CA2781041C - Spiropiperidine compounds as orl-1 receptor antagonists - Google Patents

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Publication number

CA2781041C

CA2781041C CA2781041A CA2781041A CA2781041C CA 2781041 C CA2781041 C CA 2781041C CA 2781041 A CA2781041 A CA 2781041A CA 2781041 A CA2781041 A CA 2781041A CA 2781041 C CA2781041 C CA 2781041C

Authority

CA

Canada

Prior art keywords

methyl

pyran

piperidine

pyrazol

chloro

Prior art date

2009-11-16

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.)

Expired - Fee Related

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• 108010020615 nociceptin receptor Proteins 0.000 title abstract description 31
• 239000002464 receptor antagonist Substances 0.000 title abstract description 4
• 229940044551 receptor antagonist Drugs 0.000 title abstract description 4
• JUXAVSAMVBLDKO-UHFFFAOYSA-N 1-(1-azabicyclo[2.2.2]octan-3-yl)-3-[3-(1h-indol-3-yl)-1-oxo-1-spiro[1,2-dihydroindene-3,4'-piperidine]-1'-ylpropan-2-yl]urea Chemical class C1N(CC2)CCC2C1NC(=O)NC(C(=O)N1CCC2(C3=CC=CC=C3CC2)CC1)CC1=CNC2=CC=CC=C12 JUXAVSAMVBLDKO-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 223
• 238000011282 treatment Methods 0.000 claims abstract description 35
• 208000008589 Obesity Diseases 0.000 claims abstract description 17
• 235000020824 obesity Nutrition 0.000 claims abstract description 17
• 206010033307 Overweight Diseases 0.000 claims abstract description 14
• 208000019695 Migraine disease Diseases 0.000 claims abstract description 11
• 208000020401 Depressive disease Diseases 0.000 claims abstract description 8
• -1 chloro, cyano, cyanomethyl Chemical group 0.000 claims description 106
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 84
• 150000003839 salts Chemical class 0.000 claims description 49
• 125000001153 fluoro group Chemical group F* 0.000 claims description 30
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• 239000001257 hydrogen Substances 0.000 claims description 17
• 229910052739 hydrogen Inorganic materials 0.000 claims description 17
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 14
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 11
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
• 150000002431 hydrogen Chemical group 0.000 claims description 10
• 206010027599 migraine Diseases 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 239000003085 diluting agent Substances 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 6
• 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 239000012896 selective serotonin reuptake inhibitor Substances 0.000 claims description 5
• DWYGLHSLUMTSPC-UHFFFAOYSA-N spiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1CNCCC21C(SC=C1)=C1CCO2 DWYGLHSLUMTSPC-UHFFFAOYSA-N 0.000 claims description 5
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• XXTAOIPDMBHKNU-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[1-[2-fluoro-6-(1-methylimidazol-2-yl)phenyl]-3-methylpyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1C1=NC=CN1C XXTAOIPDMBHKNU-UHFFFAOYSA-N 0.000 claims description 2
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
• JJWDJWQBHRUEIN-UHFFFAOYSA-N [4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-1-(2-fluorophenyl)pyrazol-3-yl]methanol Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(CO)=NN1C1=CC=CC=C1F JJWDJWQBHRUEIN-UHFFFAOYSA-N 0.000 claims description 2
• 125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
• PETZZCNIISAXSO-UHFFFAOYSA-N 1-[2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-fluorophenyl]-n-methylmethanamine Chemical compound CNCC1=CC=CC(F)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 PETZZCNIISAXSO-UHFFFAOYSA-N 0.000 claims 2
• ALDFBAMFJCZMRT-UHFFFAOYSA-N 1-[2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-fluorophenyl]ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 ALDFBAMFJCZMRT-UHFFFAOYSA-N 0.000 claims 2
• QTOTZWFQCWGMHS-UHFFFAOYSA-N 2-chloro-1'-[[1-(2,6-difluorophenyl)-3-methylpyrazol-4-yl]methyl]-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1F QTOTZWFQCWGMHS-UHFFFAOYSA-N 0.000 claims 2
• RBBAMCYZDBRGRI-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[1-[2-fluoro-6-(2-methylimidazol-1-yl)phenyl]-3-methylpyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1N1C=CN=C1C RBBAMCYZDBRGRI-UHFFFAOYSA-N 0.000 claims 2
• DHSXGJLFQNUKJV-UHFFFAOYSA-N [4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-1-(2,6-difluorophenyl)pyrazol-3-yl]methanol Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(CO)=NN1C1=C(F)C=CC=C1F DHSXGJLFQNUKJV-UHFFFAOYSA-N 0.000 claims 2
• GXZGKGSYYNKMCY-UHFFFAOYSA-N 1'-[[1-(2,6-difluorophenyl)-3-methylpyrazol-4-yl]methyl]-2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(F)=CC=2CCO3)C(C)=NN1C1=C(F)C=CC=C1F GXZGKGSYYNKMCY-UHFFFAOYSA-N 0.000 claims 1
• 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 claims 1
• DJNPTQOCOKRPIG-UHFFFAOYSA-N 1-[2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-fluorophenyl]-n,n-dimethylcyclopropan-1-amine Chemical compound C=1C=CC(F)=C(N2N=C(C)C(CN3CCC4(CC3)C=3SC(Cl)=CC=3C(F)(F)CO4)=C2)C=1C1(N(C)C)CC1 DJNPTQOCOKRPIG-UHFFFAOYSA-N 0.000 claims 1
• NNOVVEMYYNWICL-UHFFFAOYSA-N 1-[2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-fluorophenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=CC(F)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 NNOVVEMYYNWICL-UHFFFAOYSA-N 0.000 claims 1
• PUNBGDJMUIOGAT-UHFFFAOYSA-N 1-[2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-fluorophenyl]-n-(2-methoxyethyl)methanimine Chemical compound COCCN=CC1=CC=CC(F)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 PUNBGDJMUIOGAT-UHFFFAOYSA-N 0.000 claims 1
• VPCRVDXLPCCHMH-UHFFFAOYSA-N 1-[2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-fluorophenyl]cyclopropan-1-amine Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1C1(N)CC1 VPCRVDXLPCCHMH-UHFFFAOYSA-N 0.000 claims 1
• WODKTBZTGZUTGA-UHFFFAOYSA-N 1-[2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-methoxyphenyl]-n-methylmethanamine Chemical compound CNCC1=CC=CC(OC)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 WODKTBZTGZUTGA-UHFFFAOYSA-N 0.000 claims 1
• PDEMHIUPQTYTHT-UHFFFAOYSA-N 1-[2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]phenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=CC=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 PDEMHIUPQTYTHT-UHFFFAOYSA-N 0.000 claims 1
• SIZQFZXBQDZRFS-UHFFFAOYSA-N 1-[2-[4-[(2-chlorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-fluorophenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=CC(F)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2CCO3)=C1 SIZQFZXBQDZRFS-UHFFFAOYSA-N 0.000 claims 1
• ISBKYMUNIZSTJH-UHFFFAOYSA-N 1-[3-fluoro-2-[3-methyl-4-[(2,4,4-trifluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]pyrazol-1-yl]phenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=CC(F)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(F)=CC=2C(F)(F)CO3)=C1 ISBKYMUNIZSTJH-UHFFFAOYSA-N 0.000 claims 1
• NGMSOYNACKKJSG-UHFFFAOYSA-N 1-[3-fluoro-2-[4-[(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]phenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=CC(F)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(F)=CC=2CCO3)=C1 NGMSOYNACKKJSG-UHFFFAOYSA-N 0.000 claims 1
• DNFFHKWWGDTOTR-UHFFFAOYSA-N 2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-fluorobenzamide Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1C(N)=O DNFFHKWWGDTOTR-UHFFFAOYSA-N 0.000 claims 1
• RWQIMVHTRMFTQT-UHFFFAOYSA-N 2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]pyrazol-1-yl]-3-fluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1N1N=CC(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 RWQIMVHTRMFTQT-UHFFFAOYSA-N 0.000 claims 1
• HJAQEBQKDAJQRY-UHFFFAOYSA-N 2-[[2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-fluorophenyl]methylamino]ethanol Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1CNCCO HJAQEBQKDAJQRY-UHFFFAOYSA-N 0.000 claims 1
• XZPLGWDRMOMJEQ-UHFFFAOYSA-N 2-chloro-1'-[[1-(2,6-dimethylphenyl)-3-methylpyrazol-4-yl]methyl]-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(C)C=CC=C1C XZPLGWDRMOMJEQ-UHFFFAOYSA-N 0.000 claims 1
• XAFJTURCXWMRCN-UHFFFAOYSA-N 2-chloro-1'-[[1-(2-chlorophenyl)-3-methylpyrazol-4-yl]methyl]-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=CC=CC=C1Cl XAFJTURCXWMRCN-UHFFFAOYSA-N 0.000 claims 1
• FSXBLXIMZAECJS-UHFFFAOYSA-N 2-chloro-1'-[[1-[2-[(3,3-difluoroazetidin-1-yl)methyl]-6-fluorophenyl]-3-methylpyrazol-4-yl]methyl]-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1CN1CC(F)(F)C1 FSXBLXIMZAECJS-UHFFFAOYSA-N 0.000 claims 1
• JLCAIALDXIOVBP-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[1-(2-fluoro-6-imidazol-1-ylphenyl)-3-methylpyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1N1C=CN=C1 JLCAIALDXIOVBP-UHFFFAOYSA-N 0.000 claims 1
• KERMYBOLEOCRHH-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[1-(2-fluorophenyl)-3-methylpyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=CC=CC=C1F KERMYBOLEOCRHH-UHFFFAOYSA-N 0.000 claims 1
• FYTMHTRGHFVDOR-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[1-[2-(methoxymethyl)phenyl]-3-methylpyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound COCC1=CC=CC=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 FYTMHTRGHFVDOR-UHFFFAOYSA-N 0.000 claims 1
• NDESORITPQFVQC-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[1-[2-fluoro-6-(1h-1,2,4-triazol-5-yl)phenyl]-3-methylpyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1C=1N=CNN=1 NDESORITPQFVQC-UHFFFAOYSA-N 0.000 claims 1
• XURGFEMCAFOAGU-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[1-[2-fluoro-6-(methoxymethyl)phenyl]-3-methylpyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound COCC1=CC=CC(F)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 XURGFEMCAFOAGU-UHFFFAOYSA-N 0.000 claims 1
• GISSRLYHLGOHOP-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[1-[2-fluoro-6-(morpholin-4-ylmethyl)phenyl]-3-methylpyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1CN1CCOCC1 GISSRLYHLGOHOP-UHFFFAOYSA-N 0.000 claims 1
• HHYDBXOSCWQNSA-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[1-[2-fluoro-6-(pyrrolidin-1-ylmethyl)phenyl]-3-methylpyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1CN1CCCC1 HHYDBXOSCWQNSA-UHFFFAOYSA-N 0.000 claims 1
• LFJUFKLBEDBJPR-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[3-methyl-1-(2-methylphenyl)pyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=CC=CC=C1C LFJUFKLBEDBJPR-UHFFFAOYSA-N 0.000 claims 1
• KBYSWQYPSJYVMO-UHFFFAOYSA-N 2-chloro-4,4-difluoro-1'-[[3-methyl-1-(2-propan-2-ylphenyl)pyrazol-4-yl]methyl]spiro[5h-thieno[2,3-c]pyran-7,4'-piperidine] Chemical compound CC(C)C1=CC=CC=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)=C1 KBYSWQYPSJYVMO-UHFFFAOYSA-N 0.000 claims 1
• NQZXVSMRXPKINR-UHFFFAOYSA-N 3-chloro-2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]benzamide Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(Cl)C=CC=C1C(N)=O NQZXVSMRXPKINR-UHFFFAOYSA-N 0.000 claims 1
• VZCOGBUVJRVDEH-UHFFFAOYSA-N 3-fluoro-2-[3-methyl-4-[(2,4,4-trifluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]pyrazol-1-yl]benzamide Chemical compound C1=C(CN2CCC3(CC2)C=2SC(F)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(F)C=CC=C1C(N)=O VZCOGBUVJRVDEH-UHFFFAOYSA-N 0.000 claims 1
• KTXNEMDXEFXYKX-UHFFFAOYSA-N 3-fluoro-2-[4-[(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(F)=C1N1N=C(C)C(CN2CCC3(CC2)C=2SC(F)=CC=2CCO3)=C1 KTXNEMDXEFXYKX-UHFFFAOYSA-N 0.000 claims 1
• DFXWFQJIJYLWBM-UHFFFAOYSA-N 3-fluoro-2-[4-[(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]benzamide Chemical compound C1=C(CN2CCC3(CC2)C=2SC(F)=CC=2CCO3)C(C)=NN1C1=C(F)C=CC=C1C(N)=O DFXWFQJIJYLWBM-UHFFFAOYSA-N 0.000 claims 1
• LTVCWBVBPFSYRV-UHFFFAOYSA-N 3-fluoro-2-[4-[(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]benzonitrile Chemical compound C1=C(CN2CCC3(CC2)C=2SC(F)=CC=2CCO3)C(C)=NN1C1=C(F)C=CC=C1C#N LTVCWBVBPFSYRV-UHFFFAOYSA-N 0.000 claims 1
• IUHPYGXCRJAKHC-UHFFFAOYSA-N 3-fluoro-2-[4-[(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]pyrazol-1-yl]benzamide Chemical compound NC(=O)C1=CC=CC(F)=C1N1N=CC(CN2CCC3(CC2)C=2SC(F)=CC=2CCO3)=C1 IUHPYGXCRJAKHC-UHFFFAOYSA-N 0.000 claims 1
• GBNUMIAMFXWHBQ-UHFFFAOYSA-N [2-[4-[(2-chloro-4,4-difluorospiro[5h-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]-3-cyclopropylphenyl]methanol Chemical compound C1=C(CN2CCC3(CC2)C=2SC(Cl)=CC=2C(F)(F)CO3)C(C)=NN1C1=C(CO)C=CC=C1C1CC1 GBNUMIAMFXWHBQ-UHFFFAOYSA-N 0.000 claims 1
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