JP2013507366A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2013507366A5 JP2013507366A5 JP2012533226A JP2012533226A JP2013507366A5 JP 2013507366 A5 JP2013507366 A5 JP 2013507366A5 JP 2012533226 A JP2012533226 A JP 2012533226A JP 2012533226 A JP2012533226 A JP 2012533226A JP 2013507366 A5 JP2013507366 A5 JP 2013507366A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- phenyl
- azetidin
- trifluoromethyl
- difluoro
- 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.)
- Pending
Links
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 49
- 125000001475 halogen functional group Chemical group 0.000 claims 46
- 229910052739 hydrogen Inorganic materials 0.000 claims 27
- 239000001257 hydrogen Substances 0.000 claims 27
- 125000003545 alkoxy group Chemical group 0.000 claims 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 15
- 150000001875 compounds Chemical class 0.000 claims 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 11
- -1 hydroxypropyl Chemical group 0.000 claims 11
- 125000003118 aryl group Chemical group 0.000 claims 9
- 150000002431 hydrogen Chemical class 0.000 claims 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 7
- 125000002947 alkylene group Chemical group 0.000 claims 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims 5
- 201000010099 disease Diseases 0.000 claims 5
- 102100033839 Glucose-dependent insulinotropic receptor Human genes 0.000 claims 4
- 101000996752 Homo sapiens Glucose-dependent insulinotropic receptor Proteins 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 3
- 206010012601 diabetes mellitus Diseases 0.000 claims 3
- 230000000694 effects Effects 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 2
- KREHFNPASISMLT-UHFFFAOYSA-N 1-[3,5-difluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-4-methylsulfonylpiperazin-2-one Chemical compound O=C1CN(S(=O)(=O)C)CCN1C(C=C1F)=CC(F)=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 KREHFNPASISMLT-UHFFFAOYSA-N 0.000 claims 2
- XDZADSVOHSQVTC-UHFFFAOYSA-N 1-[3,5-difluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-4-methylsulfonylpiperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C(C=C1F)=CC(F)=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 XDZADSVOHSQVTC-UHFFFAOYSA-N 0.000 claims 2
- WUKRSOYOPHKYHF-UHFFFAOYSA-N 1-[3-fluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-4-methylsulfonylpiperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C(C=C1F)=CC=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 WUKRSOYOPHKYHF-UHFFFAOYSA-N 0.000 claims 2
- QDMSPBCJVABTJI-UHFFFAOYSA-N 1-[4-[3,5-difluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-3,6-dihydro-2h-pyridin-1-yl]-2,2,2-trifluoroethanone Chemical compound FC1=CC(C=2CCN(CC=2)C(=O)C(F)(F)F)=CC(F)=C1OC(C1)CN1CC1=CC=C(C(F)(F)F)C=C1 QDMSPBCJVABTJI-UHFFFAOYSA-N 0.000 claims 2
- MVXRMNLRWSEVMF-UHFFFAOYSA-N 2-(4-methylsulfonylpiperazin-1-yl)-5-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxypyrimidine Chemical compound C1CN(S(=O)(=O)C)CCN1C(N=C1)=NC=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 MVXRMNLRWSEVMF-UHFFFAOYSA-N 0.000 claims 2
- WXMFKKPOVWUMBQ-UHFFFAOYSA-N 2-[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]-2-[4-(trifluoromethyl)phenyl]ethanol Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(C(CO)C=2C=CC(=CC=2)C(F)(F)F)C1 WXMFKKPOVWUMBQ-UHFFFAOYSA-N 0.000 claims 2
- JKCDGKXUOWITEV-UHFFFAOYSA-N 2-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-4-(trifluoromethyl)-1,3-thiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2SC=C(N=2)C(F)(F)F)C1 JKCDGKXUOWITEV-UHFFFAOYSA-N 0.000 claims 2
- MFXBTDYTCIKRNZ-UHFFFAOYSA-N 2-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-5-(trifluoromethyl)pyrimidine Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2N=CC(=CN=2)C(F)(F)F)C1 MFXBTDYTCIKRNZ-UHFFFAOYSA-N 0.000 claims 2
- NZLZVERJPBTXAH-UHFFFAOYSA-N 2-[[4-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-4-(trifluoromethyl)-1,3-thiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CCN(CC=2SC=C(N=2)C(F)(F)F)CC1 NZLZVERJPBTXAH-UHFFFAOYSA-N 0.000 claims 2
- TZQUXHRMXLPNIR-UHFFFAOYSA-N 3-(1,1-difluoroethyl)-5-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-1,2,4-oxadiazole Chemical compound CC(F)(F)C1=NOC(CN2CC(C2)OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)=N1 TZQUXHRMXLPNIR-UHFFFAOYSA-N 0.000 claims 2
- YRYBUIINEVJSKD-UHFFFAOYSA-N 3-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-5-propan-2-yl-1,2,4-oxadiazole Chemical compound O1C(C(C)C)=NC(CN2CC(C2)OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)=N1 YRYBUIINEVJSKD-UHFFFAOYSA-N 0.000 claims 2
- BPYCLQDOGIWCMA-UHFFFAOYSA-N 3-chloro-2-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-5-(trifluoromethyl)pyridine Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2C(=CC(=CN=2)C(F)(F)F)Cl)C1 BPYCLQDOGIWCMA-UHFFFAOYSA-N 0.000 claims 2
- BMLWMQDZZOGTFR-UHFFFAOYSA-N 3-cyclopropyl-5-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2ON=C(N=2)C2CC2)C1 BMLWMQDZZOGTFR-UHFFFAOYSA-N 0.000 claims 2
- ZEZKZGIIBXPWHM-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-(naphthalen-1-ylmethyl)azetidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2C3=CC=CC=C3C=CC=2)C1 ZEZKZGIIBXPWHM-UHFFFAOYSA-N 0.000 claims 2
- YWPPYASFWVKDTH-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-(naphthalen-2-ylmethyl)azetidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2C=C3C=CC=CC3=CC=2)C1 YWPPYASFWVKDTH-UHFFFAOYSA-N 0.000 claims 2
- ZJOQZCRDOIEZFS-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[1-[4-(trifluoromethyl)phenyl]propyl]azetidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(CC)N(C1)CC1OC(C(=C1)F)=C(F)C=C1C1CCN(S(C)(=O)=O)CC1 ZJOQZCRDOIEZFS-UHFFFAOYSA-N 0.000 claims 2
- HTGDOFSBHIEUIX-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]azetidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound CN1N=C(C(F)(F)F)C=C1CN1CC(OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)C1 HTGDOFSBHIEUIX-UHFFFAOYSA-N 0.000 claims 2
- ZVDDYYQIYSBLBM-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]methyl]piperidin-4-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound CN1N=C(C(F)(F)F)C=C1CN1CCC(OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)CC1 ZVDDYYQIYSBLBM-UHFFFAOYSA-N 0.000 claims 2
- IXJJEYBHRVETLG-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[4-(3-fluorooxetan-3-yl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2C=CC(=CC=2)C2(F)COC2)C1 IXJJEYBHRVETLG-UHFFFAOYSA-N 0.000 claims 2
- XFIYFKJEPMUAMR-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-1-(oxan-4-ylsulfonyl)piperidine Chemical compound FC1=CC(C2CCN(CC2)S(=O)(=O)C2CCOCC2)=CC(F)=C1OC(C1)CN1CC1=CC=C(C(F)(F)F)C=C1 XFIYFKJEPMUAMR-UHFFFAOYSA-N 0.000 claims 2
- UUDSTMMLSWAHBI-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 UUDSTMMLSWAHBI-UHFFFAOYSA-N 0.000 claims 2
- TXVWVMBVTQWPLT-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-1-piperidin-4-ylsulfonylpiperidine Chemical compound FC1=CC(C2CCN(CC2)S(=O)(=O)C2CCNCC2)=CC(F)=C1OC(C1)CN1CC1=CC=C(C(F)(F)F)C=C1 TXVWVMBVTQWPLT-UHFFFAOYSA-N 0.000 claims 2
- FKZSXTNYXOBXQG-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-1-pyrrolidin-3-ylsulfonylpiperidine Chemical compound FC1=CC(C2CCN(CC2)S(=O)(=O)C2CNCC2)=CC(F)=C1OC(C1)CN1CC1=CC=C(C(F)(F)F)C=C1 FKZSXTNYXOBXQG-UHFFFAOYSA-N 0.000 claims 2
- UINQQGMFVPCBAR-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]pyrrolidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)CC1 UINQQGMFVPCBAR-UHFFFAOYSA-N 0.000 claims 2
- ZQGKERQYOVCALX-UHFFFAOYSA-N 4-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-2-(trifluoromethyl)-1,3-thiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2N=C(SC=2)C(F)(F)F)C1 ZQGKERQYOVCALX-UHFFFAOYSA-N 0.000 claims 2
- ILEKSOWVIGRTLK-UHFFFAOYSA-N 4-[[4-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-2-(trifluoromethyl)-1,3-thiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CCN(CC=2N=C(SC=2)C(F)(F)F)CC1 ILEKSOWVIGRTLK-UHFFFAOYSA-N 0.000 claims 2
- FYPGJSOVVLGRIC-UHFFFAOYSA-N 4-methylsulfonyl-1-[5-[1-[[4-(trifluoromethoxy)phenyl]methyl]azetidin-3-yl]oxypyrazin-2-yl]piperazin-2-one Chemical compound O=C1CN(S(=O)(=O)C)CCN1C(N=C1)=CN=C1OC1CN(CC=2C=CC(OC(F)(F)F)=CC=2)C1 FYPGJSOVVLGRIC-UHFFFAOYSA-N 0.000 claims 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical group C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims 2
- UHXGRLNXXIPHAK-UHFFFAOYSA-N 5-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-3-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2ON=C(N=2)C(F)(F)F)C1 UHXGRLNXXIPHAK-UHFFFAOYSA-N 0.000 claims 2
- PLROFIMLUNJEBN-UHFFFAOYSA-N 5-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-3-propan-2-yl-1,2,4-oxadiazole Chemical compound CC(C)C1=NOC(CN2CC(C2)OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)=N1 PLROFIMLUNJEBN-UHFFFAOYSA-N 0.000 claims 2
- RPZNXQJFTNRLGS-UHFFFAOYSA-N 5-[[4-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-3-propan-2-yl-1,2,4-oxadiazole Chemical compound CC(C)C1=NOC(CN2CCC(CC2)OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)=N1 RPZNXQJFTNRLGS-UHFFFAOYSA-N 0.000 claims 2
- WTIDTULUJMMFPP-UHFFFAOYSA-N 5-[[4-[2,6-difluoro-4-(4-fluoro-1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-3-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1(F)C(C=C1F)=CC(F)=C1OC1CCN(CC=2ON=C(N=2)C(F)(F)F)CC1 WTIDTULUJMMFPP-UHFFFAOYSA-N 0.000 claims 2
- AEZSSFAWPPJUOE-UHFFFAOYSA-N 5-[[4-[2-fluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-3-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC=C1OC1CCN(CC=2ON=C(N=2)C(F)(F)F)CC1 AEZSSFAWPPJUOE-UHFFFAOYSA-N 0.000 claims 2
- FPPYBKDYHACVIJ-UHFFFAOYSA-N 5-[[4-[3-fluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-3-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C(=C1)F)=CC=C1OC1CCN(CC=2ON=C(N=2)C(F)(F)F)CC1 FPPYBKDYHACVIJ-UHFFFAOYSA-N 0.000 claims 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 claims 2
- 208000002705 Glucose Intolerance Diseases 0.000 claims 2
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 208000029078 coronary artery disease Diseases 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 125000006001 difluoroethyl group Chemical group 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 239000008103 glucose Substances 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 230000000366 juvenile effect Effects 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 208000010125 myocardial infarction Diseases 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 201000009104 prediabetes syndrome Diseases 0.000 claims 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000000335 thiazolyl group Chemical group 0.000 claims 2
- AHJAFRIFZRLGQO-UHFFFAOYSA-N 1-[5-[1-[(4-chlorophenyl)methyl]azetidin-3-yl]oxypyridin-2-yl]-4-methylsulfonylpiperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C(N=C1)=CC=C1OC1CN(CC=2C=CC(Cl)=CC=2)C1 AHJAFRIFZRLGQO-UHFFFAOYSA-N 0.000 claims 1
- FTMFVDNBRISMBM-UHFFFAOYSA-N 1-[5-[1-[(4-methoxyphenyl)methyl]azetidin-3-yl]oxypyridin-2-yl]-4-methylsulfonylpiperazine Chemical compound C1=CC(OC)=CC=C1CN1CC(OC=2C=NC(=CC=2)N2CCN(CC2)S(C)(=O)=O)C1 FTMFVDNBRISMBM-UHFFFAOYSA-N 0.000 claims 1
- OOIYQDIPUYOXRM-UHFFFAOYSA-N 1-[5-[1-[(4-methylphenyl)methyl]azetidin-3-yl]oxypyridin-2-yl]-4-methylsulfonylpiperazine Chemical compound C1=CC(C)=CC=C1CN1CC(OC=2C=NC(=CC=2)N2CCN(CC2)S(C)(=O)=O)C1 OOIYQDIPUYOXRM-UHFFFAOYSA-N 0.000 claims 1
- JADXFOZAJSMQAV-UHFFFAOYSA-N 1-[5-[1-[[4-(difluoromethoxy)phenyl]methyl]azetidin-3-yl]oxypyridin-2-yl]-4-methylsulfonylpiperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C(N=C1)=CC=C1OC1CN(CC=2C=CC(OC(F)F)=CC=2)C1 JADXFOZAJSMQAV-UHFFFAOYSA-N 0.000 claims 1
- ZRKXJHNZKJRJIG-UHFFFAOYSA-N 1-methylsulfonyl-4-[4-[1-[(4-propan-2-ylphenyl)methyl]azetidin-3-yl]oxyphenyl]piperazine Chemical compound C1=CC(C(C)C)=CC=C1CN1CC(OC=2C=CC(=CC=2)N2CCN(CC2)S(C)(=O)=O)C1 ZRKXJHNZKJRJIG-UHFFFAOYSA-N 0.000 claims 1
- CRFIRNYALDVCNH-UHFFFAOYSA-N 1-methylsulfonyl-4-[5-[1-[(4-propan-2-ylphenyl)methyl]azetidin-3-yl]oxypyridin-2-yl]piperazine Chemical compound C1=CC(C(C)C)=CC=C1CN1CC(OC=2C=NC(=CC=2)N2CCN(CC2)S(C)(=O)=O)C1 CRFIRNYALDVCNH-UHFFFAOYSA-N 0.000 claims 1
- HJJNFIZAVLVPRN-UHFFFAOYSA-N 1-methylsulfonyl-4-[5-[1-[[3-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxypyridin-2-yl]piperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C(N=C1)=CC=C1OC1CN(CC=2C=C(C=CC=2)C(F)(F)F)C1 HJJNFIZAVLVPRN-UHFFFAOYSA-N 0.000 claims 1
- HTIAOECCZOFYCU-UHFFFAOYSA-N 1-methylsulfonyl-4-[5-[1-[[4-(trifluoromethoxy)phenyl]methyl]azetidin-3-yl]oxypyridin-2-yl]piperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C(N=C1)=CC=C1OC1CN(CC=2C=CC(OC(F)(F)F)=CC=2)C1 HTIAOECCZOFYCU-UHFFFAOYSA-N 0.000 claims 1
- NROQZUOLYKYDRH-UHFFFAOYSA-N 1-methylsulfonyl-4-[5-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxypyridin-2-yl]piperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C(N=C1)=CC=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 NROQZUOLYKYDRH-UHFFFAOYSA-N 0.000 claims 1
- FWNKUZCWCKOGKM-UHFFFAOYSA-N 1-propylsulfonyl-4-[5-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxypyridin-2-yl]piperazine Chemical compound C1CN(S(=O)(=O)CCC)CCN1C(N=C1)=CC=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 FWNKUZCWCKOGKM-UHFFFAOYSA-N 0.000 claims 1
- VUYPYGJFILRODH-UHFFFAOYSA-N 2-(4-methylsulfonylpiperazin-1-yl)-5-[1-[(4-propan-2-ylphenyl)methyl]azetidin-3-yl]oxypyrazine Chemical compound C1=CC(C(C)C)=CC=C1CN1CC(OC=2N=CC(=NC=2)N2CCN(CC2)S(C)(=O)=O)C1 VUYPYGJFILRODH-UHFFFAOYSA-N 0.000 claims 1
- BLPPBPZPVXKRKW-UHFFFAOYSA-N 2-(4-methylsulfonylpiperazin-1-yl)-5-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxypyrazine Chemical compound C1CN(S(=O)(=O)C)CCN1C(N=C1)=CN=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 BLPPBPZPVXKRKW-UHFFFAOYSA-N 0.000 claims 1
- INSKWIQMYXYATL-UHFFFAOYSA-N 2-[[4-[5-(1-methylsulfonylpiperidin-4-yl)pyrazin-2-yl]oxypiperidin-1-yl]methyl]-4-(trifluoromethyl)-1,3-thiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(N=C1)=CN=C1OC1CCN(CC=2SC=C(N=2)C(F)(F)F)CC1 INSKWIQMYXYATL-UHFFFAOYSA-N 0.000 claims 1
- OBOIAHULPQYVNO-UHFFFAOYSA-N 3-(1,1-difluoroethyl)-5-[[4-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-1,2,4-oxadiazole Chemical compound CC(F)(F)C1=NOC(CN2CCC(CC2)OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)=N1 OBOIAHULPQYVNO-UHFFFAOYSA-N 0.000 claims 1
- GWTHCKYEDANWHJ-UHFFFAOYSA-N 3-(difluoromethyl)-5-[[4-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CCN(CC=2ON=C(N=2)C(F)F)CC1 GWTHCKYEDANWHJ-UHFFFAOYSA-N 0.000 claims 1
- HQIIRGCOGOMVGR-UHFFFAOYSA-N 3-[4-[3,5-difluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]piperidin-1-yl]sulfonylpropan-1-ol Chemical compound C1CN(S(=O)(=O)CCCO)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 HQIIRGCOGOMVGR-UHFFFAOYSA-N 0.000 claims 1
- AWYYPLHYBDRNQW-UHFFFAOYSA-N 3-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-5-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CN(CC=2N=C(ON=2)C(F)(F)F)C1 AWYYPLHYBDRNQW-UHFFFAOYSA-N 0.000 claims 1
- YIEOSBYCFGPQQE-UHFFFAOYSA-N 3-[[4-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-5-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CCN(CC=2N=C(ON=2)C(F)(F)F)CC1 YIEOSBYCFGPQQE-UHFFFAOYSA-N 0.000 claims 1
- CJRXUJPBCUWSLT-UHFFFAOYSA-N 3-tert-butyl-5-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-1,2,4-oxadiazole Chemical compound CC(C)(C)C1=NOC(CN2CC(C2)OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)=N1 CJRXUJPBCUWSLT-UHFFFAOYSA-N 0.000 claims 1
- QSSTWCWREAWYBO-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[1-[4-(trifluoromethyl)phenyl]ethyl]azetidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(C)N(C1)CC1OC(C(=C1)F)=C(F)C=C1C1CCN(S(C)(=O)=O)CC1 QSSTWCWREAWYBO-UHFFFAOYSA-N 0.000 claims 1
- NCKOVDFANVCCCR-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[1-[4-(trifluoromethyl)phenyl]propan-2-yl]azetidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound C1C(OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)CN1C(C)CC1=CC=C(C(F)(F)F)C=C1 NCKOVDFANVCCCR-UHFFFAOYSA-N 0.000 claims 1
- IPSWMTDIRGLRFN-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[2-methyl-5-(trifluoromethyl)-1,2,4-triazol-3-yl]methyl]azetidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound CN1N=C(C(F)(F)F)N=C1CN1CC(OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)C1 IPSWMTDIRGLRFN-UHFFFAOYSA-N 0.000 claims 1
- JYQLNIAYJXPRLF-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[2-methyl-5-(trifluoromethyl)-1,2,4-triazol-3-yl]methyl]piperidin-4-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound CN1N=C(C(F)(F)F)N=C1CN1CCC(OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)CC1 JYQLNIAYJXPRLF-UHFFFAOYSA-N 0.000 claims 1
- SOQHVOHGNJCARW-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CCN(CC=2C=C(C=CC=2)C(F)(F)F)CC1 SOQHVOHGNJCARW-UHFFFAOYSA-N 0.000 claims 1
- TXSSQJHMVOARHI-UHFFFAOYSA-N 4-[3,5-difluoro-4-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-1-methylsulfonyl-3,6-dihydro-2h-pyridine Chemical compound C1N(S(=O)(=O)C)CCC(C=2C=C(F)C(OC3CN(CC=4C=CC(=CC=4)C(F)(F)F)C3)=C(F)C=2)=C1 TXSSQJHMVOARHI-UHFFFAOYSA-N 0.000 claims 1
- HIMHPDQNBWRSAK-UHFFFAOYSA-N 4-[3,5-difluoro-4-[3-methyl-1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxyphenyl]-1-methylsulfonylpiperidine Chemical compound C1C(C)(OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)CN1CC1=CC=C(C(F)(F)F)C=C1 HIMHPDQNBWRSAK-UHFFFAOYSA-N 0.000 claims 1
- FSVQMSDKVKBPQA-UHFFFAOYSA-N 4-methylsulfonyl-1-[5-[1-[(4-propan-2-ylphenyl)methyl]azetidin-3-yl]oxypyrazin-2-yl]piperazin-2-one Chemical compound C1=CC(C(C)C)=CC=C1CN1CC(OC=2N=CC(=NC=2)N2C(CN(CC2)S(C)(=O)=O)=O)C1 FSVQMSDKVKBPQA-UHFFFAOYSA-N 0.000 claims 1
- HICIFGBVONFQQZ-UHFFFAOYSA-N 4-methylsulfonyl-1-[5-[1-[(4-propan-2-ylphenyl)methyl]azetidin-3-yl]oxypyridin-2-yl]piperazin-2-one Chemical compound C1=CC(C(C)C)=CC=C1CN1CC(OC=2C=NC(=CC=2)N2C(CN(CC2)S(C)(=O)=O)=O)C1 HICIFGBVONFQQZ-UHFFFAOYSA-N 0.000 claims 1
- NKJQSXQYAYBVAC-UHFFFAOYSA-N 4-methylsulfonyl-1-[5-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxypyrazin-2-yl]piperazin-2-one Chemical compound O=C1CN(S(=O)(=O)C)CCN1C(N=C1)=CN=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 NKJQSXQYAYBVAC-UHFFFAOYSA-N 0.000 claims 1
- FJUMKFRWGGTZEC-UHFFFAOYSA-N 4-methylsulfonyl-1-[5-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxypyridin-2-yl]piperazin-2-one Chemical compound O=C1CN(S(=O)(=O)C)CCN1C(N=C1)=CC=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 FJUMKFRWGGTZEC-UHFFFAOYSA-N 0.000 claims 1
- XBIALPHDDHGCCI-UHFFFAOYSA-N 4-propylsulfonyl-1-[5-[1-[[4-(trifluoromethyl)phenyl]methyl]azetidin-3-yl]oxypyridin-2-yl]piperazin-2-one Chemical compound O=C1CN(S(=O)(=O)CCC)CCN1C(N=C1)=CC=C1OC1CN(CC=2C=CC(=CC=2)C(F)(F)F)C1 XBIALPHDDHGCCI-UHFFFAOYSA-N 0.000 claims 1
- ZGPRBKMQVAYTCL-UHFFFAOYSA-N 5-[[4-[2,3-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-3-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C(=C1F)F)=CC=C1OC1CCN(CC=2ON=C(N=2)C(F)(F)F)CC1 ZGPRBKMQVAYTCL-UHFFFAOYSA-N 0.000 claims 1
- WZKXEORDWPFSSG-UHFFFAOYSA-N 5-[[4-[2,5-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-3-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C(=C1)F)=CC(F)=C1OC1CCN(CC=2ON=C(N=2)C(F)(F)F)CC1 WZKXEORDWPFSSG-UHFFFAOYSA-N 0.000 claims 1
- KDQZKWKCRHXONL-UHFFFAOYSA-N 5-[[4-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-2-(trifluoromethyl)pyridine Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CCN(CC=2C=NC(=CC=2)C(F)(F)F)CC1 KDQZKWKCRHXONL-UHFFFAOYSA-N 0.000 claims 1
- GOAIPAPWWLKQTR-UHFFFAOYSA-N 5-[[4-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-3-(2-fluoropropan-2-yl)-1,2,4-oxadiazole Chemical compound CC(C)(F)C1=NOC(CN2CCC(CC2)OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)=N1 GOAIPAPWWLKQTR-UHFFFAOYSA-N 0.000 claims 1
- LDFDAFNOLBHDHI-UHFFFAOYSA-N 5-[[4-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-3-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1F)=CC(F)=C1OC1CCN(CC=2ON=C(N=2)C(F)(F)F)CC1 LDFDAFNOLBHDHI-UHFFFAOYSA-N 0.000 claims 1
- SAGRJUDCRNGPCR-UHFFFAOYSA-N 5-[[4-[3,5-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-3-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C(=C1)F)=C(F)C=C1OC1CCN(CC=2ON=C(N=2)C(F)(F)F)CC1 SAGRJUDCRNGPCR-UHFFFAOYSA-N 0.000 claims 1
- DECUEDJKHPAOEF-UHFFFAOYSA-N 5-[[4-[4-(1-methylsulfonylpiperidin-4-yl)phenoxy]piperidin-1-yl]methyl]-3-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCC1C(C=C1)=CC=C1OC1CCN(CC=2ON=C(N=2)C(F)(F)F)CC1 DECUEDJKHPAOEF-UHFFFAOYSA-N 0.000 claims 1
- PTWSXKXZUIBSQO-UHFFFAOYSA-N 5-[[4-[5-(4-methylsulfonylpiperazin-1-yl)pyrazin-2-yl]oxypiperidin-1-yl]methyl]-3-(trifluoromethyl)-1,2,4-oxadiazole Chemical compound C1CN(S(=O)(=O)C)CCN1C(N=C1)=CN=C1OC1CCN(CC=2ON=C(N=2)C(F)(F)F)CC1 PTWSXKXZUIBSQO-UHFFFAOYSA-N 0.000 claims 1
- HJTHQHQRLYFGEK-UHFFFAOYSA-N 5-tert-butyl-3-[[3-[2,6-difluoro-4-(1-methylsulfonylpiperidin-4-yl)phenoxy]azetidin-1-yl]methyl]-1,2,4-oxadiazole Chemical compound O1C(C(C)(C)C)=NC(CN2CC(C2)OC=2C(=CC(=CC=2F)C2CCN(CC2)S(C)(=O)=O)F)=N1 HJTHQHQRLYFGEK-UHFFFAOYSA-N 0.000 claims 1
- 208000010444 Acidosis Diseases 0.000 claims 1
- 206010002383 Angina Pectoris Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- GDTCWJFNPYUGAI-UHFFFAOYSA-N CS(N(CC=CC1)C1C(C=C1F)=CC(F)=C1OC1CN(CC2=CC=C(C(F)(F)F)C=C2)C1)(=O)=O Chemical compound CS(N(CC=CC1)C1C(C=C1F)=CC(F)=C1OC1CN(CC2=CC=C(C(F)(F)F)C=C2)C1)(=O)=O GDTCWJFNPYUGAI-UHFFFAOYSA-N 0.000 claims 1
- 206010007559 Cardiac failure congestive Diseases 0.000 claims 1
- 208000002177 Cataract Diseases 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims 1
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 1
- 208000032928 Dyslipidaemia Diseases 0.000 claims 1
- 206010048554 Endothelial dysfunction Diseases 0.000 claims 1
- 208000010228 Erectile Dysfunction Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 206010022489 Insulin Resistance Diseases 0.000 claims 1
- 206010022562 Intermittent claudication Diseases 0.000 claims 1
- 208000032382 Ischaemic stroke Diseases 0.000 claims 1
- 208000007976 Ketosis Diseases 0.000 claims 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 claims 1
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
- 208000002720 Malnutrition Diseases 0.000 claims 1
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 1
- 206010027417 Metabolic acidosis Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 208000001132 Osteoporosis Diseases 0.000 claims 1
- 208000031481 Pathologic Constriction Diseases 0.000 claims 1
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims 1
- 208000018262 Peripheral vascular disease Diseases 0.000 claims 1
- 206010036618 Premenstrual syndrome Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 208000032109 Transient ischaemic attack Diseases 0.000 claims 1
- 208000025865 Ulcer Diseases 0.000 claims 1
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 238000002399 angioplasty Methods 0.000 claims 1
- 206010003246 arthritis Diseases 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 208000020832 chronic kidney disease Diseases 0.000 claims 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims 1
- 208000018631 connective tissue disease Diseases 0.000 claims 1
- 208000033679 diabetic kidney disease Diseases 0.000 claims 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000008694 endothelial dysfunction Effects 0.000 claims 1
- 208000004104 gestational diabetes Diseases 0.000 claims 1
- 206010061989 glomerulosclerosis Diseases 0.000 claims 1
- 230000004153 glucose metabolism Effects 0.000 claims 1
- 201000001421 hyperglycemia Diseases 0.000 claims 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims 1
- 201000008980 hyperinsulinism Diseases 0.000 claims 1
- 208000006575 hypertriglyceridemia Diseases 0.000 claims 1
- 230000001771 impaired effect Effects 0.000 claims 1
- 201000001881 impotence Diseases 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 208000021156 intermittent vascular claudication Diseases 0.000 claims 1
- 230000004140 ketosis Effects 0.000 claims 1
- 208000002780 macular degeneration Diseases 0.000 claims 1
- 230000001071 malnutrition Effects 0.000 claims 1
- 235000000824 malnutrition Nutrition 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 208000015380 nutritional deficiency disease Diseases 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 1
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 230000000291 postprandial effect Effects 0.000 claims 1
- 201000000484 premenstrual tension Diseases 0.000 claims 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 230000000250 revascularization Effects 0.000 claims 1
- 208000037804 stenosis Diseases 0.000 claims 1
- 230000036262 stenosis Effects 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 201000010875 transient cerebral ischemia Diseases 0.000 claims 1
- 230000036269 ulceration Effects 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ZMLHBBXPXZXTSP-UHFFFAOYSA-N 2-fluoropropane Chemical group C[C](C)F ZMLHBBXPXZXTSP-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25042409P | 2009-10-09 | 2009-10-09 | |
| US61/250,424 | 2009-10-09 | ||
| US36511210P | 2010-07-16 | 2010-07-16 | |
| US61/365,112 | 2010-07-16 | ||
| PCT/US2010/051186 WO2011044001A1 (en) | 2009-10-09 | 2010-10-01 | Compounds and compositions as modulators of gpr119 activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2013507366A JP2013507366A (ja) | 2013-03-04 |
| JP2013507366A5 true JP2013507366A5 (OSRAM) | 2013-11-14 |
Family
ID=43033382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012533226A Pending JP2013507366A (ja) | 2009-10-09 | 2010-10-01 | Ｇｐｒ１１９活性モジュレーターとしての化合物および組成物 |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8575168B2 (OSRAM) |
| EP (1) | EP2486033A1 (OSRAM) |
| JP (1) | JP2013507366A (OSRAM) |
| KR (1) | KR20120092629A (OSRAM) |
| CN (1) | CN102686579A (OSRAM) |
| AR (1) | AR078550A1 (OSRAM) |
| AU (1) | AU2010303780B2 (OSRAM) |
| BR (1) | BR112012008004A2 (OSRAM) |
| CA (1) | CA2774573A1 (OSRAM) |
| EA (1) | EA201200570A1 (OSRAM) |
| IN (1) | IN2012DN02471A (OSRAM) |
| MX (1) | MX2012004078A (OSRAM) |
| TW (1) | TW201124400A (OSRAM) |
| UY (1) | UY32937A (OSRAM) |
| WO (1) | WO2011044001A1 (OSRAM) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011516557A (ja) * | 2008-04-07 | 2011-05-26 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｇｐｒ１１９活性のモジュレーターとしての化合物および組成物 |
| AR083904A1 (es) | 2010-11-18 | 2013-04-10 | Prosidion Ltd | Derivados de 1,4-pirrolidinas disustituidos y 3-il-aminas y sus usos en el tratamiento de desordenes metabolicos |
| GB201114389D0 (en) | 2011-08-22 | 2011-10-05 | Prosidion Ltd | Novel compounds |
| AU2012267556B9 (en) | 2011-06-09 | 2017-05-11 | Rhizen Pharmaceuticals Sa | Novel compounds as modulators of GPR-119 |
| AR091739A1 (es) | 2012-07-11 | 2015-02-25 | Elcelyx Therapeutics Inc | Composiciones y metodos para reducir el riesgo cardiometabolico |
| WO2014019967A1 (en) * | 2012-08-02 | 2014-02-06 | Boehringer Ingelheim International Gmbh | N-cyclopropyl-n-piperidinyl-amides, pharmaceutical compositions containing them and uses thereof |
| WO2014052619A1 (en) * | 2012-09-27 | 2014-04-03 | Irm Llc | Piperidine derivatives and compositions as modulators of gpr119 activity |
| CA2891569A1 (en) * | 2012-11-16 | 2014-05-22 | Bristol-Myers Squibb Company | Pyrrolidine gpr40 modulators |
| AU2016209321B2 (en) * | 2015-01-20 | 2019-05-09 | Boehringer Ingelheim Animal Health USA Inc. | Anthelmintic compounds, compositions and method of using thereof |
| EA202092442A3 (ru) | 2016-06-07 | 2021-08-31 | Джакобио Фармасьютикалс Ко., Лтд. | Новые гетероциклические производные, применимые в качестве ингибиторов shp2 |
| US10392366B2 (en) | 2017-02-21 | 2019-08-27 | Sanofi | Azetidine compounds as GPR119 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders |
| KR102317480B1 (ko) | 2017-03-23 | 2021-10-25 | 자코바이오 파마슈티칼스 컴퍼니 리미티드 | Shp2 억제제로서 유용한 신규한 헤테로환형 유도체 |
| LT3786160T (lt) | 2017-10-27 | 2022-09-26 | Boehringer Ingelheim International Gmbh | Piridino dariniai ir jų terapinis panaudojimas kaip trpc6 inhibitorių |
| WO2020063760A1 (en) | 2018-09-26 | 2020-04-02 | Jacobio Pharmaceuticals Co., Ltd. | Novel heterocyclic derivatives useful as shp2 inhibitors |
| PH12022552277A1 (en) | 2020-02-28 | 2024-03-04 | Kallyope Inc | Gpr40 agonists |
| CA3178994A1 (en) | 2020-05-19 | 2021-11-25 | Iyassu Sebhat | Ampk activators |
| JP2023531726A (ja) | 2020-06-26 | 2023-07-25 | キャリーオペ，インク． | Ａｍｐｋアクチベーター |
Family Cites Families (48)
| 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 |
| JPS5612114B2 (OSRAM) | 1974-06-07 | 1981-03-18 | ||
| US4231938A (en) | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| DK149080C (da) | 1980-06-06 | 1986-07-28 | Sankyo Co | Fremgangsmaade til fremstilling af derivater af ml-236b-carboxylsyre |
| US4450171A (en) | 1980-08-05 | 1984-05-22 | Merck & Co., Inc. | Antihypercholesterolemic compounds |
| US4448784A (en) | 1982-04-12 | 1984-05-15 | Hoechst-Roussel Pharmaceuticals, Inc. | 1-(Aminoalkylphenyl and aminoalkylbenzyl)-indoles and indolines and analgesic method of use thereof |
| US4499289A (en) | 1982-12-03 | 1985-02-12 | G. D. Searle & Co. | Octahydronapthalenes |
| CA1327360C (en) | 1983-11-14 | 1994-03-01 | William F. Hoffman | Oxo-analogs of mevinolin-like antihypercholesterolemic agents |
| JPS60149573A (ja) | 1984-01-13 | 1985-08-07 | Mitsubishi Petrochem Co Ltd | フエニル尿素誘導体 |
| US4613610A (en) | 1984-06-22 | 1986-09-23 | Sandoz Pharmaceuticals Corp. | Cholesterol biosynthesis inhibiting pyrazole analogs of mevalonolactone and its derivatives |
| US4686237A (en) | 1984-07-24 | 1987-08-11 | Sandoz Pharmaceuticals Corp. | Erythro-(E)-7-[3'-C1-3 alkyl-1'-(3",5"-dimethylphenyl)naphth-2'-yl]-3,5-dihydroxyhept-6-enoic acids and derivatives thereof |
| US4647576A (en) | 1984-09-24 | 1987-03-03 | Warner-Lambert Company | Trans-6-[2-(substitutedpyrrol-1-yl)alkyl]-pyran-2-one inhibitors of cholesterol synthesis |
| HU198005B (en) | 1984-12-04 | 1989-07-28 | Sandoz Ag | Process for producing mevqlolakton, derivatives, its indene-analogues and pharmaceutical compositions containing them |
| US4668794A (en) | 1985-05-22 | 1987-05-26 | Sandoz Pharm. Corp. | Intermediate imidazole acrolein analogs |
| KR900001212B1 (ko) | 1985-10-25 | 1990-02-28 | 산도즈 파마슈티칼스 코오포레이숀 | 메바로노락톤 및 그것의 유도체의 헤테로사이클릭 유사체 및 그것의 생산방법 및 약학적인 그것의 용도 |
| FR2596393B1 (fr) | 1986-04-01 | 1988-06-03 | Sanofi Sa | Derives de l'acide hydroxy-3 dihydroxyoxophosphorio-4 butanoique, leur procede de preparation, leur application comme medicament et les compositions les renfermant |
| PT87539B (pt) | 1987-05-22 | 1992-09-30 | Squibb & Sons Inc | Processo para a preparacao de inibidores da reductase de hmg-coa contendo fosforo e novos intermediarios |
| US5506219A (en) | 1988-08-29 | 1996-04-09 | E. R. Squibb & Sons, Inc. | Pyridine anchors for HMG-CoA reductase inhibitors |
| JP2969359B2 (ja) * | 1989-01-13 | 1999-11-02 | 武田薬品工業株式会社 | 環状アミン化合物 |
| US5753675A (en) | 1989-03-03 | 1998-05-19 | Novartis Pharmaceuticals Corporation | Quinoline analogs of mevalonolactone and derivatives thereof |
| HUT64023A (en) | 1991-03-22 | 1993-11-29 | Sandoz Ag | Process for producing aminoguanidine derivatives and pharmaceutical compositions comprising such compounds |
| TW225528B (OSRAM) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| US5776983A (en) | 1993-12-21 | 1998-07-07 | Bristol-Myers Squibb Company | Catecholamine surrogates useful as β3 agonists |
| US5488064A (en) | 1994-05-02 | 1996-01-30 | Bristol-Myers Squibb Company | Benzo 1,3 dioxole derivatives |
| 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 |
| EP0873361B1 (en) | 1995-12-13 | 2006-11-02 | The Regents Of The University Of California | Crystals of the ligand-binding domain of the thyroid hormone receptor complexed to a ligand |
| US5770615A (en) | 1996-04-04 | 1998-06-23 | Bristol-Myers Squibb Company | Catecholamine surrogates useful as β3 agonists |
| GB9713739D0 (en) | 1997-06-27 | 1997-09-03 | Karobio Ab | Thyroid receptor ligands |
| IL140622A0 (en) | 1998-07-06 | 2002-02-10 | Bristol Myers Squibb Co | Biphenyl sufonamide derivatives, pharmaceutical compositions containing the same and methods for the preparation thereof |
| CO5150173A1 (es) | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
| TW200303742A (en) | 2001-11-21 | 2003-09-16 | Novartis Ag | Organic compounds |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| GB0224084D0 (en) * | 2002-10-16 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
| MXPA05005425A (es) | 2002-11-22 | 2005-11-23 | Japan Tobacco Inc | Heterociclos que contienen nitrogeno, biciclicos, fusionados. |
| US20040185559A1 (en) | 2003-03-21 | 2004-09-23 | Isis Pharmaceuticals Inc. | Modulation of diacylglycerol acyltransferase 1 expression |
| TWI345974B (en) | 2003-07-30 | 2011-08-01 | Xenon Pharmaceuticals Inc | Pyridazine derivatives and their use in the inhibition of stearoyl-coa desaturase |
| JP2007501801A (ja) | 2003-08-07 | 2007-02-01 | 日本たばこ産業株式会社 | ピロロ［１，２−ｂ］ピリダジン誘導体 |
| GB0325192D0 (en) | 2003-10-29 | 2003-12-03 | Astrazeneca Ab | Method of use |
| AR051596A1 (es) | 2004-10-26 | 2007-01-24 | Irm Llc | Compuestos heterociclicos condensados nitrogenados como inhibidores de la actividad del receptor canabinoide 1; composiciones farmaceuticas que los contienen y su empleo en la preparacion de medicamentos para el tratamiento de trastornos alimentarios |
| US20090203676A1 (en) * | 2005-06-30 | 2009-08-13 | Oscar Barba | G-protein Coupled Receptor Agonists |
| AU2006331882A1 (en) * | 2005-12-21 | 2007-07-05 | Schering Corporation | Phenoxypiperidines and analogs thereof useful as histamine H3 antagonists |
| GB0607196D0 (en) * | 2006-04-11 | 2006-05-17 | Prosidion Ltd | G-protein coupled receptor agonists |
| EP2094683B1 (en) * | 2006-12-06 | 2011-10-12 | GlaxoSmithKline LLC | Bicyclic compounds and use as antidiabetics |
| BRPI0817211A2 (pt) * | 2007-09-20 | 2017-05-16 | Irm Llc | composto composições como moduladores da atividade de gpr119 |
| GB0720390D0 (en) * | 2007-10-18 | 2007-11-28 | Prosidion Ltd | G-Protein coupled receptor agonists |
| GB0720389D0 (en) * | 2007-10-18 | 2008-11-12 | Prosidion Ltd | G-Protein Coupled Receptor Agonists |
| JP2011516557A (ja) * | 2008-04-07 | 2011-05-26 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｇｐｒ１１９活性のモジュレーターとしての化合物および組成物 |
-
2010
- 2010-10-01 CN CN2010800453177A patent/CN102686579A/zh active Pending
- 2010-10-01 IN IN2471DEN2012 patent/IN2012DN02471A/en unknown
- 2010-10-01 BR BR112012008004A patent/BR112012008004A2/pt not_active IP Right Cessation
- 2010-10-01 MX MX2012004078A patent/MX2012004078A/es active IP Right Grant
- 2010-10-01 KR KR1020127011865A patent/KR20120092629A/ko not_active Abandoned
- 2010-10-01 JP JP2012533226A patent/JP2013507366A/ja active Pending
- 2010-10-01 EP EP10763952A patent/EP2486033A1/en not_active Withdrawn
- 2010-10-01 CA CA2774573A patent/CA2774573A1/en not_active Abandoned
- 2010-10-01 EA EA201200570A patent/EA201200570A1/ru unknown
- 2010-10-01 US US12/896,735 patent/US8575168B2/en not_active Expired - Fee Related
- 2010-10-01 WO PCT/US2010/051186 patent/WO2011044001A1/en not_active Ceased
- 2010-10-01 AU AU2010303780A patent/AU2010303780B2/en not_active Ceased
- 2010-10-07 AR ARP100103648A patent/AR078550A1/es unknown
- 2010-10-08 TW TW099134498A patent/TW201124400A/zh unknown
- 2010-10-08 UY UY0001032937A patent/UY32937A/es not_active Application Discontinuation
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2013507366A5 (OSRAM) | ||
| TWI358409B (en) | Heteroaryl substituted piperidine derivatives | |
| JP2006518763A5 (OSRAM) | ||
| AU2010303780B2 (en) | Compounds and compositions as modulators of GPR119 activity | |
| US8507512B2 (en) | Soluble guanylate cyclase activators | |
| US9763957B2 (en) | Autotaxin inhibitors | |
| US7678796B2 (en) | MGluR5 modulators I | |
| US9150575B2 (en) | Piperidinylpyrazolopyridine derivative | |
| JP2012528847A5 (OSRAM) | ||
| EP2556056A1 (en) | Modulators of the gpr119 receptor and the treatment of disorders related thereto | |
| TW201038586A (en) | Sulfonamide derivatives | |
| RU2009147733A (ru) | Пиридилпиперидновые антагонисты рецептора орексинов | |
| EA018703B1 (ru) | Соединения и композиции в качестве модуляторов активности gpr119 | |
| RU2010115260A (ru) | Соединения и композиции в качестве модуляторов активности gpr119 | |
| JP2017512184A5 (OSRAM) | ||
| WO2012117996A1 (ja) | Ｇｐｒ１１９作動薬 | |
| KR20110130476A (ko) | 대사성 장애의 치료용 화합물 | |
| WO2012145361A1 (en) | Modulators of the gpr119 receptor and the treatment of disorders related thereto | |
| WO2013055910A1 (en) | Modulators of the gpr119 receptor and the treatment of disorders related thereto | |
| JP2008513405A5 (OSRAM) | ||
| CN1980912A (zh) | 吡唑衍生物 | |
| JP2014001144A (ja) | Ｇｐｒ１１９作動薬 | |
| AU2016289079A1 (en) | Novel imide derivatives and use thereof as medicine | |
| WO2025224512A1 (ko) | Hsd17b13 (17-beta-hydroxysteroid dehydrogenase 13) 억제제로서 신규 화합물 및 이를 포함하는 약학적 조성물 | |
| TW201102374A (en) | Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment |