JP2007512346A - ４−オキソ−４，５−ジヒドロ−フラン−２−カルボン酸誘導体およびその代謝関連障害の処置方法 - Google Patents

Info

Publication number

JP2007512346A

JP2007512346A JP2006541430A JP2006541430A JP2007512346A JP 2007512346 A JP2007512346 A JP 2007512346A JP 2006541430 A JP2006541430 A JP 2006541430A JP 2006541430 A JP2006541430 A JP 2006541430A JP 2007512346 A JP2007512346 A JP 2007512346A

Authority

JP

Japan

Prior art keywords

methyl

phenyl

furan

oxo

dihydro

Prior art date

2003-11-21

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 96
• 230000004060 metabolic process Effects 0.000 title claims description 3
• BMZBEWUYETVZAG-UHFFFAOYSA-N 4-oxofuran-2-carboxylic acid Chemical class OC(=O)C1=CC(=O)CO1 BMZBEWUYETVZAG-UHFFFAOYSA-N 0.000 title abstract description 7
• 150000001875 compounds Chemical class 0.000 claims abstract description 320
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 93
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 47
• 238000011282 treatment Methods 0.000 claims abstract description 46
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 45
• 230000002503 metabolic effect Effects 0.000 claims abstract description 43
• 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 34
• 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 31
• 150000003839 salts Chemical class 0.000 claims abstract description 26
• 239000000556 agonist Substances 0.000 claims abstract description 23
• 208000029078 coronary artery disease Diseases 0.000 claims abstract description 21
• 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 20
• 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 20
• 208000011580 syndromic disease Diseases 0.000 claims abstract description 9
• -1 C 1-6 alkylureyl Chemical group 0.000 claims description 201
• 125000000217 alkyl group Chemical group 0.000 claims description 91
• 125000001072 heteroaryl group Chemical group 0.000 claims description 73
• 125000001424 substituent group Chemical group 0.000 claims description 70
• 229910052736 halogen Inorganic materials 0.000 claims description 57
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 56
• 150000002367 halogens Chemical class 0.000 claims description 56
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 54
• 239000003814 drug Substances 0.000 claims description 41
• 125000003118 aryl group Chemical group 0.000 claims description 38
• 125000003545 alkoxy group Chemical group 0.000 claims description 36
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 36
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 35
• 201000010099 disease Diseases 0.000 claims description 35
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 34
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 32
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 32
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 32
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 32
• 241001465754 Metazoa Species 0.000 claims description 32
• 125000004423 acyloxy group Chemical group 0.000 claims description 32
• 125000004995 haloalkylthio group Chemical group 0.000 claims description 32
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 32
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 31
• 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 claims description 31
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 30
• 125000005363 dialkylsulfonamide group Chemical group 0.000 claims description 30
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
• 125000004749 (C1-C6) haloalkylsulfinyl group Chemical group 0.000 claims description 29
• 125000005432 dialkylcarboxamide group Chemical group 0.000 claims description 29
• 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 28
• 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 28
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
• 229910052799 carbon Inorganic materials 0.000 claims description 25
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 25
• LDRXFNRHMPVZBO-UHFFFAOYSA-N 5-(cyclopenten-1-yl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1CCCC=1C1(C)OC(C(O)=O)=CC1=O LDRXFNRHMPVZBO-UHFFFAOYSA-N 0.000 claims description 24
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
• 229910052739 hydrogen Inorganic materials 0.000 claims description 22
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 21
• 125000003107 substituted aryl group Chemical group 0.000 claims description 20
• 230000015572 biosynthetic process Effects 0.000 claims description 19
• 239000003112 inhibitor Substances 0.000 claims description 18
• 238000003786 synthesis reaction Methods 0.000 claims description 18
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
• 239000003937 drug carrier Substances 0.000 claims description 17
• 238000004519 manufacturing process Methods 0.000 claims description 17
• 229940077274 Alpha glucosidase inhibitor Drugs 0.000 claims description 16
• 239000003888 alpha glucosidase inhibitor Substances 0.000 claims description 16
• 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 15
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 15
• 238000002560 therapeutic procedure Methods 0.000 claims description 13
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 12
• 229940123208 Biguanide Drugs 0.000 claims description 11
• 229910052794 bromium Inorganic materials 0.000 claims description 11
• 239000003623 enhancer Substances 0.000 claims description 11
• 229910052731 fluorine Inorganic materials 0.000 claims description 11
• YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 claims description 10
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 10
• BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 claims description 10
• 239000003795 chemical substances by application Substances 0.000 claims description 10
• PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims description 10
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 10
• 125000001624 naphthyl group Chemical group 0.000 claims description 10
• 239000012453 solvate Substances 0.000 claims description 10
• 229940031439 squalene Drugs 0.000 claims description 10
• TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 claims description 10
• 208000008589 Obesity Diseases 0.000 claims description 9
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 9
• 230000003143 atherosclerotic effect Effects 0.000 claims description 9
• 235000020824 obesity Nutrition 0.000 claims description 9
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 8
• 239000005541 ACE inhibitor Substances 0.000 claims description 8
• 201000004502 glycogen storage disease II Diseases 0.000 claims description 8
• VMKNMLFSCDCNTE-UHFFFAOYSA-N 5-(3-bromophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=CC(Br)=CC=1C1(C)OC(C(O)=O)=CC1=O VMKNMLFSCDCNTE-UHFFFAOYSA-N 0.000 claims description 7
• 208000002705 Glucose Intolerance Diseases 0.000 claims description 7
• 206010020772 Hypertension Diseases 0.000 claims description 7
• 229910052801 chlorine Inorganic materials 0.000 claims description 7
• 208000019622 heart disease Diseases 0.000 claims description 7
• 238000002156 mixing Methods 0.000 claims description 7
• 201000009104 prediabetes syndrome Diseases 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims description 6
• 241000124008 Mammalia Species 0.000 claims description 6
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 6
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
• PXRNPXRNTIDHKJ-UHFFFAOYSA-N 5-methyl-5-(5-methylthiophen-2-yl)-4-oxofuran-2-carboxylic acid Chemical compound S1C(C)=CC=C1C1(C)C(=O)C=C(C(O)=O)O1 PXRNPXRNTIDHKJ-UHFFFAOYSA-N 0.000 claims description 5
• 229940118148 Aldose reductase inhibitor Drugs 0.000 claims description 5
• 239000003288 aldose reductase inhibitor Substances 0.000 claims description 5
• 230000003914 insulin secretion Effects 0.000 claims description 5
• PJBNTDIGQYUCGW-UHFFFAOYSA-N methyl 5-(5-chlorothiophen-2-yl)-5-methyl-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC=C(Cl)S1 PJBNTDIGQYUCGW-UHFFFAOYSA-N 0.000 claims description 5
• GSJDSFMRZXYCRX-UHFFFAOYSA-N methyl 5-methyl-5-(5-methylthiophen-2-yl)-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC=C(C)S1 GSJDSFMRZXYCRX-UHFFFAOYSA-N 0.000 claims description 5
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 4
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
• 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims description 4
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
• 208000006011 Stroke Diseases 0.000 claims description 4
• 229940123464 Thiazolidinedione Drugs 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
• XQJZHAUMCAIKFO-UHFFFAOYSA-N methyl 5-(4-bromothiophen-2-yl)-5-methyl-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC(Br)=CS1 XQJZHAUMCAIKFO-UHFFFAOYSA-N 0.000 claims description 4
• 239000004031 partial agonist Substances 0.000 claims description 4
• ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 claims description 3
• ALXBEPHGSHCMBN-UHFFFAOYSA-N 5-(3,5-difluorophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C(F)=CC(F)=CC=1C1(C)OC(C(O)=O)=CC1=O ALXBEPHGSHCMBN-UHFFFAOYSA-N 0.000 claims description 3
• DCWNQFBOTWDFNR-UHFFFAOYSA-N 5-(3-chlorophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=CC(Cl)=CC=1C1(C)OC(C(O)=O)=CC1=O DCWNQFBOTWDFNR-UHFFFAOYSA-N 0.000 claims description 3
• HUOYXUKHQBGESB-UHFFFAOYSA-N 5-(3-ethylphenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound CCC1=CC=CC(C2(C)C(C=C(O2)C(O)=O)=O)=C1 HUOYXUKHQBGESB-UHFFFAOYSA-N 0.000 claims description 3
• BLOJHYLVLSDXLQ-UHFFFAOYSA-N 5-(3-fluorophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=CC(F)=CC=1C1(C)OC(C(O)=O)=CC1=O BLOJHYLVLSDXLQ-UHFFFAOYSA-N 0.000 claims description 3
• QJKQNKXFEZQYQP-UHFFFAOYSA-N 5-(3-iodophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=CC(I)=CC=1C1(C)OC(C(O)=O)=CC1=O QJKQNKXFEZQYQP-UHFFFAOYSA-N 0.000 claims description 3
• YFPAONQFZGAYEZ-UHFFFAOYSA-N 5-(4-bromo-5-methylthiophen-2-yl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound BrC1=C(C)SC(C2(C)C(C=C(O2)C(O)=O)=O)=C1 YFPAONQFZGAYEZ-UHFFFAOYSA-N 0.000 claims description 3
• YHFHOBUUFHAIJY-UHFFFAOYSA-N 5-(4-bromothiophen-2-yl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C(Br)=CSC=1C1(C)OC(C(O)=O)=CC1=O YHFHOBUUFHAIJY-UHFFFAOYSA-N 0.000 claims description 3
• WJDLYZAOTHNUJX-UHFFFAOYSA-N 5-(5-bromothiophen-3-yl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1SC(Br)=CC=1C1(C)OC(C(O)=O)=CC1=O WJDLYZAOTHNUJX-UHFFFAOYSA-N 0.000 claims description 3
• OIUBTTBLZOOEFX-UHFFFAOYSA-N 5-(5-chlorothiophen-2-yl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=C(Cl)SC=1C1(C)OC(C(O)=O)=CC1=O OIUBTTBLZOOEFX-UHFFFAOYSA-N 0.000 claims description 3
• JPZPZVVRVYTIHX-UHFFFAOYSA-N 5-(5-chlorothiophen-3-yl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1SC(Cl)=CC=1C1(C)OC(C(O)=O)=CC1=O JPZPZVVRVYTIHX-UHFFFAOYSA-N 0.000 claims description 3
• GIOPESNBNCSBLX-UHFFFAOYSA-N 5-methyl-4-oxo-5-[3-(trifluoromethyl)phenyl]furan-2-carboxylic acid Chemical compound C=1C=CC(C(F)(F)F)=CC=1C1(C)OC(C(O)=O)=CC1=O GIOPESNBNCSBLX-UHFFFAOYSA-N 0.000 claims description 3
• SZAVHIWMBRHRGF-UHFFFAOYSA-N 5-methyl-4-oxo-5-thiophen-2-ylfuran-2-carboxylic acid Chemical compound C=1C=CSC=1C1(C)OC(C(O)=O)=CC1=O SZAVHIWMBRHRGF-UHFFFAOYSA-N 0.000 claims description 3
• GRUPRIDVEUNNIP-UHFFFAOYSA-N 5-methyl-4-oxo-5-thiophen-3-ylfuran-2-carboxylic acid Chemical compound C1=CSC=C1C1(C)OC(C(O)=O)=CC1=O GRUPRIDVEUNNIP-UHFFFAOYSA-N 0.000 claims description 3
• UOXNSDQVISINNS-UHFFFAOYSA-N 5-methyl-5-(3-methylphenyl)-4-oxofuran-2-carboxylic acid Chemical compound CC1=CC=CC(C2(C)C(C=C(O2)C(O)=O)=O)=C1 UOXNSDQVISINNS-UHFFFAOYSA-N 0.000 claims description 3
• 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 claims description 3
• 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 claims description 3
• YPMMNDVOYQLHIX-UHFFFAOYSA-N methyl 5-(3-bromophenyl)-5-methyl-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC=CC(Br)=C1 YPMMNDVOYQLHIX-UHFFFAOYSA-N 0.000 claims description 3
• ZTLLDBJMDZIAQP-UHFFFAOYSA-N methyl 5-(5-bromothiophen-3-yl)-5-methyl-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CSC(Br)=C1 ZTLLDBJMDZIAQP-UHFFFAOYSA-N 0.000 claims description 3
• SFKSKFHIKWBWME-UHFFFAOYSA-N methyl 5-(5-chlorothiophen-3-yl)-5-methyl-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CSC(Cl)=C1 SFKSKFHIKWBWME-UHFFFAOYSA-N 0.000 claims description 3
• ZRNYKLLJEIBOST-UHFFFAOYSA-N methyl 5-methyl-4-oxo-5-(3-phenylphenyl)furan-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC=CC(C=2C=CC=CC=2)=C1 ZRNYKLLJEIBOST-UHFFFAOYSA-N 0.000 claims description 3
• SUUNVIHQZOEGPA-UHFFFAOYSA-N methyl 5-methyl-4-oxo-5-(3-thiophen-2-ylphenyl)furan-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC=CC(C=2SC=CC=2)=C1 SUUNVIHQZOEGPA-UHFFFAOYSA-N 0.000 claims description 3
• DGTZAUKZDBYWNN-UHFFFAOYSA-N methyl 5-methyl-4-oxo-5-thiophen-2-ylfuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC=CS1 DGTZAUKZDBYWNN-UHFFFAOYSA-N 0.000 claims description 3
• YFVYMZBCJBUWNH-UHFFFAOYSA-N methyl 5-methyl-4-oxo-5-thiophen-3-ylfuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CSC=C1 YFVYMZBCJBUWNH-UHFFFAOYSA-N 0.000 claims description 3
• ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 2
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 2
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
• 230000001925 catabolic effect Effects 0.000 claims description 2
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
• 150000003857 carboxamides Chemical class 0.000 claims 5
• 125000003396 thiol group Chemical class [H]S* 0.000 claims 5
• TVRUYIIGGOWPAG-UHFFFAOYSA-N 4-oxo-5-phenyl-5-(trifluoromethyl)furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC(=O)C1(C(F)(F)F)C1=CC=CC=C1 TVRUYIIGGOWPAG-UHFFFAOYSA-N 0.000 claims 1
• AZQHSNYXCFYODD-UHFFFAOYSA-N 5-(2,4-difluorophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=C(F)C=C(F)C=1C1(C)OC(C(O)=O)=CC1=O AZQHSNYXCFYODD-UHFFFAOYSA-N 0.000 claims 1
• NLWVUJBQWNYFGM-UHFFFAOYSA-N 5-(2,5-dichlorophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C(Cl)=CC=C(Cl)C=1C1(C)OC(C(O)=O)=CC1=O NLWVUJBQWNYFGM-UHFFFAOYSA-N 0.000 claims 1
• NINDTCSJSZFQTN-UHFFFAOYSA-N 5-(2,6-difluorophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound FC=1C=CC=C(F)C=1C1(C)OC(C(O)=O)=CC1=O NINDTCSJSZFQTN-UHFFFAOYSA-N 0.000 claims 1
• VUJKPKCBMUEMHQ-UHFFFAOYSA-N 5-(2-fluorophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=CC=C(F)C=1C1(C)OC(C(O)=O)=CC1=O VUJKPKCBMUEMHQ-UHFFFAOYSA-N 0.000 claims 1
• NFCWTNPYAANPJO-UHFFFAOYSA-N 5-(3,4-difluorophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=C(F)C(F)=CC=1C1(C)OC(C(O)=O)=CC1=O NFCWTNPYAANPJO-UHFFFAOYSA-N 0.000 claims 1
• RLXNZMWKPKPBFR-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C(Cl)=CC(Cl)=CC=1C1(C)OC(C(O)=O)=CC1=O RLXNZMWKPKPBFR-UHFFFAOYSA-N 0.000 claims 1
• RCCLJOBPQSVKOB-UHFFFAOYSA-N 5-(3-cyanophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=CC(C#N)=CC=1C1(C)OC(C(O)=O)=CC1=O RCCLJOBPQSVKOB-UHFFFAOYSA-N 0.000 claims 1
• AAJWNMBSTFQBSD-UHFFFAOYSA-N 5-(3-ethenylphenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=CC(C=C)=CC=1C1(C)OC(C(O)=O)=CC1=O AAJWNMBSTFQBSD-UHFFFAOYSA-N 0.000 claims 1
• KJRXFRPWDMVTLR-UHFFFAOYSA-N 5-(3-methoxyphenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound COC1=CC=CC(C2(C)C(C=C(O2)C(O)=O)=O)=C1 KJRXFRPWDMVTLR-UHFFFAOYSA-N 0.000 claims 1
• XZXUIFUBIDTNOU-UHFFFAOYSA-N 5-(4-fluorophenyl)-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C)OC(C(O)=O)=CC1=O XZXUIFUBIDTNOU-UHFFFAOYSA-N 0.000 claims 1
• CRGARTVGZYPKJA-UHFFFAOYSA-N 5-cyclopentyl-5-methyl-4-oxofuran-2-carboxylic acid Chemical compound C1CCCC1C1(C)OC(C(O)=O)=CC1=O CRGARTVGZYPKJA-UHFFFAOYSA-N 0.000 claims 1
• SUHZZFNDVLWPTL-UHFFFAOYSA-N 5-ethyl-4-oxo-5-phenylfuran-2-carboxylic acid Chemical compound C=1C=CC=CC=1C1(CC)OC(C(O)=O)=CC1=O SUHZZFNDVLWPTL-UHFFFAOYSA-N 0.000 claims 1
• WNEGYBNWNXRKDH-UHFFFAOYSA-N 5-methyl-4-oxo-5-(3-phenylphenyl)furan-2-carboxylic acid Chemical compound C=1C=CC(C=2C=CC=CC=2)=CC=1C1(C)OC(C(O)=O)=CC1=O WNEGYBNWNXRKDH-UHFFFAOYSA-N 0.000 claims 1
• USBLGWSXFJWTQZ-UHFFFAOYSA-N 5-methyl-4-oxo-5-pyridin-3-ylfuran-2-carboxylic acid Chemical compound C=1C=CN=CC=1C1(C)OC(C(O)=O)=CC1=O USBLGWSXFJWTQZ-UHFFFAOYSA-N 0.000 claims 1
• IGVRQQOEOAUGSS-UHFFFAOYSA-N 5-methyl-5-(4-methylthiophen-2-yl)-4-oxofuran-2-carboxylic acid Chemical compound CC1=CSC(C2(C)C(C=C(O2)C(O)=O)=O)=C1 IGVRQQOEOAUGSS-UHFFFAOYSA-N 0.000 claims 1
• NNWGOUJBCKZULC-UHFFFAOYSA-N 5-methyl-5-(5-methylthiophen-3-yl)-4-oxofuran-2-carboxylic acid Chemical compound S1C(C)=CC(C2(C)C(C=C(O2)C(O)=O)=O)=C1 NNWGOUJBCKZULC-UHFFFAOYSA-N 0.000 claims 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims 1
• 208000018152 Cerebral disease Diseases 0.000 claims 1
• BPQHHASGVYPMQM-UHFFFAOYSA-N methyl 5-(3,5-dichlorophenyl)-5-methyl-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC(Cl)=CC(Cl)=C1 BPQHHASGVYPMQM-UHFFFAOYSA-N 0.000 claims 1
• BCEWABKEWWNHSP-UHFFFAOYSA-N methyl 5-(3-cyanophenyl)-5-methyl-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC=CC(C#N)=C1 BCEWABKEWWNHSP-UHFFFAOYSA-N 0.000 claims 1
• DBVXEVCHXXIWPM-UHFFFAOYSA-N methyl 5-(3-ethylphenyl)-5-methyl-4-oxofuran-2-carboxylate Chemical compound CCC1=CC=CC(C2(C)C(C=C(O2)C(=O)OC)=O)=C1 DBVXEVCHXXIWPM-UHFFFAOYSA-N 0.000 claims 1
• LMPQLRZQMZLROX-UHFFFAOYSA-N methyl 5-(3-iodophenyl)-5-methyl-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC=CC(I)=C1 LMPQLRZQMZLROX-UHFFFAOYSA-N 0.000 claims 1
• HBUOEASWESAVQT-UHFFFAOYSA-N methyl 5-(4-bromo-5-methylthiophen-2-yl)-5-methyl-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC(Br)=C(C)S1 HBUOEASWESAVQT-UHFFFAOYSA-N 0.000 claims 1
• RDGIUTCDQQVCRJ-UHFFFAOYSA-N methyl 5-cyclopentyl-5-methyl-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1CCCC1 RDGIUTCDQQVCRJ-UHFFFAOYSA-N 0.000 claims 1
• ZOBWWBIPYMZPLO-UHFFFAOYSA-N methyl 5-methyl-5-(3-methylphenyl)-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC=CC(C)=C1 ZOBWWBIPYMZPLO-UHFFFAOYSA-N 0.000 claims 1
• PVWBVCKXOMEZLW-UHFFFAOYSA-N methyl 5-methyl-5-(4-methylthiophen-2-yl)-4-oxofuran-2-carboxylate Chemical compound O1C(C(=O)OC)=CC(=O)C1(C)C1=CC(C)=CS1 PVWBVCKXOMEZLW-UHFFFAOYSA-N 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 50
• 150000002148 esters Chemical class 0.000 abstract description 5
• 230000000144 pharmacologic effect Effects 0.000 abstract description 5
• 102000005962 receptors Human genes 0.000 description 56
• 108020003175 receptors Proteins 0.000 description 56
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 50
• 208000035475 disorder Diseases 0.000 description 45
• 238000005481 NMR spectroscopy Methods 0.000 description 41
• 239000000243 solution Substances 0.000 description 35
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 27
• 125000005392 carboxamide group Chemical class NC(=O)* 0.000 description 27
• 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 27
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 27
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
• 150000003573 thiols Chemical class 0.000 description 27
• 239000004480 active ingredient Substances 0.000 description 24
• 238000002360 preparation method Methods 0.000 description 24
• 239000002585 base Substances 0.000 description 20
• 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 20
• 238000009739 binding Methods 0.000 description 20
• 235000012000 cholesterol Nutrition 0.000 description 20
• 230000000694 effects Effects 0.000 description 20
• 229960001031 glucose Drugs 0.000 description 20
• 208000024891 symptom Diseases 0.000 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 description 19
• 230000027455 binding Effects 0.000 description 19
• 239000000126 substance Substances 0.000 description 19
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
• 108010010234 HDL Lipoproteins Proteins 0.000 description 18
• 102000015779 HDL Lipoproteins Human genes 0.000 description 18
• 239000008280 blood Substances 0.000 description 18
• 229940079593 drug Drugs 0.000 description 18
• 239000008103 glucose Substances 0.000 description 18
• 210000004369 blood Anatomy 0.000 description 17
• 241000699670 Mus sp. Species 0.000 description 16
• 235000019439 ethyl acetate Nutrition 0.000 description 16
• 239000000843 powder Substances 0.000 description 16
• 238000012360 testing method Methods 0.000 description 16
• 238000006243 chemical reaction Methods 0.000 description 15
• 239000007788 liquid Substances 0.000 description 15
• 235000001968 nicotinic acid Nutrition 0.000 description 15
• 239000011664 nicotinic acid Substances 0.000 description 15
• 239000003826 tablet Substances 0.000 description 15
• 238000003556 assay Methods 0.000 description 14
• 235000021588 free fatty acids Nutrition 0.000 description 14
• 229960003512 nicotinic acid Drugs 0.000 description 14
• 239000008177 pharmaceutical agent Substances 0.000 description 13
• 230000004044 response Effects 0.000 description 13
• 102000004877 Insulin Human genes 0.000 description 12
• 108090001061 Insulin Proteins 0.000 description 12
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• 239000002775 capsule Substances 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 12
• 239000002552 dosage form Substances 0.000 description 12
• 238000009472 formulation Methods 0.000 description 12
• 229940125396 insulin Drugs 0.000 description 12
• 206010012601 diabetes mellitus Diseases 0.000 description 11
• 239000003446 ligand Substances 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• 238000001727 in vivo Methods 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• 108010016731 PPAR gamma Proteins 0.000 description 9
• 229940100389 Sulfonylurea Drugs 0.000 description 9
• 235000005911 diet Nutrition 0.000 description 9
• 230000037213 diet Effects 0.000 description 9
• 230000003834 intracellular effect Effects 0.000 description 9
• 229910052740 iodine Inorganic materials 0.000 description 9
• 239000007787 solid Substances 0.000 description 9
• 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 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• 108010007622 LDL Lipoproteins Proteins 0.000 description 8
• 102000007330 LDL Lipoproteins Human genes 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 125000001188 haloalkyl group Chemical group 0.000 description 8
• 239000000543 intermediate Substances 0.000 description 8
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
• 239000011541 reaction mixture Substances 0.000 description 8
• 108010076365 Adiponectin Proteins 0.000 description 7
• 150000001408 amides Chemical class 0.000 description 7
• 238000002648 combination therapy Methods 0.000 description 7
• 230000007423 decrease Effects 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• 229940124597 therapeutic agent Drugs 0.000 description 7
• SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• 102000011690 Adiponectin Human genes 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• 102000000019 Sterol Esterase Human genes 0.000 description 6
• 108010055297 Sterol Esterase Proteins 0.000 description 6
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 239000002333 angiotensin II receptor antagonist Substances 0.000 description 6
• 238000010171 animal model Methods 0.000 description 6
• 239000012131 assay buffer Substances 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 239000003085 diluting agent Substances 0.000 description 6
• 238000000338 in vitro Methods 0.000 description 6
• 238000002347 injection Methods 0.000 description 6
• 239000007924 injection Substances 0.000 description 6
• 239000007937 lozenge Substances 0.000 description 6
• 229950004994 meglitinide Drugs 0.000 description 6
• 210000004379 membrane Anatomy 0.000 description 6
• 239000012528 membrane Substances 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• 238000006722 reduction reaction Methods 0.000 description 6
• 239000002904 solvent Substances 0.000 description 6
• 239000003981 vehicle Substances 0.000 description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 5
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
• 241000283984 Rodentia Species 0.000 description 5
• 229910004298 SiO 2 Inorganic materials 0.000 description 5
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 5
• 125000002252 acyl group Chemical group 0.000 description 5
• 239000000443 aerosol Substances 0.000 description 5
• 239000005557 antagonist Substances 0.000 description 5
• 239000000883 anti-obesity agent Substances 0.000 description 5
• 229940125710 antiobesity agent Drugs 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• 150000004283 biguanides Chemical class 0.000 description 5
• 239000011230 binding agent Substances 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 125000003636 chemical group Chemical group 0.000 description 5
• 239000002270 dispersing agent Substances 0.000 description 5
• 239000000839 emulsion Substances 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• 239000004615 ingredient Substances 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 230000009871 nonspecific binding Effects 0.000 description 5
• 239000012044 organic layer Substances 0.000 description 5
• 239000000546 pharmaceutical excipient Substances 0.000 description 5
• 230000008569 process Effects 0.000 description 5
• 239000000651 prodrug Substances 0.000 description 5
• 229940002612 prodrug Drugs 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• 239000000829 suppository Substances 0.000 description 5
• 239000000375 suspending agent Substances 0.000 description 5
• 229910052722 tritium Inorganic materials 0.000 description 5
• 0 *C1(*)OC(C(O*)=O)=C(*)C1=O Chemical compound *C1(*)OC(C(O*)=O)=C(*)C1=O 0.000 description 4
• UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 4
• SIEPUBRNELHUPJ-UHFFFAOYSA-N 3-(5-bromothiophen-3-yl)-3-hydroxybutan-2-one Chemical compound CC(=O)C(C)(O)C1=CSC(Br)=C1 SIEPUBRNELHUPJ-UHFFFAOYSA-N 0.000 description 4
• 108010010803 Gelatin Proteins 0.000 description 4
• 238000008214 LDL Cholesterol Methods 0.000 description 4
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
• 241000699666 Mus <mouse, genus> Species 0.000 description 4
• 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 4
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• 210000001789 adipocyte Anatomy 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 230000015556 catabolic process Effects 0.000 description 4
• 206010008118 cerebral infarction Diseases 0.000 description 4
• 208000026106 cerebrovascular disease Diseases 0.000 description 4
• 239000003086 colorant Substances 0.000 description 4
• 229940125753 fibrate Drugs 0.000 description 4
• 239000000796 flavoring agent Substances 0.000 description 4
• 239000007789 gas Substances 0.000 description 4
• 239000008273 gelatin Substances 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• 235000011852 gelatine desserts Nutrition 0.000 description 4
• 125000000623 heterocyclic group Chemical group 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 230000000670 limiting effect Effects 0.000 description 4
• 150000002632 lipids Chemical class 0.000 description 4
• 108010022197 lipoprotein cholesterol Proteins 0.000 description 4
• 229910052744 lithium Inorganic materials 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 239000002243 precursor Substances 0.000 description 4
• 230000002265 prevention Effects 0.000 description 4
• 150000003254 radicals Chemical class 0.000 description 4
• 230000028327 secretion Effects 0.000 description 4
• 239000007921 spray Substances 0.000 description 4
• 239000008107 starch Substances 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• 238000010189 synthetic method Methods 0.000 description 4
• 239000002562 thickening agent Substances 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• 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 3
• KYCFMILLCSOADS-UHFFFAOYSA-N 2-bromo-4-but-2-en-2-ylthiophene Chemical compound CC=C(C)C1=CSC(Br)=C1 KYCFMILLCSOADS-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 206010002091 Anaesthesia Diseases 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 229920002261 Corn starch Polymers 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 3
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 3
• 206010060378 Hyperinsulinaemia Diseases 0.000 description 3
• 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 3
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
• 240000007472 Leucaena leucocephala Species 0.000 description 3
• QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 3
• 102000012132 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 241000282887 Suidae Species 0.000 description 3
• 238000010521 absorption reaction Methods 0.000 description 3
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 239000000654 additive Substances 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 230000037005 anaesthesia Effects 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 150000001450 anions Chemical class 0.000 description 3
• 239000002830 appetite depressant Substances 0.000 description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
• 239000001768 carboxy methyl cellulose Substances 0.000 description 3
• 150000001735 carboxylic acids Chemical class 0.000 description 3
• 239000008120 corn starch Substances 0.000 description 3
• 230000000875 corresponding effect Effects 0.000 description 3
• 239000006071 cream Substances 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• 238000003745 diagnosis Methods 0.000 description 3
• 235000014113 dietary fatty acids Nutrition 0.000 description 3
• 239000000194 fatty acid Substances 0.000 description 3
• 229930195729 fatty acid Natural products 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 235000013305 food Nutrition 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 230000036541 health Effects 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 201000001421 hyperglycemia Diseases 0.000 description 3
• 230000003451 hyperinsulinaemic effect Effects 0.000 description 3
• 201000008980 hyperinsulinism Diseases 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 229940125425 inverse agonist Drugs 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 235000019626 lipase activity Nutrition 0.000 description 3
• 230000037356 lipid metabolism Effects 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• 229910052757 nitrogen Inorganic materials 0.000 description 3
• 239000002773 nucleotide Substances 0.000 description 3
• 125000003729 nucleotide group Chemical group 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 125000004430 oxygen atom Chemical group O* 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 229940044601 receptor agonist Drugs 0.000 description 3
• 239000000018 receptor agonist Substances 0.000 description 3
• 239000002464 receptor antagonist Substances 0.000 description 3
• 229940044551 receptor antagonist Drugs 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 210000000813 small intestine Anatomy 0.000 description 3
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
• 239000003381 stabilizer Substances 0.000 description 3
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 229930192474 thiophene Natural products 0.000 description 3
• KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
• XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 2
• RWBLWXCGQLZKLK-USVTTYPOSA-N (2s)-2-[(2-aminoacetyl)amino]-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[2-[[(2s)-1-[[(2s)-1-[[(2s)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxob Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(N)=O)NC(=O)CN)C(C)C)C1=CN=CN1 RWBLWXCGQLZKLK-USVTTYPOSA-N 0.000 description 2
• CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
• 125000006002 1,1-difluoroethyl group Chemical group 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
• ODRKWPAKOZGXHK-UHFFFAOYSA-N 2-(5-bromothiophen-3-yl)butane-2,3-diol Chemical compound CC(O)C(C)(O)C1=CSC(Br)=C1 ODRKWPAKOZGXHK-UHFFFAOYSA-N 0.000 description 2
• 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 2
• UUHPDADIATTZKN-UHFFFAOYSA-N 3-(cyclohexen-1-yl)-3-hydroxybutan-2-one Chemical compound CC(=O)C(C)(O)C1=CCCCC1 UUHPDADIATTZKN-UHFFFAOYSA-N 0.000 description 2
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000006163 5-membered heteroaryl group Chemical group 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
• 102000054930 Agouti-Related Human genes 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 2
• 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• 102000014914 Carrier Proteins Human genes 0.000 description 2
• 108010078791 Carrier Proteins Proteins 0.000 description 2
• 101710150887 Cholecystokinin A Proteins 0.000 description 2
• 229910020366 ClO 4 Inorganic materials 0.000 description 2
• 229920002911 Colestipol Polymers 0.000 description 2
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
• 108010023302 HDL Cholesterol Proteins 0.000 description 2
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
• 206010060800 Hot flush Diseases 0.000 description 2
• 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 description 2
• 229940122199 Insulin secretagogue Drugs 0.000 description 2
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 102000016267 Leptin Human genes 0.000 description 2
• 108010092277 Leptin Proteins 0.000 description 2
• 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 2
• IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 2
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 2
• 102000004316 Oxidoreductases Human genes 0.000 description 2
• 108090000854 Oxidoreductases Proteins 0.000 description 2
• 101710184309 Probable sucrose-6-phosphate hydrolase Proteins 0.000 description 2
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 238000000692 Student's t-test Methods 0.000 description 2
• 102400000472 Sucrase Human genes 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
• 229930006000 Sucrose Natural products 0.000 description 2
• 101710112652 Sucrose-6-phosphate hydrolase Proteins 0.000 description 2
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
• FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 2
• FYJKEHKQUPSJDH-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;potassium Chemical compound [K].C[Si](C)(C)N[Si](C)(C)C FYJKEHKQUPSJDH-UHFFFAOYSA-N 0.000 description 2
• 229960002632 acarbose Drugs 0.000 description 2
• XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 2
• 229960001138 acetylsalicylic acid Drugs 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
• 102000030621 adenylate cyclase Human genes 0.000 description 2
• 108060000200 adenylate cyclase Proteins 0.000 description 2
• 210000000577 adipose tissue Anatomy 0.000 description 2
• 150000001336 alkenes Chemical class 0.000 description 2
• 125000005422 alkyl sulfonamido group Chemical group 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• 102000004139 alpha-Amylases Human genes 0.000 description 2
• 108090000637 alpha-Amylases Proteins 0.000 description 2
• 102000016679 alpha-Glucosidases Human genes 0.000 description 2
• 108010028144 alpha-Glucosidases Proteins 0.000 description 2
• 229940024171 alpha-amylase Drugs 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 230000003243 anti-lipolytic effect Effects 0.000 description 2
• 239000003529 anticholesteremic agent Substances 0.000 description 2
• 229940127226 anticholesterol agent Drugs 0.000 description 2
• 210000000709 aorta Anatomy 0.000 description 2
• 210000000702 aorta abdominal Anatomy 0.000 description 2
• 210000002376 aorta thoracic Anatomy 0.000 description 2
• 230000036528 appetite Effects 0.000 description 2
• 235000019789 appetite Nutrition 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 2
• 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 description 2
• 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 description 2
• 125000004266 aziridin-1-yl group Chemical group [H]C1([H])N(*)C1([H])[H] 0.000 description 2
• 125000004267 aziridin-2-yl group Chemical group [H]N1C([H])([H])C1([H])* 0.000 description 2
• KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 2
• 229960000516 bezafibrate Drugs 0.000 description 2
• IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 2
• 229960002802 bromocriptine Drugs 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 2
• 229960003009 clopidogrel Drugs 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• 229960002604 colestipol Drugs 0.000 description 2
• GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 2
• 229940125904 compound 1 Drugs 0.000 description 2
• 229940125833 compound 23 Drugs 0.000 description 2
• 230000002596 correlated effect Effects 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 231100000517 death Toxicity 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 229910052805 deuterium Inorganic materials 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
• 230000029087 digestion Effects 0.000 description 2
• 102000038379 digestive enzymes Human genes 0.000 description 2
• 108091007734 digestive enzymes Proteins 0.000 description 2
• 150000002009 diols Chemical class 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• UFJGNEVQYHKAKE-UHFFFAOYSA-N dithian-3-ol Chemical compound OC1CCCSS1 UFJGNEVQYHKAKE-UHFFFAOYSA-N 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000006274 endogenous ligand Substances 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• BLHLJVCOVBYQQS-UHFFFAOYSA-N ethyllithium Chemical compound [Li]CC BLHLJVCOVBYQQS-UHFFFAOYSA-N 0.000 description 2
• 239000013604 expression vector Substances 0.000 description 2
• 238000013213 extrapolation Methods 0.000 description 2
• OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 2
• 229960000815 ezetimibe Drugs 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 229960002297 fenofibrate Drugs 0.000 description 2
• YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• 230000002140 halogenating effect Effects 0.000 description 2
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 238000003384 imaging method Methods 0.000 description 2
• 238000005462 in vivo assay Methods 0.000 description 2
• 239000004026 insulin derivative Substances 0.000 description 2
• 235000011073 invertase Nutrition 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 229960002725 isoflurane Drugs 0.000 description 2
• 210000004731 jugular vein Anatomy 0.000 description 2
• 150000002576 ketones Chemical class 0.000 description 2
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical class O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 2
• 230000003902 lesion Effects 0.000 description 2
• 230000004130 lipolysis Effects 0.000 description 2
• XBEREOHJDYAKDA-UHFFFAOYSA-N lithium;propane Chemical compound [Li+].CC[CH2-] XBEREOHJDYAKDA-UHFFFAOYSA-N 0.000 description 2
• 239000006210 lotion Substances 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• 208000030159 metabolic disease Diseases 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
• 229960001110 miglitol Drugs 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• 208000031225 myocardial ischemia Diseases 0.000 description 2
• 210000003928 nasal cavity Anatomy 0.000 description 2
• 239000006199 nebulizer Substances 0.000 description 2
• 229940105631 nembutal Drugs 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
• 238000006772 olefination reaction Methods 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 125000001715 oxadiazolyl group Chemical group 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
• 229920001592 potato starch Polymers 0.000 description 2
• 238000000159 protein binding assay Methods 0.000 description 2
• 229940121649 protein inhibitor Drugs 0.000 description 2
• 239000012268 protein inhibitor Substances 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 239000000719 purinergic P2Y receptor antagonist Substances 0.000 description 2
• 229960001455 quinapril Drugs 0.000 description 2
• JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000000241 respiratory effect Effects 0.000 description 2
• 230000006965 reversible inhibition Effects 0.000 description 2
• JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 2
• 150000004671 saturated fatty acids Chemical class 0.000 description 2
• 235000003441 saturated fatty acids Nutrition 0.000 description 2
• 238000007423 screening assay Methods 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 229960004425 sibutramine Drugs 0.000 description 2
• UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 230000009870 specific binding Effects 0.000 description 2
• 229960002909 spirapril Drugs 0.000 description 2
• HRWCVUIFMSZDJS-SZMVWBNQSA-N spirapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCS2)C(O)=O)CC1=CC=CC=C1 HRWCVUIFMSZDJS-SZMVWBNQSA-N 0.000 description 2
• 108700035424 spirapril Proteins 0.000 description 2
• 235000000891 standard diet Nutrition 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 238000007910 systemic administration Methods 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• 150000001467 thiazolidinediones Chemical class 0.000 description 2
• 230000008719 thickening Effects 0.000 description 2
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 2
• 125000000464 thioxo group Chemical group S=* 0.000 description 2
• PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 2
• 229960005001 ticlopidine Drugs 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• CMSGWTNRGKRWGS-NQIIRXRSSA-N torcetrapib Chemical compound COC(=O)N([C@H]1C[C@@H](CC)N(C2=CC=C(C=C21)C(F)(F)F)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CMSGWTNRGKRWGS-NQIIRXRSSA-N 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 229940116362 tragacanth Drugs 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 150000003626 triacylglycerols Chemical class 0.000 description 2
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
• 239000013598 vector Substances 0.000 description 2
• 210000003462 vein Anatomy 0.000 description 2
• 229960001729 voglibose Drugs 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
• QYYZXEPEVBXNNA-QGZVFWFLSA-N (1R)-2-acetyl-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-methylsulfonyl-1,3-dihydroisoindole-1-carboxamide Chemical compound C(C)(=O)N1[C@H](C2=CC=C(C=C2C1)S(=O)(=O)C)C(=O)NC1=CC=C(C=C1)C(C(F)(F)F)(C(F)(F)F)O QYYZXEPEVBXNNA-QGZVFWFLSA-N 0.000 description 1
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• VXEVKSKAINMPFG-QWUNSSNDSA-N (2S)-5-[[(5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-5-oxopentanoyl]amino]propanoyl]amino]propanoyl]amino]-6-[[(2S)-4-carboxy-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-(carboxymethylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxobutan-2-yl]amino]-6-oxohexyl]amino]-2-(hexadecanoylamino)-5-hydroxypentanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(NCCCC[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)N)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC6=CNC=N6)N)O)C(=O)O VXEVKSKAINMPFG-QWUNSSNDSA-N 0.000 description 1
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
• HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
• BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
• CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
• BEDKDDPMXRCHPJ-UHFFFAOYSA-N 1-(5-bromothiophen-3-yl)ethanone Chemical compound CC(=O)C1=CSC(Br)=C1 BEDKDDPMXRCHPJ-UHFFFAOYSA-N 0.000 description 1
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
• PMGZJNCIQHGNLT-UHFFFAOYSA-N 1-[bis(2,2-dimethylpropanoyloxymethoxy)phosphoryl]-4-(3-phenoxyphenyl)butane-1-sulfonic acid Chemical compound CC(C)(C)C(=O)OCOP(=O)(OCOC(=O)C(C)(C)C)C(S(O)(=O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 PMGZJNCIQHGNLT-UHFFFAOYSA-N 0.000 description 1
• UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
• HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
• IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 description 1
• YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
• TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• KXROTPXCYDXGSC-UHFFFAOYSA-N 2-methyl-1,3-dithiane Chemical compound CC1SCCCS1 KXROTPXCYDXGSC-UHFFFAOYSA-N 0.000 description 1
• YZQLWPMZQVHJED-UHFFFAOYSA-N 2-methylpropanethioic acid S-[2-[[[1-(2-ethylbutyl)cyclohexyl]-oxomethyl]amino]phenyl] ester Chemical compound C=1C=CC=C(SC(=O)C(C)C)C=1NC(=O)C1(CC(CC)CC)CCCCC1 YZQLWPMZQVHJED-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• DJQOOSBJCLSSEY-UHFFFAOYSA-N Acipimox Chemical compound CC1=CN=C(C(O)=O)C=[N+]1[O-] DJQOOSBJCLSSEY-UHFFFAOYSA-N 0.000 description 1
• 208000030090 Acute Disease Diseases 0.000 description 1
• 108700021677 Agouti-Related Proteins 0.000 description 1
• FHHHOYXPRDYHEZ-COXVUDFISA-N Alacepril Chemical compound CC(=O)SC[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FHHHOYXPRDYHEZ-COXVUDFISA-N 0.000 description 1
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-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
• 229940127438 Amylin Agonists Drugs 0.000 description 1
• 108050000824 Angiotensin II receptor Proteins 0.000 description 1
• 102000008873 Angiotensin II receptor Human genes 0.000 description 1
• 101710095342 Apolipoprotein B Proteins 0.000 description 1
• 102100040202 Apolipoprotein B-100 Human genes 0.000 description 1
• 102000018616 Apolipoproteins B Human genes 0.000 description 1
• 108010027006 Apolipoproteins B Proteins 0.000 description 1
• 200000000007 Arterial disease Diseases 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
• XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
• 102000013585 Bombesin Human genes 0.000 description 1
• 108010051479 Bombesin Proteins 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 238000009010 Bradford assay Methods 0.000 description 1
• 208000032841 Bulimia Diseases 0.000 description 1
• 206010006550 Bulimia nervosa Diseases 0.000 description 1
• KYCFMILLCSOADS-UTCJRWHESA-N C/C=C(/C)\c1c[s]c(Br)c1 Chemical compound C/C=C(/C)\c1c[s]c(Br)c1 KYCFMILLCSOADS-UTCJRWHESA-N 0.000 description 1
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
• 239000002083 C09CA01 - Losartan Substances 0.000 description 1
• FPFGVFBQUVULCT-UHFFFAOYSA-N CC(C(C)(C(C1)=CSC1Br)O)O Chemical compound CC(C(C)(C(C1)=CSC1Br)O)O FPFGVFBQUVULCT-UHFFFAOYSA-N 0.000 description 1
• ZMXSJWGMKRXCLT-UHFFFAOYSA-N CC(C1(C)SCCCS1)(C1=CCCCC1)O Chemical compound CC(C1(C)SCCCS1)(C1=CCCCC1)O ZMXSJWGMKRXCLT-UHFFFAOYSA-N 0.000 description 1
• WZSGORNHMKJGII-UHFFFAOYSA-N CC1(C2=CCCCC2)OC(C(O)=O)=CC1=O Chemical compound CC1(C2=CCCCC2)OC(C(O)=O)=CC1=O WZSGORNHMKJGII-UHFFFAOYSA-N 0.000 description 1
• AAYKCDKHWYBBAC-UHFFFAOYSA-N CC1(C2=CCCCC2)OC(C(OC)=O)=CC1=O Chemical compound CC1(C2=CCCCC2)OC(C(OC)=O)=CC1=O AAYKCDKHWYBBAC-UHFFFAOYSA-N 0.000 description 1
• LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• 229940123158 Cannabinoid CB1 receptor antagonist Drugs 0.000 description 1
• 206010008479 Chest Pain Diseases 0.000 description 1
• 206010051914 Cholesterosis Diseases 0.000 description 1
• 229920001268 Cholestyramine Polymers 0.000 description 1
• 208000017667 Chronic Disease Diseases 0.000 description 1
• 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
• 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
• 108020004705 Codon Proteins 0.000 description 1
• 229940126657 Compound 17 Drugs 0.000 description 1
• MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
• UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-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
• ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 description 1
• NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 description 1
• 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
• 239000004375 Dextrin Substances 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• 208000000059 Dyspnea Diseases 0.000 description 1
• 206010013975 Dyspnoeas Diseases 0.000 description 1
• 108010061435 Enalapril Proteins 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 108010011459 Exenatide Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• GGUVRMBIEPYOKL-WMVCGJOFSA-N GW 409544 Chemical compound C([C@H](NC(/C)=C\C(=O)C=1C=CC=CC=1)C(O)=O)C(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 GGUVRMBIEPYOKL-WMVCGJOFSA-N 0.000 description 1
• YDBLKRPLXZNVNB-UHFFFAOYSA-N GW 501516 Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC=C(OCC(O)=O)C(C)=C1 YDBLKRPLXZNVNB-UHFFFAOYSA-N 0.000 description 1
• 102400001370 Galanin Human genes 0.000 description 1
• 101800002068 Galanin Proteins 0.000 description 1
• 108010016122 Ghrelin Receptors Proteins 0.000 description 1
• 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 1
• 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
• 102100039256 Growth hormone secretagogue receptor type 1 Human genes 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000928179 Homo sapiens Agouti-related protein Proteins 0.000 description 1
• 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 101710125793 Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 1
• 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
• 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• 102000000853 LDL receptors Human genes 0.000 description 1
• 108010001831 LDL receptors Proteins 0.000 description 1
• 229940122942 Leptin receptor agonist Drugs 0.000 description 1
• 229940086609 Lipase inhibitor Drugs 0.000 description 1
• 108010007859 Lisinopril Proteins 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 108010000410 MSH receptor Proteins 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 1
• 102400001132 Melanin-concentrating hormone Human genes 0.000 description 1
• 101800002739 Melanin-concentrating hormone Proteins 0.000 description 1
• 102100034216 Melanocyte-stimulating hormone receptor Human genes 0.000 description 1
• 101710151321 Melanostatin Proteins 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 229920000881 Modified starch Polymers 0.000 description 1
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
• 102400000064 Neuropeptide Y Human genes 0.000 description 1
• 108700010041 Nicotinic acid receptor Proteins 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 229940123730 Orexin receptor antagonist Drugs 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010033307 Overweight Diseases 0.000 description 1
• 208000031481 Pathologic Constriction Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229940127495 Peroxisome Proliferator-activated Receptor gamma Agonists Drugs 0.000 description 1
• 241000009328 Perro Species 0.000 description 1
• 238000003527 Peterson olefination reaction Methods 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• 208000004880 Polyuria Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• 238000000297 Sandmeyer reaction Methods 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 208000007718 Stable Angina Diseases 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 238000006859 Swern oxidation reaction Methods 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
• 102000005630 Urocortins Human genes 0.000 description 1
• 108010059705 Urocortins Proteins 0.000 description 1
• 238000007239 Wittig reaction Methods 0.000 description 1
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
• QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 1
• QKNDAUTYSODFJV-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;sodium Chemical compound [Na].C[Si](C)(C)N[Si](C)(C)C QKNDAUTYSODFJV-UHFFFAOYSA-N 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 102000005421 acetyltransferase Human genes 0.000 description 1
• 108020002494 acetyltransferase Proteins 0.000 description 1
• DFDGRKNOFOJBAJ-UHFFFAOYSA-N acifran Chemical compound C=1C=CC=CC=1C1(C)OC(C(O)=O)=CC1=O DFDGRKNOFOJBAJ-UHFFFAOYSA-N 0.000 description 1
• 229950000146 acifran Drugs 0.000 description 1
• 229960003526 acipimox Drugs 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 229960005305 adenosine Drugs 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000000048 adrenergic agonist Substances 0.000 description 1
• 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 229950007884 alacepril Drugs 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000004703 alkoxides Chemical class 0.000 description 1
• 125000003282 alkyl amino group Chemical group 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 230000006538 anaerobic glycolysis Effects 0.000 description 1
• 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
• 230000000702 anti-platelet effect Effects 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940127218 antiplatelet drug Drugs 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 208000011775 arteriosclerosis disease Diseases 0.000 description 1
• 239000008122 artificial sweetener Substances 0.000 description 1
• 235000021311 artificial sweeteners Nutrition 0.000 description 1
• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 108010014210 axokine Proteins 0.000 description 1
• 235000015278 beef Nutrition 0.000 description 1
• 229960004530 benazepril Drugs 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
• DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 210000000941 bile Anatomy 0.000 description 1
• 239000003613 bile acid Substances 0.000 description 1
• 229920000080 bile acid sequestrant Polymers 0.000 description 1
• 229940096699 bile acid sequestrants Drugs 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 229960000074 biopharmaceutical Drugs 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 229960004111 buformin Drugs 0.000 description 1
• XSEUMFJMFFMCIU-UHFFFAOYSA-N buformin Chemical compound CCCC\N=C(/N)N=C(N)N XSEUMFJMFFMCIU-UHFFFAOYSA-N 0.000 description 1
• 239000004067 bulking agent Substances 0.000 description 1
• SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 1
• 229960001058 bupropion Drugs 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 239000003555 cannabinoid 1 receptor antagonist Substances 0.000 description 1
• 229960000830 captopril Drugs 0.000 description 1
• FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 150000001723 carbon free-radicals Chemical class 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 238000010531 catalytic reduction reaction Methods 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 1
• 229960005110 cerivastatin Drugs 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
• RCTYPNKXASFOBE-UHFFFAOYSA-M chloromercury Chemical compound [Hg]Cl RCTYPNKXASFOBE-UHFFFAOYSA-M 0.000 description 1
• 230000001906 cholesterol absorption Effects 0.000 description 1
• 150000001840 cholesterol esters Chemical class 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 description 1
• 229960005025 cilazapril Drugs 0.000 description 1
• 229960001214 clofibrate Drugs 0.000 description 1
• KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 229940125797 compound 12 Drugs 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940126142 compound 16 Drugs 0.000 description 1
• 229940125782 compound 2 Drugs 0.000 description 1
• 229940125810 compound 20 Drugs 0.000 description 1
• 229940126086 compound 21 Drugs 0.000 description 1
• 229940126208 compound 22 Drugs 0.000 description 1
• 229940125961 compound 24 Drugs 0.000 description 1
• 229940125846 compound 25 Drugs 0.000 description 1
• 229940125851 compound 27 Drugs 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• 229940125898 compound 5 Drugs 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 230000001186 cumulative effect Effects 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
• 229960005227 delapril Drugs 0.000 description 1
• WOUOLAUOZXOLJQ-MBSDFSHPSA-N delapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N(CC(O)=O)C1CC2=CC=CC=C2C1)CC1=CC=CC=C1 WOUOLAUOZXOLJQ-MBSDFSHPSA-N 0.000 description 1
• 239000000551 dentifrice Substances 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 239000012954 diazonium Substances 0.000 description 1
• 150000001989 diazonium salts Chemical class 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• 150000001993 dienes Chemical class 0.000 description 1
• 238000011496 digital image analysis Methods 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
• 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 230000035622 drinking Effects 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 210000005069 ears Anatomy 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 229960000873 enalapril Drugs 0.000 description 1
• GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
• 229960002680 enalaprilat Drugs 0.000 description 1
• LZFZMUMEGBBDTC-QEJZJMRPSA-N enalaprilat (anhydrous) Chemical compound C([C@H](N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 LZFZMUMEGBBDTC-QEJZJMRPSA-N 0.000 description 1
• 150000002085 enols Chemical class 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 229960002179 ephedrine Drugs 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• JHYNXXDQQHTCHJ-UHFFFAOYSA-M ethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC)C1=CC=CC=C1 JHYNXXDQQHTCHJ-UHFFFAOYSA-M 0.000 description 1
• 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
• 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 230000001610 euglycemic effect Effects 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 229960001519 exenatide Drugs 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000012025 fluorinating agent Substances 0.000 description 1
• 238000011010 flushing procedure Methods 0.000 description 1
• 229960003765 fluvastatin Drugs 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 229960002490 fosinopril Drugs 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000003349 gelling agent Substances 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 229960004580 glibenclamide Drugs 0.000 description 1
• WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
• 229960004346 glimepiride Drugs 0.000 description 1
• ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
• 229960001381 glipizide Drugs 0.000 description 1
• 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 1
• 229940124750 glucocorticoid receptor agonist Drugs 0.000 description 1
• 230000004110 gluconeogenesis Effects 0.000 description 1
• 230000009229 glucose formation Effects 0.000 description 1
• 230000006377 glucose transport Effects 0.000 description 1
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
• MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
• 229940029575 guanosine Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 125000004440 haloalkylsulfinyl group Chemical group 0.000 description 1
• 125000004441 haloalkylsulfonyl group Chemical group 0.000 description 1
• 230000005802 health problem Effects 0.000 description 1
• 231100000304 hepatotoxicity Toxicity 0.000 description 1
• 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
• 125000005241 heteroarylamino group Chemical group 0.000 description 1
• 229960001340 histamine Drugs 0.000 description 1
• 238000010562 histological examination Methods 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• 239000003667 hormone antagonist Substances 0.000 description 1
• 102000055839 human AGRP Human genes 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 230000003345 hyperglycaemic effect Effects 0.000 description 1
• 229960001195 imidapril Drugs 0.000 description 1
• KLZWOWYOHUKJIG-BPUTZDHNSA-N imidapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1C(N(C)C[C@H]1C(O)=O)=O)CC1=CC=CC=C1 KLZWOWYOHUKJIG-BPUTZDHNSA-N 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 239000005414 inactive ingredient Substances 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 230000026045 iodination Effects 0.000 description 1
• 238000006192 iodination reaction Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 229940039781 leptin Drugs 0.000 description 1
• 230000002366 lipolytic effect Effects 0.000 description 1
• 229960002701 liraglutide Drugs 0.000 description 1
• 229960002394 lisinopril Drugs 0.000 description 1
• CZRQXSDBMCMPNJ-ZUIPZQNBSA-N lisinopril dihydrate Chemical compound O.O.C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 CZRQXSDBMCMPNJ-ZUIPZQNBSA-N 0.000 description 1
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
• WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 230000007056 liver toxicity Effects 0.000 description 1
• KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
• 229960004773 losartan Drugs 0.000 description 1
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
• 229960004844 lovastatin Drugs 0.000 description 1
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 229960000299 mazindol Drugs 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 description 1
• BQPIGGFYSBELGY-UHFFFAOYSA-N mercury(2+) Chemical compound [Hg+2] BQPIGGFYSBELGY-UHFFFAOYSA-N 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 229910052987 metal hydride Inorganic materials 0.000 description 1
• 150000004681 metal hydrides Chemical class 0.000 description 1
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
• 229960003105 metformin Drugs 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• QTABOWCQAPYNPP-UHFFFAOYSA-N methyl 2,2,2-trimethoxyacetate Chemical compound COC(=O)C(OC)(OC)OC QTABOWCQAPYNPP-UHFFFAOYSA-N 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 230000003228 microsomal effect Effects 0.000 description 1
• 108010038232 microsomal triglyceride transfer protein Proteins 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 235000019426 modified starch Nutrition 0.000 description 1
• SLZIZIJTGAYEKK-CIJSCKBQSA-N molport-023-220-247 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CNC=N1 SLZIZIJTGAYEKK-CIJSCKBQSA-N 0.000 description 1
• 238000000465 moulding Methods 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000006095 n-butyl sulfinyl group Chemical group 0.000 description 1
• 125000006126 n-butyl sulfonyl group Chemical group 0.000 description 1
• 125000006093 n-propyl sulfinyl group Chemical group 0.000 description 1
• 125000006124 n-propyl sulfonyl group Chemical group 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
• 229960000698 nateglinide Drugs 0.000 description 1
• PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 description 1
• 229950001628 netoglitazone Drugs 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 1
• 230000002474 noradrenergic effect Effects 0.000 description 1
• 229940127221 norepinephrine reuptake inhibitor Drugs 0.000 description 1
• 230000001019 normoglycemic effect Effects 0.000 description 1
• URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 125000003835 nucleoside group Chemical group 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 125000000962 organic group Chemical group 0.000 description 1
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
• 229960001243 orlistat Drugs 0.000 description 1
• 150000002905 orthoesters Chemical class 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 230000007310 pathophysiology Effects 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 229960002582 perindopril Drugs 0.000 description 1
• IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 210000003200 peritoneal cavity Anatomy 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229960003243 phenformin Drugs 0.000 description 1
• ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
• 229960003562 phentermine Drugs 0.000 description 1
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
• 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 229960005095 pioglitazone Drugs 0.000 description 1
• VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
• 229960002797 pitavastatin Drugs 0.000 description 1
• 239000000902 placebo Substances 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 208000015768 polyposis Diseases 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical group [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
• RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
• 229960003611 pramlintide Drugs 0.000 description 1
• 108010029667 pramlintide Proteins 0.000 description 1
• NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 description 1
• 229960002847 prasterone Drugs 0.000 description 1
• GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
• ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 239000011241 protective layer Substances 0.000 description 1
• 229940076372 protein antagonist Drugs 0.000 description 1
• KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
• 229960003908 pseudoephedrine Drugs 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 239000000700 radioactive tracer Substances 0.000 description 1
• 229960003401 ramipril Drugs 0.000 description 1
• HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 238000001525 receptor binding assay Methods 0.000 description 1
• 239000002469 receptor inverse agonist Substances 0.000 description 1
• 230000006798 recombination Effects 0.000 description 1
• 238000005215 recombination Methods 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000008929 regeneration Effects 0.000 description 1
• 238000011069 regeneration method Methods 0.000 description 1
• 238000000611 regression analysis Methods 0.000 description 1
• 230000013333 regulation of fatty acid metabolic process Effects 0.000 description 1
• 229960002354 repaglinide Drugs 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 238000011808 rodent model Methods 0.000 description 1
• 229960004586 rosiglitazone Drugs 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 239000012363 selectfluor Substances 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 239000003352 sequestering agent Substances 0.000 description 1
• 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
• 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
• 208000013220 shortness of breath Diseases 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
• WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 238000005507 spraying Methods 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 230000036262 stenosis Effects 0.000 description 1
• 208000037804 stenosis Diseases 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• 125000001174 sulfone group Chemical group 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 229940127230 sympathomimetic drug Drugs 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000003760 tallow Substances 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 description 1
• 229950004704 tesaglitazar Drugs 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000000101 thioether group Chemical group 0.000 description 1
• 229940104230 thymidine Drugs 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 238000003354 tissue distribution assay Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229950004514 torcetrapib Drugs 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000440 toxicity profile Toxicity 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
• 229940029284 trichlorofluoromethane Drugs 0.000 description 1
• HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
• 229940038773 trisodium citrate Drugs 0.000 description 1
• 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
• 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
• DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
• 229940045145 uridine Drugs 0.000 description 1
• 239000000777 urocortin Substances 0.000 description 1
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 239000011345 viscous material Substances 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• 235000019156 vitamin B Nutrition 0.000 description 1
• 239000011720 vitamin B Substances 0.000 description 1
• 229940046001 vitamin b complex Drugs 0.000 description 1
• 150000003722 vitamin derivatives Chemical class 0.000 description 1
• 238000011680 zucker rat Methods 0.000 description 1