CA2490138A1 - Novel tetrahydropyridine derivatives as renin inhibitors - Google Patents

Info

Publication number

CA2490138A1

CA2490138A1 CA002490138A CA2490138A CA2490138A1 CA 2490138 A1 CA2490138 A1 CA 2490138A1 CA 002490138 A CA002490138 A CA 002490138A CA 2490138 A CA2490138 A CA 2490138A CA 2490138 A1 CA2490138 A1 CA 2490138A1

Authority

CA

Canada

Prior art keywords

phenyl

carboxylic acid

ethoxy

tetrahydropyridine

amide

Prior art date

2002-06-27

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical class C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 title abstract description 7
• 239000002461 renin inhibitor Substances 0.000 title description 13
• 229940086526 renin-inhibitors Drugs 0.000 title description 12
• 150000001875 compounds Chemical class 0.000 claims abstract description 358
• 238000000034 method Methods 0.000 claims abstract description 191
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 138
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 130
• -1 racemates Chemical class 0.000 claims description 76
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 74
• 239000000203 mixture Substances 0.000 claims description 56
• 239000002904 solvent Chemical class 0.000 claims description 37
• 150000003839 salts Chemical class 0.000 claims description 26
• 125000003118 aryl group Chemical group 0.000 claims description 22
• 125000000217 alkyl group Chemical group 0.000 claims description 19
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 16
• 201000006370 kidney failure Diseases 0.000 claims description 16
• 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 claims description 14
• GCJYLAWVUWEHLW-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]cyclopropanamine Chemical compound ClC1=CC=CC=C1CNC1CC1 GCJYLAWVUWEHLW-UHFFFAOYSA-N 0.000 claims description 14
• 230000036454 renin-angiotensin system Effects 0.000 claims description 14
• 238000011282 treatment Methods 0.000 claims description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
• 229910052736 halogen Inorganic materials 0.000 claims description 13
• 150000002367 halogens Chemical class 0.000 claims description 13
• 206010019280 Heart failures Diseases 0.000 claims description 11
• 239000012876 carrier material Substances 0.000 claims description 11
• 201000010099 disease Diseases 0.000 claims description 11
• 206010020772 Hypertension Diseases 0.000 claims description 10
• 125000001072 heteroaryl group Chemical group 0.000 claims description 10
• 125000003545 alkoxy group Chemical group 0.000 claims description 9
• 125000003342 alkenyl group Chemical group 0.000 claims description 8
• 125000002947 alkylene group Chemical group 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
• KJYVKUQRRKDPAX-UHFFFAOYSA-N n-[(2,3-dichlorophenyl)methyl]cyclopropanamine Chemical compound ClC1=CC=CC(CNC2CC2)=C1Cl KJYVKUQRRKDPAX-UHFFFAOYSA-N 0.000 claims description 8
• 229910052757 nitrogen Inorganic materials 0.000 claims description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
• 238000011321 prophylaxis Methods 0.000 claims description 8
• 239000005541 ACE inhibitor Substances 0.000 claims description 7
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 7
• XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 claims description 7
• 206010063897 Renal ischaemia Diseases 0.000 claims description 6
• 125000004450 alkenylene group Chemical group 0.000 claims description 6
• 229910052739 hydrogen Inorganic materials 0.000 claims description 6
• 239000001257 hydrogen Substances 0.000 claims description 6
• 230000000877 morphologic effect Effects 0.000 claims description 6
• 208000031225 myocardial ischemia Diseases 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 125000006193 alkinyl group Chemical group 0.000 claims description 5
• 125000000623 heterocyclic group Chemical group 0.000 claims description 5
• SASNBVQSOZSTPD-UHFFFAOYSA-N n-methylphenethylamine Chemical compound CNCCC1=CC=CC=C1 SASNBVQSOZSTPD-UHFFFAOYSA-N 0.000 claims description 5
• 208000037803 restenosis Diseases 0.000 claims description 5
• 125000001424 substituent group Chemical group 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
• 208000002249 Diabetes Complications Diseases 0.000 claims description 4
• 206010012655 Diabetic complications Diseases 0.000 claims description 4
• 208000010228 Erectile Dysfunction Diseases 0.000 claims description 4
• 208000010412 Glaucoma Diseases 0.000 claims description 4
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 4
• 206010038419 Renal colic Diseases 0.000 claims description 4
• 238000007675 cardiac surgery Methods 0.000 claims description 4
• 239000003795 chemical substances by application Substances 0.000 claims description 4
• 201000001881 impotence Diseases 0.000 claims description 4
• 210000000056 organ Anatomy 0.000 claims description 4
• 238000002054 transplantation Methods 0.000 claims description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
• 230000002792 vascular Effects 0.000 claims description 4
• 238000007631 vascular surgery Methods 0.000 claims description 4
• DTJKAALGEAHUIV-UHFFFAOYSA-N 2-(2-chlorophenyl)-n-methylethanamine Chemical compound CNCCC1=CC=CC=C1Cl DTJKAALGEAHUIV-UHFFFAOYSA-N 0.000 claims description 3
• WHLZWBOMTMVMNW-UHFFFAOYSA-N 4-[4-[2-[2-chloro-4-(trifluoromethyl)phenoxy]ethoxy]phenyl]-n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C(F)(F)F)=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)C=C1 WHLZWBOMTMVMNW-UHFFFAOYSA-N 0.000 claims description 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
• IIMKJJVXXCJZJX-UHFFFAOYSA-N FC(F)(F)C1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(Cl)=C(Cl)C=3)Cl)=CC=2)=C1Cl Chemical compound FC(F)(F)C1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(Cl)=C(Cl)C=3)Cl)=CC=2)=C1Cl IIMKJJVXXCJZJX-UHFFFAOYSA-N 0.000 claims description 3
• 229910052740 iodine Inorganic materials 0.000 claims description 3
• RZBOMSOHMOVUES-UHFFFAOYSA-N 2-(2-chlorophenyl)ethanamine Chemical compound NCCC1=CC=CC=C1Cl RZBOMSOHMOVUES-UHFFFAOYSA-N 0.000 claims description 2
• FREYDRAEKMXQOM-UHFFFAOYSA-N 4-[4-[2-(1,3-benzodioxol-5-yloxy)ethoxy]phenyl]-n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC(F)(F)C1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C=C4OCOC4=CC=3)=CC=2)=C1Cl FREYDRAEKMXQOM-UHFFFAOYSA-N 0.000 claims description 2
• METTZHPEYGYBLC-UHFFFAOYSA-N 4-[4-[2-(1,3-benzodioxol-5-yloxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C=C4OCOC4=CC=3)=CC=2)=C1C METTZHPEYGYBLC-UHFFFAOYSA-N 0.000 claims description 2
• JAYUVWYXJOIPAP-UHFFFAOYSA-N 4-[4-[2-(2-bromo-5-fluorophenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(Br)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)=C1 JAYUVWYXJOIPAP-UHFFFAOYSA-N 0.000 claims description 2
• FIKPVBOZTALOIJ-UHFFFAOYSA-N 4-[4-[2-(2-bromo-5-fluorophenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC=C(F)C=3)Br)=CC=2)=C1C FIKPVBOZTALOIJ-UHFFFAOYSA-N 0.000 claims description 2
• MKDSJHRSXBWOCM-UHFFFAOYSA-N 4-[4-[2-(2-chloro-4,5-dimethylphenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C1=C(C)C(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C)C=CC=2)C)C2CC2)C=C1 MKDSJHRSXBWOCM-UHFFFAOYSA-N 0.000 claims description 2
• WHTCWJJUDHYVSP-UHFFFAOYSA-N 4-[4-[2-(2-chloro-4,5-dimethylphenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2-fluoro-5-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=C(F)C(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(C)=C(C)C=3)Cl)=CC=2)=C1 WHTCWJJUDHYVSP-UHFFFAOYSA-N 0.000 claims description 2
• PRVXVDMJBASGMZ-UHFFFAOYSA-N 4-[4-[2-(2-chloro-5-fluorophenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(Cl)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)=C1 PRVXVDMJBASGMZ-UHFFFAOYSA-N 0.000 claims description 2
• GNNWAEGFKWAMAN-UHFFFAOYSA-N 4-[4-[2-(3-chloro-2,6-difluorophenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(Cl)C(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)C=C1 GNNWAEGFKWAMAN-UHFFFAOYSA-N 0.000 claims description 2
• DETFOAQXXGPHST-UHFFFAOYSA-N 4-[4-[2-(3-chloro-2,6-difluorophenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=C(Cl)C=CC=3F)F)=CC=2)=C1C DETFOAQXXGPHST-UHFFFAOYSA-N 0.000 claims description 2
• DGIHJKQEJKQGFD-UHFFFAOYSA-N 4-[4-[2-(3-chloro-2,6-difluorophenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(3-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=C(Cl)C=CC=3F)F)=CC=2)=C1 DGIHJKQEJKQGFD-UHFFFAOYSA-N 0.000 claims description 2
• KJCYTFYNSMCLAA-UHFFFAOYSA-N 4-[4-[2-(4-chloro-2-methoxyphenoxy)ethoxy]phenyl]-n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(Cl)=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)C=C1 KJCYTFYNSMCLAA-UHFFFAOYSA-N 0.000 claims description 2
• HZYJQIWTYIOFAJ-UHFFFAOYSA-N 4-[4-[2-(4-chloro-2-methylphenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC(Cl)=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)C=C1 HZYJQIWTYIOFAJ-UHFFFAOYSA-N 0.000 claims description 2
• AHMHYPIVEQYELH-UHFFFAOYSA-N 4-[4-[2-[2-chloro-4-(trifluoromethyl)phenoxy]ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C(F)(F)F)=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)C=C1 AHMHYPIVEQYELH-UHFFFAOYSA-N 0.000 claims description 2
• MHDWLMJRDDNZFV-UHFFFAOYSA-N 4-[4-[2-[2-chloro-4-(trifluoromethyl)phenoxy]ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(=CC=3)C(F)(F)F)Cl)=CC=2)=C1C MHDWLMJRDDNZFV-UHFFFAOYSA-N 0.000 claims description 2
• ZKFMOUQSZRSTGS-UHFFFAOYSA-N 4-[4-[3-(2,5-difluorophenoxy)propyl]phenyl]-N-methyl-N-(2-phenylethyl)-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C=1C=C(CCCOC=2C(=CC=C(F)C=2)F)C=CC=1C=1CCNCC=1C(=O)N(C)CCC1=CC=CC=C1 ZKFMOUQSZRSTGS-UHFFFAOYSA-N 0.000 claims description 2
• OUPMEDDKMUSRRH-UHFFFAOYSA-N 4-[4-[3-(2-chlorophenoxy)propyl]phenyl]-N-methyl-N-(2-phenylethyl)-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C=1C=C(CCCOC=2C(=CC=CC=2)Cl)C=CC=1C=1CCNCC=1C(=O)N(C)CCC1=CC=CC=C1 OUPMEDDKMUSRRH-UHFFFAOYSA-N 0.000 claims description 2
• NRSFDDAJOMGPGP-UHFFFAOYSA-N 4-[4-[3-(2-chlorophenoxy)propyl]phenyl]-n-[(2-chlorophenyl)methyl]-n-cyclopropyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC=CC=C1CN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=CC=CC=2)Cl)=CC=1)C1CC1 NRSFDDAJOMGPGP-UHFFFAOYSA-N 0.000 claims description 2
• ANBXUCYGLLJTDE-UHFFFAOYSA-N 4-[4-[3-(2-chlorophenoxy)propyl]phenyl]-n-[2-(2-chlorophenyl)ethyl]-n-methyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C=1C=C(CCCOC=2C(=CC=CC=2)Cl)C=CC=1C=1CCNCC=1C(=O)N(C)CCC1=CC=CC=C1Cl ANBXUCYGLLJTDE-UHFFFAOYSA-N 0.000 claims description 2
• WRCBVZFXOCIDGQ-UHFFFAOYSA-N C1=C(C)C(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)C=C1 Chemical compound C1=C(C)C(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)C=C1 WRCBVZFXOCIDGQ-UHFFFAOYSA-N 0.000 claims description 2
• DHFCSLYUIZTYKQ-UHFFFAOYSA-N C1=C(C)C(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 Chemical compound C1=C(C)C(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 DHFCSLYUIZTYKQ-UHFFFAOYSA-N 0.000 claims description 2
• VEIBNJCMXVMAQF-UHFFFAOYSA-N CC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)=C1F Chemical compound CC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)=C1F VEIBNJCMXVMAQF-UHFFFAOYSA-N 0.000 claims description 2
• XPBXUTKBHHGCHS-UHFFFAOYSA-N COC1=CC=C(Cl)C=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 Chemical compound COC1=CC=C(Cl)C=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 XPBXUTKBHHGCHS-UHFFFAOYSA-N 0.000 claims description 2
• BCYASNVUNQKJTB-UHFFFAOYSA-N ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C=C(Cl)C=CC=2)C2CC2)C=C1 Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C=C(Cl)C=CC=2)C2CC2)C=C1 BCYASNVUNQKJTB-UHFFFAOYSA-N 0.000 claims description 2
• KXDLKMJTRMJENM-UHFFFAOYSA-N ClC1=CC=CC=C1CCNC(=O)C1=C(C=2C=CC(CCCOC=3C(=CC=CC=3)Cl)=CC=2)CCNC1 Chemical compound ClC1=CC=CC=C1CCNC(=O)C1=C(C=2C=CC(CCCOC=3C(=CC=CC=3)Cl)=CC=2)CCNC1 KXDLKMJTRMJENM-UHFFFAOYSA-N 0.000 claims description 2
• XYDBRXAGMFJYGH-UHFFFAOYSA-N FC1=CC=C(Cl)C(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=3OCOC=3C=2)Cl)C2CC2)C=C1 Chemical compound FC1=CC=C(Cl)C(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=3OCOC=3C=2)Cl)C2CC2)C=C1 XYDBRXAGMFJYGH-UHFFFAOYSA-N 0.000 claims description 2
• IHAMFTOGKUIYBG-UHFFFAOYSA-N FC1=CC=C(Cl)C(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 Chemical compound FC1=CC=C(Cl)C(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 IHAMFTOGKUIYBG-UHFFFAOYSA-N 0.000 claims description 2
• FKOQCORMKWULIS-UHFFFAOYSA-N FC1=CC=C(Cl)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)=C1 Chemical compound FC1=CC=C(Cl)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)=C1 FKOQCORMKWULIS-UHFFFAOYSA-N 0.000 claims description 2
• AVPMMQQQOBDXEZ-UHFFFAOYSA-N FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)NCCC=2C(=CC=CC=2)Cl)=C1 Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)NCCC=2C(=CC=CC=2)Cl)=C1 AVPMMQQQOBDXEZ-UHFFFAOYSA-N 0.000 claims description 2
• TXIZFDVXNXOOPZ-UHFFFAOYSA-N FC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)=C1F Chemical compound FC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)=C1F TXIZFDVXNXOOPZ-UHFFFAOYSA-N 0.000 claims description 2
• 241001465754 Metazoa Species 0.000 claims description 2
• FUPBGNVTRRWNMO-UHFFFAOYSA-N N-[3-(2-chlorophenyl)propyl]-4-[4-[2-(2,6-dichloro-4-fluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)NCCCC=2C(=CC=CC=2)Cl)C=C1 FUPBGNVTRRWNMO-UHFFFAOYSA-N 0.000 claims description 2
• ZUJANRGPQVDJIO-UHFFFAOYSA-N N-[3-(2-chlorophenyl)propyl]-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)NCCCC=2C(=CC=CC=2)Cl)C=C1 ZUJANRGPQVDJIO-UHFFFAOYSA-N 0.000 claims description 2
• GVXNXDGYLTVAER-UHFFFAOYSA-N N-[3-(2-chlorophenyl)propyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)NCCCC=2C(=CC=CC=2)Cl)=C1F GVXNXDGYLTVAER-UHFFFAOYSA-N 0.000 claims description 2
• 239000002934 diuretic Substances 0.000 claims description 2
• 229940030606 diuretics Drugs 0.000 claims description 2
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
• 208000017169 kidney disease Diseases 0.000 claims description 2
• RSRBKMUEMCUIJF-UHFFFAOYSA-N n-[(2-bromophenyl)methyl]-n-cyclopropyl-4-[4-[2-(2,4,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC(F)=CC(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 RSRBKMUEMCUIJF-UHFFFAOYSA-N 0.000 claims description 2
• GVQRJSYTZDQDTF-UHFFFAOYSA-N n-[(2-bromophenyl)methyl]-n-cyclopropyl-4-[4-[2-(2,5-dichlorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC=C(Cl)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)=C1 GVQRJSYTZDQDTF-UHFFFAOYSA-N 0.000 claims description 2
• BVMONVKYWICDMH-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]-n-cyclopropyl-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)=C1F BVMONVKYWICDMH-UHFFFAOYSA-N 0.000 claims description 2
• IBGMBHJAMRNNLB-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]-n-cyclopropyl-4-[4-[3-(2,5-difluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)=C1 IBGMBHJAMRNNLB-UHFFFAOYSA-N 0.000 claims description 2
• WLBDSAMBHDWDLJ-UHFFFAOYSA-N n-[(3-chlorophenyl)methyl]-n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C=C(Cl)C=CC=2)C2CC2)C=C1 WLBDSAMBHDWDLJ-UHFFFAOYSA-N 0.000 claims description 2
• GAVJDCQXQNPGIR-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-4-[4-[3-(2,5-difluorophenoxy)propyl]phenyl]-n-methyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C=1C=C(CCCOC=2C(=CC=C(F)C=2)F)C=CC=1C=1CCNCC=1C(=O)N(C)CCC1=CC=CC=C1Cl GAVJDCQXQNPGIR-UHFFFAOYSA-N 0.000 claims description 2
• DOXUDNPSZOLHMI-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-n-cyclopropyl-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CCC=2C(=CC=CC=2)Cl)C2CC2)=C1F DOXUDNPSZOLHMI-UHFFFAOYSA-N 0.000 claims description 2
• NVIDPHICWKVZEO-UHFFFAOYSA-N n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)C=C1 NVIDPHICWKVZEO-UHFFFAOYSA-N 0.000 claims description 2
• BUKFHJLQFXQXID-UHFFFAOYSA-N n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-4-[4-[2-(2,6-difluoro-3-methylphenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)=C1F BUKFHJLQFXQXID-UHFFFAOYSA-N 0.000 claims description 2
• KQLHTYFRFVVCFG-UHFFFAOYSA-N n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-4-[4-[2-(2-fluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)C=C1 KQLHTYFRFVVCFG-UHFFFAOYSA-N 0.000 claims description 2
• DXKFIWJUHWCCII-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,3-dichlorophenoxy)ethoxy]phenyl]-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=C(Cl)C=CC=3)Cl)=CC=2)=C1C DXKFIWJUHWCCII-UHFFFAOYSA-N 0.000 claims description 2
• VWTMZTDMQGUISR-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,5-dichlorophenoxy)ethoxy]phenyl]-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC=C(Cl)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)=C1 VWTMZTDMQGUISR-UHFFFAOYSA-N 0.000 claims description 2
• ADXFRUBZWDKAKF-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,5-dichlorophenoxy)ethoxy]phenyl]-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC=C(Cl)C=3)Cl)=CC=2)=C1C ADXFRUBZWDKAKF-UHFFFAOYSA-N 0.000 claims description 2
• CSZTZLUZEKYHIN-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-fluorophenoxy)ethoxy]phenyl]-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(F)=CC=3Cl)Cl)=CC=2)=C1C CSZTZLUZEKYHIN-UHFFFAOYSA-N 0.000 claims description 2
• HDDIRCDRQXPDLH-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-fluorophenoxy)ethoxy]phenyl]-n-[(2-fluoro-5-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=C(F)C(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(F)=CC=3Cl)Cl)=CC=2)=C1 HDDIRCDRQXPDLH-UHFFFAOYSA-N 0.000 claims description 2
• SBJHBHPXWCJVGB-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-fluorophenoxy)ethoxy]phenyl]-n-[(3,5-difluorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC(F)=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(F)=CC=3Cl)Cl)=CC=2)=C1 SBJHBHPXWCJVGB-UHFFFAOYSA-N 0.000 claims description 2
• YEINQISTDIZAQY-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-fluorophenoxy)ethoxy]phenyl]-n-[(3,5-dimethoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(F)=CC=3Cl)Cl)=CC=2)=C1 YEINQISTDIZAQY-UHFFFAOYSA-N 0.000 claims description 2
• GHNVYNWDJXRPAN-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-fluorophenoxy)ethoxy]phenyl]-n-[[3-(trifluoromethoxy)phenyl]methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C=C(OC(F)(F)F)C=CC=2)C2CC2)C=C1 GHNVYNWDJXRPAN-UHFFFAOYSA-N 0.000 claims description 2
• WHYZTWUXNYYKEF-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-n-[(2-fluoro-5-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=C(F)C(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(C)=CC=3Cl)Cl)=CC=2)=C1 WHYZTWUXNYYKEF-UHFFFAOYSA-N 0.000 claims description 2
• VRPGPAGCRYVLMT-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-n-[(3,4-dimethoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C(=O)C=1CNCCC=1C=1C=CC(OCCOC=2C(=CC(C)=CC=2Cl)Cl)=CC=1)C1CC1 VRPGPAGCRYVLMT-UHFFFAOYSA-N 0.000 claims description 2
• HVZUNLVNOSXEIJ-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-n-[(3,5-difluorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C=C(F)C=C(F)C=2)C2CC2)C=C1 HVZUNLVNOSXEIJ-UHFFFAOYSA-N 0.000 claims description 2
• PYLGJGUNBJTIJE-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-n-[(3,5-dimethoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(C)=CC=3Cl)Cl)=CC=2)=C1 PYLGJGUNBJTIJE-UHFFFAOYSA-N 0.000 claims description 2
• JXLFQDMWYFNGSU-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-n-[(3-methylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(C)=CC=3Cl)Cl)=CC=2)=C1 JXLFQDMWYFNGSU-UHFFFAOYSA-N 0.000 claims description 2
• XHZRNWLLQXATCF-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-n-[[3-(trifluoromethoxy)phenyl]methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C=C(OC(F)(F)F)C=CC=2)C2CC2)C=C1 XHZRNWLLQXATCF-UHFFFAOYSA-N 0.000 claims description 2
• UILBLJKGEPQSJY-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-difluoro-3-methylphenoxy)ethoxy]phenyl]-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=C(C)C=CC=3F)F)=CC=2)=C1C UILBLJKGEPQSJY-UHFFFAOYSA-N 0.000 claims description 2
• XBZBUNYFHDRCSR-UHFFFAOYSA-N n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-4-[4-[2-(2,3,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=C(F)C=CC=3F)F)=CC=2)=C1C XBZBUNYFHDRCSR-UHFFFAOYSA-N 0.000 claims description 2
• WXKNSKDTTOYEPS-UHFFFAOYSA-N n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-4-[4-[2-(2,4,5-trichlorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(Cl)=C(Cl)C=3)Cl)=CC=2)=C1C WXKNSKDTTOYEPS-UHFFFAOYSA-N 0.000 claims description 2
• VYUXXHVGFQGRLI-UHFFFAOYSA-N n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-4-[4-[2-(2,4,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(F)=CC=3F)F)=CC=2)=C1C VYUXXHVGFQGRLI-UHFFFAOYSA-N 0.000 claims description 2
• BGTOFZQHCGWVAP-UHFFFAOYSA-N n-cyclopropyl-n-[(2-fluorophenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=CC=C1CN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=C(F)C=CC=2F)F)=CC=1)C1CC1 BGTOFZQHCGWVAP-UHFFFAOYSA-N 0.000 claims description 2
• KXSVBVYKOXTLEA-UHFFFAOYSA-N n-cyclopropyl-n-[(2-methylphenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC=C1CN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=C(F)C=CC=2F)F)=CC=1)C1CC1 KXSVBVYKOXTLEA-UHFFFAOYSA-N 0.000 claims description 2
• WNWCEXPQIIFIBP-UHFFFAOYSA-N n-cyclopropyl-n-[(3,5-dimethoxyphenyl)methyl]-4-[4-[2-(2,4,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(F)=CC=3F)F)=CC=2)=C1 WNWCEXPQIIFIBP-UHFFFAOYSA-N 0.000 claims description 2
• YWGZKLRWTSHDKB-UHFFFAOYSA-N n-cyclopropyl-n-[(3,5-dimethoxyphenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(CCCOC=3C(=C(F)C=CC=3F)F)=CC=2)=C1 YWGZKLRWTSHDKB-UHFFFAOYSA-N 0.000 claims description 2
• XKFWZYDNBSWSSD-UHFFFAOYSA-N n-cyclopropyl-n-[2-(2-methylphenyl)ethyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC=C1CCN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=C(F)C=CC=2F)F)=CC=1)C1CC1 XKFWZYDNBSWSSD-UHFFFAOYSA-N 0.000 claims description 2
• XBVPVGJVPQEDQE-UHFFFAOYSA-N n-cyclopropyl-n-[2-(3-methylphenoxy)ethyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(OCCN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(CCCOC=3C(=C(F)C=CC=3F)F)=CC=2)=C1 XBVPVGJVPQEDQE-UHFFFAOYSA-N 0.000 claims description 2
• NFRPVBVBVJEDEB-UHFFFAOYSA-N n-cyclopropyl-n-[2-(4-fluorophenyl)ethyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C1=CC(F)=CC=C1CCN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=C(F)C=CC=2F)F)=CC=1)C1CC1 NFRPVBVBVJEDEB-UHFFFAOYSA-N 0.000 claims description 2
• VXZZJQBCCVUFEI-UHFFFAOYSA-N n-cyclopropyl-n-[2-(4-methoxyphenoxy)ethyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C1=CC(OC)=CC=C1OCCN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=C(F)C=CC=2F)F)=CC=1)C1CC1 VXZZJQBCCVUFEI-UHFFFAOYSA-N 0.000 claims description 2
• FBUDTQSNZRKBAS-UHFFFAOYSA-N n-cyclopropyl-n-[[3-(trifluoromethyl)phenyl]methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C=C(C=CC=2)C(F)(F)F)C2CC2)=C1F FBUDTQSNZRKBAS-UHFFFAOYSA-N 0.000 claims description 2
• 230000001506 immunosuppresive effect Effects 0.000 claims 3
• 208000002815 pulmonary hypertension Diseases 0.000 claims 3
• GZTTVDHEWLHAJI-UHFFFAOYSA-N 4-[4-[2-(2-chloro-4,5-dimethylphenoxy)ethoxy]phenyl]-n-[(2-chlorophenyl)methyl]-n-cyclopropyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C1=C(C)C(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 GZTTVDHEWLHAJI-UHFFFAOYSA-N 0.000 claims 2
• 208000035475 disorder Diseases 0.000 claims 2
• FZYRIFYKIDJJIM-UHFFFAOYSA-N 4-[4-[2-(1,3-benzodioxol-5-yloxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C=C4OCOC4=CC=3)=CC=2)=C1Cl FZYRIFYKIDJJIM-UHFFFAOYSA-N 0.000 claims 1
• FCBHZJRONUTASY-UHFFFAOYSA-N 4-[4-[2-(2-bromo-5-fluorophenoxy)ethoxy]phenyl]-n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(Br)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)=C1 FCBHZJRONUTASY-UHFFFAOYSA-N 0.000 claims 1
• ICNGAYNLQGGPTR-UHFFFAOYSA-N 4-[4-[2-(2-bromo-5-fluorophenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2-fluoro-5-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=C(F)C(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC=C(F)C=3)Br)=CC=2)=C1 ICNGAYNLQGGPTR-UHFFFAOYSA-N 0.000 claims 1
• AXXBTTOIIFUQQR-UHFFFAOYSA-N 4-[4-[2-(2-chloro-4,5-dimethylphenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C1=C(C)C(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)C=C1 AXXBTTOIIFUQQR-UHFFFAOYSA-N 0.000 claims 1
• HVEMAYQYZSYOGZ-UHFFFAOYSA-N 4-[4-[2-(2-chloro-4,5-dimethylphenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(3,5-dimethoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(C)=C(C)C=3)Cl)=CC=2)=C1 HVEMAYQYZSYOGZ-UHFFFAOYSA-N 0.000 claims 1
• JMUJGIPCNDMYNG-UHFFFAOYSA-N 4-[4-[2-(2-chloro-4,5-dimethylphenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(3-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(C)=C(C)C=3)Cl)=CC=2)=C1 JMUJGIPCNDMYNG-UHFFFAOYSA-N 0.000 claims 1
• WZOOWBZCJFOLAU-UHFFFAOYSA-N 4-[4-[2-(3-chloro-2,6-difluorophenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2-fluoro-5-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=C(F)C(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=C(Cl)C=CC=3F)F)=CC=2)=C1 WZOOWBZCJFOLAU-UHFFFAOYSA-N 0.000 claims 1
• MPZVIMKAJUUMSX-UHFFFAOYSA-N 4-[4-[2-(4-chloro-2-methoxyphenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(Cl)=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)C=C1 MPZVIMKAJUUMSX-UHFFFAOYSA-N 0.000 claims 1
• OZEMDWYPAFICGO-UHFFFAOYSA-N 4-[4-[2-(4-chloro-2-methoxyphenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(Cl)=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C)C=CC=2)C)C2CC2)C=C1 OZEMDWYPAFICGO-UHFFFAOYSA-N 0.000 claims 1
• CTAYAKNXEZEAIV-UHFFFAOYSA-N 4-[4-[2-(4-chloro-2-methoxyphenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(3-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(Cl)=CC=3)OC)=CC=2)=C1 CTAYAKNXEZEAIV-UHFFFAOYSA-N 0.000 claims 1
• QXPZBKGYFZEZEL-UHFFFAOYSA-N 4-[4-[2-(4-chloro-2-methylphenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(Cl)=CC=3)C)=CC=2)=C1C QXPZBKGYFZEZEL-UHFFFAOYSA-N 0.000 claims 1
• OFJPCRUQKSZFFI-UHFFFAOYSA-N 4-[4-[2-[2-chloro-4-(trifluoromethyl)phenoxy]ethoxy]phenyl]-n-cyclopropyl-n-[(2-fluoro-5-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=C(F)C(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(=CC=3)C(F)(F)F)Cl)=CC=2)=C1 OFJPCRUQKSZFFI-UHFFFAOYSA-N 0.000 claims 1
• FRVXKYFYNIRBTK-UHFFFAOYSA-N 4-[4-[2-[2-chloro-4-(trifluoromethyl)phenoxy]ethoxy]phenyl]-n-cyclopropyl-n-[(3,5-dimethoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(=CC=3)C(F)(F)F)Cl)=CC=2)=C1 FRVXKYFYNIRBTK-UHFFFAOYSA-N 0.000 claims 1
• POUMYTOBNJHZMG-UHFFFAOYSA-N 4-[4-[2-[2-chloro-4-(trifluoromethyl)phenoxy]ethoxy]phenyl]-n-cyclopropyl-n-[(3-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(=CC=3)C(F)(F)F)Cl)=CC=2)=C1 POUMYTOBNJHZMG-UHFFFAOYSA-N 0.000 claims 1
• OGAAYTOBPWFVJM-UHFFFAOYSA-N 4-[4-[3-(2-bromo-5-fluorophenoxy)propyl]phenyl]-N-[3-(2-chlorophenyl)propyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(Br)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)NCCCC=2C(=CC=CC=2)Cl)=C1 OGAAYTOBPWFVJM-UHFFFAOYSA-N 0.000 claims 1
• GNQKDXQPKKYVIX-UHFFFAOYSA-N 4-[4-[3-(2-bromo-5-fluorophenoxy)propyl]phenyl]-n-[(2-chlorophenyl)methyl]-n-cyclopropyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(Br)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)=C1 GNQKDXQPKKYVIX-UHFFFAOYSA-N 0.000 claims 1
• ZUESJUDDPXQLMZ-UHFFFAOYSA-N 4-[4-[3-(2-bromo-5-fluorophenoxy)propyl]phenyl]-n-cyclopropyl-n-(2-phenylethyl)-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(Br)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CCC=2C=CC=CC=2)C2CC2)=C1 ZUESJUDDPXQLMZ-UHFFFAOYSA-N 0.000 claims 1
• IHMWNGLGFOAQIL-UHFFFAOYSA-N 4-[4-[3-(2-bromo-5-fluorophenoxy)propyl]phenyl]-n-cyclopropyl-n-[(2-methylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC=C1CN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=CC=C(F)C=2)Br)=CC=1)C1CC1 IHMWNGLGFOAQIL-UHFFFAOYSA-N 0.000 claims 1
• NJOFHEKRDZOEQT-UHFFFAOYSA-N 4-[4-[3-(2-bromo-5-fluorophenoxy)propyl]phenyl]-n-cyclopropyl-n-[(3,5-dimethoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(CCCOC=3C(=CC=C(F)C=3)Br)=CC=2)=C1 NJOFHEKRDZOEQT-UHFFFAOYSA-N 0.000 claims 1
• XQYYULLHWJYZAL-UHFFFAOYSA-N 4-[4-[3-(2-bromo-5-fluorophenoxy)propyl]phenyl]-n-cyclopropyl-n-[2-(2-methylphenyl)ethyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC=C1CCN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=CC=C(F)C=2)Br)=CC=1)C1CC1 XQYYULLHWJYZAL-UHFFFAOYSA-N 0.000 claims 1
• WFVATWGXIDKWIS-UHFFFAOYSA-N 4-[4-[3-(2-bromo-5-fluorophenoxy)propyl]phenyl]-n-cyclopropyl-n-[2-(4-methoxyphenoxy)ethyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C1=CC(OC)=CC=C1OCCN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=CC=C(F)C=2)Br)=CC=1)C1CC1 WFVATWGXIDKWIS-UHFFFAOYSA-N 0.000 claims 1
• VIODYOKNCDHZFQ-UHFFFAOYSA-N 4-[4-[3-(2-bromo-5-fluorophenoxy)propyl]phenyl]-n-cyclopropyl-n-[2-(4-methylphenyl)ethyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C1=CC(C)=CC=C1CCN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=CC=C(F)C=2)Br)=CC=1)C1CC1 VIODYOKNCDHZFQ-UHFFFAOYSA-N 0.000 claims 1
• FARWTHWBIOVJJC-UHFFFAOYSA-N C1=C(Cl)C(Cl)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 Chemical compound C1=C(Cl)C(Cl)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 FARWTHWBIOVJJC-UHFFFAOYSA-N 0.000 claims 1
• ALRAJGXWWVYELK-UHFFFAOYSA-N CC1=CC=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 Chemical compound CC1=CC=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 ALRAJGXWWVYELK-UHFFFAOYSA-N 0.000 claims 1
• 229940127291 Calcium channel antagonist Drugs 0.000 claims 1
• OTLPERQYNGOBIS-UHFFFAOYSA-N ClC1=CC(C(F)(F)F)=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 Chemical compound ClC1=CC(C(F)(F)F)=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 OTLPERQYNGOBIS-UHFFFAOYSA-N 0.000 claims 1
• WDHFIBYLEHQMSD-UHFFFAOYSA-N ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 Chemical compound ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 WDHFIBYLEHQMSD-UHFFFAOYSA-N 0.000 claims 1
• HFFCIISYYZYXCI-UHFFFAOYSA-N ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=3OCOC=3C=2)Cl)C2CC2)C=C1 Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=3OCOC=3C=2)Cl)C2CC2)C=C1 HFFCIISYYZYXCI-UHFFFAOYSA-N 0.000 claims 1
• VTYIIZUVQDRYRB-UHFFFAOYSA-N ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 VTYIIZUVQDRYRB-UHFFFAOYSA-N 0.000 claims 1
• PFJIQTUZWJDERG-UHFFFAOYSA-N ClC1=CC=C(Cl)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)=C1 Chemical compound ClC1=CC=C(Cl)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)=C1 PFJIQTUZWJDERG-UHFFFAOYSA-N 0.000 claims 1
• 229940118365 Endothelin receptor antagonist Drugs 0.000 claims 1
• GKRQFFSIKMBNHK-UHFFFAOYSA-N FC(F)(F)C1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC=C(Cl)C=3)Cl)=CC=2)=C1Cl Chemical compound FC(F)(F)C1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC=C(Cl)C=3)Cl)=CC=2)=C1Cl GKRQFFSIKMBNHK-UHFFFAOYSA-N 0.000 claims 1
• OLVGEAPIVLCIKR-UHFFFAOYSA-N FC1=CC(F)=CC(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=3OCOC=3C=2)Cl)C2CC2)C=C1 Chemical compound FC1=CC(F)=CC(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=3OCOC=3C=2)Cl)C2CC2)C=C1 OLVGEAPIVLCIKR-UHFFFAOYSA-N 0.000 claims 1
• IQVORVLRQPMRKW-UHFFFAOYSA-N FC1=CC(F)=CC(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 Chemical compound FC1=CC(F)=CC(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)C=C1 IQVORVLRQPMRKW-UHFFFAOYSA-N 0.000 claims 1
• MHPMUOLTQHTPJN-UHFFFAOYSA-N FC1=CC=C(Br)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)=C1 Chemical compound FC1=CC=C(Br)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)=C1 MHPMUOLTQHTPJN-UHFFFAOYSA-N 0.000 claims 1
• KBEHMJSCZWAJTH-UHFFFAOYSA-N FC1=CC=C(Cl)C(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 Chemical compound FC1=CC=C(Cl)C(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 KBEHMJSCZWAJTH-UHFFFAOYSA-N 0.000 claims 1
• LWSCOOCITHJCCU-UHFFFAOYSA-N FC1=CC=C(Cl)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)=C1 Chemical compound FC1=CC=C(Cl)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)=C1 LWSCOOCITHJCCU-UHFFFAOYSA-N 0.000 claims 1
• AKEQEMZQFYHDOV-UHFFFAOYSA-N FC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)=C1F Chemical compound FC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)=C1F AKEQEMZQFYHDOV-UHFFFAOYSA-N 0.000 claims 1
• UDOQLGRMKZQLQM-UHFFFAOYSA-N FC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)=C1Cl Chemical compound FC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Cl)C2CC2)=C1Cl UDOQLGRMKZQLQM-UHFFFAOYSA-N 0.000 claims 1
• ZCQSFBNDZYIGSG-UHFFFAOYSA-N N-[3-(2-chlorophenyl)propyl]-4-[4-[2-(2,3,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)NCCCC=2C(=CC=CC=2)Cl)=C1F ZCQSFBNDZYIGSG-UHFFFAOYSA-N 0.000 claims 1
• ZRHDKZNZBZJVRJ-UHFFFAOYSA-N N-[3-(2-chlorophenyl)propyl]-4-[4-[2-(2,4,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC(F)=CC(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)NCCCC=2C(=CC=CC=2)Cl)C=C1 ZRHDKZNZBZJVRJ-UHFFFAOYSA-N 0.000 claims 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
• 239000012190 activator Substances 0.000 claims 1
• 239000002671 adjuvant Substances 0.000 claims 1
• 239000002160 alpha blocker Substances 0.000 claims 1
• 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 1
• 239000002876 beta blocker Substances 0.000 claims 1
• 230000008482 dysregulation Effects 0.000 claims 1
• 239000002308 endothelin receptor antagonist Substances 0.000 claims 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
• RRSKYUYPYDGIBO-UHFFFAOYSA-N n-[(2-bromophenyl)methyl]-n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-fluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 RRSKYUYPYDGIBO-UHFFFAOYSA-N 0.000 claims 1
• JUEODLHKAZFLJE-UHFFFAOYSA-N n-[(2-bromophenyl)methyl]-n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)C=C1 JUEODLHKAZFLJE-UHFFFAOYSA-N 0.000 claims 1
• CXTIEGAAIQHSRL-UHFFFAOYSA-N n-[(2-bromophenyl)methyl]-n-cyclopropyl-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)Br)C2CC2)=C1F CXTIEGAAIQHSRL-UHFFFAOYSA-N 0.000 claims 1
• YDZNMBMMNHDVNE-UHFFFAOYSA-N n-[(2-chloro-6-fluorophenyl)methyl]-n-cyclopropyl-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2F)Cl)C2CC2)=C1F YDZNMBMMNHDVNE-UHFFFAOYSA-N 0.000 claims 1
• LXQBLTBTZRDJQI-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]-n-cyclopropyl-4-[4-[2-(2,3-dichlorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC=CC=C1CN(C(=O)C=1CNCCC=1C=1C=CC(OCCOC=2C(=C(Cl)C=CC=2)Cl)=CC=1)C1CC1 LXQBLTBTZRDJQI-UHFFFAOYSA-N 0.000 claims 1
• OEZUJBMRZGNRQY-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]-n-cyclopropyl-4-[4-[2-(2,6-dichlorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC=CC=C1CN(C(=O)C=1CNCCC=1C=1C=CC(OCCOC=2C(=CC=CC=2Cl)Cl)=CC=1)C1CC1 OEZUJBMRZGNRQY-UHFFFAOYSA-N 0.000 claims 1
• JMJPCXBNPMVLMG-UHFFFAOYSA-N n-[(3-chlorophenyl)methyl]-n-cyclopropyl-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C=C(Cl)C=CC=2)C2CC2)=C1F JMJPCXBNPMVLMG-UHFFFAOYSA-N 0.000 claims 1
• UGHYFXCFSPRNIX-UHFFFAOYSA-N n-[(6-chloro-1,3-benzodioxol-5-yl)methyl]-4-[4-[2-(4-chloro-2-methoxyphenoxy)ethoxy]phenyl]-n-cyclopropyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(Cl)=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=3OCOC=3C=2)Cl)C2CC2)C=C1 UGHYFXCFSPRNIX-UHFFFAOYSA-N 0.000 claims 1
• QKLMJNNFDZNKQO-UHFFFAOYSA-N n-[(6-chloro-1,3-benzodioxol-5-yl)methyl]-4-[4-[2-[2-chloro-4-(trifluoromethyl)phenoxy]ethoxy]phenyl]-n-cyclopropyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C(F)(F)F)=CC=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=3OCOC=3C=2)Cl)C2CC2)C=C1 QKLMJNNFDZNKQO-UHFFFAOYSA-N 0.000 claims 1
• PZKPLEJUDSZPAR-UHFFFAOYSA-N n-[(6-chloro-1,3-benzodioxol-5-yl)methyl]-n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=CC=3OCOC=3C=2)Cl)C2CC2)C=C1 PZKPLEJUDSZPAR-UHFFFAOYSA-N 0.000 claims 1
• JIUPCKOSJCGVJL-UHFFFAOYSA-N n-[(6-chloro-1,3-benzodioxol-5-yl)methyl]-n-cyclopropyl-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=3OCOC=3C=2)Cl)C2CC2)=C1F JIUPCKOSJCGVJL-UHFFFAOYSA-N 0.000 claims 1
• YBRFYHPFFKRRIN-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-4-[4-[3-[(2-methoxyphenyl)methoxy]propoxy]phenyl]-n-methyl-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=CC=C1COCCCOC1=CC=C(C=2CCNCC=2C(=O)N(C)CCC=2C(=CC=CC=2)Cl)C=C1 YBRFYHPFFKRRIN-UHFFFAOYSA-N 0.000 claims 1
• FEUCSOMEHFIGSS-UHFFFAOYSA-N n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-4-[4-[2-(2,4,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC(F)=CC(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)C=C1 FEUCSOMEHFIGSS-UHFFFAOYSA-N 0.000 claims 1
• DCRRKGNNLVDPBW-UHFFFAOYSA-N n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-fluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)C=C1 DCRRKGNNLVDPBW-UHFFFAOYSA-N 0.000 claims 1
• CYKNCYJCHMRSGH-UHFFFAOYSA-N n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(C=CC=2)C(F)(F)F)Cl)C2CC2)=C1F CYKNCYJCHMRSGH-UHFFFAOYSA-N 0.000 claims 1
• UGRNCMOBEXTPMA-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,5-dichlorophenoxy)ethoxy]phenyl]-n-[(3,5-dimethoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC=C(Cl)C=3)Cl)=CC=2)=C1 UGRNCMOBEXTPMA-UHFFFAOYSA-N 0.000 claims 1
• VMGPSNAFEFJJPZ-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-fluorophenoxy)ethoxy]phenyl]-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(F)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)C=C1 VMGPSNAFEFJJPZ-UHFFFAOYSA-N 0.000 claims 1
• FMTLMIDADBADOY-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)C=C1 FMTLMIDADBADOY-UHFFFAOYSA-N 0.000 claims 1
• OBNLHGZOWUMYNL-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(C)C=CC=2)C)C2CC2)C=C1 OBNLHGZOWUMYNL-UHFFFAOYSA-N 0.000 claims 1
• BXVDHBNLVXCTPN-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-n-[(3-methoxyphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(C)=CC=3Cl)Cl)=CC=2)=C1 BXVDHBNLVXCTPN-UHFFFAOYSA-N 0.000 claims 1
• ABRBXBOXWBLKLD-UHFFFAOYSA-N n-cyclopropyl-n-(2-phenylethyl)-4-[4-[2-(2,3,5-trimethylphenoxy)ethyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC(C)=C(C)C(OCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CCC=2C=CC=CC=2)C2CC2)=C1 ABRBXBOXWBLKLD-UHFFFAOYSA-N 0.000 claims 1
• ZNNLEYGKPJUHNQ-UHFFFAOYSA-N n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-4-[4-[2-(2,3,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)=C1F ZNNLEYGKPJUHNQ-UHFFFAOYSA-N 0.000 claims 1
• HDQPTIPOGOEXBF-UHFFFAOYSA-N n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-4-[4-[2-(2,4,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC(F)=CC(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)C=C1 HDQPTIPOGOEXBF-UHFFFAOYSA-N 0.000 claims 1
• ORCKZUQGCHBZBY-UHFFFAOYSA-N n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-4-[4-[2-(2,6-difluoro-3-methylphenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)=C1F ORCKZUQGCHBZBY-UHFFFAOYSA-N 0.000 claims 1
• AACNNDPTVFTJPH-UHFFFAOYSA-N n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=C(F)C(OCCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)=C1F AACNNDPTVFTJPH-UHFFFAOYSA-N 0.000 claims 1
• CUZHRNDKGMASKA-UHFFFAOYSA-N n-cyclopropyl-n-[(2,3-difluorophenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound FC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(CCCOC=3C(=C(F)C=CC=3F)F)=CC=2)=C1F CUZHRNDKGMASKA-UHFFFAOYSA-N 0.000 claims 1
• IAHJGXLQQDMRIQ-UHFFFAOYSA-N n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(CCCOC=3C(=C(F)C=CC=3F)F)=CC=2)=C1C IAHJGXLQQDMRIQ-UHFFFAOYSA-N 0.000 claims 1
• VDYXNMDTCPOGGV-UHFFFAOYSA-N n-cyclopropyl-n-[(2-fluoro-5-methoxyphenyl)methyl]-4-[4-[2-(2,4,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=C(F)C(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(F)=CC=3F)F)=CC=2)=C1 VDYXNMDTCPOGGV-UHFFFAOYSA-N 0.000 claims 1
• QAGNFLCUCZFIDL-UHFFFAOYSA-N n-cyclopropyl-n-[(2-fluoro-5-methoxyphenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=C(F)C(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(CCCOC=3C(=C(F)C=CC=3F)F)=CC=2)=C1 QAGNFLCUCZFIDL-UHFFFAOYSA-N 0.000 claims 1
• YDSLMDXEOLXWOR-UHFFFAOYSA-N n-cyclopropyl-n-[(2-methylphenyl)methyl]-4-[4-[2-(2,3,5-trimethylphenoxy)ethyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC(C)=C(C)C(OCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C(=CC=CC=2)C)C2CC2)=C1 YDSLMDXEOLXWOR-UHFFFAOYSA-N 0.000 claims 1
• BIGVOWXPWIYXKE-UHFFFAOYSA-N n-cyclopropyl-n-[(3,4-dimethoxyphenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=C(F)C=CC=2F)F)=CC=1)C1CC1 BIGVOWXPWIYXKE-UHFFFAOYSA-N 0.000 claims 1
• BRJCKPJOCLSBHO-UHFFFAOYSA-N n-cyclopropyl-n-[(3-fluoro-2-methylphenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=C(F)C=CC=C1CN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=C(F)C=CC=2F)F)=CC=1)C1CC1 BRJCKPJOCLSBHO-UHFFFAOYSA-N 0.000 claims 1
• QGGJOTOQZNLIGD-UHFFFAOYSA-N n-cyclopropyl-n-[(3-methoxyphenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(CCCOC=3C(=C(F)C=CC=3F)F)=CC=2)=C1 QGGJOTOQZNLIGD-UHFFFAOYSA-N 0.000 claims 1
• GYRDTPYSLXPJCF-UHFFFAOYSA-N n-cyclopropyl-n-[(3-methylphenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(CCCOC=3C(=C(F)C=CC=3F)F)=CC=2)=C1 GYRDTPYSLXPJCF-UHFFFAOYSA-N 0.000 claims 1
• IYEVDYHMIMZNNG-UHFFFAOYSA-N n-cyclopropyl-n-[2-(3-methoxyphenoxy)ethyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound COC1=CC=CC(OCCN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(CCCOC=3C(=C(F)C=CC=3F)F)=CC=2)=C1 IYEVDYHMIMZNNG-UHFFFAOYSA-N 0.000 claims 1
• KIZRFMZYNFOFNA-UHFFFAOYSA-N n-cyclopropyl-n-[2-(4-methylphenyl)ethyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound C1=CC(C)=CC=C1CCN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=C(F)C=CC=2F)F)=CC=1)C1CC1 KIZRFMZYNFOFNA-UHFFFAOYSA-N 0.000 claims 1
• ATWFXAVUNFGOGR-UHFFFAOYSA-N n-cyclopropyl-n-[[3-(trifluoromethyl)phenyl]methyl]-4-[4-[2-(2,3,5-trimethylphenoxy)ethyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound CC1=CC(C)=C(C)C(OCCC=2C=CC(=CC=2)C=2CCNCC=2C(=O)N(CC=2C=C(C=CC=2)C(F)(F)F)C2CC2)=C1 ATWFXAVUNFGOGR-UHFFFAOYSA-N 0.000 claims 1
• 239000011591 potassium Substances 0.000 claims 1
• 229910052700 potassium Inorganic materials 0.000 claims 1
• 229960003975 potassium Drugs 0.000 claims 1
• 230000000948 sympatholitic effect Effects 0.000 claims 1
• 229940124549 vasodilator Drugs 0.000 claims 1
• 239000003071 vasodilator agent Substances 0.000 claims 1
• 238000002360 preparation method Methods 0.000 abstract description 13
• 108090000783 Renin Proteins 0.000 abstract description 7
• 102100028255 Renin Human genes 0.000 abstract description 6
• 239000003112 inhibitor Substances 0.000 abstract description 4
• 239000004480 active ingredient Substances 0.000 abstract description 2
• 230000008569 process Effects 0.000 abstract description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 201
• 229910052731 fluorine Inorganic materials 0.000 description 105
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
• 238000000746 purification Methods 0.000 description 56
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 48
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
• 235000019439 ethyl acetate Nutrition 0.000 description 39
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 38
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 36
• 150000001408 amides Chemical class 0.000 description 36
• 230000002829 reductive effect Effects 0.000 description 36
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• 239000008279 sol Substances 0.000 description 25
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 23
• 239000000284 extract Substances 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 description 20
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 18
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 18
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 17
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
• YXEOEPYIBGTLML-UHFFFAOYSA-N 2,6-dichloro-4-methylphenol Chemical compound CC1=CC(Cl)=C(O)C(Cl)=C1 YXEOEPYIBGTLML-UHFFFAOYSA-N 0.000 description 14
• 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
• 125000005647 linker group Chemical group 0.000 description 13
• 125000006239 protecting group Chemical group 0.000 description 13
• BOJVIFKSTRCIRJ-UHFFFAOYSA-N 2,6-dichloro-4-fluorophenol Chemical compound OC1=C(Cl)C=C(F)C=C1Cl BOJVIFKSTRCIRJ-UHFFFAOYSA-N 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• WUNLJPBYWUHZBW-UHFFFAOYSA-N OC=O.ClC1=CC=CC(CNC2CC2)=C1Cl Chemical compound OC=O.ClC1=CC=CC(CNC2CC2)=C1Cl WUNLJPBYWUHZBW-UHFFFAOYSA-N 0.000 description 11
• 150000001412 amines Chemical class 0.000 description 11
• 125000004432 carbon atom Chemical group C* 0.000 description 11
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 11
• 239000011541 reaction mixture Substances 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
• QQFWMPUXPLBWTG-UHFFFAOYSA-N 2,4,6-trifluorophenol Chemical compound OC1=C(F)C=C(F)C=C1F QQFWMPUXPLBWTG-UHFFFAOYSA-N 0.000 description 9
• PSOJLBXHRBFLLQ-UHFFFAOYSA-N 2-chloro-4,5-dimethylphenol Chemical compound CC1=CC(O)=C(Cl)C=C1C PSOJLBXHRBFLLQ-UHFFFAOYSA-N 0.000 description 9
• QTOPAGRYIXCNRU-UHFFFAOYSA-N N-[(2-chlorophenyl)methyl]cyclopropanamine formic acid Chemical compound OC=O.ClC1=CC=CC=C1CNC1CC1 QTOPAGRYIXCNRU-UHFFFAOYSA-N 0.000 description 9
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• FHJASOFOOHMYBM-UHFFFAOYSA-N CC1=CC=CC(CNC2CC2)=C1C.OC=O Chemical compound CC1=CC=CC(CNC2CC2)=C1C.OC=O FHJASOFOOHMYBM-UHFFFAOYSA-N 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• 239000003814 drug Substances 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• YNWKEXMSQQUMEL-UHFFFAOYSA-N 2-chloro-4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1Cl YNWKEXMSQQUMEL-UHFFFAOYSA-N 0.000 description 7
• HBEQRYUULOHKLW-UHFFFAOYSA-N N-[(2-bromophenyl)methyl]cyclopropanamine formic acid Chemical compound OC=O.BrC1=CC=CC=C1CNC1CC1 HBEQRYUULOHKLW-UHFFFAOYSA-N 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 239000000243 solution Substances 0.000 description 7
• QSFGUSFDWCVXNR-UHFFFAOYSA-N 2,3,6-trifluorophenol Chemical compound OC1=C(F)C=CC(F)=C1F QSFGUSFDWCVXNR-UHFFFAOYSA-N 0.000 description 6
• RANCECPPZPIPNO-UHFFFAOYSA-N 2,5-dichlorophenol Chemical compound OC1=CC(Cl)=CC=C1Cl RANCECPPZPIPNO-UHFFFAOYSA-N 0.000 description 6
• 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• SGSRDJRDHRFKII-UHFFFAOYSA-N N-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]cyclopropanamine formic acid Chemical compound OC=O.FC(F)(F)C1=CC=CC(CNC2CC2)=C1Cl SGSRDJRDHRFKII-UHFFFAOYSA-N 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 230000008878 coupling Effects 0.000 description 6
• 238000010168 coupling process Methods 0.000 description 6
• 238000005859 coupling reaction Methods 0.000 description 6
• BTBDLUOYLCXSMK-UHFFFAOYSA-N n-[(3,5-dimethoxyphenyl)methyl]cyclopropanamine Chemical compound COC1=CC(OC)=CC(CNC2CC2)=C1 BTBDLUOYLCXSMK-UHFFFAOYSA-N 0.000 description 6
• 239000002243 precursor Substances 0.000 description 6
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 6
• HUVAOAVBKOVPBZ-UHFFFAOYSA-N 2-bromo-5-fluorophenol Chemical compound OC1=CC(F)=CC=C1Br HUVAOAVBKOVPBZ-UHFFFAOYSA-N 0.000 description 5
• CCLYWHXHYLQWQK-UHFFFAOYSA-N 3-chloro-2,6-difluorophenol Chemical compound OC1=C(F)C=CC(Cl)=C1F CCLYWHXHYLQWQK-UHFFFAOYSA-N 0.000 description 5
• FVZQMMMRFNURSH-UHFFFAOYSA-N 4-chloro-2-methoxyphenol Chemical compound COC1=CC(Cl)=CC=C1O FVZQMMMRFNURSH-UHFFFAOYSA-N 0.000 description 5
• OARNNZHAZQOEKB-UHFFFAOYSA-N COC(C=C1)=CC(CNC2CC2)=C1F.OC=O Chemical compound COC(C=C1)=CC(CNC2CC2)=C1F.OC=O OARNNZHAZQOEKB-UHFFFAOYSA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• DUMNQQNVATWWOV-UHFFFAOYSA-N N-[(6-chloro-1,3-benzodioxol-5-yl)methyl]cyclopropanamine formic acid Chemical compound OC=O.ClC1=CC=2OCOC=2C=C1CNC1CC1 DUMNQQNVATWWOV-UHFFFAOYSA-N 0.000 description 5
• 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 5
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 5
• 125000005530 alkylenedioxy group Chemical group 0.000 description 5
• 125000005529 alkyleneoxy group Chemical group 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• CRIMYHBFDHWKQY-UHFFFAOYSA-N n-[(2,3-dimethylphenyl)methyl]cyclopropanamine Chemical compound CC1=CC=CC(CNC2CC2)=C1C CRIMYHBFDHWKQY-UHFFFAOYSA-N 0.000 description 5
• VRDMJNOXKZMLTF-UHFFFAOYSA-N n-[(6-chloro-1,3-benzodioxol-5-yl)methyl]cyclopropanamine Chemical compound ClC1=CC=2OCOC=2C=C1CNC1CC1 VRDMJNOXKZMLTF-UHFFFAOYSA-N 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 235000019198 oils Nutrition 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 5
• QMDFHZOGAYONLN-UHFFFAOYSA-N 1,2,3,4-tetrahydropyridine-3-carboxylic acid Chemical compound OC(=O)C1CNC=CC1 QMDFHZOGAYONLN-UHFFFAOYSA-N 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
• 125000003070 2-(2-chlorophenyl)ethyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 4
• 239000001828 Gelatine Substances 0.000 description 4
• XCHARIIIZLLEBL-UHFFFAOYSA-N Medicagenic acid 3-O-beta-D-glucoside Chemical compound C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C(O)=O)C)(C)C1=CCC2C3(C)CC(O)C4OC1OC(CO)C(O)C(O)C1O XCHARIIIZLLEBL-UHFFFAOYSA-N 0.000 description 4
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 239000012267 brine Substances 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 238000006243 chemical reaction Methods 0.000 description 4
• 208000029078 coronary artery disease Diseases 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• SBKDFWWYKALTKE-UHFFFAOYSA-N n-[(2-bromophenyl)methyl]cyclopropanamine Chemical compound BrC1=CC=CC=C1CNC1CC1 SBKDFWWYKALTKE-UHFFFAOYSA-N 0.000 description 4
• CUPDQCKBQJVOMC-UHFFFAOYSA-N n-[(2-fluoro-5-methoxyphenyl)methyl]cyclopropanamine Chemical compound COC1=CC=C(F)C(CNC2CC2)=C1 CUPDQCKBQJVOMC-UHFFFAOYSA-N 0.000 description 4
• WYQUCNZBUBLJHN-UHFFFAOYSA-N n-[(2-methylphenyl)methyl]cyclopropanamine Chemical compound CC1=CC=CC=C1CNC1CC1 WYQUCNZBUBLJHN-UHFFFAOYSA-N 0.000 description 4
• POYWLSASJPZKQR-UHFFFAOYSA-N n-[2-(2-methylphenyl)ethyl]cyclopropanamine Chemical compound CC1=CC=CC=C1CCNC1CC1 POYWLSASJPZKQR-UHFFFAOYSA-N 0.000 description 4
• CEQDKNLDFWAMEL-UHFFFAOYSA-N n-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]cyclopropanamine Chemical compound FC(F)(F)C1=CC=CC(CNC2CC2)=C1Cl CEQDKNLDFWAMEL-UHFFFAOYSA-N 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• 229920005862 polyol Polymers 0.000 description 4
• 150000003077 polyols Chemical class 0.000 description 4
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 238000004809 thin layer chromatography Methods 0.000 description 4
• DIWGZVQKFSFNLH-UHFFFAOYSA-N 1-(2-chlorophenyl)-n-methylmethanamine Chemical compound CNCC1=CC=CC=C1Cl DIWGZVQKFSFNLH-UHFFFAOYSA-N 0.000 description 3
• OALMQEMOLLYBNO-UHFFFAOYSA-N 1-[2-(4-bromophenyl)ethoxy]-2,3,5-trimethylbenzene Chemical compound CC1=CC(C)=C(C)C(OCCC=2C=CC(Br)=CC=2)=C1 OALMQEMOLLYBNO-UHFFFAOYSA-N 0.000 description 3
• UMPSXRYVXUPCOS-UHFFFAOYSA-N 2,3-dichlorophenol Chemical compound OC1=CC=CC(Cl)=C1Cl UMPSXRYVXUPCOS-UHFFFAOYSA-N 0.000 description 3
• LHJGJYXLEPZJPM-UHFFFAOYSA-N 2,4,5-trichlorophenol Chemical compound OC1=CC(Cl)=C(Cl)C=C1Cl LHJGJYXLEPZJPM-UHFFFAOYSA-N 0.000 description 3
• YKCLAAQQWYPEDW-UHFFFAOYSA-N 2,6-difluoro-3-methylphenol Chemical compound CC1=CC=C(F)C(O)=C1F YKCLAAQQWYPEDW-UHFFFAOYSA-N 0.000 description 3
• CMQOZIKIOASEIN-UHFFFAOYSA-N 2-chloro-5-fluorophenol Chemical compound OC1=CC(F)=CC=C1Cl CMQOZIKIOASEIN-UHFFFAOYSA-N 0.000 description 3
• 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 description 3
• PJQCUMVGSKEOMN-UHFFFAOYSA-N 3-cyclohexylpyrrolidine Chemical compound C1NCCC1C1CCCCC1 PJQCUMVGSKEOMN-UHFFFAOYSA-N 0.000 description 3
• RHPUJHQBPORFGV-UHFFFAOYSA-N 4-chloro-2-methylphenol Chemical compound CC1=CC(Cl)=CC=C1O RHPUJHQBPORFGV-UHFFFAOYSA-N 0.000 description 3
• JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 3
• YCDFKRSJFMPRHP-UHFFFAOYSA-N COC1=CC(CNC2CC2)=CC(OC)=C1.OC=O Chemical compound COC1=CC(CNC2CC2)=CC(OC)=C1.OC=O YCDFKRSJFMPRHP-UHFFFAOYSA-N 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
• ZDTJBAZWKQJWGC-UHFFFAOYSA-N N-[(2-chlorophenyl)methyl]cyclopropanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.ClC1=CC=CC=C1CNC1CC1 ZDTJBAZWKQJWGC-UHFFFAOYSA-N 0.000 description 3
• LGTHQVZLKKDDBO-UHFFFAOYSA-N N-[2-(2-chlorophenyl)ethyl]-N-methylpyridine-3-carboxamide Chemical compound ClC1=C(C=CC=C1)CCN(C(=O)C=1C=NC=CC1)C LGTHQVZLKKDDBO-UHFFFAOYSA-N 0.000 description 3
• NSGDYZCDUPSTQT-UHFFFAOYSA-N N-[5-bromo-1-[(4-fluorophenyl)methyl]-4-methyl-2-oxopyridin-3-yl]cycloheptanecarboxamide Chemical compound Cc1c(Br)cn(Cc2ccc(F)cc2)c(=O)c1NC(=O)C1CCCCCC1 NSGDYZCDUPSTQT-UHFFFAOYSA-N 0.000 description 3
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 150000001299 aldehydes Chemical class 0.000 description 3
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 3
• 125000005605 benzo group Chemical group 0.000 description 3
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
• 239000011575 calcium Substances 0.000 description 3
• 239000000460 chlorine Substances 0.000 description 3
• 238000011097 chromatography purification Methods 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 3
• ORZRHMRDNOCKDU-UHFFFAOYSA-N n-[(3,4-dimethoxyphenyl)methyl]cyclopropanamine Chemical compound C1=C(OC)C(OC)=CC=C1CNC1CC1 ORZRHMRDNOCKDU-UHFFFAOYSA-N 0.000 description 3
• WRRVCXHKEDNRNB-UHFFFAOYSA-N n-[(3,5-difluorophenyl)methyl]cyclopropanamine Chemical compound FC1=CC(F)=CC(CNC2CC2)=C1 WRRVCXHKEDNRNB-UHFFFAOYSA-N 0.000 description 3
• VALINFAZSMPKJJ-UHFFFAOYSA-N n-[(3-chlorophenyl)methyl]cyclopropanamine Chemical compound ClC1=CC=CC(CNC2CC2)=C1 VALINFAZSMPKJJ-UHFFFAOYSA-N 0.000 description 3
• NUPAMNLYORQZRV-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]cyclopropanamine Chemical compound COC1=CC=CC(CNC2CC2)=C1 NUPAMNLYORQZRV-UHFFFAOYSA-N 0.000 description 3
• LJBFNXZKZYKGFY-UHFFFAOYSA-N n-[(3-methylphenyl)methyl]cyclopropanamine Chemical compound CC1=CC=CC(CNC2CC2)=C1 LJBFNXZKZYKGFY-UHFFFAOYSA-N 0.000 description 3
• WJFXKLXJOHUXCU-UHFFFAOYSA-N n-[2-(3-methoxyphenoxy)ethyl]cyclopropanamine Chemical compound COC1=CC=CC(OCCNC2CC2)=C1 WJFXKLXJOHUXCU-UHFFFAOYSA-N 0.000 description 3
• GEDRFLMRWRNXGV-UHFFFAOYSA-N n-[2-(4-methoxyphenoxy)ethyl]cyclopropanamine Chemical compound C1=CC(OC)=CC=C1OCCNC1CC1 GEDRFLMRWRNXGV-UHFFFAOYSA-N 0.000 description 3
• BNLAPXNSMIAMIO-UHFFFAOYSA-N n-[2-(4-methylphenyl)ethyl]cyclopropanamine Chemical compound C1=CC(C)=CC=C1CCNC1CC1 BNLAPXNSMIAMIO-UHFFFAOYSA-N 0.000 description 3
• ANCFTHKEGKDXKD-UHFFFAOYSA-N n-[[3-(trifluoromethoxy)phenyl]methyl]cyclopropanamine Chemical compound FC(F)(F)OC1=CC=CC(CNC2CC2)=C1 ANCFTHKEGKDXKD-UHFFFAOYSA-N 0.000 description 3
• 125000004430 oxygen atom Chemical group O* 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• 239000003208 petroleum Substances 0.000 description 3
• 239000000825 pharmaceutical preparation Substances 0.000 description 3
• 150000003335 secondary amines Chemical class 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• 125000004434 sulfur atom Chemical group 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
• 239000001993 wax Substances 0.000 description 3
• 239000011592 zinc chloride Substances 0.000 description 3
• 235000005074 zinc chloride Nutrition 0.000 description 3
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 3
• VLSDXINSOMDCBK-BQYQJAHWSA-N (E)-1,1'-azobis(N,N-dimethylformamide) Chemical compound CN(C)C(=O)\N=N\C(=O)N(C)C VLSDXINSOMDCBK-BQYQJAHWSA-N 0.000 description 2
• UKBFNAFIUSTHIV-UHFFFAOYSA-N 1-(3-chloropropoxymethyl)-2-methoxybenzene Chemical compound COC1=CC=CC=C1COCCCCl UKBFNAFIUSTHIV-UHFFFAOYSA-N 0.000 description 2
• BTHQFDICYSHLNB-UHFFFAOYSA-N 1-bromo-4-[3-[(2-methoxyphenyl)methoxy]propoxy]benzene Chemical compound COC1=CC=CC=C1COCCCOC1=CC=C(Br)C=C1 BTHQFDICYSHLNB-UHFFFAOYSA-N 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• OGRAOKJKVGDSFR-UHFFFAOYSA-N 2,3,5-trimethylphenol Chemical compound CC1=CC(C)=C(C)C(O)=C1 OGRAOKJKVGDSFR-UHFFFAOYSA-N 0.000 description 2
• PDNJEKGOELBWNC-UHFFFAOYSA-N 2-(2-chlorophenyl)-N-methylethanamine formic acid Chemical compound OC=O.CNCCC1=CC=CC=C1Cl PDNJEKGOELBWNC-UHFFFAOYSA-N 0.000 description 2
• 239000001431 2-methylbenzaldehyde Substances 0.000 description 2
• WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 2
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 2
• 102000004881 Angiotensinogen Human genes 0.000 description 2
• 108090001067 Angiotensinogen Proteins 0.000 description 2
• 108010064733 Angiotensins Proteins 0.000 description 2
• 102000015427 Angiotensins Human genes 0.000 description 2
• 108010017640 Aspartic Acid Proteases Proteins 0.000 description 2
• 102000004580 Aspartic Acid Proteases Human genes 0.000 description 2
• 101800004538 Bradykinin Proteins 0.000 description 2
• 102400000967 Bradykinin Human genes 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• ISKUAPWCMTUSNY-UHFFFAOYSA-N CC1=CC=CC(CNC2CC2)=C1.OC=O Chemical compound CC1=CC=CC(CNC2CC2)=C1.OC=O ISKUAPWCMTUSNY-UHFFFAOYSA-N 0.000 description 2
• ABYUMOLHWDLHFU-UHFFFAOYSA-N COC1=CC=CC(CNC2CC2)=C1.OC=O Chemical compound COC1=CC=CC(CNC2CC2)=C1.OC=O ABYUMOLHWDLHFU-UHFFFAOYSA-N 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 102000003858 Chymases Human genes 0.000 description 2
• 108090000227 Chymases Proteins 0.000 description 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
• 239000004129 EU approved improving agent Substances 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• FRAJKHKFXURVNI-UHFFFAOYSA-N N-[(3-chlorophenyl)methyl]cyclopropanamine formic acid Chemical compound OC=O.ClC1=CC=CC(CNC2CC2)=C1 FRAJKHKFXURVNI-UHFFFAOYSA-N 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 229920001213 Polysorbate 20 Polymers 0.000 description 2
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 239000003513 alkali Substances 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
• QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 230000007211 cardiovascular event Effects 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 125000004093 cyano group Chemical group *C#N 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 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 2
• 238000011161 development Methods 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• VDDXQSUSMHZCLS-UHFFFAOYSA-N ethenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC=C VDDXQSUSMHZCLS-UHFFFAOYSA-N 0.000 description 2
• RGFUCKMAZMCXNU-UHFFFAOYSA-N ethyl 1-benzyl-4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(OS(=O)(=O)C(F)(F)F)CCN1CC1=CC=CC=C1 RGFUCKMAZMCXNU-UHFFFAOYSA-N 0.000 description 2
• 239000003925 fat Substances 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 230000014509 gene expression Effects 0.000 description 2
• 125000005456 glyceride group Chemical group 0.000 description 2
• 238000003018 immunoassay Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• ILHIZUJWNGLALK-UHFFFAOYSA-N n-(2-phenylethyl)cyclopropanamine Chemical compound C1CC1NCCC1=CC=CC=C1 ILHIZUJWNGLALK-UHFFFAOYSA-N 0.000 description 2
• UZYPFBRRGVZJNV-UHFFFAOYSA-N n-[(2-fluorophenyl)methyl]cyclopropanamine Chemical compound FC1=CC=CC=C1CNC1CC1 UZYPFBRRGVZJNV-UHFFFAOYSA-N 0.000 description 2
• NTIIWMOYVFPRJN-UHFFFAOYSA-N n-[(3-fluoro-2-methylphenyl)methyl]cyclopropanamine Chemical compound CC1=C(F)C=CC=C1CNC1CC1 NTIIWMOYVFPRJN-UHFFFAOYSA-N 0.000 description 2
• NJHZDGHFBLATGX-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]cyclopropanamine Chemical compound ClC1=CC=CC=C1CCNC1CC1 NJHZDGHFBLATGX-UHFFFAOYSA-N 0.000 description 2
• NJDGRXSBVMPMQX-UHFFFAOYSA-N n-[2-(4-fluorophenyl)ethyl]cyclopropanamine Chemical compound C1=CC(F)=CC=C1CCNC1CC1 NJDGRXSBVMPMQX-UHFFFAOYSA-N 0.000 description 2
• WHYACTZEDMPXKM-UHFFFAOYSA-N n-cyclopropyl-n-[(3,5-dimethoxyphenyl)methyl]pyridine-3-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C2CC2)C(=O)C=2C=NC=CC=2)=C1 WHYACTZEDMPXKM-UHFFFAOYSA-N 0.000 description 2
• 235000001968 nicotinic acid Nutrition 0.000 description 2
• 239000011664 nicotinic acid Substances 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 238000006268 reductive amination reaction Methods 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 2
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
• MCCTUAKNFRUXLR-UHFFFAOYSA-N 2,3-dichloro-4-methylphenol Chemical compound CC1=CC=C(O)C(Cl)=C1Cl MCCTUAKNFRUXLR-UHFFFAOYSA-N 0.000 description 1
• LLMLNAVBOAMOEE-UHFFFAOYSA-N 2,3-dichlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1Cl LLMLNAVBOAMOEE-UHFFFAOYSA-N 0.000 description 1
• UIFVCPMLQXKEEU-UHFFFAOYSA-N 2,3-dimethylbenzaldehyde Chemical compound CC1=CC=CC(C=O)=C1C UIFVCPMLQXKEEU-UHFFFAOYSA-N 0.000 description 1
• WZYCJQIETJWHJB-UHFFFAOYSA-N 2,4-difluoro-3-methylphenol Chemical compound CC1=C(F)C=CC(O)=C1F WZYCJQIETJWHJB-UHFFFAOYSA-N 0.000 description 1
• INXKVYFOWNAVMU-UHFFFAOYSA-N 2,5-difluorophenol Chemical compound OC1=CC(F)=CC=C1F INXKVYFOWNAVMU-UHFFFAOYSA-N 0.000 description 1
• AFUKNJHPZAVHGQ-UHFFFAOYSA-N 2,5-dimethoxy-Benzaldehyde Chemical compound COC1=CC=C(OC)C(C=O)=C1 AFUKNJHPZAVHGQ-UHFFFAOYSA-N 0.000 description 1
• HOLHYSJJBXSLMV-UHFFFAOYSA-N 2,6-dichlorophenol Chemical compound OC1=C(Cl)C=CC=C1Cl HOLHYSJJBXSLMV-UHFFFAOYSA-N 0.000 description 1
• XMPLZIVCTGUIQP-UHFFFAOYSA-N 2-(2-chlorophenyl)-N-methylethanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CNCCC1=CC=CC=C1Cl XMPLZIVCTGUIQP-UHFFFAOYSA-N 0.000 description 1
• IUJAAIZKRJJZGQ-UHFFFAOYSA-N 2-(2-chlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1Cl IUJAAIZKRJJZGQ-UHFFFAOYSA-N 0.000 description 1
• SBRGWAFEPMFZIO-UHFFFAOYSA-N 2-(2-chlorophenyl)ethanamine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NCCC1=CC=CC=C1Cl SBRGWAFEPMFZIO-UHFFFAOYSA-N 0.000 description 1
• XLEDVBLQFNWZIA-UHFFFAOYSA-N 2-(2-chlorophenyl)ethanamine;formic acid Chemical compound OC=O.NCCC1=CC=CC=C1Cl XLEDVBLQFNWZIA-UHFFFAOYSA-N 0.000 description 1
• RZWGTXHSYZGXKF-UHFFFAOYSA-N 2-(2-methylphenyl)acetic acid Chemical compound CC1=CC=CC=C1CC(O)=O RZWGTXHSYZGXKF-UHFFFAOYSA-N 0.000 description 1
• AHDPQRIYMMZJTF-UHFFFAOYSA-N 2-(3-methoxyphenoxy)acetic acid Chemical compound COC1=CC=CC(OCC(O)=O)=C1 AHDPQRIYMMZJTF-UHFFFAOYSA-N 0.000 description 1
• XQQJFOBOGNCTRJ-UHFFFAOYSA-N 2-(4-bromophenoxy)ethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCOC1=CC=C(Br)C=C1 XQQJFOBOGNCTRJ-UHFFFAOYSA-N 0.000 description 1
• PMOSJSPFNDUAFY-UHFFFAOYSA-N 2-(4-bromophenyl)ethanol Chemical compound OCCC1=CC=C(Br)C=C1 PMOSJSPFNDUAFY-UHFFFAOYSA-N 0.000 description 1
• GXXXUZIRGXYDFP-UHFFFAOYSA-N 2-(4-methylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1 GXXXUZIRGXYDFP-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• MEYRABVEYCFHHB-UHFFFAOYSA-N 2-bromo-4-fluorophenol Chemical compound OC1=CC=C(F)C=C1Br MEYRABVEYCFHHB-UHFFFAOYSA-N 0.000 description 1
• NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 1
• IXIZSAAJTPZUBU-UHFFFAOYSA-N 2-chloro-3,6-difluorophenol Chemical compound OC1=C(F)C=CC(F)=C1Cl IXIZSAAJTPZUBU-UHFFFAOYSA-N 0.000 description 1
• KUNCMOAFNYLOSC-UHFFFAOYSA-N 2-chloro-3-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(C=O)=C1Cl KUNCMOAFNYLOSC-UHFFFAOYSA-N 0.000 description 1
• WRLCYWVNEFOAAQ-UHFFFAOYSA-N 2-chloro-4-(trifluoromethyl)phenol;phenol Chemical compound OC1=CC=CC=C1.OC1=CC=C(C(F)(F)F)C=C1Cl WRLCYWVNEFOAAQ-UHFFFAOYSA-N 0.000 description 1
• YPNZJHFXFVLXSE-UHFFFAOYSA-N 2-chloro-6-methylphenol Chemical compound CC1=CC=CC(Cl)=C1O YPNZJHFXFVLXSE-UHFFFAOYSA-N 0.000 description 1
• ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
• ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
• DKIQXHIAEMGZGO-UHFFFAOYSA-N 2-fluoro-5-methoxybenzaldehyde Chemical compound COC1=CC=C(F)C(C=O)=C1 DKIQXHIAEMGZGO-UHFFFAOYSA-N 0.000 description 1
• ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 1
• QQOMQLYQAXGHSU-UHFFFAOYSA-N 236TMPh Natural products CC1=CC=C(C)C(O)=C1C QQOMQLYQAXGHSU-UHFFFAOYSA-N 0.000 description 1
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• PUUIXFLXHJDDIV-UHFFFAOYSA-N 2h-pyridine-1,3-dicarboxylic acid Chemical compound OC(=O)N1CC(C(O)=O)=CC=C1 PUUIXFLXHJDDIV-UHFFFAOYSA-N 0.000 description 1
• ASOFZHSTJHGQDT-UHFFFAOYSA-N 3,5-difluorobenzaldehyde Chemical compound FC1=CC(F)=CC(C=O)=C1 ASOFZHSTJHGQDT-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• UCOOAWXAPBWIJQ-UHFFFAOYSA-N 3-(2-chlorophenyl)propan-1-amine 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NCCCC1=CC=CC=C1Cl UCOOAWXAPBWIJQ-UHFFFAOYSA-N 0.000 description 1
• HJZXLWYINMAUIT-UHFFFAOYSA-N 3-(2-chlorophenyl)propan-1-amine formic acid Chemical compound OC=O.NCCCC1=CC=CC=C1Cl HJZXLWYINMAUIT-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• ABFYEILPZWAIBN-UHFFFAOYSA-N 3-(iminomethylideneamino)-n,n-dimethylpropan-1-amine;hydrochloride Chemical compound Cl.CN(C)CCCN=C=N ABFYEILPZWAIBN-UHFFFAOYSA-N 0.000 description 1
• FQEVHRCPXFKJHF-UHFFFAOYSA-N 3-(trifluoromethoxy)benzaldehyde Chemical compound FC(F)(F)OC1=CC=CC(C=O)=C1 FQEVHRCPXFKJHF-UHFFFAOYSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• JMRPFKGSKYTUSD-UHFFFAOYSA-N 3-chloro-2-methoxyphenol Chemical compound COC1=C(O)C=CC=C1Cl JMRPFKGSKYTUSD-UHFFFAOYSA-N 0.000 description 1
• SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 1
• GJMPSRSMBJLKKB-UHFFFAOYSA-N 3-methylphenylacetic acid Chemical compound CC1=CC=CC(CC(O)=O)=C1 GJMPSRSMBJLKKB-UHFFFAOYSA-N 0.000 description 1
• HNZKCQSYLUGBSS-UHFFFAOYSA-N 4-[4-(3-hydroxypropyl)phenyl]-3,6-dihydro-2h-pyridine-1,5-dicarboxylic acid Chemical compound C1=CC(CCCO)=CC=C1C1=C(C(O)=O)CN(C(O)=O)CC1 HNZKCQSYLUGBSS-UHFFFAOYSA-N 0.000 description 1
• CTECYKJGQIOYML-UHFFFAOYSA-N 4-[4-[2-(1,3-benzodioxol-5-yloxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide;formic acid Chemical compound OC=O.ClC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C=C4OCOC4=CC=3)=CC=2)=C1Cl CTECYKJGQIOYML-UHFFFAOYSA-N 0.000 description 1
• YGMFOLLYCHPICB-UHFFFAOYSA-N 4-[4-[2-(2,5-dichlorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxylic acid Chemical compound C1CNCC(C(=O)O)=C1C(C=C1)=CC=C1OCCOC1=CC(Cl)=CC=C1Cl YGMFOLLYCHPICB-UHFFFAOYSA-N 0.000 description 1
• UXINOWYDRKLJHA-UHFFFAOYSA-N 4-[4-[2-(2-bromo-5-fluorophenoxy)ethoxy]phenyl]-n-cyclopropyl-n-[(2,3-dimethylphenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide;formic acid Chemical compound OC=O.CC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC=C(F)C=3)Br)=CC=2)=C1C UXINOWYDRKLJHA-UHFFFAOYSA-N 0.000 description 1
• IEBLAFHYIWKOCK-UHFFFAOYSA-N 4-[4-[2-(3-chloro-2,6-difluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxylic acid Chemical compound C1CNCC(C(=O)O)=C1C(C=C1)=CC=C1OCCOC1=C(F)C=CC(Cl)=C1F IEBLAFHYIWKOCK-UHFFFAOYSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
• WVTNKCOAFNRABI-UHFFFAOYSA-N 4-oxopiperidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CNCCC1=O WVTNKCOAFNRABI-UHFFFAOYSA-N 0.000 description 1
• CLPAHLNMHOOBCY-UHFFFAOYSA-N 4-oxopiperidine-1,3-dicarboxylic acid Chemical compound OC(=O)C1CN(C(O)=O)CCC1=O CLPAHLNMHOOBCY-UHFFFAOYSA-N 0.000 description 1
• DCYZIIPQBQXHMI-UHFFFAOYSA-N 5-[(2-chlorophenyl)methyl-cyclopropylcarbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound ClC1=C(CN(C(=O)C2=C(CCN(C2)C(=O)O)C2=CC=C(C=C2)OCCO)C2CC2)C=CC=C1 DCYZIIPQBQXHMI-UHFFFAOYSA-N 0.000 description 1
• LZXQRJJHMVARDT-UHFFFAOYSA-N 5-[(6-chloro-1,3-benzodioxol-5-yl)methyl-cyclopropylcarbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound ClC=1C(=CC2=C(OCO2)C1)CN(C(=O)C1=C(CCN(C1)C(=O)O)C1=CC=C(C=C1)OCCO)C1CC1 LZXQRJJHMVARDT-UHFFFAOYSA-N 0.000 description 1
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
• YCZNPAQXPVSXRO-UHFFFAOYSA-N 5-[3-(2-chlorophenyl)propylcarbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound ClC1=C(CCCNC(=O)C2=C(CCN(C2)C(=O)O)C2=CC=C(C=C2)OCCO)C=CC=C1 YCZNPAQXPVSXRO-UHFFFAOYSA-N 0.000 description 1
• GMLALMAGXLKCST-UHFFFAOYSA-N 5-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-cyclopropylcarbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound ClC1=C(CN(C(=O)C2=C(CCN(C2)C(=O)O)C2=CC=C(C=C2)OCCO)C2CC2)C=CC=C1C(F)(F)F GMLALMAGXLKCST-UHFFFAOYSA-N 0.000 description 1
• LRYACIJZRQHUIA-UHFFFAOYSA-N 5-[cyclopropyl-[(2,3-dichlorophenyl)methyl]carbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound C1(CC1)N(C(=O)C1=C(CCN(C1)C(=O)O)C1=CC=C(C=C1)OCCO)CC1=C(C(=CC=C1)Cl)Cl LRYACIJZRQHUIA-UHFFFAOYSA-N 0.000 description 1
• GHAQHFLEWRHQTE-UHFFFAOYSA-N 5-[cyclopropyl-[(2,3-dimethylphenyl)methyl]carbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound C1(CC1)N(C(=O)C1=C(CCN(C1)C(=O)O)C1=CC=C(C=C1)OCCO)CC1=C(C(=CC=C1)C)C GHAQHFLEWRHQTE-UHFFFAOYSA-N 0.000 description 1
• NIAFORHGZVAXOA-UHFFFAOYSA-N 5-[cyclopropyl-[(2-fluoro-5-methoxyphenyl)methyl]carbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound C1(CC1)N(C(=O)C1=C(CCN(C1)C(=O)O)C1=CC=C(C=C1)OCCO)CC1=C(C=CC(=C1)OC)F NIAFORHGZVAXOA-UHFFFAOYSA-N 0.000 description 1
• HJZVPWONOWLQIE-UHFFFAOYSA-N 5-[cyclopropyl-[(3,4-dimethoxyphenyl)methyl]carbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound C1(CC1)N(C(=O)C1=C(CCN(C1)C(=O)O)C1=CC=C(C=C1)OCCO)CC1=CC(=C(C=C1)OC)OC HJZVPWONOWLQIE-UHFFFAOYSA-N 0.000 description 1
• FCDIYKUZGZHGOA-UHFFFAOYSA-N 5-[cyclopropyl-[(3,5-dimethoxyphenyl)methyl]carbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound C1(CC1)N(C(=O)C1=C(CCN(C1)C(=O)O)C1=CC=C(C=C1)OCCO)CC1=CC(=CC(=C1)OC)OC FCDIYKUZGZHGOA-UHFFFAOYSA-N 0.000 description 1
• XZKMAQMEPAXSSN-UHFFFAOYSA-N 5-[cyclopropyl-[(3-methoxyphenyl)methyl]carbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound C1(CC1)N(C(=O)C1=C(CCN(C1)C(=O)O)C1=CC=C(C=C1)OCCO)CC1=CC(=CC=C1)OC XZKMAQMEPAXSSN-UHFFFAOYSA-N 0.000 description 1
• AWAVIRRCTHXXTQ-UHFFFAOYSA-N 5-[cyclopropyl-[[3-(trifluoromethoxy)phenyl]methyl]carbamoyl]-4-[4-(2-hydroxyethoxy)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound C1(CC1)N(C(=O)C1=C(CCN(C1)C(=O)O)C1=CC=C(C=C1)OCCO)CC1=CC(=CC=C1)OC(F)(F)F AWAVIRRCTHXXTQ-UHFFFAOYSA-N 0.000 description 1
• DXKLRELFBTVMDZ-UHFFFAOYSA-N 5-chloro-5,6-difluorocyclohexa-1,3-dien-1-ol Chemical compound OC1=CC=CC(F)(Cl)C1F DXKLRELFBTVMDZ-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• SDWIEOOLBNRWGT-UHFFFAOYSA-N 6-[4-[2-(2,3,5-trimethylphenoxy)ethyl]phenyl]-3,6-dihydro-2H-pyridine-1,5-dicarboxylic acid Chemical compound CC1=C(OCCC2=CC=C(C=C2)C2N(CCC=C2C(=O)O)C(=O)O)C=C(C=C1C)C SDWIEOOLBNRWGT-UHFFFAOYSA-N 0.000 description 1
• VRNADRCOROWLJC-UHFFFAOYSA-N 6-chloro-1,3-benzodioxole-5-carbaldehyde Chemical compound C1=C(C=O)C(Cl)=CC2=C1OCO2 VRNADRCOROWLJC-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• 101150059573 AGTR1 gene Proteins 0.000 description 1
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• 208000028185 Angioedema Diseases 0.000 description 1
• 101800000734 Angiotensin-1 Proteins 0.000 description 1
• 102400000344 Angiotensin-1 Human genes 0.000 description 1
• 101800000733 Angiotensin-2 Proteins 0.000 description 1
• 102400000345 Angiotensin-2 Human genes 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 239000002083 C09CA01 - Losartan Substances 0.000 description 1
• KKKNVIPTNKCMQO-UHFFFAOYSA-N C1CC1N(CC2=C(C(=CC=C2)C(F)(F)F)Cl)C(=O)C3=C(CCNC3)C4=CC=C(C=C4)OCCOC5=C(C=C(C=C5F)F)F.C(=O)O Chemical compound C1CC1N(CC2=C(C(=CC=C2)C(F)(F)F)Cl)C(=O)C3=C(CCNC3)C4=CC=C(C=C4)OCCOC5=C(C=C(C=C5F)F)F.C(=O)O KKKNVIPTNKCMQO-UHFFFAOYSA-N 0.000 description 1
• CJHVVXZSHAMOHE-UHFFFAOYSA-N C1CC1N(CC2=C(C(=CC=C2)C(F)(F)F)Cl)C(=O)C3=C(CCNC3)C4=CC=C(C=C4)OCCOC5=C(C=CC(=C5F)F)F.C(=O)O Chemical compound C1CC1N(CC2=C(C(=CC=C2)C(F)(F)F)Cl)C(=O)C3=C(CCNC3)C4=CC=C(C=C4)OCCOC5=C(C=CC(=C5F)F)F.C(=O)O CJHVVXZSHAMOHE-UHFFFAOYSA-N 0.000 description 1
• IPRBCEVDPWLRSE-UHFFFAOYSA-N CC1=C(CNC2CC2)C=CC=C1F.OC=O Chemical compound CC1=C(CNC2CC2)C=CC=C1F.OC=O IPRBCEVDPWLRSE-UHFFFAOYSA-N 0.000 description 1
• RRNKXCBLTTZEJD-UHFFFAOYSA-N CC1=CC(=C(C(=C1)Cl)OCCOC2=CC=C(C=C2)C3=C(CNCC3)C(=O)N(CC4=C(C(=CC=C4)C(F)(F)F)Cl)C5CC5)Cl.C(=O)O Chemical compound CC1=CC(=C(C(=C1)Cl)OCCOC2=CC=C(C=C2)C3=C(CNCC3)C(=O)N(CC4=C(C(=CC=C4)C(F)(F)F)Cl)C5CC5)Cl.C(=O)O RRNKXCBLTTZEJD-UHFFFAOYSA-N 0.000 description 1
• LXIZRBILOPONHK-UHFFFAOYSA-N CC1=CC=CC(CN(C2CC2)C(C2=CC=CN=C2)=O)=C1C.OC=O Chemical compound CC1=CC=CC(CN(C2CC2)C(C2=CC=CN=C2)=O)=C1C.OC=O LXIZRBILOPONHK-UHFFFAOYSA-N 0.000 description 1
• 101150041968 CDC13 gene Proteins 0.000 description 1
• KKOQRQMITMUTKB-UHFFFAOYSA-N CN(CCC1=CC=CC=C1)C(C(CNCC1)=C1C1=CC=C(CCCOC2=CC=CC=C2Cl)C=C1)=O.OC=O Chemical compound CN(CCC1=CC=CC=C1)C(C(CNCC1)=C1C1=CC=C(CCCOC2=CC=CC=C2Cl)C=C1)=O.OC=O KKOQRQMITMUTKB-UHFFFAOYSA-N 0.000 description 1
• WUIYJGKXCFAUAI-UHFFFAOYSA-N CNCCC1=CC=CC=C1.OC(C(F)(F)F)=O Chemical compound CNCCC1=CC=CC=C1.OC(C(F)(F)F)=O WUIYJGKXCFAUAI-UHFFFAOYSA-N 0.000 description 1
• HECAYCJDYDDQBZ-UHFFFAOYSA-N COC(C=C1)=CC(CN(C2CC2)C(C2=CC=CN=C2)=O)=C1F.OC=O Chemical compound COC(C=C1)=CC(CN(C2CC2)C(C2=CC=CN=C2)=O)=C1F.OC=O HECAYCJDYDDQBZ-UHFFFAOYSA-N 0.000 description 1
• CFBNTPJSZZDOIN-UHFFFAOYSA-N COC1=CC(CN(C2CC2)C(C2=CC=CN=C2)=O)=CC(OC)=C1.OC(C(F)(F)F)=O Chemical compound COC1=CC(CN(C2CC2)C(C2=CC=CN=C2)=O)=CC(OC)=C1.OC(C(F)(F)F)=O CFBNTPJSZZDOIN-UHFFFAOYSA-N 0.000 description 1
• SYBJIDGOLBRWQX-UHFFFAOYSA-N COC1=CC=C(CNC2CC2)C=C1OC.OC=O Chemical compound COC1=CC=C(CNC2CC2)C=C1OC.OC=O SYBJIDGOLBRWQX-UHFFFAOYSA-N 0.000 description 1
• DTSZMWFYIOROAQ-UHFFFAOYSA-N COC1=CC=CC(CN(C2CC2)C(C2=CC=CN=C2)=O)=C1.OC=O Chemical compound COC1=CC=CC(CN(C2CC2)C(C2=CC=CN=C2)=O)=C1.OC=O DTSZMWFYIOROAQ-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 206010011224 Cough Diseases 0.000 description 1
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
• 229930105110 Cyclosporin A Natural products 0.000 description 1
• 108010036949 Cyclosporine Proteins 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 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 1
• 101710198144 Endopolygalacturonase I Proteins 0.000 description 1
• 102000010180 Endothelin receptor Human genes 0.000 description 1
• 108050001739 Endothelin receptor Proteins 0.000 description 1
• 206010017533 Fungal infection Diseases 0.000 description 1
• 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
• CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• FSSTVMNYQPQTIL-UHFFFAOYSA-N N-[(2-chloro-6-fluorophenyl)methyl]cyclopropanamine formic acid Chemical compound OC=O.FC1=CC=CC(Cl)=C1CNC1CC1 FSSTVMNYQPQTIL-UHFFFAOYSA-N 0.000 description 1
• MBHVTYBEFNFUDJ-UHFFFAOYSA-N N-cyclopropyl-N-[(2,3-dimethylphenyl)methyl]pyridine-3-carboxamide Chemical compound C1(CC1)N(C(=O)C=1C=NC=CC1)CC1=C(C(=CC=C1)C)C MBHVTYBEFNFUDJ-UHFFFAOYSA-N 0.000 description 1
• RECOXPHQKDNHQR-UHFFFAOYSA-N N-cyclopropyl-N-[(3-methoxyphenyl)methyl]pyridine-3-carboxamide Chemical compound C1(CC1)N(C(=O)C=1C=NC=CC1)CC1=CC(=CC=C1)OC RECOXPHQKDNHQR-UHFFFAOYSA-N 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 208000025047 Non-histaminic angioedema Diseases 0.000 description 1
• UGNBYRKFUNKUJV-UHFFFAOYSA-N OC(C(F)(F)F)=O.O=C(C1=CC=CN=C1)N(CC(C=CC=C1)=C1Cl)C1CC1 Chemical compound OC(C(F)(F)F)=O.O=C(C1=CC=CN=C1)N(CC(C=CC=C1)=C1Cl)C1CC1 UGNBYRKFUNKUJV-UHFFFAOYSA-N 0.000 description 1
• YACBFBAJSLVRNT-UHFFFAOYSA-N OC=O.COc1ccc(Cl)cc1OCCOc1ccc(cc1)C1=C(CNCC1)C(=O)N(Cc1ccccc1Br)C1CC1 Chemical compound OC=O.COc1ccc(Cl)cc1OCCOc1ccc(cc1)C1=C(CNCC1)C(=O)N(Cc1ccccc1Br)C1CC1 YACBFBAJSLVRNT-UHFFFAOYSA-N 0.000 description 1
• OCNLSBNZUNIKPU-UHFFFAOYSA-N OC=O.Cc1cc(Cl)c(OCCOc2ccc(cc2)C2=C(CNCC2)C(=O)N(Cc2cccc(Cl)c2)C2CC2)c(Cl)c1 Chemical compound OC=O.Cc1cc(Cl)c(OCCOc2ccc(cc2)C2=C(CNCC2)C(=O)N(Cc2cccc(Cl)c2)C2CC2)c(Cl)c1 OCNLSBNZUNIKPU-UHFFFAOYSA-N 0.000 description 1
• QLCNZXMXJNJEPK-UHFFFAOYSA-N OC=O.FC1=CC=CC(CNC2CC2)=C1F Chemical compound OC=O.FC1=CC=CC(CNC2CC2)=C1F QLCNZXMXJNJEPK-UHFFFAOYSA-N 0.000 description 1
• SYJGQIMGEUGQGO-UHFFFAOYSA-N OC=O.O=C(C(CNCC1)=C1C(C=C1)=CC=C1OCCOC(C(F)=CC(F)=C1)=C1F)NCCCC1=CC=CC=C1Cl Chemical compound OC=O.O=C(C(CNCC1)=C1C(C=C1)=CC=C1OCCOC(C(F)=CC(F)=C1)=C1F)NCCCC1=CC=CC=C1Cl SYJGQIMGEUGQGO-UHFFFAOYSA-N 0.000 description 1
• XJIISZIKWOVFCY-UHFFFAOYSA-N OC=O.O=C(C(CNCC1)=C1C1=CC=C(CCCOC2=CC=CC=C2Cl)C=C1)NCCC1=CC=CC=C1Cl Chemical compound OC=O.O=C(C(CNCC1)=C1C1=CC=C(CCCOC2=CC=CC=C2Cl)C=C1)NCCC1=CC=CC=C1Cl XJIISZIKWOVFCY-UHFFFAOYSA-N 0.000 description 1
• PQRYCAADPJXQMX-UHFFFAOYSA-N OC=O.O=C(C1=CC=CN=C1)N(CC(C=CC=C1)=C1Br)C1CC1 Chemical compound OC=O.O=C(C1=CC=CN=C1)N(CC(C=CC=C1)=C1Br)C1CC1 PQRYCAADPJXQMX-UHFFFAOYSA-N 0.000 description 1
• QDPVEASRIBMTCE-UHFFFAOYSA-N OC=O.O=C(C1=CC=CN=C1)N(CC(C=CC=C1C(F)(F)F)=C1Cl)C1CC1 Chemical compound OC=O.O=C(C1=CC=CN=C1)N(CC(C=CC=C1C(F)(F)F)=C1Cl)C1CC1 QDPVEASRIBMTCE-UHFFFAOYSA-N 0.000 description 1
• JLYBKJNPNWBCFY-UHFFFAOYSA-N OC=O.O=C(C1=CC=CN=C1)N(CC(C=CC=C1Cl)=C1Cl)C1CC1 Chemical compound OC=O.O=C(C1=CC=CN=C1)N(CC(C=CC=C1Cl)=C1Cl)C1CC1 JLYBKJNPNWBCFY-UHFFFAOYSA-N 0.000 description 1
• WSEKSLVARLTFCY-UHFFFAOYSA-N OC=O.O=C(C1=CC=CN=C1)NCCCC(C=CC=C1)=C1Cl Chemical compound OC=O.O=C(C1=CC=CN=C1)NCCCC(C=CC=C1)=C1Cl WSEKSLVARLTFCY-UHFFFAOYSA-N 0.000 description 1
• IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
• YYVFXSYQSOZCOQ-UHFFFAOYSA-N Oxyquinoline sulfate Chemical compound [O-]S([O-])(=O)=O.C1=C[NH+]=C2C(O)=CC=CC2=C1.C1=C[NH+]=C2C(O)=CC=CC2=C1 YYVFXSYQSOZCOQ-UHFFFAOYSA-N 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• 101710191566 Probable endopolygalacturonase I Proteins 0.000 description 1
• 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
• 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
• 102000012479 Serine Proteases Human genes 0.000 description 1
• 108010022999 Serine Proteases Proteins 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 229930182558 Sterol Chemical class 0.000 description 1
• 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 1
• 229930006000 Sucrose Natural products 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
• 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
• 208000032594 Vascular Remodeling Diseases 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 238000010640 amide synthesis reaction Methods 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
• 229950006323 angiotensin ii Drugs 0.000 description 1
• 229940127282 angiotensin receptor antagonist Drugs 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 1
• 125000005603 azodicarboxylic group Chemical group 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 125000001743 benzylic group Chemical group 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 229910000085 borane Inorganic materials 0.000 description 1
• 239000012888 bovine serum Substances 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000005569 butenylene group Chemical group 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
• 239000000920 calcium hydroxide Substances 0.000 description 1
• 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000001913 cellulose Chemical class 0.000 description 1
• 229920002678 cellulose Chemical class 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000012707 chemical precursor Substances 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• 125000004803 chlorobenzyl group Chemical group 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 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 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000005828 desilylation reaction Methods 0.000 description 1
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
• 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 description 1
• 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
• 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 1
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
• YPFMNHZRNXPYBG-UHFFFAOYSA-N ethyl 1-benzyl-4-oxopiperidin-1-ium-3-carboxylate;chloride Chemical compound Cl.C1CC(=O)C(C(=O)OCC)CN1CC1=CC=CC=C1 YPFMNHZRNXPYBG-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 150000002191 fatty alcohols Chemical class 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• VKAYSLWIGYKPPE-UHFFFAOYSA-N formic acid N-[[3-(trifluoromethoxy)phenyl]methyl]cyclopropanamine Chemical compound OC=O.FC(OC1=CC=CC(CNC2CC2)=C1)(F)F VKAYSLWIGYKPPE-UHFFFAOYSA-N 0.000 description 1
• RQBPENWFKQAPFB-UHFFFAOYSA-N formic acid N-methyl-2-phenylethanamine Chemical compound OC=O.CNCCC1=CC=CC=C1 RQBPENWFKQAPFB-UHFFFAOYSA-N 0.000 description 1
• 150000004675 formic acid derivatives Chemical class 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 150000002314 glycerols Chemical class 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000005553 heteroaryloxy group Chemical group 0.000 description 1
• 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 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• BRADBAOVPACOQQ-UHFFFAOYSA-N hydron;methyl 1-benzyl-4-oxopiperidine-3-carboxylate;chloride Chemical compound Cl.C1CC(=O)C(C(=O)OC)CN1CC1=CC=CC=C1 BRADBAOVPACOQQ-UHFFFAOYSA-N 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000003978 infusion fluid Substances 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 229960004903 invert sugar Drugs 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 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
• 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
• 239000008101 lactose Substances 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 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
• OVWYEQOVUDKZNU-UHFFFAOYSA-N m-tolualdehyde Chemical compound CC1=CC=CC(C=O)=C1 OVWYEQOVUDKZNU-UHFFFAOYSA-N 0.000 description 1
• 201000004792 malaria Diseases 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• PHTILULPLFUXPS-UHFFFAOYSA-N methyl 1-benzyl-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OC)CN1CC1=CC=CC=C1 PHTILULPLFUXPS-UHFFFAOYSA-N 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 230000002107 myocardial effect Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• INJAMPFEUYMVHZ-UHFFFAOYSA-N n-[(2,3-difluorophenyl)methyl]cyclopropanamine Chemical compound FC1=CC=CC(CNC2CC2)=C1F INJAMPFEUYMVHZ-UHFFFAOYSA-N 0.000 description 1
• VNFABSKAJCALBZ-UHFFFAOYSA-N n-[(2-chloro-6-fluorophenyl)methyl]cyclopropanamine Chemical compound FC1=CC=CC(Cl)=C1CNC1CC1 VNFABSKAJCALBZ-UHFFFAOYSA-N 0.000 description 1
• LUVQDOPJNGGUDF-UHFFFAOYSA-N n-[2-(3-methylphenoxy)ethyl]cyclopropanamine Chemical compound CC1=CC=CC(OCCNC2CC2)=C1 LUVQDOPJNGGUDF-UHFFFAOYSA-N 0.000 description 1
• AOMAZSZEDRDSIF-UHFFFAOYSA-N n-[[3-(trifluoromethyl)phenyl]methyl]cyclopropanamine Chemical compound FC(F)(F)C1=CC=CC(CNC2CC2)=C1 AOMAZSZEDRDSIF-UHFFFAOYSA-N 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
• LEGSVKJTMKALHV-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,3-dichlorophenoxy)ethoxy]phenyl]-n-[(2,3-dichlorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide Chemical compound ClC1=CC=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=C(Cl)C=CC=3)Cl)=CC=2)=C1Cl LEGSVKJTMKALHV-UHFFFAOYSA-N 0.000 description 1
• ZLDQCJLPGHHKFB-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-fluorophenoxy)ethoxy]phenyl]-n-[(3,5-difluorophenyl)methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide;formic acid Chemical compound OC=O.FC1=CC(F)=CC(CN(C2CC2)C(=O)C=2CNCCC=2C=2C=CC(OCCOC=3C(=CC(F)=CC=3Cl)Cl)=CC=2)=C1 ZLDQCJLPGHHKFB-UHFFFAOYSA-N 0.000 description 1
• IWIMKIOIHMTPKW-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-n-[[3-(trifluoromethoxy)phenyl]methyl]-1,2,3,6-tetrahydropyridine-5-carboxamide;formic acid Chemical compound OC=O.ClC1=CC(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C=C(OC(F)(F)F)C=CC=2)C2CC2)C=C1 IWIMKIOIHMTPKW-UHFFFAOYSA-N 0.000 description 1
• TYJSYBHCDUQYIJ-UHFFFAOYSA-N n-cyclopropyl-n-[(2,3-dichlorophenyl)methyl]-4-[4-[2-(2,4,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide;formic acid Chemical compound OC=O.FC1=CC(F)=CC(F)=C1OCCOC1=CC=C(C=2CCNCC=2C(=O)N(CC=2C(=C(Cl)C=CC=2)Cl)C2CC2)C=C1 TYJSYBHCDUQYIJ-UHFFFAOYSA-N 0.000 description 1
• ZBSHLNZCBHHXFH-UHFFFAOYSA-N n-cyclopropyl-n-[(2-fluorophenyl)methyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.FC1=CC=CC=C1CN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=C(F)C=CC=2F)F)=CC=1)C1CC1 ZBSHLNZCBHHXFH-UHFFFAOYSA-N 0.000 description 1
• FLUOYFHUVNGDDR-UHFFFAOYSA-N n-cyclopropyl-n-[2-(4-methylphenyl)ethyl]-4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(C)=CC=C1CCN(C(=O)C=1CNCCC=1C=1C=CC(CCCOC=2C(=C(F)C=CC=2F)F)=CC=1)C1CC1 FLUOYFHUVNGDDR-UHFFFAOYSA-N 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 102000013415 peroxidase activity proteins Human genes 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 229920001223 polyethylene glycol Chemical class 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 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
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 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
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 230000011514 reflex Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000029865 regulation of blood pressure Effects 0.000 description 1
• 238000007127 saponification reaction 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
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 239000002594 sorbent Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 150000003432 sterols Chemical class 0.000 description 1
• 235000003702 sterols Nutrition 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000012976 tarts Nutrition 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 238000005809 transesterification reaction Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000006493 trifluoromethyl benzyl group Chemical group 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 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
• 238000010792 warming Methods 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1