JP2007510629A - 新規ｍｃｈ受容体アンタゴニスト - Google Patents
新規ｍｃｈ受容体アンタゴニスト Download PDFInfo
- Publication number
- JP2007510629A JP2007510629A JP2006536645A JP2006536645A JP2007510629A JP 2007510629 A JP2007510629 A JP 2007510629A JP 2006536645 A JP2006536645 A JP 2006536645A JP 2006536645 A JP2006536645 A JP 2006536645A JP 2007510629 A JP2007510629 A JP 2007510629A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- phenoxy
- oxadiazol
- group
- ethylsulfanylmethyl
- 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
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- 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 title description 3
- 102000006953 melanin-concentrating hormone receptor activity proteins Human genes 0.000 title 1
- 239000002464 receptor antagonist Substances 0.000 title 1
- 229940044551 receptor antagonist Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 150
- 208000008589 Obesity Diseases 0.000 claims abstract description 20
- 235000020824 obesity Nutrition 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 101800002739 Melanin-concentrating hormone Proteins 0.000 claims abstract description 14
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 5
- ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 102000047659 melanin-concentrating hormone Human genes 0.000 claims abstract description 4
- -1 —O-aryl Chemical group 0.000 claims description 117
- 238000000034 method Methods 0.000 claims description 85
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 46
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 125000005647 linker group Chemical group 0.000 claims description 21
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 17
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- MVWGDEIHAMVCEQ-UHFFFAOYSA-N n,n-dimethyl-1-[1-methylsulfonyl-6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]indol-2-yl]methanamine Chemical compound C1=C2N(S(C)(=O)=O)C(CN(C)C)=CC2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 MVWGDEIHAMVCEQ-UHFFFAOYSA-N 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- ROYQQLMXAJXHOL-UHFFFAOYSA-N 5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-2-(2-piperidin-1-ylethyl)-3h-isoindol-1-one Chemical compound C1C2=CC(C=3OC(CSCCOC=4C=CC=CC=4)=NN=3)=CC=C2C(=O)N1CCN1CCCCC1 ROYQQLMXAJXHOL-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 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
- FGDTVLQNKWSOJO-UHFFFAOYSA-N n,n-dimethyl-1-[1-methylsulfonyl-5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]indol-2-yl]methanamine Chemical compound C=1C=C2N(S(C)(=O)=O)C(CN(C)C)=CC2=CC=1C(O1)=NN=C1CSCCOC1=CC=CC=C1 FGDTVLQNKWSOJO-UHFFFAOYSA-N 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- KGFUPXNXKMTREV-BTJKTKAUSA-N (z)-but-2-enedioic acid;n,n-dimethyl-1-[6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1h-indol-3-yl]methanamine Chemical compound OC(=O)\C=C/C(O)=O.C=1C=C2C(CN(C)C)=CNC2=CC=1C(O1)=NN=C1CSCCOC1=CC=CC=C1 KGFUPXNXKMTREV-BTJKTKAUSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- GTGMJBRHGYLFMK-UHFFFAOYSA-N n,n-dimethyl-1-[5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1-benzofuran-2-yl]methanamine;oxalic acid Chemical compound OC(=O)C(O)=O.C=1C=C2OC(CN(C)C)=CC2=CC=1C(O1)=NN=C1CSCCOC1=CC=CC=C1 GTGMJBRHGYLFMK-UHFFFAOYSA-N 0.000 claims description 4
- MEQGXPXYVTZVHQ-UHFFFAOYSA-N n,n-dimethyl-1-[6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1h-indol-2-yl]methanamine Chemical compound C1=C2NC(CN(C)C)=CC2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 MEQGXPXYVTZVHQ-UHFFFAOYSA-N 0.000 claims description 4
- CRPQTFQASNDDOH-UHFFFAOYSA-N n,n-dimethyl-1-[6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]naphthalen-2-yl]methanamine Chemical compound C1=CC2=CC(CN(C)C)=CC=C2C=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 CRPQTFQASNDDOH-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- FWMVAFWOQYSPSU-ODZAUARKSA-N C(\C=C/C(=O)O)(=O)O.O1N=NC=C1 Chemical compound C(\C=C/C(=O)O)(=O)O.O1N=NC=C1 FWMVAFWOQYSPSU-ODZAUARKSA-N 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 claims 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 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- FVZSEZORVQWGNL-UHFFFAOYSA-N n,n-dimethyl-1-[1-methyl-5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]indol-3-yl]methanamine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C2C(CN(C)C)=CN(C)C2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 FVZSEZORVQWGNL-UHFFFAOYSA-N 0.000 claims description 3
- UWTZXSGHOKFTGN-UHFFFAOYSA-N n,n-dimethyl-1-[1-methyl-6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]indol-2-yl]methanamine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C2N(C)C(CN(C)C)=CC2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 UWTZXSGHOKFTGN-UHFFFAOYSA-N 0.000 claims description 3
- CZUYHBPJKIDCQA-UHFFFAOYSA-N n,n-dimethyl-1-[5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1h-indol-3-yl]methanamine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C2C(CN(C)C)=CNC2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 CZUYHBPJKIDCQA-UHFFFAOYSA-N 0.000 claims description 3
- KXXVTHPNMUULHT-UHFFFAOYSA-N n,n-dimethyl-1-[6-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1-benzofuran-2-yl]methanamine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C2OC(CN(C)C)=CC2=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 KXXVTHPNMUULHT-UHFFFAOYSA-N 0.000 claims description 3
- ZUYUUAIKJFTKND-UHFFFAOYSA-N n,n-dimethyl-4-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]naphthalen-1-amine Chemical compound C12=CC=CC=C2C(N(C)C)=CC=C1C(O1)=NN=C1CSCCOC1=CC=CC=C1 ZUYUUAIKJFTKND-UHFFFAOYSA-N 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 2
- 125000005518 carboxamido group Chemical group 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 2
- 239000000651 prodrug Substances 0.000 claims description 2
- 229940002612 prodrug Drugs 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims 2
- BDJAEZRIGNCQBZ-UHFFFAOYSA-N methylcyclobutane Chemical compound CC1CCC1 BDJAEZRIGNCQBZ-UHFFFAOYSA-N 0.000 claims 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 claims 2
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methylcyclopentane Chemical compound CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 claims 2
- 125000002393 azetidinyl group Chemical group 0.000 claims 1
- PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 claims 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 claims 1
- VNXBKJFUJUWOCW-UHFFFAOYSA-N methylcyclopropane Chemical compound CC1CC1 VNXBKJFUJUWOCW-UHFFFAOYSA-N 0.000 claims 1
- QMZSETBPQAVBMN-UHFFFAOYSA-N n,n-dimethyl-1-[5-[5-(2-phenoxyethylsulfanylmethyl)-1,3,4-oxadiazol-2-yl]-1h-indol-2-yl]methanamine Chemical compound C=1C=C2NC(CN(C)C)=CC2=CC=1C(O1)=NN=C1CSCCOC1=CC=CC=C1 QMZSETBPQAVBMN-UHFFFAOYSA-N 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 239000003667 hormone antagonist Substances 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 95
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 74
- 239000000243 solution Substances 0.000 description 70
- 238000010168 coupling process Methods 0.000 description 64
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
- 239000007787 solid Substances 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 46
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 239000002904 solvent Substances 0.000 description 46
- 238000005859 coupling reaction Methods 0.000 description 44
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 238000004587 chromatography analysis Methods 0.000 description 34
- 230000008878 coupling Effects 0.000 description 34
- 238000007429 general method Methods 0.000 description 34
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000003921 oil Substances 0.000 description 30
- 235000019198 oils Nutrition 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- 238000004458 analytical method Methods 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- 239000002585 base Substances 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 24
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 20
- 239000012442 inert solvent Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 18
- 235000019502 Orange oil Nutrition 0.000 description 17
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 17
- 239000010502 orange oil Substances 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 16
- 230000010933 acylation Effects 0.000 description 16
- 238000005917 acylation reaction Methods 0.000 description 16
- 150000001412 amines Chemical class 0.000 description 15
- 238000005755 formation reaction Methods 0.000 description 13
- 125000002524 organometallic group Chemical group 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- 238000005694 sulfonylation reaction Methods 0.000 description 13
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 230000006103 sulfonylation Effects 0.000 description 12
- 239000004202 carbamide Substances 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- 102400001132 Melanin-concentrating hormone Human genes 0.000 description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- 238000005804 alkylation reaction Methods 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical group [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- LJZPPWWHKPGCHS-UHFFFAOYSA-N propargyl chloride Chemical compound ClCC#C LJZPPWWHKPGCHS-UHFFFAOYSA-N 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 229960002073 sertraline Drugs 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
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 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
- 229940095064 tartrate Drugs 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- DHWBYAACHDUFAT-UHFFFAOYSA-N tricyclopentylphosphane Chemical compound C1CCCC1P(C1CCCC1)C1CCCC1 DHWBYAACHDUFAT-UHFFFAOYSA-N 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 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
- 230000001960 triggered effect Effects 0.000 description 1
- IGNTWNVBGLNYDV-UHFFFAOYSA-N triisopropylphosphine Chemical compound CC(C)P(C(C)C)C(C)C IGNTWNVBGLNYDV-UHFFFAOYSA-N 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940002552 xenical Drugs 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US51344903P | 2003-10-22 | 2003-10-22 | |
| PCT/US2004/032314 WO2005040157A2 (en) | 2003-10-22 | 2004-10-21 | Novel mch receptor antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007510629A true JP2007510629A (ja) | 2007-04-26 |
| JP2007510629A5 JP2007510629A5 (https=) | 2007-11-22 |
Family
ID=34520102
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006536645A Pending JP2007510629A (ja) | 2003-10-22 | 2004-10-21 | 新規ｍｃｈ受容体アンタゴニスト |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20070135485A1 (https=) |
| EP (1) | EP1723126A2 (https=) |
| JP (1) | JP2007510629A (https=) |
| CA (1) | CA2542220A1 (https=) |
| WO (1) | WO2005040157A2 (https=) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1657242A4 (en) | 2003-08-15 | 2008-10-29 | Banyu Pharma Co Ltd | imidazopyridine |
| TW200613272A (en) | 2004-08-13 | 2006-05-01 | Astrazeneca Ab | Isoindolone compounds and their use as metabotropic glutamate receptor potentiators |
| JP5031745B2 (ja) * | 2005-08-12 | 2012-09-26 | アストラゼネカ アクチボラグ | 代謝型グルタミン酸受容体増強性イソインドロン |
| US7807706B2 (en) | 2005-08-12 | 2010-10-05 | Astrazeneca Ab | Metabotropic glutamate-receptor-potentiating isoindolones |
| RU2008120619A (ru) * | 2005-10-26 | 2009-12-10 | БЕРИНГЕР ИНГЕЛЬХАЙМ ИНТЕРНАЦИОНАЛЬ ГмбХ (DE) | (гетеро)арилы, обладающие антагонистической активностью по отношению к меланинконцентрирующему гормону |
| CA2626220A1 (en) | 2005-12-21 | 2007-06-28 | Janssen Pharmaceutica N.V. | Novel substituted pyrazinone derivatives for use in mch-1 mediated diseases |
| US8492378B2 (en) | 2006-08-03 | 2013-07-23 | Takeda Pharmaceutical Company Limited | GSK-3β inhibitor |
| EP2102208B1 (en) | 2006-12-05 | 2014-04-23 | Janssen Pharmaceutica NV | Novel substituted diaza spiro pyridinone derivatives for use in mch-1 mediated diseases |
| TWI417100B (zh) | 2007-06-07 | 2013-12-01 | Astrazeneca Ab | 二唑衍生物及其作為代謝型麩胺酸受體增效劑-８４２之用途 |
| US7790760B2 (en) | 2008-06-06 | 2010-09-07 | Astrazeneca Ab | Metabotropic glutamate receptor isoxazole ligands and their use as potentiators 286 |
| US8586792B2 (en) | 2011-12-28 | 2013-11-19 | Divi's Laboratories Ltd. | Process for the preparation of 4-iodo-3-nitrobenzamide |
| SG11201407999TA (en) | 2012-06-01 | 2015-01-29 | Univ Singapore | ICMT Inhibitors |
| WO2014078733A1 (en) | 2012-11-16 | 2014-05-22 | The Regents Of The University Of California | Pictet-spengler ligation for protein chemical modification |
| US9310374B2 (en) | 2012-11-16 | 2016-04-12 | Redwood Bioscience, Inc. | Hydrazinyl-indole compounds and methods for producing a conjugate |
| EP3373937B1 (en) | 2015-11-09 | 2021-12-22 | R.P. Scherer Technologies, LLC | Anti-cd22 antibody-maytansine conjugates and methods of use thereof |
| US12441707B2 (en) | 2019-12-30 | 2025-10-14 | Tyra Biosciences, Inc. | Indazole compounds |
| KR20230152654A (ko) | 2020-12-30 | 2023-11-03 | 타이라 바이오사이언시스, 인크. | 키나아제 억제제로서의 인다졸 화합물 |
| US20240300939A1 (en) | 2021-06-14 | 2024-09-12 | Scorpion Therapeutics, Inc. | Urea derivatives which can be used to treat cancer |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06100558A (ja) * | 1990-01-17 | 1994-04-12 | Merck Sharp & Dohme Ltd | インドール置換５員複素芳香環化合物 |
| WO1995028400A1 (en) * | 1994-04-14 | 1995-10-26 | Glaxo Group Limited | Novel benzofused 5-membered heterocyclic rings for the treatment of migraine |
| JP2001518925A (ja) * | 1997-03-24 | 2001-10-16 | アール．ピー．シェーラー リミテッド | 医薬組成物 |
| WO2002036590A1 (en) * | 2000-11-02 | 2002-05-10 | Amrad Operations Pty Ltd | 3-oxadiazol-5-yl-1-aminoalkyl-1h-indole derivatives |
| WO2002074758A2 (en) * | 2001-03-16 | 2002-09-26 | Abbott Laboratories | Novel amines as histamine-3 receptor ligands and their therapeutic applications |
| JP2005529923A (ja) * | 2002-05-13 | 2005-10-06 | イーライ・リリー・アンド・カンパニー | 肥満および糖尿病の治療におけるメラニン凝集ホルモンアンタゴニストとして使用するための多環式化合物 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2204616C (en) | 1995-09-18 | 2002-12-17 | Ranjan Mukherjee | Ppar gamma antagonists for treating obesity |
| WO1997020822A1 (en) | 1995-12-01 | 1997-06-12 | Novartis Ag | Quinazolin-2,4-diazirines as npy receptor antagonist |
| AU7692996A (en) | 1995-12-01 | 1997-06-27 | Ciba-Geigy Ag | Receptor antagonists |
| AU1328197A (en) | 1995-12-01 | 1997-06-19 | Synaptic Pharmaceutical Corporation | Aryl sulfonamide and sulfamide derivatives and uses thereof |
| AU7692696A (en) | 1995-12-01 | 1997-06-27 | Novartis Ag | Heteroaryl derivatives |
| AU7626496A (en) | 1995-12-01 | 1997-06-27 | Ciba-Geigy Ag | Heteroaryl compounds |
| AU721452B2 (en) | 1996-02-02 | 2000-07-06 | Merck & Co., Inc. | Antidiabetic agents |
| ATE293963T1 (de) | 1996-02-02 | 2005-05-15 | Merck & Co Inc | Verfahren zur behandlung von diabetes und verwandter krankheitszustände. |
| WO1997028149A1 (en) | 1996-02-02 | 1997-08-07 | Merck & Co., Inc. | Method for raising hdl cholesterol levels |
| WO1997028137A1 (en) | 1996-02-02 | 1997-08-07 | Merck & Co., Inc. | Heterocyclic derivatives as antidiabetic and antiobesity agents |
| GB9606805D0 (en) | 1996-03-30 | 1996-06-05 | Glaxo Wellcome Inc | Medicaments |
| EP1218336A2 (en) * | 1999-09-20 | 2002-07-03 | Takeda Chemical Industries, Ltd. | Melanin concentrating hormone antagonist |
| WO2003087046A1 (en) * | 2002-04-09 | 2003-10-23 | 7Tm Pharma A/S | Novel aminotetraline compounds for use in mch receptor related disorders |
-
2004
- 2004-10-21 CA CA002542220A patent/CA2542220A1/en not_active Abandoned
- 2004-10-21 US US10/575,815 patent/US20070135485A1/en not_active Abandoned
- 2004-10-21 JP JP2006536645A patent/JP2007510629A/ja active Pending
- 2004-10-21 WO PCT/US2004/032314 patent/WO2005040157A2/en not_active Ceased
- 2004-10-21 EP EP04809828A patent/EP1723126A2/en not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06100558A (ja) * | 1990-01-17 | 1994-04-12 | Merck Sharp & Dohme Ltd | インドール置換５員複素芳香環化合物 |
| WO1995028400A1 (en) * | 1994-04-14 | 1995-10-26 | Glaxo Group Limited | Novel benzofused 5-membered heterocyclic rings for the treatment of migraine |
| JP2001518925A (ja) * | 1997-03-24 | 2001-10-16 | アール．ピー．シェーラー リミテッド | 医薬組成物 |
| WO2002036590A1 (en) * | 2000-11-02 | 2002-05-10 | Amrad Operations Pty Ltd | 3-oxadiazol-5-yl-1-aminoalkyl-1h-indole derivatives |
| WO2002074758A2 (en) * | 2001-03-16 | 2002-09-26 | Abbott Laboratories | Novel amines as histamine-3 receptor ligands and their therapeutic applications |
| JP2005529923A (ja) * | 2002-05-13 | 2005-10-06 | イーライ・リリー・アンド・カンパニー | 肥満および糖尿病の治療におけるメラニン凝集ホルモンアンタゴニストとして使用するための多環式化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1723126A2 (en) | 2006-11-22 |
| WO2005040157A2 (en) | 2005-05-06 |
| US20070135485A1 (en) | 2007-06-14 |
| WO2005040157A3 (en) | 2006-09-28 |
| CA2542220A1 (en) | 2005-05-06 |
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