CO—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-S(O) m , R 15 R 16 NS(O) m , R 15 R 16 NS(O) m (C 1 -C 6 )alkyl, R 15 S(O) m R 16 N, or R 15 S(O) m R 16 N(C 1 -C 6 )alkyl;
R 5 is (C 3 -C 10 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl, (C 2 -C 6 )alkoxy(C 1 -C 6 )alkyl, piperazinyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthio(C 1 -C 6 )alkyl, (C 6 -C 10 )arylthio(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfinyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfinyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfonyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfonyl(C 1 -C 6 )alkyl, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amino, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, or (C 2 -C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by one to five cyano, nitro, halo, deuterium, hydroxy, carboxy, (C 1 -C 6 )acylamino, (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino, amino(C 1 -C 6 )acyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl or ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl;
or R 5 is R 13 CO(C 1 -C 6 )alkyl, R 13 CO(C 7 -C 10 )cycloalkyl, R 14 , R 14 (C 1 -C 6 )alkyl or R 14 (C 7 -C 10 )cycloalkyl;
or R 5 is a group of the formula
or R 5 is a group of the formula
R 6 is hydrogen, (C 1 -C 6 )alkyl, trifluoromethyl, trifluoromethyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl(difluoromethylene), (C 1 -C 3 )alkyl(difluoromethylene)(C 1 -C 3 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )acyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl, ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl, (C 6 -C 10 )aryl, (C 5 -C 9 )heteroaryl, (C 6 -C 10 )aryl(C 1 -C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl(C 3 -C 6 )alkyl, hydroxy(C 2 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 2 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 2 -C 6 )alkyl, piperazinyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthio(C 1 -C 6 )alkyl, (C 6 -C 10 )arylthio(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfinyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfinyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfonyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfonyl(C 1 -C 6 )alkyl, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )alkyl, R 13 CO(C 1 -C 6 )alkyl or R 14 (C 2 -C 6 )alkyl;
R 7 and R 8 are each independently hydrogen, (C 1 -C 6 )alkyl, amino, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl)amino, (C 1 -C 6 )acylamino, (C 1 -C 6 )acyl(C 1 -C 6 )alkylamino, carboxy, (C 1 -C 6 )alkoxyacyl, (C 1 -C 6 )alkylaminoacyl, ((C 1 -C 6 )alkyl) 2 aminoacyl, aminoacyl, trifluoromethyl, trifluoromethyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl(difluoromethylene), (C 1 -C 3 )alkyl(difluoromethylene)(C 1 -C 3 )alkyl, (C 6 -C 10 )aryl, (C 5 -C 9 )heteroaryl, (C 6 -C 10 )aryl(C 1 -C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, piperazinyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl, piperidyl, (C 1 -C 6 )alkylpiperidyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthio(C 1 -C 6 )alkyl, (C 6 -C 10 )arylthio(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfinyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfinyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfonyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfonyl(C 1 -C 6 )alkyl, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )alkyl, R 13 CO(C 1 -C 6 )alkyl, R 13 CO(C 3 -C 10 )cycloalkyl R 14 , R 14 (C 1 -C 6 )alkyl or R 14 (C 3 -C 10 )cycloalkyl; or a group of the formula
R 9 is trifluoromethyl(C 1 -C 6 )alkyl, (C 1 -C 3 )alkyl(difluoromethylene)(C 1 -C 3 )alkyl, or (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five carboxy, cyano, amino, hydroxy, (C 1 -C 6 )alkoxy, halo, (C 1 -C 6 )alkyl S(O) m , R 15 R 16 NS(O) m , (C 1 -C 6 )acyl, (C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy-CO—NH, (C 1 -C 6 )alkylamino-CO—, R 15 R 16 N—CO—O—, R 15 R 16 N—CO—(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkylamino, amino(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl, nitro, cyano(C 1 -C 6 )alkyl, nitro(C 1 -C 6 )alkyl, trifluoromethyl, trifluoromethyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamino, (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino, amino(C 1 -C 6 )acyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl, or ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl;
or R 9 is (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 10 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl, (C 2 -C 6 )alkoxy(C 1 -C 6 )alkyl, piperazinyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthio(C 1 -C 6 )alkyl, (C 6 -C 10 )arylthio(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfinyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfinyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfonyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfonyl(C 1 -C 6 )alkyl, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amino, or (C 1 -C 6 )alkyl wherein the alkyl group is optionally substituted by one to five cyano, nitro, hydroxy, carboxy, (C 1 -C 6 )acylamino, (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino, amino(C 1 -C 6 )acyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl or ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl;
or R 9 is R 13 CO(C 1 -C 6 )alkyl, R 13 CO(C 7 -C 10 )cycloalkyl, R 14 , R 14 (C 1 -C 6 )alkyl or R 14 (C 7 -C 10 )cycloalkyl;
or R 9 is a group of the formula
R 13 is R 20 O or R 20 R 21 N;
R 14 is (C 2 -C 9 )heterocycloalkyl, (C 1 -C 6 )acylpiperazino, (C 6 -C 10 )arylpiperazino, (C 5 -C 9 )heteroarylpiperazino, (C 1 -C 6 )alkylpiperazino, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpiperazino, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkylpiperazino, morpholino, thiomorpholino, piperidino, pyrrolidino, piperidyl, (C 1 -C 6 )alkylpiperidinyl, (C 6 -C 10 )arylpiperidyl, (C 5 -C 9 )heteroarylpiperidyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpiperidyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkylpiperidyl or (C 1 -C 6 )acylpiperidyl;
R 15 and R 16 are each independently hydrogen or (C 1 -C 6 )alkyl;
R 17 and R 18 are each independently hydrogen, (C 1 -C 6 )alkyl, piperidyl, (C 1 -C 6 )alkylpiperidyl, (C 6 -C 10 )arylpiperidyl, (C 5 -C 9 )heteroarylpiperidyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpiperidyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkylpiperidyl, (C 1 -C 6 )acylpiperidyl, (C 6 -C 10 )aryl, (C 5 -C 9 )heteroaryl, (C 6 -C 10 )aryl(C 1 -C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, R 22 (C 1 -C 6 )alkyl, (C 1 -C 5 )alkyl(CHR 22 )(C 1 -C 6 )alkyl; R 23 (C 1 -C 6 )alkyl, or (C 1 -C 5 )alkyl(CHR 23 )(C 1 -C 6 )alkyl;
R 20 and R 21 are each independently hydrogen, deuterium, (C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkyl or (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkyl;
R 22 is hydroxy, (C 1 -C 6 )acyloxy, (C 1 -C 6 )alkoxy, piperazino, (C 1 -C 6 )acylamino, (C 1 -C 6 )alkylthio, (C 6 -C 10 )arylthio, (C 1 -C 6 )alkylsulfinyl, (C 6 -C 10 )arylsulfinyl, (C 1 -C 6 )alkysulfoxyl, (C 6 -C 10 )arylsulfoxyl, amino, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl) 2 amino, (C 1 -C 6 )acylpiperazino, (C 1 -C 6 )alkylpiperazino, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpiperazino, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkylpiperazino, morpholino, thiomorpholino, piperidino or pyrrolidino;
R 23 is piperidyl, (C 1 -C 6 )alkylpiperidyl, (C 6 -C 10 )arylpiperidyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpiperidyl, (C 5 -C 9 )heteroarylpiperidyl or (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkylpiperidyl;
F, K, and P are each independently oxygen, S(O) d , NR 6 or CR 7 R 8 ;
Z is hydroxy, (C 1 -C 6 )alkoxy or NR 17 R 18 ;
d, m, q, w, and y are each independently is 0, 1 or 2;
g, h, and j are each independently 0 to 6;
p and x are each independently is 0, 1, 2 or 3;
with the proviso that when R 4 is hydrogen, unsubstituted (C 1 -C 6 )alkyl or unsubstituted (C 3 -C 10 )cycloalkyl, R 5 cannot be (C 6 -C 10 )aryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl or (C 5 -C 9 )hiteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl; and R 14 cannot be (C 2 -C 9 )heterocycloalkyl, morpholino, thiomorphlino, piperidino, pyrrolidino, piperidinyl or (C 1 -C 6 )alkylpiperidyl;
with the proviso that the sp 2 and sp carbons of alkenyl of alkynyl cannot be substituted by hydroxy or amino;
with the proviso that when R 4 is hydrogen, R 5 cannot be amino (C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl, or (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl;
with the proviso that both R 4 and R 5 cannot both be hydroxy (C 1 -C 6 )alkyl; and
with the proviso that the (C 3 -C 10 )cycloalkyl group of R 5 contains zero levels of unsaturation.
2. A compound according to claim 1 , wherein R 1 is NR 4 R 5 .
3. A compound according to claim 1 , wherein R 4 is hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by hydroxy, amino, trifluoromethyl, (C 1 -C 6 )acyloxy, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl) 2 amino or (C 1 -C 6 )acylamino; or R 4 is (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by hydroxy, trifluoromethyl or (C 1 -C 6 )acyloxy.
4. A compound according to claim 1 , wherein R 5 is (C 7 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five deuterium, hydroxy, halo, (C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )acyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl, ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl, (C 1 -C 6 )acylamino, (C 1 -C 6 )alkoxy-CO—NH, (C 1 -C 6 )alkylamino-CO—, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl, R 15 S(O) m R 16 N, or R 15 S(O) m R 16 N(C 1 -C 6 )alkyl.
5. A compound according to claim 1 , wherein R 2 and R 3 are each independently selected from the group consisting of hydrogen, halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 10 )cycloalkyl, (C 3 -C 10 )cycloalkoxy, (C 2 -C 9 )heterocycloalkyl, (C 5 -C 9 )heteroaryl or (C 6 -C 10 )aryl.