BG104918A - Бензотиофени, бензофурани и индоли, полезни при лечение на резистентност към инсулин и хипергликемия - Google Patents

Бензотиофени, бензофурани и индоли, полезни при лечение на резистентност към инсулин и хипергликемия Download PDF

Info

Publication number: BG104918A
Authority: BG; Bulgaria
Prior art keywords: carbon atoms; thiophen; bromo; dimethylnaphtho; alkyl
Prior art date: 1998-05-12

Application number

BG104918A

Other languages

Bulgarian (bg)

English (en)

Inventor

Jay Wrobel

Arlene Joan Dietrich

Madelene Miyoko Antane

Original Assignee

Wyeth

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

2000-11-07

Publication date

2001-08-31

2000-11-07 Application filed by Wyeth filed Critical Wyeth

2001-08-31 Publication of BG104918A publication Critical patent/BG104918A/bg

Links

208000001072 type 2 diabetes mellitus Diseases 0.000 title claims abstract description 25
206010022489 Insulin Resistance Diseases 0.000 title claims abstract description 18
201000001421 hyperglycemia Diseases 0.000 title claims abstract description 9
238000011282 treatment Methods 0.000 title description 12
150000002475 indoles Chemical class 0.000 title description 4
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title description 2
150000001907 coumarones Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 248
150000003839 salts Chemical class 0.000 claims abstract description 48
208000030159 metabolic disease Diseases 0.000 claims abstract description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 598
125000000217 alkyl group Chemical group 0.000 claims description 340
-1 nitro, amino Chemical group 0.000 claims description 312
125000003118 aryl group Chemical group 0.000 claims description 193
229910052760 oxygen Inorganic materials 0.000 claims description 166
229910052717 sulfur Inorganic materials 0.000 claims description 164
229910052736 halogen Inorganic materials 0.000 claims description 156
150000002367 halogens Chemical group 0.000 claims description 155
125000003710 aryl alkyl group Chemical group 0.000 claims description 148
229910052739 hydrogen Inorganic materials 0.000 claims description 131
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 125
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 119
238000000034 method Methods 0.000 claims description 108
125000003545 alkoxy group Chemical group 0.000 claims description 94
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 92
125000004414 alkyl thio group Chemical group 0.000 claims description 86
125000005163 aryl sulfanyl group Chemical group 0.000 claims description 86
239000001257 hydrogen Substances 0.000 claims description 75
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 67
229910052757 nitrogen Inorganic materials 0.000 claims description 57
239000002253 acid Substances 0.000 claims description 29
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 24
150000002148 esters Chemical class 0.000 claims description 20
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 18
239000008103 glucose Substances 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
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 15
125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 15
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 13
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 10
125000000753 cycloalkyl group Chemical group 0.000 claims description 10
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 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000006310 cycloalkyl amino group Chemical group 0.000 claims description 8
YMRIDJQAEZFTSC-UHFFFAOYSA-N 2,3-dihydro-1h-tetrazole Chemical compound N1NC=NN1 YMRIDJQAEZFTSC-UHFFFAOYSA-N 0.000 claims description 6
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 description 6
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 6
125000004104 aryloxy group Chemical group 0.000 claims description 6
150000001993 dienes Chemical class 0.000 claims description 6
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
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 5
XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims description 5
229940098779 methanesulfonic acid Drugs 0.000 claims description 5
LKZFOXQFGOWOFV-RUZDIDTESA-N (2r)-2-[2,6-dibromo-4-(2,3-dimethylbenzo[f][1]benzofuran-4-yl)phenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=C(Br)C=C(C=C1Br)C=1C2=CC=CC=C2C=C2OC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 LKZFOXQFGOWOFV-RUZDIDTESA-N 0.000 claims description 4
WUVZDRGSJTXWLK-HSZRJFAPSA-N (2r)-2-[2,6-dibromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=C(Br)C=C(C=C1Br)C=1C2=CC=CC=C2C(Br)=C2SC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 WUVZDRGSJTXWLK-HSZRJFAPSA-N 0.000 claims description 4
SZSACUNWWXOZTE-MUUNZHRXSA-N (2r)-2-[4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-diethylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=C(CC)C=C(C=C1CC)C=1C2=CC=CC=C2C=C2SC(C)=C(C)C2=1)C(O)=O)C1=CC=CC=C1 SZSACUNWWXOZTE-MUUNZHRXSA-N 0.000 claims description 4
WQYJUZXQLDIQRR-XMMPIXPASA-N (2r)-2-[4-(9-bromo-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(Br)=C2SC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 WQYJUZXQLDIQRR-XMMPIXPASA-N 0.000 claims description 4
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 4
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 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
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 3
NIVVBCJDFYRHCI-HHHXNRCGSA-N (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-diethylphenoxy]-3-phenylpropanoic acid 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)=O)C1=CC=CC=C1 NIVVBCJDFYRHCI-HHHXNRCGSA-N 0.000 claims description 3
ACFOEGKNILPKQT-HHHXNRCGSA-N (2r)-2-[4-(9-bromo-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(Br)=C2SC(C)=C(C)C2=1)C(O)=O)C1=CC=CC=C1 ACFOEGKNILPKQT-HHHXNRCGSA-N 0.000 claims description 3
FONCZICQWCUXEB-VWLOTQADSA-N (2s)-2-[4-(9-bromo-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(Br)=C2SC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 FONCZICQWCUXEB-VWLOTQADSA-N 0.000 claims description 3
UOTUFQTUQYABEE-UHFFFAOYSA-N 2-[2,6-dibromo-4-[9-bromo-3-methyl-2-(morpholin-4-ylmethyl)benzo[f][1]benzothiol-4-yl]phenoxy]-3-phenylpropanoic acid Chemical compound S1C2=C(Br)C3=CC=CC=C3C(C=3C=C(Br)C(OC(CC=4C=CC=CC=4)C(O)=O)=C(Br)C=3)=C2C(C)=C1CN1CCOCC1 UOTUFQTUQYABEE-UHFFFAOYSA-N 0.000 claims description 3
JIQFJKZCONURFT-UHFFFAOYSA-N 2-[6-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-nitrocyclohexa-2,4-dien-1-yl]oxy-3-phenylpropanoic acid Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C(C=C1)=CC(Br)([N+]([O-])=O)C1OC(C(O)=O)CC1=CC=CC=C1 JIQFJKZCONURFT-UHFFFAOYSA-N 0.000 claims description 3
RHCPVYFEAIQYDW-UHFFFAOYSA-N 2-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-nitrophenol Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC(Br)=C(O)C([N+]([O-])=O)=C1 RHCPVYFEAIQYDW-UHFFFAOYSA-N 0.000 claims description 3
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 3
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 3
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 3
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 3
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 description 2
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
CBHDMUREVYTNQY-XMMPIXPASA-N (2r)-2-[2,6-dibromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenoxy]-4-phenylbutanoic acid Chemical compound C([C@@H](OC1=C(Br)C=C(C=C1Br)C=1C2=CC=CC=C2C(Br)=C2SC(=C(C2=1)C)C)C(O)=O)CC1=CC=CC=C1 CBHDMUREVYTNQY-XMMPIXPASA-N 0.000 claims description 2
FNEMACCUMJTTBP-AREMUKBSSA-N (2r)-2-[2,6-dibromo-4-[9-bromo-2-(diethylaminomethyl)-3-methylbenzo[f][1]benzothiol-4-yl]phenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=C(Br)C=C(C=C1Br)C=1C2=CC=CC=C2C(Br)=C2SC(=C(C2=1)C)CN(CC)CC)C(O)=O)C1=CC=CC=C1 FNEMACCUMJTTBP-AREMUKBSSA-N 0.000 claims description 2
CTHBDHMCQDBRAF-GDLZYMKVSA-N (2r)-2-[4-(9-bromo-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(Br)=C2SC(C)=C(C)C2=1)C(O)=O)C1=CC=CC=C1 CTHBDHMCQDBRAF-GDLZYMKVSA-N 0.000 claims description 2
FONCZICQWCUXEB-RUZDIDTESA-N (2r)-2-[4-(9-bromo-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(Br)=C2SC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 FONCZICQWCUXEB-RUZDIDTESA-N 0.000 claims description 2
NQUOLSOKXAJOIQ-GDLZYMKVSA-N (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-cyclopentylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=CC=C(C=C1C1CCCC1)C=1C2=CC=CC=C2C(Br)=C2SC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 NQUOLSOKXAJOIQ-GDLZYMKVSA-N 0.000 claims description 2
RIJYOJYECIIBET-XMMPIXPASA-N (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=CC=C(C=C1)C=1C2=CC=CC=C2C(Br)=C2SC(=C(C2=1)C)C)C(O)=O)C1=CC=CC=C1 RIJYOJYECIIBET-XMMPIXPASA-N 0.000 claims description 2
CBHDMUREVYTNQY-DEOSSOPVSA-N (2s)-2-[2,6-dibromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenoxy]-4-phenylbutanoic acid Chemical compound C([C@H](OC1=C(Br)C=C(C=C1Br)C=1C2=CC=CC=C2C(Br)=C2SC(=C(C2=1)C)C)C(O)=O)CC1=CC=CC=C1 CBHDMUREVYTNQY-DEOSSOPVSA-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
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 description 2
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 description 2
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 description 2
VXEIVRNXKJSYQN-AREMUKBSSA-N 2-[[(2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-dimethylphenoxy]-3-phenylpropanoyl]amino]acetic acid Chemical compound C([C@@H](OC1=C(C)C=C(C=C1C)C=1C2=CC=CC=C2C(Br)=C2SC(=C(C2=1)C)C)C(=O)NCC(O)=O)C1=CC=CC=C1 VXEIVRNXKJSYQN-AREMUKBSSA-N 0.000 claims description 2
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 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
DZBHLHKHCSWJGW-UHFFFAOYSA-N 3-bromo-5-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-methoxyaniline Chemical compound C1=C(Br)C(OC)=C(N)C=C1C1=C(C(C)=C(C)S2)C2=C(Br)C2=CC=CC=C12 DZBHLHKHCSWJGW-UHFFFAOYSA-N 0.000 claims description 2
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 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
125000003342 alkenyl group Chemical group 0.000 claims description 2
241000124008 Mammalia Species 0.000 claims 6
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 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 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
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 1
BDVHLEGHMVGUTI-HHHXNRCGSA-N (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-propylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=CC=C(C=C1CCC)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C(O)=O)C1=CC=CC=C1 BDVHLEGHMVGUTI-HHHXNRCGSA-N 0.000 claims 1
BSMWXSYGXCHETM-JGCGQSQUSA-N (2r)-2-[4-[9-bromo-2-(diethylaminomethyl)-3-methylbenzo[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(Br)=C2SC(=C(C2=1)C)CN(CC)CC)C(O)=O)C1=CC=CC=C1 BSMWXSYGXCHETM-JGCGQSQUSA-N 0.000 claims 1
IEBRZIIBAPSORL-GDLZYMKVSA-N 2-[[(2r)-2-[4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-diethylphenoxy]-3-phenylpropanoyl]amino]acetic acid Chemical compound C([C@@H](OC1=C(CC)C=C(C=C1CC)C=1C2=CC=CC=C2C=C2SC(C)=C(C)C2=1)C(=O)NCC(O)=O)C1=CC=CC=C1 IEBRZIIBAPSORL-GDLZYMKVSA-N 0.000 claims 1
LLFOKYWCITZTHK-UHFFFAOYSA-N 2-bromo-4-(2,3-dimethylbenzo[f][1]benzofuran-4-yl)-6-ethylphenol Chemical compound BrC1=C(O)C(CC)=CC(C=2C3=CC=CC=C3C=C3OC(C)=C(C)C3=2)=C1 LLFOKYWCITZTHK-UHFFFAOYSA-N 0.000 claims 1
XTZBJGXRMMUQLS-UHFFFAOYSA-N 2-cyclopentyl-4-(2,3-dimethylbenzo[f][1]benzofuran-4-yl)phenol Chemical compound C=12C(C)=C(C)OC2=CC2=CC=CC=C2C=1C(C=1)=CC=C(O)C=1C1CCCC1 XTZBJGXRMMUQLS-UHFFFAOYSA-N 0.000 claims 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
SBSWKHATWUQLAF-UHFFFAOYSA-N 4-[2-bromo-4-(2,3-dimethylbenzo[f][1]benzofuran-4-yl)-6-ethylphenoxy]butanamide Chemical compound BrC1=C(OCCCC(N)=O)C(CC)=CC(C=2C3=CC=CC=C3C=C3OC(C)=C(C)C3=2)=C1 SBSWKHATWUQLAF-UHFFFAOYSA-N 0.000 claims 1
ZKPPGOXSBKLANU-UHFFFAOYSA-N 4-[2-bromo-4-(2,3-dimethylbenzo[f][1]benzofuran-4-yl)-6-ethylphenoxy]butanoic acid Chemical compound BrC1=C(OCCCC(O)=O)C(CC)=CC(C=2C3=CC=CC=C3C=C3OC(C)=C(C)C3=2)=C1 ZKPPGOXSBKLANU-UHFFFAOYSA-N 0.000 claims 1
MVRJGCHPXLNZSK-UHFFFAOYSA-N 4-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-cyclopentylphenoxy]butanoic acid Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C(C=1)=CC=C(OCCCC(O)=O)C=1C1CCCC1 MVRJGCHPXLNZSK-UHFFFAOYSA-N 0.000 claims 1
VWPPSXPYUIEDAH-UHFFFAOYSA-N 9-bromo-2,3-dimethylbenzo[f][1]benzothiole Chemical compound BrC1=C2C=CC=CC2=CC2=C1SC(=C2C)C VWPPSXPYUIEDAH-UHFFFAOYSA-N 0.000 claims 1
DFLUHPCOXUZOKK-LLVKDONJSA-N C1=C(Br)C(O[C@H](C)C(O)=O)=C(Br)C=C1C1=C(C(C)=C(C)S2)C2=C(Br)C2=CC=CC=C12 Chemical compound C1=C(Br)C(O[C@H](C)C(O)=O)=C(Br)C=C1C1=C(C(C)=C(C)S2)C2=C(Br)C2=CC=CC=C12 DFLUHPCOXUZOKK-LLVKDONJSA-N 0.000 claims 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 1
AWIKRLCVAGLQIH-UHFFFAOYSA-N [9-bromo-4-(4-methoxy-3,5-dimethylphenyl)-3-methylbenzo[f][1]benzothiol-2-yl]methyl acetate Chemical compound C1=C(C)C(OC)=C(C)C=C1C1=C(C(C)=C(COC(C)=O)S2)C2=C(Br)C2=CC=CC=C12 AWIKRLCVAGLQIH-UHFFFAOYSA-N 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
UEPQCJBWEDLWNG-UHFFFAOYSA-N methyl 2-[3-bromo-5-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-methoxyanilino]acetate Chemical compound BrC1=C(OC)C(NCC(=O)OC)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 UEPQCJBWEDLWNG-UHFFFAOYSA-N 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
RFCZNDAOQSTUHT-UHFFFAOYSA-N tert-butyl n-[3-bromo-5-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-hydroxyphenyl]carbamate Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC(Br)=C(O)C(NC(=O)OC(C)(C)C)=C1 RFCZNDAOQSTUHT-UHFFFAOYSA-N 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 276
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 192
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 180
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 152
239000007787 solid Substances 0.000 description 132
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 130
229910052794 bromium Inorganic materials 0.000 description 125
239000000243 solution Substances 0.000 description 112
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 94
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 94
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 92
238000004458 analytical method Methods 0.000 description 82
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 78
239000002904 solvent Substances 0.000 description 74
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 67
239000011541 reaction mixture Substances 0.000 description 60
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 59
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 57
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 46
229960000583 acetic acid Drugs 0.000 description 45
239000000460 chlorine Substances 0.000 description 45
229910052801 chlorine Inorganic materials 0.000 description 45
229940093499 ethyl acetate Drugs 0.000 description 43
235000019439 ethyl acetate Nutrition 0.000 description 43
238000003756 stirring Methods 0.000 description 43
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
239000000203 mixture Substances 0.000 description 41
239000003208 petroleum Substances 0.000 description 41
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 40
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 40
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 description 39
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
238000006243 chemical reaction Methods 0.000 description 35
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
SODQFLRLAOALCF-UHFFFAOYSA-N 1lambda3-bromacyclohexa-1,3,5-triene Chemical compound Br1=CC=CC=C1 SODQFLRLAOALCF-UHFFFAOYSA-N 0.000 description 33
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 28
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 27
239000000741 silica gel Substances 0.000 description 27
229910002027 silica gel Inorganic materials 0.000 description 27
238000002844 melting Methods 0.000 description 26
230000008018 melting Effects 0.000 description 26
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 26
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 24
150000004702 methyl esters Chemical class 0.000 description 24
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 23
150000002989 phenols Chemical class 0.000 description 23
239000012071 phase Substances 0.000 description 22
230000000694 effects Effects 0.000 description 21
239000012267 brine Substances 0.000 description 20
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 20
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
239000002156 adsorbate Substances 0.000 description 19
206010012601 diabetes mellitus Diseases 0.000 description 19
239000000725 suspension Substances 0.000 description 19
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
102000004877 Insulin Human genes 0.000 description 18
108090001061 Insulin Proteins 0.000 description 18
229940125396 insulin Drugs 0.000 description 18
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Substances [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 17
229910000027 potassium carbonate Inorganic materials 0.000 description 17
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 16
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 16
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
238000003818 flash chromatography Methods 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
238000004587 chromatography analysis Methods 0.000 description 14
235000002639 sodium chloride Nutrition 0.000 description 14
238000012360 testing method Methods 0.000 description 14
150000008044 alkali metal hydroxides Chemical class 0.000 description 13
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 12
241000699670 Mus sp. Species 0.000 description 12
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 12
239000007864 aqueous solution Substances 0.000 description 12
238000004128 high performance liquid chromatography Methods 0.000 description 12
NMPPJJIBQQCOOI-VIFPVBQESA-N methyl (2s)-2-hydroxy-3-phenylpropanoate Chemical compound COC(=O)[C@@H](O)CC1=CC=CC=C1 NMPPJJIBQQCOOI-VIFPVBQESA-N 0.000 description 12
102000003746 Insulin Receptor Human genes 0.000 description 11
108010001127 Insulin Receptor Proteins 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
229910052740 iodine Inorganic materials 0.000 description 11
239000011734 sodium Substances 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 10
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
239000003153 chemical reaction reagent Substances 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
239000000284 extract Substances 0.000 description 10
239000012362 glacial acetic acid Substances 0.000 description 10
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 10
HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
235000011056 potassium acetate Nutrition 0.000 description 10
238000000746 purification Methods 0.000 description 10
VOXXWSYKYCBWHO-QMMMGPOBSA-N (S)-3-phenyllactic acid Chemical compound OC(=O)[C@@H](O)CC1=CC=CC=C1 VOXXWSYKYCBWHO-QMMMGPOBSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
229950005499 carbon tetrachloride Drugs 0.000 description 9
239000000758 substrate Substances 0.000 description 9
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 9
BIHYFOLIQODFPD-UHFFFAOYSA-N 5-benzyl-2,3-dimethylthiophene Chemical compound S1C(C)=C(C)C=C1CC1=CC=CC=C1 BIHYFOLIQODFPD-UHFFFAOYSA-N 0.000 description 8
VOXXWSYKYCBWHO-UHFFFAOYSA-N HO-Phe-OH Natural products OC(=O)C(O)CC1=CC=CC=C1 VOXXWSYKYCBWHO-UHFFFAOYSA-N 0.000 description 8
229910021578 Iron(III) chloride Inorganic materials 0.000 description 8
241000700159 Rattus Species 0.000 description 8
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
229910052799 carbon Inorganic materials 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
239000012456 homogeneous solution Substances 0.000 description 8
239000003880 polar aprotic solvent Substances 0.000 description 8
230000008569 process Effects 0.000 description 8
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 8
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 8
238000006751 Mitsunobu reaction Methods 0.000 description 7
150000001735 carboxylic acids Chemical class 0.000 description 7
239000006184 cosolvent Substances 0.000 description 7
239000003480 eluent Substances 0.000 description 7
239000012442 inert solvent Substances 0.000 description 7
229910052700 potassium Inorganic materials 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
102000004169 proteins and genes Human genes 0.000 description 7
108090000623 proteins and genes Proteins 0.000 description 7
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
101001087394 Homo sapiens Tyrosine-protein phosphatase non-receptor type 1 Proteins 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
208000008589 Obesity Diseases 0.000 description 6
229910019142 PO4 Inorganic materials 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
230000008859 change Effects 0.000 description 6
150000005690 diesters Chemical class 0.000 description 6
229940079593 drug Drugs 0.000 description 6
239000003814 drug Substances 0.000 description 6
239000006260 foam Substances 0.000 description 6
229910052500 inorganic mineral Inorganic materials 0.000 description 6
210000004185 liver Anatomy 0.000 description 6
230000003228 microsomal effect Effects 0.000 description 6
235000010755 mineral Nutrition 0.000 description 6
239000011707 mineral Substances 0.000 description 6
235000020824 obesity Nutrition 0.000 description 6
239000010452 phosphate Substances 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
108020000494 protein-tyrosine phosphatase Proteins 0.000 description 6
VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical class OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 5
CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical class OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 description 5
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
206010060378 Hyperinsulinaemia Diseases 0.000 description 5
206010020772 Hypertension Diseases 0.000 description 5
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 5
125000002252 acyl group Chemical group 0.000 description 5
229910000288 alkali metal carbonate Inorganic materials 0.000 description 5
150000008041 alkali metal carbonates Chemical class 0.000 description 5
239000002585 base Substances 0.000 description 5
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 5
239000008280 blood Substances 0.000 description 5
210000004369 blood Anatomy 0.000 description 5
238000005893 bromination reaction Methods 0.000 description 5
IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 5
230000003197 catalytic effect Effects 0.000 description 5
229940088598 enzyme Drugs 0.000 description 5
230000003451 hyperinsulinaemic effect Effects 0.000 description 5
201000008980 hyperinsulinism Diseases 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
150000002828 nitro derivatives Chemical class 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
239000000523 sample Substances 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 5
210000001519 tissue Anatomy 0.000 description 5
FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 5
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
201000001320 Atherosclerosis Diseases 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
229920001213 Polysorbate 20 Polymers 0.000 description 4
102100028516 Receptor-type tyrosine-protein phosphatase U Human genes 0.000 description 4
241000283984 Rodentia Species 0.000 description 4
JRPUWPFUPIWBIV-UHFFFAOYSA-N S1C2=C(Br)C3=CC=CC=C3C(C=3C(=C(Br)C(O)=CC=3)Br)=C2C(C)=C1CN1CCOCC1 Chemical compound S1C2=C(Br)C3=CC=CC=C3C(C=3C(=C(Br)C(O)=CC=3)Br)=C2C(C)=C1CN1CCOCC1 JRPUWPFUPIWBIV-UHFFFAOYSA-N 0.000 description 4
241000907663 Siproeta stelenes Species 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
229910021626 Tin(II) chloride Inorganic materials 0.000 description 4
102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 description 4
150000001242 acetic acid derivatives Chemical class 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
DBFGMZALESGYRS-UHFFFAOYSA-N benzo[f][1]benzofuran Chemical group C1=CC=C2C=C(OC=C3)C3=CC2=C1 DBFGMZALESGYRS-UHFFFAOYSA-N 0.000 description 4
CYKIHIBNSFRKQP-UHFFFAOYSA-N benzo[f][1]benzothiole Chemical group C1=CC=C2C=C(SC=C3)C3=CC2=C1 CYKIHIBNSFRKQP-UHFFFAOYSA-N 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000012496 blank sample Substances 0.000 description 4
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
230000000052 comparative effect Effects 0.000 description 4
125000001153 fluoro group Chemical group F* 0.000 description 4
239000011630 iodine Substances 0.000 description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 4
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
KJRCEJOSASVSRA-UHFFFAOYSA-N propane-2-thiol Chemical compound CC(C)S KJRCEJOSASVSRA-UHFFFAOYSA-N 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000010561 standard procedure Methods 0.000 description 4
235000011150 stannous chloride Nutrition 0.000 description 4
239000007858 starting material Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 4
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 3
BZYUMXXOAYSFOW-UHFFFAOYSA-N 2,3-dimethylthiophene Chemical compound CC=1C=CSC=1C BZYUMXXOAYSFOW-UHFFFAOYSA-N 0.000 description 3
VPWNQTHUCYMVMZ-UHFFFAOYSA-N 4,4'-sulfonyldiphenol Chemical class C1=CC(O)=CC=C1S(=O)(=O)C1=CC=C(O)C=C1 VPWNQTHUCYMVMZ-UHFFFAOYSA-N 0.000 description 3
MGWPAOVQVURSBV-UHFFFAOYSA-N 4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-diethylphenol Chemical compound CCC1=C(O)C(CC)=CC(C=2C3=CC=CC=C3C=C3SC(C)=C(C)C3=2)=C1 MGWPAOVQVURSBV-UHFFFAOYSA-N 0.000 description 3
IODYQWBSUXFDEJ-UHFFFAOYSA-N 4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-dimethylphenol Chemical compound C=12C(C)=C(C)SC2=CC2=CC=CC=C2C=1C1=CC(C)=C(O)C(C)=C1 IODYQWBSUXFDEJ-UHFFFAOYSA-N 0.000 description 3
KTPLQTZSARXILB-UHFFFAOYSA-N 4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-fluorophenol Chemical compound C=12C(C)=C(C)SC2=CC2=CC=CC=C2C=1C1=CC=C(O)C(F)=C1 KTPLQTZSARXILB-UHFFFAOYSA-N 0.000 description 3
NNNOJINDJOJVPU-UHFFFAOYSA-N 4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(C=2C3=CC=CC=C3C=C3SC(C)=C(C)C3=2)=C1 NNNOJINDJOJVPU-UHFFFAOYSA-N 0.000 description 3
RAMFURPENSFESZ-UHFFFAOYSA-N 4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-cyclopentylphenol Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C(C=1)=CC=C(O)C=1C1CCCC1 RAMFURPENSFESZ-UHFFFAOYSA-N 0.000 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 description 3
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 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
229930185605 Bisphenol Natural products 0.000 description 3
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
208000002705 Glucose Intolerance Diseases 0.000 description 3
206010018429 Glucose tolerance impaired Diseases 0.000 description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
239000011609 ammonium molybdate Substances 0.000 description 3
229940010552 ammonium molybdate Drugs 0.000 description 3
229910052786 argon Inorganic materials 0.000 description 3
125000004391 aryl sulfonyl group Chemical group 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000000872 buffer Substances 0.000 description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
239000010949 copper Substances 0.000 description 3
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 3
230000017858 demethylation Effects 0.000 description 3
238000010520 demethylation reaction Methods 0.000 description 3
238000006209 dephosphorylation reaction Methods 0.000 description 3
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
125000004494 ethyl ester group Chemical group 0.000 description 3
229960001269 glycine hydrochloride Drugs 0.000 description 3
239000005457 ice water Substances 0.000 description 3
229910052744 lithium Inorganic materials 0.000 description 3
239000000463 material Substances 0.000 description 3
230000004060 metabolic process Effects 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
LSDPWZHWYPCBBB-UHFFFAOYSA-N methyl mercaptane Natural products SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 3
210000003205 muscle Anatomy 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
150000003009 phosphonic acids Chemical class 0.000 description 3
239000011591 potassium Substances 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 3
125000004076 pyridyl group Chemical group 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000011347 resin Substances 0.000 description 3
229920005989 resin Polymers 0.000 description 3
238000012552 review Methods 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000001632 sodium acetate Substances 0.000 description 3
235000017281 sodium acetate Nutrition 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000008259 solid foam Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
239000000829 suppository Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
230000009466 transformation Effects 0.000 description 3
WXTOQRWRYJZFNG-UHFFFAOYSA-N (2-benzyl-4,5-dimethylfuran-3-yl)-(3,5-dibromo-4-methoxyphenyl)methanone Chemical compound C1=C(Br)C(OC)=C(Br)C=C1C(=O)C1=C(CC=2C=CC=CC=2)OC(C)=C1C WXTOQRWRYJZFNG-UHFFFAOYSA-N 0.000 description 2
SGODYLJPDLPNAF-UHFFFAOYSA-N (2-benzyl-4,5-dimethylthiophen-3-yl)-(3,5-diethyl-4-methoxyphenyl)methanone Chemical compound CCC1=C(OC)C(CC)=CC(C(=O)C2=C(SC(C)=C2C)CC=2C=CC=CC=2)=C1 SGODYLJPDLPNAF-UHFFFAOYSA-N 0.000 description 2
WBGOKSLLTNGGJR-UHFFFAOYSA-N (2-benzyl-4,5-dimethylthiophen-3-yl)-(4-methoxy-3,5-dimethylphenyl)methanone Chemical compound C1=C(C)C(OC)=C(C)C=C1C(=O)C1=C(CC=2C=CC=CC=2)SC(C)=C1C WBGOKSLLTNGGJR-UHFFFAOYSA-N 0.000 description 2
ZPSUVWUQYKIFTG-UHFFFAOYSA-N (2-benzyl-4,5-dimethylthiophen-3-yl)-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)C1=C(CC=2C=CC=CC=2)SC(C)=C1C ZPSUVWUQYKIFTG-UHFFFAOYSA-N 0.000 description 2
SFNBAPJDUBXJPL-RUZDIDTESA-N (2r)-2-[2-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-ethylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=C(Br)C=C(C=C1CC)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C(O)=O)C1=CC=CC=C1 SFNBAPJDUBXJPL-RUZDIDTESA-N 0.000 description 2
PGLMYLRQHITYKV-AREMUKBSSA-N (2r)-2-[2-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-propan-2-ylphenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=C(Br)C=C(C=C1C(C)C)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C(O)=O)C1=CC=CC=C1 PGLMYLRQHITYKV-AREMUKBSSA-N 0.000 description 2
QGCXZMCJUKRQBF-UHFFFAOYSA-N 1,1,1-trichloro-2-methylpropan-2-ol;tetrahydrate Chemical compound O.O.O.O.CC(C)(O)C(Cl)(Cl)Cl QGCXZMCJUKRQBF-UHFFFAOYSA-N 0.000 description 2
FNAKEOXYWBWIRT-UHFFFAOYSA-N 2,3-dibromophenol Chemical class OC1=CC=CC(Br)=C1Br FNAKEOXYWBWIRT-UHFFFAOYSA-N 0.000 description 2
YPJVJVIQWWXEHO-UHFFFAOYSA-N 2,3-diiodophenol Chemical compound OC1=CC=CC(I)=C1I YPJVJVIQWWXEHO-UHFFFAOYSA-N 0.000 description 2
SXERGJJQSKIUIC-UHFFFAOYSA-N 2-Phenoxypropionic acid Chemical compound OC(=O)C(C)OC1=CC=CC=C1 SXERGJJQSKIUIC-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
ANZUZRAUHDHSCJ-UHFFFAOYSA-N 2-butan-2-yl-4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenol Chemical compound C1=C(O)C(C(C)CC)=CC(C=2C3=CC=CC=C3C=C3SC(C)=C(C)C3=2)=C1 ANZUZRAUHDHSCJ-UHFFFAOYSA-N 0.000 description 2
CRKKTEAIMOFLSQ-UHFFFAOYSA-N 2-cyclopentyl-4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenol Chemical compound C=12C(C)=C(C)SC2=CC2=CC=CC=C2C=1C(C=1)=CC=C(O)C=1C1CCCC1 CRKKTEAIMOFLSQ-UHFFFAOYSA-N 0.000 description 2
BSQKBHXYEKVKMN-UHFFFAOYSA-N 3-methylthiophene-2-carbaldehyde Chemical compound CC=1C=CSC=1C=O BSQKBHXYEKVKMN-UHFFFAOYSA-N 0.000 description 2
FWLQWHILNOIWBZ-UHFFFAOYSA-N 4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-di(propan-2-yl)phenol Chemical compound CC(C)C1=C(O)C(C(C)C)=CC(C=2C3=CC=CC=C3C=C3SC(C)=C(C)C3=2)=C1 FWLQWHILNOIWBZ-UHFFFAOYSA-N 0.000 description 2
NZZQWEGRIAMKQD-UHFFFAOYSA-N 4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-ethylphenol Chemical compound C1=C(O)C(CC)=CC(C=2C3=CC=CC=C3C=C3SC(C)=C(C)C3=2)=C1 NZZQWEGRIAMKQD-UHFFFAOYSA-N 0.000 description 2
BZMUSEQATJODAD-UHFFFAOYSA-N 4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-dimethylphenol Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC(C)=C(O)C(C)=C1 BZMUSEQATJODAD-UHFFFAOYSA-N 0.000 description 2
KKZRFBRFUBDOOK-UHFFFAOYSA-N 4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 KKZRFBRFUBDOOK-UHFFFAOYSA-N 0.000 description 2
VSMDINRNYYEDRN-UHFFFAOYSA-N 4-iodophenol Chemical compound OC1=CC=C(I)C=C1 VSMDINRNYYEDRN-UHFFFAOYSA-N 0.000 description 2
ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 2
FRLNGHBISDFXOX-UHFFFAOYSA-N 5-benzyl-2,3-dimethylfuran Chemical compound O1C(C)=C(C)C=C1CC1=CC=CC=C1 FRLNGHBISDFXOX-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
229910015900 BF3 Inorganic materials 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 2
JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
GPCAAJLJWSXQMG-UHFFFAOYSA-N [4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-di(propan-2-yl)phenyl] acetate Chemical compound CC(C)C1=C(OC(C)=O)C(C(C)C)=CC(C=2C3=CC=CC=C3C=C3SC(C)=C(C)C3=2)=C1 GPCAAJLJWSXQMG-UHFFFAOYSA-N 0.000 description 2
WGGPGJXULMCXFZ-UHFFFAOYSA-N [4-(9-bromo-2,3-dimethylbenzo[f][1]benzofuran-4-yl)-2,6-diethylphenyl] acetate Chemical compound CCC1=C(OC(C)=O)C(CC)=CC(C=2C3=CC=CC=C3C(Br)=C3OC(C)=C(C)C3=2)=C1 WGGPGJXULMCXFZ-UHFFFAOYSA-N 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
239000012378 ammonium molybdate tetrahydrate Substances 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
FIXLYHHVMHXSCP-UHFFFAOYSA-H azane;dihydroxy(dioxo)molybdenum;trioxomolybdenum;tetrahydrate Chemical compound N.N.N.N.N.N.O.O.O.O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O[Mo](O)(=O)=O.O[Mo](O)(=O)=O.O[Mo](O)(=O)=O FIXLYHHVMHXSCP-UHFFFAOYSA-H 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
210000004204 blood vessel Anatomy 0.000 description 2
230000037396 body weight Effects 0.000 description 2
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
239000002775 capsule Substances 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
150000001733 carboxylic acid esters Chemical class 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 2
229950009226 ciglitazone Drugs 0.000 description 2
239000004927 clay Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 2
239000006071 cream Substances 0.000 description 2
230000034994 death Effects 0.000 description 2
231100000517 death Toxicity 0.000 description 2
230000007547 defect Effects 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
238000001514 detection method Methods 0.000 description 2
DLZIINHWAMZIBZ-UHFFFAOYSA-N diiodomethoxy(diiodo)methane Chemical compound IC(I)OC(I)I DLZIINHWAMZIBZ-UHFFFAOYSA-N 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
235000013305 food Nutrition 0.000 description 2
238000009472 formulation Methods 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
QFWPJPIVLCBXFJ-UHFFFAOYSA-N glymidine Chemical compound N1=CC(OCCOC)=CN=C1NS(=O)(=O)C1=CC=CC=C1 QFWPJPIVLCBXFJ-UHFFFAOYSA-N 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
238000001802 infusion Methods 0.000 description 2
NWMAFUPEQLTLPX-UHFFFAOYSA-N iodo(iodomethoxy)methane Chemical class ICOCI NWMAFUPEQLTLPX-UHFFFAOYSA-N 0.000 description 2
VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 description 2
208000023589 ischemic disease Diseases 0.000 description 2
NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
150000007517 lewis acids Chemical class 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229940107698 malachite green Drugs 0.000 description 2
FDZZZRQASAIRJF-UHFFFAOYSA-M malachite green Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC=CC=1)=C1C=CC(=[N+](C)C)C=C1 FDZZZRQASAIRJF-UHFFFAOYSA-M 0.000 description 2
238000005259 measurement Methods 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
210000001589 microsome Anatomy 0.000 description 2
230000006892 negative regulation of dephosphorylation Effects 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
239000012038 nucleophile Substances 0.000 description 2
UTZPGFZOSLGODE-UHFFFAOYSA-N oxo(phenyl)-$l^{5}-arsane Chemical compound O=[AsH2]C1=CC=CC=C1 UTZPGFZOSLGODE-UHFFFAOYSA-N 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
229910000160 potassium phosphate Inorganic materials 0.000 description 2
235000011009 potassium phosphates Nutrition 0.000 description 2
150000003858 primary carboxamides Chemical group 0.000 description 2
OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 description 2
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
125000000719 pyrrolidinyl group Chemical group 0.000 description 2
239000011535 reaction buffer Substances 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
230000011664 signaling Effects 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
150000003459 sulfonic acid esters Chemical class 0.000 description 2
125000000542 sulfonic acid group Chemical group 0.000 description 2
150000003462 sulfoxides Chemical class 0.000 description 2
WMGWLIAIMDFMIQ-UHFFFAOYSA-N sulfuroiodidic acid Chemical class OS(I)(=O)=O WMGWLIAIMDFMIQ-UHFFFAOYSA-N 0.000 description 2
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
150000003536 tetrazoles Chemical class 0.000 description 2
229930192474 thiophene Natural products 0.000 description 2
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
235000019786 weight gain Nutrition 0.000 description 2
UDDBRJGGGUMTQZ-UHFFFAOYSA-N (2,6-dimethylphenyl) acetate Chemical compound CC(=O)OC1=C(C)C=CC=C1C UDDBRJGGGUMTQZ-UHFFFAOYSA-N 0.000 description 1
AKJLLKIUDLREKE-UHFFFAOYSA-N (2-benzyl-4,5-dimethylfuran-3-yl)-(3,5-diethyl-4-methoxyphenyl)methanone Chemical compound CCC1=C(OC)C(CC)=CC(C(=O)C2=C(OC(C)=C2C)CC=2C=CC=CC=2)=C1 AKJLLKIUDLREKE-UHFFFAOYSA-N 0.000 description 1
BXXCUWUAKOGCQM-UHFFFAOYSA-N (2-benzyl-4,5-dimethylthiophen-3-yl)-(3-butan-2-yl-4-methoxyphenyl)methanone Chemical compound C1=C(OC)C(C(C)CC)=CC(C(=O)C=2C(=C(C)SC=2CC=2C=CC=CC=2)C)=C1 BXXCUWUAKOGCQM-UHFFFAOYSA-N 0.000 description 1
APYBBGQSYBJVDK-UHFFFAOYSA-N (2-benzyl-4,5-dimethylthiophen-3-yl)-(3-cyclopentyl-4-methoxyphenyl)methanone Chemical compound COC1=CC=C(C(=O)C=2C(=C(C)SC=2CC=2C=CC=CC=2)C)C=C1C1CCCC1 APYBBGQSYBJVDK-UHFFFAOYSA-N 0.000 description 1
LKOYHVRROZUTGF-UHFFFAOYSA-N (2-benzyl-4,5-dimethylthiophen-3-yl)-(3-ethyl-4-methoxyphenyl)methanone Chemical compound C1=C(OC)C(CC)=CC(C(=O)C2=C(SC(C)=C2C)CC=2C=CC=CC=2)=C1 LKOYHVRROZUTGF-UHFFFAOYSA-N 0.000 description 1
IXDQGJOPGVQWQI-UHFFFAOYSA-N (2-benzyl-4,5-dimethylthiophen-3-yl)-(3-fluoro-4-methoxyphenyl)methanone Chemical compound C1=C(F)C(OC)=CC=C1C(=O)C1=C(CC=2C=CC=CC=2)SC(C)=C1C IXDQGJOPGVQWQI-UHFFFAOYSA-N 0.000 description 1
OHQOMWGAJMGIHJ-UHFFFAOYSA-N (2-benzyl-4,5-dimethylthiophen-3-yl)-(4-methoxy-3-propan-2-ylphenyl)methanone Chemical compound C1=C(C(C)C)C(OC)=CC=C1C(=O)C(C(=C(C)S1)C)=C1CC1=CC=CC=C1 OHQOMWGAJMGIHJ-UHFFFAOYSA-N 0.000 description 1
KVDKOCFPUUABOQ-UHFFFAOYSA-N (2-benzyl-4,5-dimethylthiophen-3-yl)-[4-methoxy-3,5-di(propan-2-yl)phenyl]methanone Chemical compound C1=C(C(C)C)C(OC)=C(C(C)C)C=C1C(=O)C(C(=C(C)S1)C)=C1CC1=CC=CC=C1 KVDKOCFPUUABOQ-UHFFFAOYSA-N 0.000 description 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 description 1
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 description 1
VWTGUCRWZOQMEO-QOHVGFNKSA-N (2r)-2-[6-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-cyclopentylcyclohexa-2,4-dien-1-yl]oxy-3-phenylpropanoic acid Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C(C=CC1O[C@H](CC=2C=CC=CC=2)C(O)=O)=CC1(Br)C1CCCC1 VWTGUCRWZOQMEO-QOHVGFNKSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
MRXDGVXSWIXTQL-HYHFHBMOSA-N (2s)-2-[[(1s)-1-(2-amino-1,4,5,6-tetrahydropyrimidin-6-yl)-2-[[(2s)-4-methyl-1-oxo-1-[[(2s)-1-oxo-3-phenylpropan-2-yl]amino]pentan-2-yl]amino]-2-oxoethyl]carbamoylamino]-3-phenylpropanoic acid Chemical compound C([C@H](NC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C=O)C1NC(N)=NCC1)C(O)=O)C1=CC=CC=C1 MRXDGVXSWIXTQL-HYHFHBMOSA-N 0.000 description 1
JNJCEALGCZSIGB-VIFPVBQESA-N (2s)-2-hydroxy-4-phenylbutanoic acid Chemical compound OC(=O)[C@@H](O)CCC1=CC=CC=C1 JNJCEALGCZSIGB-VIFPVBQESA-N 0.000 description 1
ULLLXDOAOQBNST-UHFFFAOYSA-N (4,5-dimethylthiophen-2-yl)-phenylmethanol Chemical compound S1C(C)=C(C)C=C1C(O)C1=CC=CC=C1 ULLLXDOAOQBNST-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
RLOMWTGAHPLPGX-UHFFFAOYSA-N 2,3-dimethylbenzo[f][1]benzothiole Chemical compound C1=CC=C2C=C(C(=C(C)S3)C)C3=CC2=C1 RLOMWTGAHPLPGX-UHFFFAOYSA-N 0.000 description 1
TYRKBXRIDIIVHV-UHFFFAOYSA-N 2,6-dibromo-4-(2,3-dimethylbenzo[f][1]benzofuran-4-yl)phenol Chemical compound C=12C(C)=C(C)OC2=CC2=CC=CC=C2C=1C1=CC(Br)=C(O)C(Br)=C1 TYRKBXRIDIIVHV-UHFFFAOYSA-N 0.000 description 1
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 description 1
TVPDDKXZHKJUPX-UHFFFAOYSA-N 2-(cyanomethoxy)acetonitrile Chemical compound N#CCOCC#N TVPDDKXZHKJUPX-UHFFFAOYSA-N 0.000 description 1
PACPJYRUCIRQSL-UHFFFAOYSA-N 2-(dicyanomethoxy)propanedinitrile Chemical compound N#CC(C#N)OC(C#N)C#N PACPJYRUCIRQSL-UHFFFAOYSA-N 0.000 description 1
MUVIJSJPQONWPF-MUUNZHRXSA-N 2-[[(2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-diethylphenoxy]-3-phenylpropanoyl]amino]acetic acid 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)NCC(O)=O)C1=CC=CC=C1 MUVIJSJPQONWPF-MUUNZHRXSA-N 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
SHTCHFOWQYEBTD-UHFFFAOYSA-N 2-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-butan-2-ylphenol Chemical compound BrC1=C(O)C(C(C)CC)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 SHTCHFOWQYEBTD-UHFFFAOYSA-N 0.000 description 1
MHKRYWNJWAQNFI-UHFFFAOYSA-N 2-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-ethylphenol Chemical compound BrC1=C(O)C(CC)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 MHKRYWNJWAQNFI-UHFFFAOYSA-N 0.000 description 1
JHEKSKQMOBLXQS-UHFFFAOYSA-N 2-cyclopentylphenol Chemical compound OC1=CC=CC=C1C1CCCC1 JHEKSKQMOBLXQS-UHFFFAOYSA-N 0.000 description 1
KQDJTBPASNJQFQ-UHFFFAOYSA-N 2-iodophenol Chemical class OC1=CC=CC=C1I KQDJTBPASNJQFQ-UHFFFAOYSA-N 0.000 description 1
VCRSXSFOKOVCRV-UHFFFAOYSA-N 2-thiophen-3-ylphenol Chemical compound OC1=CC=CC=C1C1=CSC=C1 VCRSXSFOKOVCRV-UHFFFAOYSA-N 0.000 description 1
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
NAHPGFGVWWKSFU-UHFFFAOYSA-N 3,5-dibromo-4-methoxybenzoic acid Chemical compound COC1=C(Br)C=C(C(O)=O)C=C1Br NAHPGFGVWWKSFU-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
HQWDXGYZIJEWSE-UHFFFAOYSA-N 3-phenyl-2-(2-propan-2-ylphenoxy)propanoic acid Chemical compound C(C)(C)C1=CC=CC=C1OC(C(=O)O)CC1=CC=CC=C1 HQWDXGYZIJEWSE-UHFFFAOYSA-N 0.000 description 1
XQDKOANVSQEFEK-UHFFFAOYSA-N 4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenol Chemical compound C=12C(C)=C(C)SC2=CC2=CC=CC=C2C=1C1=CC=C(O)C=C1 XQDKOANVSQEFEK-UHFFFAOYSA-N 0.000 description 1
NQQFDGJAJWNHOK-UHFFFAOYSA-N 4-(9-bromo-2,3-dimethylbenzo[f][1]benzofuran-4-yl)-2,6-diethylphenol Chemical compound CCC1=C(O)C(CC)=CC(C=2C3=CC=CC=C3C(Br)=C3OC(C)=C(C)C3=2)=C1 NQQFDGJAJWNHOK-UHFFFAOYSA-N 0.000 description 1
KRXRPOGONPCXEE-UHFFFAOYSA-N 4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-di(propan-2-yl)phenol Chemical compound CC(C)C1=C(O)C(C(C)C)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 KRXRPOGONPCXEE-UHFFFAOYSA-N 0.000 description 1
OHGDAULKPYQQBP-UHFFFAOYSA-N 4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-diethylphenol Chemical compound CCC1=C(O)C(CC)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 OHGDAULKPYQQBP-UHFFFAOYSA-N 0.000 description 1
JCFACBFCXLZSCZ-UHFFFAOYSA-N 4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-fluorophenol Chemical compound C=12C(C)=C(C)SC2=C(Br)C2=CC=CC=C2C=1C1=CC=C(O)C(F)=C1 JCFACBFCXLZSCZ-UHFFFAOYSA-N 0.000 description 1
YXCYUOXSDJZWJG-UHFFFAOYSA-N 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=CC(O)=CC=3)=C2C(C)=C1CN1CCOCC1 YXCYUOXSDJZWJG-UHFFFAOYSA-N 0.000 description 1
BEJYDMQQZUACPW-UHFFFAOYSA-N 4-bromo-2,6-diethylaniline Chemical compound CCC1=CC(Br)=CC(CC)=C1N BEJYDMQQZUACPW-UHFFFAOYSA-N 0.000 description 1
WXVQURJGDUNJCS-UHFFFAOYSA-N 4-methoxy-3,5-dimethylbenzoic acid Chemical compound COC1=C(C)C=C(C(O)=O)C=C1C WXVQURJGDUNJCS-UHFFFAOYSA-N 0.000 description 1
OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
KRBBGMOONSUDGO-UHFFFAOYSA-N 5-bromo-1,3-thiazolidine-2,4-dione Chemical compound BrC1SC(=O)NC1=O KRBBGMOONSUDGO-UHFFFAOYSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
244000144725 Amygdalus communis Species 0.000 description 1
235000011437 Amygdalus communis Nutrition 0.000 description 1
108010087765 Antipain Proteins 0.000 description 1
108010039627 Aprotinin Proteins 0.000 description 1
206010003497 Asphyxia Diseases 0.000 description 1
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
ZVWZLJDTCAWHDE-AREMUKBSSA-N CC1=C(SC2=C(C3=CC=CC=C3C(=C12)C4=CC(=C(C(=C4)Br)O[C@H](CC5=CC=CC=C5)C(=O)O)C(C)(C)C)Br)C Chemical compound CC1=C(SC2=C(C3=CC=CC=C3C(=C12)C4=CC(=C(C(=C4)Br)O[C@H](CC5=CC=CC=C5)C(=O)O)C(C)(C)C)Br)C ZVWZLJDTCAWHDE-AREMUKBSSA-N 0.000 description 1
UNPYEWOTKRWGPY-UHFFFAOYSA-N CC1=C(SC2=C(C3=CC=CC=C3C(=C12)C4=CC=C(C=C4)CC(=O)O)Br)C Chemical compound CC1=C(SC2=C(C3=CC=CC=C3C(=C12)C4=CC=C(C=C4)CC(=O)O)Br)C UNPYEWOTKRWGPY-UHFFFAOYSA-N 0.000 description 1
DYKSIEYXWFMBCC-UHFFFAOYSA-N CC1=C(SC2=C(C3=CC=CC=C3C(=C12)C4=CC=C(C=C4)CC(=O)O)Br)CCl Chemical compound CC1=C(SC2=C(C3=CC=CC=C3C(=C12)C4=CC=C(C=C4)CC(=O)O)Br)CCl DYKSIEYXWFMBCC-UHFFFAOYSA-N 0.000 description 1
WKYURNOZIUVCHW-UHFFFAOYSA-N CC1=CC(=CC(=C1CC(=O)O)C)C2=C3C(=C(SC3=C(C4=CC=CC=C42)Br)C)C Chemical compound CC1=CC(=CC(=C1CC(=O)O)C)C2=C3C(=C(SC3=C(C4=CC=CC=C42)Br)C)C WKYURNOZIUVCHW-UHFFFAOYSA-N 0.000 description 1
CSDXJPHEFZUJOF-UHFFFAOYSA-N CC1=CC(=CC(=C1CC(=O)O)C)C2=C3C(=C(SC3=CC4=CC=CC=C42)C)C Chemical compound CC1=CC(=CC(=C1CC(=O)O)C)C2=C3C(=C(SC3=CC4=CC=CC=C42)C)C CSDXJPHEFZUJOF-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
OLVPQBGMUGIKIW-UHFFFAOYSA-N Chymostatin Natural products C=1C=CC=CC=1CC(C=O)NC(=O)C(C(C)CC)NC(=O)C(C1NC(N)=NCC1)NC(=O)NC(C(O)=O)CC1=CC=CC=C1 OLVPQBGMUGIKIW-UHFFFAOYSA-N 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
101100522280 Dictyostelium discoideum ptpA1-2 gene Proteins 0.000 description 1
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical class COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
208000007530 Essential hypertension Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
101100466198 Mus musculus Ptpra gene Proteins 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
101150006497 PTP-1 gene Proteins 0.000 description 1
102000052651 Pancreatic hormone Human genes 0.000 description 1
101800001268 Pancreatic hormone Proteins 0.000 description 1
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
108091005682 Receptor kinases Proteins 0.000 description 1
101710138741 Receptor-type tyrosine-protein phosphatase F Proteins 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
235000021307 Triticum Nutrition 0.000 description 1
241000209140 Triticum Species 0.000 description 1
101710116241 Tyrosine-protein phosphatase non-receptor type 11 Proteins 0.000 description 1
102100033019 Tyrosine-protein phosphatase non-receptor type 11 Human genes 0.000 description 1
238000005644 Wolff-Kishner reduction reaction Methods 0.000 description 1
ADAYZIXKKRZIMX-UHFFFAOYSA-N [4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-diethylphenyl] acetate Chemical compound CCC1=C(OC(C)=O)C(CC)=CC(C=2C3=CC=CC=C3C=C3SC(C)=C(C)C3=2)=C1 ADAYZIXKKRZIMX-UHFFFAOYSA-N 0.000 description 1
YKJYVCIZAJHTRP-UHFFFAOYSA-N [4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-dimethylphenyl] acetate Chemical compound C1=C(C)C(OC(=O)C)=C(C)C=C1C1=C(C(C)=C(C)S2)C2=CC2=CC=CC=C12 YKJYVCIZAJHTRP-UHFFFAOYSA-N 0.000 description 1
JGVFEJBTHOWEAW-UHFFFAOYSA-N [4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-propan-2-ylphenyl] acetate Chemical compound C1=C(OC(C)=O)C(C(C)C)=CC(C=2C3=CC=CC=C3C=C3SC(C)=C(C)C3=2)=C1 JGVFEJBTHOWEAW-UHFFFAOYSA-N 0.000 description 1
LLRBBFWBVOVYGA-UHFFFAOYSA-N [4-(2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenyl] acetate Chemical compound C1=CC(OC(=O)C)=CC=C1C1=C(C(C)=C(C)S2)C2=CC2=CC=CC=C12 LLRBBFWBVOVYGA-UHFFFAOYSA-N 0.000 description 1
RRAYCAXSGAKZPD-UHFFFAOYSA-N [4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-di(propan-2-yl)phenyl] acetate Chemical compound CC(C)C1=C(OC(C)=O)C(C(C)C)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 RRAYCAXSGAKZPD-UHFFFAOYSA-N 0.000 description 1
PLMVOVVSTRNZAF-UHFFFAOYSA-N [4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2,6-diethylphenyl] acetate Chemical compound CCC1=C(OC(C)=O)C(CC)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 PLMVOVVSTRNZAF-UHFFFAOYSA-N 0.000 description 1
WAALYIKQHNPALZ-UHFFFAOYSA-N [4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-cyclopentylphenyl] acetate Chemical compound CC(=O)OC1=CC=C(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)C=C1C1CCCC1 WAALYIKQHNPALZ-UHFFFAOYSA-N 0.000 description 1
DZKFUFWPHNPARP-UHFFFAOYSA-N [4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-fluorophenyl] acetate Chemical compound C1=C(F)C(OC(=O)C)=CC=C1C1=C(C(C)=C(C)S2)C2=C(Br)C2=CC=CC=C12 DZKFUFWPHNPARP-UHFFFAOYSA-N 0.000 description 1
KTTXLTMNDWONOF-UHFFFAOYSA-N [4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-propan-2-ylphenyl] acetate Chemical compound C1=C(OC(C)=O)C(C(C)C)=CC(C=2C3=CC=CC=C3C(Br)=C3SC(C)=C(C)C3=2)=C1 KTTXLTMNDWONOF-UHFFFAOYSA-N 0.000 description 1
MCJCMPYIPPYNQQ-UHFFFAOYSA-N [4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenyl] acetate Chemical compound C1=CC(OC(=O)C)=CC=C1C1=C(C(C)=C(C)S2)C2=C(Br)C2=CC=CC=C12 MCJCMPYIPPYNQQ-UHFFFAOYSA-N 0.000 description 1
RBPZRTFWTYBMRQ-UHFFFAOYSA-N [4-[9-bromo-2-(chloromethyl)-3-methylbenzo[f][1]benzothiol-4-yl]phenyl] acetate Chemical compound C1=CC(OC(=O)C)=CC=C1C1=C(C(C)=C(CCl)S2)C2=C(Br)C2=CC=CC=C12 RBPZRTFWTYBMRQ-UHFFFAOYSA-N 0.000 description 1
KOOADCGQJDGAGA-UHFFFAOYSA-N [amino(dimethyl)silyl]methane Chemical compound C[Si](C)(C)N KOOADCGQJDGAGA-UHFFFAOYSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
230000009102 absorption Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
MGSKVZWGBWPBTF-UHFFFAOYSA-N aebsf Chemical compound NCCC1=CC=C(S(F)(=O)=O)C=C1 MGSKVZWGBWPBTF-UHFFFAOYSA-N 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical group 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
125000004448 alkyl carbonyl group Chemical group 0.000 description 1
125000005196 alkyl carbonyloxy group Chemical group 0.000 description 1
150000001348 alkyl chlorides Chemical class 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
150000001356 alkyl thiols Chemical class 0.000 description 1
235000020224 almond Nutrition 0.000 description 1
UAMZETBJZRERCQ-UHFFFAOYSA-N alpha-aminopropionitrile Chemical compound CC(N)C#N UAMZETBJZRERCQ-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 1
235000018660 ammonium molybdate Nutrition 0.000 description 1
MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
239000003472 antidiabetic agent Substances 0.000 description 1
SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
229940054051 antipsychotic indole derivative Drugs 0.000 description 1
229960004405 aprotinin Drugs 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
239000008122 artificial sweetener Substances 0.000 description 1
235000021311 artificial sweeteners Nutrition 0.000 description 1
150000001504 aryl thiols Chemical class 0.000 description 1
238000003556 assay Methods 0.000 description 1
UAZDIGCOBKKMPU-UHFFFAOYSA-O azanium;azide Chemical compound [NH4+].[N-]=[N+]=[N-] UAZDIGCOBKKMPU-UHFFFAOYSA-O 0.000 description 1
PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000002146 bilateral effect Effects 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
JBIKOPZNNQPZLH-UHFFFAOYSA-N bis(trifluoromethyl)mercury Chemical compound FC(F)(F)[Hg]C(F)(F)F JBIKOPZNNQPZLH-UHFFFAOYSA-N 0.000 description 1
YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
230000031709 bromination Effects 0.000 description 1
CVDGHGWEHQIJTE-UHFFFAOYSA-N bromo(bromomethoxy)methane Chemical compound BrCOCBr CVDGHGWEHQIJTE-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229960005069 calcium Drugs 0.000 description 1
235000001465 calcium Nutrition 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
238000007707 calorimetry Methods 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
108010086192 chymostatin Proteins 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
238000007333 cyanation reaction Methods 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
238000010908 decantation Methods 0.000 description 1
230000030609 dephosphorylation Effects 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
USQBBPIGNSWXPQ-UHFFFAOYSA-N dibromo(dibromomethoxy)methane Chemical compound BrC(Br)OC(Br)Br USQBBPIGNSWXPQ-UHFFFAOYSA-N 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
BNKDGTGYTVFGBY-UHFFFAOYSA-N diethoxyphosphorylmethyl trifluoromethanesulfonate Chemical compound CCOP(=O)(OCC)COS(=O)(=O)C(F)(F)F BNKDGTGYTVFGBY-UHFFFAOYSA-N 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000003651 drinking water Substances 0.000 description 1
235000020188 drinking water Nutrition 0.000 description 1
238000007908 dry granulation Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
ZJYKSSGYDPNKQS-NSHDSACASA-N ethyl (2s)-2-hydroxy-4-phenylbutanoate Chemical compound CCOC(=O)[C@@H](O)CCC1=CC=CC=C1 ZJYKSSGYDPNKQS-NSHDSACASA-N 0.000 description 1
NGWWADTUHUUBAK-UHFFFAOYSA-N ethyl 2-(3-pyridin-3-ylphenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(C=2C=NC=CC=2)=C1 NGWWADTUHUUBAK-UHFFFAOYSA-N 0.000 description 1
VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
150000002240 furans Chemical class 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
230000003345 hyperglycaemic effect Effects 0.000 description 1
230000001631 hypertensive effect Effects 0.000 description 1
229940126904 hypoglycaemic agent Drugs 0.000 description 1
239000007943 implant Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910052816 inorganic phosphate Inorganic materials 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000003914 insulin secretion Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
230000026045 iodination Effects 0.000 description 1
238000006192 iodination reaction Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
108010052968 leupeptin Proteins 0.000 description 1
239000007788 liquid Substances 0.000 description 1
150000002641 lithium Chemical class 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
210000001853 liver microsome Anatomy 0.000 description 1
238000011068 loading method Methods 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
230000006371 metabolic abnormality Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
YQCIWBXEVYWRCW-UHFFFAOYSA-N methane;sulfane Chemical group C.S YQCIWBXEVYWRCW-UHFFFAOYSA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
XMTFXFMWFYRVIJ-XMMPIXPASA-N methyl (2r)-2-[2,6-dibromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenoxy]-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)Br)C1=CC=CC=C1 XMTFXFMWFYRVIJ-XMMPIXPASA-N 0.000 description 1
LURDKPSPKKCHFI-AREMUKBSSA-N methyl (2r)-2-[2-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-ethylphenoxy]-3-phenylpropanoate Chemical compound C([C@@H](OC1=C(Br)C=C(C=C1CC)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C(=O)OC)C1=CC=CC=C1 LURDKPSPKKCHFI-AREMUKBSSA-N 0.000 description 1
VDPDFUXCCOTPTK-HHHXNRCGSA-N methyl (2r)-2-[2-bromo-4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-6-propan-2-ylphenoxy]-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)C(C)C)C1=CC=CC=C1 VDPDFUXCCOTPTK-HHHXNRCGSA-N 0.000 description 1
UCGZTBKHBYBLPZ-SSEXGKCCSA-N methyl (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-cyclopentylphenoxy]-3-phenylpropanoate Chemical compound C([C@H](C(=O)OC)OC=1C(=CC(=CC=1)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C1CCCC1)C1=CC=CC=C1 UCGZTBKHBYBLPZ-SSEXGKCCSA-N 0.000 description 1
PEGZOXFHIDEKBO-RUZDIDTESA-N methyl (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)-2-fluorophenoxy]-3-phenylpropanoate Chemical compound C([C@H](C(=O)OC)OC=1C(=CC(=CC=1)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)F)C1=CC=CC=C1 PEGZOXFHIDEKBO-RUZDIDTESA-N 0.000 description 1
PNQFGCOZTJKROA-RUZDIDTESA-N methyl (2r)-2-[4-(9-bromo-2,3-dimethylbenzo[f][1]benzothiol-4-yl)phenoxy]-3-phenylpropanoate Chemical compound C([C@H](C(=O)OC)OC=1C=CC(=CC=1)C=1C2=CC=CC=C2C(Br)=C2SC(C)=C(C)C2=1)C1=CC=CC=C1 PNQFGCOZTJKROA-RUZDIDTESA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000012022 methylating agents‎ Substances 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
150000002763 monocarboxylic acids Chemical class 0.000 description 1
YFCUZWYIPBUQBD-ZOWNYOTGSA-N n-[(3s)-7-amino-1-chloro-2-oxoheptan-3-yl]-4-methylbenzenesulfonamide;hydron;chloride Chemical compound Cl.CC1=CC=C(S(=O)(=O)N[C@@H](CCCCN)C(=O)CCl)C=C1 YFCUZWYIPBUQBD-ZOWNYOTGSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000002560 nitrile group Chemical group 0.000 description 1
RBXVOQPAMPBADW-UHFFFAOYSA-N nitrous acid;phenol Chemical class ON=O.OC1=CC=CC=C1 RBXVOQPAMPBADW-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
238000007410 oral glucose tolerance test Methods 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
239000004025 pancreas hormone Substances 0.000 description 1
229940032957 pancreatic hormone Drugs 0.000 description 1
239000008188 pellet Substances 0.000 description 1
108010091212 pepstatin Proteins 0.000 description 1
FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxy-acetic acid Natural products OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 1
229950009215 phenylbutanoic acid Drugs 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
239000006187 pill Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
239000013641 positive control Substances 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
235000012015 potatoes Nutrition 0.000 description 1
229920003124 powdered cellulose Polymers 0.000 description 1
235000019814 powdered cellulose Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000003825 pressing Methods 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
238000002731 protein assay Methods 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
239000000700 radioactive tracer Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
239000003507 refrigerant Substances 0.000 description 1
230000029892 regulation of protein phosphorylation Effects 0.000 description 1
230000008060 renal absorption Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
239000011775 sodium fluoride Substances 0.000 description 1
235000013024 sodium fluoride Nutrition 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000004289 sodium hydrogen sulphite Substances 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
VLHOVNZJTJUSQU-UHFFFAOYSA-M sodium;carbonofluoridate Chemical compound [Na+].[O-]C(F)=O VLHOVNZJTJUSQU-UHFFFAOYSA-M 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical class OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
210000002820 sympathetic nervous system Anatomy 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000004685 tetrahydrates Chemical class 0.000 description 1
230000035924 thermogenesis Effects 0.000 description 1
239000010409 thin film Substances 0.000 description 1
238000000844 transformation Methods 0.000 description 1
PPLMQFARLJLZAO-UHFFFAOYSA-N triethyl(iodo)silane Chemical compound CC[Si](I)(CC)CC PPLMQFARLJLZAO-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000001993 wax Substances 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
238000005303 weighing Methods 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1

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

Landscapes

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

BG104918A 1998-05-12 2000-11-07 Бензотиофени, бензофурани и индоли, полезни при лечение на резистентност към инсулин и хипергликемия BG104918A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US7671298A	1998-05-12	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
BG104918A true BG104918A (bg)	2001-08-31

Family

ID=22133746

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG104918A BG104918A (bg)	1998-05-12	2000-11-07	Бензотиофени, бензофурани и индоли, полезни при лечение на резистентност към инсулин и хипергликемия

Country Status (22)

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

Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6472545B2 (en)	2000-08-29	2002-10-29	Abbott Laboratories	Protein tyrosine phosphatase inhibitors
WO2002018363A2 (en) *	2000-08-29	2002-03-07	Abbott Laboratories	3-phenyl-propanoic acid derivatives as protein tyrosine phosphatase inhibitors
AU2001292518A1 (en) *	2000-09-26	2002-04-08	Biovitrum Ab	Novel compounds
US6498182B2 (en)	2000-09-26	2002-12-24	Biovitrum Ab	Compounds
US6969730B2 (en)	2001-03-16	2005-11-29	Abbott Laboratories	Amines as histamine-3 receptor ligands and their therapeutic applications
AR034375A1 (es) *	2001-06-07	2004-02-18	Wyeth Corp	Combinacion de un inhibidor de ptpasa y un agente de sulfonilurea
US20030022896A1 (en) *	2001-06-07	2003-01-30	Wyeth	PTPase inhibitors for improving cardiovascular risk profile
US20020198202A1 (en) *	2001-06-07	2002-12-26	Wyeth	Combination of a PTPase inhibitor and an antilipemic agent
US6734197B2 (en)	2001-06-07	2004-05-11	Wyeth	Combination therapy for type II diabetes or Syndrome X
WO2002098414A1 (en) *	2001-06-07	2002-12-12	Wyeth	Methods using ptpase inhibitors and insulin
US20020198201A1 (en) *	2001-06-07	2002-12-26	Wyeth	Combination of a PTPase inhibitor and an aldose reductase inhibitor
US20030055058A1 (en) *	2001-06-07	2003-03-20	Wyeth	Combination of a PTPase inhibitor and an ACE inhibitor
US20030013709A1 (en) *	2001-06-07	2003-01-16	Wyeth	Combination of a PTPase inhibitor and an alpha-glucosidase inhibitor
US20020198203A1 (en) *	2001-06-07	2002-12-26	Wyeth	Combination of a PTPase inhibitor and a thiazolidinedione agent
TWI224101B (en)	2001-06-20	2004-11-21	Wyeth Corp	Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
DK1397130T3 (da)	2001-06-20	2007-11-12	Wyeth Corp	Substituerede indolsyrederivater som inhibitorer af plasminogenaktivatorinhibitor-1 (PAI-1)
JP2005508355A (ja) *	2001-10-19	2005-03-31	トランス　テック　ファーマ，インコーポレイテッド	治療薬としてのビス−ヘテロアリールアルカン
US6984645B2 (en)	2001-11-16	2006-01-10	Bristol-Myers Squibb Company	Dual inhibitors of adipocyte fatty acid binding protein and keratinocyte fatty acid binding protein
EP1452530A4 (en)	2001-12-03	2005-11-30	Japan Tobacco Inc	AZOL CONNECTION AND THEIR MEDICAL USE
ITMI20022172A1 (it) *	2002-10-14	2004-04-15	Clariant Lsm Italia Spa	Processo per la preparazione di 3-alchil-tiofeni-2, 5-disostituiti.
JP2006514637A (ja)	2002-12-10	2006-05-11	ワイス	プラスミノーゲン活性化因子の阻害因子−１（ｐａｉ−１）の阻害剤としての置換３−カルボニル−１ｈ−インドール−１−イル酢酸誘導体
ATE430731T1 (de)	2002-12-10	2009-05-15	Wyeth Corp	Substituierte indoloxoacetylaminoessigsäurederivate als inhibitoren des plasminogenaktivatorinhibitors-1 (pai-1)
UA80453C2 (en)	2002-12-10	2007-09-25		Derivatives of substituted dyhydropyranoindol-3,4-dion as inhibitors of plasminogen activator inhibitor-1 (pai-1)
DK1569899T3 (da)	2002-12-10	2006-10-23	Wyeth Corp	Substituerede 3-alkyl- og 3-arylalkyl-1H-indol-1-yl-eddikesyrederivater som inhibitorer af plasminogenaktivator-inhibitor-1 (PAI-1)
DE60324183D1 (en)	2002-12-10	2008-11-27	Wyeth Corp	Aryl-, aryloxy- und alkyloxysubstituierte 1h-indol-3-yl-glyoxylsäurederivateals inhibitoren des plasminogenaktivatorinhibitors-1 (pai-1)
WO2004106542A1 (ja)	2003-05-29	2004-12-09	Sankyo Company, Limited	インスリン抵抗性改善剤及びそのスクリーニング方法
US7504401B2 (en)	2003-08-29	2009-03-17	Locus Pharmaceuticals, Inc.	Anti-cancer agents and uses thereof
US7420083B2 (en)	2003-09-25	2008-09-02	Wyeth	Substituted aryloximes
US7268159B2 (en)	2003-09-25	2007-09-11	Wyeth	Substituted indoles
US7141592B2 (en)	2003-09-25	2006-11-28	Wyeth	Substituted oxadiazolidinediones
US7534894B2 (en)	2003-09-25	2009-05-19	Wyeth	Biphenyloxy-acids
US7371759B2 (en)	2003-09-25	2008-05-13	Bristol-Myers Squibb Company	HMG-CoA reductase inhibitors and method
US7411083B2 (en)	2003-09-25	2008-08-12	Wyeth	Substituted acetic acid derivatives
US7442805B2 (en)	2003-09-25	2008-10-28	Wyeth	Substituted sulfonamide-indoles
US7163954B2 (en)	2003-09-25	2007-01-16	Wyeth	Substituted naphthyl benzothiophene acids
US7265148B2 (en)	2003-09-25	2007-09-04	Wyeth	Substituted pyrrole-indoles
US7351726B2 (en)	2003-09-25	2008-04-01	Wyeth	Substituted oxadiazolidinediones
US7342039B2 (en)	2003-09-25	2008-03-11	Wyeth	Substituted indole oximes
US7332521B2 (en)	2003-09-25	2008-02-19	Wyeth	Substituted indoles
US7582773B2 (en)	2003-09-25	2009-09-01	Wyeth	Substituted phenyl indoles
US7446201B2 (en)	2003-09-25	2008-11-04	Wyeth	Substituted heteroaryl benzofuran acids
US7435837B2 (en)	2003-10-24	2008-10-14	Wyeth	Dihydrobenzofuranyl alkanamine derivatives and methods for using same
FR2862645B1 (fr) *	2003-11-20	2007-06-22	Merck Sante Sas	Composes antidiabetiques contenant des derives benzofuranes, benzothiophenes
US7420059B2 (en)	2003-11-20	2008-09-02	Bristol-Myers Squibb Company	HMG-CoA reductase inhibitors and method
CN101044127A (zh)	2004-08-23	2007-09-26	惠氏公司	用作纤溶酶原激活剂抑制剂－1的噻唑基－萘基酸
US7186749B2 (en)	2004-08-23	2007-03-06	Wyeth	Pyrrolo-naphthyl acids and methods for using them
BRPI0514544A (pt)	2004-08-23	2008-06-17	Wyeth Corp	ácidos de oxazol-naftila como moduladores de inibidor tipo-1 de ativador de plasminogênio (pai-1)
WO2007022321A2 (en)	2005-08-17	2007-02-22	Wyeth	Substituted indoles and use thereof
US8969514B2 (en)	2007-06-04	2015-03-03	Synergy Pharmaceuticals, Inc.	Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
WO2008151257A2 (en)	2007-06-04	2008-12-11	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
WO2009149279A2 (en)	2008-06-04	2009-12-10	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
CA2730603C (en)	2008-07-16	2019-09-24	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
GB0822486D0 (en)	2008-12-10	2009-01-14	Univ Liverpool	Compounds for use in the treatment of pain
US9616097B2 (en)	2010-09-15	2017-04-11	Synergy Pharmaceuticals, Inc.	Formulations of guanylate cyclase C agonists and methods of use
US9486433B2 (en)	2012-10-12	2016-11-08	Mochida Pharmaceuticals Co. Ltd.	Compositions and methods for treating non-alcoholic steatohepatitis
WO2014142364A2 (en)	2013-03-15	2014-09-18	Mochida Pharmaceutical Co., Ltd.	Compositions and methods for treating non-alcoholic steatohepatitis
EP2970384A1 (en)	2013-03-15	2016-01-20	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase and their uses
US10441560B2 (en)	2013-03-15	2019-10-15	Mochida Pharmaceutical Co., Ltd.	Compositions and methods for treating non-alcoholic steatohepatitis
WO2014151200A2 (en)	2013-03-15	2014-09-25	Synergy Pharmaceuticals Inc.	Compositions useful for the treatment of gastrointestinal disorders
AU2014274812B2 (en)	2013-06-05	2018-09-27	Bausch Health Ireland Limited	Ultra-pure agonists of guanylate cyclase C, method of making and using same
CN106749169B (zh) *	2016-11-07	2020-04-21	浙江工业大学	一种Ertiprotafib的手性制备方法
CN107033122B (zh) *	2017-05-19	2019-06-14	南方医科大学	一种n-芳基-2-噻吩酰胺类衍生物及其制备方法和用途
JP7470342B2 (ja)	2018-04-26	2024-04-18	国立大学法人東京工業大学	多能性幹細胞の分化促進方法

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1242970A (en) *	1968-08-15	1971-08-18	Parke Davis & Co	NEW BENZO[b]THIOPHENEACETIC ACID COMPOUNDS AND METHODS FOR THEIR PRODUCTION
US3639422A (en) *	1969-07-28	1972-02-01	Parke Davis & Co	4-phenylindole-1 (and 7)-acetic acids
US3682976A (en) *	1970-02-16	1972-08-08	Parke Davis & Co	Phenyl benzofuran acetic acid compounds
GB8417559D0 (en) *	1984-07-10	1984-08-15	Pfizer Ltd	Anti-diarrhoeal agents
FR2599740B1 (fr) *	1986-06-05	1988-08-12	Rhone Poulenc Sante	Derives de benzo(b)thiophene de benzo(b)furannecarboxamides, leurs procedes de preparation et les medicaments les contenant
JPH01135766A (ja) *	1987-11-20	1989-05-29	Tanabe Seiyaku Co Ltd	ビフェニル誘導体
US5110825A (en) *	1989-12-28	1992-05-05	Shionogi & Co., Ltd.	Benzofuran derivative
US5340833A (en) *	1992-05-01	1994-08-23	Eisai Co., Ltd.	Urokinase inhibitors
DE4425613A1 (de) *	1994-07-20	1996-01-25	Bayer Ag	5-gliedrige Heteroaryl-oxazolidinone

1999
- 1999-05-01 HR HR20000767A patent/HRP20000767A2/hr not_active Application Discontinuation
- 1999-05-10 EE EEP200000653A patent/EE200000653A/xx unknown
- 1999-05-10 HU HU0101792A patent/HUP0101792A3/hu unknown
- 1999-05-10 AU AU38939/99A patent/AU756337B2/en not_active Ceased
- 1999-05-10 EA EA200001175A patent/EA200001175A1/ru unknown
- 1999-05-10 TW TW088107532A patent/TW510900B/zh active
- 1999-05-10 EP EP99921829A patent/EP1077969A1/en not_active Withdrawn
- 1999-05-10 JP JP2000550841A patent/JP2002516321A/ja active Pending
- 1999-05-10 WO PCT/US1999/010209 patent/WO1999061435A1/en not_active Ceased
- 1999-05-10 ID IDW20002311A patent/ID26244A/id unknown
- 1999-05-10 BR BR9911779-7A patent/BR9911779A/pt not_active IP Right Cessation
- 1999-05-10 TR TR2000/03333T patent/TR200003333T2/xx unknown
- 1999-05-10 PL PL99344081A patent/PL344081A1/xx not_active Application Discontinuation
- 1999-05-10 IL IL13913299A patent/IL139132A0/xx unknown
- 1999-05-10 CN CN99808367A patent/CN1308626A/zh active Pending
- 1999-05-10 KR KR1020007012649A patent/KR20010043539A/ko not_active Withdrawn
- 1999-05-10 SK SK1699-2000A patent/SK16992000A3/sk unknown
- 1999-05-10 CA CA002330620A patent/CA2330620A1/en not_active Abandoned
- 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

Also Published As

Publication number	Publication date
ZA200005961B (en)	2001-10-24
CN1308626A (zh)	2001-08-15
BR9911779A (pt)	2001-02-06
CA2330620A1 (en)	1999-12-02
NO20005677L (no)	2000-12-05
AR015294A1 (es)	2001-04-18
IL139132A0 (en)	2001-11-25
AU3893999A (en)	1999-12-13
HRP20000767A2 (en)	2001-10-31
TW510900B (en)	2002-11-21
ID26244A (id)	2000-12-07
AU756337B2 (en)	2003-01-09
WO1999061435A1 (en)	1999-12-02
NO20005677D0 (no)	2000-11-10
KR20010043539A (ko)	2001-05-25
JP2002516321A (ja)	2002-06-04
HUP0101792A3 (en)	2003-01-28
SK16992000A3 (sk)	2001-04-09
HUP0101792A2 (hu)	2002-01-28
TR200003333T2 (tr)	2001-02-21
PL344081A1 (en)	2001-09-24
EP1077969A1 (en)	2001-02-28
EE200000653A (et)	2002-04-15
EA200001175A1 (ru)	2001-06-25

Publication	Publication Date	Title
BG104918A (bg)	2001-08-31	Бензотиофени, бензофурани и индоли, полезни при лечение на резистентност към инсулин и хипергликемия
US6251936B1 (en)	2001-06-26	Benzothiophenes, benzofurans, and indoles useful in the treatment of insulin resistance and hyperglycemia
US6166069A (en)	2000-12-26	Phenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
CA2330623A1 (en)	1999-11-18	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
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
EP1077965A1 (en)	2001-02-28	Phenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
EP1077967A2 (en)	2001-02-28	Biphenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
WO1999058522A1 (en)	1999-11-18	Naphtho[2,3-b]heteroar-4-yl derivatives
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
US6248764B1 (en)	2001-06-19	Furans, benzofurans, and 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
US6340676B2 (en)	2002-01-22	4-aryl-1-oxa-9-thia-cyclopenta (b) fluorenes
CZ20004182A3 (cs)	2001-03-14	Deriváty benzothiofenu, benzofuranu a indolu
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
MXPA00011091A (en)	2001-07-31	Benzothiophenes, benzofurans, and indoles useful in the treatment of insulin resistance and hyperglycemia
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