RU2603637C2 - Замещённые пиразолопиримидины как активаторы глюкоцереброзидазы - Google Patents
Замещённые пиразолопиримидины как активаторы глюкоцереброзидазы Download PDFInfo
- Publication number
- RU2603637C2 RU2603637C2 RU2013126094/04A RU2013126094A RU2603637C2 RU 2603637 C2 RU2603637 C2 RU 2603637C2 RU 2013126094/04 A RU2013126094/04 A RU 2013126094/04A RU 2013126094 A RU2013126094 A RU 2013126094A RU 2603637 C2 RU2603637 C2 RU 2603637C2
- Authority
- RU
- Russia
- Prior art keywords
- carboxamide
- pyrimidine
- difluoromethyl
- dihydropyrazolo
- alkyl
- Prior art date
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- 108010017544 Glucosylceramidase Proteins 0.000 title claims abstract description 20
- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 title abstract description 10
- 102000004547 Glucosylceramidase Human genes 0.000 title description 14
- 239000012190 activator Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 104
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 22
- 208000015872 Gaucher disease Diseases 0.000 claims abstract description 19
- 208000024891 symptom Diseases 0.000 claims abstract description 10
- HVZPJBKUFRREQC-UHFFFAOYSA-N n-(4-ethynylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1=CC=C(C#C)C=C1 HVZPJBKUFRREQC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 101150028412 GBA gene Proteins 0.000 claims abstract description 7
- 102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 54
- -1 [1,3] dioxolyl Chemical group 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
- 125000001424 substituent group Chemical group 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical class 0.000 claims description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 24
- 125000004076 pyridyl group Chemical group 0.000 claims description 24
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 11
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 8
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 125000004639 dihydroindenyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 7
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 230000035772 mutation Effects 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
- 210000000265 leukocyte Anatomy 0.000 claims description 3
- YSSQOFFSTKULPW-UHFFFAOYSA-N n-(4-ethylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(CC)=CC=C1NC(=O)C1=C2N=C(C)C=C(C)N2N=C1 YSSQOFFSTKULPW-UHFFFAOYSA-N 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 4
- LPCQBTAOTIZGAE-UHFFFAOYSA-N 2h-pyrimidine-1-carboxamide Chemical compound NC(=O)N1CN=CC=C1 LPCQBTAOTIZGAE-UHFFFAOYSA-N 0.000 claims 3
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims 2
- KMOYDBZAUGGJNC-UHFFFAOYSA-N 7-(difluoromethyl)-n-(4-ethylphenyl)-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(CC)=CC=C1NC(=O)C1=C2N=C(C)C=C(C(F)F)N2N=C1 KMOYDBZAUGGJNC-UHFFFAOYSA-N 0.000 claims 2
- YHAVWNXZFBVYOJ-UHFFFAOYSA-N chembl1725455 Chemical compound C1=NN2C(C(F)F)=CC(=C3CC3)NC2=C1C(=O)NC1=CC=CC=C1SC1=CC=CC=C1 YHAVWNXZFBVYOJ-UHFFFAOYSA-N 0.000 claims 2
- NBVXSTLIUNQXBT-UHFFFAOYSA-N chembl3185251 Chemical compound CCOC1=CC=CC=C1NC(=O)C1=C(NC(=C)C=C2C(F)F)N2N=C1 NBVXSTLIUNQXBT-UHFFFAOYSA-N 0.000 claims 2
- UYRSGEMAVXKNAN-UHFFFAOYSA-N n-(3,4-dichlorophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1=CC=C(Cl)C(Cl)=C1 UYRSGEMAVXKNAN-UHFFFAOYSA-N 0.000 claims 2
- MCQYBGOYJAACFA-UHFFFAOYSA-N n-(4-tert-butylcyclohexyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1CCC(C(C)(C)C)CC1 MCQYBGOYJAACFA-UHFFFAOYSA-N 0.000 claims 2
- IVHLMTIZKQNVGP-UHFFFAOYSA-N n-(4-tert-butylcyclohexyl)-7-methyl-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C)=CC(C=3C=CC=CC=3)=NC2=C1C(=O)NC1CCC(C(C)(C)C)CC1 IVHLMTIZKQNVGP-UHFFFAOYSA-N 0.000 claims 2
- ZRJZMBZYIIHIKP-UHFFFAOYSA-N (5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=C2N=C(C)C=C(C)N2N=C1 ZRJZMBZYIIHIKP-UHFFFAOYSA-N 0.000 claims 1
- KLFXDMIVOKQLJQ-UHFFFAOYSA-N (5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-[4-(4-nitrophenyl)piperazin-1-yl]methanone Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)N(CC1)CCN1C1=CC=C([N+]([O-])=O)C=C1 KLFXDMIVOKQLJQ-UHFFFAOYSA-N 0.000 claims 1
- HQECLAJCHXWXHB-UHFFFAOYSA-N (5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-pyrrolidin-1-ylmethanone Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)N1CCCC1 HQECLAJCHXWXHB-UHFFFAOYSA-N 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- JMBFLTLAOSJEEW-UHFFFAOYSA-N 5,7-dimethyl-N-(3,4,5-trimethoxyphenyl)-3-pyrazolo[1,5-a]pyrimidinecarboxamide Chemical compound COC1=C(OC)C(OC)=CC(NC(=O)C2=C3N=C(C)C=C(C)N3N=C2)=C1 JMBFLTLAOSJEEW-UHFFFAOYSA-N 0.000 claims 1
- CGRNXIVXFQQADA-UHFFFAOYSA-N 5,7-dimethyl-n-(2-methylphenyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1=CC=CC=C1C CGRNXIVXFQQADA-UHFFFAOYSA-N 0.000 claims 1
- NICJTSHRYBTHAS-UHFFFAOYSA-N 5,7-dimethyl-n-(2-methylpropyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound CC1=CC(C)=NC2=C(C(=O)NCC(C)C)C=NN21 NICJTSHRYBTHAS-UHFFFAOYSA-N 0.000 claims 1
- YZZVXMLMYKWHNE-UHFFFAOYSA-N 5,7-dimethyl-n-(4-methylphenyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(C)=CC=C1NC(=O)C1=C2N=C(C)C=C(C)N2N=C1 YZZVXMLMYKWHNE-UHFFFAOYSA-N 0.000 claims 1
- ONGSAYSLHZBWEP-UHFFFAOYSA-N 5,7-dimethyl-n-[3-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1=CC=CC(C(F)(F)F)=C1 ONGSAYSLHZBWEP-UHFFFAOYSA-N 0.000 claims 1
- YBKYTNNBXFZNFF-UHFFFAOYSA-N 5,7-dimethyl-n-[4-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1=CC=C(C(F)(F)F)C=C1 YBKYTNNBXFZNFF-UHFFFAOYSA-N 0.000 claims 1
- XCIDHWANBYVQSB-UHFFFAOYSA-N 5,7-dimethyl-n-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1=CC=CC=C1 XCIDHWANBYVQSB-UHFFFAOYSA-N 0.000 claims 1
- HMIGLJHJZOAEQL-UHFFFAOYSA-N 5,7-dimethyl-n-propan-2-ylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound CC1=CC(C)=NC2=C(C(=O)NC(C)C)C=NN21 HMIGLJHJZOAEQL-UHFFFAOYSA-N 0.000 claims 1
- OPYMGGPOPIVVNR-UHFFFAOYSA-N 5-cyclopropylidene-7-(difluoromethyl)-N-(1-methylpiperidin-4-yl)-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1CN(C)CCC1NC(=O)C1=C(NC(C=C2C(F)F)=C3CC3)N2N=C1 OPYMGGPOPIVVNR-UHFFFAOYSA-N 0.000 claims 1
- CYEFRDZGYTWHFV-UHFFFAOYSA-N 5-cyclopropylidene-7-(difluoromethyl)-N-(3,4-difluorophenyl)-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C3CC3)NC2=C1C(=O)NC1=CC=C(F)C(F)=C1 CYEFRDZGYTWHFV-UHFFFAOYSA-N 0.000 claims 1
- GTZRFXVCWJKLEH-UHFFFAOYSA-N 5-cyclopropylidene-7-(difluoromethyl)-N-(6-methylpyridin-2-yl)-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound CC1=CC=CC(NC(=O)C2=C3N(C(=CC(N3)=C3CC3)C(F)F)N=C2)=N1 GTZRFXVCWJKLEH-UHFFFAOYSA-N 0.000 claims 1
- GZJZTGQDRYURCA-UHFFFAOYSA-N 5-cyclopropylidene-7-(difluoromethyl)-N-[(1-methylpyrazol-4-yl)methyl]-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN(C)C=C1CNC(=O)C1=C(NC(C=C2C(F)F)=C3CC3)N2N=C1 GZJZTGQDRYURCA-UHFFFAOYSA-N 0.000 claims 1
- XFZIBFQRHNQJHW-UHFFFAOYSA-N 5-cyclopropylidene-7-(difluoromethyl)-N-pyridin-3-yl-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C3CC3)NC2=C1C(=O)NC1=CC=CN=C1 XFZIBFQRHNQJHW-UHFFFAOYSA-N 0.000 claims 1
- PFBZJDASYDABLN-UHFFFAOYSA-N 5-cyclopropylidene-N-(3,5-dichlorophenyl)-7-(difluoromethyl)-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C3CC3)NC2=C1C(=O)NC1=CC(Cl)=CC(Cl)=C1 PFBZJDASYDABLN-UHFFFAOYSA-N 0.000 claims 1
- MUFXADBLCQQICZ-UHFFFAOYSA-N 5-methyl-n-(4-methylphenyl)-7-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(C)=CC=C1NC(=O)C1=C2N=C(C)C=C(C=3C=CC=CC=3)N2N=C1 MUFXADBLCQQICZ-UHFFFAOYSA-N 0.000 claims 1
- SVBPNHUWOFJWEG-UHFFFAOYSA-N 5-methyl-n-[4-(trifluoromethyl)phenyl]-6,7,8,9-tetrahydropyrazolo[1,5-a]quinazoline-3-carboxamide Chemical compound C1=NN2C=3CCCCC=3C(C)=NC2=C1C(=O)NC1=CC=C(C(F)(F)F)C=C1 SVBPNHUWOFJWEG-UHFFFAOYSA-N 0.000 claims 1
- YDKKMPMIQSIIKC-UHFFFAOYSA-N 7-(difluoromethyl)-5-methyl-n-(4-methylphenyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(C)=CC=C1NC(=O)C1=C2N=C(C)C=C(C(F)F)N2N=C1 YDKKMPMIQSIIKC-UHFFFAOYSA-N 0.000 claims 1
- VCRFPNNYMJNLSQ-UHFFFAOYSA-N 7-(difluoromethyl)-5-methyl-n-[4-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C(F)F)N2N=CC=1C(=O)NC1=CC=C(C(F)(F)F)C=C1 VCRFPNNYMJNLSQ-UHFFFAOYSA-N 0.000 claims 1
- YBSJLAJXNRBCFV-UHFFFAOYSA-N 7-(difluoromethyl)-5-methylidene-N-[[2-(trifluoromethyl)phenyl]methyl]-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C)NC2=C1C(=O)NCC1=CC=CC=C1C(F)(F)F YBSJLAJXNRBCFV-UHFFFAOYSA-N 0.000 claims 1
- GYTXCTZGTSUBPR-UHFFFAOYSA-N 7-(difluoromethyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]-5-methylidene-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CCNC(=O)C1=C(NC(=C)C=C2C(F)F)N2N=C1 GYTXCTZGTSUBPR-UHFFFAOYSA-N 0.000 claims 1
- WICPNVMYTPNMIV-UHFFFAOYSA-N 7-(difluoromethyl)-n-(4-ethynylphenyl)-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C(F)F)N2N=CC=1C(=O)NC1=CC=C(C#C)C=C1 WICPNVMYTPNMIV-UHFFFAOYSA-N 0.000 claims 1
- XUGXXWWPSTYHED-UHFFFAOYSA-N 7-(difluoromethyl)-n-[1-[(4-fluorophenyl)methyl]pyrazol-4-yl]-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(C=3C=CC=CC=3)=NC2=C1C(=O)NC(=C1)C=NN1CC1=CC=C(F)C=C1 XUGXXWWPSTYHED-UHFFFAOYSA-N 0.000 claims 1
- VCRLHFWEGPKVQW-UHFFFAOYSA-N N,N-dicyclohexyl-5-cyclopropylidene-7-(difluoromethyl)-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C3CC3)NC2=C1C(=O)N(C1CCCCC1)C1CCCCC1 VCRLHFWEGPKVQW-UHFFFAOYSA-N 0.000 claims 1
- FYMHBWNKWMMBPY-UHFFFAOYSA-N N-(2,3-dihydro-1,4-benzodioxin-6-yl)-5,7-dimethyl-3-pyrazolo[1,5-a]pyrimidinecarboxamide Chemical compound O1CCOC2=CC(NC(=O)C=3C=NN4C(C)=CC(=NC4=3)C)=CC=C21 FYMHBWNKWMMBPY-UHFFFAOYSA-N 0.000 claims 1
- IJHKKHPENYDANX-UHFFFAOYSA-N N-(2,3-dihydro-1H-inden-5-yl)-5,7-dimethyl-3-pyrazolo[1,5-a]pyrimidinecarboxamide Chemical compound C1=C2CCCC2=CC(NC(=O)C=2C=NN3C(C)=CC(=NC3=2)C)=C1 IJHKKHPENYDANX-UHFFFAOYSA-N 0.000 claims 1
- KDXQSDAPHUEXSJ-UHFFFAOYSA-N N-(3-acetylphenyl)-5,7-dimethyl-3-pyrazolo[1,5-a]pyrimidinecarboxamide Chemical compound CC(=O)C1=CC=CC(NC(=O)C2=C3N=C(C)C=C(C)N3N=C2)=C1 KDXQSDAPHUEXSJ-UHFFFAOYSA-N 0.000 claims 1
- OEPHUHZIEWQNMV-UHFFFAOYSA-N N-(4-bromo-2-chlorophenyl)-5-cyclopropylidene-7-(difluoromethyl)-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C3CC3)NC2=C1C(=O)NC1=CC=C(Br)C=C1Cl OEPHUHZIEWQNMV-UHFFFAOYSA-N 0.000 claims 1
- YLOVOAWHCHJWRE-UHFFFAOYSA-N N-(4-bromophenyl)-5-cyclopropylidene-7-(difluoromethyl)-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C3CC3)NC2=C1C(=O)NC1=CC=C(Br)C=C1 YLOVOAWHCHJWRE-UHFFFAOYSA-N 0.000 claims 1
- GGBNAHMOTCFJHS-UHFFFAOYSA-N N-(5-bromopyridin-2-yl)-5-cyclopropylidene-7-(difluoromethyl)-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C3CC3)NC2=C1C(=O)NC1=CC=C(Br)C=N1 GGBNAHMOTCFJHS-UHFFFAOYSA-N 0.000 claims 1
- XLUAAOIBRIUDQP-UHFFFAOYSA-N N-[(2-chlorophenyl)methyl]-7-(difluoromethyl)-5-methylidene-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C)NC2=C1C(=O)NCC1=CC=CC=C1Cl XLUAAOIBRIUDQP-UHFFFAOYSA-N 0.000 claims 1
- ZFIIFXLGSQPYGE-UHFFFAOYSA-N N-[(4-chlorophenyl)methyl]-7-(difluoromethyl)-5-methylidene-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C)NC2=C1C(=O)NCC1=CC=C(Cl)C=C1 ZFIIFXLGSQPYGE-UHFFFAOYSA-N 0.000 claims 1
- LTMDNLJNRQSOEA-UHFFFAOYSA-N N-[2-(2-chlorophenyl)ethyl]-7-(difluoromethyl)-5-methylidene-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=NN2C(C(F)F)=CC(=C)NC2=C1C(=O)NCCC1=CC=CC=C1Cl LTMDNLJNRQSOEA-UHFFFAOYSA-N 0.000 claims 1
- PWYSFEDEWYZHQH-UHFFFAOYSA-N [7-(difluoromethyl)-5-methylidene-4H-pyrazolo[1,5-a]pyrimidin-3-yl]-(4-pyridin-2-ylpiperazin-1-yl)methanone Chemical compound C1=NN2C(C(F)F)=CC(=C)NC2=C1C(=O)N(CC1)CCN1C1=CC=CC=N1 PWYSFEDEWYZHQH-UHFFFAOYSA-N 0.000 claims 1
- XMBVLXDWUPESNP-UHFFFAOYSA-N [7-(difluoromethyl)-5-methylidene-4H-pyrazolo[1,5-a]pyrimidin-3-yl]-piperidin-1-ylmethanone Chemical compound C1=NN2C(C(F)F)=CC(=C)NC2=C1C(=O)N1CCCCC1 XMBVLXDWUPESNP-UHFFFAOYSA-N 0.000 claims 1
- 125000005011 alkyl ether group Chemical group 0.000 claims 1
- HTBKKXHYVBAOLT-UHFFFAOYSA-N chembl1700435 Chemical compound C1=CC(C(C)CC)=CC=C1NC(=O)C1=C(NC(=C)C=C2C(F)F)N2N=C1 HTBKKXHYVBAOLT-UHFFFAOYSA-N 0.000 claims 1
- BLWPNCPHSRWMOK-UHFFFAOYSA-N chembl1714232 Chemical compound N1C2=C(C(=O)NC=3C=C4CCCC4=CC=3)C=NN2C(C(F)F)=CC1=C1CC1 BLWPNCPHSRWMOK-UHFFFAOYSA-N 0.000 claims 1
- XPZTZQKJXDOKPR-UHFFFAOYSA-N chembl1716885 Chemical compound C1=NN2C(C(F)(F)F)=CC(=C3CC3)NC2=C1C(=O)NC1=CC=CC=C1SC1=CC=CC=C1 XPZTZQKJXDOKPR-UHFFFAOYSA-N 0.000 claims 1
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| US42094610P | 2010-12-08 | 2010-12-08 | |
| US61/420,946 | 2010-12-08 | ||
| PCT/US2011/063928 WO2012078855A1 (en) | 2010-12-08 | 2011-12-08 | Substituted pyrazolopyrimidines as glucocerebrosidase activators |
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| RU2013126094A RU2013126094A (ru) | 2015-01-20 |
| RU2603637C2 true RU2603637C2 (ru) | 2016-11-27 |
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| MX (2) | MX354506B (enExample) |
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| PT (2) | PT3366688T (enExample) |
| RS (1) | RS63320B1 (enExample) |
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| SI (2) | SI2649075T1 (enExample) |
| TR (1) | TR201810523T4 (enExample) |
| WO (1) | WO2012078855A1 (enExample) |
| ZA (1) | ZA201304215B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2809824C1 (ru) * | 2023-09-08 | 2023-12-19 | Федеральное государственное бюджетное учреждение "Петербургский институт ядерной физики им. Б.П. Константинова Национального исследовательского центра "Курчатовский институт" (НИЦ "Курчатовский институт" - ПИЯФ) | Аллостерический фармакологический шаперон, восстанавливающий функцию глюкоцереброзидазы |
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| ES2681218T3 (es) | 2010-12-08 | 2018-09-12 | The U.S.A. As Represented By The Secretary, Department Of Health And Human Services | Pirazolopirimidinas sustituidas como activadoras de la glucocerebrosidasa |
| EP2723746A1 (en) | 2011-06-22 | 2014-04-30 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| CA2840224C (en) * | 2011-06-22 | 2019-08-13 | The General Hospital Corporation | Treatment of proteinopathies |
| AU2012272898A1 (en) | 2011-06-24 | 2013-04-11 | Amgen Inc. | TRPM8 antagonists and their use in treatments |
| CA2839699A1 (en) | 2011-06-24 | 2012-12-27 | Amgen Inc. | Trpm8 antagonists and their use in treatments |
| CN104394869A (zh) * | 2011-10-20 | 2015-03-04 | 葛兰素史密斯克莱有限责任公司 | 用作沉默调节蛋白调节剂的取代的双环氮杂杂环化合物和类似物 |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US8952009B2 (en) | 2012-08-06 | 2015-02-10 | Amgen Inc. | Chroman derivatives as TRPM8 inhibitors |
| US9340546B2 (en) | 2012-12-07 | 2016-05-17 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| WO2014143242A1 (en) | 2013-03-15 | 2014-09-18 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| JP2016512239A (ja) | 2013-03-15 | 2016-04-25 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼの阻害剤として有用な化合物 |
| US9663519B2 (en) | 2013-03-15 | 2017-05-30 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| EA201690713A1 (ru) | 2013-10-04 | 2016-08-31 | Инфинити Фармасьютикалз, Инк. | Гетероциклические соединения и их применения |
| WO2015051241A1 (en) | 2013-10-04 | 2015-04-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| WO2015085132A1 (en) | 2013-12-06 | 2015-06-11 | Vertex Pharmaceuticals Incorporated | 2-amino-6-fluoro-n-[5-fluoro-pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-3-carboxamide compound useful as atr kinase inhibitor, its preparation, different solid forms and radiolabelled derivatives thereof |
| EP4066834A1 (en) | 2014-03-19 | 2022-10-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders |
| CN107074863B (zh) | 2014-06-05 | 2019-12-03 | 沃泰克斯药物股份有限公司 | Atr激酶抑制剂的制备方法及其不同的固体形式 |
| CA2950780C (en) | 2014-06-17 | 2023-05-16 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of chk1 and atr inhibitors |
| US9708348B2 (en) | 2014-10-03 | 2017-07-18 | Infinity Pharmaceuticals, Inc. | Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof |
| CN107108638A (zh) | 2014-11-03 | 2017-08-29 | 拜耳制药股份公司 | 哌啶基吡唑并嘧啶酮及其用途 |
| WO2016073891A1 (en) | 2014-11-06 | 2016-05-12 | Lysosomal Therapeutics Inc. | Substituted pyrrolo[1,2-a]pyrimidines and their use in the treatment of medical disorders |
| SMT202400187T1 (it) | 2014-11-06 | 2024-07-09 | Bial R&D Investments S A | Pirazolo(1,5-a)pirimidine sostituite e loro utilizzo nel trattamento di disturbi medici |
| ES2958391T3 (es) | 2014-11-06 | 2024-02-08 | Bial R&D Invest S A | Imidazo[1,5-a]pirimidinas sustituidas y su uso en el tratamiento de trastornos médicos |
| WO2017004408A1 (en) | 2015-07-01 | 2017-01-05 | Northwestern University | Substituted 4-methyl-pyrrolo[1.2-a]pyrimidine-8-carboxamide compounds and uses thereof for modulating glucocerebrosidase activity |
| WO2017040879A1 (en) * | 2015-09-04 | 2017-03-09 | Lysosomal Therapeutics Inc. | Thiazolo(3,2-a) pyrimidinone and other heterobicyclic pyrimidinone compounds for use in medical therapy |
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