JP2002516321A - インスリン耐性および高血糖の治療に有用なベンゾチオフェン、ベンゾフラン、およびインドール - Google Patents

インスリン耐性および高血糖の治療に有用なベンゾチオフェン、ベンゾフラン、およびインドール

Info

Publication number: JP2002516321A
Authority: JP; Japan
Prior art keywords: carbon atoms; dimethyl; naphtho; bromo; thiophen
Prior art date: 1998-05-12
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

Application number

JP2000550841A

Other languages

English (en)

Japanese (ja)

Inventor

ジェイ・エドワード・ローベル

アーリーン・ジョーン・ディートリック

マデリーン・ミヨコ・アンテイン

Original Assignee

アメリカン・ホーム・プロダクツ・コーポレイション

Priority date (The priority date 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 date listed.)

1998-05-12

Filing date

1999-05-10

Publication date

2002-06-04

1999-05-10 Application filed by アメリカン・ホーム・プロダクツ・コーポレイション filed Critical アメリカン・ホーム・プロダクツ・コーポレイション

2002-06-04 Publication of JP2002516321A publication Critical patent/JP2002516321A/ja

Status Pending legal-status Critical Current

Links

208000001072 type 2 diabetes mellitus Diseases 0.000 title claims abstract description 27
206010022489 Insulin Resistance Diseases 0.000 title claims abstract description 17
201000001421 hyperglycemia Diseases 0.000 title claims abstract description 11
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title description 6
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title description 6
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title description 3
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title description 3
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 63
150000003839 salts Chemical class 0.000 claims abstract description 52
208000030159 metabolic disease Diseases 0.000 claims abstract description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 561
125000000217 alkyl group Chemical group 0.000 claims description 335
-1 nitro, amino Chemical group 0.000 claims description 327
150000001875 compounds Chemical class 0.000 claims description 287
125000003118 aryl group Chemical group 0.000 claims description 194
229910052736 halogen Inorganic materials 0.000 claims description 164
150000002367 halogens Chemical class 0.000 claims description 163
125000003710 aryl alkyl group Chemical group 0.000 claims description 153
229910052760 oxygen Inorganic materials 0.000 claims description 152
229910052717 sulfur Inorganic materials 0.000 claims description 152
229910052739 hydrogen Inorganic materials 0.000 claims description 130
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 123
125000003545 alkoxy group Chemical group 0.000 claims description 91
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 90
125000005163 aryl sulfanyl group Chemical group 0.000 claims description 88
229910052757 nitrogen Inorganic materials 0.000 claims description 82
125000004414 alkyl thio group Chemical group 0.000 claims description 79
239000001257 hydrogen Substances 0.000 claims description 74
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 37
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 25
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 24
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 description 19
239000008103 glucose Substances 0.000 claims description 19
229940125396 insulin Drugs 0.000 claims description 18
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 17
102000004877 Insulin Human genes 0.000 claims description 17
108090001061 Insulin Proteins 0.000 claims description 17
229910052799 carbon Inorganic materials 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 14
239000003814 drug Substances 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
235000019260 propionic acid Nutrition 0.000 claims description 9
230000005764 inhibitory process Effects 0.000 claims description 8
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 8
YMRIDJQAEZFTSC-UHFFFAOYSA-N 2,3-dihydro-1h-tetrazole Chemical compound N1NC=NN1 YMRIDJQAEZFTSC-UHFFFAOYSA-N 0.000 claims description 7
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 7
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 6
125000004104 aryloxy group Chemical group 0.000 claims description 6
125000006310 cycloalkyl amino group Chemical group 0.000 claims description 6
DADVNWPKORBKAA-UHFFFAOYSA-N 6-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-nitrocyclohexa-2,4-dien-1-ol Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC(Br)([N+]([O-])=O)C(O)C=C1 DADVNWPKORBKAA-UHFFFAOYSA-N 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
125000002897 diene group Chemical group 0.000 claims description 5
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
229950009215 phenylbutanoic acid Drugs 0.000 claims description 5
DTOSLKDCIXNWRZ-UHFFFAOYSA-N 2,6-dibromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenol Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC(Br)=C(O)C(Br)=C1 DTOSLKDCIXNWRZ-UHFFFAOYSA-N 0.000 claims description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 4
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
FYDTTWDGNADGFK-UHFFFAOYSA-N 4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenol Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC=C(O)C=C1 FYDTTWDGNADGFK-UHFFFAOYSA-N 0.000 claims description 3
230000002401 inhibitory effect Effects 0.000 claims description 3
FXORFBFZAHBWIC-MRXNPFEDSA-N (2r)-2-[2,6-dibromo-4-(2,3-dimethyl-9-phenylsulfanylbenzo[f][1]benzothiol-4-yl)phenoxy]propanoic acid Chemical compound C1=C(Br)C(O[C@H](C)C(O)=O)=C(Br)C=C1C(C1=CC=CC=C11)=C(C(C)=C(C)S2)C2=C1SC1=CC=CC=C1 FXORFBFZAHBWIC-MRXNPFEDSA-N 0.000 claims description 2
VOHWEAVTNNNDAV-SSEXGKCCSA-N (2r)-2-[2-cyclopentyl-4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=CC=C(C=C1C1CCCC1)C=1C2=CC=CC=C2C=C2SC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 VOHWEAVTNNNDAV-SSEXGKCCSA-N 0.000 claims description 2
XYMFWFMKKQGAOQ-QGZVFWFLSA-N (2r)-2-[2-cyclopentyl-4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenoxy]propanoic acid Chemical compound OC(=O)[C@@H](C)OC1=CC=C(C=2C3=CC=CC=C3C=C3SC(C)=C(C)C3=2)C=C1C1CCCC1 XYMFWFMKKQGAOQ-QGZVFWFLSA-N 0.000 claims description 2
PWGGPFARYFWXFE-AREMUKBSSA-N (2r)-2-[4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-dimethylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=C(C)C=C(C=C1C)C=1C2=CC=CC=C2C=C2SC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 PWGGPFARYFWXFE-AREMUKBSSA-N 0.000 claims description 2
GOKOXSOVGCALER-RUZDIDTESA-N (2r)-2-[4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-fluorophenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=CC=C(C=C1F)C=1C2=CC=CC=C2C=C2SC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 GOKOXSOVGCALER-RUZDIDTESA-N 0.000 claims description 2
DEDAJYFSMOZFMF-MUUNZHRXSA-N (2r)-2-[4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-propan-2-ylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=CC=C(C=C1C(C)C)C=1C2=CC=CC=C2C=C2SC(C)=C(C)C2=1)C(O)=O)C1=CC=CC=C1 DEDAJYFSMOZFMF-MUUNZHRXSA-N 0.000 claims description 2
YJSKKYXMKLNJHQ-UHFFFAOYSA-N 2,6-dibromo-4-[9-bromo-2-(diethylaminomethyl)-3-methylbenzo[f][1]benzothiol-4-yl]phenol Chemical compound C=12C(C)=C(CN(CC)CC)SC2=C(Br)C2=CC=CC=C2C=1C1=CC(Br)=C(O)C(Br)=C1 YJSKKYXMKLNJHQ-UHFFFAOYSA-N 0.000 claims description 2
VLEGJCJPDDFESC-UHFFFAOYSA-N 2,6-dibromo-4-[9-bromo-3-methyl-2-(morpholin-4-ylmethyl)benzo[f][1]benzothiol-4-yl]phenol Chemical compound S1C2=C(Br)C3=CC=CC=C3C(C=3C=C(Br)C(O)=C(Br)C=3)=C2C(C)=C1CN1CCOCC1 VLEGJCJPDDFESC-UHFFFAOYSA-N 0.000 claims description 2
BMVMSCADCQQBNY-UHFFFAOYSA-N 2-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenol Chemical compound C=12C(C)=C(C)SC2=CC2=CC=CC=C2C=1C1=CC=CC=C1O BMVMSCADCQQBNY-UHFFFAOYSA-N 0.000 claims description 2
YFTHHCRTKXURKH-UHFFFAOYSA-N 2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-di(propan-2-yl)phenoxy]acetic acid Chemical compound CC(C)C1=C(OCC(O)=O)C(C(C)C)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 YFTHHCRTKXURKH-UHFFFAOYSA-N 0.000 claims description 2
JYLCIXQRFYGEAE-UHFFFAOYSA-N 2-amino-6-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenol Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC(N)=C(O)C(Br)=C1 JYLCIXQRFYGEAE-UHFFFAOYSA-N 0.000 claims description 2
KMOBQTBRQNRVQL-UHFFFAOYSA-N 2-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-propan-2-ylphenol Chemical compound BrC1=C(O)C(C(C)C)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 KMOBQTBRQNRVQL-UHFFFAOYSA-N 0.000 claims description 2
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
ZQDKWFBAFUXBST-UHFFFAOYSA-N 4-(2,3-dimethyl-9-phenylsulfanylbenzo[f][1]benzothiol-4-yl)phenol Chemical compound C12=CC=CC=C2C(C=2C=CC(O)=CC=2)=C2C(C)=C(C)SC2=C1SC1=CC=CC=C1 ZQDKWFBAFUXBST-UHFFFAOYSA-N 0.000 claims description 2
CMHYVMDFPSLQGX-UHFFFAOYSA-N 4-(2,3-dimethylbenzo[f][1]benzofuran-4-yl)-2,6-diethylphenol Chemical compound CCC1=C(O)C(CC)=CC(C=2C3=CC=CC=C3C=C3OC(C)=C(C)C3=2)=C1 CMHYVMDFPSLQGX-UHFFFAOYSA-N 0.000 claims description 2
OYHZWLRDRACBCR-UHFFFAOYSA-N 4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-nitrophenol Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC=C(O)C([N+]([O-])=O)=C1 OYHZWLRDRACBCR-UHFFFAOYSA-N 0.000 claims description 2
CURDELKOPHWSTA-UHFFFAOYSA-N 4-[9-bromo-2-(diethylaminomethyl)-3-methylbenzo[f][1]benzothiol-4-yl]phenol Chemical compound C=12C(C)=C(CN(CC)CC)SC2=C(Br)C2=CC=CC=C2C=1C1=CC=C(O)C=C1 CURDELKOPHWSTA-UHFFFAOYSA-N 0.000 claims description 2
BFRRBIRWMQUEGS-UHFFFAOYSA-N 9-bromo-4-(3-bromo-2-methoxy-5-nitrophenyl)-2,3-dimethylbenzo[f][1]benzothiole Chemical compound COC1=C(Br)C=C([N+]([O-])=O)C=C1C1=C(C(C)=C(C)S2)C2=C(Br)C2=CC=CC=C12 BFRRBIRWMQUEGS-UHFFFAOYSA-N 0.000 claims description 2
KHRNWPFHHRZBJP-UHFFFAOYSA-N [4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenyl] methanesulfonate Chemical compound C=12C(C)=C(C)SC2=CC2=CC=CC=C2C=1C1=CC=C(OS(C)(=O)=O)C=C1 KHRNWPFHHRZBJP-UHFFFAOYSA-N 0.000 claims description 2
YBGOWILNHUTXCX-UHFFFAOYSA-N [4-(9-iodo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenyl] methanesulfonate Chemical compound C=12C(C)=C(C)SC2=C(I)C2=CC=CC=C2C=1C1=CC=C(OS(C)(=O)=O)C=C1 YBGOWILNHUTXCX-UHFFFAOYSA-N 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 28
241000124008 Mammalia Species 0.000 claims 6
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims 5
230000001404 mediated effect Effects 0.000 claims 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 2
BPCAZHXMWHBCMV-GDLZYMKVSA-N (2r)-2-[2,6-dibromo-4-(2,3-dimethyl-9-phenylsulfanylbenzo[f][1]benzothiol-4-yl)phenoxy]-3-phenylpropanoic acid Chemical compound C12=CC=CC=C2C(C=2C=C(Br)C(O[C@H](CC=3C=CC=CC=3)C(O)=O)=C(Br)C=2)=C2C(C)=C(C)SC2=C1SC1=CC=CC=C1 BPCAZHXMWHBCMV-GDLZYMKVSA-N 0.000 claims 1
JGIRDKSSVIOQPU-SSEXGKCCSA-N (2r)-2-[4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-di(propan-2-yl)phenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=C(C(C)C)C=C(C=C1C(C)C)C=1C2=CC=CC=C2C=C2SC(C)=C(C)C2=1)C(O)=O)C1=CC=CC=C1 JGIRDKSSVIOQPU-SSEXGKCCSA-N 0.000 claims 1
KERJZLJLWIJSLZ-HHHXNRCGSA-N (2r)-2-[4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-ethylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=CC=C(C=C1CC)C=1C2=CC=CC=C2C=C2SC(C)=C(C)C2=1)C(O)=O)C1=CC=CC=C1 KERJZLJLWIJSLZ-HHHXNRCGSA-N 0.000 claims 1
LOWURJWSVHYTAV-JWPKJQAESA-N (2r)-2-[4-(9-bromo-2,3-dimethyl-1-oxobenzo[f][1]benzothiol-4-yl)-2,6-dimethylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=C(C)C=C(C=C1C)C=1C2=CC=CC=C2C(Br)=C2S(=O)C(C)=C(C=12)C)C(O)=O)C1=CC=CC=C1 LOWURJWSVHYTAV-JWPKJQAESA-N 0.000 claims 1
INYXFAWXXWVFBP-MRXNPFEDSA-N (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-cyclopentylphenoxy]propanoic acid Chemical compound OC(=O)[C@@H](C)OC1=CC=C(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)C=C1C1CCCC1 INYXFAWXXWVFBP-MRXNPFEDSA-N 0.000 claims 1
KFKYBCSQCXMALN-AREMUKBSSA-N (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-ethylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=CC=C(C=C1CC)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C(O)=O)C1=CC=CC=C1 KFKYBCSQCXMALN-AREMUKBSSA-N 0.000 claims 1
GBQTYLAQGXLQOV-UHFFFAOYSA-N 2,6-dibromo-4-(2,3-dimethyl-9-phenylsulfanylbenzo[f][1]benzothiol-4-yl)phenol Chemical compound C12=CC=CC=C2C(C=2C=C(Br)C(O)=C(Br)C=2)=C2C(C)=C(C)SC2=C1SC1=CC=CC=C1 GBQTYLAQGXLQOV-UHFFFAOYSA-N 0.000 claims 1
IWVDPVRBDLFFKF-UHFFFAOYSA-N 2-[2,6-dibromo-4-[9-bromo-3-methyl-2-(morpholin-4-ylmethyl)benzo[f][1]benzothiol-4-yl]phenoxy]propanoic acid Chemical compound C1=C(Br)C(OC(C)C(O)=O)=C(Br)C=C1C1=C(C(C)=C(CN2CCOCC2)S2)C2=C(Br)C2=CC=CC=C12 IWVDPVRBDLFFKF-UHFFFAOYSA-N 0.000 claims 1
CZLNLNKNODCPPF-UHFFFAOYSA-N 2-[3-bromo-5-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-methoxyanilino]acetic acid Chemical compound C1=C(NCC(O)=O)C(OC)=C(Br)C=C1C1=C(C(C)=C(C)S2)C2=C(Br)C2=CC=CC=C12 CZLNLNKNODCPPF-UHFFFAOYSA-N 0.000 claims 1
PFBBZEQYIVORNG-UHFFFAOYSA-N 2-[6-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-nitrocyclohexa-2,4-dien-1-yl]oxyacetic acid Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC(Br)([N+]([O-])=O)C(OCC(O)=O)C=C1 PFBBZEQYIVORNG-UHFFFAOYSA-N 0.000 claims 1
IFSFZIDCRMWDQW-UHFFFAOYSA-N 2-amino-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenol Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC=C(O)C(N)=C1 IFSFZIDCRMWDQW-UHFFFAOYSA-N 0.000 claims 1
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CKMCBFXLTSUJAW-FYJJZCTHSA-N methyl (2r)-2-[2-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-butan-2-ylphenoxy]-3-phenylpropanoate Chemical compound C([C@@H](OC1=C(Br)C=C(C=C1C(C)CC)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C(=O)OC)C1=CC=CC=C1 CKMCBFXLTSUJAW-FYJJZCTHSA-N 0.000 description 1
SXEQQROCBMXXBO-GDLZYMKVSA-N methyl (2r)-2-[2-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-cyclopentylphenoxy]-3-phenylpropanoate Chemical compound C([C@H](C(=O)OC)OC=1C(=CC(=CC=1Br)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C1CCCC1)C1=CC=CC=C1 SXEQQROCBMXXBO-GDLZYMKVSA-N 0.000 description 1
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NZKDYDDKOVDCBQ-MUUNZHRXSA-N methyl (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzofuran-4-yl)-2,6-diethylphenoxy]-3-phenylpropanoate Chemical compound C([C@@H](OC1=C(CC)C=C(C=C1CC)C=1C2=CC=CC=C2C(Br)=C2OC(C)=C(C)C2=1)C(=O)OC)C1=CC=CC=C1 NZKDYDDKOVDCBQ-MUUNZHRXSA-N 0.000 description 1
FCJWFFVJOJGQOF-SSEXGKCCSA-N methyl (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-di(propan-2-yl)phenoxy]-3-phenylpropanoate Chemical compound C([C@H](C(=O)OC)OC=1C(=CC(=CC=1C(C)C)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C(C)C)C1=CC=CC=C1 FCJWFFVJOJGQOF-SSEXGKCCSA-N 0.000 description 1
SRALLAXTRPIFAY-MUUNZHRXSA-N methyl (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-diethylphenoxy]-3-phenylpropanoate Chemical compound C([C@@H](OC1=C(CC)C=C(C=C1CC)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C(=O)OC)C1=CC=CC=C1 SRALLAXTRPIFAY-MUUNZHRXSA-N 0.000 description 1
CMSDGXFQALPQEZ-QGZVFWFLSA-N methyl (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-cyclopentylphenoxy]propanoate Chemical compound COC(=O)[C@@H](C)OC1=CC=C(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)C=C1C1CCCC1 CMSDGXFQALPQEZ-QGZVFWFLSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/92—Naphthofurans; Hydrogenated naphthofurans
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/74—Naphthothiophenes

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Diabetes (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Endocrinology (AREA)
Hematology (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Furan Compounds (AREA)

JP2000550841A 1998-05-12 1999-05-10 インスリン耐性および高血糖の治療に有用なベンゾチオフェン、ベンゾフラン、およびインドール Pending JP2002516321A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US7671298A	1998-05-12	1998-05-12
US09/076,712		1998-05-12
PCT/US1999/010209 WO1999061435A1 (en)	1998-05-12	1999-05-10	Benzothiophenes, benzofurans, and indoles useful in the treatment of insulin resistance and hyperglycemia

Publications (1)

Publication Number	Publication Date
JP2002516321A true JP2002516321A (ja)	2002-06-04

Family

ID=22133746

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP2000550841A Pending JP2002516321A (ja)	1998-05-12	1999-05-10	インスリン耐性および高血糖の治療に有用なベンゾチオフェン、ベンゾフラン、およびインドール

Country Status (22)

Country	Link
EP (1)	EP1077969A1 (bg)
JP (1)	JP2002516321A (bg)
KR (1)	KR20010043539A (bg)
CN (1)	CN1308626A (bg)
AR (1)	AR015294A1 (bg)
AU (1)	AU756337B2 (bg)
BG (1)	BG104918A (bg)
BR (1)	BR9911779A (bg)
CA (1)	CA2330620A1 (bg)
EA (1)	EA200001175A1 (bg)
EE (1)	EE200000653A (bg)
HR (1)	HRP20000767A2 (bg)
HU (1)	HUP0101792A3 (bg)
ID (1)	ID26244A (bg)
IL (1)	IL139132A0 (bg)
NO (1)	NO20005677L (bg)
PL (1)	PL344081A1 (bg)
SK (1)	SK16992000A3 (bg)
TR (1)	TR200003333T2 (bg)
TW (1)	TW510900B (bg)
WO (1)	WO1999061435A1 (bg)
ZA (1)	ZA200005961B (bg)

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JP2006508082A (ja) *	2002-10-14	2006-03-09	クラリアント・ライフ・サイエンス・モレキユールズ（イタリア）・エツセ・ピー・アー	２，５−二置換３−アルキルチオフェンの調製方法
JP2012511558A (ja) *	2008-12-10	2012-05-24	ザ・ユニヴァーシティ・オヴ・ダンディー	疼痛の治療で使用するための化合物

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1999
- 1999-05-01 HR HR20000767A patent/HRP20000767A2/hr not_active Application Discontinuation
- 1999-05-10 HU HU0101792A patent/HUP0101792A3/hu unknown
- 1999-05-10 AU AU38939/99A patent/AU756337B2/en not_active Ceased
- 1999-05-10 BR BR9911779-7A patent/BR9911779A/pt not_active IP Right Cessation
- 1999-05-10 EA EA200001175A patent/EA200001175A1/ru unknown
- 1999-05-10 IL IL13913299A patent/IL139132A0/xx unknown
- 1999-05-10 ID IDW20002311A patent/ID26244A/id unknown
- 1999-05-10 CA CA002330620A patent/CA2330620A1/en not_active Abandoned
- 1999-05-10 TR TR2000/03333T patent/TR200003333T2/xx unknown
- 1999-05-10 CN CN99808367A patent/CN1308626A/zh active Pending
- 1999-05-10 TW TW088107532A patent/TW510900B/zh active
- 1999-05-10 PL PL99344081A patent/PL344081A1/xx not_active Application Discontinuation
- 1999-05-10 EP EP99921829A patent/EP1077969A1/en not_active Withdrawn
- 1999-05-10 EE EEP200000653A patent/EE200000653A/xx unknown
- 1999-05-10 SK SK1699-2000A patent/SK16992000A3/sk unknown
- 1999-05-10 KR KR1020007012649A patent/KR20010043539A/ko not_active Withdrawn
- 1999-05-10 WO PCT/US1999/010209 patent/WO1999061435A1/en not_active Application Discontinuation
- 1999-05-10 JP JP2000550841A patent/JP2002516321A/ja active Pending
- 1999-05-12 AR ARP990102229A patent/AR015294A1/es unknown
2000
- 2000-10-24 ZA ZA200005961A patent/ZA200005961B/xx unknown
- 2000-11-07 BG BG104918A patent/BG104918A/bg unknown
- 2000-11-10 NO NO20005677A patent/NO20005677L/no not_active Application Discontinuation

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2006508082A (ja) *	2002-10-14	2006-03-09	クラリアント・ライフ・サイエンス・モレキユールズ（イタリア）・エツセ・ピー・アー	２，５−二置換３−アルキルチオフェンの調製方法
JP2012511558A (ja) *	2008-12-10	2012-05-24	ザ・ユニヴァーシティ・オヴ・ダンディー	疼痛の治療で使用するための化合物

Also Published As

Publication number	Publication date
NO20005677L (no)	2000-12-05
CN1308626A (zh)	2001-08-15
WO1999061435A1 (en)	1999-12-02
ID26244A (id)	2000-12-07
HUP0101792A3 (en)	2003-01-28
TR200003333T2 (tr)	2001-02-21
CA2330620A1 (en)	1999-12-02
BR9911779A (pt)	2001-02-06
KR20010043539A (ko)	2001-05-25
EE200000653A (et)	2002-04-15
EA200001175A1 (ru)	2001-06-25
HRP20000767A2 (en)	2001-10-31
AR015294A1 (es)	2001-04-18
AU756337B2 (en)	2003-01-09
PL344081A1 (en)	2001-09-24
NO20005677D0 (no)	2000-11-10
SK16992000A3 (sk)	2001-04-09
TW510900B (en)	2002-11-21
HUP0101792A2 (hu)	2002-01-28
AU3893999A (en)	1999-12-13
ZA200005961B (en)	2001-10-24
EP1077969A1 (en)	2001-02-28
IL139132A0 (en)	2001-11-25
BG104918A (bg)	2001-08-31

Publication	Publication Date	Title
JP2002516321A (ja)	2002-06-04	インスリン耐性および高血糖の治療に有用なベンゾチオフェン、ベンゾフラン、およびインドール
US6251936B1 (en)	2001-06-26	Benzothiophenes, benzofurans, and indoles useful in the treatment of insulin resistance and hyperglycemia
JP2002514638A (ja)	2002-05-21	インスリン抵抗性および高血糖症の治療に有用な１１−アリール−ベンゾ［ｂ］ナフト［２，３−ｄ］フラン類および１１−アリール−ベンゾ［ｂ］ナフト［２，３−ｄ］チオフェン類
JP4476624B2 (ja)	2010-06-09	プラスミノゲンアクチベーターインヒビター１（ｐａｉ−１）のインヒビターとしてのナフチルベンゾフラン誘導体
US6166069A (en)	2000-12-26	Phenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
US5223510A (en)	1993-06-29	Alkylaminoalkyl derivatives of benzofuran, benzothiophene, indole and indolizine, process for their preparation and compositions containing them
EP1077967B1 (en)	2002-12-04	Biphenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
JP2002514639A (ja)	2002-05-21	ナフト［２，３−ｂ］ヘテロアリー−４−イル誘導体
JP2002514636A (ja)	2002-05-21	インスリン抵抗性または高血糖症の治療に有用なフェニルオキソ−酢酸類
EP1569900B1 (en)	2006-06-28	Substituted 3-carbonyl-1-yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (pai-1)
HU211294A9 (en)	1995-11-28	Unsaturated hydroxyalkylquinoline acids as leukotriene antagonist
CA2538354A1 (en)	2005-04-07	Substituted naphthyl benzothiophene acids
US6110962A (en)	2000-08-29	11-aryl-benzo[B]naphtho[2,3-D]furans and 11-aryl-benzo[B]naphtho[2,3-D]thiophenes useful in the treatment of insulin resistance and hyperglycemia
US6057316A (en)	2000-05-02	4-aryl-1-oxa-9-thia-cyclopenta[b]fluorenes
US6121271A (en)	2000-09-19	Naphtho[2,3-B]heteroar-4-yl derivatives
US6001867A (en)	1999-12-14	1-aryl-dibenzothiophenes
US6221902B1 (en)	2001-04-24	Biphenyl sulfonyl aryl carboxylic acids useful in the treatment of insulin resistance and hyperglycemia
JP2002514631A (ja)	2002-05-21	インスリン耐性および高血糖症の治療に有用なオキサゾール−アリール−カルボン酸
JP2002514637A (ja)	2002-05-21	インスリン耐性および高血糖症の治療に有用なビフェニルスルホニルアリールカルボン酸
US6281238B1 (en)	2001-08-28	4-aryl-1-oxa-9-thia-cylopenta[B]fluorenes
MXPA00011091A (en)	2001-07-31	Benzothiophenes, benzofurans, and indoles useful in the treatment of insulin resistance and hyperglycemia
CZ20004182A3 (cs)	2001-03-14	Deriváty benzothiofenu, benzofuranu a indolu
MXPA00011089A (en)	2001-07-31	11-aryl-benzo[b]naphtho[2,3-d]furans and 11-aryl-benzo[b]naphtho[2,3-d]thiophenes useful in the treatment of insulin resistance and hyperglycemia
MXPA00011086A (en)	2001-07-31	Biphenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia

JP2002516321A - インスリン耐性および高血糖の治療に有用なベンゾチオフェン、ベンゾフラン、およびインドール - Google Patents

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Publications (1)

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ID=22133746

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Country Status (22)

Cited By (2)

Families Citing this family (61)

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