JP5852099B2 - ある種のアミノ−ピリミジン、その組成物、及びそれを用いるための方法 - Google Patents
ある種のアミノ−ピリミジン、その組成物、及びそれを用いるための方法 Download PDFInfo
- Publication number
- JP5852099B2 JP5852099B2 JP2013506329A JP2013506329A JP5852099B2 JP 5852099 B2 JP5852099 B2 JP 5852099B2 JP 2013506329 A JP2013506329 A JP 2013506329A JP 2013506329 A JP2013506329 A JP 2013506329A JP 5852099 B2 JP5852099 B2 JP 5852099B2
- Authority
- JP
- Japan
- Prior art keywords
- fluoro
- pyrimidin
- pyridyl
- amino
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title claims description 24
- 239000000203 mixture Substances 0.000 title description 84
- 150000005005 aminopyrimidines Chemical class 0.000 title description 2
- -1 fluoro-cyclobutyl Chemical group 0.000 claims description 323
- 150000001875 compounds Chemical class 0.000 claims description 288
- 125000000217 alkyl group Chemical group 0.000 claims description 189
- 125000001424 substituent group Chemical group 0.000 claims description 119
- 229910052736 halogen Inorganic materials 0.000 claims description 106
- 150000003839 salts Chemical class 0.000 claims description 102
- 150000002367 halogens Chemical class 0.000 claims description 101
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 87
- 229910052799 carbon Inorganic materials 0.000 claims description 85
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 77
- 125000003118 aryl group Chemical group 0.000 claims description 75
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 67
- 229910052739 hydrogen Inorganic materials 0.000 claims description 63
- 239000001257 hydrogen Substances 0.000 claims description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 60
- 201000010099 disease Diseases 0.000 claims description 52
- 125000001188 haloalkyl group Chemical group 0.000 claims description 50
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 48
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
- 239000003814 drug Substances 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 35
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 33
- 238000002360 preparation method Methods 0.000 claims description 33
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 28
- 208000035475 disorder Diseases 0.000 claims description 25
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 20
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 19
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims description 18
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 18
- 125000004076 pyridyl group Chemical group 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 208000002320 spinal muscular atrophy Diseases 0.000 claims description 14
- 206010049565 Muscle fatigue Diseases 0.000 claims description 13
- 206010028417 myasthenia gravis Diseases 0.000 claims description 13
- 125000002971 oxazolyl group Chemical group 0.000 claims description 11
- 230000027455 binding Effects 0.000 claims description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 9
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 125000001425 triazolyl group Chemical group 0.000 claims description 9
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 201000000585 muscular atrophy Diseases 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 7
- 206010028289 Muscle atrophy Diseases 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 208000018360 neuromuscular disease Diseases 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 4
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 4
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 238000001990 intravenous administration Methods 0.000 claims description 4
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 4
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 4
- 229960000581 salicylamide Drugs 0.000 claims description 4
- 230000001114 myogenic effect Effects 0.000 claims description 3
- 230000007170 pathology Effects 0.000 claims description 3
- GGNIKGLUPSHSBV-UHFFFAOYSA-N thiazole-5-carboxamide Chemical compound NC(=O)C1=CN=CS1 GGNIKGLUPSHSBV-UHFFFAOYSA-N 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 150000002222 fluorine compounds Chemical group 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 238000007912 intraperitoneal administration Methods 0.000 claims description 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 5
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims 4
- HFTYFPMQJYOUDV-UHFFFAOYSA-N 3-[2-[[1-(3-chloropyridin-2-yl)-3-fluorocyclobutyl]methylamino]pyrimidin-5-yl]-4-fluorobenzamide Chemical compound NC(=O)C1=CC=C(F)C(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)Cl)=NC=2)=C1 HFTYFPMQJYOUDV-UHFFFAOYSA-N 0.000 claims 2
- KGHBJWWSFKAZLS-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-4-hydroxy-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(O)C(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 KGHBJWWSFKAZLS-UHFFFAOYSA-N 0.000 claims 2
- VUIIOPSQIKJMMT-UHFFFAOYSA-N 4-fluoro-3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-2-hydroxybenzamide Chemical compound NC(=O)C1=CC=C(F)C(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1O VUIIOPSQIKJMMT-UHFFFAOYSA-N 0.000 claims 2
- 230000003796 beauty Effects 0.000 claims 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 2
- 230000020763 muscle atrophy Effects 0.000 claims 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- JFRNWAZVGXCUCN-UHFFFAOYSA-N 1-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-n-(2-hydroxyethyl)pyrazole-4-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1N1C=C(C(=O)NCCO)C=N1 JFRNWAZVGXCUCN-UHFFFAOYSA-N 0.000 claims 1
- MDNVZALGEFGGFH-UHFFFAOYSA-N 1-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]pyrazole-4-carbonitrile Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1N1C=C(C#N)C=N1 MDNVZALGEFGGFH-UHFFFAOYSA-N 0.000 claims 1
- RSYSEQDVNSWBPL-UHFFFAOYSA-N 1-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]pyrazole-4-carboxylic acid Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1N1C=C(C(O)=O)C=N1 RSYSEQDVNSWBPL-UHFFFAOYSA-N 0.000 claims 1
- XHHKYNGZADSJKL-UHFFFAOYSA-N 1-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CCC1 XHHKYNGZADSJKL-UHFFFAOYSA-N 0.000 claims 1
- MSQGDLQAXGPPIH-UHFFFAOYSA-N 1-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-methylpyrrole-3-carboxamide Chemical compound C1=C(C(=O)NC)C=CN1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 MSQGDLQAXGPPIH-UHFFFAOYSA-N 0.000 claims 1
- VCISOFXGBZISCJ-UHFFFAOYSA-N 1-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]pyrazole-4-carbonitrile Chemical compound C1C(F)CC1(C=1C(=CC=CN=1)F)CNC1=NC=C(N2N=CC(=C2)C#N)C=N1 VCISOFXGBZISCJ-UHFFFAOYSA-N 0.000 claims 1
- PZMZMOMAXUURFR-UHFFFAOYSA-N 1-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]pyrrole-3-carboxylic acid Chemical compound C1=C(C(=O)O)C=CN1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 PZMZMOMAXUURFR-UHFFFAOYSA-N 0.000 claims 1
- WCVIODUPLHVMFF-UHFFFAOYSA-N 1-amino-n-[[2-[2-[2-(3-fluoropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]cyclopropane-1-carboxamide Chemical compound N=1C=CC=C(F)C=1C(C)(C)NC(N=C1)=NC=C1C(S1)=NC=C1CNC(=O)C1(N)CC1 WCVIODUPLHVMFF-UHFFFAOYSA-N 0.000 claims 1
- ZVXKYWHJBYIYNI-UHFFFAOYSA-N 1h-pyrazole-4-carboxamide Chemical compound NC(=O)C=1C=NNC=1 ZVXKYWHJBYIYNI-UHFFFAOYSA-N 0.000 claims 1
- WBKYMOUZOCAHIF-UHFFFAOYSA-N 2-[1-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]pyrazol-4-yl]propan-2-ol Chemical compound C1=C(C(C)(O)C)C=NN1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1Cl WBKYMOUZOCAHIF-UHFFFAOYSA-N 0.000 claims 1
- WPFSWVCCVBXJSL-UHFFFAOYSA-N 2-[2-[(1-pyridin-2-ylcyclobutyl)methylamino]pyrimidin-5-yl]-1,3-thiazole-5-carbonitrile Chemical compound S1C(C#N)=CN=C1C(C=N1)=CN=C1NCC1(C=2N=CC=CC=2)CCC1 WPFSWVCCVBXJSL-UHFFFAOYSA-N 0.000 claims 1
- OGMRZLWFOOYSIM-UHFFFAOYSA-N 2-[2-[(1-pyridin-2-ylcyclobutyl)methylamino]pyrimidin-5-yl]-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)N)=CN=C1C(C=N1)=CN=C1NCC1(C=2N=CC=CC=2)CCC1 OGMRZLWFOOYSIM-UHFFFAOYSA-N 0.000 claims 1
- JKPWAVAKGKNGJJ-UHFFFAOYSA-N 2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-oxazole-4-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC(C(N)=O)=CO1 JKPWAVAKGKNGJJ-UHFFFAOYSA-N 0.000 claims 1
- AWSNPVBZSZBUIJ-UHFFFAOYSA-N 2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-oxazole-4-carboxylic acid Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC(C(O)=O)=CO1 AWSNPVBZSZBUIJ-UHFFFAOYSA-N 0.000 claims 1
- ANDQCHOEWVUFRE-UHFFFAOYSA-N 2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-oxazole-5-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC=C(C(N)=O)O1 ANDQCHOEWVUFRE-UHFFFAOYSA-N 0.000 claims 1
- XYBKWGDSAOCZII-UHFFFAOYSA-N 2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-oxazole-5-carboxylic acid Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC=C(C(O)=O)O1 XYBKWGDSAOCZII-UHFFFAOYSA-N 0.000 claims 1
- MOSZYASDTYCAIZ-UHFFFAOYSA-N 2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-4-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC(C(N)=O)=CS1 MOSZYASDTYCAIZ-UHFFFAOYSA-N 0.000 claims 1
- NJNDHODFICPWFF-UHFFFAOYSA-N 2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-4-carboxylic acid Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC(C(O)=O)=CS1 NJNDHODFICPWFF-UHFFFAOYSA-N 0.000 claims 1
- KTTWJUJOGIGYTE-UHFFFAOYSA-N 2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-5-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC=C(C(N)=O)S1 KTTWJUJOGIGYTE-UHFFFAOYSA-N 0.000 claims 1
- IJVPKAGLBHOBOH-UHFFFAOYSA-N 2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]pyridine-4-carbonitrile Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=CC(C#N)=CC=N1 IJVPKAGLBHOBOH-UHFFFAOYSA-N 0.000 claims 1
- IWOLQJULJSZQHN-UHFFFAOYSA-N 2-[2-[2-(3-fluoropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-4-carbonitrile Chemical compound N=1C=CC=C(F)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC(C#N)=CS1 IWOLQJULJSZQHN-UHFFFAOYSA-N 0.000 claims 1
- ZAXXIDVVVBJGMF-UHFFFAOYSA-N 2-[2-[2-(3-fluoropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-4-carboxamide Chemical compound N=1C=CC=C(F)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC(C(N)=O)=CS1 ZAXXIDVVVBJGMF-UHFFFAOYSA-N 0.000 claims 1
- PWEQIUBVHSJJRD-UHFFFAOYSA-N 2-[2-[2-(3-fluoropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-5-carbonitrile Chemical compound N=1C=CC=C(F)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC=C(C#N)S1 PWEQIUBVHSJJRD-UHFFFAOYSA-N 0.000 claims 1
- SPMBZQHLWNPDLX-UHFFFAOYSA-N 2-[2-[2-(3-fluoropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-5-carboxamide Chemical compound N=1C=CC=C(F)C=1C(C)(C)NC(N=C1)=NC=C1C1=NC=C(C(N)=O)S1 SPMBZQHLWNPDLX-UHFFFAOYSA-N 0.000 claims 1
- FQEPYBPQTONVOR-UHFFFAOYSA-N 2-[2-[2-(4-methoxypyrimidin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-5-carboxamide Chemical compound COC1=CC=NC(C(C)(C)NC=2N=CC(=CN=2)C=2SC(=CN=2)C(N)=O)=N1 FQEPYBPQTONVOR-UHFFFAOYSA-N 0.000 claims 1
- OITUJPXEQHXTQO-UHFFFAOYSA-N 2-[2-[2-[6-(difluoromethoxy)pyridin-2-yl]propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-5-carboxamide Chemical compound C=1C=CC(OC(F)F)=NC=1C(C)(C)NC(N=C1)=NC=C1C1=NC=C(C(N)=O)S1 OITUJPXEQHXTQO-UHFFFAOYSA-N 0.000 claims 1
- MVQYTMWRVRBCFJ-UHFFFAOYSA-N 2-[2-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]acetonitrile Chemical compound FC1=CC=CN=C1C1(CNC=2N=CC(=CN=2)C=2SC(CC#N)=CN=2)CCC1 MVQYTMWRVRBCFJ-UHFFFAOYSA-N 0.000 claims 1
- OVNIWMCKZKWXRL-UHFFFAOYSA-N 2-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-thiazole-4-carboxamide Chemical compound NC(=O)C1=CSC(C=2C=NC(NCC3(CCC3)C=3C(=CC=CN=3)F)=NC=2)=N1 OVNIWMCKZKWXRL-UHFFFAOYSA-N 0.000 claims 1
- DCAJCCDTXZHROW-UHFFFAOYSA-N 2-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC(C=2C=NC(NCC3(CCC3)C=3C(=CC=CN=3)F)=NC=2)=N1 DCAJCCDTXZHROW-UHFFFAOYSA-N 0.000 claims 1
- JEDWFYOSBMWFNN-UHFFFAOYSA-N 2-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-thiazole-5-carbonitrile Chemical compound FC1=CC=CN=C1C1(CNC=2N=CC(=CN=2)C=2SC(=CN=2)C#N)CCC1 JEDWFYOSBMWFNN-UHFFFAOYSA-N 0.000 claims 1
- VTTRAIDITYVAOB-UHFFFAOYSA-N 2-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)N)=CN=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CCC1 VTTRAIDITYVAOB-UHFFFAOYSA-N 0.000 claims 1
- ICVQYCRUKKEAIM-UHFFFAOYSA-N 2-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-methylpyridine-4-carboxamide Chemical compound CNC(=O)C1=CC=NC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 ICVQYCRUKKEAIM-UHFFFAOYSA-N 0.000 claims 1
- ZYYCQMVOCBTMLL-UHFFFAOYSA-N 2-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-methylpyrimidine-4-carboxamide Chemical compound CNC(=O)C1=CC=NC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=N1 ZYYCQMVOCBTMLL-UHFFFAOYSA-N 0.000 claims 1
- YWEIBBVCUULUAH-UHFFFAOYSA-N 2-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]pyridine-4-carbonitrile Chemical compound C1C(F)CC1(C=1C(=CC=CN=1)F)CNC1=NC=C(C=2N=CC=C(C=2)C#N)C=N1 YWEIBBVCUULUAH-UHFFFAOYSA-N 0.000 claims 1
- CLAQNGFILQRSDM-UHFFFAOYSA-N 2-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]pyrimidine-4-carbonitrile Chemical compound C1C(F)CC1(C=1C(=CC=CN=1)F)CNC1=NC=C(C=2N=C(C=CN=2)C#N)C=N1 CLAQNGFILQRSDM-UHFFFAOYSA-N 0.000 claims 1
- VBMKIFLBBUGGKR-UHFFFAOYSA-N 2-[4-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1H-pyrazol-5-yl]acetic acid Chemical compound ClC=1C(=NC=CC1)C(C)(C)NC1=NC=C(C=N1)C=1C(=NNC1)CC(=O)O VBMKIFLBBUGGKR-UHFFFAOYSA-N 0.000 claims 1
- KHYUTJNOEOZTHD-UHFFFAOYSA-N 2-[4-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1H-pyrazol-5-yl]ethanol Chemical compound ClC=1C(=NC=CC1)C(C)(C)NC1=NC=C(C=N1)C=1C(=NNC1)CCO KHYUTJNOEOZTHD-UHFFFAOYSA-N 0.000 claims 1
- ZBZSKNSKLUSZQC-UHFFFAOYSA-N 2-[4-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]-4-methylpyrimidin-5-yl]phenyl]acetic acid Chemical compound N=1C=C(C=2C=CC(CC(O)=O)=CC=2)C(C)=NC=1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 ZBZSKNSKLUSZQC-UHFFFAOYSA-N 0.000 claims 1
- FGFYAKBZSDQFBW-UHFFFAOYSA-N 3-[2-[2-(2-chloropyridin-3-yl)propan-2-ylamino]pyrimidin-5-yl]-4-fluorobenzamide Chemical compound C=1C=CN=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=CC(C(N)=O)=CC=C1F FGFYAKBZSDQFBW-UHFFFAOYSA-N 0.000 claims 1
- SDKUOLVIZVGCHJ-UHFFFAOYSA-N 3-[2-[2-(2-methylsulfanylphenyl)propan-2-ylamino]pyrimidin-5-yl]benzonitrile Chemical compound CSC1=CC=CC=C1C(C)(C)NC1=NC=C(C=2C=C(C=CC=2)C#N)C=N1 SDKUOLVIZVGCHJ-UHFFFAOYSA-N 0.000 claims 1
- TWLJIILWLIGQFS-UHFFFAOYSA-N 3-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,2,4-oxadiazole-5-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=NOC(C(N)=O)=N1 TWLJIILWLIGQFS-UHFFFAOYSA-N 0.000 claims 1
- IBBHVIXGDVJQEA-UHFFFAOYSA-N 3-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-4-fluorobenzamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=CC(C(N)=O)=CC=C1F IBBHVIXGDVJQEA-UHFFFAOYSA-N 0.000 claims 1
- OWNQTCZCWNCMLV-UHFFFAOYSA-N 3-[2-[2-(3-methylsulfanylpyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]benzonitrile Chemical compound CSC1=CC=CN=C1C(C)(C)NC1=NC=C(C=2C=C(C=CC=2)C#N)C=N1 OWNQTCZCWNCMLV-UHFFFAOYSA-N 0.000 claims 1
- MCRCNYNTKZDKNM-UHFFFAOYSA-N 3-[2-[2-(4-methylsulfanylphenyl)propan-2-ylamino]pyrimidin-5-yl]benzonitrile Chemical compound C1=CC(SC)=CC=C1C(C)(C)NC1=NC=C(C=2C=C(C=CC=2)C#N)C=N1 MCRCNYNTKZDKNM-UHFFFAOYSA-N 0.000 claims 1
- IMOVJRPIQPNYLA-UHFFFAOYSA-N 3-[2-[2-[3-(difluoromethyl)pyridin-2-yl]propan-2-ylamino]pyrimidin-5-yl]-4-fluorobenzamide Chemical compound N=1C=CC=C(C(F)F)C=1C(C)(C)NC(N=C1)=NC=C1C1=CC(C(N)=O)=CC=C1F IMOVJRPIQPNYLA-UHFFFAOYSA-N 0.000 claims 1
- YEDWIKMJGDFIFY-UHFFFAOYSA-N 3-[2-[2-[3-(difluoromethyl)pyridin-2-yl]propan-2-ylamino]pyrimidin-5-yl]-4-fluorobenzonitrile Chemical compound N=1C=CC=C(C(F)F)C=1C(C)(C)NC(N=C1)=NC=C1C1=CC(C#N)=CC=C1F YEDWIKMJGDFIFY-UHFFFAOYSA-N 0.000 claims 1
- AVNXVPQLGJLNMJ-UHFFFAOYSA-N 3-[2-[2-[6-(difluoromethoxy)pyridin-2-yl]propan-2-ylamino]pyrimidin-5-yl]-4-fluorobenzamide Chemical compound C=1C=CC(OC(F)F)=NC=1C(C)(C)NC(N=C1)=NC=C1C1=CC(C(N)=O)=CC=C1F AVNXVPQLGJLNMJ-UHFFFAOYSA-N 0.000 claims 1
- JPXOECSSCIEUSG-UHFFFAOYSA-N 3-[2-[[1-(3-chloropyridin-2-yl)-3,3-difluorocyclobutyl]methylamino]pyrimidin-5-yl]-4-fluorobenzamide Chemical compound NC(=O)C1=CC=C(F)C(C=2C=NC(NCC3(CC(F)(F)C3)C=3C(=CC=CN=3)Cl)=NC=2)=C1 JPXOECSSCIEUSG-UHFFFAOYSA-N 0.000 claims 1
- LUZNZFZXAFCMMS-UHFFFAOYSA-N 3-[2-[[1-(3-chloropyridin-2-yl)-3-fluorocyclobutyl]amino]pyrimidin-5-yl]-4-fluorobenzamide Chemical compound NC(=O)C1=CC=C(F)C(C=2C=NC(NC3(CC(F)C3)C=3C(=CC=CN=3)Cl)=NC=2)=C1 LUZNZFZXAFCMMS-UHFFFAOYSA-N 0.000 claims 1
- XXBNWBPFYLEIBY-UHFFFAOYSA-N 3-[2-[[1-(3-chloropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-4-fluorobenzamide Chemical compound NC(=O)C1=CC=C(F)C(C=2C=NC(NCC3(CCC3)C=3C(=CC=CN=3)Cl)=NC=2)=C1 XXBNWBPFYLEIBY-UHFFFAOYSA-N 0.000 claims 1
- HBLWDIIICJZOFZ-UHFFFAOYSA-N 3-[2-[[1-(3-chloropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)Cl)CCC1 HBLWDIIICJZOFZ-UHFFFAOYSA-N 0.000 claims 1
- NORMSBFBXPEFJU-UHFFFAOYSA-N 3-[2-[[1-(3-chloropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]benzonitrile Chemical compound ClC1=CC=CN=C1C1(CNC=2N=CC(=CN=2)C=2C=C(C=CC=2)C#N)CCC1 NORMSBFBXPEFJU-UHFFFAOYSA-N 0.000 claims 1
- FXMRHOFDYSCOCR-UHFFFAOYSA-N 3-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-4-hydroxy-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(O)C(C=2C=NC(NCC3(CCC3)C=3C(=CC=CN=3)F)=NC=2)=C1 FXMRHOFDYSCOCR-UHFFFAOYSA-N 0.000 claims 1
- YDZIFNVXFVGJTF-UHFFFAOYSA-N 3-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-4-hydroxybenzamide Chemical compound NC(=O)C1=CC=C(O)C(C=2C=NC(NCC3(CCC3)C=3C(=CC=CN=3)F)=NC=2)=C1 YDZIFNVXFVGJTF-UHFFFAOYSA-N 0.000 claims 1
- VHSKGUPNDTZVDO-UHFFFAOYSA-N 3-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(C=2C=NC(NCC3(CCC3)C=3C(=CC=CN=3)F)=NC=2)=C1 VHSKGUPNDTZVDO-UHFFFAOYSA-N 0.000 claims 1
- NJONITICUPZCFB-UHFFFAOYSA-N 3-[2-[[2-(3-chloropyridin-2-yl)-2-methylpropyl]amino]pyrimidin-5-yl]-4-fluorobenzamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)CNC(N=C1)=NC=C1C1=CC(C(N)=O)=CC=C1F NJONITICUPZCFB-UHFFFAOYSA-N 0.000 claims 1
- WJILSPGBTCDVAT-UHFFFAOYSA-N 3-[2-[[2-(4-fluorophenyl)-2-methylpropyl]amino]pyrimidin-5-yl]benzamide Chemical compound C=1C=C(F)C=CC=1C(C)(C)CNC(N=C1)=NC=C1C1=CC=CC(C(N)=O)=C1 WJILSPGBTCDVAT-UHFFFAOYSA-N 0.000 claims 1
- FFECQHBVDQSVNI-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]-6-oxo-1h-pyrimidin-5-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2C(=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)O)=C1 FFECQHBVDQSVNI-UHFFFAOYSA-N 0.000 claims 1
- IIKAAANMNDALGF-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1h-pyridazin-6-one Chemical compound C1C(F)CC1(C=1C(=CC=CN=1)F)CNC1=NC=C(C2=NNC(=O)C=C2)C=N1 IIKAAANMNDALGF-UHFFFAOYSA-N 0.000 claims 1
- KJUUBBFJAYIPAP-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1h-pyridin-2-one Chemical compound OC1=NC=CC=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 KJUUBBFJAYIPAP-UHFFFAOYSA-N 0.000 claims 1
- UHBIRAZILJFDLH-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-2-hydroxy-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1O UHBIRAZILJFDLH-UHFFFAOYSA-N 0.000 claims 1
- BYNGIDMTRBTCKL-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-2-hydroxybenzamide Chemical compound NC(=O)C1=CC=CC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1O BYNGIDMTRBTCKL-UHFFFAOYSA-N 0.000 claims 1
- YAQHACFJLYJXDD-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-4-hydroxybenzamide Chemical compound NC(=O)C1=CC=C(O)C(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 YAQHACFJLYJXDD-UHFFFAOYSA-N 0.000 claims 1
- VINHPEWSHTVFNF-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 VINHPEWSHTVFNF-UHFFFAOYSA-N 0.000 claims 1
- ZFEUSZDPJCJOMW-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-(1-methylazetidin-3-yl)benzamide Chemical compound C1N(C)CC1NC(=O)C1=CC=CC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 ZFEUSZDPJCJOMW-UHFFFAOYSA-N 0.000 claims 1
- KCZHAECRNUAPNO-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-(1-methylsulfonylazetidin-3-yl)benzamide Chemical compound C1N(S(=O)(=O)C)CC1NC(=O)C1=CC=CC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 KCZHAECRNUAPNO-UHFFFAOYSA-N 0.000 claims 1
- LGLKUFIOSMVRJI-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-(3-hydroxycyclobutyl)benzamide Chemical compound C1C(O)CC1NC(=O)C1=CC=CC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 LGLKUFIOSMVRJI-UHFFFAOYSA-N 0.000 claims 1
- ONTVPTLKNCVJAR-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 ONTVPTLKNCVJAR-UHFFFAOYSA-N 0.000 claims 1
- XKOKGPYAVOJEGJ-UHFFFAOYSA-N 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-methylsulfonylbenzamide Chemical compound CS(=O)(=O)NC(=O)C1=CC=CC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 XKOKGPYAVOJEGJ-UHFFFAOYSA-N 0.000 claims 1
- KDSOMSUECWHXDO-UHFFFAOYSA-N 4-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-2-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=CSC(C(N)=O)=N1 KDSOMSUECWHXDO-UHFFFAOYSA-N 0.000 claims 1
- MWCUTWONXOTBHJ-UHFFFAOYSA-N 4-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]amino]pyrimidin-5-yl]pyridine-2-carbonitrile Chemical compound FC1=CC=CN=C1C1(NC=2N=CC(=CN=2)C=2C=C(N=CC=2)C#N)CCC1 MWCUTWONXOTBHJ-UHFFFAOYSA-N 0.000 claims 1
- ZWLVTFPQDBFYMP-UHFFFAOYSA-N 4-[2-[[1-(4-fluorophenyl)cyclobutyl]amino]pyrimidin-5-yl]pyridine-2-carbonitrile Chemical compound C1=CC(F)=CC=C1C1(NC=2N=CC(=CN=2)C=2C=C(N=CC=2)C#N)CCC1 ZWLVTFPQDBFYMP-UHFFFAOYSA-N 0.000 claims 1
- LQYSCRXCPSPMGQ-UHFFFAOYSA-N 4-[2-[[2-(4-fluorophenyl)-2-methylpropyl]amino]pyrimidin-5-yl]benzamide Chemical compound C=1C=C(F)C=CC=1C(C)(C)CNC(N=C1)=NC=C1C1=CC=C(C(N)=O)C=C1 LQYSCRXCPSPMGQ-UHFFFAOYSA-N 0.000 claims 1
- JJFHSOLNOCHAPU-UHFFFAOYSA-N 4-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]-4-methylpyrimidin-5-yl]benzonitrile Chemical compound N=1C=C(C=2C=CC(=CC=2)C#N)C(C)=NC=1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 JJFHSOLNOCHAPU-UHFFFAOYSA-N 0.000 claims 1
- SPBRHZACBZTXRZ-UHFFFAOYSA-N 4-fluoro-3-[2-[2-(3-methoxypyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]benzonitrile Chemical compound COC1=CC=CN=C1C(C)(C)NC1=NC=C(C=2C(=CC=C(C=2)C#N)F)C=N1 SPBRHZACBZTXRZ-UHFFFAOYSA-N 0.000 claims 1
- WUGRHVRPYAOBNO-UHFFFAOYSA-N 4-fluoro-3-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(F)C(C=2C=NC(NCC3(CCC3)C=3C(=CC=CN=3)F)=NC=2)=C1 WUGRHVRPYAOBNO-UHFFFAOYSA-N 0.000 claims 1
- IMROZIIJRSWTTB-UHFFFAOYSA-N 4-fluoro-3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-(1-methylazetidin-3-yl)benzamide Chemical compound C1N(C)CC1NC(=O)C1=CC=C(F)C(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 IMROZIIJRSWTTB-UHFFFAOYSA-N 0.000 claims 1
- IBVHVJUWJOCQNL-UHFFFAOYSA-N 4-fluoro-3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-(3-hydroxycyclobutyl)benzamide Chemical compound C1C(O)CC1NC(=O)C1=CC=C(F)C(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 IBVHVJUWJOCQNL-UHFFFAOYSA-N 0.000 claims 1
- JKSLDPJHCPGXNE-UHFFFAOYSA-N 4-fluoro-3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(F)C(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 JKSLDPJHCPGXNE-UHFFFAOYSA-N 0.000 claims 1
- HUIZJJVUYNJEBO-UHFFFAOYSA-N 5-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3,4-oxadiazole-2-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=NN=C(C(N)=O)O1 HUIZJJVUYNJEBO-UHFFFAOYSA-N 0.000 claims 1
- HUOVRILEILUAIZ-UHFFFAOYSA-N 5-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3,4-thiadiazole-2-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=NN=C(C(N)=O)S1 HUOVRILEILUAIZ-UHFFFAOYSA-N 0.000 claims 1
- YHEZXSATLBRJGB-UHFFFAOYSA-N 5-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazole-2-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=CN=C(C(N)=O)S1 YHEZXSATLBRJGB-UHFFFAOYSA-N 0.000 claims 1
- HMIHAUZECOBECW-UHFFFAOYSA-N 5-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1-methylpyrazole-3-carboxamide Chemical compound CN1N=C(C(N)=O)C=C1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1Cl HMIHAUZECOBECW-UHFFFAOYSA-N 0.000 claims 1
- XGEJDGYNABRHBI-UHFFFAOYSA-N 5-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-2-methoxypyridine-3-carboxamide Chemical compound C1=C(C(N)=O)C(OC)=NC=C1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1Cl XGEJDGYNABRHBI-UHFFFAOYSA-N 0.000 claims 1
- XRKASKBMNGDMIO-UHFFFAOYSA-N 5-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-2-methylpyrazole-3-carboxamide Chemical compound C1=C(C(N)=O)N(C)N=C1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1Cl XRKASKBMNGDMIO-UHFFFAOYSA-N 0.000 claims 1
- ODTDIRUTNANHAP-UHFFFAOYSA-N 5-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]thiophene-2-carboxylic acid Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C1=CC=C(C(O)=O)S1 ODTDIRUTNANHAP-UHFFFAOYSA-N 0.000 claims 1
- AKXTZWQANKIFHN-UHFFFAOYSA-N 5-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]amino]pyrimidin-5-yl]-1h-indazole-3-carbonitrile Chemical compound FC1=CC=CN=C1C1(NC=2N=CC(=CN=2)C=2C=C3C(C#N)=NNC3=CC=2)CCC1 AKXTZWQANKIFHN-UHFFFAOYSA-N 0.000 claims 1
- FTQICUWBFNJTQA-UHFFFAOYSA-N 5-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]amino]pyrimidin-5-yl]-1h-indazole-3-carboxamide Chemical compound C1=C2C(C(=O)N)=NNC2=CC=C1C(C=N1)=CN=C1NC1(C=2C(=CC=CN=2)F)CCC1 FTQICUWBFNJTQA-UHFFFAOYSA-N 0.000 claims 1
- UKBOIWYQFVUCOZ-UHFFFAOYSA-N 5-[2-[[2-(4-fluorophenyl)-2-methylpropyl]amino]pyrimidin-5-yl]pyridine-3-carbonitrile Chemical compound C=1C=C(F)C=CC=1C(C)(C)CNC(N=C1)=NC=C1C1=CN=CC(C#N)=C1 UKBOIWYQFVUCOZ-UHFFFAOYSA-N 0.000 claims 1
- ZDKDTOHZFVUDCH-UHFFFAOYSA-N 5-[2-[[2-(4-fluorophenyl)-2-methylpropyl]amino]pyrimidin-5-yl]pyridine-3-carboxamide Chemical compound C=1C=C(F)C=CC=1C(C)(C)CNC(N=C1)=NC=C1C1=CN=CC(C(N)=O)=C1 ZDKDTOHZFVUDCH-UHFFFAOYSA-N 0.000 claims 1
- HHCLKZZKSZUECC-UHFFFAOYSA-N 5-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1h-pyridin-2-one Chemical compound C1=NC(O)=CC=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 HHCLKZZKSZUECC-UHFFFAOYSA-N 0.000 claims 1
- UUZYRGUOQLUGJQ-UHFFFAOYSA-N 5-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1h-pyrimidin-2-one Chemical compound C1=NC(O)=NC=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 UUZYRGUOQLUGJQ-UHFFFAOYSA-N 0.000 claims 1
- XRWJGSLZJTWEFJ-UHFFFAOYSA-N 5-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1h-pyrimidine-2,4-dione Chemical compound C1C(F)CC1(C=1C(=CC=CN=1)F)CNC1=NC=C(C=2C(NC(=O)NC=2)=O)C=N1 XRWJGSLZJTWEFJ-UHFFFAOYSA-N 0.000 claims 1
- ZAGARRDWYYZGRQ-UHFFFAOYSA-N 5-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-2-hydroxybenzamide Chemical compound C1=C(O)C(C(=O)N)=CC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 ZAGARRDWYYZGRQ-UHFFFAOYSA-N 0.000 claims 1
- CSNNCUFNLMHGMU-UHFFFAOYSA-N 5-fluoro-6-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]pyridin-3-ol Chemical compound FC1=CC(O)=CN=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 CSNNCUFNLMHGMU-UHFFFAOYSA-N 0.000 claims 1
- APHPYXFYBPHMBC-UHFFFAOYSA-N 6-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-2,3-dihydroimidazo[2,1-b][1,3]thiazole-3-carboxylic acid Chemical compound N=1C=C(C=2N=C3SCC(N3C=2)C(O)=O)C=NC=1NC(C)(C)C1=NC=CC=C1Cl APHPYXFYBPHMBC-UHFFFAOYSA-N 0.000 claims 1
- KQLRFMURJWLWQW-UHFFFAOYSA-N 6-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1h-pyrimidine-2,4-dione Chemical compound C1C(F)CC1(C=1C(=CC=CN=1)F)CNC1=NC=C(C=2NC(=O)NC(=O)C=2)C=N1 KQLRFMURJWLWQW-UHFFFAOYSA-N 0.000 claims 1
- PFUYXXHYZLDTGE-UHFFFAOYSA-N 6-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]pyridin-3-ol Chemical compound N1=CC(O)=CC=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 PFUYXXHYZLDTGE-UHFFFAOYSA-N 0.000 claims 1
- DCTOVCBSGVCWLO-UHFFFAOYSA-N 6-fluoro-5-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]amino]pyrimidin-5-yl]-1h-indazole-3-carbonitrile Chemical compound FC1=CC=CN=C1C1(NC=2N=CC(=CN=2)C=2C(=CC=3NN=C(C=3C=2)C#N)F)CCC1 DCTOVCBSGVCWLO-UHFFFAOYSA-N 0.000 claims 1
- VYCAWMHSAZFYHL-UHFFFAOYSA-N 6-fluoro-5-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]amino]pyrimidin-5-yl]-1h-indazole-3-carboxamide Chemical compound C1=C2C(C(=O)N)=NNC2=CC(F)=C1C(C=N1)=CN=C1NC1(C=2C(=CC=CN=2)F)CCC1 VYCAWMHSAZFYHL-UHFFFAOYSA-N 0.000 claims 1
- XWZGQMVTWBATLI-UHFFFAOYSA-N 7-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-dihydroindol-2-one Chemical compound C1C(F)CC1(C=1C(=CC=CN=1)F)CNC1=NC=C(C=2C=3NC(=O)CC=3C=CC=2)C=N1 XWZGQMVTWBATLI-UHFFFAOYSA-N 0.000 claims 1
- PWSBVKRUGZJBOV-UHFFFAOYSA-N 7-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-2,3-dihydroisoindol-1-one Chemical compound C1C(F)CC1(C=1C(=CC=CN=1)F)CNC1=NC=C(C=2C=3C(=O)NCC=3C=CC=2)C=N1 PWSBVKRUGZJBOV-UHFFFAOYSA-N 0.000 claims 1
- BCOCKHSQCQGJMD-UHFFFAOYSA-N N-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methyl]-4-methoxy-N-methyl-5-phenylpyrimidin-2-amine Chemical compound COC1=NC(N(C)CC2(CC(F)C2)C=2C(=CC=CN=2)F)=NC=C1C1=CC=CC=C1 BCOCKHSQCQGJMD-UHFFFAOYSA-N 0.000 claims 1
- ADDCVJHOYDFZJX-UHFFFAOYSA-N ethyl 2-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(C=2C=NC(NCC3(CCC3)C=3C(=CC=CN=3)F)=NC=2)=N1 ADDCVJHOYDFZJX-UHFFFAOYSA-N 0.000 claims 1
- JTXFWOQSOIEYPX-UHFFFAOYSA-N ethyl 5-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3,4-oxadiazole-2-carboxylate Chemical compound O1C(C(=O)OCC)=NN=C1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1Cl JTXFWOQSOIEYPX-UHFFFAOYSA-N 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- QIOKQFZXWSYMJR-UHFFFAOYSA-N methyl 3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-4-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(O)C(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 QIOKQFZXWSYMJR-UHFFFAOYSA-N 0.000 claims 1
- UQBJPXKMIYURNX-UHFFFAOYSA-N methyl 4-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1-methylimidazole-2-carboxylate Chemical compound CN1C(C(=O)OC)=NC(C=2C=NC(NC(C)(C)C=3C(=CC=CN=3)Cl)=NC=2)=C1 UQBJPXKMIYURNX-UHFFFAOYSA-N 0.000 claims 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
- LXRCGANSRJJBJI-UHFFFAOYSA-N n-(1-acetylazetidin-3-yl)-3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]benzamide Chemical compound C1N(C(=O)C)CC1NC(=O)C1=CC=CC(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 LXRCGANSRJJBJI-UHFFFAOYSA-N 0.000 claims 1
- CQHQRVVBBYDMHQ-UHFFFAOYSA-N n-(1-acetylazetidin-3-yl)-4-fluoro-3-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]benzamide Chemical compound C1N(C(=O)C)CC1NC(=O)C1=CC=C(F)C(C=2C=NC(NCC3(CC(F)C3)C=3C(=CC=CN=3)F)=NC=2)=C1 CQHQRVVBBYDMHQ-UHFFFAOYSA-N 0.000 claims 1
- ACKJSUCRCCFOSF-UHFFFAOYSA-N n-(3-amino-3-oxopropyl)-1-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]pyrazole-4-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1N1C=C(C(=O)NCCC(N)=O)C=N1 ACKJSUCRCCFOSF-UHFFFAOYSA-N 0.000 claims 1
- HMPQREPBMNIFHJ-UHFFFAOYSA-N n-[2-[2-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 HMPQREPBMNIFHJ-UHFFFAOYSA-N 0.000 claims 1
- ACTUVDIBDDCINH-UHFFFAOYSA-N n-[5-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1h-indazol-3-yl]acetamide Chemical compound C1=C2C(NC(=O)C)=NNC2=CC=C1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1Cl ACTUVDIBDDCINH-UHFFFAOYSA-N 0.000 claims 1
- RVUMBURSXHHKSN-UHFFFAOYSA-N n-[[1-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]pyrazol-4-yl]methyl]acetamide Chemical compound C1=C(CNC(=O)C)C=NN1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1Cl RVUMBURSXHHKSN-UHFFFAOYSA-N 0.000 claims 1
- QXEJDGXILAGHPM-UHFFFAOYSA-N n-[[2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]-2-hydroxy-2-methylpropanamide Chemical compound S1C(CNC(=O)C(C)(O)C)=CN=C1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1Cl QXEJDGXILAGHPM-UHFFFAOYSA-N 0.000 claims 1
- RKJTZLSTYCGSPY-UHFFFAOYSA-N n-[[2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]-2-oxo-1,3-dihydroimidazole-4-carboxamide Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC(N=C1)=NC=C1C(S1)=NC=C1CNC(=O)C1=CNC(=O)N1 RKJTZLSTYCGSPY-UHFFFAOYSA-N 0.000 claims 1
- QNJVPMHDFYNNHU-UHFFFAOYSA-N n-[[2-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]acetamide Chemical compound S1C(CNC(=O)C)=CN=C1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1Cl QNJVPMHDFYNNHU-UHFFFAOYSA-N 0.000 claims 1
- LTXWKEOXLRJLGO-UHFFFAOYSA-N n-[[2-[2-[2-(3-fluoropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]-1h-imidazole-5-carboxamide Chemical compound N=1C=CC=C(F)C=1C(C)(C)NC(N=C1)=NC=C1C(S1)=NC=C1CNC(=O)C1=CN=CN1 LTXWKEOXLRJLGO-UHFFFAOYSA-N 0.000 claims 1
- UYFSMFGTAWQQKB-UHFFFAOYSA-N n-[[2-[2-[2-(3-fluoropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]-2-oxo-1,3-dihydroimidazole-4-carboxamide Chemical compound N=1C=CC=C(F)C=1C(C)(C)NC(N=C1)=NC=C1C(S1)=NC=C1CNC(=O)C1=CNC(=O)N1 UYFSMFGTAWQQKB-UHFFFAOYSA-N 0.000 claims 1
- AUGVLNGNZNZIPL-UHFFFAOYSA-N n-[[2-[2-[2-(3-fluoropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]acetamide Chemical compound S1C(CNC(=O)C)=CN=C1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1F AUGVLNGNZNZIPL-UHFFFAOYSA-N 0.000 claims 1
- XEWJXFYJHMVHLN-UHFFFAOYSA-N n-[[2-[2-[[1-(3-chloropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]acetamide Chemical compound S1C(CNC(=O)C)=CN=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)Cl)CCC1 XEWJXFYJHMVHLN-UHFFFAOYSA-N 0.000 claims 1
- YBIXLQITUKECNS-UHFFFAOYSA-N n-[[2-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]acetamide Chemical compound S1C(CNC(=O)C)=CN=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CCC1 YBIXLQITUKECNS-UHFFFAOYSA-N 0.000 claims 1
- UJAGLMFMGLCRAZ-UHFFFAOYSA-N n-[[3-[2-[2-(3-fluoropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]phenyl]methyl]acetamide Chemical compound CC(=O)NCC1=CC=CC(C=2C=NC(NC(C)(C)C=3C(=CC=CN=3)F)=NC=2)=C1 UJAGLMFMGLCRAZ-UHFFFAOYSA-N 0.000 claims 1
- OMBORNJCRLXXEN-UHFFFAOYSA-N n-[[4-[2-[2-(3-fluoropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]phenyl]methyl]acetamide Chemical compound C1=CC(CNC(=O)C)=CC=C1C(C=N1)=CN=C1NC(C)(C)C1=NC=CC=C1F OMBORNJCRLXXEN-UHFFFAOYSA-N 0.000 claims 1
- IMJNPNIXPZKPJT-UHFFFAOYSA-N n-tert-butyl-5-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]pyridazine-3-carboxamide Chemical compound N1=NC(C(=O)NC(C)(C)C)=CC(C=2C=NC(NC(C)(C)C=3C(=CC=CN=3)Cl)=NC=2)=C1 IMJNPNIXPZKPJT-UHFFFAOYSA-N 0.000 claims 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims 1
- MQXWPWOCXGARRK-UHFFFAOYSA-N reldesemtiv Chemical compound C1=C(C(=O)N)C=CN1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CC(F)C1 MQXWPWOCXGARRK-UHFFFAOYSA-N 0.000 claims 1
- PYXJWJHDYHTKMU-UHFFFAOYSA-N tert-butyl n-[[2-[2-[(1-pyridin-2-ylcyclobutyl)methylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]carbamate Chemical compound S1C(CNC(=O)OC(C)(C)C)=CN=C1C(C=N1)=CN=C1NCC1(C=2N=CC=CC=2)CCC1 PYXJWJHDYHTKMU-UHFFFAOYSA-N 0.000 claims 1
- CTGLDVLQSOPECY-UHFFFAOYSA-N tert-butyl n-[[2-[2-[[1-(3-chloropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]carbamate Chemical compound S1C(CNC(=O)OC(C)(C)C)=CN=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)Cl)CCC1 CTGLDVLQSOPECY-UHFFFAOYSA-N 0.000 claims 1
- WPBBJNPMOKYLRJ-UHFFFAOYSA-N tert-butyl n-[[2-[2-[[1-(3-fluoropyridin-2-yl)cyclobutyl]methylamino]pyrimidin-5-yl]-1,3-thiazol-5-yl]methyl]carbamate Chemical compound S1C(CNC(=O)OC(C)(C)C)=CN=C1C(C=N1)=CN=C1NCC1(C=2C(=CC=CN=2)F)CCC1 WPBBJNPMOKYLRJ-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 139
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 67
- 238000006243 chemical reaction Methods 0.000 description 65
- 235000019439 ethyl acetate Nutrition 0.000 description 61
- 239000000243 solution Substances 0.000 description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 210000003205 muscle Anatomy 0.000 description 50
- 239000007787 solid Substances 0.000 description 48
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 46
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 42
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- 125000000392 cycloalkenyl group Chemical group 0.000 description 42
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 38
- 210000002027 skeletal muscle Anatomy 0.000 description 38
- 239000012044 organic layer Substances 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 102000003505 Myosin Human genes 0.000 description 35
- 108060008487 Myosin Proteins 0.000 description 33
- 210000001087 myotubule Anatomy 0.000 description 33
- 239000011734 sodium Substances 0.000 description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
- 125000003710 aryl alkyl group Chemical group 0.000 description 32
- 125000001624 naphthyl group Chemical group 0.000 description 32
- 102000007469 Actins Human genes 0.000 description 29
- 108010085238 Actins Proteins 0.000 description 29
- 125000001072 heteroaryl group Chemical group 0.000 description 28
- 229910052757 nitrogen Inorganic materials 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- 239000003921 oil Substances 0.000 description 25
- 235000019198 oils Nutrition 0.000 description 25
- 239000012267 brine Substances 0.000 description 24
- 125000003367 polycyclic group Chemical group 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- 102000004903 Troponin Human genes 0.000 description 22
- 108090001027 Troponin Proteins 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- 210000002235 sarcomere Anatomy 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 125000003342 alkenyl group Chemical group 0.000 description 21
- 108010030743 Tropomyosin Proteins 0.000 description 20
- 102000005937 Tropomyosin Human genes 0.000 description 20
- 125000000304 alkynyl group Chemical group 0.000 description 20
- 238000010898 silica gel chromatography Methods 0.000 description 20
- 150000001721 carbon Chemical group 0.000 description 19
- 229940079593 drug Drugs 0.000 description 18
- 239000010410 layer Substances 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- 229940124597 therapeutic agent Drugs 0.000 description 17
- 125000004429 atom Chemical group 0.000 description 16
- 239000011575 calcium Substances 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- 239000000843 powder Substances 0.000 description 16
- 229910052717 sulfur Inorganic materials 0.000 description 16
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 15
- 206010028372 Muscular weakness Diseases 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 102000013534 Troponin C Human genes 0.000 description 15
- 239000000835 fiber Substances 0.000 description 15
- 210000003365 myofibril Anatomy 0.000 description 15
- 208000036119 Frailty Diseases 0.000 description 14
- 208000021642 Muscular disease Diseases 0.000 description 14
- 108010065729 Troponin I Proteins 0.000 description 14
- 239000000460 chlorine Chemical group 0.000 description 14
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 102000013394 Troponin I Human genes 0.000 description 13
- 238000007792 addition Methods 0.000 description 13
- 206010003549 asthenia Diseases 0.000 description 13
- 239000000872 buffer Substances 0.000 description 13
- 229910052791 calcium Inorganic materials 0.000 description 13
- 239000011737 fluorine Substances 0.000 description 13
- 229910052731 fluorine Inorganic materials 0.000 description 13
- 230000036961 partial effect Effects 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 208000010428 Muscle Weakness Diseases 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- 230000001965 increasing effect Effects 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 12
- 238000003419 tautomerization reaction Methods 0.000 description 12
- 102000004987 Troponin T Human genes 0.000 description 11
- 108090001108 Troponin T Proteins 0.000 description 11
- 230000004913 activation Effects 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000008188 pellet Substances 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 239000002552 dosage form Substances 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 125000005842 heteroatom Chemical group 0.000 description 10
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 10
- 239000012453 solvate Substances 0.000 description 10
- 208000011580 syndromic disease Diseases 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 239000012634 fragment Substances 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 230000004118 muscle contraction Effects 0.000 description 9
- 230000001590 oxidative effect Effects 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- 239000011593 sulfur Substances 0.000 description 9
- 206010006895 Cachexia Diseases 0.000 description 8
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 102000001708 Protein Isoforms Human genes 0.000 description 8
- 108010029485 Protein Isoforms Proteins 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 229910001424 calcium ion Inorganic materials 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 210000003632 microfilament Anatomy 0.000 description 8
- 201000006938 muscular dystrophy Diseases 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 229910000160 potassium phosphate Inorganic materials 0.000 description 8
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 7
- 208000029578 Muscle disease Diseases 0.000 description 7
- 239000012190 activator Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 206010016256 fatigue Diseases 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- 235000011009 potassium phosphates Nutrition 0.000 description 7
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- 108091006112 ATPases Proteins 0.000 description 6
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
- 201000009623 Myopathy Diseases 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000008602 contraction Effects 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 238000011065 in-situ storage Methods 0.000 description 6
- 230000004220 muscle function Effects 0.000 description 6
- 125000006574 non-aromatic ring group Chemical group 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 208000033808 peripheral neuropathy Diseases 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- 206010010356 Congenital anomaly Diseases 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 208000006011 Stroke Diseases 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 230000032683 aging Effects 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 5
- 239000011536 extraction buffer Substances 0.000 description 5
- 210000003128 head Anatomy 0.000 description 5
- 210000002161 motor neuron Anatomy 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 201000001119 neuropathy Diseases 0.000 description 5
- 230000007823 neuropathy Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 125000006413 ring segment Chemical group 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- 229940125913 troponin activator Drugs 0.000 description 5
- DHGRRSSFDBJARB-UHFFFAOYSA-N 2-(4-fluorophenyl)-2-methylpropan-1-amine Chemical compound NCC(C)(C)C1=CC=C(F)C=C1 DHGRRSSFDBJARB-UHFFFAOYSA-N 0.000 description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
- 101150003085 Pdcl gene Proteins 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 230000005496 eutectics Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 230000001771 impaired effect Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000033001 locomotion Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 210000004165 myocardium Anatomy 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 0 **c1c(*)nc(N(*)C(C2)(CC2(*)[Rn])c2ccccn2)nc1* Chemical compound **c1c(*)nc(N(*)C(C2)(CC2(*)[Rn])c2ccccn2)nc1* 0.000 description 3
- GNTKFUARIPLYGN-UHFFFAOYSA-N 1-(3-fluoropyridin-2-yl)cyclobutan-1-amine Chemical compound N=1C=CC=C(F)C=1C1(N)CCC1 GNTKFUARIPLYGN-UHFFFAOYSA-N 0.000 description 3
- XVPDCACJJBQDIA-UHFFFAOYSA-N 1-(3-fluoropyridin-2-yl)cyclobutane-1-carbonitrile Chemical compound FC1=CC=CN=C1C1(C#N)CCC1 XVPDCACJJBQDIA-UHFFFAOYSA-N 0.000 description 3
- MCHGXLXKBRYWIV-UHFFFAOYSA-N 1-(6-fluoropyridin-2-yl)cyclobutane-1-carbonitrile Chemical compound FC1=CC=CC(C2(CCC2)C#N)=N1 MCHGXLXKBRYWIV-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- ZJFDRIWVFOAVJE-UHFFFAOYSA-N 2-[6-(difluoromethoxy)pyridin-2-yl]-2-methylpropanamide Chemical compound NC(=O)C(C)(C)C1=CC=CC(OC(F)F)=N1 ZJFDRIWVFOAVJE-UHFFFAOYSA-N 0.000 description 3
- UZULTGHUEVKCIP-UHFFFAOYSA-N 2-[6-(difluoromethoxy)pyridin-2-yl]-2-methylpropanenitrile Chemical compound N#CC(C)(C)C1=CC=CC(OC(F)F)=N1 UZULTGHUEVKCIP-UHFFFAOYSA-N 0.000 description 3
- JHZYZQJOYZEZFL-UHFFFAOYSA-N 2-methyl-2-(6-oxo-1h-pyridin-2-yl)propanenitrile Chemical compound N#CC(C)(C)C1=CC=CC(=O)N1 JHZYZQJOYZEZFL-UHFFFAOYSA-N 0.000 description 3
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 206010022562 Intermittent claudication Diseases 0.000 description 3
- 102000004016 L-Type Calcium Channels Human genes 0.000 description 3
- 108090000420 L-Type Calcium Channels Proteins 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000005392 Spasm Diseases 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229920004890 Triton X-100 Polymers 0.000 description 3
- 239000013504 Triton X-100 Substances 0.000 description 3
- YAVOMXHKTLHWOE-UHFFFAOYSA-N [1-(3-fluoropyridin-2-yl)cyclobutyl]methanamine Chemical compound N=1C=CC=C(F)C=1C1(CN)CCC1 YAVOMXHKTLHWOE-UHFFFAOYSA-N 0.000 description 3
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 3
- 229960004373 acetylcholine Drugs 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 150000005829 chemical entities Chemical class 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 208000020832 chronic kidney disease Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 210000004292 cytoskeleton Anatomy 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 229940011871 estrogen Drugs 0.000 description 3
- 239000000262 estrogen Substances 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 208000021156 intermittent vascular claudication Diseases 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 208000030175 lameness Diseases 0.000 description 3
- 210000002414 leg Anatomy 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 235000013372 meat Nutrition 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 229960002985 medroxyprogesterone acetate Drugs 0.000 description 3
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- SSYZIFCEOSSERB-UHFFFAOYSA-N methyl n-[1-(3-fluoropyridin-2-yl)cyclobutyl]carbamate Chemical compound N=1C=CC=C(F)C=1C1(NC(=O)OC)CCC1 SSYZIFCEOSSERB-UHFFFAOYSA-N 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000007383 nerve stimulation Effects 0.000 description 3
- 230000002232 neuromuscular Effects 0.000 description 3
- 210000000715 neuromuscular junction Anatomy 0.000 description 3
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 125000005412 pyrazyl group Chemical group 0.000 description 3
- 125000005495 pyridazyl group Chemical group 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 229960004181 riluzole Drugs 0.000 description 3
- 239000000849 selective androgen receptor modulator Substances 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 3
- WWYNJERNGUHSAO-XUDSTZEESA-N (+)-Norgestrel Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 WWYNJERNGUHSAO-XUDSTZEESA-N 0.000 description 2
- YZVFSQQHQPPKNX-UHFFFAOYSA-N 1,3-thiazole-5-carboxylic acid Chemical compound OC(=O)C1=CN=CS1 YZVFSQQHQPPKNX-UHFFFAOYSA-N 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 2
- DLDPBPUXBQGZPH-UHFFFAOYSA-N 1-(3-fluoropyridin-2-yl)cyclobutane-1-carboxamide Chemical compound N=1C=CC=C(F)C=1C1(C(=O)N)CCC1 DLDPBPUXBQGZPH-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 2
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical compound C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 2
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 2
- JHQBLYITVCBGTO-UHFFFAOYSA-N 2-(4-fluorophenyl)acetonitrile Chemical compound FC1=CC=C(CC#N)C=C1 JHQBLYITVCBGTO-UHFFFAOYSA-N 0.000 description 2
- PUZKHMMXXQVYCK-UHFFFAOYSA-N 2-(6-fluoropyridin-2-yl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)C1=CC=CC(F)=N1 PUZKHMMXXQVYCK-UHFFFAOYSA-N 0.000 description 2
- AQNYYGFOZLZLMY-UHFFFAOYSA-N 2-(6-methoxypyridin-2-yl)-2-methylpropanenitrile Chemical compound COC1=CC=CC(C(C)(C)C#N)=N1 AQNYYGFOZLZLMY-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 2
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- VQNDBXJTIJKJPV-UHFFFAOYSA-N 2h-triazolo[4,5-b]pyridine Chemical compound C1=CC=NC2=NNN=C21 VQNDBXJTIJKJPV-UHFFFAOYSA-N 0.000 description 2
- ZSYMMINAALNVSH-UHFFFAOYSA-N 2h-triazolo[4,5-c]pyridine Chemical compound C1=NC=CC2=NNN=C21 ZSYMMINAALNVSH-UHFFFAOYSA-N 0.000 description 2
- GIIGHSIIKVOWKZ-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidine Chemical compound N1=CN=CC2=NNN=C21 GIIGHSIIKVOWKZ-UHFFFAOYSA-N 0.000 description 2
- UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
- WGJUBVJZKNTGRC-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine Chemical class N1=CN=C2CNCCC2=C1 WGJUBVJZKNTGRC-UHFFFAOYSA-N 0.000 description 2
- STXKJIIHKFGUCY-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical class C1=NC=C2CNCCC2=N1 STXKJIIHKFGUCY-UHFFFAOYSA-N 0.000 description 2
- NGQWAFWYMICPNC-UHFFFAOYSA-N 5-[2-[[2-(4-fluorophenyl)-2-methylpropyl]amino]pyrimidin-5-yl]-1h-indazol-3-amine Chemical compound N=1C=C(C=2C=C3C(N)=NNC3=CC=2)C=NC=1NCC(C)(C)C1=CC=C(F)C=C1 NGQWAFWYMICPNC-UHFFFAOYSA-N 0.000 description 2
- NERQVYFIYOWGLJ-UHFFFAOYSA-N 5-bromo-n-[2-(4-fluorophenyl)-2-methylpropyl]pyrimidin-2-amine Chemical compound C=1C=C(F)C=CC=1C(C)(C)CNC1=NC=C(Br)C=N1 NERQVYFIYOWGLJ-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 206010000159 Abnormal loss of weight Diseases 0.000 description 2
- 108010052946 Activin Receptors Proteins 0.000 description 2
- 102000018918 Activin Receptors Human genes 0.000 description 2
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 102100039939 Growth/differentiation factor 8 Human genes 0.000 description 2
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 2
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 2
- 102100022745 Laminin subunit alpha-2 Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000016285 Movement disease Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- 108030001204 Myosin ATPases Proteins 0.000 description 2
- 102000005640 Myosin Type II Human genes 0.000 description 2
- 108010045128 Myosin Type II Proteins 0.000 description 2
- 108010056852 Myostatin Proteins 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- 108090000445 Parathyroid hormone Proteins 0.000 description 2
- 102000003982 Parathyroid hormone Human genes 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- RVOLLAQWKVFTGE-UHFFFAOYSA-N Pyridostigmine Chemical compound CN(C)C(=O)OC1=CC=C[N+](C)=C1 RVOLLAQWKVFTGE-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 102000013009 Pyruvate Kinase Human genes 0.000 description 2
- 108020005115 Pyruvate Kinase Proteins 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 206010054880 Vascular insufficiency Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- CDGFEINVQHEUQV-UHFFFAOYSA-N [1,3]thiazolo[5,4-d]pyrimidine Chemical compound N1=CN=C2SC=NC2=C1 CDGFEINVQHEUQV-UHFFFAOYSA-N 0.000 description 2
- HBFKEYQZLXAIRU-UHFFFAOYSA-N [1-(6-methoxypyridin-2-yl)cyclobutyl]methanamine Chemical compound COC1=CC=CC(C2(CN)CCC2)=N1 HBFKEYQZLXAIRU-UHFFFAOYSA-N 0.000 description 2
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000036982 action potential Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 239000003263 anabolic agent Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 125000004069 aziridinyl group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000004773 chlorofluoromethyl group Chemical group [H]C(F)(Cl)* 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000010668 complexation reaction Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 201000006815 congenital muscular dystrophy Diseases 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- GFBLFDSCAKHHGX-UHFFFAOYSA-N cyclobutanecarbonitrile Chemical compound N#CC1CCC1 GFBLFDSCAKHHGX-UHFFFAOYSA-N 0.000 description 2
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 201000001981 dermatomyositis Diseases 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 210000000744 eyelid Anatomy 0.000 description 2
- 230000008921 facial expression Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 102000034356 gene-regulatory proteins Human genes 0.000 description 2
- 108091006104 gene-regulatory proteins Proteins 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 208000003532 hypothyroidism Diseases 0.000 description 2
- 230000002989 hypothyroidism Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 150000002500 ions Chemical group 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960004400 levonorgestrel Drugs 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- TZAHBEDEIXQQDT-UHFFFAOYSA-N methyl 2-[[2-(4-fluorophenyl)-2-methylpropyl]amino]pyrimidine-5-carboxylate Chemical compound N1=CC(C(=O)OC)=CN=C1NCC(C)(C)C1=CC=C(F)C=C1 TZAHBEDEIXQQDT-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 230000036473 myasthenia Effects 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 231100000862 numbness Toxicity 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 2
- 229960001243 orlistat Drugs 0.000 description 2
- 239000000199 parathyroid hormone Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 229960003562 phentermine Drugs 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 208000005987 polymyositis Diseases 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 229960002290 pyridostigmine Drugs 0.000 description 2
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 150000003246 quinazolines Chemical class 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 201000005572 sensory peripheral neuropathy Diseases 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 230000012232 skeletal muscle contraction Effects 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- DDWBRNXDKNIQDY-UHFFFAOYSA-N thieno[2,3-d]pyrimidine Chemical compound N1=CN=C2SC=CC2=C1 DDWBRNXDKNIQDY-UHFFFAOYSA-N 0.000 description 2
- 102000004217 thyroid hormone receptors Human genes 0.000 description 2
- 108090000721 thyroid hormone receptors Proteins 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000000472 traumatic effect Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- ZISSAWUMDACLOM-UHFFFAOYSA-N triptane Chemical compound CC(C)C(C)(C)C ZISSAWUMDACLOM-UHFFFAOYSA-N 0.000 description 2
- 208000023577 vascular insufficiency disease Diseases 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- JRHPOFJADXHYBR-HTQZYQBOSA-N (1r,2r)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@@H]1CCCC[C@H]1NC JRHPOFJADXHYBR-HTQZYQBOSA-N 0.000 description 1
- YTCIHPTZKKWKKC-UHFFFAOYSA-N (2-chloropyrimidin-5-yl)boronic acid Chemical compound OB(O)C1=CN=C(Cl)N=C1 YTCIHPTZKKWKKC-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- YRBRJLWZJHRXBG-SSDOTTSWSA-N (2s)-2-(4-fluorophenyl)propan-1-amine Chemical compound NC[C@@H](C)C1=CC=C(F)C=C1 YRBRJLWZJHRXBG-SSDOTTSWSA-N 0.000 description 1
- NWQWNCILOXTTHF-HLCSKTDOSA-N (2s)-6-amino-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](N)C)C(=O)N[C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CNC=N1 NWQWNCILOXTTHF-HLCSKTDOSA-N 0.000 description 1
- WZHKXNSOCOQYQX-FUAFALNISA-N (2s)-6-amino-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](N)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CN=CN1 WZHKXNSOCOQYQX-FUAFALNISA-N 0.000 description 1
- HRNLPPBUBKMZMT-SSSXJSFTSA-N (2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-aminopropanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](C)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(=O)[C@H](N)C)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 HRNLPPBUBKMZMT-SSSXJSFTSA-N 0.000 description 1
- AKFTZXKFTPPCIB-UHFFFAOYSA-N (3-boronophenyl)carbamic acid Chemical compound OB(O)C1=CC=CC(NC(O)=O)=C1 AKFTZXKFTPPCIB-UHFFFAOYSA-N 0.000 description 1
- YJEJISGIPNUDBB-UHFFFAOYSA-N (3-bromo-6-fluoro-2-methoxyphenyl)boronic acid Chemical compound COC1=C(Br)C=CC(F)=C1B(O)O YJEJISGIPNUDBB-UHFFFAOYSA-N 0.000 description 1
- OLKIYJDSLMKNLC-UHFFFAOYSA-N (3-cyano-4-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(C#N)=C1 OLKIYJDSLMKNLC-UHFFFAOYSA-N 0.000 description 1
- VBTQNVGPCAESPO-GUYCJALGSA-N (4s)-4-benzyl-3-[(2s)-2-(4-fluorophenyl)propanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@@H]1N(C(OC1)=O)C(=O)[C@@H](C)C=1C=CC(F)=CC=1)C1=CC=CC=C1 VBTQNVGPCAESPO-GUYCJALGSA-N 0.000 description 1
- KNKOUDKOHSNMEL-UHFFFAOYSA-N (7-oxo-5,6-dihydro-4h-1-benzothiophen-4-yl)urea Chemical compound NC(=O)NC1CCC(=O)C2=C1C=CS2 KNKOUDKOHSNMEL-UHFFFAOYSA-N 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- 125000006718 (C3-C7) heterocycloalkenyl group Chemical group 0.000 description 1
- 125000006721 (C5-C10) heteroaryl (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000006587 (C5-C10) heteroarylene group Chemical group 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- NTCBUXIQMLORSI-GIDUJCDVSA-N (e)-1-[4-(4-bromophenyl)phenyl]-3-phenylprop-2-en-1-one Chemical compound C1=CC(Br)=CC=C1C1=CC=C(C(=O)\C=C\C=2C=CC=CC=2)C=C1 NTCBUXIQMLORSI-GIDUJCDVSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- FNQJDLTXOVEEFB-UHFFFAOYSA-N 1,2,3-benzothiadiazole Chemical compound C1=CC=C2SN=NC2=C1 FNQJDLTXOVEEFB-UHFFFAOYSA-N 0.000 description 1
- SLLFVLKNXABYGI-UHFFFAOYSA-N 1,2,3-benzoxadiazole Chemical compound C1=CC=C2ON=NC2=C1 SLLFVLKNXABYGI-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- SWEICGMKXPNXNU-UHFFFAOYSA-N 1,2-dihydroindazol-3-one Chemical compound C1=CC=C2C(O)=NNC2=C1 SWEICGMKXPNXNU-UHFFFAOYSA-N 0.000 description 1
- TVYCYSWASMVOMJ-UHFFFAOYSA-N 1,2-dihydropyrazolo[3,4-d][1,3]thiazol-3-one Chemical compound N1=CSC2=C1NNC2=O TVYCYSWASMVOMJ-UHFFFAOYSA-N 0.000 description 1
- FUOSTELFLYZQCW-UHFFFAOYSA-N 1,2-oxazol-3-one Chemical compound OC=1C=CON=1 FUOSTELFLYZQCW-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 1
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 1
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- HUCXRCCJHDFVCI-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-c]pyridin-2-one Chemical compound C1=NC=C2NC(=O)CC2=C1 HUCXRCCJHDFVCI-UHFFFAOYSA-N 0.000 description 1
- IHRRHTILSRVFPW-UHFFFAOYSA-N 1,3-dihydropyrrolo[3,2-b]pyridin-2-one Chemical compound C1=CC=C2NC(=O)CC2=N1 IHRRHTILSRVFPW-UHFFFAOYSA-N 0.000 description 1
- YAUVSURSWJMKFT-UHFFFAOYSA-N 1,3-dihydropyrrolo[3,2-c]pyridin-2-one Chemical compound N1=CC=C2NC(=O)CC2=C1 YAUVSURSWJMKFT-UHFFFAOYSA-N 0.000 description 1
- ABJFBJGGLJVMAQ-UHFFFAOYSA-N 1,4-dihydroquinoxaline-2,3-dione Chemical compound C1=CC=C2NC(=O)C(=O)NC2=C1 ABJFBJGGLJVMAQ-UHFFFAOYSA-N 0.000 description 1
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 description 1
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 description 1
- VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical compound C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 description 1
- VSOSXKMEQPYESP-UHFFFAOYSA-N 1,6-naphthyridine Chemical compound C1=CN=CC2=CC=CN=C21 VSOSXKMEQPYESP-UHFFFAOYSA-N 0.000 description 1
- MXBVNILGVJVVMH-UHFFFAOYSA-N 1,7-naphthyridine Chemical compound C1=NC=CC2=CC=CN=C21 MXBVNILGVJVVMH-UHFFFAOYSA-N 0.000 description 1
- NUBQKPWHXMGDLP-UHFFFAOYSA-N 1-[4-benzyl-2-hydroxy-5-[(2-hydroxy-2,3-dihydro-1h-inden-1-yl)amino]-5-oxopentyl]-n-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide;sulfuric acid Chemical compound OS(O)(=O)=O.C1CN(CC(O)CC(CC=2C=CC=CC=2)C(=O)NC2C3=CC=CC=C3CC2O)C(C(=O)NC(C)(C)C)CN1CC1=CC=CN=C1 NUBQKPWHXMGDLP-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical compound N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 description 1
- FUAXXVSVFLEVSF-UHFFFAOYSA-N 1h-2,1-benzoxazol-3-one Chemical compound C1=CC=C2C(=O)ONC2=C1 FUAXXVSVFLEVSF-UHFFFAOYSA-N 0.000 description 1
- GVLRTOYGRNLSDW-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyridine Chemical compound C1=CC=C2C=NNC2=N1 GVLRTOYGRNLSDW-UHFFFAOYSA-N 0.000 description 1
- KNYHISBJRQVMAZ-UHFFFAOYSA-N 1h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C=NNC2=C1 KNYHISBJRQVMAZ-UHFFFAOYSA-N 0.000 description 1
- LLKAAPMRHULVSQ-UHFFFAOYSA-N 1h-pyrazolo[3,4-d][1,3]thiazole Chemical compound N1N=CC2=C1N=CS2 LLKAAPMRHULVSQ-UHFFFAOYSA-N 0.000 description 1
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 description 1
- WCXFPLXZZSWROM-UHFFFAOYSA-N 1h-pyrazolo[4,3-c]pyridine Chemical compound C1=NC=C2C=NNC2=C1 WCXFPLXZZSWROM-UHFFFAOYSA-N 0.000 description 1
- PDRSZUAQTFBWPF-UHFFFAOYSA-N 1h-pyrazolo[4,3-d][1,3]thiazole Chemical compound C1=NNC2=C1N=CS2 PDRSZUAQTFBWPF-UHFFFAOYSA-N 0.000 description 1
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- PCYWMDGJYQAMCR-UHFFFAOYSA-N 1h-pyrrole-3-carbonitrile Chemical compound N#CC=1C=CNC=1 PCYWMDGJYQAMCR-UHFFFAOYSA-N 0.000 description 1
- XLKDJOPOOHHZAN-UHFFFAOYSA-N 1h-pyrrolo[2,3-c]pyridine Chemical compound C1=NC=C2NC=CC2=C1 XLKDJOPOOHHZAN-UHFFFAOYSA-N 0.000 description 1
- XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 description 1
- SRSKXJVMVSSSHB-UHFFFAOYSA-N 1h-pyrrolo[3,2-c]pyridine Chemical compound N1=CC=C2NC=CC2=C1 SRSKXJVMVSSSHB-UHFFFAOYSA-N 0.000 description 1
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 1
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
- SSNMISUJOQAFRR-UHFFFAOYSA-N 2,6-naphthyridine Chemical compound N1=CC=C2C=NC=CC2=C1 SSNMISUJOQAFRR-UHFFFAOYSA-N 0.000 description 1
- HCMMECMKVPHMDE-UHFFFAOYSA-N 2,7-naphthyridine Chemical compound C1=NC=C2C=NC=CC2=C1 HCMMECMKVPHMDE-UHFFFAOYSA-N 0.000 description 1
- BYQSYJDHZJUGLI-UHFFFAOYSA-N 2-(2-bromo-1,3-thiazol-5-yl)acetonitrile Chemical compound BrC1=NC=C(CC#N)S1 BYQSYJDHZJUGLI-UHFFFAOYSA-N 0.000 description 1
- MLTZCNARUQTCBM-UHFFFAOYSA-N 2-(3-fluoropyridin-2-yl)acetonitrile Chemical compound FC1=CC=CN=C1CC#N MLTZCNARUQTCBM-UHFFFAOYSA-N 0.000 description 1
- UOEIWAZNZTXYSC-UHFFFAOYSA-N 2-(4-fluorophenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)C1=CC=C(F)C=C1 UOEIWAZNZTXYSC-UHFFFAOYSA-N 0.000 description 1
- SIOJFYRPBYGHOO-UHFFFAOYSA-N 2-(4-fluorophenyl)acetyl chloride Chemical compound FC1=CC=C(CC(Cl)=O)C=C1 SIOJFYRPBYGHOO-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- PZUVWOFDKURYCQ-UHFFFAOYSA-N 2-[6-(difluoromethoxy)pyridin-2-yl]propan-2-amine Chemical compound CC(C)(N)C1=CC=CC(OC(F)F)=N1 PZUVWOFDKURYCQ-UHFFFAOYSA-N 0.000 description 1
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 1
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 1
- BMJRRGRTDQLVQY-UHFFFAOYSA-N 2-bromo-1-[2-[2-(3-chloropyridin-2-yl)propan-2-ylamino]pyrimidin-5-yl]ethanone Chemical compound N=1C=CC=C(Cl)C=1C(C)(C)NC1=NC=C(C(=O)CBr)C=N1 BMJRRGRTDQLVQY-UHFFFAOYSA-N 0.000 description 1
- SVAZIMBLBHOVIR-UHFFFAOYSA-N 2-chloro-3-fluoropyridine Chemical compound FC1=CC=CN=C1Cl SVAZIMBLBHOVIR-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- DTAQWZLHBRGFBQ-UHFFFAOYSA-N 2-fluoro-5-[2-[[2-(4-fluorophenyl)-2-methylpropyl]amino]pyrimidin-5-yl]benzonitrile Chemical compound C=1C=C(F)C=CC=1C(C)(C)CNC(N=C1)=NC=C1C1=CC=C(F)C(C#N)=C1 DTAQWZLHBRGFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- 108010070743 3(or 17)-beta-hydroxysteroid dehydrogenase Proteins 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- ACZGCWSMSTYWDQ-UHFFFAOYSA-N 3h-1-benzofuran-2-one Chemical compound C1=CC=C2OC(=O)CC2=C1 ACZGCWSMSTYWDQ-UHFFFAOYSA-N 0.000 description 1
- ARTAFUJPRUWRJK-UHFFFAOYSA-N 3h-1-benzothiophen-2-one Chemical compound C1=CC=C2SC(=O)CC2=C1 ARTAFUJPRUWRJK-UHFFFAOYSA-N 0.000 description 1
- NSSBUSDEHNCUIY-UHFFFAOYSA-N 3h-2-benzothiophen-1-one Chemical compound C1=CC=C2C(=O)SCC2=C1 NSSBUSDEHNCUIY-UHFFFAOYSA-N 0.000 description 1
- SLGVJLNVPYQNNK-UHFFFAOYSA-N 3h-cinnolin-4-one Chemical compound C1=CC=C2C(=O)CN=NC2=C1 SLGVJLNVPYQNNK-UHFFFAOYSA-N 0.000 description 1
- HETSDWRDICBRSQ-UHFFFAOYSA-N 3h-quinolin-4-one Chemical compound C1=CC=C2C(=O)CC=NC2=C1 HETSDWRDICBRSQ-UHFFFAOYSA-N 0.000 description 1
- BCRHMAZIUFJNEM-UHFFFAOYSA-N 4,5-dihydropyrrolo[3,4-d][1,3]thiazol-6-one Chemical compound N1=CSC2=C1CNC2=O BCRHMAZIUFJNEM-UHFFFAOYSA-N 0.000 description 1
- LHCOVOKZWQYODM-CPEOKENHSA-N 4-amino-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one;1-[(2r,4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1.O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 LHCOVOKZWQYODM-CPEOKENHSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- POILWHVDKZOXJZ-UHFFFAOYSA-N 4-hydroxypent-3-en-2-one Chemical compound CC(O)=CC(C)=O POILWHVDKZOXJZ-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 1
- RKYBOAKGTWOIFJ-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine Chemical class C1=NC=C2CCCNC2=N1 RKYBOAKGTWOIFJ-UHFFFAOYSA-N 0.000 description 1
- VRUDHVVJIWFTGM-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidine Chemical class N1=CN=C2CCCNC2=C1 VRUDHVVJIWFTGM-UHFFFAOYSA-N 0.000 description 1
- SMSHIXOEBWOYJS-UHFFFAOYSA-N 5,6,7,8-tetrahydroquinazoline Chemical class C1=NC=C2CCCCC2=N1 SMSHIXOEBWOYJS-UHFFFAOYSA-N 0.000 description 1
- PEAOEIWYQVXZMB-UHFFFAOYSA-N 5-bromo-2-chloropyridine Chemical compound ClC1=CC=C(Br)C=N1 PEAOEIWYQVXZMB-UHFFFAOYSA-N 0.000 description 1
- CTWZYPZCDJKBRS-UHFFFAOYSA-N 5-bromo-2-fluoropyrimidine Chemical compound FC1=NC=C(Br)C=N1 CTWZYPZCDJKBRS-UHFFFAOYSA-N 0.000 description 1
- BJUPTJXRJDXLHF-UHFFFAOYSA-N 6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound N1=CN=C2CCCC2=C1 BJUPTJXRJDXLHF-UHFFFAOYSA-N 0.000 description 1
- PANGDCFLXUDHDI-UHFFFAOYSA-N 6,7-dihydro-5h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NCCC2=C1 PANGDCFLXUDHDI-UHFFFAOYSA-N 0.000 description 1
- NBXIOQTYZWAAEB-UHFFFAOYSA-N 6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidine Chemical compound C1=NC=C2CNCC2=N1 NBXIOQTYZWAAEB-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 108010079335 AMG 745 Proteins 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000005964 Acibenzolar-S-methyl Substances 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 102100027647 Activin receptor type-2B Human genes 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 1
- 201000006935 Becker muscular dystrophy Diseases 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 108030001720 Bontoxilysin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- XPLQOFPOALZTLJ-GIYVLMGKSA-N C1[C@@H](NC(=O)O1)CC2=CC=CC=C2.C1[C@@H](N(C(=O)O1)C(=O)CC2=CC=C(C=C2)F)CC3=CC=CC=C3 Chemical compound C1[C@@H](NC(=O)O1)CC2=CC=CC=C2.C1[C@@H](N(C(=O)O1)C(=O)CC2=CC=C(C=C2)F)CC3=CC=CC=C3 XPLQOFPOALZTLJ-GIYVLMGKSA-N 0.000 description 1
- NZSLWHICVBIQTK-UHFFFAOYSA-N C=C(C1)CC1(c(nccc1)c1F)C#N Chemical compound C=C(C1)CC1(c(nccc1)c1F)C#N NZSLWHICVBIQTK-UHFFFAOYSA-N 0.000 description 1
- ZRWMAMOBIQQJSA-UHFFFAOYSA-N C=C(C1)CC1C#N Chemical compound C=C(C1)CC1C#N ZRWMAMOBIQQJSA-UHFFFAOYSA-N 0.000 description 1
- AAJGCLATIIHQGM-UHFFFAOYSA-N CC(C)(C)OC(N(CC(C1)(CC1=[F])c(nccc1)c1F)c(nc1)ncc1-[n](cc1)cc1C#N)=O Chemical compound CC(C)(C)OC(N(CC(C1)(CC1=[F])c(nccc1)c1F)c(nc1)ncc1-[n](cc1)cc1C#N)=O AAJGCLATIIHQGM-UHFFFAOYSA-N 0.000 description 1
- IXTOPLFTCADDEN-UHFFFAOYSA-N CC(C)(C1=C(C=CC=N1)Cl)NC2=NC=C(C=N2)CC=O Chemical compound CC(C)(C1=C(C=CC=N1)Cl)NC2=NC=C(C=N2)CC=O IXTOPLFTCADDEN-UHFFFAOYSA-N 0.000 description 1
- KTFSZXMJRAOPBM-UHFFFAOYSA-N CC(C)(c1ncccc1Cl)Nc(nc1)ncc1-c1c[n](c(C(N)=O)c[s]2)c2n1 Chemical compound CC(C)(c1ncccc1Cl)Nc(nc1)ncc1-c1c[n](c(C(N)=O)c[s]2)c2n1 KTFSZXMJRAOPBM-UHFFFAOYSA-N 0.000 description 1
- WYBCGBVYIUQGQT-UHFFFAOYSA-N COc1nc(C2(CCC2)C#N)ccc1 Chemical compound COc1nc(C2(CCC2)C#N)ccc1 WYBCGBVYIUQGQT-UHFFFAOYSA-N 0.000 description 1
- RVIWSZDOYHFHGG-ODIXNEOGSA-N C[C@H](CN1C(=O)C2=CC=CC=C2C1=O)C3=CC=C(C=C3)F.C[C@H](CO)C1=CC=C(C=C1)F Chemical compound C[C@H](CN1C(=O)C2=CC=CC=C2C1=O)C3=CC=C(C=C3)F.C[C@H](CO)C1=CC=C(C=C1)F RVIWSZDOYHFHGG-ODIXNEOGSA-N 0.000 description 1
- PMGLXGPNYILPNI-JAEXWWEUSA-N C[C@H](CO)C1=CC=C(C=C1)F.C[C@@H](C1=CC=C(C=C1)F)C(=O)N2[C@H](COC2=O)CC3=CC=CC=C3 Chemical compound C[C@H](CO)C1=CC=C(C=C1)F.C[C@@H](C1=CC=C(C=C1)F)C(=O)N2[C@H](COC2=O)CC3=CC=CC=C3 PMGLXGPNYILPNI-JAEXWWEUSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108090000625 Cathepsin K Proteins 0.000 description 1
- 102000004171 Cathepsin K Human genes 0.000 description 1
- 208000015374 Central core disease Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
- 101000936911 Chionoecetes opilio Sarcoplasmic/endoplasmic reticulum calcium ATPase Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 208000004117 Congenital Myasthenic Syndromes Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 235000017788 Cydonia oblonga Nutrition 0.000 description 1
- 102000010831 Cytoskeletal Proteins Human genes 0.000 description 1
- 108010037414 Cytoskeletal Proteins Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 102100034067 Dehydrogenase/reductase SDR family member 11 Human genes 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 108010092674 Enkephalins Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- RSEPBGGWRJCQGY-RBRWEJTLSA-N Estradiol valerate Chemical compound C1CC2=CC(O)=CC=C2[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCC)[C@@]1(C)CC2 RSEPBGGWRJCQGY-RBRWEJTLSA-N 0.000 description 1
- KGWDUNBJIMUFAP-KVVVOXFISA-N Ethanolamine Oleate Chemical compound NCCO.CCCCCCCC\C=C/CCCCCCCC(O)=O KGWDUNBJIMUFAP-KVVVOXFISA-N 0.000 description 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
- 206010015829 Extraocular muscle paresis Diseases 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- TUNARGMXIPKYIE-YPFXGUDJSA-N F[C@H](C1)C[C@]1(CNc1ncccn1)c(nccc1)c1F Chemical compound F[C@H](C1)C[C@]1(CNc1ncccn1)c(nccc1)c1F TUNARGMXIPKYIE-YPFXGUDJSA-N 0.000 description 1
- BHEZWQNYNXZXQB-UHFFFAOYSA-N Fc1cccnc1[ClH+] Chemical compound Fc1cccnc1[ClH+] BHEZWQNYNXZXQB-UHFFFAOYSA-N 0.000 description 1
- MBTGBRYMJKYYOE-UHFFFAOYSA-N Fc1nc(F)ccc1 Chemical compound Fc1nc(F)ccc1 MBTGBRYMJKYYOE-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010017065 Foster-Kennedy Syndrome Diseases 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- 206010017711 Gangrene Diseases 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 1
- 206010053185 Glycogen storage disease type II Diseases 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 description 1
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 201000002980 Hyperparathyroidism Diseases 0.000 description 1
- 206010020844 Hyperthermia malignant Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 208000000038 Hypoparathyroidism Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 238000000023 Kugelrohr distillation Methods 0.000 description 1
- 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical class C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 201000009342 Limb-girdle muscular dystrophy Diseases 0.000 description 1
- 229940127470 Lipase Inhibitors Drugs 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 description 1
- 229940124761 MMP inhibitor Drugs 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000018717 Malignant hyperthermia of anesthesia Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 1
- 206010068836 Metabolic myopathy Diseases 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 201000002169 Mitochondrial myopathy Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 108091005975 Myofilaments Proteins 0.000 description 1
- 206010028643 Myopathy endocrine Diseases 0.000 description 1
- 241000872931 Myoporum sandwicense Species 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- 208000010316 Myotonia congenita Diseases 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- WJJRHLHOIIXVGB-QUWSVYMGSA-N NCc(cc1)c[n]1-c1cnc(NC[C@](C2)(C[C@H]2F)c(nccc2)c2F)nc1 Chemical compound NCc(cc1)c[n]1-c1cnc(NC[C@](C2)(C[C@H]2F)c(nccc2)c2F)nc1 WJJRHLHOIIXVGB-QUWSVYMGSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010029315 Neuromuscular blockade Diseases 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 1
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 208000011623 Obstructive Lung disease Diseases 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 239000007990 PIPES buffer Substances 0.000 description 1
- 108010015181 PPAR delta Proteins 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 102000000536 PPAR gamma Human genes 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 206010033892 Paraplegia Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010034203 Pectus Carinatum Diseases 0.000 description 1
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- MFOCDFTXLCYLKU-CMPLNLGQSA-N Phendimetrazine Chemical compound O1CCN(C)[C@@H](C)[C@@H]1C1=CC=CC=C1 MFOCDFTXLCYLKU-CMPLNLGQSA-N 0.000 description 1
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
- 208000014993 Pituitary disease Diseases 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 208000010366 Postpoliomyelitis syndrome Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 206010037779 Radiculopathy Diseases 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 101100437153 Rattus norvegicus Acvr2b gene Proteins 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- 102000019027 Ryanodine Receptor Calcium Release Channel Human genes 0.000 description 1
- OKRZTZSFLHGZLL-UHFFFAOYSA-N S1C=NC=2C=NC=CC21.S2C=CC=1C=NC=CC12 Chemical compound S1C=NC=2C=NC=CC21.S2C=CC=1C=NC=CC12 OKRZTZSFLHGZLL-UHFFFAOYSA-N 0.000 description 1
- IRHXGOXEBNJUSN-YOXDLBRISA-N Saquinavir mesylate Chemical compound CS(O)(=O)=O.C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 IRHXGOXEBNJUSN-YOXDLBRISA-N 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 101710142969 Somatoliberin Proteins 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
- QHMBSVQNZZTUGM-UHFFFAOYSA-N Trans-Cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- HWHLPVGTWGOCJO-UHFFFAOYSA-N Trihexyphenidyl Chemical group C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 HWHLPVGTWGOCJO-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 108010048673 Vitronectin Receptors Proteins 0.000 description 1
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- FJWGYAHXMCUOOM-QHOUIDNNSA-N [(2s,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6s)-4,5-dinitrooxy-2-(nitrooxymethyl)-6-[(2r,3r,4s,5r,6s)-4,5,6-trinitrooxy-2-(nitrooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-3,5-dinitrooxy-6-(nitrooxymethyl)oxan-4-yl] nitrate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O)O[C@H]1[C@@H]([C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@@H](CO[N+]([O-])=O)O1)O[N+]([O-])=O)CO[N+](=O)[O-])[C@@H]1[C@@H](CO[N+]([O-])=O)O[C@@H](O[N+]([O-])=O)[C@H](O[N+]([O-])=O)[C@H]1O[N+]([O-])=O FJWGYAHXMCUOOM-QHOUIDNNSA-N 0.000 description 1
- XUTIDUCSRSNKKP-UHFFFAOYSA-N [1,2]oxazolo[4,5-b]pyridine Chemical compound C1=CN=C2C=NOC2=C1 XUTIDUCSRSNKKP-UHFFFAOYSA-N 0.000 description 1
- AMIWTKBQVQQBBS-UHFFFAOYSA-N [1,2]oxazolo[4,5-c]pyridine Chemical compound C1=NC=C2C=NOC2=C1 AMIWTKBQVQQBBS-UHFFFAOYSA-N 0.000 description 1
- DITTYRBIXKVOTK-UHFFFAOYSA-N [1,2]oxazolo[5,4-b]pyridine Chemical compound C1=CC=C2C=NOC2=N1 DITTYRBIXKVOTK-UHFFFAOYSA-N 0.000 description 1
- WXTRHHSZKLAHHV-UHFFFAOYSA-N [1,2]oxazolo[5,4-c]pyridine Chemical compound N1=CC=C2C=NOC2=C1 WXTRHHSZKLAHHV-UHFFFAOYSA-N 0.000 description 1
- ZTAPFURKEMZRSQ-UHFFFAOYSA-N [1,2]thiazolo[4,5-b]pyridine Chemical compound C1=CN=C2C=NSC2=C1 ZTAPFURKEMZRSQ-UHFFFAOYSA-N 0.000 description 1
- HUMJZSMCTXGAMD-UHFFFAOYSA-N [1,2]thiazolo[4,5-c]pyridine Chemical compound C1=NC=C2C=NSC2=C1 HUMJZSMCTXGAMD-UHFFFAOYSA-N 0.000 description 1
- VTIVYUBSVCXRPI-UHFFFAOYSA-N [1,2]thiazolo[5,4-b]pyridine Chemical compound C1=CC=C2C=NSC2=N1 VTIVYUBSVCXRPI-UHFFFAOYSA-N 0.000 description 1
- YBAGZQVTZXUQEU-UHFFFAOYSA-N [1,2]thiazolo[5,4-c]pyridine Chemical compound N1=CC=C2C=NSC2=C1 YBAGZQVTZXUQEU-UHFFFAOYSA-N 0.000 description 1
- ZATXVRSLQDRAHZ-UHFFFAOYSA-N [1,3]oxazolo[4,5-c]pyridine Chemical compound N1=CC=C2OC=NC2=C1 ZATXVRSLQDRAHZ-UHFFFAOYSA-N 0.000 description 1
- BFPLMTPHDFFMTG-UHFFFAOYSA-N [1,3]oxazolo[5,4-b]pyridine Chemical compound C1=CN=C2OC=NC2=C1 BFPLMTPHDFFMTG-UHFFFAOYSA-N 0.000 description 1
- XRVDKIQEFCJTBZ-UHFFFAOYSA-N [1,3]oxazolo[5,4-c]pyridine Chemical compound C1=NC=C2OC=NC2=C1 XRVDKIQEFCJTBZ-UHFFFAOYSA-N 0.000 description 1
- BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 1
- YWBULOYFCXZCGF-UHFFFAOYSA-N [1,3]thiazolo[4,5-d]pyrimidine Chemical class C1=NC=C2SC=NC2=N1 YWBULOYFCXZCGF-UHFFFAOYSA-N 0.000 description 1
- WFIHKLWVLPBMIQ-UHFFFAOYSA-N [1,3]thiazolo[5,4-b]pyridine Chemical compound C1=CN=C2SC=NC2=C1 WFIHKLWVLPBMIQ-UHFFFAOYSA-N 0.000 description 1
- FHIMYVFGWKCROK-UHFFFAOYSA-N [1,3]thiazolo[5,4-c]pyridine Chemical compound C1=NC=C2SC=NC2=C1 FHIMYVFGWKCROK-UHFFFAOYSA-N 0.000 description 1
- YTFIUHZHMLAERQ-UHFFFAOYSA-N [1-(4-fluorophenyl)cyclobutyl]methanamine Chemical compound C=1C=C(F)C=CC=1C1(CN)CCC1 YTFIUHZHMLAERQ-UHFFFAOYSA-N 0.000 description 1
- TYNMKBSYEUUDOM-UHFFFAOYSA-N [3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methanamine Chemical compound N=1C=CC=C(F)C=1C1(CN)CC(F)C1 TYNMKBSYEUUDOM-UHFFFAOYSA-N 0.000 description 1
- 210000000579 abdominal fat Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 238000003811 acetone extraction Methods 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 108010057453 activin receptor type II-B Proteins 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000027093 acute inflammatory demyelinating polyradiculoneuropathy Diseases 0.000 description 1
- 239000000362 adenosine triphosphatase inhibitor Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 239000000695 adrenergic alpha-agonist Substances 0.000 description 1
- 108010083553 alanyl-histidyl-(2-naphthyl)alanyl-tryptophyl-phenylalanyl-lysinamide Proteins 0.000 description 1
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 229940062527 alendronate Drugs 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- FPQFYIAXQDXNOR-QDKLYSGJSA-N alpha-Zearalenol Chemical compound O=C1O[C@@H](C)CCC[C@H](O)CCC\C=C\C2=CC(O)=CC(O)=C21 FPQFYIAXQDXNOR-QDKLYSGJSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- 229940124325 anabolic agent Drugs 0.000 description 1
- 229940070021 anabolic steroids Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 230000000798 anti-retroviral effect Effects 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 229940127226 anticholesterol agent Drugs 0.000 description 1
- 229940052651 anticholinergic tertiary amines Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000008321 arterial blood flow Effects 0.000 description 1
- 208000030137 articulation disease Diseases 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 108010014210 axokine Proteins 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 150000001539 azetidines Chemical class 0.000 description 1
- 150000001541 aziridines Chemical class 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 229960000794 baclofen Drugs 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- DMSMPAJRVJJAGA-UHFFFAOYSA-N benzo[d]isothiazol-3-one Chemical compound C1=CC=C2C(=O)NSC2=C1 DMSMPAJRVJJAGA-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- VIQRCOQXIHFJND-UHFFFAOYSA-N bicyclo[2.2.2]oct-2-ene Chemical compound C1CC2CCC1C=C2 VIQRCOQXIHFJND-UHFFFAOYSA-N 0.000 description 1
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical compound C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229940053031 botulinum toxin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical group 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000005510 but-1-en-2-yl group Chemical group 0.000 description 1
- HGXJOXHYPGNVNK-UHFFFAOYSA-N butane;ethenoxyethane;tin Chemical compound CCCC[Sn](CCCC)(CCCC)C(=C)OCC HGXJOXHYPGNVNK-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 150000001669 calcium Chemical class 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229940069978 calcium supplement Drugs 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000001914 calming effect Effects 0.000 description 1
- 229950011318 cannabidiol Drugs 0.000 description 1
- QHMBSVQNZZTUGM-ZWKOTPCHSA-N cannabidiol Chemical compound OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-ZWKOTPCHSA-N 0.000 description 1
- ZTGXAWYVTLUPDT-UHFFFAOYSA-N cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CC=C(C)C1 ZTGXAWYVTLUPDT-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 201000007303 central core myopathy Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- MVCQKIKWYUURMU-UHFFFAOYSA-N cetilistat Chemical compound C1=C(C)C=C2C(=O)OC(OCCCCCCCCCCCCCCCC)=NC2=C1 MVCQKIKWYUURMU-UHFFFAOYSA-N 0.000 description 1
- 229950002397 cetilistat Drugs 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 208000019902 chronic diarrheal disease Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- RRGUKTPIGVIEKM-UHFFFAOYSA-N cilostazol Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 RRGUKTPIGVIEKM-UHFFFAOYSA-N 0.000 description 1
- 229960004588 cilostazol Drugs 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 201000011474 congenital myopathy Diseases 0.000 description 1
- 229940035811 conjugated estrogen Drugs 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 150000001975 deuterium Chemical group 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 229960002656 didanosine Drugs 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- XXEPPPIWZFICOJ-UHFFFAOYSA-N diethylpropion Chemical compound CCN(CC)C(C)C(=O)C1=CC=CC=C1 XXEPPPIWZFICOJ-UHFFFAOYSA-N 0.000 description 1
- 229960004890 diethylpropion Drugs 0.000 description 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- PCXRACLQFPRCBB-ZWKOTPCHSA-N dihydrocannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)C)CCC(C)=C1 PCXRACLQFPRCBB-ZWKOTPCHSA-N 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000010102 embolization Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 229960000610 enoxaparin Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229960004766 estradiol valerate Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 229940031124 ethanolamine oleate Drugs 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000028327 extreme fatigue Diseases 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- LYINKTVZUSKQEQ-UHFFFAOYSA-N furan-3-one Chemical compound O=C1COC=C1 LYINKTVZUSKQEQ-UHFFFAOYSA-N 0.000 description 1
- RCFDIXKVOHJQPP-UHFFFAOYSA-N furo[2,3-b]pyridine Chemical compound C1=CN=C2OC=CC2=C1 RCFDIXKVOHJQPP-UHFFFAOYSA-N 0.000 description 1
- ZYXBIOIYWUIXSM-UHFFFAOYSA-N furo[2,3-c]pyridine Chemical compound C1=NC=C2OC=CC2=C1 ZYXBIOIYWUIXSM-UHFFFAOYSA-N 0.000 description 1
- YRTCKZIKGWZNCU-UHFFFAOYSA-N furo[3,2-b]pyridine Chemical compound C1=CC=C2OC=CC2=N1 YRTCKZIKGWZNCU-UHFFFAOYSA-N 0.000 description 1
- WJDMEHCIRPKRRQ-UHFFFAOYSA-N furo[3,2-c]pyridine Chemical compound N1=CC=C2OC=CC2=C1 WJDMEHCIRPKRRQ-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 208000007345 glycogen storage disease Diseases 0.000 description 1
- 201000004502 glycogen storage disease II Diseases 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 108010015153 growth hormone releasing hexapeptide Proteins 0.000 description 1
- 239000003324 growth hormone secretagogue Substances 0.000 description 1
- 108010085742 growth hormone-releasing peptide-2 Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012145 high-salt buffer Substances 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 239000003668 hormone analog Substances 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 1
- UFBBWLWUIISIPW-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole Chemical compound C1=CSC2=NC=CN21 UFBBWLWUIISIPW-UHFFFAOYSA-N 0.000 description 1
- UNNMBHYRLHXKLF-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole-3-carboxamide Chemical compound S1C=2N(C(=C1)C(=O)N)C=CN=2 UNNMBHYRLHXKLF-UHFFFAOYSA-N 0.000 description 1
- DUMUNAZNDFRJPK-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole-3-carboxylic acid Chemical compound C1=CN2C(C(=O)O)=CSC2=N1 DUMUNAZNDFRJPK-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 208000023692 inborn mitochondrial myopathy Diseases 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 201000008319 inclusion body myositis Diseases 0.000 description 1
- 125000003114 inden-1-yl group Chemical group [H]C1=C([H])C([H])(*)C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 229960004243 indinavir sulfate Drugs 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- MGIYRDNGCNKGJU-UHFFFAOYSA-N isothiazolinone Chemical compound O=C1C=CSN1 MGIYRDNGCNKGJU-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 229940033984 lamivudine / zidovudine Drugs 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 208000020442 loss of weight Diseases 0.000 description 1
- 239000003055 low molecular weight heparin Substances 0.000 description 1
- 229940127215 low-molecular weight heparin Drugs 0.000 description 1
- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 239000011654 magnesium acetate Substances 0.000 description 1
- 235000011285 magnesium acetate Nutrition 0.000 description 1
- 229940069446 magnesium acetate Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 201000007004 malignant hyperthermia Diseases 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229960000299 mazindol Drugs 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- 230000010120 metabolic dysregulation Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- AWUPLMYXZJKHEG-UHFFFAOYSA-N methyl 2-chloro-2,2-difluoroacetate Chemical compound COC(=O)C(F)(F)Cl AWUPLMYXZJKHEG-UHFFFAOYSA-N 0.000 description 1
- VJOKXLBQCKCWLV-UHFFFAOYSA-N methyl 2-chloropyrimidine-5-carboxylate Chemical compound COC(=O)C1=CN=C(Cl)N=C1 VJOKXLBQCKCWLV-UHFFFAOYSA-N 0.000 description 1
- HBGFOXSEQMZATI-UHFFFAOYSA-N methyl 4-hydroxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate Chemical compound COC(=O)C1=CC=C(O)C(B2OC(C)(C)C(C)(C)O2)=C1 HBGFOXSEQMZATI-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 206010065579 multifocal motor neuropathy Diseases 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 208000016334 muscle symptom Diseases 0.000 description 1
- 230000005996 muscular dysfunction Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000029264 myotonic syndrome Diseases 0.000 description 1
- TUNARGMXIPKYIE-UHFFFAOYSA-N n-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methyl]pyrimidin-2-amine Chemical compound C1C(F)CC1(C=1C(=CC=CN=1)F)CNC1=NC=CC=N1 TUNARGMXIPKYIE-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000003880 negative regulation of appetite Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960002362 neostigmine Drugs 0.000 description 1
- LULNWZDBKTWDGK-UHFFFAOYSA-M neostigmine bromide Chemical compound [Br-].CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 LULNWZDBKTWDGK-UHFFFAOYSA-M 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 208000013315 neuromuscular junction disease Diseases 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- 229960000417 norgestimate Drugs 0.000 description 1
- KIQQMECNKUGGKA-NMYWJIRASA-N norgestimate Chemical compound O/N=C/1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(OC(C)=O)C#C)[C@@H]4[C@@H]3CCC2=C\1 KIQQMECNKUGGKA-NMYWJIRASA-N 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- OGIKSURTYJLRMP-UHFFFAOYSA-N oxadiazolo[4,5-b]pyridine Chemical compound C1=CN=C2N=NOC2=C1 OGIKSURTYJLRMP-UHFFFAOYSA-N 0.000 description 1
- LBWZSUHDRDWJEC-UHFFFAOYSA-N oxadiazolo[4,5-c]pyridine Chemical compound C1=NC=CC2=C1N=NO2 LBWZSUHDRDWJEC-UHFFFAOYSA-N 0.000 description 1
- RWXCVESEMJNNMF-UHFFFAOYSA-N oxadiazolo[5,4-b]pyridine Chemical compound C1=CN=C2ON=NC2=C1 RWXCVESEMJNNMF-UHFFFAOYSA-N 0.000 description 1
- SVMOLIXMHXABPH-UHFFFAOYSA-N oxadiazolo[5,4-c]pyridine Chemical compound C1=NC=CC2=C1ON=N2 SVMOLIXMHXABPH-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 1
- 150000002921 oxetanes Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 208000035824 paresthesia Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001476 pentoxifylline Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960000436 phendimetrazine Drugs 0.000 description 1
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
- 229960000395 phenylpropanolamine Drugs 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229960001697 physostigmine Drugs 0.000 description 1
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
- 230000006584 pituitary dysfunction Effects 0.000 description 1
- 208000017402 pituitary gland disease Diseases 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 208000006473 polyradiculopathy Diseases 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229960000208 pralmorelin Drugs 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 229940127293 prostanoid Drugs 0.000 description 1
- 150000003814 prostanoids Chemical class 0.000 description 1
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical class N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 1
- BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical class C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 1
- PAQYIEZTLSDLQO-UHFFFAOYSA-N pyrido[3,4-d]pyrimidine Chemical class N1=CN=C2C=NC=CC2=C1 PAQYIEZTLSDLQO-UHFFFAOYSA-N 0.000 description 1
- PLZDHJUUEGCXJH-UHFFFAOYSA-N pyrido[4,3-d]pyrimidine Chemical class C1=NC=C2C=NC=CC2=N1 PLZDHJUUEGCXJH-UHFFFAOYSA-N 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- FFRYUAVNPBUEIC-UHFFFAOYSA-N quinoxalin-2-ol Chemical compound C1=CC=CC2=NC(O)=CN=C21 FFRYUAVNPBUEIC-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 108700015048 receptor decoy activity proteins Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- 108091052345 ryanodine receptor (TC 1.A.3.1) family Proteins 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- 229960003542 saquinavir mesylate Drugs 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 208000000943 scapulohumeral muscular dystrophy Diseases 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000000276 sedentary effect Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 1
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- 210000003875 slow muscle fiber Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 102000009076 src-Family Kinases Human genes 0.000 description 1
- 108010087686 src-Family Kinases Proteins 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960001203 stavudine Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229950007447 sulbenox Drugs 0.000 description 1
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 description 1
- ZRUHSJRHKVQPAU-UHFFFAOYSA-N tert-butyl n-(5-bromopyrimidin-2-yl)-n-[[1-(3-chloropyridin-2-yl)cyclobutyl]methyl]carbamate Chemical compound N=1C=C(Br)C=NC=1N(C(=O)OC(C)(C)C)CC1(C=2C(=CC=CN=2)Cl)CCC1 ZRUHSJRHKVQPAU-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- GNXPUXGOQIHJLJ-UHFFFAOYSA-N thiadiazolo[4,5-b]pyridine Chemical compound C1=CN=C2N=NSC2=C1 GNXPUXGOQIHJLJ-UHFFFAOYSA-N 0.000 description 1
- HKMXLNRHGNWKJG-UHFFFAOYSA-N thiadiazolo[4,5-c]pyridine Chemical compound C1=NC=CC2=C1N=NS2 HKMXLNRHGNWKJG-UHFFFAOYSA-N 0.000 description 1
- QKTRRACPJVYJNU-UHFFFAOYSA-N thiadiazolo[5,4-b]pyridine Chemical compound C1=CN=C2SN=NC2=C1 QKTRRACPJVYJNU-UHFFFAOYSA-N 0.000 description 1
- DNWLQCBSEZHTMF-UHFFFAOYSA-N thiadiazolo[5,4-c]pyridine Chemical compound C1=NC=CC2=C1SN=N2 DNWLQCBSEZHTMF-UHFFFAOYSA-N 0.000 description 1
- SMZMHUCIDGHERP-UHFFFAOYSA-N thieno[2,3-b]pyridine Chemical compound C1=CN=C2SC=CC2=C1 SMZMHUCIDGHERP-UHFFFAOYSA-N 0.000 description 1
- GDQBPBMIAFIRIU-UHFFFAOYSA-N thieno[2,3-c]pyridine Chemical compound C1=NC=C2SC=CC2=C1 GDQBPBMIAFIRIU-UHFFFAOYSA-N 0.000 description 1
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
- RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical class C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 229960001032 trihexyphenidyl Drugs 0.000 description 1
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- UPCXAARSWVHVLY-UHFFFAOYSA-N tris(2-hydroxyethyl)azanium;acetate Chemical compound CC(O)=O.OCCN(CCO)CCO UPCXAARSWVHVLY-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 108010013477 troponin-tropomyosin complex Proteins 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229960002300 zeranol Drugs 0.000 description 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
- 229960002555 zidovudine Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- 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
- A61K31/495—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
-
- 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
- A61K31/495—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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
R1は、水素、ハロゲン、CN、C1〜6アルキル、C1〜6ハロアルキル、C(O)ORa、C(O)NRbRc、ORa、NRbRc、C6〜10アリール及び5〜10員ヘテロアリールから選択され;
R2は、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、5〜10員ヘテロアリール及びNRbRcから選択され、前記のC3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール及び5〜10員ヘテロアリール基のそれぞれはハロゲン、CN、オキソ、(CH2)nORa、(CH2)nOC(O)Ra、(CH2)nOC(O)ORa、(CH2)nOC(O)NRbRc、(CH2)nNRbRc、(CH2)nNRdC(O)Ra、(CH2)nNRdC(O)ORa、(CH2)nNRdC(O)NRbRc、(CH2)nNRdC(O)C(O)NRbRc、(CH2)nNRdC(S)Ra、(CH2)nNRdC(S)ORa、(CH2)nNRdC(S)NRbRc、(CH2)nNRdC(NRe)NRbRc、(CH2)nNRdS(O)Ra、(CH2)nNRdSO2Ra、(CH2)nNRdSO2NRbRc、(CH2)nC(O)Ra、(CH2)nC(O)ORa、(CH2)nC(O)NRbRc、(CH2)nC(S)Ra、(CH2)nC(S)ORa、(CH2)nC(S)NRbRc、(CH2)nC(NRe)NRbRc、(CH2)nSRa、(CH2)nS(O)Ra、(CH2)nSO2Ra、(CH2)nSO2NRbRc、C1〜6アルキル、C1〜6ハロアルキル、C2〜6アルケニル、C2〜6アルキニル、(CH2)nC3〜8シクロアルキル、(CH2)n3〜8員ヘテロシクロアルキル、(CH2)nC6〜10アリール及び(CH2)n5〜10員ヘテロアリールから選択される1、2、3、4又は5個の置換基で場合により置換されており、前記のC1−6アルキル、C2〜6アルケニル、C2〜6アルキニル、(CH2)nC3〜8シクロアルキル、(CH2)n3〜8員ヘテロシクロアルキル、(CH2)nC6〜10アリール及び(CH2)n5〜10員ヘテロアリール基のそれぞれは1、2、3、4又は5個のRf置換基で場合により置換されており;
R3は、水素、ハロゲン、CN、C1〜6アルキル、C1〜6ハロアルキル、C(O)ORa、C(O)NRbRc、ORa、NRbRc、C6〜10アリール及び5〜10員ヘテロアリールから選択され;
R4は、水素、C1〜6アルキル、C1〜6ハロアルキル、C(O)Ra、C(O)ORa、C(O)NRbRc及びSO2Raから選択され;
R5及びR6は、それぞれ、水素、ハロゲン、C1〜6アルキル及びC1〜6ハロアルキルから独立に選択され;
あるいは、R5及びR6は、それらが結合されている炭素原子と一緒になって、それぞれハロゲン、CN、オキソ、ORa、OC(O)Ra、OC(O)ORa、NRbRc、C(O)Ra、C(O)ORa、C(O)NRbRc、S(O)Ra、SO2Ra、SO2NRbRc、C1〜6アルキル及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換された、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル又は3〜8員ヘテロシクロアルケニルを形成しており;
R7は、それぞれハロゲン、CN、オキソ、ORa、OC(O)Ra、OC(O)ORa、OC(O)NRbRc、NRbRc、NRdC(O)Ra、NRdC(O)ORa、NRdC(O)NRbRc、NRdC(O)C(O)NRbRc、NRdC(S)Ra、NRdC(S)ORa、NRdC(S)NRbRc、NRdC(NRe)NRbRc、NRdS(O)Ra、NRdSO2Ra、NRdSO2NRbRc、C(O)Ra、C(O)ORa、C(O)NRbRc、C(S)Ra、C(S)ORa、C(S)NRbRc、C(NRe)NRbRc、SRa、S(O)Ra、SO2Ra、SO2NRbRc、C1〜6アルキル、C1〜6ハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル、及び5〜10員ヘテロアリールから選択される1、2、3、4又は5個の置換基で場合により置換された、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール及び5〜10員ヘテロアリールから選択され、前記のC1〜6アルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル及び5〜10員ヘテロアリール基のそれぞれは1、2、3、4又は5個のRf置換基で場合により置換されており;
R8及びR9は、それぞれの存在時には、それぞれ、水素、ハロゲン及びC1〜6アルキルから独立に選択され;
Xは、結合、−(CH2)p−、−(CH2)pC(O)(CH2)q−、−(CH2)pO(CH2)q−、−(CH2)pS(CH2)q−、−(CH2)pNRd(CH2)q−、−(CH2)pC(O)O(CH2)q−、−(CH2)pOC(O)(CH2)q−、−(CH2)pNRdC(O)(CH2)q−、−(CH2)pC(O)NRd(CH2)q−、−(CH2)pNRdC(O)NRd(CH2)q−、−(CH2)pNRdSO2(CH2)q−、及び−(CH2)pSO2NRd(CH2)q−から選択され;
あるいは、X、R2及びR3は、それらが結合されている炭素原子と一緒になって、酸素、窒素及び硫黄から選択される1個又はそれ以上のヘテロ原子を場合により含有している、及び1つ又はそれ以上の二重結合を場合により含有している、及び1、2、3、4又は5個のRf置換基で場合により置換された5〜6員環を形成しており;
Raは、それぞれの存在時には、水素、C1〜6アルキル、C1〜6ハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル及び5〜10員ヘテロアリールから独立に選択され、前記のC1〜6アルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル及び5〜10員ヘテロアリール基のそれぞれは1、2、3、4又は5個のRf置換基で場合により置換されており;
Rb及びRcは、それぞれの存在時には、それぞれ、水素、C1〜6アルキル、C1〜6ハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル、5〜10員ヘテロアリール、C(O)Rg、C(O)ORg、C(O)NRiRj及びSO2Rgから独立に選択され、前記のC1〜6アルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル及び5〜10員ヘテロアリール基のそれぞれは1、2、3、4又は5個のRf置換基で場合により置換されており;
Rdは、それぞれの存在時には、水素及びC1〜6アルキルから独立に選択され;
Reは、それぞれの存在時には、水素、CN、OH、C1〜6アルコキシ、C1〜6アルキル及びC1〜6ハロアルキルから独立に選択され;
Rfは、それぞれの存在時には、ハロゲン、CN、ORh、OC(O)Rh、OC(O)ORh、OC(O)NRiRj、NRiRj、NRdC(O)Rh、NRdC(O)ORh、NRdC(O)NRiRj、NRdC(O)C(O)NRiRj、NRdC(S)Rh、NRdC(S)ORh、NRdC(S)NRiRj、NRdC(NRe)NRiRj、NRdS(O)Rh、NRdSO2Rh、NRdSO2NRiRj、C(O)Rh、C(O)ORh、C(O)NRiRj、C(S)Rh、C(S)ORh、C(S)NRiRj、C(NRe)NRiRj、SRh、S(O)Rh、SO2Rh、SO2NRiRj、C1〜6アルキル、C1〜6ハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル及び5〜10員ヘテロアリールから独立に選択され、前記のC1〜6アルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル及び5〜10員ヘテロアリール基のそれぞれは1、2、3、4又は5個のRk置換基で場合により置換されており;
又は、単一炭素原子に結合された2つのRf置換基は、それら2つが結合されている炭素原子と一緒になって、カルボニル、C3〜8シクロアルキル及び3〜8員ヘテロシクロアルキルから選択される基を形成しており;
Rgは、それぞれの存在時には、それぞれハロゲン、CN、OH、C1〜6アルコキシ、C1〜6アルキル及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換された、C1〜6アルキル、C1〜6ハロアルキル、フェニル、ナフチル、及びC7〜11アラルキルから独立に選択され;
Rhは、それぞれの存在時には、水素、C1〜6アルキル、C1〜6ハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル及び5〜10員ヘテロアリールから独立に選択され、前記のC1〜6アルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル及び5〜10員ヘテロアリール基のそれぞれは1、2、3、4又は5個のRk置換基で場合により置換されており;
Ri及びRjは、それぞれの存在時には、それぞれ、水素、C1〜6アルキル、C1〜6ハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル、5〜10員ヘテロアリール、C(O)Rg、及びC(O)ORgから独立に選択され、前記のC1〜6アルキル、C1〜6ハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜8シクロアルキル、C3〜8シクロアルケニル、3〜8員ヘテロシクロアルキル、3〜8員ヘテロシクロアルケニル、C6〜10アリール、C7〜11アラルキル及び5〜10員ヘテロアリール基のそれぞれはハロゲン、CN、OH、C1〜6アルコキシ、C1〜6アルキル及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換されており;
Rkは、それぞれの存在時には、ハロゲン、CN、OH、C1〜6アルコキシ、NH2、NH(C1〜6アルキル)、N(C1〜6アルキル)2、NHC(O)C1〜6アルキル、NHC(O)C7〜11アラルキル、NHC(O)OC1〜6アルキル、NHC(O)OC7〜11アラルキル、OC(O)C1〜6アルキル、OC(O)C7〜11アラルキル、OC(O)OC1〜6アルキル、OC(O)OC7〜11アラルキル、C(O)C1〜6アルキル、C(O)C7〜11アラルキル、C(O)OC1〜6アルキル、C(O)OC7〜11アラルキル、C1〜6アルキル、C1〜6ハロアルキル、C2〜6アルケニル、及びC2〜6アルキニルから独立に選択され、前記の各C1〜6アルキル、C2〜6アルケニル、C2〜6アルキニル、及びC7〜11アラルキル置換基は、OH、C1〜6アルコキシ、NH2、NH(C1〜6アルキル)、N(C1〜6アルキル)2、NHC(O)C1〜6アルキル、NHC(O)C7〜11アラルキル、NHC(O)OC1〜6アルキル、及びNHC(O)OC7〜11アラルキルから選択される1、2又は3個の置換基で場合により置換されており;
又は、単一炭素原子に結合された2つのRk置換基は、それら2つが結合されている炭素原子と一緒になって、カルボニル基を形成しており;
mは、0、1又は2であり;
nは、それぞれの存在時には、独立に、0、1又は2であり;
pは、0、1又は2であり;
qは、0、1又は2である]
で表される化合物又はその薬学的に許容される塩である。
etal Troponin Activator, CK-2017357, Reduces Muscle Fatigue in an in situ Model of Vascular Insufficiency”, Society for Vascular Medicine's 2010 Annual Meeting: 21st Annual Scientific Sessions, Cleveland, OH, April 2010;を参照されたい)。
(S)−4−ベンジルオキサゾリジン−2−オン(10g、58mmol、1.0当量)/100mL THFの冷却(−78℃)溶液にn−BuLi(40mL、1.6M/ヘキサン、64mmol、1.1当量)を滴下で加えた。30分間撹拌した後、4−フルオロフェニルアセチルクロリド(10g、58mmol、1.0当量)を滴下で加えた。さらに30分間撹拌した後、この反応混合物を室温まで温めた。この反応を飽和NH4Cl水溶液でクエンチし、ジクロロメタンで抽出し、そうしてブラインで洗浄した。その有機層をこのあと硫酸ナトリウムで乾燥させ、濾過し、そうして真空で濃縮した。シリカゲルによる精製(10〜20%EtOAc/ヘキサン)により表題化合物が濃い油状物(14.7g、81%)としてもたらされた。
(S)−4−ベンジル−3−(2−(4−フルオロフェニル)アセチル)オキサゾリジン−2−オン(5.1g、16.3mmol、1.0当量)/乾燥THF(100mL)の室温溶液にヨードメタン(1.0mL、16.2mmol、1.0当量)をシリンジにより加えた。得られた混合物を−78℃まで冷却し、そうしてNaHMDS(8.15mL、2M/THF、16.3mmol、1.0当量)をシリンジにより滴下で加えた。−78℃で15分間撹拌した後、この反応混合物を室温まで温めた。この反応を飽和NH4Cl水溶液でクエンチし、そうしてEtOAcで希釈した。その有機層をブラインで洗浄し、Na2SO4で乾燥させ、濾過し、真空で濃縮した。シリカゲルクロマトグラフィーによる精製(7〜20%EtOAc/ヘキサン)により表題化合物(2.6g、49%)がもたらされた。
(S)−4−ベンジル−3−((S)−2−(4−フルオロフェニル)プロパノイル)オキサゾリジン−2−オン(1.8g、5.5mmol、1.0当量)/THF(18mL)の室温溶液にNaBH4(1.0g、26.4mmol、4.8当量)/水(6.0mL)の溶液を加えた。この反応混合物を室温で3時間撹拌し、その後1M HCl水溶液を注意を払いながら加えることによりクエンチした。この反応混合物を水及び酢酸エチルで希釈した。その層を分離させ、その有機層を続いてブラインで洗浄し、Na2SO4で乾燥させ、濾過し、真空で濃縮した。シリカゲルクロマトグラフィーによる精製(10〜75%EtOAc/ヘキサン)により表題化合物(0.824g、97%)がもたらされた。
(S)−2−(4−フルオロフェニル)プロパン−1−オール(0.82g、5.35mmol、1.0当量)+フタルイミド(0.82g、5.6mmol、1.05当量)+トリフェニルホスフィン(2.1g、8.03mmol、1.5当量)/乾燥THF(18mL)の溶液にジエチルアゾジカルボキシラート(3.6mL、15%/トルエン、8.0mmol、1.5当量)を滴下で加えた。この反応混合物を72時間に亘って撹拌し、その後真空で濃縮した。シリカゲルクロマトグラフィーによる精製(15〜25%EtOAc/ヘキサン)により表題化合物(0.9g、59%)がもたらされた。
(S)−2−(2−(4−フルオロフェニル)プロピル)イソインドリン−1,3−ジオン(900mg、3.2mmol、1.0当量)/トルエン(14mL)の室温溶液にヒドラジン水和物(1.4mL、45mmol、14当量)をシリンジにより加えた。得られた混合物を80℃に30分間加熱し、その後室温まで冷却させた。得られた溶液をその反応混合物中の固形物からデカントし、そうしてその固形物をさらなるトルエンで洗浄した。合わせた有機層を合わせ、真空で濃縮すると、表題化合物(491mg、99%)がもたらされた(これはさらに精製することなく用いた)。
2−クロロ−3−フルオロピリジン(3.0g、23mmol、1.0当量)+アセトニトリル(1.3mL、25mmol、1.1当量)/トルエン(50mL)の0℃溶液にナトリウムヘキサメチルジシラジド(NaHMDS)(2.0M/THF、13mL、25mmol、1.1当量)を加えた。得られた混合物を0℃で2時間撹拌し、その後EtOAcと水とに分配させた。その水層をEtOAcで抽出し、合わせた有機相を飽和NaClで洗浄し、Na2SO4で乾燥させ、真空で濃縮すると、粗製所望生成物が油状物としてもたらされ、これをさらに精製することなく用いた。
2−(3−フルオロピリジン−2−イル)アセトニトリルに対して2,6−ジフルオロピリジン(5.0g、43mmol、1.0当量)+シクロブチルカルボニトリル(3.5g、43mmol、1.0当量)+NaHMDS(2.0M/THF、24mL、47mmol、1.1当量)/トルエン(100mL)で上記と同じ手順を加え、溶離液として25%EtOAc/ヘキサンを用いるシリカゲルでの精製を行うことにより所望生成物(4.9g、64%)を無色の油状物として得た。
窒素下0℃にある無水メタノール(6.0mL)にナトリウム金属(約1g)を加え、この混合物を30分間撹拌した。この反応混合物に1−(6−フルオロピリジン−2−イル)シクロブタンカルボニトリル(1.6g、9.1mmol)を加え、その後75℃まで加熱し、45分間撹拌した。この溶液を室温まで冷却させ、水とEtOAcとに分配させた。その層を分離させ、その水相をEtOAcで抽出し、そうしてその合わせた有機相を飽和NaClで洗浄し、Na2SO4で乾燥させ、そうして真空で濃縮して、所望生成物(1.7g、97%)を無色の油状物として得た。
1−(6−メトキシピリジン−2−イル)シクロブタンカルボニトリル(1.7g、8.8mmol、1.0当量)/THF(20mL)の撹拌溶液にリチウムアルミニウムヒドリド溶液(1.0M/THF、11mL、11mmol、1.1当量)を加えた。この混合物を1.5時間還流させ、室温まで冷却させた。水(0.43mL)をゆっくり加え、その後0.43mLの3M NaOHを加え、次いで0.43mLの水を3回加えた(フィーザー・フィーザー後処理)。得られた混合物を珪藻土に通して濾過し、THFで濯ぎ洗いした。その合わせた有機物をNa2SO4で乾燥させ、乾固まで濃縮して、所望生成物(1.6g、97%)を粘稠な油状物として得た。
DMSO(60mL)が入っている250mL丸底フラスコに1−(3−フルオロピリジン−2−イル)シクロブタンカルボニトリル(2.96g、16.8mmol、1.0当量)を加え、この混合物を均質になるまで撹拌した。炭酸カリウム(7.0g、50.4mmol、3.0当量)をこのあと加え、この反応混合物を0℃まで冷却させ、次いで35%過酸化水素(6.5mL)を加えた。この反応を30分間0℃で撹拌し、その後室温まで温めた。この時点で、反応を水(50mL)及び酢酸エチル(100mL)で希釈した。分離漏斗に移して震盪した後、その有機層を水層から離し、その後ブライン(3×50mL)で洗浄した。この有機層をこのあとNa2SO4で乾燥させ、濾過し、そうして濃縮して粗製の固形物を得、これをシリカゲルクロマトグラフィー(10%EtOAC/ヘキサン)により精製して、1.92g(59%)の1−(3−フルオロピリジン−2−イル)シクロブタンカルボキサミドを白色の固形物として得た。
1−(3−フルオロピリジン−2−イル)シクロブタンカルボキサミド(1.92g、9.88mmol、1.0当量)をメタノール(20mL)に溶解させ、水酸化カリウム(1.11g、19.8mmol、2.0当量)を加えた。この反応を均質になるまで超音波処理し、その後ヨードソベンゼンジアセタート(4.77g、14.8mmol、1.5当量)を加えた。この反応を20分間撹拌し、その後水(100mL)及び酢酸エチル(125mL)で希釈した。分離漏斗に移して震盪した後、その有機層を水層から離し、その後その水層をEtOAc(50mL)で抽出した。合わせた有機層をこのあとNa2SO4で乾燥させ、濾過し、そうして濃縮して粗製の油状物を得、これをシリカゲルクロマトグラフィー(40%EtOAC/ヘキサン)により精製して、1.47g(67%)のメチル1−(3−フルオロピリジン−2−イル)シクロブチルカルバマートを白色の固形物として得た。
20mLマイクロ波反応バイアルにメチル1−(3−フルオロピリジン−2−イル)シクロブチルカルバマート(1.47g、6.56mmol、1.0当量)、エタノール(12mL)及び3N水酸化ナトリウム水溶液(7mL)を加えた。この反応混合物をマイクロ波反応器中30分間150℃で加熱した。そのエタノールを減圧下で蒸発させ、この混合物を酢酸エチル(30mL)で抽出した。その水層をこのあと酢酸エチル(2×30mL)で抽出した。有機層を合わせ、Na2SO4で乾燥させ、濾過し、そうして濃縮して、1−(3−フルオロピリジン−2−イル)シクロブタンアミン(1.01g、93%)を粗製黄色油状物として得た(これは次の反応ステップでさらに精製することなく用いた)。
20ドラムバイアルに2−クロロ−5−ブロモピリジン(440mg、2.3mmol、1.1当量)、2−(4−フルオロフェニル)−2−メチルプロパン−1−アミン(350mg、2.1mmol、1.0当量)、DIPEA(1.0mL、5.7mmol、2.7当量)、及びトルエン(5mL)を加えた。このバイアルをオイルバス中80℃に加熱し、12時間撹拌し、濃縮し、そうしてシリカゲルカラムクロマトグラフィー(0−30%EtOAc/ヘキサン)により精製して、270mg(40%)の5−ブロモ−N−(2−(4−フルオロフェニル)−2−メチルプロピル)ピリミジン−2−アミンを白色の固形物として得た。
5mLマイクロ波反応容器に5−ブロモ−N−(2−(4−フルオロフェニル)−2−メチルプロピル)ピリミジン−2−アミン(267mg、0.8mmol、1.0当量)、3−シアノ−4−フルオロフェニルボロン酸(203mg、1.2mmol、1.5当量)、Cl2Pd(dppf)(60mg、82μmol、0.1当量)、炭酸カリウム(1.2mLの2N水溶液、2.4mmol、3.0当量)、及びジオキサン(4mL)を加えた。この反応をマイクロ波反応器中20分間120℃で加熱した。その水層を反応から除去し、そうしてその有機層を直接逆相カラムクロマトグラフィーにより精製して、220mg(73%)の2−フルオロ−5−(2−(2−(4−フルオロフェニル)−2−メチルプロピルアミノ)ピリミジン−5−イル)ベンゾニトリルを白色の固形物として得た。
5mLマイクロ波反応容器に2−フルオロ−5−(2−(2−(4−フルオロフェニル)−2−メチルプロピルアミノ)ピリミジン−5−イル)ベンゾニトリル(220mg、0.6mmol)、ヒドラジン(500μL)、及びプロパノール(5mL)を加えた。この反応を120℃まで加熱し、3時間撹拌した。反応を濃縮し、逆相カラムクロマトグラフィーにより精製して、95mg(42%)の5−(2−(2−(4−フルオロフェニル)−2−メチルプロピルアミノ)ピリミジン−5−イル)−1H−インダゾール−3−アミンを白色の固形物(m/z [M+H] = 377.1)として得た。
撹拌棒装着マイクロ波バイアル中5−ブロモ−2−フルオロピリミジン(1.0g、5.6mmol、1.0当量)+2−(4−フルオロフェニル)−2−メチルプロパン−1−アミン(1.05g、6.3mmol、1.1当量)/イソプロパノール(12mL)の溶液に炭酸カリウム(3.68g、11.2mmol、2.0当量)を加えた。バイアルにマイクロ波バイアルキャップを装着し、45分間120℃に加熱した。この反応混合物を濾過してその固体炭酸カリウムを除去し、真空で濃縮した。その残留物をEtOAc及び水に溶解させた後、その有機層をブラインで洗浄し、硫酸ナトリウムで乾燥させ、真空で濃縮した。シリカゲルクロマトグラフィーによる精製(3%〜5%MeOH/DCM)により表題化合物が黄色の固形物(1.15g、65%)としてもたらされた(m/z [M+H] = 324.2)。
撹拌棒装着マイクロ波バイアルに固体としての5−ブロモ−N−(2−(4−フルオロフェニル)−2−メチルプロピル)ピリミジン−2−アミン(75mg、0.23mmol、1.0当量)、3−(カルボキシアミノ)フェニルボロン酸(25mg、0.35mmol、1.5当量)及び(dppf)PdCl2(18mg、0.23mmol、1.0当量)を加えた。バイアルにゴム隔膜を取り付け、5分間窒素流でパージした。窒素スパージ済みジオキサン(1mL)及び2N K2CO3水溶液(0.5mL)をシリンジにより加え、そうしてそのゴム隔膜を素早くマイクロ波バイアルキャップで置き換えた。反応をマイクロ波反応器中125℃で30分間加熱した後、LCMS分析は、そのアリールブロミドが消費されたことを示した。この反応混合物をEtOAcで希釈した。その有機層を飽和NaHCO3水溶液で1回そしてブラインで1回洗浄した。合わせた水層をEtOAcで1回洗浄し、そうして合わせた有機層を硫酸ナトリウムで乾燥させ、濾過し、そうして真空で濃縮した。シリカゲルクロマトグラフィー(3%〜10%MeOH/DCM)による精製により表題化合物が淡黄色の固形物(44mg、52%)としてもたらされた(m/z [M+H] = 365.3)。
2−クロロ−3−フルオロピリジン(80.0g、611mmol、1.0当量)+シクロブタンカルボニトリル(49.5g、611mmol、1.0当量)/トルエン(500mL)の0℃溶液にナトリウムヘキサメチルジシラジド(2.0M/THF、306mL、612mmol、1.0当量)を滴下式で加えた。得られた混合物をゆっくり室温まで温め、一晩撹拌した。反応をこのあと水(500mL)でクエンチし、そうしてその有機層を水層から分離させた。その水層をEtOAc(2×300mL)で抽出し、そうして合わせた有機相を飽和ブライン溶液で洗浄し(2×400mL)、Na2SO4で乾燥させ、濃縮して、粗製の黄色の油状物を得、そうしてシリカゲル(2〜10%EtOAc/ヘキサン)でのクロマトグラフィー処理により、1−(3−フルオロピリジン−2−イル)シクロブタンカルボニトリル(88g、83%)を淡黄色の油状物として得た。
1−(3−フルオロピリジン−2−イル)シクロブタンカルボニトリル(88g、500mmol、1.0当量)/THF(400mL)の0℃溶液にLAH(2M/THF、575mL、1.15mol)を1時間かけて滴下式で加えた。この反応をこのあと室温まで温め、15分間撹拌した。反応が完結した後、元の0℃まで冷却させ、ゆっくり水(43mL)、3N NaOH(43mL)、及び水(125mL)でクエンチした。クエンチした反応を30分間撹拌し、その後セライトに通して濾過した。その濾液を濃縮し、真空で乾燥させて、(1−(3−フルオロピリジン−2−イル)シクロブチル)メタンアミン(80g、88%)を粗製黄色油状物として得、これを精製することなく用いた。
2,6−ジフルオロピリジン(69.6g、605mmol、1.0当量)+イソブチロニトリル(41.7g、610mmol、1.0当量)/トルエン(500mL)の0℃溶液にナトリウムヘキサメチルジシラジド(2.0M/THF、302mL、605mmol、1.0当量)を滴下式で加えた。得られた混合物をゆっくり室温まで温め、一晩撹拌した。反応をこのあと水(500mL)でクエンチし、そうしてその有機層を水層から離した。この水層をEtOAc(2×300mL)で抽出し、そうして合わせた有機相を飽和ブライン溶液(2×400mL)で洗浄し、Na2SO4で乾燥させ、濃縮して粗製の黄色の油状物を得、そうしてシリカゲル(2〜10%EtOAc/ヘキサン)でクロマトグラフィー処理して、2−(6−フルオロピリジン−2−イル)−2−メチルプロパンニトリル(55.7g、56%)を透明の油状物として得た。
2−(6−フルオロピリジン−2−イル)−2−メチルプロパンニトリル(10g)/メタノール(30mL)の溶液にナトリウムメトキシド(50mLの30%メタノール中溶液)を加えた。この反応を1時間還流し、室温まで冷却し、酢酸エチル(400mL)に注ぎ入れ、そうしてブライン(3×200mL)で洗浄した。その有機層をNa2SO4で乾燥させ、濃縮して、2−(6−メトキシピリジン−2−イル)−2−メチルプロパンニトリル(9.8g、92%)を淡黄色の油状物として得た。
20ドラムマイクロ波バイアルに2−(6−メトキシピリジン−2−イル)−2−メチルプロパンニトリル(7g、40mmol)及び4N HCl/ジオキサン(15mL)を加えた。この反応をこのあと密封し、マイクロ波反応器中30分間190℃で加熱した。この反応を上記手順を用いて6回繰り返した。この各反応を合わせ、濾過した。得られた白色の固形物を20%EtOAc/ヘキサンで洗浄し、その後真空で乾燥させると、2−メチル−2−(6−オキソ−1,6−ジヒドロピリジン−2−イル)プロパンニトリル(24.7g、77%)が白色の固形物としてもたらされた。
100mL丸底フラスコに2−メチル−2−(6−オキソ−1,6−ジヒドロピリジン−2−イル)プロパンニトリル(8.2g、51mmol、1.0当量)、メチルクロロジフルオロアセタート(14.9g、103mmol、2.0当量)、炭酸セシウム(23.3g、71mmol、1.4当量)、及びDMF(100mL)を加えた。この反応を95℃まで加熱し、3時間撹拌した。反応をこのあと水(100mL)でクエンチし、EtOAc(500mL)で希釈した。その有機層をその水層から離した。その水層をEtOAc(100mL)で抽出し、そうして合わせた有機相を飽和ブライン溶液で洗浄し(3×200mL)、Na2SO4で乾燥させ、濃縮し、そうしてシリカゲル(2〜5%EtOAc/ヘキサン)でクロマトグラフィー処理して、2−(6−(ジフルオロメトキシ)ピリジン−2−イル)−2−メチルプロパンニトリル(6.2g、57%)を透明な油状物として得た。
1L丸底フラスコに2−(6−(ジフルオロメトキシ)ピリジン−2−イル)−2−メチルプロパンニトリル(19.2g、91mmol、1当量)、炭酸カリウム(37.0g、270mmol、3当量)、及びDMSO(150mL)を加えた。この反応を0℃まで冷却し、30%過酸化水素(25mL)をゆっくり10分かけて2mLずつ加えた。この反応をこのあと室温まで温め、1時間撹拌した。出発物質が消費された後、この反応を酢酸エチル(600mL)に注ぎ入れ、ブライン(3×300mL)で洗浄し、Na2SO4で乾燥させ、そうして濃縮して、2−(6−(ジフルオロメトキシ)ピリジン−2−イル)−2−メチルプロパンアミド(20g、97%)を透明な油状物として得た。
500mL丸底フラスコに2−(6−(ジフルオロメトキシ)ピリジン−2−イル)−2−メチルプロパンアミド(20.0g、91mmol、1当量)及びメタノール(150mL)を加えた。この混合物を0℃まで冷却し、水酸化ナトリウム溶液(7.3gを150mLのメタノールに溶解、182mmol、2.0当量)を加えた。この反応を2分間撹拌し、ヨードソベンゼンジアセタート(40.8g、127mmol、1.4当量)を加えた。この反応を2時間ゆっくり室温まで温めながら撹拌した。反応をこのあと酢酸エチル(700mL)に注ぎ入れ、飽和ブライン溶液で洗浄し(2×400mL)、Na2SO4で乾燥させ、濃縮し、そうしてシリカゲル(10〜20%EtOAc/ヘキサン)でクロマトグラフィー処理して、メチル2−(6−(ジフルオロメトキシ)ピリジン−2−イル)プロパン−2−イルカルバマート(12.4g、55%)を白色の固形物として得た。
2−(6−(ジフルオロメトキシ)ピリジン−2−イル)プロパン−2−イルカルバマート(12.4g、48mmol)/アセトニトリル(50mL)の溶液にTMSI(10mL)を加えた。この反応を30分間撹拌し、その後メタノール(100mL)+水(5mL)に注ぎ入れた。この混合物を濃縮し、酢酸エチル(200mL)に溶解させ、次いで1N NaOH(2×30mL)で洗浄した。その有機層を分離し、Na2SO4で乾燥させ、濃縮し、そうしてシリカゲル(50%EtOAc/ヘキサン、その後5〜20%MeOH/CH2Cl2)でクロマトグラフィー処理することにより、2−(6−(ジフルオロメトキシ)ピリジン−2−イル)プロパン−2−アミン(8.8g、92%)を黄色の油状物として得た。
3−メチレンシクロブタンカルボニトリル(150g、1.61mol、1当量)及び2−クロロ−3−フルオロピリジン(212g、1.61mmol、1当量)/トルエン(1L)の溶液にNaHMDS(2M/THF、885mL、1.1当量)を0〜10℃にて滴下で加えた。添加完了後、この反応混合物を室温まで温め、一晩撹拌し、そうしてNH4Cl(飽和)溶液でクエンチした。その有機層を水(2×500mL)及びブライン(500mL)で洗浄し、Na2SO4で乾燥させ、濾過し、そうして濃縮して、粗製表題化合物(272g、90%)を得た(これはさらに精製することなく次のステップで用いた)。LRMS (M+H+) m/z 189.1。
1−(3−フルオロピリジン−2−イル)−3−メチレンシクロブタンカルボニトリル(272g、1.45mol)+RuCl3・H2O(9.0g、0.044mol)/DCM(1L)+アセトニトリル(1L)+水(1.5L)混合液の混合物に固体NaIO4(1235g、5.8mol)を10〜30℃にて少しずつ加えた。添加完了後、この反応を15℃で1時間及び室温で一晩撹拌した。固体沈殿物を濾去し、DCM(2×1000mL)で洗浄した。その有機層を水(2×500mL)及びブライン(500mL)で洗浄し、Na2SO4で乾燥させ、そうして濃縮すると、粗製表題化合物が暗色の固形物(238g、86.3%)としてもたらされた。LRMS (M+H+) m/z 191.1。
1−(3−フルオロピリジン−2−イル)−3−オキソシクロブタンカルボニトリル(231g、1.22mol)/DCM(2L)+MeOH(200mL)の溶液にNaBH4を−78℃にて少しずつ加えた。この反応混合物を1時間−78℃で撹拌し、メタノール+水(1/1)混合物でクエンチした。その有機層を水(500mL×3)で洗浄し、Na2SO4で乾燥させ、そうして濃縮した。この残留物をシリカゲル(50%EtOAc/ヘキサン)で精製すると、表題化合物がアンバー色の油状物(185.8g、77.5%)としてもたらされた。LRMS (M+H+) m/z 193.2。
1−(3−フルオロピリジン−2−イル)−3−ヒドロキシシクロブタンカルボニトリル(185g、0.96mol)/DCM(1L)の溶液にDASTを0〜10℃にて少しずつ加えた。添加完了後、反応を6時間還流した。反応を室温まで冷却し、飽和NaHCO3溶液に注ぎ入れた。この混合物を分離させ、その有機層を水で洗浄し、Na2SO4で乾燥させ、そうして濃縮した。この残留物をシリカゲル(100%DCM)で精製すると、表題化合物が8:1トランス:シス混合物の茶色の油状物(116g、62%)としてもたらされた。この茶色の油状物(107g)を70℃でトルエン(110mL)+ヘキサン(330mL)に溶解させた。この溶液を0℃まで冷却し、一晩0℃で撹拌した。その沈殿物を濾過し、ヘキサンで洗浄すると、そのトランス異性体が白色の固形物(87.3g、81.6%)としてもたらされた。LRMS (M+H+) m/z 195.1。
トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブタンカルボニトリル(71g、0.37mol)+ラネーニッケル(約7g)/7Nメタノール(700mL)中アンモニアに水素(60psi)を2日間チャージした。反応をセライトパッドに通して濾過し、メタノールで洗浄した。その濾液を高真空下で濃縮すると、表題化合物が薄緑色の油状物(70g、97.6%)としてもたらされた。LRMS (M+H+) m/z 199.2。
t−ブチル5−ブロモピリミジン−2−イル((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチル)カルバマート(1.0g、2.8mmol)/15mLのトルエン(窒素で脱ガス済み)の溶液にヨウ化銅(100mg、0.6mmol)、リン酸カリウム(1.31g、6.2mmol)、トランス−N,N’−ジメチルシクロヘキサン−1,2−ジアミン(320mg、2.2mmol)、及び3−シアノピロール(310mg、3.6mmol)を加えた。この反応を100℃まで加熱し、2時間撹拌した。反応をこのあと濃縮し、シリカゲルクロマトグラフィー(EtOAc/ヘキサン)により精製して、1.1gのt−ブチル5−(3−シアノ−1H−ピロール−1−イル)ピリミジン−2−イル(((トランス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチル)カルバマートを透明な油状物として得た。
t−ブチル5−(3−シアノ−1H−ピロール−1−イル)ピリミジン−2−イル(((トランス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチル)カルバマート(1.1g、3.1mmol)/DMSO(10mL)の溶液に炭酸カリウム(1.3g、9.3mmol)を加えた。この混合物を0℃まで冷却し、過酸化水素(3mL)をゆっくり時間をかけて加えた。この反応を室温まで温め、90分間撹拌した。反応をEtOAc(75mL)で希釈し、ブライン(50mL)で3回洗浄した。その有機層をこのあとNa2SO4で乾燥させ、濾過し、そうして濃縮して粗製の固形物を得、これをシリカゲルクロマトグラフィー(10%MeOH/CH2Cl2)により精製して、1.07gの1−(2−(((トランス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−1H−ピロール−3−カルボキサミドを白色の固形物として得た。この化合物を25%TFA/CH2Cl2に溶解させ、1時間撹拌した。反応をこのあと濃縮し、酢酸エチル(75mL)に溶解させ、そうして炭酸カリウムで3回洗浄した。その有機層をこのあとNa2SO4で乾燥させ、濾過し、そうして濃縮して粗製の固形物を得、これを75%酢酸エチル/ヘキサンで細砕した。エタノールスラリーを超音波処理し、濾過して、500mgの1−(2−(((トランス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−1H−ピロール−3−カルボキサミドを白色の固形物(M+H=385)として得た。
250mL丸底フラスコにt−ブチル5−ブロモピリミジン−2−イル((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチル)カルバマート(5.0g、11.0mmol)、3−ブロモ−6−フルオロ−2−メトキシフェニルボロン酸(2.7g、11.0mmol)、(dppf)PdCl2(0.80g、1.1mmol)、ジオキサン(25mL窒素で10分間脱ガス済み)、K2CO3(3.0g、22mmol)、及び水(4mL)を加えた。この混合物を95℃まで加熱し、一晩撹拌した。反応混合物をこのあと酢酸エチル(200mL)に注ぎ入れ、NaHCO3(50mL)及びブライン(50mL)で順次に洗浄し、そうしてその後Na2SO4で乾燥させ、濾過し、濃縮し、そうしてシリカゲルクロマトグラフィーにより精製して、2.4g(4.1mmol)の5−(3−ブロモ−6−フルオロ−2−メトキシフェニル)−N−((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチル)ピリミジン−2−アミンを淡黄色の固形物として得た。この固形物にシアン化亜鉛(0.76g、6.5mmol)、Pd(PPh3)4(2.9g、2.5mmol)、及びDMF(25mL)を加えた。この混合物を2時間100℃に加熱し、その後EtOAcで希釈し、飽和NaHCO3水溶液及びブラインで洗浄した。その有機層を硫酸ナトリウムで乾燥させ、濾過し、濃縮し、そうして逆相クロマトグラフィーを用いて精製し、1.1グラムの4−フルオロ−3−(2−((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−2−メトキシベンゾニトリルを得た。
4−フルオロ−3−(2−((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−2−メトキシベンゾニトリル(1.0g、1.9mmol)、K2CO3(0.8g、5.7mmol)、及びDMSO(5mL)を丸底フラスコ中に合わせ、0℃まで冷却した。H2O2(8.0mLの35%溶液)を滴下で加えた。この反応を室温まで温め、1時間撹拌した。反応混合物をEtOAcで希釈し、飽和NaHCO3水溶液及びブラインで洗浄した(3回)。その有機層を硫酸ナトリウムで乾燥させ、濾過し、そうして濃縮し、そして逆相クロマトグラフィーにより精製して、0.55g(1mmol)の4−フルオロ−3−(2−((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−2−メトキシベンズアミドを白色の固形物として得た。この化合物をピリジン(6mL)及びLiI(1.22g、9mmol)と混合し、マイクロ波反応器中15分間125℃で加熱した。この反応混合物をEtOAcで希釈し、飽和NaHCO3水溶液及びブラインで洗浄した。その有機層を硫酸ナトリウムで乾燥させ、濾過し、そうして濃縮し、そして逆相クロマトグラフィーにより精製して、163mgの4−フルオロ−3−(2−((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−2−ヒドロキシベンズアミドを白色の固形物(M+H+430.1)として得た。
20mLマイクロ波管に5−ブロモ−N−(((トランス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチル)ピリミジン−2−アミン(1.2g、3.8mmol)、メチル4−ヒドロキシ−3−(4,4,5,5−テトラメチル−1,3,2−ジオキサボロラン−2−イル)ベンゾアート(1.1g、4.0mmol)、(dppf)PdCl2(0.25g、0.38mmol)、ジオキサン(15mL)、K2CO3(1.4g、10.1mmol)、及び水(3mL)を加えた。この混合物を135℃まで加熱し、15分間撹拌した。この反応混合物をこのあと酢酸エチル(200mL)に注ぎ入れ、ブライン(50mL)で洗浄し、そうしてNa2SO4で乾燥させ、濾過し、濃縮し、そうしてシリカゲルクロマトグラフィー(EtOAc/ヘキサン)により精製して、0.65gのメチル3−(2−(((トランス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−4−ヒドロキシベンゾアートを黄褐色の固形物として得た。この化合物をメタノール(7mL)に溶解させ、KOH(2mLの3N水溶液)を加えた。この反応を1時間80℃で撹拌し、その後濃縮した。この粗製の残留物を逆相クロマトグラフィーにより精製して、0.24gの3−(2−(((トランス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−4−ヒドロキシ安息香酸を白色の固形物として得た。
50mL丸底フラスコに3−(2−(((トランス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−4−ヒドロキシ安息香酸(147mg、0.36mmol)、HATU(204mg、0.54mmol)、HOBT(72mg、0.54mmol)、メチルアミンヒドロクロリド(239mg、3.6mmol)、DIPEA(187μL、1.1mmol)、及びDMF(1.5mL)を加えた。この反応混合物を一晩室温で撹拌した。反応混合物を濃縮し、逆相クロマトグラフィーにより精製して、93mgの3−(2−((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−4−ヒドロキシ−N−メチルベンズアミドを白色の固形物(M+H=412.1)として得た。
ジオキサン(50mL、脱ガス済み)の撹拌溶液に5−ブロモ−N−(2−(3−クロロピリジン−2−イル)プロパン−2−イル)ピリミジン−2−アミン(3.0g、12mmol)、Cl2Pd(PPh3)2(0.65g、1.2mmol)、及びトリブチル(1−エトキシビニル)スズ(2.66mL、13.8mmol)を加えた。この反応を90℃まで加熱し、2時間撹拌した。反応をこのあと濃縮し、その後EtOAc(100mL)及びフッ化カリウム(50mLの飽和水溶液)を加えた。この混合物を10分間撹拌し、その後セライトのパッドに通して濾過した。この濾液を濃縮し、その後THF(20mL)+水(20mL)に溶解させた。NBS(4.9g、27.6mmol)をこのあと加え、そうしてこの反応を室温にて20分間撹拌した。反応混合物を酢酸エチル(200mL)に注ぎ入れ、飽和重炭酸ナトリウム水溶液(50mL)で洗浄し、Na2SO4で乾燥させ、濾過し、濃縮し、そうしてシリカゲルクロマトグラフィーにより精製して、1.5gの2−ブロモ−1−(2−(2−(3−クロロピリジン−2−イル)プロパン−2−イルアミノ)ピリミジン−5−イル)エタノンを白色の粉末として得た。
20ドラムバイアルに2−ブロモ−1−(2−(2−(3−クロロピリジン−2−イル)プロパン−2−イルアミノ)ピリミジン−5−イル)エタノン(103mg、0.28mmol)、エチル−2−アミノチアゾール−4−カルボキシラート(48mg、0.28mmol)、及びメチルエチルケトン(2mL)を加えた。この混合物を密封管中で90℃に加熱し、一晩撹拌した。反応を濃縮し、シリカゲルクロマトグラフィー(EtOAc/ヘキサン)により精製して、33mgのエチル6−(2−(2−(3−クロロピリジン−2−イル)プロパン−2−イルアミノ)ピリミジン−5−イル)イミダゾ[2,1−b]チアゾール−3−カルボキシラートを黄褐色の固形物として得た。この化合物をメタノール(1mL)に溶解させ、水酸化アンモニウム(3mL)を加えた。得られた混合物をマイクロ波反応器中135℃に加熱し、15分間撹拌した。反応を濃縮し、その後HBTU(68mg、179μmol)、HOBt(24mg、179μmol)、NH4Cl(48mg、1.1mmol)、DIPEA(78μL、441μmol)、及びNMP(2mL)を加えた。この反応を2時間撹拌し、その後直接逆相クロマトグラフィーにより精製して、18mgの6−(2−(2−(3−クロロピリジン−2−イル)プロパン−2−イルアミノ)ピリミジン−5−イル)イミダゾ[2,1−b]チアゾール−3−カルボキサミドをオフホワイト色の固形物(M+H=414.1)として得た。
4−ブロモピコリノニトリル(11.8g、74.5mmol)、2−クロロピリミジン−5−イルボロン酸(15.0g、82.0mmol)、(dppf)PdCl2(5.5g、7.45mmol)、ジオキサン(150mL、窒素で脱ガス済み)、及び2N K2CO3水溶液(33mL)を丸底フラスコ中に合わせ、一晩100℃で加熱した。この高温混合物をセライトのパッドに通して濾過し、EtOAcで希釈し、水で洗浄し、濃縮し、そうしてシリカゲルクロマトグラフィーを用いて精製して、4−(2−クロロピリミジン−5−イル)ピコリノニトリルを褐色の固形物(2.1g、13%)として得た。
4−(2−クロロピリミジン−5−イル)ピコリノニトリル(0.9g、4.2mmol)、(3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メタンアミン(1.0g、5.0mmol)、DIPEA(1mL)、及びACN(20mL)を混合し、4時間90℃で加熱した。この反応混合物を濃縮し、EtOAcで希釈し、そうして飽和NaHCO3水溶液及びブラインで洗浄した。その有機層を硫酸ナトリウムで乾燥させ、濾過し、濃縮し、そうして逆相クロマトグラフィーを用いて精製して、4−(2−(((シス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)ピコリノニトリルを透明な油状物として得た(シス異性体が最初に溶離する)。この化合物をこのあとDMSO(3mL)、K2CO3(200mg)、及びH2O2(2mL)で処理した。この反応混合物を4時間撹拌し、その後EtOAcで希釈し、ブラインで洗浄した。その有機層を硫酸ナトリウムで乾燥させ、濾過し、濃縮し、そうして逆相クロマトグラフィーを用いて精製して、93mgの4−(2−(((シス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)ピコリンアミドをオフホワイト色の固形物(m/z [M+H] = 397.2)として得た。
速骨格筋原線維の調製
ウサギ骨格筋原線維をHerrmann et al. (Biochem. 32(28):7255-7263(1993))の方法に従って調製した。氷上で貯蔵しておいた、Pel−Freez Biologicals(Arkansas)から購入のウサギ腰筋から、筋原線維を、注文から2日以内の間に、調製した。ミンチした筋肉をOmni−Macroホモジナイザーを用いて5mM EDTA及び0.5%Triton X−100含有10体積の氷冷「標準」バッファー(50mM Tris、pH7.4、0.1M酢酸カリウム、5mM KCl、2mM DTT、0.2mM PMSF、10μMロイペプチン、5μMペプスタチン、及び0.5mMナトリウムアジド)にホモジナイズした。低速遠心(10分間3000rpm)により筋原線維を回収し、細胞膜を確実に除去するためバッファー含有Triton X−100中で2回洗浄した。Triton洗浄の後、筋原線維を2mM酢酸マグネシウム含有「標準」バッファー中で3回洗浄した。アッセイバッファー(12mM PIPES、pH6.8、60mM KCl、1mM DTT)中で最終洗浄を行い、液体窒素中−80℃瞬間凍結・貯蔵するための10%スクロースにもっていった。
特許製品であるPUMA(商標)アッセイ装置(例えば、米国特許第6,410,254号明細書、同第6,743,599号明細書、同第7,202,051号明細書、及び同第7,378,254号明細書を参照されたい)を用いて筋肉筋原線維調製物の酵素活性を測定することにより速線維活性化物質を特定した。機械ホモジナイズし、洗浄剤(トリトンX−100)で洗浄して細胞膜を除去してあるウサギ骨格筋(およそ90%速線維)から筋原線維調製物はなっていた。この調製物はすべての筋節構成員を天然の配置に保持し、酵素活性はなおカルシウムによって調節されていた。筋原線維懸濁液及びその筋原線維の酵素活性をその最大値の25%まで増大させるのに十分なカルシウムの濃度(pCa25と呼ぶ)を用いて化合物は試験された。酵素活性は、ピルビン酸キナーゼ・乳酸デヒドロゲナーゼ連結酵素系を介して追跡された。このアッセイはNADHを酸化することによりミオシン生成ADPをATPに再生するものであり、340nmにおける吸収の変化をもたらす。バッファー系は、pH6.8の12mM Pipes、2mM MgCl2、1mM DTTであった(PM12バッファー)。データは、化合物が酵素活性を40%だけ増大させた濃度である、AC1.4として記録された。結果は後の表2にまとめられている。
粉末調製
1. 体積は、ミンチした筋肉の約1000g当たりで記載されている。
1. 心筋左室を切開する。心膜組織及び脂肪を可能なかぎり多く除去する。予冷却された肉挽き器で挽く。秤量する。
1. 1グラムの粉末当たり20mlのバッファーA(後を参照、以下のステップのそれぞれにおいては使用直前にBME及びATPを加える)で(先に説明したように)粉末を抽出する(10g当たり200ml)。150gの粉末には4L大型ビーカーを使用する。激しく混合して粉末を溶解させる。4℃で撹拌する(30分間)。
溶液A:0.3M KCl、0.15Mリン酸カリウム、0.02M EDTA、0.005M MgCl2、0.001M ATP、pH6.5。
ウサギ腰筋塩抽出物からの沈殿によりミオシンを調製し、その後キモトリプシンでの消化により可溶S1フラクションを調製する(Margossian and Lowey, 1982)。
Claims (63)
- 式I:
R1は、水素であり;
R2は、C 6〜10アリール、及び5〜10員ヘテロアリールから選択され、前記のC 6〜10アリール及び5〜10員ヘテロアリール基のそれぞれはハロゲン、CN、オキソ、(CH2)nORa、(CH2)nNRbRc、(CH2)nNRdC(O)Ra、(CH2)nNRdC(O)ORa、(CH2)nNRdSO2Ra、(CH2)nC(O)ORa、(CH2)nC(O)NRbRc、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換されており、前記のC1〜6アルキルは1、2、3、4又は5個のRf置換基で場合により置換されており;
R3は、水素、ハロゲン、C 1〜6アルキル、及びC1〜6ハロアルキルから選択され;
R4は、水素であり;
R5及びR6は、それぞれ、C 1〜6アルキルから独立に選択され;
あるいは、R5及びR6は、それらが結合されている炭素原子と一緒になって、1又は2個のハロゲンで場合により置換された、C3〜8シクロアルキル基を形成しており;
R7は、それぞれハロゲン、ORa、SRa、S(O)Ra、SO2Ra、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換された、C 6〜10アリール及び5〜10員ヘテロアリールから選択され;
R8及びR9は、それぞれの存在時には、それぞれ水素であり;
Xは結合であり;
Raは、それぞれの存在時には、水素、C1〜6アルキル、C1〜6ハロアルキル、C 3〜8シクロアルキル、3〜8員ヘテロシクロアルキル、及び5〜10員ヘテロアリールから独立に選択され、前記のC1〜6アルキル、C 3〜8シクロアルキル、3〜8員ヘテロシクロアルキル、及び5〜10員ヘテロアリール基のそれぞれは1、2、3、4又は5個のRf置換基で場合により置換されており;
Rb及びRcは、それぞれの存在時には、それぞれ、水素、C1〜6アルキル、C1〜6ハロアルキル、C 3〜8シクロアルキル、及び3〜8員ヘテロシクロアルキルから独立に選択され、前記のC1〜6アルキル、及びC3〜8シクロアルキルのそれぞれは1、2、3、4又は5個のRf置換基で場合により置換されており;
Rdは、それぞれの存在時には、水素であり;
R fは、それぞれの存在時には、ハロゲン、CN、ORh、NRiRj、NRdC(O)ORh、C(O)Rh、C(O)NRiRj、SO2Rh、C 1〜6アルキル、及びC1〜6ハロアルキルから独立に選択され;
Rgは、それぞれの存在時には、C 1〜6アルキル、及びC1〜6ハロアルキルから独立に選択され;
Rhは、それぞれの存在時には、水素、C1〜6アルキル、及びC1〜6ハロアルキルから独立に選択され;
Ri及びRjは、それぞれの存在時には、それぞれ、水素、C1〜6アルキル、及びC1〜6ハロアルキルから独立に選択され;
mは、0又は1であり;
nは、それぞれの存在時には、独立に、0、1又は2である]
で表される化合物又はその薬学的に許容される塩。 - mが0である、請求項1に記載の化合物又はその薬学的に許容される塩。
- mが1である、請求項1に記載の化合物又はその薬学的に許容される塩。
- R5及びR6が、それぞれ、C1〜6アルキルである、請求項1〜3のいずれかに記載の化合物又はその薬学的に許容される塩。
- R5及びR6が、それぞれ、メチルである、請求項4に記載の化合物又はその薬学的に許容される塩。
- R5及びR6が、それらが結合されている炭素原子と一緒になって、1又は2個のハロゲンで場合により置換されたC3〜8シクロアルキルを形成している、請求項1に記載の化合物又はその薬学的に許容される塩。
- R5及びR6が、それらが結合されている炭素原子と一緒になってシクロブチルを形成している、請求項6に記載の化合物又はその薬学的に許容される塩。
- R5及びR6が、それらが結合されている炭素原子と一緒になって、1又は2個のハロゲンで置換されたシクロブチルを形成している、請求項6に記載の化合物又はその薬学的に許容される塩。
- R5及びR6が、それらが結合されている炭素原子と一緒になって、3−フルオロシクロブチル及び3,3−ジフルオロシクロブチルから選択される基を形成している、請求項8に記載の化合物又はその薬学的に許容される塩。
- Rm及びRnの一方が水素であり、他方がハロゲンである、請求項10に記載の化合物又はその薬学的に許容される塩。
- ハロゲンとR7とが、シクロブチル環上で互いに対してトランス配置にある、請求項11に記載の化合物又はその薬学的に許容される塩。
- ハロゲンとR7とが、シクロブチル環上で互いに対してシス配置にある、請求項11に記載の化合物又はその薬学的に許容される塩。
- Rm及びRnの一方が水素であり、他方がフッ素である、請求項10〜13のいずれかに記載の化合物又はその薬学的に許容される塩。
- R7が、ハロゲン、ORa、SRa、S(O)Ra、SO2Ra、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換されたフェニルである、請求項1〜14のいずれかに記載の化合物又はその薬学的に許容される塩。
- R7が、ハロゲン、ORa、SRa、S(O)Ra、SO2Ra、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換された5〜10員ヘテロアリールである、請求項1〜14のいずれかに記載の化合物又はその薬学的に許容される塩。
- R7が、ハロゲン、ORa、SRa、S(O)Ra、SO2Ra、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換されたピリジルである、請求項16に記載の化合物又はその薬学的に許容される塩。
- R7が、ハロゲン、ORa、SRa、S(O)Ra、SO2Ra、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換された2−ピリジルである、請求項17に記載の化合物又はその薬学的に許容される塩。
- R2が、ハロゲン、CN、(CH2)nORa、(CH2)nNRbRc、(CH2)nNRdC(O)Ra、(CH2)nNRdC(O)ORa、(CH2)nNRdSO2Ra、(CH2)nC(O)ORa、(CH2)nC(O)NRbRc、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換されたフェニルであり、前記のC1〜6アルキルが1、2、3、4又は5個のRf置換基で場合により置換されている、請求項1〜18のいずれかに記載の化合物又はその薬学的に許容される塩。
- R2が、ハロゲン、CN、オキソ、(CH2)nORa、(CH2)nNRbRc、(CH2)nNRdC(O)Ra、(CH2)nNRdC(O)ORa、(CH2)nNRdSO2Ra、(CH2)nC(O)ORa、(CH2)nC(O)NRbRc、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換された5〜10員ヘテロアリールであり、前記のC1〜6アルキルが1、2、3、4又は5個のRf置換基で場合により置換されている、請求項1〜18のいずれかに記載の化合物又はその薬学的に許容される塩。
- R2が、それぞれハロゲン、CN、オキソ、(CH2)nORa、(CH2)nNRbRc、(CH2)nNRdC(O)Ra、(CH2)nNRdC(O)ORa、(CH2)nNRdSO2Ra、(CH2)nC(O)ORa、(CH2)nC(O)NRbRc、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2、3又は4個の置換基で場合により置換された、ピリジル、ピリミジル、ピラジル、ピリダジル、ピロリル、チオフェニル、チアゾリル、イソチアゾリル、チアジアゾリル、オキサゾリル、イソオキサゾリル、オキサジアゾリル、イミダゾリル、トリアゾリル及びテトラゾリルから選択され、前記のC1〜6アルキルが1、2、3、4又は5個のRf置換基で場合により置換されている、請求項20に記載の化合物又はその薬学的に許容される塩。
- R2が、それぞれ(CH2)nC(O)ORa及び(CH2)nC(O)NRbRcから選択される置換基で場合により置換され;及びハロゲン、CN、オキソ、(CH2)nORa、(CH2)nNRbRc、(CH2)nNRdC(O)Ra、(CH2)nNRdC(O)ORa、(CH2)nNRdSO2Ra、(CH2)nC(O)ORa、(CH2)nC(O)NRbRc、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2又は3個のさらなる置換基で場合により置換された;ピリジル、ピリミジル、ピラジル、ピリダジル、ピロリル、チオフェニル、チアゾリル、イソチアゾリル、チアジアゾリル、オキサゾリル、イソオキサゾリル、オキサジアゾリル、イミダゾリル、トリアゾリル及びテトラゾリルから選択され、前記のC1〜6アルキルが1、2、3、4又は5個のRf置換基で場合により置換されている、請求項21に記載の化合物又はその薬学的に許容される塩。
- R2が、それぞれ(CH2)nC(O)NRbRcで置換された、フラニル、ピロリル、チオフェニル、チアゾリル、イソチアゾリル、チアジアゾリル、オキサゾリル、イソオキサゾリル、オキサジアゾリル、イミダゾリル、トリアゾリル及びテトラゾリルから選択される、請求項22に記載の化合物又はその薬学的に許容される塩。
- R2が、それぞれハロゲン、CN、オキソ、(CH2)nORa、(CH2)nNRbRc、(CH2)nNRdC(O)Ra、(CH2)nNRdC(O)ORa、(CH2)nNRdSO2Ra、(CH2)nC(O)ORa、(CH2)nC(O)NRbRc、C 1〜6アルキル、及びC1〜6ハロアルキルから選択される1、2、3又は4個の置換基で場合により置換された、インドリル、インダゾリル、及びベンゾイミダゾリルから選択され、前記のC1〜6アルキルが1、2、3、4又は5個のRf置換基で場合により置換されている、請求項20に記載の化合物又はその薬学的に許容される塩。
- R3が、水素、ハロゲン、CN、CF3及びメチルから選択される、請求項1〜24のいずれかに記載の化合物又はその薬学的に許容される塩。
- R3が、水素である、請求項25に記載の化合物又はその薬学的に許容される塩。
- mが0であり;
R 2 が、ハロゲン、CN、オキソ、(CH 2 ) n OR a 、(CH 2 ) n NR b R c 、(CH 2 ) n NR d C(O)R a 、(CH 2 ) n NR d C(O)OR a 、(CH 2 ) n NR d SO 2 R a 、(CH 2 ) n C(O)OR a 、(CH 2 ) n C(O)NR b R c 、C 1〜6 アルキル、及びC 1〜6 ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換されたフェニル及び5〜10員ヘテロアリールから選択され、前記のC 1〜6 アルキルが1、2、3、4又は5個のR f 置換基で場合により置換されており;
R 3 が水素であり;
R 5 がメチルであり;
R 6 がメチルであり;並びに
R 7 が、ハロゲン、OR a 、SR a 、S(O)R a 、SO 2 R a 、C 1〜6 アルキル、及びC 1〜6 ハロアルキルから選択される1、2又は3個の置換基で場合により置換されたフェニル及びピリジルから選択される、
請求項1に記載の化合物又はその薬学的に許容される塩。 - mが0であり;
R 2 が、ハロゲン、CN、オキソ、(CH 2 ) n OR a 、(CH 2 ) n NR b R c 、(CH 2 ) n NR d C(O)R a 、(CH 2 ) n NR d C(O)OR a 、(CH 2 ) n NR d SO 2 R a 、(CH 2 ) n C(O)OR a 、(CH 2 ) n C(O)NR b R c 、C 1〜6 アルキル、及びC 1〜6 ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換されたフェニル及び5〜10員ヘテロアリールから選択され、前記のC 1〜6 アルキルが1、2、3、4又は5個のR f 置換基で場合により置換されており;
R 3 が水素であり;
R 5 及びR 6 が、それらが結合されている炭素原子と一緒になって、1又は2個のハロゲンで場合により置換されたシクロブチルを形成しており;並びに
R 7 が、ハロゲン、OR a 、SR a 、S(O)R a 、SO 2 R a 、C 1〜6 アルキル、及びC 1〜6 ハロアルキルから選択される1、2又は3個の置換基で場合により置換されたフェニル及びピリジルから選択される、
請求項1に記載の化合物又はその薬学的に許容される塩。 - mが1であり;
R 2 が、ハロゲン、CN、オキソ、(CH 2 ) n OR a 、(CH 2 ) n NR b R c 、(CH 2 ) n NR d C(O)R a 、(CH 2 ) n NR d C(O)OR a 、(CH 2 ) n NR d SO 2 R a 、(CH 2 ) n C(O)OR a 、(CH 2 ) n C(O)NR b R c 、C 1〜6 アルキル、及びC 1〜6 ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換されたフェニル及び5〜10員ヘテロアリールから選択され、前記のC 1〜6 アルキルが1、2、3、4又は5個のR f 置換基で場合により置換されており;
R 3 が水素であり;
R 5 がメチルであり;
R 6 がメチルであり;並びに
R 7 が、ハロゲン、OR a 、SR a 、S(O)R a 、SO 2 R a 、C 1〜6 アルキル、及びC 1〜6 ハロアルキルから選択される1、2又は3個の置換基で場合により置換されたフェニル及びピリジルから選択される、
請求項1に記載の化合物又はその薬学的に許容される塩。 - mが1であり;
R 2 が、ハロゲン、CN、オキソ、(CH 2 ) n OR a 、(CH 2 ) n NR b R c 、(CH 2 ) n NR d C(O)R a 、(CH 2 ) n NR d C(O)OR a 、(CH 2 ) n NR d SO 2 R a 、(CH 2 ) n C(O)OR a 、(CH 2 ) n C(O)NR b R c 、C 1〜6 アルキル、及びC 1〜6 ハロアルキルから選択される1、2、3、4又は5個の置換基で場合により置換されたフェニル及び5〜10員ヘテロアリールから選択され、前記のC 1〜6 アルキルが1、2、3、4又は5個のR f 置換基で場合により置換されており;
R 3 が水素であり;
R 5 及びR 6 が、それらが結合されている炭素原子と一緒になって、1又は2個のハロゲンで場合により置換されたシクロブチルを形成しており;並びに
R 7 が、ハロゲン、OR a 、SR a 、S(O)R a 、SO 2 R a 、C 1〜6 アルキル、及びC 1〜6 ハロアルキルから選択される1、2又は3個の置換基で場合により置換されたフェニル及びピリジルから選択される、
請求項1に記載の化合物又はその薬学的に許容される塩。 - 4−フルオロ−3−(2−{[2−(3−フルオロ(2−ピリジル))−2−メチルプロピル]アミノ}ピリミジン−5−イル)ベンズアミドである請求項1の化合物又はその薬学的に許容される塩。
- 4−フルオロ−3−[2−({[(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ベンズアミドである請求項1の化合物又はその薬学的に許容される塩。
- 4−フルオロ−3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ベンズアミドである請求項1の化合物又はその薬学的に許容される塩。
- {4−フルオロ−3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−メチルカルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- {4−フルオロ−3−[2−({[トランス−3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−メチルカルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 4−フルオロ−3−(2−((3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−2−ヒドロキシベンズアミドである請求項1の化合物又はその薬学的に許容される塩。
- 4−フルオロ−3−(2−((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−2−ヒドロキシベンズアミドである請求項1の化合物又はその薬学的に許容される塩。
- 3−(2−((3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−4−ヒドロキシ−N−メチルベンズアミドである請求項1の化合物又はその薬学的に許容される塩。
- 3−(2−((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−4−ヒドロキシ−N−メチルベンズアミドである請求項1の化合物又はその薬学的に許容される塩。
- 4−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリジン−2−カルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 4−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリジン−2−カルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 4−[2−({[トランス−3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリジン−2−カルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 1−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピラゾール−4−カルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 1−[2−({[トランス−3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピラゾール−4−カルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 1−(2−((3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−1H−ピロール−3−カルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 1−(2−(((トランス)−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)−1H−ピロール−3−カルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 2−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−5−カルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 2−(2−(2−((1−(3−クロロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)チアゾール−5−イル)アセトアミドである請求項1の化合物又はその薬学的に許容される塩。
- 2−(2−((3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)チアゾール−5−カルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 2−(2−((トランス−3−フルオロ−1−(3−フルオロピリジン−2−イル)シクロブチル)メチルアミノ)ピリミジン−5−イル)チアゾール−5−カルボキサミドである請求項1の化合物又はその薬学的に許容される塩。
- 以下から選択される請求項1の化合物またはその薬学的に許容される塩:
2−[2−({1−[6−(ジフルオロメトキシ)(2−ピリジル)]−イソプロピル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−5−カルボキサミド;
2−(2−{[1−(4−メトキシピリミジン−2−イル)−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−5−カルボキサミド;
3−[2−({1−[6−(ジフルオロメトキシ)(2−ピリジル)]−イソプロピル}アミノ)ピリミジン−5−イル]−4−フルオロベンズアミド;
3−[2−({1−[6−(ジフルオロメトキシ)(2−ピリジル)]−イソプロピル}アミノ)ピリミジン−5−イル]ベンズアミド;
3−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ベンズアミド;
4−フルオロ−3−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ベンズアミド;
N−{[4−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)フェニル]メチル}アセトアミド;
[5−(2−アミノピリミジン−5−イル)ピリミジン−2−イル][1−(3−フルオロ(2−ピリジル))−イソプロピル]アミン;
2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−5−カルボキサミド;
メチル2−[4−フルオロ−3−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)フェニル]アセタート;
N−{[3−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)フェニル]メチル}アセトアミド;
3−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ベンズアミド;
3−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−4−フルオロベンズアミド;
1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−カルボニトリル;
1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−カルボキサミド;
2−[4−フルオロ−3−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)フェニル]アセトアミド;
2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピリミジン−4−カルボキサミド;
{5−[5−(アミノメチル)(1,3−チアゾール−2−イル)]ピリミジン−2−イル}[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミン;
N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−5−イル]メチル}アセトアミド;
2−アミノ−N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−5−イル)]メチル}アセトアミド;
N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−5−イル)]メチル}イミダゾール−5−イルカルボキサミド;
N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−5−イル)]メチル}(2−ヒドロキシイミダゾール−5−イル)カルボキサミド;
(アミノシクロプロピル)−N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−5−イル)]メチル}カルボキサミド;
((2R)ピロリジン−2−イル)−N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−5−イル)]メチル}カルボキサミド;
((2S)ピロリジン−2−イル)−N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−5−イル)]メチル}カルボキサミド;
N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−4−イル]メチル}アセトアミド;
2−[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−4−イル]アセトアミド;
1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピロール−3−カルボキサミド;
1−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−カルボキサミド;
{5−[4−(アミノメチル)(1,3−チアゾール−2−イル)]ピリミジン−2−イル}[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミン;
2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−4−カルボニトリル;
2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−4−カルボキサミド;
2−アミノ−N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−4−イル)]メチル}アセトアミド;
((2S)ピロリジン−2−イル)−N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−4−イル)]メチル}カルボキサミド;
((2R)ピロリジン−2−イル)−N−{[2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−4−イル)]メチル}カルボキサミド;
2−(2−{[1−(3−フルオロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−5−カルボニトリル;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−5−カルボキサミド;
1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−カルボン酸;
N−(2−カルバモイルエチル)[1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−イル]カルボキサミド;
[1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−イル]−N−(2−ヒドロキシエチル)カルボキサミド;
2−[1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−イル]プロパン−2−オール;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)イソオキサゾール−3−カルボキサミド;
[1−(3−クロロ(2−ピリジル))−イソプロピル](5−ピラゾール−4−イルピリミジン−2−イル)アミン;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピリジン−3−カルボキサミド;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)チオフェン−2−カルボン酸;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)チオフェン−2−カルボキサミド;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−オキサゾール−4−カルボキサミド;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−オキサゾール−4−カルボン酸;
[1−(3−クロロ(2−ピリジル))−イソプロピル](5−ピロロ[3,2−b]ピリジン−6−イルピリミジン−2−イル)アミン;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−オキサゾール−5−カルボキサミド;
4−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピリジン−2−カルボキサミド;
4−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−2−カルボキサミド;
[5−(3−アミノ(1H−インダゾール−5−イル))ピリミジン−2−イル][1−(3−クロロ(2−ピリジル))−イソプロピル]アミン;
3−(2−{[1−メチル−1−(4−メチルチオフェニル)エチル]アミノ}ピリミジン−5−イル)ベンゼンカルボニトリル;
3−(2−{[1−メチル−1−(2−メチルチオフェニル)エチル]アミノ}ピリミジン−5−イル)ベンゼンカルボニトリル;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−3−カルボキサミド;
3−(2−(2−(4−(メチルスルフィニル)フェニル)プロパン−2−イルアミノ)ピリミジン−5−イル)ベンズアミド;
3−[2−({1−メチル−1−[4−(メチルスルホニル)フェニル]エチル}アミノ)ピリミジン−5−イル]ベンズアミド;
3−[2−({1−メチル−1−[2−(メチルスルホニル)フェニル]エチル}アミノ)ピリミジン−5−イル]ベンズアミド;
3−[2−({1−メチル−1−[3−(メチルスルホニル)(2−ピリジル)]エチル}アミノ)ピリミジン−5−イル]ベンズアミド;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−4−カルボキサミド;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−4−カルボン酸;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−オキサゾール−5−カルボン酸;
3−(2−{[1−メチル−1−(3−メチルチオ(2−ピリジル))エチル]アミノ}ピリミジン−5−イル)ベンゼンカルボニトリル;
3−(2−{[1−メチル−1−(2−メチルチオフェニル)エチル]アミノ}ピリミジン−5−イル)ベンズアミド;
3−(2−(2−(2−(メチルスルフィニル)フェニル)プロパン−2−イルアミノ)ピリミジン−5−イル)ベンズアミド;
3−(2−{[1−メチル−1−(3−メチルチオ(2−ピリジル))エチル]アミノ}ピリミジン−5−イル)ベンズアミド;
3−(2−(2−(3−(メチルスルフィニル)ピリジン−2−イル)プロパン−2−イルアミノ)ピリミジン−5−イル)ベンズアミド;
3−[2−({1−[3−(ジフルオロメチル)(2−ピリジル)]−イソプロピル}アミノ)ピリミジン−5−イル]−4−フルオロベンゼンカルボニトリル;
3−[2−({1−[3−(ジフルオロメチル)(2−ピリジル)]−イソプロピル}アミノ)ピリミジン−5−イル]−4−フルオロベンズアミド;
(5−(5H−1,2,3,4−テトラゾール−5−イル)ピリミジン−2−イル)[1−(3−クロロ(2−ピリジル))−イソプロピル]アミン;
エチル5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3,4−オキサジアゾール−2−カルボキシラート;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3,4−オキサジアゾール−2−カルボキサミド;
メチル4−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)チオフェン−2−カルボキシラート;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−2−カルボキサミド;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3,4−チアジアゾール−2−カルボキサミド;
メチル4−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1−メチルイミダゾール−2−カルボキシラート;
6−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピリジン−2−カルボキサミド;
3−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,2,4−オキサジアゾール−5−カルボキサミド;
エチル5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,2,4−オキサジアゾール−3−カルボキシラート;
[5−(3−アミノ(1H−インダゾール−5−イル))ピリミジン−2−イル][1−(3−フルオロ(2−ピリジル))−イソプロピル]アミン;
4−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)チオフェン−2−カルボキサミド;
[1−(3−クロロ(2−ピリジル))−イソプロピル](5−(1,2,4−オキサジアゾール−5−イル)ピリミジン−2−イル)アミン;
4−フルオロ−3−(2−{[1−(3−メトキシ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ベンゼンカルボニトリル;
4−フルオロ−3−(2−{[1−メチル−1−(3−メチル(2−ピリジル))エチル]アミノ}ピリミジン−5−イル)ベンズアミド;
4−フルオロ−3−(2−{[1−(3−メトキシ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ベンズアミド;
{5−[5−(アミノメチル)(1,3−チアゾール−2−イル)]ピリミジン−2−イル}[1−(3−クロロ(2−ピリジル))−イソプロピル]アミン;
N−{[2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−5−イル]メチル}アセトアミド;
N−{[2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−5−イル)]メチル}−2−ヒドロキシ−2−メチルプロパンアミド;
N−{[2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−5−イル)]メチル}(2−ヒドロキシイミダゾール−4−イル)カルボキサミド;
3−(2−{[1−(3−クロロ−6−ヒドロキシ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ベンズアミド;
3−(2−{[1−(3−クロロ−6−メトキシ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ベンズアミド;
[1−(3−クロロ(2−ピリジル))−イソプロピル](5−(1,3−チアゾール−2−イル)ピリミジン−2−イル)アミン;
2−[4−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾリル]エタン−1−オール;
2−[4−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾリル]酢酸;
2−[4−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾリル]アセトアミド;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピリジン−4−カルボニトリル;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピリジン−4−カルボキサミド;
N−{[1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−イル]メチル}アセトアミド;
3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ベンズアミド;
6−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−2−ピロリノ[3,2−b]ピリジン−2−オン;
6−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)イミダゾ[2,1−b]1,3−チアゾリン−2−カルボキサミド;
[5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)(1H−インダゾール−3−イル)](メチルスルホニル)アミン;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1−メチルピラゾール−3−カルボキサミド;
3−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1−メチルピラゾール−5−カルボキサミド;
6−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)イミダゾ[2,1−b]1,3−チアゾリン−3−カルボキサミド;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−2−メトキシピリジン−3−カルボニトリル;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−2−メトキシピリジン−3−カルボキサミド;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−2−オキソヒドロピリジン−3−カルボキサミド;
2−[(tert−ブトキシ)カルボニルアミノ]−N−{[1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−イル]メチル}アセトアミド;
2−アミノ−N−{[1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−イル]メチル}アセトアミド;
3−[(tert−ブトキシ)カルボニルアミノ]−N−{[1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−イル]メチル}プロパンアミド;
3−アミノ−N−{[1−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピラゾール−4−イル]メチル}プロパンアミド;
エチル3−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)イソオキサゾール−5−カルボキシラート;
3−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)イソオキサゾール−5−カルボキサミド;
(5−(1H−インダゾール−5−イル)ピリミジン−2−イル)[1−(3−クロロ(2−ピリジル))−イソプロピル]アミン;
N−[5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−1H−インダゾール−3−イル]アセトアミド;
6−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピリミジン−4−カルボキサミド;
メチル6−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピリミジン−4−カルボキシラート;
3−(2−{[1−(2−クロロ(3−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−4−フルオロベンズアミド;
6−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)イミダゾ[2,1−b]1,3−チアゾリン−3−カルボン酸;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−4−ヒドロイミダゾ[1,2−a]ピリジン−6−カルボン酸;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−4−ヒドロイミダゾ[1,2−a]ピリジン−6−カルボキサミド;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−4−ヒドロイミダゾ[1,2−a]ピリジン−8−カルボキサミド;
2−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)−4−ヒドロイミダゾ[1,2−a]ピリジン−7−カルボキサミド;
5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピリダジン−3−カルボキサミド;
N−(tert−ブチル)[5−(2−{[1−(3−クロロ(2−ピリジル))−イソプロピル]アミノ}ピリミジン−5−イル)ピリダジン−3−イル]カルボキサミド。 - 以下から選択される請求項1の化合物またはその薬学的に許容される塩:
4−フルオロ−3−(2−{[(3−フルオロ(2−ピリジル))シクロブチル]アミノ}ピリミジン−5−イル)ベンズアミド;
4−(2−{[(4−フルオロフェニル)シクロブチル]アミノ}ピリミジン−5−イル)ピリジン−2−カルボニトリル;
4−フルオロ−3−(2−{[(4−フルオロフェニル)シクロブチル]アミノ}ピリミジン−5−イル)ベンズアミド;
4−(2−{[(3−フルオロ−2−ピリジル)シクロブチル]アミノ}ピリミジン−5−イル)ピリジン−2−カルボニトリル;
4−(2−{[(3−フルオロ−2−ピリジル)シクロブチル]アミノ}ピリミジン−5−イル)ピリジン−2−カルボキサミド;
4−(2−{[(4−フルオロフェニル)シクロブチル]アミノ}ピリミジン−5−イル)ピリジン−2−カルボキサミド;
(5−(1H−インダゾール−5−イル)ピリミジン−2−イル)[(3−フルオロ(2−ピリジル))シクロブチル]アミン;
5−(2−{[(3−フルオロ−2−ピリジル)シクロブチル]アミノ}ピリミジン−5−イル)−1H−インダゾール−3−カルボニトリル;
5−(2−{[(3−フルオロ−2−ピリジル)シクロブチル]アミノ}ピリミジン−5−イル)−1H−インダゾール−3−カルボキサミド;
[5−(6−フルオロ(1H−インダゾール−5−イル))ピリミジン−2−イル][(3−フルオロ(2−ピリジル))シクロブチル]アミン;
6−フルオロ−5−(2−{[(3−フルオロ(2−ピリジル))シクロブチル]アミノ}ピリミジン−5−イル)−1H−インダゾール−3−カルボニトリル;
6−フルオロ−5−(2−{[(3−フルオロ(2−ピリジル))シクロブチル]アミノ}ピリミジン−5−イル)−1H−インダゾール−3−カルボキサミド;
3−(2−{[1−(3−クロロ(2−ピリジル))−3−フルオロシクロブチル]アミノ}ピリミジン−5−イル)−4−フルオロベンズアミド。 - 以下から選択される請求項1の化合物またはその薬学的に許容される塩:
4−(2−{[2−(4−フルオロフェニル)−2−メチルプロピル]アミノ}ピリミジン−5−イル)ベンズアミド;
3−(2−{[2−(4−フルオロフェニル)−2−メチルプロピル]アミノ}ピリミジン−5−イル)ベンズアミド;
5−(2−{[2−(4−フルオロフェニル)−2−メチルプロピル]アミノ}ピリミジン−5−イル)ピリジン−3−カルボニトリル;
5−(2−{[2−(4−フルオロフェニル)−2−メチルプロピル]アミノ}ピリミジン−5−イル)ピリジン−3−カルボキサミド;
5−(2−{[2−(4−フルオロフェニル)−2−メチルプロピル]アミノ}ピリミジン−5−イル)−3−ヒドロベンズイミダゾール−2−オン;
[5−(3−アミノ(1H−インダゾール−5−イル))ピリミジン−2−イル][2−(4−フルオロフェニル)−2−メチルプロピル]アミン;
3−(2−{[2−(3−フルオロ(2−ピリジル))−2−メチルプロピル]アミノ}ピリミジン−5−イル)ベンズアミド;
2−(2−{[2−(3−フルオロ(2−ピリジル))−2−メチルプロピル]アミノ}ピリミジン−5−イル)ピリミジン−4−カルボキサミド;
3−(2−{[2−(3−クロロ(2−ピリジル))−2−メチルプロピル]アミノ}ピリミジン−5−イル)ベンズアミド;
3−(2−{[2−(3−クロロ(2−ピリジル))−2−メチルプロピル]アミノ}ピリミジン−5−イル)−4−フルオロベンズアミド。 - 以下から選択される請求項1の化合物またはその薬学的に許容される塩:
エチル1−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピラゾール−4−カルボキシラート;
1−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピラゾール−4−カルボキサミド;
1−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピラゾール−4−カルボン酸;
2−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−4−カルボキサミド;
エチル2−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−4−カルボキシラート;
2−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−4−カルボン酸;
2−(2−{[(2−ピリジルシクロブチル)メチル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−5−カルボキサミド;
2−(2−{[(2−ピリジルシクロブチル)メチル]アミノ}ピリミジン−5−イル)−1,3−チアゾール−5−カルボニトリル;
2−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−5−カルボニトリル;
{4−[6−({[(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリダジン−3−イル]ピリミジン−2−イル}(メチルスルホニル)アミン;
3−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]ベンズアミド;
1−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピラゾール−4−カルボニトリル;
3−[2−({[1−(3−クロロ(2−ピリジル))−3−フルオロシクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−フルオロベンズアミド;
3−[2−({[1−(3−クロロ(2−ピリジル))−3−フルオロシクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−フルオロベンズアミド;
4−フルオロ−3−(2−{[(3−フルオロ−1−(2−ピリジル)シクロブチル)メチル]アミノ}ピリミジン−5−イル)ベンズアミド;
4−フルオロ−3−(2−{[(3−フルオロ−1−(2−ピリジル)シクロブチル)メチル]アミノ}ピリミジン−5−イル)ベンズアミド;
3−[2−({[(3−クロロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−フルオロベンズアミド;
3−[2−({[(3−クロロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]ベンズアミド;
3−(2−{[(2−ピリジルシクロブチル)メチル]アミノ}ピリミジン−5−イル)ベンズアミド;
4−フルオロ−3−(2−{[(2−ピリジルシクロブチル)メチル]アミノ}ピリミジン−5−イル)ベンズアミド;
3−[2−({[(3−クロロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−フルオロベンゼンカルボニトリル;
3−[2−({[(3−クロロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]ベンゼンカルボニトリル;
メチル1−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピロール−3−カルボキシラート;
1−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピロール−3−カルボン酸;
1−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピロール−3−カルボキサミド;
{3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−(メチルスルホニル)カルボキサミド;
2−{2−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−5−イル}エタンニトリル;
2−{2−[2−({[(3−クロロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−5−イル}アセトアミド;
3−[2−({[1−(3−クロロ(2−ピリジル))−3,3−ジフルオロシクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−フルオロベンズアミド;
3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)−4−メチルピリミジン−5−イル]ベンズアミド;
2−{2−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−5−イル}アセトアミド;
2−{2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−5−イル}アセトアミド;
(tert−ブトキシ)−N−({2−[2−({[(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル](1,3−チアゾール−5−イル)}メチル)カルボキサミド;
{5−[5−(アミノメチル)(1,3−チアゾール−2−イル)]ピリミジン−2−イル}{[(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
N−({2−[2−({[(3−フルオロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−5−イル}メチル)アセトアミド;
(tert−ブトキシ)−N−({2−[2−({[(3−クロロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル](1,3−チアゾール−5−イル)}メチル)カルボキサミド;
{5−[5−(アミノメチル)(1,3−チアゾール−2−イル)]ピリミジン−2−イル}{[(3−クロロ(2−ピリジル))シクロブチル]メチル}アミン;
N−({2−[2−({[(3−クロロ−2−ピリジル)シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−5−イル}メチル)アセトアミド;
({2−[2−({[(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル](1,3−チアゾール−5−イル)}メチル)(メチルスルホニル)アミン;
2−{2−[2−({[1−(3−クロロ(2−ピリジル))−3−フルオロシクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−チアゾール−5−イル}アセトアミド;
(tert−ブトキシ)−N−{[2−(2−{[(2−ピリジルシクロブチル)メチル]アミノ}ピリミジン−5−イル)(1,3−チアゾール−5−イル)]メチル}カルボキサミド;
{3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−メチルカルボキサミド;
{3−[2−({[(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−メチルカルボキサミド;
{4−フルオロ−3−[2−({[(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−メチルカルボキサミド;
{3−[2−({[(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−ヒドロキシフェニル}−N−メチルカルボキサミド;
3−[2−({[(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−ヒドロキシベンズアミド;
{3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−ヒドロキシフェニル}−N−メチルカルボキサミド;
3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−ヒドロキシベンズアミド;
{1−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピロール−3−イル}−N−メチルカルボキサミド;
{2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル](4−ピリジル)}−N−メチルカルボキサミド;
{[(3−フルオロ(2−ピリジル))シクロブチル]メチル}(5−イミダゾール−2−イルピリミジン−2−イル)アミン;
7−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]インドリン−2−オン;
3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−ヒドロキシ安息香酸;
メチル3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−ヒドロキシベンゾエート;
1−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−6−オキソヒドロピリジン−3−カルボン酸;
1−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−6−オキソヒドロピリジン−3−カルボキサミド;
2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリミジン−4−カルボニトリル;
{2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリミジン−4−イル}−N−メチルカルボキサミド;
2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリミジン−4−カルボキサミド;
7−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]イソインドリン−1−オン;
{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}[5−(2−フルオロフェニル)ピリミジン−2−イル]アミン;
2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ベンズアミド;
2−{2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}アセトアミド;
N−{2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}アセトアミド;
2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ベンゼン−1,4−ジカルボキサミド;
4−フルオロ−2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ベンズアミド;
2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリジン−4−カルボニトリル;
2−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリジン−4−カルボキサミド;
2−{3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)−4−メチルピリミジン−5−イル]フェニル}アセトアミド;
4−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)−4−メチルピリミジン−5−イル]ベンゼンカルボニトリル;
4−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)−4−メチルピリミジン−5−イル]ベンズアミド;
6−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリジン−3−オール;
[5−(5−アミノピラジン−2−イル)ピリミジン−2−イル]{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
5−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−2−ヒドロキシベンズアミド;
2−{4−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)−4−メチルピリミジン−5−イル]フェニル}アセトアミド;
2−{4−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)−4−メチルピリミジン−5−イル]フェニル}酢酸;
[5−(2−アミノ−5−メチルピリミジン−4−イル)ピリミジン−2−イル]{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
[5−(2−アミノ−4−メチルピリミジン−5−イル)ピリミジン−2−イル]{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリジン−2−オール;
[5−(6−アミノピリダジン−3−イル)ピリミジン−2−イル]{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
[5−(2−アミノピリミジン−5−イル)ピリミジン−2−イル]{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
5−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリジン−2−オール;
{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}[5−(6−メトキシ(3−ピリジル))ピリミジン−2−イル]アミン;
[5−(6−アミノピラジン−2−イル)ピリミジン−2−イル]{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
[5−(2−アミノピリミジン−4−イル)ピリミジン−2−イル]{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
[5−(2−アミノ−5−フルオロピリミジン−4−イル)ピリミジン−2−イル]{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)−4−メトキシピリミジン−5−イル]ベンズアミド;
3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)−4−ヒドロキシピリミジン−5−イル]安息香酸;
3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)−4−ヒドロキシピリミジン−5−イル]ベンズアミド;
5−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリミジン−2−オール;
{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}[5−(2−メトキシピリミジン−5−イル)ピリミジン−2−イル]アミン;
6−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリダジン−3−オール;
{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}[5−(6−メトキシピリダジン−3−イル)ピリミジン−2−イル]アミン;
1−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−4−ヒドロキシヒドロピリジン−2−オン;
5−フルオロ−6−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ピリジン−3−オール;
{3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−(1−メチルアゼチジン−3−イル)カルボキサミド;
{4−フルオロ−3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−(1−メチルアゼチジン−3−イル)カルボキサミド;
N−(1−アセチルアゼチジン−3−イル){3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}カルボキサミド;
N−(1−アセチルアゼチジン−3−イル){4−フルオロ−3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}カルボキサミド;
{4−フルオロ−3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−[1−(メチルスルホニル)アゼチジン−3−イル]カルボキサミド;
{3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−[1−(メチルスルホニル)アゼチジン−3−イル]カルボキサミド;
{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}(4−メトキシ−5−フェニルピリミジン−2−イル)アミン;
{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}(4−メトキシ−5−フェニルピリミジン−2−イル)アミン;
{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}(4−メトキシ−5−フェニルピリミジン−2−イル)メチルアミン;
{3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−(3−ヒドロキシシクロブチル)カルボキサミド;
{4−フルオロ−3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]フェニル}−N−(3−ヒドロキシシクロブチル)カルボキサミド;
4−フルオロ−3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−2−ヒドロキシベンズアミド;
3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−2−ヒドロキシベンズアミド;
[5−(2,6−ジメトキシピリミジン−4−イル)ピリミジン−2−イル]{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
[5−(2,4−ジメトキシピリミジン−5−イル)ピリミジン−2−イル]{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミン;
6−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−ジヒドロピリミジン−2,4−ジオン;
5−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−1,3−ジヒドロピリミジン−2,4−ジオン;
3−アミノ−6−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ヒドロピラジン−2−オン;
{3−[2−({[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]−2−ヒドロキシフェニル}−N−メチルカルボキサミド;
{[3−フルオロ−1−(3−フルオロ(2−ピリジル))シクロブチル]メチル}[5−(3−メトキシ−6−メチル(2−ピリジル))ピリミジン−2−イル]アミン;
3−[2−({[3−フルオロ−1−(3−フルオロ−6−メチル(2−ピリジル))シクロブチル]メチル}アミノ)ピリミジン−5−イル]ベンズアミド。 - 請求項1〜54のいずれかに記載の化合物又はその薬学的に許容される塩を含んでいる医薬組成物。
- 医薬組成物が、経口、舌下、皮下、非経口、静脈内、鼻腔内、局所、経皮、腹腔内、筋内、肺内、膣内、直腸内、又は眼内投与用に製剤化されている、請求項55に記載の医薬組成物。
- 医薬組成物が、経口投与用に製剤化されている、請求項55に記載の医薬組成物。
- 神経筋障害、筋肉消耗の病態、筋原性疾患、リハビリテーション関連障害、末梢血管疾患、末梢動脈疾患、虚弱、筋萎縮及び疲労、代謝症候群、慢性疲労症候群及び肥満から選択される疾患又は病態の治療用医薬を調製するための、請求項1〜54のいずれかに記載の化合物又はその薬学的に許容される塩の使用。
- 筋萎縮性側索硬化症(ALS)、脊髄性筋萎縮症(SMA)及び重症筋無力症から選択される疾患の治療用医薬を調製するための、請求項1〜54のいずれかに記載の化合物又はその薬学的に許容される塩の使用。
- 末梢血管疾患及び末梢動脈疾患から選択される疾患の治療用医薬を調製するための、請求項1〜54のいずれかに記載の化合物又はその薬学的に許容される塩の使用。
- 神経筋障害、筋肉消耗の病態、筋原性疾患、リハビリテーション関連障害、末梢血管疾患、末梢動脈疾患、虚弱、筋萎縮及び疲労、代謝症候群、慢性疲労症候群及び肥満から選択される疾患又は病態の治療のための、請求項55〜57のいずれかに記載の医薬組成物。
- 筋萎縮性側索硬化症(ALS)、脊髄性筋萎縮症(SMA)及び重症筋無力症から選択される疾患の治療のための、請求項55〜57のいずれかに記載の医薬組成物。
- 末梢血管疾患及び末梢動脈疾患から選択される疾患の治療のための、請求項55〜57のいずれかに記載の医薬組成物。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US32759710P | 2010-04-23 | 2010-04-23 | |
US61/327,597 | 2010-04-23 | ||
US41229910P | 2010-11-10 | 2010-11-10 | |
US61/412,299 | 2010-11-10 | ||
PCT/US2011/033614 WO2011133888A1 (en) | 2010-04-23 | 2011-04-22 | Certain amino-pyrimidines, compositions thereof, and methods for their use |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013525377A JP2013525377A (ja) | 2013-06-20 |
JP5852099B2 true JP5852099B2 (ja) | 2016-02-03 |
Family
ID=44834530
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013506329A Active JP5852099B2 (ja) | 2010-04-23 | 2011-04-22 | ある種のアミノ−ピリミジン、その組成物、及びそれを用いるための方法 |
Country Status (34)
Country | Link |
---|---|
US (7) | US8962632B2 (ja) |
EP (3) | EP2560653B1 (ja) |
JP (1) | JP5852099B2 (ja) |
KR (2) | KR102003030B1 (ja) |
CN (3) | CN103025331B (ja) |
AR (1) | AR081331A1 (ja) |
AU (1) | AU2011242575C1 (ja) |
BR (1) | BR112012026951B1 (ja) |
CA (1) | CA2796637C (ja) |
CL (1) | CL2012002944A1 (ja) |
CO (1) | CO6620055A2 (ja) |
CY (2) | CY1117809T1 (ja) |
DK (2) | DK3127540T3 (ja) |
EA (2) | EA028079B1 (ja) |
EC (1) | ECSP12012293A (ja) |
ES (2) | ES2784279T3 (ja) |
HK (2) | HK1180604A1 (ja) |
HR (2) | HRP20160827T1 (ja) |
HU (2) | HUE028953T2 (ja) |
IL (2) | IL222467A (ja) |
LT (2) | LT2560653T (ja) |
ME (2) | ME02439B (ja) |
MX (1) | MX2012012189A (ja) |
MY (2) | MY193277A (ja) |
NZ (1) | NZ603594A (ja) |
PH (1) | PH12016502037A1 (ja) |
PL (2) | PL3127540T3 (ja) |
PT (2) | PT3127540T (ja) |
RS (2) | RS54948B1 (ja) |
SG (1) | SG184959A1 (ja) |
SI (2) | SI2560653T1 (ja) |
SM (1) | SMT201600226B (ja) |
TW (1) | TWI520737B (ja) |
WO (1) | WO2011133888A1 (ja) |
Families Citing this family (75)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8748623B2 (en) | 2009-02-17 | 2014-06-10 | Syntrix Biosystems, Inc. | Pyridinecarboxamides as CXCR2 modulators |
AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
WO2011133920A1 (en) | 2010-04-23 | 2011-10-27 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
EP2608672B1 (en) * | 2010-08-23 | 2020-12-16 | Syntrix Biosystems, Inc. | Aminopyridine- and aminopyrimidinecarboxamides as cxcr2 modulators |
AR083797A1 (es) | 2010-11-10 | 2013-03-20 | Novartis Ag | Succinato de dimetil-amida del acido 7-ciclopentil-2-(5-piperazin-1-il-piridin-2-il-amino)-7h-pirrolo-[2,3-d]pirimidin-6-carboxilico, proceso para prepararla, intermediarios de dicha sintesis y proceso de preparacion de los mismos |
WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
WO2013046136A1 (en) | 2011-09-27 | 2013-04-04 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh |
JP5966014B2 (ja) * | 2011-11-28 | 2016-08-10 | ノバルティス アーゲー | 新規トリフルオロメチル−オキサジアゾール誘導体および疾患の処置におけるその使用 |
UY34632A (es) | 2012-02-24 | 2013-05-31 | Novartis Ag | Compuestos de oxazolidin- 2- ona y usos de los mismos |
JP6345645B2 (ja) * | 2012-04-02 | 2018-06-20 | サイトキネティックス, インコーポレイテッド | 横隔膜機能を向上させるための方法 |
JP6352244B2 (ja) * | 2012-04-11 | 2018-07-04 | サイトキネティックス, インコーポレイテッド | 骨格筋疲労に対する耐性を向上させるための方法 |
SG11201408238WA (en) | 2012-06-13 | 2015-01-29 | Incyte Corp | Substituted tricyclic compounds as fgfr inhibitors |
US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
US9296733B2 (en) | 2012-11-12 | 2016-03-29 | Novartis Ag | Oxazolidin-2-one-pyrimidine derivative and use thereof for the treatment of conditions, diseases and disorders dependent upon PI3 kinases |
US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
AP2015008707A0 (en) | 2013-03-14 | 2015-09-30 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh |
EA035095B1 (ru) | 2013-04-19 | 2020-04-27 | Инсайт Холдингс Корпорейшн | Бициклические гетероциклы в качестве ингибиторов fgfr |
US10046002B2 (en) | 2013-08-02 | 2018-08-14 | Syntrix Biosystems Inc. | Method for treating cancer using chemokine antagonists |
US8969365B2 (en) | 2013-08-02 | 2015-03-03 | Syntrix Biosystems, Inc. | Thiopyrimidinecarboxamides as CXCR1/2 modulators |
US10561676B2 (en) | 2013-08-02 | 2020-02-18 | Syntrix Biosystems Inc. | Method for treating cancer using dual antagonists of CXCR1 and CXCR2 |
JPWO2015163435A1 (ja) | 2014-04-24 | 2017-04-20 | 田辺三菱製薬株式会社 | 新規2−アミノ−ピリジン及び2−アミノ−ピリミジン誘導体及びその医薬用途 |
US20170042890A1 (en) | 2014-04-29 | 2017-02-16 | Cytokinetics, Inc. | Methods of reducing decline in vital capacity |
CA2957804C (en) | 2014-09-09 | 2023-04-04 | Astellas Pharma Inc. | Pharmaceutical composition for prevention and/or treatment of urinary incontinence |
US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
CR20170390A (es) | 2015-02-20 | 2017-10-23 | Incyte Holdings Corp | Heterociclos biciclicos como inhibidores de fgfr |
US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
WO2016149160A1 (en) * | 2015-03-15 | 2016-09-22 | Sunshine Lake Pharma Co., Ltd. | Substituted aminopyrimidine compounds and methods of use |
CN105111151B (zh) * | 2015-04-17 | 2018-09-28 | 成都理工大学 | 作为PPAR-γ调节剂的氨基嘧啶衍生物 |
CA2987179C (en) | 2015-05-29 | 2020-08-25 | Pfizer Inc. | Heterocyclic compounds as inhibitors of vanin-1 enzyme |
JP6560436B2 (ja) | 2015-07-27 | 2019-08-14 | チョン クン ダン ファーマシューティカル コーポレーション | ヒストン脱アセチル化酵素6阻害剤としての1,3,4−オキサジアゾールスルホンアミド誘導体化合物及びこれを含有する薬剤学的組成物 |
AU2016299485B2 (en) | 2015-07-27 | 2019-02-07 | Chong Kun Dang Pharmaceutical Corp. | 1,3,4-oxadiazole amide derivative compound as histone deacetylase 6 inhibitor, and pharmaceutical composition containing same |
BR112017027798B1 (pt) | 2015-07-27 | 2023-12-19 | Chong Kun Dang Pharmaceutical Corp | Compostos de derivado de 1,3,4-oxadiazol sulfamida como inibidor de histona desacetilase 6 e a composição farmacêutica que compreende os mesmos |
ES2903214T3 (es) | 2015-08-04 | 2022-03-31 | Chong Kun Dang Pharmaceutical Corp | Compuestos derivados de 1,3,4-oxadiazol como inhibidores de la histona desacetilasa 6 y la composición farmacéutica que comprende los mismos |
PL3362445T3 (pl) * | 2015-10-12 | 2023-08-07 | Chong Kun Dang Pharmaceutical Corp. | Związki będące pochodnymi oksadiazoloamin jako inhibitor deacetylazy histonowej 6 oraz kompozycja farmaceutyczna obejmujące takie związki |
KR20180120701A (ko) | 2016-02-12 | 2018-11-06 | 아스테라스 세이야쿠 가부시키가이샤 | 테트라히드로이소퀴놀린 유도체 |
RU2019100559A (ru) | 2016-07-14 | 2020-07-14 | Пфайзер Инк. | Новые пиримидиновые карбоксамиды в качестве ингибиторов фермента ванин-1 |
US10660909B2 (en) | 2016-11-17 | 2020-05-26 | Syntrix Biosystems Inc. | Method for treating cancer using chemokine antagonists |
US10357493B2 (en) | 2017-03-10 | 2019-07-23 | Selenity Therapeutics (Bermuda), Ltd. | Metalloenzyme inhibitor compounds |
US10961242B2 (en) | 2017-05-17 | 2021-03-30 | Legochem Biosciences, Inc. | Compounds as autotaxin inhibitors and pharmaceutical compositions comprising the same |
KR101798840B1 (ko) * | 2017-05-17 | 2017-11-17 | 주식회사 레고켐 바이오사이언스 | 신규 오토탁신 저해 화합물 및 이를 함유하는 약제학적 조성물 |
AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
RU2020105929A (ru) | 2017-08-04 | 2021-09-06 | Скайхоук Терапьютикс, Инк. | Способы и композиции для модулирования сплайсинга |
CN111936490A (zh) | 2017-11-20 | 2020-11-13 | 西奈山伊坎医学院 | 激酶抑制剂化合物和组合物及使用方法 |
SG11202006085PA (en) * | 2017-12-26 | 2020-07-29 | Cytokinetics Inc | Process for the preparation of an amino-pyrimidine and intermediates thereof |
WO2019134661A1 (zh) * | 2018-01-03 | 2019-07-11 | 南京明德新药研发股份有限公司 | 异吲哚啉酮及其衍生物作为csf-1r抑制剂 |
CN111819193A (zh) | 2018-01-05 | 2020-10-23 | 西奈山伊坎医学院 | 增加胰腺β细胞增殖的方法、治疗方法以及组合物 |
US11866427B2 (en) | 2018-03-20 | 2024-01-09 | Icahn School Of Medicine At Mount Sinai | Kinase inhibitor compounds and compositions and methods of use |
SG11202010636VA (en) | 2018-05-04 | 2020-11-27 | Incyte Corp | Solid forms of an fgfr inhibitor and processes for preparing the same |
WO2019213506A1 (en) | 2018-05-04 | 2019-11-07 | Incyte Corporation | Salts of an fgfr inhibitor |
CN110483440A (zh) * | 2018-06-11 | 2019-11-22 | 上海睿升化工科技有限公司 | 一种2-(2-溴-1,3-噻唑-5-基)乙腈的制备方法 |
KR102316234B1 (ko) | 2018-07-26 | 2021-10-22 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이를 포함하는 약제학적 조성물 |
CA3118904A1 (en) | 2018-11-06 | 2020-05-14 | Edgewise Therapeutics, Inc. | Pyridazinone compounds and uses thereof |
BR112021008905A2 (pt) | 2018-11-06 | 2021-08-10 | Edgewise Therapeutics, Inc. | compostos de piridazinona e usos dos mesmos |
US20220064146A1 (en) * | 2018-12-31 | 2022-03-03 | Icahn School Of Medicine At Mount Sinai | Kinase inhibitor compounds and compositions and methods of use |
JP2022521467A (ja) | 2019-02-05 | 2022-04-08 | スカイホーク・セラピューティクス・インコーポレーテッド | スプライシングを調節するための方法および組成物 |
EP3920928A4 (en) | 2019-02-06 | 2022-09-28 | Skyhawk Therapeutics, Inc. | METHODS AND COMPOSITIONS FOR MODULATION OF SPLICING |
US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
KR20240096847A (ko) | 2019-05-16 | 2024-06-26 | 넥서스 파마슈티칼스, 인크. | 에페드린 또는 에페드린 염을 포함하는 조성물 및 그의 제조 및 사용 방법 |
MA56396A (fr) | 2019-06-27 | 2022-05-04 | Cytokinetics Inc | Polymorphes de 1-(2-((((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)méthyl)amino)pyrimidin-5-yl)-1h-pyrrole-3-carboxamide |
WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
CR20220169A (es) | 2019-10-14 | 2022-10-27 | Incyte Corp | Heterociclos bicíclicos como inhibidores de fgfr |
WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
CA3162010A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Derivatives of an fgfr inhibitor |
JP2023505258A (ja) | 2019-12-04 | 2023-02-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
WO2021231572A1 (en) * | 2020-05-13 | 2021-11-18 | Edgewise Therapeutics, Inc. | Pyridazinone compounds for the treatment of neuromuscular diseases |
WO2021231565A1 (en) * | 2020-05-13 | 2021-11-18 | Edgewise Therapeutics, Inc. | Pyridazinone compounds for the treatment of neuromuscular diseases |
CN116261452A (zh) * | 2020-07-15 | 2023-06-13 | 艾福姆德尤股份有限公司 | 用于治疗与sting活性有关的疾病的化合物和组合物 |
GB2598768A (en) * | 2020-09-11 | 2022-03-16 | Moa Tech Limited | Herbicidal heterocyclic derivatives |
TW202233602A (zh) * | 2020-10-27 | 2022-09-01 | 美商艾尼納製藥公司 | 可用於治療5-ht2a血清素受體相關疾病之作為5-ht2a血清素受體調節劑之嘧啶衍生物 |
IL302665A (en) | 2020-11-06 | 2023-07-01 | Cytokinetics Inc | Bicyclic 1,4-diazepenones and their therapeutic uses |
CA3220274A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
WO2024064745A1 (en) | 2022-09-21 | 2024-03-28 | Cytokinetics, Incorporated | Synthesis of reldesemtiv |
Family Cites Families (263)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB284425A (en) | 1926-11-22 | 1928-02-02 | James Last | Improvements in and relating to sand or like moulds for making castings |
CH361573A (de) * | 1957-07-12 | 1962-04-30 | Cilag Chemie Aktiengesellschaf | Verfahren zur Herstellung neuer 5-Aminomethyl-pyrimidine |
US3239345A (en) | 1965-02-15 | 1966-03-08 | Estrogenic compounds and animal growth promoters | |
JPS5416487B1 (ja) | 1970-03-17 | 1979-06-22 | ||
US4411890A (en) | 1981-04-14 | 1983-10-25 | Beckman Instruments, Inc. | Synthetic peptides having pituitary growth hormone releasing activity |
GB1345880A (en) | 1971-06-18 | 1974-02-06 | Cepbepe | Pyridazine derivatives |
US4036979A (en) | 1974-01-25 | 1977-07-19 | American Cyanamid Company | Compositions containing 4,5,6,7-tetrahydrobenz[b]thien-4-yl-ureas or derivatives and methods of enhancing growth rate |
US4157392A (en) | 1977-05-17 | 1979-06-05 | Diamond Shamrock Corporation | Pharmacologically active substituted 1,2,4-triazines |
HU175471B (hu) | 1977-06-13 | 1980-08-28 | Gyogyszerkutato Intezet | Sposob poluchenija novykh proizvodnykh 3-skobka-1-pirazolil-skobka zakryta-piridazina |
DE2730467A1 (de) | 1977-07-06 | 1979-01-18 | Basf Ag | Benzylpyrimidine, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
FR2510997A1 (fr) | 1981-08-10 | 1983-02-11 | Sanofi Sa | Nouveaux derives de la methyl-4 phenyl-6 pyridazine, procede pour leur preparation et medicaments actifs sur le systeme nerveux central en contenant |
FR2540115B1 (fr) | 1983-01-28 | 1985-06-07 | Sanofi Sa | Derive de la pyridazine ayant une action psychotrope, son mode de preparation et les medicaments en contenant |
CA1218655A (en) | 1983-01-28 | 1987-03-03 | Kathleen Biziere | Process for the preparation of pyridazine derivatives having a psychotropic action |
US4868183A (en) | 1986-07-21 | 1989-09-19 | Otsuka Pharmaceutical Factory, Inc. | N-pyrazinyl substituted P-aminophenols |
JPS63165376A (ja) | 1986-12-27 | 1988-07-08 | Nippon Soda Co Ltd | オキサ(チア)ジアゾ−ル誘導体その製造方法及び殺ダニ剤 |
EP0296864B1 (en) | 1987-06-25 | 1993-09-15 | Dowelanco | Process for preparing ureas |
WO1989007110A1 (en) | 1988-01-28 | 1989-08-10 | Eastman Kodak Company | Polypeptide compounds having growth hormone releasing activity |
ATE113607T1 (de) | 1988-01-28 | 1994-11-15 | Polygen Holding Corp | Polypeptidverbindungen mit wachstumshormonfreisetzender aktivität. |
JPH01261381A (ja) | 1988-04-12 | 1989-10-18 | Nippon Soda Co Ltd | オキサ(チア)ジアゾール誘導体、その製造方法及び殺ダニ剤 |
FR2636628B1 (fr) | 1988-08-25 | 1990-12-28 | Sanofi Sa | Derives du thiadiazole-1,3,4, leur procede d'obtention et compositions pharmaceutiques en contenant |
JPH02164863A (ja) | 1988-12-15 | 1990-06-25 | Otsuka Pharmaceut Co Ltd | p−アミノフェノール誘導体の製造方法 |
FR2663326B2 (fr) | 1989-11-17 | 1992-10-16 | Sanofi Sa | Derives de la pyridazine, procede de preparation et compositions pharmaceutiques en contenant. |
US5631255A (en) | 1989-02-07 | 1997-05-20 | Sanofi | Pyridazine derivatives |
US5461053A (en) | 1989-02-07 | 1995-10-24 | Sanofi | Pyridazine derivatives |
GR900100380A (el) | 1989-05-20 | 1991-10-10 | Fisons Plc | Μέ?οδος παρασκευής αντι-φλεγμονωδών παραγώγων αμινοφενόλης. |
IL96891A0 (en) | 1990-01-17 | 1992-03-29 | Merck Sharp & Dohme | Indole-substituted five-membered heteroaromatic compounds,their preparation and pharmaceutical compositions containing them |
GB9008123D0 (en) | 1990-04-10 | 1990-06-06 | Lilly Industries Ltd | Pharmaceutical compounds |
US5208248A (en) | 1991-01-11 | 1993-05-04 | Merck Sharpe & Dohme, Ltd. | Indazole-substituted five-membered heteroaromatic compounds |
US5317103A (en) | 1991-01-15 | 1994-05-31 | Merck Sharp & Dohme Limited | Indole-substituted five-membered heteroaromatic compounds as 5-HT1 agonists |
JP2651755B2 (ja) | 1991-03-01 | 1997-09-10 | 富士写真フイルム株式会社 | ハロゲン化銀カラー写真感光材料 |
IL101291A0 (en) | 1991-03-22 | 1992-11-15 | Nippon Soda Co | 2-pyridine derivatives,their preparation and their use as fungicides |
US5114958A (en) | 1991-05-09 | 1992-05-19 | Warner-Lambert Company | 1,2,4-oxadiazole and 1,2,4-thiadiazole derivatives of fenamates as antiinflammatory agents |
FR2676444B1 (fr) | 1991-05-16 | 1995-03-10 | Sanofi Elf | Nouveaux derives d'amino-3 pyridazines actifs sur le systeme nerveux central, procede de preparation et compositions pharmaceutiques en contenant. |
JPH06509574A (ja) | 1991-08-03 | 1994-10-27 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 5−ht↓4レセプターアンタゴニスト |
US5663146A (en) | 1991-08-22 | 1997-09-02 | Administrators Of The Tulane Educational Fund | Polypeptide analogues having growth hormone releasing activity |
JPH05117255A (ja) | 1991-10-25 | 1993-05-14 | Nippon Soda Co Ltd | オキサジアゾール及びチアジアゾール誘導体、その製法 |
HUT69739A (en) | 1992-03-26 | 1995-09-28 | Dowelanco | Process for producing n-heterocyclic nitroanilines and fungicides containing the compounds |
US5654322A (en) | 1992-08-11 | 1997-08-05 | Wakunaga Seiyaku Kabushiki Kaisha | Biphenylmethane derivatives and pharmaceuticals containing the same |
AU6436394A (en) | 1993-06-15 | 1995-01-03 | Pfizer Inc. | H2-antagonists as immune stimulants in bacterial infections of cattle or swine |
ZW8594A1 (en) | 1993-08-11 | 1994-10-12 | Bayer Ag | Substituted azadioxacycbalkenes |
DE4331178A1 (de) * | 1993-09-14 | 1995-03-16 | Hoechst Schering Agrevo Gmbh | Substituierte Pyridine und Pyrimidine, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel und Fungizide |
US5776983A (en) | 1993-12-21 | 1998-07-07 | Bristol-Myers Squibb Company | Catecholamine surrogates useful as β3 agonists |
DE4424788A1 (de) | 1993-12-22 | 1995-06-29 | Bayer Ag | Arylessigsäurederivate |
US6008257A (en) | 1994-01-28 | 1999-12-28 | Bayer Aktiengesellschaft | Hydroxamic-acid derivatives, method of preparing them and their use as fungicides |
GB9405347D0 (en) | 1994-03-18 | 1994-05-04 | Agrevo Uk Ltd | Fungicides |
DE69535592T2 (de) | 1994-03-25 | 2008-06-12 | Isotechnika, Inc., Edmonton | Verbesserung der effektivität von arzneimitteln duren deuterierung |
US6334997B1 (en) | 1994-03-25 | 2002-01-01 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
US5488064A (en) | 1994-05-02 | 1996-01-30 | Bristol-Myers Squibb Company | Benzo 1,3 dioxole derivatives |
US5922751A (en) | 1994-06-24 | 1999-07-13 | Euro-Celtique, S.A. | Aryl pyrazole compound for inhibiting phosphodiesterase IV and methods of using same |
PT779884E (pt) | 1994-09-09 | 2000-10-31 | Bayer Ag | Derivados de imidoacidos e sua utilizacao como pesticidas |
US5491134A (en) | 1994-09-16 | 1996-02-13 | Bristol-Myers Squibb Company | Sulfonic, phosphonic or phosphiniic acid β3 agonist derivatives |
US5541204A (en) | 1994-12-02 | 1996-07-30 | Bristol-Myers Squibb Company | Aryloxypropanolamine β 3 adrenergic agonists |
KR19990014855A (ko) | 1995-05-17 | 1999-02-25 | 미암리 디, 메코너헤이 | 살진균성 시클릭 아미드 |
EP0836384A1 (en) | 1995-06-20 | 1998-04-22 | E.I. Du Pont De Nemours And Company | Arthropodicidal and fungicidal cyclic amides |
TW502026B (en) | 1995-06-20 | 2002-09-11 | Zeneca Ltd | Aromatic compounds useful as antagonists of e-type prostaglandins, processes for the preparation thereof, pharmaceutical compositions comprising the compounds, and intermediates |
TW434240B (en) | 1995-06-20 | 2001-05-16 | Zeneca Ltd | Aromatic compounds, preparation thereof and pharmaceutical composition comprising same |
EP0752421B1 (en) | 1995-07-07 | 2005-10-12 | AstraZeneca AB | Ortho-substituted aromatic compounds, containing three (het)aryl moieties, their preparation and their use as prostaglandin E2-(PGE2)-antagonists |
DE19525969A1 (de) | 1995-07-17 | 1997-01-23 | Bayer Ag | Etherderivate |
US20070173465A9 (en) | 1995-10-11 | 2007-07-26 | Monahan Sean D | Expression of zeta negative and zeta positive nucleic acids using a dystrophin gene |
CN1056370C (zh) | 1995-10-17 | 2000-09-13 | 化学工业部沈阳化工研究院 | 具有除草活性的4-芳氧(硫或氨)基嘧啶衍生物及其制备 |
DE69636677D1 (de) | 1995-12-13 | 2006-12-14 | Univ California | Kristalle der mit einem Ligand komplexierten Ligandenbindedomäne des Schilddrüsenhormonrezeptors |
US5729399A (en) | 1995-12-13 | 1998-03-17 | International Business Machines Corporation | Contact start/stop disk drive with minimized head-disk wear in textured landing zone |
US6114537A (en) | 1996-02-26 | 2000-09-05 | Apotex Inc. | Process for scavenging thiols |
AU706497B2 (en) | 1996-04-03 | 1999-06-17 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
JP2000507595A (ja) | 1996-04-03 | 2000-06-20 | メルク エンド カンパニー インコーポレーテッド | ファルネシルプロテイントランスフェラーゼの阻害剤 |
US5874452A (en) | 1996-04-03 | 1999-02-23 | Merck & Co., Inc. | Biheteroaryl inhibitors of farnesyl-protein transferase |
US5859035A (en) | 1996-04-03 | 1999-01-12 | Merck & Co., Inc. | Arylheteroaryl inhibitors of farnesyl-protein transferase |
US5854265A (en) | 1996-04-03 | 1998-12-29 | Merck & Co., Inc. | Biheteroaryl inhibitors of farnesyl-protein transferase |
CA2249665A1 (en) | 1996-04-03 | 1997-10-09 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
CA2249639A1 (en) | 1996-04-03 | 1997-10-09 | Neville J. Anthony | Inhibitors of farnesyl-protein transferase |
US5883105A (en) | 1996-04-03 | 1999-03-16 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
US5770615A (en) | 1996-04-04 | 1998-06-23 | Bristol-Myers Squibb Company | Catecholamine surrogates useful as β3 agonists |
TW414795B (en) | 1996-07-01 | 2000-12-11 | Yamanouchi Pharma Co Ltd | A thiophene derivative and the pharmaceutical composition |
JP2000516583A (ja) | 1996-08-01 | 2000-12-12 | イー・アイ・デユポン・ドウ・ヌムール・アンド・カンパニー | 殺節足動物性および殺菌・殺カビ性の環状アミド類 |
WO1998023155A1 (en) | 1996-11-26 | 1998-06-04 | E.I. Du Pont De Nemours And Company | Arthropodicidal and fungicidal cyclic amides |
US6187797B1 (en) | 1996-12-23 | 2001-02-13 | Dupont Pharmaceuticals Company | Phenyl-isoxazoles as factor XA Inhibitors |
US5939439A (en) | 1996-12-30 | 1999-08-17 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
HRP980093A2 (en) | 1997-02-28 | 1998-12-31 | Lilly Co Eli | Heterocyclic compounds, pharmaceutical compositions comprising same, and methods for inhibiting "beta"-amyloid peptide release and/or its synthesis by use of such compounds |
US6699853B2 (en) | 1997-06-16 | 2004-03-02 | Hoechst Schering Agrevo Gmbh | 4-haloalkyl-3-heterocyclylpyridines, 4-haloalkyl-5-heterocyclyl-pyrimidines and 4-trifluoromethyl-3-oxadiazolylpyridines, processes for their preparation, compositions comprising them, and their use as pesticides |
DE19725450A1 (de) | 1997-06-16 | 1998-12-17 | Hoechst Schering Agrevo Gmbh | 4-Haloalkyl-3-heterocyclylpyridine und 4-Haloalkyl-5-heterocyclylpyrimidine, Verfahren zu ihrer Herstellung, sie enthaltende Mittel und ihre Verwendung als Schädlingsbekämpfungsmittel |
GB9713739D0 (en) | 1997-06-27 | 1997-09-03 | Karobio Ab | Thyroid receptor ligands |
GB9716446D0 (en) | 1997-08-05 | 1997-10-08 | Agrevo Uk Ltd | Fungicides |
AU3289299A (en) | 1998-02-19 | 1999-09-06 | Tularik Inc. | Antiviral agents |
US6506782B1 (en) | 1998-02-27 | 2003-01-14 | Athena Neurosciences, Inc. | Heterocyclic compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
DE19824175A1 (de) | 1998-05-29 | 1999-12-02 | Novartis Ag | Amino-azol-Verbindungen |
US6093724A (en) | 1998-08-18 | 2000-07-25 | Ucb, S.A. | Muscarinic agonists and antagonists |
AU1324300A (en) | 1998-10-26 | 2000-05-15 | Vertex Pharmaceuticals Incorporated | Pentacyclic compounds useful as inhibitors of hepatitis c virus ns3 helicase |
AU1455500A (en) | 1998-10-29 | 2000-05-22 | Trega Biosciences, Inc. | Oxadiazole, thiadiazole and triazole derivatives and combinatorial libraries thereof |
US20040053900A1 (en) | 1998-12-23 | 2004-03-18 | Pharmacia Corporation | Method of using a COX-2 inhibitor and an aromatase inhibitor as a combination therapy |
GB9828442D0 (en) | 1998-12-24 | 1999-02-17 | Karobio Ab | Novel thyroid receptor ligands and method II |
EP1035115B1 (en) | 1999-02-24 | 2004-09-29 | F. Hoffmann-La Roche Ag | 4-Phenylpyridine derivatives and their use as NK-1 receptor antagonists |
JP2000281579A (ja) | 1999-03-29 | 2000-10-10 | Sumitomo Pharmaceut Co Ltd | オキサジアゾリル−1,4−ジヒドロピリジン誘導体を含有するプロテオグリカン生成促進剤 |
US6548529B1 (en) | 1999-04-05 | 2003-04-15 | Bristol-Myers Squibb Company | Heterocyclic containing biphenyl aP2 inhibitors and method |
US6410254B1 (en) | 1999-05-18 | 2002-06-25 | Cytokinetics | Compositions and assays utilizing ADP or phosphate for detecting protein modulators |
US6743599B1 (en) | 1999-05-18 | 2004-06-01 | Cytokinetics, Inc. | Compositions and assays utilizing ADP or phosphate for detecting protein modulators |
US7202051B1 (en) | 1999-05-18 | 2007-04-10 | Cytokinetics, Inc. | Compositions and assays utilizing ADP or phosphate for detecting protein modulators |
PL353476A1 (en) | 1999-07-23 | 2003-11-17 | Shionogi & Co, Ltd. | Th2 differentiation inhibitors |
DE50001813D1 (de) | 1999-08-12 | 2003-05-22 | Basf Ag | Substituierte benzoxazole |
EP1078632A1 (en) | 1999-08-16 | 2001-02-28 | Sanofi-Synthelabo | Use of monoamine oxydase inhibitors for the manufacture of drugs intended for the treatment of obesity |
JP4144978B2 (ja) | 1999-09-09 | 2008-09-03 | 富士フイルム株式会社 | 1,2,4−チアジアゾール誘導体の合成法 |
US6844367B1 (en) | 1999-09-17 | 2005-01-18 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
US6632815B2 (en) | 1999-09-17 | 2003-10-14 | Millennium Pharmaceuticals, Inc. | Inhibitors of factor Xa |
WO2001021160A2 (en) | 1999-09-23 | 2001-03-29 | Axxima Pharmaceuticals Aktiengesellschaft | Carboxymide and aniline derivatives as selective inhibitors of pathogens |
GB9927844D0 (en) * | 1999-11-26 | 2000-01-26 | Glaxo Group Ltd | Chemical compounds |
JP2003517474A (ja) | 1999-11-29 | 2003-05-27 | ノバルティス アクチエンゲゼルシャフト | 殺虫性n−ヘテロアリールアルファ−アルコキシイミノ−カルボキサミド |
NZ518931A (en) | 1999-12-02 | 2004-02-27 | Novartis Ag | Aminoheterocyclyamides as Pesticides and Antiparasitic Agents |
US6602872B1 (en) | 1999-12-13 | 2003-08-05 | Merck & Co., Inc. | Substituted pyridazines having cytokine inhibitory activity |
WO2001046165A2 (en) | 1999-12-16 | 2001-06-28 | Novartis Ag | N-heteroaryl-amides and their use as parasiticides |
TWI284639B (en) | 2000-01-24 | 2007-08-01 | Shionogi & Co | A compound having thrombopoietin receptor agonistic effect |
US20020002171A1 (en) | 2000-01-28 | 2002-01-03 | Chalquest Richard R. | Materials and methods for killing nematodes and nematode eggs |
DE10006453A1 (de) | 2000-02-14 | 2001-08-16 | Bayer Ag | Piperidylcarbonsäuren als Integrinantagonisten |
US7078536B2 (en) | 2001-03-14 | 2006-07-18 | Genesoft Pharmaceuticals, Inc. | Charged compounds comprising a nucleic acid binding moiety and uses therefor |
EP1273287A1 (en) | 2000-04-04 | 2003-01-08 | Shionogi & Co., Ltd. | Oily compositions containing highly fat-soluble drugs |
WO2001076582A1 (fr) | 2000-04-05 | 2001-10-18 | Shionogi & Co., Ltd. | Micro-emulsions huile dans eau contenant des composes tricycliques ou des preconcentres de ceux-ci |
US6552033B1 (en) | 2000-05-16 | 2003-04-22 | The Procter & Gamble Co. | Imidazo-containing heterocyclic compounds, their compositions and uses |
GB0012671D0 (en) * | 2000-05-24 | 2000-07-19 | Merck Sharp & Dohme | Therapeutic agents |
WO2002000647A1 (en) | 2000-06-23 | 2002-01-03 | Bristol-Myers Squibb Pharma Company | Heteroaryl-phenyl substituted factor xa inhibitors |
NZ523184A (en) | 2000-06-23 | 2004-06-25 | Bristol Myers Squibb Pharma Co | 1 - (heteroaryl-phenyl) - condensed pyrazol derivatives as factor Xa inhibitors |
PE20020384A1 (es) | 2000-07-21 | 2002-05-28 | Schering Corp | PEPTIDOS COMO INHIBIDORES DE LA PROTEASA SERINA NS3/NS4a DEL VIRUS DE LA HEPATITIS C |
FR2812633A1 (fr) | 2000-08-04 | 2002-02-08 | Aventis Cropscience Sa | Derives de phenyl(thio)urees et phenyl(thio)carbamates fongicides |
EP1178036A1 (en) | 2000-08-04 | 2002-02-06 | Aventis Cropscience S.A. | Fungicidal phenylimidate derivatives |
EP1180512A1 (en) | 2000-08-04 | 2002-02-20 | Aventis Cropscience S.A. | Fungicidal phenylimine derivatives |
EP1178035B1 (en) | 2000-08-04 | 2008-07-30 | Bayer CropScience S.A. | Fungicidal phenylimine derivatives |
AU2002214626A1 (en) | 2000-09-29 | 2002-04-08 | Cor Therapeutics, Inc. | Quaternary amines and related inhibitors of factor xa |
US6667326B1 (en) | 2000-11-16 | 2003-12-23 | Novartis Animal Health Us, Inc. | Pesticidal aminoheterocyclamide compounds |
AUPR213700A0 (en) | 2000-12-18 | 2001-01-25 | Biota Scientific Management Pty Ltd | Antiviral agents |
JP2002212169A (ja) | 2001-01-12 | 2002-07-31 | Sumitomo Pharmaceut Co Ltd | 5員複素芳香環化合物 |
EP1354880A4 (en) | 2001-01-26 | 2004-08-25 | Shionogi & Co | HALOGEN COMPOUNDS HAVING AGONISM TOWARDS THROMBOPOIETIN RECEPTOR |
WO2002059099A1 (fr) | 2001-01-26 | 2002-08-01 | Shionogi & Co., Ltd. | Composes cycliques presentant un agonisme envers le recepteur de thrombopoietine |
CA2440374A1 (en) | 2001-03-14 | 2002-09-19 | Takayuki Maruyama | A pharmaceutical composition for the treatment of depression comprising the ep1 antagonist as active ingredient |
US6960595B2 (en) | 2001-03-23 | 2005-11-01 | Bristol-Myers Squibb Pharma Company | 5-6 to 5-7 Heterobicycles as factor Xa inhibitors |
JP2002305083A (ja) | 2001-04-04 | 2002-10-18 | Mitsubishi Chemicals Corp | 有機電界発光素子 |
KR20040004705A (ko) | 2001-06-08 | 2004-01-13 | 시토비아 인크. | 카스파제의 활성제 및 아폽토시스의 유도제로서의 치환된3-아릴-5-아릴-[1,2,4]-옥사디아졸과 유사체 및 이의 용도 |
TWI320039B (en) | 2001-09-21 | 2010-02-01 | Lactam-containing compounds and derivatives thereof as factor xa inhibitors | |
US6825221B2 (en) | 2001-10-18 | 2004-11-30 | Allergan, Inc. | Arylsulfanyl and heteroarylsulfanyl derivatives for treating pain |
US6921762B2 (en) | 2001-11-16 | 2005-07-26 | Amgen Inc. | Substituted indolizine-like compounds and methods of use |
WO2003043655A1 (fr) | 2001-11-19 | 2003-05-30 | Ono Pharmaceutical Co., Ltd. | Remedes pour la frequence urinaire |
US20050113283A1 (en) | 2002-01-18 | 2005-05-26 | David Solow-Cordero | Methods of treating conditions associated with an EDG-4 receptor |
US6995144B2 (en) | 2002-03-14 | 2006-02-07 | Eisai Co., Ltd. | Nitrogen containing heterocyclic compounds and medicines containing the same |
US20040110757A1 (en) | 2002-03-21 | 2004-06-10 | Thomas Arrhenius | Flt-1 ligands and their uses in the treatment of diseases regulatable by angiogenesis |
US7229987B2 (en) | 2002-05-13 | 2007-06-12 | Eli Lilly And Company | Multicyclic compounds for use as melanin concentrating hormone antagonists in the treatment of obesity and diabetes |
US7119111B2 (en) | 2002-05-29 | 2006-10-10 | Amgen, Inc. | 2-oxo-1,3,4-trihydroquinazolinyl derivatives and methods of use |
US7232616B2 (en) | 2002-06-13 | 2007-06-19 | Tsinghua University | Organic electroluminescent materials and devices made from such materials |
EP1515964A1 (en) * | 2002-06-14 | 2005-03-23 | ALTANA Pharma AG | Substituted diaminopyrimidines |
AU2003244098A1 (en) * | 2002-06-28 | 2004-01-19 | Yamanouchi Pharmaceutical Co., Ltd. | Diaminopyrimidinecarboxa mide derivative |
AU2003257300B2 (en) | 2002-08-07 | 2010-01-21 | Neuraxon Inc. | Amino benzothiazole compounds with NOS inhibitory activity |
AR040847A1 (es) | 2002-08-09 | 2005-04-20 | Astrazeneca Ab | 1,2,4-oxadiazoles como moduladores de receptores de glutamato metabotropicos, para el tratamiento de desordenes neurologicos y psiquiatricos |
WO2004022561A1 (en) * | 2002-09-04 | 2004-03-18 | Schering Corporation | Pyrazolopyrimidines as cyclin-dependent kinase inhibitors |
JP4487774B2 (ja) | 2002-09-30 | 2010-06-23 | 萬有製薬株式会社 | 2−アミノベンズイミダゾール誘導体 |
DE60316013T2 (de) | 2002-11-04 | 2008-05-29 | Vertex Pharmaceuticals Inc., Cambridge | Heteroaryl-pyrimidinderivate als jak-inhibitoren |
AU2003276201A1 (en) | 2002-11-11 | 2004-06-03 | Bayer Healthcare Ag | Phenyl or heteroaryl amino alkane derivatives as ip receptor antagonist |
BR0317600A (pt) | 2002-12-20 | 2005-11-29 | Pharmacia Corp | ácidos heteroarilalcanóicos como derivados de antagonistas de receptor de integrina |
US20040147561A1 (en) | 2002-12-27 | 2004-07-29 | Wenge Zhong | Pyrid-2-one derivatives and methods of use |
US7202257B2 (en) | 2003-12-24 | 2007-04-10 | Deciphera Pharmaceuticals, Llc | Anti-inflammatory medicaments |
TW200418835A (en) | 2003-01-24 | 2004-10-01 | Tanabe Seiyaku Co | A pyrazolopyrimidine compound and a process for preparing the same |
CN100345853C (zh) | 2003-01-24 | 2007-10-31 | 田边制药株式会社 | 吡唑并嘧啶化合物及其制备方法 |
AR042956A1 (es) * | 2003-01-31 | 2005-07-13 | Vertex Pharma | Inhibidores de girasa y usos de los mismos |
US7157455B2 (en) * | 2003-02-10 | 2007-01-02 | Hoffmann-La Roche Inc. | 4-Aminopyrimidine-5-one derivatives |
US7223788B2 (en) | 2003-02-14 | 2007-05-29 | Sanofi-Aventis Deutschland Gmbh | Substituted N-aryl heterocycles, process for their preparation and their use as medicaments |
EP1594842A1 (en) | 2003-02-22 | 2005-11-16 | MERCK PATENT GmbH | Cyanopyridone derivatives as liquid crystals |
US20050187266A1 (en) | 2003-04-15 | 2005-08-25 | Pfizer Inc | Alpha substituted carboxylic acids |
PT1635824E (pt) | 2003-06-03 | 2009-11-24 | Novartis Ag | Inibidores de p-38 à base de heterociclos de 5 membros |
WO2004108133A2 (en) | 2003-06-05 | 2004-12-16 | Vertex Pharmaceuticals Incorporated | Modulators of vr1 receptor |
EP1354876B1 (fr) | 2003-06-13 | 2005-04-27 | Les Laboratoires Servier | Nouveau procédé de synthèse de l'acide (2S, 3aS, 7aS)-perhydroindole-2-carboxylique et de ses esters, et application à la synthèse du perindopril |
WO2005000309A2 (en) | 2003-06-27 | 2005-01-06 | Ionix Pharmaceuticals Limited | Chemical compounds |
AU2004259012C1 (en) * | 2003-07-23 | 2012-08-02 | Exelixis, Inc. | Anaplastic lymphoma kinase modulators and methods of use |
WO2005019190A2 (en) | 2003-08-20 | 2005-03-03 | Vertex Pharmaceuticals Incorporated | (4 -amino -1,2, 5-oxadiazol-4-yl) -hetξroaromatic compounds useful as protein kinase inhibitors |
US7378409B2 (en) | 2003-08-21 | 2008-05-27 | Bristol-Myers Squibb Company | Substituted cycloalkylamine derivatives as modulators of chemokine receptor activity |
JP4638436B2 (ja) | 2003-09-26 | 2011-02-23 | エグゼリクシス, インコーポレイテッド | c−Metモジュレーターおよびその使用 |
KR101104100B1 (ko) | 2003-11-19 | 2012-01-12 | 제이엔씨 석유 화학 주식회사 | 광 중합성 액정 조성물, 그의 중합체 또는 중합체 조성물및 광학보상 소자 |
WO2005051932A1 (ja) | 2003-11-28 | 2005-06-09 | Nippon Soda Co., Ltd. | アリール複素環誘導体および農園芸用殺菌剤および殺虫剤 |
GB0328295D0 (en) | 2003-12-05 | 2004-01-07 | Muscagen Ltd | Therapeutic compounds |
US20070191336A1 (en) | 2003-12-24 | 2007-08-16 | Flynn Daniel L | Anti-inflammatory medicaments |
US7319108B2 (en) | 2004-01-25 | 2008-01-15 | Sanofi-Aventis Deutschland Gmbh | Aryl-substituted heterocycles, process for their preparation and their use as medicaments |
WO2005077373A2 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Treatment of gastro-esophageal reflux disease (gerd) |
WO2005077368A2 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Treatment of gastro-esophageal reflux disease (gerd) |
WO2005077345A1 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Compounds for the treatment of gastro-esophageal reflux disease |
EP1717230B1 (en) | 2004-02-13 | 2014-08-06 | Msd K.K. | Fused-ring 4-oxopyrimidine derivative |
US7585881B2 (en) | 2004-02-18 | 2009-09-08 | Astrazeneca Ab | Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
DE102004008141A1 (de) | 2004-02-19 | 2005-09-01 | Abbott Gmbh & Co. Kg | Guanidinverbindungen und ihre Verwendung als Bindungspartner für 5-HT5-Rezeptoren |
JP5319113B2 (ja) * | 2004-03-26 | 2013-10-16 | メチルジーン インコーポレイテッド | ヒストンデアセチラーゼの阻害剤 |
EP1749827A4 (en) | 2004-03-30 | 2010-04-21 | Kyowa Hakko Kirin Co Ltd | ANTITUMOR AGENTS |
EP1731513A4 (en) | 2004-03-30 | 2007-10-31 | Daiichi Seiyaku Co | PHENOXYACETIC ACID DERIVATIVE AND MEDICAMENT CONTAINING THE SAME |
EP1771432B1 (en) | 2004-03-31 | 2010-12-08 | Janssen Pharmaceutica NV | Non-imidazole heterocyclic compounds as histamine h3 receptor modulators |
CN1972914A (zh) | 2004-03-31 | 2007-05-30 | 詹森药业有限公司 | 作为组胺h3受体配合体的非咪唑杂环化合物 |
AR049333A1 (es) | 2004-04-02 | 2006-07-19 | Vertex Pharma | Azaindoles inhibidores de proteinquinasas rock y otras proteinas quinasas. composiciones farmaceuticas. |
US7439369B2 (en) | 2004-06-22 | 2008-10-21 | Loa Alamos National Security, Llc | Method and system for hydrogen evolution and storage |
JP4942654B2 (ja) | 2004-08-23 | 2012-05-30 | イーライ リリー アンド カンパニー | ヒスタミンh3受容体薬剤、製剤及び治療的使用 |
JP4972804B2 (ja) | 2004-08-31 | 2012-07-11 | Msd株式会社 | 新規置換イミダゾール誘導体 |
WO2006050389A2 (en) | 2004-11-02 | 2006-05-11 | Northwestern University | Pyridazine compounds, compositions and methods |
JP2008519034A (ja) * | 2004-11-03 | 2008-06-05 | 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 | イオンチャネル調節剤としてのピリミジン誘導体および使用方法 |
WO2006058074A1 (en) | 2004-11-22 | 2006-06-01 | Vertex Pharmaceuticals Incorporated | Pyrrolopyrazines and pyrazolopyrazines useful as inhibitors of protein kinases |
US7652009B2 (en) * | 2004-11-30 | 2010-01-26 | Amgem Inc. | Substituted heterocycles and methods of use |
US20070123572A1 (en) | 2005-11-28 | 2007-05-31 | Kalypsys, Inc. | Novel method of preparation of 5-chloro-3-imidazol-1-yl-[1,2,4]thiadiazole and (3-imidazol-1-yl-[1,2,4]thiadiazol-5yl)-dialkyl-amines |
US7786132B2 (en) * | 2004-12-17 | 2010-08-31 | Amgen Inc. | Aminopyrimidine compounds and methods of use |
JP2008526777A (ja) | 2005-01-05 | 2008-07-24 | ライジェル ファーマシューティカルズ, インコーポレイテッド | ユビキチンリガーゼインヒビター |
KR20070100894A (ko) | 2005-01-19 | 2007-10-12 | 브리스톨-마이어스 스큅 컴퍼니 | 혈전색전성 장애 치료용 p2y1 수용체 억제제로서의2-페녹시-n-(1,3,4-티아디졸-2-일)피리딘-3-아민 유도체및 관련 화합물 |
AU2006208042A1 (en) | 2005-01-25 | 2006-08-03 | Neurogen Corporation | Substituted pyridazinyl-and pyrimidinyl-quinolin-4-ylamine analogues |
MX2007009017A (es) | 2005-01-26 | 2007-09-19 | Schering Corp | Derivados de 3-(indazol-5-il)-(1,2,4)triazina y compuestos relacionados como inhibidores de proteina cinasa para el tratamiento de cancer. |
WO2006084186A2 (en) | 2005-02-04 | 2006-08-10 | Senomyx, Inc. | Compounds comprising linked hetero aryl moieties and their use as novel umami flavor modifiers, tastants and taste enhancers for comestible compositions |
PT1853588E (pt) * | 2005-02-16 | 2008-08-25 | Astrazeneca Ab | Compostos químicos |
JP2006274133A (ja) | 2005-03-30 | 2006-10-12 | Fuji Photo Film Co Ltd | 液晶組成物、位相差板及び楕円偏光板 |
AU2006231646A1 (en) | 2005-04-06 | 2006-10-12 | Exelixis, Inc. | C-Met modulators and methods of use |
EP1890697B1 (en) | 2005-06-07 | 2015-03-04 | Pharmacopeia, LLC | Azinone and diazinone v3 inhibitors for depression and stress disorders |
ES2375929T3 (es) | 2005-07-04 | 2012-03-07 | High Point Pharmaceuticals, Llc | Antagonistas del receptor histamina h3. |
WO2007012642A1 (de) | 2005-07-29 | 2007-02-01 | Basf Aktiengesellschaft | 7-amino-6-thiadiazolyl- und -oxadiazolyl- 1 , 2 , 4-triazolo [1 , 5 -a] pyrimidin- verbindungen und ihre verwendung zur bekämpfung von schadpilzen |
US8093401B2 (en) | 2005-08-04 | 2012-01-10 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
WO2007019344A1 (en) | 2005-08-04 | 2007-02-15 | Sirtris Pharmaceuticals, Inc. | Imidazo [2,1-b] thiayole derivatives as sirtuin modulating compounds |
KR20080047410A (ko) | 2005-08-23 | 2008-05-28 | 아이알엠 엘엘씨 | 면역억제제 화합물 및 조성물 |
JP2007093918A (ja) | 2005-09-28 | 2007-04-12 | Fujifilm Corp | 光学ローパスフィルター、およびその製造方法 |
JP2007093919A (ja) | 2005-09-28 | 2007-04-12 | Fujifilm Corp | 光学ローパスフィルター、およびその製造方法 |
WO2007037010A1 (ja) | 2005-09-29 | 2007-04-05 | Daiichi Pharmaceutical Co., Ltd. | フェノキシ酢酸誘導体及びそれを用いた医薬 |
US7531482B2 (en) | 2005-10-21 | 2009-05-12 | Dow Agrosciences Llc | Thieno-pyrimidine compounds having fungicidal activity |
JP5243960B2 (ja) | 2005-10-21 | 2013-07-24 | ダウ アグロサイエンシィズ エルエルシー | 殺菌活性を有するチエノ−ピリミジン化合物 |
AR057982A1 (es) | 2005-10-26 | 2008-01-09 | Boehringer Ingelheim Int | Compuestos de [hetero) arilo con actividad antagonista de mch y composicion farmaceutica que comprende estos compuestos |
KR101331768B1 (ko) | 2005-11-08 | 2013-11-22 | 버텍스 파마슈티칼스 인코포레이티드 | Atp 결합 카세트 수송체의 헤테로사이클릭 조정제 |
CN103214483B (zh) | 2005-12-13 | 2014-12-17 | 因塞特公司 | 作为两面神激酶抑制剂的杂芳基取代的吡咯并[2,3-b]吡啶和吡咯并[2,3-b]嘧啶 |
WO2007075377A2 (en) | 2005-12-15 | 2007-07-05 | Cytokinetics, Inc. | Certain chemical entities, compositions and methods |
US7825120B2 (en) | 2005-12-15 | 2010-11-02 | Cytokinetics, Inc. | Certain substituted ((piperazin-1-ylmethyl)benzyl)ureas |
EP1959962A2 (en) | 2005-12-16 | 2008-08-27 | Cytokinetics, Inc. | Certain chemical entities, compositions, and methods |
WO2007075896A2 (en) | 2005-12-22 | 2007-07-05 | Kemia, Inc. | Heterocyclic cytokine inhibitors |
WO2007076460A2 (en) | 2005-12-23 | 2007-07-05 | Kalypsys, Inc. | Substituted thiazole ureas useful as inhibitors of protein kinases |
ZA200807715B (en) | 2006-03-09 | 2009-11-25 | Pharmacopeia Inc | 9-Heteroarylpurine MNK2 inhibitors for treating metabolic disorders |
JP5243696B2 (ja) | 2006-03-17 | 2013-07-24 | 田辺三菱製薬株式会社 | ベンゼン誘導体 |
SI2007752T1 (sl) | 2006-03-31 | 2010-12-31 | Janssen Pharmaceutica Nv | Benzoimidazol-2-il pirimidini in pirazini kot modulatorji histamin H4 receptorja |
MX2008013308A (es) | 2006-04-19 | 2008-10-27 | Serono Lab | Nuevos derivados de arilaminopiridina heteroaril-sustituidos como inhibidores de mek. |
KR101464385B1 (ko) | 2006-04-19 | 2014-11-21 | 노파르티스 아게 | 6-o-치환된 벤즈옥사졸 및 벤조티아졸 화합물, 및 csf-1r 신호전달의 억제 방법 |
WO2007127475A2 (en) | 2006-04-28 | 2007-11-08 | Northwestern University | Pyridazines for demyelinating diseases and neuropathic pain |
US9150507B2 (en) | 2006-04-28 | 2015-10-06 | Shionogi & Co., Ltd. | Amine derivative having NPY Y5 receptor antagonistic activity |
WO2007130383A2 (en) | 2006-04-28 | 2007-11-15 | Northwestern University | Compositions and treatments using pyridazine compounds and secretases |
AU2007257959A1 (en) | 2006-06-09 | 2007-12-21 | Kemia, Inc. | Therapy using cytokine inhibitors |
US8435774B2 (en) | 2006-06-28 | 2013-05-07 | Qiagen Gmbh | Enhancing reactivation of thermostable reversibly inactivated enzymes |
UA95298C2 (ru) | 2006-07-07 | 2011-07-25 | Бьёрингер Ингельхайм Интернациональ Гмбх | Фенилзамещенные гетероарильные производные и их применение в качестве противоопухолевых средств |
WO2008013622A2 (en) | 2006-07-27 | 2008-01-31 | E. I. Du Pont De Nemours And Company | Fungicidal azocyclic amides |
US8227603B2 (en) | 2006-08-01 | 2012-07-24 | Cytokinetics, Inc. | Modulating skeletal muscle |
CA2660699A1 (en) * | 2006-08-30 | 2008-03-06 | Biovitrum Ab (Publ) | Pyridine compounds for treating gpr119 related disorders |
WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
WO2008071646A1 (en) | 2006-12-11 | 2008-06-19 | Boehringer Ingelheim International Gmbh | New pyridazine derivatives with mch antagonistic activity and medicaments comprising these compounds |
DE102007002717A1 (de) | 2007-01-18 | 2008-07-24 | Merck Patent Gmbh | Heterocyclische Indazolderivate |
WO2009011285A1 (ja) * | 2007-07-13 | 2009-01-22 | Taisho Pharmaceutical Co., Ltd. | ヘテロアリールベンゼン化合物 |
GB0720444D0 (en) | 2007-10-18 | 2007-11-28 | Glaxo Group Ltd | Novel compounds |
US7943619B2 (en) | 2007-12-04 | 2011-05-17 | Hoffmann-La Roche Inc. | Isoxazolo-pyridazine derivatives |
TW200940537A (en) | 2008-02-26 | 2009-10-01 | Astrazeneca Ab | Heterocyclic urea derivatives and methods of use thereof |
WO2009131958A2 (en) | 2008-04-21 | 2009-10-29 | Institute For Oneworld Health | Compounds, compositions and methods comprising triazine derivatives |
WO2009131947A2 (en) | 2008-04-21 | 2009-10-29 | Institute For Oneworld Health | Compounds, compositions and methods comprising pyridazine derivatives |
CL2009001345A1 (es) | 2008-06-04 | 2010-06-11 | Astrazeneca Ab | Compuestos derivados de 1-piridin-2-il-urea y 1-pirimidin-2-il-urea sustituidos, inhibidores de adn girasa y topoisomerasa iv; composicion farmaceutica; y su uso en tratamiento de infecciones bacterianas como neumonia adquirida intrahospitalariamente, infecciones a la piel, bronquitis, sinusitis, entre otras enfermedades. |
WO2009152168A2 (en) | 2008-06-09 | 2009-12-17 | Awd. Pharma Gmbh & Co. Kg | Carboxylic acid salts of 2-amino-3-carbethoxyamino-6-(4-fluoro-benzylamino)-pyridine |
JP2011526911A (ja) | 2008-06-30 | 2011-10-20 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ベンゾイミダゾール−2−イルピリミジン誘導体を製造する方法 |
US20100025641A1 (en) | 2008-08-04 | 2010-02-04 | Fujifilm Corporation | Infrared region selective reflection coat and infrared region selective reflection film |
WO2010022121A1 (en) | 2008-08-20 | 2010-02-25 | Schering Corporation | Substituted pyridine and pyrimidine derivatives and their use in treating viral infections |
JP2010132590A (ja) | 2008-12-03 | 2010-06-17 | Astellas Pharma Inc | オキサジアゾール化合物 |
AU2010231694A1 (en) * | 2009-03-30 | 2011-10-06 | Astellas Pharma Inc. | Pyrimidine compound |
WO2011032169A2 (en) | 2009-09-14 | 2011-03-17 | Phusis Therapeutics Inc. | Pharmaceutical compositions and formulations including inhibitors of the pleckstrin homology domain and methods for using same |
AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
WO2011133920A1 (en) | 2010-04-23 | 2011-10-27 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
CA2822017C (en) | 2010-12-23 | 2015-04-07 | Pfizer Inc. | Glucagon receptor modulators |
JP2014510105A (ja) | 2011-03-22 | 2014-04-24 | アムジエン・インコーポレーテツド | Pim阻害剤としてのアゾール化合物 |
US8759380B2 (en) | 2011-04-22 | 2014-06-24 | Cytokinetics, Inc. | Certain heterocycles, compositions thereof, and methods for their use |
JP6345645B2 (ja) | 2012-04-02 | 2018-06-20 | サイトキネティックス, インコーポレイテッド | 横隔膜機能を向上させるための方法 |
JP6352244B2 (ja) | 2012-04-11 | 2018-07-04 | サイトキネティックス, インコーポレイテッド | 骨格筋疲労に対する耐性を向上させるための方法 |
US20170042890A1 (en) | 2014-04-29 | 2017-02-16 | Cytokinetics, Inc. | Methods of reducing decline in vital capacity |
CA2957804C (en) * | 2014-09-09 | 2023-04-04 | Astellas Pharma Inc. | Pharmaceutical composition for prevention and/or treatment of urinary incontinence |
-
2011
- 2011-04-20 AR ARP110101386A patent/AR081331A1/es active IP Right Grant
- 2011-04-22 KR KR1020177026330A patent/KR102003030B1/ko active IP Right Grant
- 2011-04-22 NZ NZ603594A patent/NZ603594A/en unknown
- 2011-04-22 TW TW100113963A patent/TWI520737B/zh active
- 2011-04-22 CA CA2796637A patent/CA2796637C/en active Active
- 2011-04-22 MX MX2012012189A patent/MX2012012189A/es active IP Right Grant
- 2011-04-22 MY MYPI2017000156A patent/MY193277A/en unknown
- 2011-04-22 PL PL16164963T patent/PL3127540T3/pl unknown
- 2011-04-22 SI SI201130887A patent/SI2560653T1/sl unknown
- 2011-04-22 JP JP2013506329A patent/JP5852099B2/ja active Active
- 2011-04-22 DK DK16164963.7T patent/DK3127540T3/da active
- 2011-04-22 MY MYPI2012004643A patent/MY163498A/en unknown
- 2011-04-22 ME MEP-2016-137A patent/ME02439B/me unknown
- 2011-04-22 PT PT161649637T patent/PT3127540T/pt unknown
- 2011-04-22 EP EP11772782.6A patent/EP2560653B1/en active Active
- 2011-04-22 SG SG2012078002A patent/SG184959A1/en unknown
- 2011-04-22 PL PL11772782.6T patent/PL2560653T3/pl unknown
- 2011-04-22 CN CN201180021468.3A patent/CN103025331B/zh active Active
- 2011-04-22 LT LTEP11772782.6T patent/LT2560653T/lt unknown
- 2011-04-22 LT LTEP16164963.7T patent/LT3127540T/lt unknown
- 2011-04-22 ES ES16164963T patent/ES2784279T3/es active Active
- 2011-04-22 CN CN202010640406.1A patent/CN112047926A/zh active Pending
- 2011-04-22 KR KR1020127029536A patent/KR101781484B1/ko active IP Right Grant
- 2011-04-22 ES ES11772782.6T patent/ES2586302T3/es active Active
- 2011-04-22 EA EA201201378A patent/EA028079B1/ru unknown
- 2011-04-22 EP EP16164963.7A patent/EP3127540B1/en active Active
- 2011-04-22 EA EA201700230A patent/EA037350B1/ru not_active IP Right Cessation
- 2011-04-22 AU AU2011242575A patent/AU2011242575C1/en active Active
- 2011-04-22 PH PH12016502037A patent/PH12016502037A1/en unknown
- 2011-04-22 ME MEP-2020-68A patent/ME03766B/me unknown
- 2011-04-22 HU HUE11772782A patent/HUE028953T2/en unknown
- 2011-04-22 SI SI201131854T patent/SI3127540T1/sl unknown
- 2011-04-22 US US13/642,206 patent/US8962632B2/en active Active
- 2011-04-22 EP EP20153402.1A patent/EP3698795A1/en active Pending
- 2011-04-22 HU HUE16164963A patent/HUE048815T2/hu unknown
- 2011-04-22 RS RS20160554A patent/RS54948B1/sr unknown
- 2011-04-22 BR BR112012026951-8A patent/BR112012026951B1/pt active IP Right Grant
- 2011-04-22 CN CN201610048645.1A patent/CN105712974B/zh active Active
- 2011-04-22 DK DK11772782.6T patent/DK2560653T3/en active
- 2011-04-22 PT PT117727826T patent/PT2560653T/pt unknown
- 2011-04-22 RS RS20200376A patent/RS60137B1/sr unknown
- 2011-04-22 WO PCT/US2011/033614 patent/WO2011133888A1/en active Application Filing
-
2012
- 2012-10-15 IL IL222467A patent/IL222467A/en active IP Right Grant
- 2012-10-22 CL CL2012002944A patent/CL2012002944A1/es unknown
- 2012-10-24 CO CO12189881A patent/CO6620055A2/es active IP Right Grant
- 2012-11-09 EC ECSP12012293 patent/ECSP12012293A/es unknown
-
2013
- 2013-07-09 HK HK13107992.8A patent/HK1180604A1/zh unknown
-
2014
- 2014-03-20 US US14/220,252 patent/US9018223B2/en active Active
-
2015
- 2015-01-12 US US14/594,315 patent/US9730886B2/en active Active
-
2016
- 2016-07-08 HR HRP20160827TT patent/HRP20160827T1/hr unknown
- 2016-07-12 SM SM201600226T patent/SMT201600226B/it unknown
- 2016-07-12 CY CY20161100664T patent/CY1117809T1/el unknown
- 2016-12-20 HK HK16114454A patent/HK1226068A1/zh unknown
-
2017
- 2017-07-10 US US15/645,977 patent/US10272030B2/en active Active
- 2017-08-07 IL IL253870A patent/IL253870B/en active IP Right Grant
-
2019
- 2019-03-13 US US16/352,626 patent/US10765624B2/en active Active
-
2020
- 2020-04-03 HR HRP20200549TT patent/HRP20200549T1/hr unknown
- 2020-04-14 CY CY20201100347T patent/CY1122944T1/el unknown
- 2020-07-28 US US16/941,079 patent/US11369565B2/en active Active
-
2022
- 2022-05-20 US US17/750,090 patent/US20230026651A1/en active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5852099B2 (ja) | ある種のアミノ−ピリミジン、その組成物、及びそれを用いるための方法 | |
US9994528B2 (en) | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use | |
EP3127541B1 (en) | Certain amino-pyridazines, compositions thereof, and methods of their use |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20130830 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130830 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140310 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20150108 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150113 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150410 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150508 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20151110 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20151203 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5852099 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |