EA027569B1 - Производные пиридина - Google Patents

Info

Publication number

EA027569B1

EA027569B1 EA201591567A EA201591567A EA027569B1 EA 027569 B1 EA027569 B1 EA 027569B1 EA 201591567 A EA201591567 A EA 201591567A EA 201591567 A EA201591567 A EA 201591567A EA 027569 B1 EA027569 B1 EA 027569B1

Authority

EA

Eurasian Patent Office

Prior art keywords

cyclopropyl

pyridin

butyl

tert

oxadiazole

Prior art date

2013-03-26

Links

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• Global Dossier
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• 150000003222 pyridines Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 370
• 239000003814 drug Substances 0.000 claims abstract description 7
• -1 6-oxa-1-azaspiro [3.3] heptyl Chemical group 0.000 claims description 113
• 238000011282 treatment Methods 0.000 claims description 98
• 238000000034 method Methods 0.000 claims description 47
• 230000000302 ischemic effect Effects 0.000 claims description 21
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 20
• 206010016654 Fibrosis Diseases 0.000 claims description 17
• 208000006011 Stroke Diseases 0.000 claims description 17
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 15
• 206010028980 Neoplasm Diseases 0.000 claims description 14
• 206010063837 Reperfusion injury Diseases 0.000 claims description 14
• 229910052739 hydrogen Inorganic materials 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 14
• 101710187022 Cannabinoid receptor 2 Proteins 0.000 claims description 13
• 102100036214 Cannabinoid receptor 2 Human genes 0.000 claims description 13
• 229910052736 halogen Inorganic materials 0.000 claims description 13
• 239000001257 hydrogen Substances 0.000 claims description 13
• 230000002265 prevention Effects 0.000 claims description 13
• 230000004761 fibrosis Effects 0.000 claims description 12
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 10
• 206010046851 Uveitis Diseases 0.000 claims description 10
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
• 210000004185 liver Anatomy 0.000 claims description 10
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
• 208000010125 myocardial infarction Diseases 0.000 claims description 10
• 208000004644 retinal vein occlusion Diseases 0.000 claims description 10
• 230000001052 transient effect Effects 0.000 claims description 10
• 201000001320 Atherosclerosis Diseases 0.000 claims description 9
• 208000031229 Cardiomyopathies Diseases 0.000 claims description 9
• 208000010412 Glaucoma Diseases 0.000 claims description 9
• 208000002193 Pain Diseases 0.000 claims description 9
• 206010037660 Pyrexia Diseases 0.000 claims description 9
• 201000007737 Retinal degeneration Diseases 0.000 claims description 9
• 206010042953 Systemic sclerosis Diseases 0.000 claims description 9
• 150000002367 halogens Chemical class 0.000 claims description 9
• 208000002780 macular degeneration Diseases 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• 208000011580 syndromic disease Diseases 0.000 claims description 9
• 230000009885 systemic effect Effects 0.000 claims description 9
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 8
• 208000024827 Alzheimer disease Diseases 0.000 claims description 8
• 206010008190 Cerebrovascular accident Diseases 0.000 claims description 8
• 208000032544 Cicatrix Diseases 0.000 claims description 8
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 8
• 206010051920 Glomerulonephropathy Diseases 0.000 claims description 8
• 206010019280 Heart failures Diseases 0.000 claims description 8
• 206010061218 Inflammation Diseases 0.000 claims description 8
• 208000002260 Keloid Diseases 0.000 claims description 8
• 208000018737 Parkinson disease Diseases 0.000 claims description 8
• 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 8
• 201000009594 Systemic Scleroderma Diseases 0.000 claims description 8
• ATQVBSVAXDRWFW-HBMCJLEFSA-N [(1r)-2-(4-hydroxyphenyl)-1-[[(2s)-1-[[(2s)-3-methyl-2-(methylamino)butanoyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]ethyl]phosphonic acid Chemical compound C([C@@H](C(=O)NC(=O)[C@H](C(C)C)NC)N[C@@H](CC=1C=CC(O)=CC=1)P(O)(O)=O)C1=CC=CC=C1 ATQVBSVAXDRWFW-HBMCJLEFSA-N 0.000 claims description 8
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 8
• 208000026106 cerebrovascular disease Diseases 0.000 claims description 8
• 206010012601 diabetes mellitus Diseases 0.000 claims description 8
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 8
• 230000001969 hypertrophic effect Effects 0.000 claims description 8
• 230000004054 inflammatory process Effects 0.000 claims description 8
• 210000001117 keloid Anatomy 0.000 claims description 8
• 208000031225 myocardial ischemia Diseases 0.000 claims description 8
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 8
• 231100000241 scar Toxicity 0.000 claims description 8
• 230000037387 scars Effects 0.000 claims description 8
• 230000003685 thermal hair damage Effects 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 201000006417 multiple sclerosis Diseases 0.000 claims description 7
• UAWJZDSNZLBNHZ-UHFFFAOYSA-N 3-tert-butyl-5-[5-cyclopropyl-4-(2,2-difluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound CC(C)(C)C1=NOC(C=2N=CC(=C(OCC(F)F)C=2)C2CC2)=N1 UAWJZDSNZLBNHZ-UHFFFAOYSA-N 0.000 claims description 6
• IGIGFJUOSNGGEA-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OCC(F)(F)F)C=2)C2CC2)=N1 IGIGFJUOSNGGEA-UHFFFAOYSA-N 0.000 claims description 6
• OAYJCQBZUOXJSK-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-(oxan-4-yloxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OC3CCOCC3)C=2)C2CC2)=N1 OAYJCQBZUOXJSK-UHFFFAOYSA-N 0.000 claims description 6
• 208000007788 Acute Liver Failure Diseases 0.000 claims description 6
• 206010000804 Acute hepatic failure Diseases 0.000 claims description 6
• 231100000836 acute liver failure Toxicity 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
• AOWAIUQTZMRKFW-UHFFFAOYSA-N 3-tert-butyl-5-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound CC(C)(C)C1=NOC(C=2N=CC(=C(OCC(F)(F)F)C=2)C2CC2)=N1 AOWAIUQTZMRKFW-UHFFFAOYSA-N 0.000 claims description 5
• FNTFQKRXWGZWIY-UHFFFAOYSA-N 3-tert-butyl-5-[5-cyclopropyl-4-(oxan-4-yloxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound CC(C)(C)c1noc(n1)-c1cc(OC2CCOCC2)c(cn1)C1CC1 FNTFQKRXWGZWIY-UHFFFAOYSA-N 0.000 claims description 5
• OABRLYVFUBJJPZ-UHFFFAOYSA-N 5-tert-butyl-3-[4-(cyclopropylmethoxy)-5-methylsulfonylpyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OCC3CC3)C=2)S(C)(=O)=O)=N1 OABRLYVFUBJJPZ-UHFFFAOYSA-N 0.000 claims description 5
• UJKBYEMHLKTICY-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-(2-ethoxyethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound CCOCCOC1=CC(C=2N=C(ON=2)C(C)(C)C)=NC=C1C1CC1 UJKBYEMHLKTICY-UHFFFAOYSA-N 0.000 claims description 5
• ZUGIJKPPOJHXRW-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-(3-methoxybutoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound COC(C)CCOC1=CC(C=2N=C(ON=2)C(C)(C)C)=NC=C1C1CC1 ZUGIJKPPOJHXRW-UHFFFAOYSA-N 0.000 claims description 5
• JIVTXHUQNIITHJ-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-(4-fluorophenoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OC=3C=CC(F)=CC=3)C=2)C2CC2)=N1 JIVTXHUQNIITHJ-UHFFFAOYSA-N 0.000 claims description 5
• VMSHTNPDBYFZHE-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-(oxetan-3-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OCC3COC3)C=2)C2CC2)=N1 VMSHTNPDBYFZHE-UHFFFAOYSA-N 0.000 claims description 5
• XETZVHSZEJBYHI-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-(oxolan-2-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OCC3OCCC3)C=2)C2CC2)=N1 XETZVHSZEJBYHI-UHFFFAOYSA-N 0.000 claims description 5
• YUKWEOINOQTYRZ-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-(oxolan-3-yloxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OC3COCC3)C=2)C2CC2)=N1 YUKWEOINOQTYRZ-UHFFFAOYSA-N 0.000 claims description 5
• XUBLJNIOGAIIMR-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-[(3-methyloxetan-3-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OCC3(C)COC3)C=2)C2CC2)=N1 XUBLJNIOGAIIMR-UHFFFAOYSA-N 0.000 claims description 5
• XFXOXFLOMYPHBI-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-[(5-fluoropyridin-2-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole Chemical compound CC(C)(C)c1nc(no1)-c1cc(OCc2ccc(F)cn2)c(cn1)C1CC1 XFXOXFLOMYPHBI-UHFFFAOYSA-N 0.000 claims description 5
• 206010052779 Transplant rejections Diseases 0.000 claims description 5
• 239000000556 agonist Substances 0.000 claims description 5
• 125000002393 azetidinyl group Chemical group 0.000 claims description 5
• 230000007882 cirrhosis Effects 0.000 claims description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 208000017169 kidney disease Diseases 0.000 claims description 5
• 201000002793 renal fibrosis Diseases 0.000 claims description 5
• KVFRXZASAOBHCO-UHFFFAOYSA-N 2-(5-tert-butyl-1h-imidazol-2-yl)-5-(3,3-difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)pyridine Chemical compound N1C(C(C)(C)C)=CN=C1C1=CC(OCC(F)(F)F)=C(N2CC(F)(F)C2)C=N1 KVFRXZASAOBHCO-UHFFFAOYSA-N 0.000 claims description 4
• RJAVWJXYLHZJBO-UHFFFAOYSA-N 2-tert-butyl-5-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,3,4-oxadiazole Chemical compound CC(C)(C)c1nnc(o1)-c1cc(OCC(F)(F)F)c(cn1)C1CC1 RJAVWJXYLHZJBO-UHFFFAOYSA-N 0.000 claims description 4
• XJXRVGULPJQRKD-UHFFFAOYSA-N 2-tert-butyl-5-[5-cyclopropyl-4-(oxan-4-yloxy)pyridin-2-yl]-1,3,4-oxadiazole Chemical compound CC(C)(C)c1nnc(o1)-c1cc(OC2CCOCC2)c(cn1)C1CC1 XJXRVGULPJQRKD-UHFFFAOYSA-N 0.000 claims description 4
• YOULCKZIZCRFKI-UHFFFAOYSA-N 3-cyclopropyl-5-[5-(3,3-difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound FC(F)(F)COC1=CC(C=2ON=C(N=2)C2CC2)=NC=C1N1CC(F)(F)C1 YOULCKZIZCRFKI-UHFFFAOYSA-N 0.000 claims description 4
• ZSASVUGBERTODS-UHFFFAOYSA-N 3-cyclopropyl-5-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound FC(F)(F)COC1=CC(C=2ON=C(N=2)C2CC2)=NC=C1C1CC1 ZSASVUGBERTODS-UHFFFAOYSA-N 0.000 claims description 4
• QVMMRHICIJCFLC-UHFFFAOYSA-N 5-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-3-methyl-1,2,4-oxadiazole Chemical compound CC1=NOC(C=2N=CC(=C(OCC3CC3)C=2)C2CC2)=N1 QVMMRHICIJCFLC-UHFFFAOYSA-N 0.000 claims description 4
• RLIQVMMSZNAHLH-UHFFFAOYSA-N 5-tert-butyl-2-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,3-oxazole Chemical compound O1C(C(C)(C)C)=CN=C1C1=CC(OCC2CC2)=C(C2CC2)C=N1 RLIQVMMSZNAHLH-UHFFFAOYSA-N 0.000 claims description 4
• RESZPWREOKJYOD-UHFFFAOYSA-N 5-tert-butyl-3-[4-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OCC3CC3)C=2)N2CC(F)(F)C2)=N1 RESZPWREOKJYOD-UHFFFAOYSA-N 0.000 claims description 4
• MPGAWRWCELQBBI-UHFFFAOYSA-N 5-tert-butyl-3-[5-(3,3-difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OCC(F)(F)F)C=2)N2CC(F)(F)C2)=N1 MPGAWRWCELQBBI-UHFFFAOYSA-N 0.000 claims description 4
• HTUYGJMIBCCOFV-UHFFFAOYSA-N 5-tert-butyl-3-[5-chloro-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(Cl)=C(OCC(F)(F)F)C=2)=N1 HTUYGJMIBCCOFV-UHFFFAOYSA-N 0.000 claims description 4
• XAIZFSWQRNKAFS-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-(2,2-difluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound CC(C)(C)c1nc(no1)-c1cc(OCC(F)F)c(cn1)C1CC1 XAIZFSWQRNKAFS-UHFFFAOYSA-N 0.000 claims description 4
• KSELSOJUYOSGQZ-UHFFFAOYSA-N 5-tert-butyl-3-[5-cyclopropyl-4-[(4-fluorophenyl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OCC=3C=CC(F)=CC=3)C=2)C2CC2)=N1 KSELSOJUYOSGQZ-UHFFFAOYSA-N 0.000 claims description 4
• SUQUGLUPVWSCTH-UHFFFAOYSA-N 5-tert-butyl-3-[5-methylsulfonyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OCC(F)(F)F)C=2)S(C)(=O)=O)=N1 SUQUGLUPVWSCTH-UHFFFAOYSA-N 0.000 claims description 4
• HQYNXYZZLHRXKT-UHFFFAOYSA-N 5-tert-butyl-3-[6-chloro-5-cyclopropyl-4-(oxan-4-yloxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound CC(C)(C)c1nc(no1)-c1cc(OC2CCOCC2)c(C2CC2)c(Cl)n1 HQYNXYZZLHRXKT-UHFFFAOYSA-N 0.000 claims description 4
• CDDKIHSHTJFBLR-UHFFFAOYSA-N 5-tert-butyl-3-[6-chloro-5-cyclopropyl-4-[(4-fluorophenyl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole Chemical compound CC(C)(C)c1nc(no1)-c1cc(OCc2ccc(F)cc2)c(C2CC2)c(Cl)n1 CDDKIHSHTJFBLR-UHFFFAOYSA-N 0.000 claims description 4
• 206010023421 Kidney fibrosis Diseases 0.000 claims description 4
• 230000001154 acute effect Effects 0.000 claims description 4
• 239000000460 chlorine Substances 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 125000006001 difluoroethyl group Chemical group 0.000 claims description 4
• 230000000694 effects Effects 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• NORGKQSFMOVZTH-UHFFFAOYSA-N 1-[2-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-cyclopropylpyridin-4-yl]pyrrolidin-3-ol Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(N3CC(O)CC3)C=2)C2CC2)=N1 NORGKQSFMOVZTH-UHFFFAOYSA-N 0.000 claims description 3
• AKSFJNNWWVUINI-UHFFFAOYSA-N 1-[3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]cyclopropan-1-ol Chemical compound N=1C(C=2N=CC(=C(OCC(F)(F)F)C=2)C2CC2)=NOC=1C1(O)CC1 AKSFJNNWWVUINI-UHFFFAOYSA-N 0.000 claims description 3
• YBLVURTZMKBLSJ-UHFFFAOYSA-N 1-[3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]cyclopropan-1-ol Chemical compound N=1C(C=2N=CC(=C(OCC3CC3)C=2)C2CC2)=NOC=1C1(O)CC1 YBLVURTZMKBLSJ-UHFFFAOYSA-N 0.000 claims description 3
• TWZOZGASCPQPBA-UHFFFAOYSA-N 1-[6-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-4-(cyclopropylmethoxy)pyridin-3-yl]-6-oxa-1-azaspiro[3.3]heptane Chemical compound O1C(C(C)(C)C)=NC(C=2N=CC(=C(OCC3CC3)C=2)N2C3(COC3)CC2)=N1 TWZOZGASCPQPBA-UHFFFAOYSA-N 0.000 claims description 3
• VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 claims description 3
• VPMWTKZJXOPHMS-UHFFFAOYSA-N 2-[3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]propan-2-ol Chemical compound O1C(C(C)(O)C)=NC(C=2N=CC(=C(OCC3CC3)C=2)C2CC2)=N1 VPMWTKZJXOPHMS-UHFFFAOYSA-N 0.000 claims description 3
• POEMRGVWNWEWHJ-UHFFFAOYSA-N 2-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-3-oxa-1-azaspiro[4.5]dec-1-ene Chemical compound FC(F)(F)COC1=CC(C=2OCC3(N=2)CCCCC3)=NC=C1C1CC1 POEMRGVWNWEWHJ-UHFFFAOYSA-N 0.000 claims description 3
• YTRYLIDQOLNHSK-UHFFFAOYSA-N 2-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-4,4-diethyl-5h-1,3-oxazole Chemical compound CCC1(CC)COC(C=2N=CC(=C(OCC(F)(F)F)C=2)C2CC2)=N1 YTRYLIDQOLNHSK-UHFFFAOYSA-N 0.000 claims description 3
• WYWLXKCEFJPFTK-UHFFFAOYSA-N 2-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-4-methyl-4-(2-methylpropyl)-1h-imidazol-5-one Chemical compound N1C(=O)C(CC(C)C)(C)N=C1C1=CC(OCC(F)(F)F)=C(C2CC2)C=N1 WYWLXKCEFJPFTK-UHFFFAOYSA-N 0.000 claims description 3
• QCKGGBWGYDTGSW-UHFFFAOYSA-N 2-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-4-methyl-4-propan-2-yl-1h-imidazol-5-one Chemical compound N1C(=O)C(C(C)C)(C)N=C1C1=CC(OCC(F)(F)F)=C(C2CC2)C=N1 QCKGGBWGYDTGSW-UHFFFAOYSA-N 0.000 claims description 3
• OIJDLVWTTOVNHT-UHFFFAOYSA-N 2-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-5,5-dimethyl-4h-1,3-oxazole Chemical compound O1C(C)(C)CN=C1C1=CC(OCC(F)(F)F)=C(C2CC2)C=N1 OIJDLVWTTOVNHT-UHFFFAOYSA-N 0.000 claims description 3
• OTHNBCCZCWKBPD-UHFFFAOYSA-N 2-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-3-oxa-1-azaspiro[4.5]dec-1-ene Chemical compound C1CC1COC1=CC(C=2OCC3(N=2)CCCCC3)=NC=C1C1CC1 OTHNBCCZCWKBPD-UHFFFAOYSA-N 0.000 claims description 3
• NMHFZCVAQZPHOP-UHFFFAOYSA-N 2-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-4,4-diethyl-5h-1,3-oxazole Chemical compound CCC1(CC)COC(C=2N=CC(=C(OCC3CC3)C=2)C2CC2)=N1 NMHFZCVAQZPHOP-UHFFFAOYSA-N 0.000 claims description 3
• KENVCMHAFPIUMM-UHFFFAOYSA-N 2-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-4-ethyl-4,5-dihydro-1,3-oxazole Chemical compound CCC1COC(C=2N=CC(=C(OCC3CC3)C=2)C2CC2)=N1 KENVCMHAFPIUMM-UHFFFAOYSA-N 0.000 claims description 3
• UCTPRPVWILHNJG-UHFFFAOYSA-N 3-[5-(3,3-difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-5-(1-methylcyclopropyl)-1,2,4-oxadiazole Chemical compound N=1C(C=2N=CC(=C(OCC(F)(F)F)C=2)N2CC(F)(F)C2)=NOC=1C1(C)CC1 UCTPRPVWILHNJG-UHFFFAOYSA-N 0.000 claims description 3
• HMUPXUIISJZXTJ-UHFFFAOYSA-N 3-[5-chloro-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-5-cyclopropyl-1,2,4-oxadiazole Chemical compound C1=C(Cl)C(OCC(F)(F)F)=CC(C=2N=C(ON=2)C2CC2)=N1 HMUPXUIISJZXTJ-UHFFFAOYSA-N 0.000 claims description 3
• DWXXOPWEWPSUAD-UHFFFAOYSA-N 3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole Chemical compound FC(F)(F)COC1=CC(C2=NOC=N2)=NC=C1C1CC1 DWXXOPWEWPSUAD-UHFFFAOYSA-N 0.000 claims description 3
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• CESUXLKAADQNTB-UHFFFAOYSA-N tert-butanesulfinamide Chemical compound CC(C)(C)S(N)=O CESUXLKAADQNTB-UHFFFAOYSA-N 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• UIJXHKXIOCDSEB-UHFFFAOYSA-N tert-butyl 3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(O)C1 UIJXHKXIOCDSEB-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 125000001302 tertiary amino group Chemical group 0.000 description 1
• PCZOZSATUTWXIC-UHFFFAOYSA-N tetraethylazanium;cyanide Chemical compound N#[C-].CC[N+](CC)(CC)CC PCZOZSATUTWXIC-UHFFFAOYSA-N 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• 238000007070 tosylation reaction Methods 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• 125000000725 trifluoropropyl group Chemical group [H]C([H])(*)C([H])([H])C(F)(F)F 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1