AU2003229746A1 - Novel tetrahydropyridine derivatives as renin inhibitors - Google Patents
Novel tetrahydropyridine derivatives as renin inhibitors Download PDFInfo
- Publication number
- AU2003229746A1 AU2003229746A1 AU2003229746A AU2003229746A AU2003229746A1 AU 2003229746 A1 AU2003229746 A1 AU 2003229746A1 AU 2003229746 A AU2003229746 A AU 2003229746A AU 2003229746 A AU2003229746 A AU 2003229746A AU 2003229746 A1 AU2003229746 A1 AU 2003229746A1
- Authority
- AU
- Australia
- Prior art keywords
- carboxylic acid
- phenyl
- ethoxy
- tetrahydropyridine
- amide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000002461 renin inhibitor Substances 0.000 title description 12
- 229940086526 renin-inhibitors Drugs 0.000 title description 11
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical class C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims description 354
- 238000000034 method Methods 0.000 claims description 194
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 153
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 139
- -1 racemates Chemical class 0.000 claims description 84
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 63
- 239000000203 mixture Substances 0.000 claims description 56
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 51
- 239000002904 solvent Chemical class 0.000 claims description 37
- 150000001408 amides Chemical class 0.000 claims description 34
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- GCJYLAWVUWEHLW-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]cyclopropanamine Chemical compound ClC1=CC=CC=C1CNC1CC1 GCJYLAWVUWEHLW-UHFFFAOYSA-N 0.000 claims description 17
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 16
- 201000006370 kidney failure Diseases 0.000 claims description 16
- 239000011664 nicotinic acid Substances 0.000 claims description 15
- 230000036454 renin-angiotensin system Effects 0.000 claims description 15
- 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
- 235000001968 nicotinic acid Nutrition 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
- CRIMYHBFDHWKQY-UHFFFAOYSA-N n-[(2,3-dimethylphenyl)methyl]cyclopropanamine Chemical compound CC1=CC=CC(CNC2CC2)=C1C CRIMYHBFDHWKQY-UHFFFAOYSA-N 0.000 claims description 12
- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 206010020772 Hypertension Diseases 0.000 claims description 10
- 239000002253 acid Substances 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
- KJYVKUQRRKDPAX-UHFFFAOYSA-N n-[(2,3-dichlorophenyl)methyl]cyclopropanamine Chemical compound ClC1=CC=CC(CNC2CC2)=C1Cl KJYVKUQRRKDPAX-UHFFFAOYSA-N 0.000 claims description 9
- 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 claims description 9
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- PFZAREPYJMRPPQ-UHFFFAOYSA-N 4-[4-[3-(2,3,6-trifluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxylic acid Chemical compound C1CNCC(C(=O)O)=C1C(C=C1)=CC=C1CCCOC1=C(F)C=CC(F)=C1F PFZAREPYJMRPPQ-UHFFFAOYSA-N 0.000 claims description 8
- 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
- 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
- 206010063897 Renal ischaemia Diseases 0.000 claims description 7
- 125000004450 alkenylene group Chemical group 0.000 claims description 7
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 7
- 208000031225 myocardial ischemia Diseases 0.000 claims description 7
- CUPDQCKBQJVOMC-UHFFFAOYSA-N n-[(2-fluoro-5-methoxyphenyl)methyl]cyclopropanamine Chemical compound COC1=CC=C(F)C(CNC2CC2)=C1 CUPDQCKBQJVOMC-UHFFFAOYSA-N 0.000 claims description 7
- BTBDLUOYLCXSMK-UHFFFAOYSA-N n-[(3,5-dimethoxyphenyl)methyl]cyclopropanamine Chemical compound COC1=CC(OC)=CC(CNC2CC2)=C1 BTBDLUOYLCXSMK-UHFFFAOYSA-N 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000000623 heterocyclic 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
- WYQUCNZBUBLJHN-UHFFFAOYSA-N n-[(2-methylphenyl)methyl]cyclopropanamine Chemical compound CC1=CC=CC=C1CNC1CC1 WYQUCNZBUBLJHN-UHFFFAOYSA-N 0.000 claims description 6
- SASNBVQSOZSTPD-UHFFFAOYSA-N n-methylphenethylamine Chemical compound CNCCC1=CC=CC=C1 SASNBVQSOZSTPD-UHFFFAOYSA-N 0.000 claims description 6
- XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- QTDZOWFRBNTPQR-UHFFFAOYSA-N Guvacine Natural products OC(=O)C1=CCCNC1 QTDZOWFRBNTPQR-UHFFFAOYSA-N 0.000 claims description 5
- 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
- VALINFAZSMPKJJ-UHFFFAOYSA-N n-[(3-chlorophenyl)methyl]cyclopropanamine Chemical compound ClC1=CC=CC(CNC2CC2)=C1 VALINFAZSMPKJJ-UHFFFAOYSA-N 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- DTJKAALGEAHUIV-UHFFFAOYSA-N 2-(2-chlorophenyl)-n-methylethanamine Chemical compound CNCCC1=CC=CC=C1Cl DTJKAALGEAHUIV-UHFFFAOYSA-N 0.000 claims description 4
- IBVNNEPIXJSRAS-UHFFFAOYSA-N 3-(2-chlorophenyl)propan-1-amine Chemical compound NCCCC1=CC=CC=C1Cl IBVNNEPIXJSRAS-UHFFFAOYSA-N 0.000 claims description 4
- 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
- 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- ORZRHMRDNOCKDU-UHFFFAOYSA-N n-[(3,4-dimethoxyphenyl)methyl]cyclopropanamine Chemical compound C1=C(OC)C(OC)=CC=C1CNC1CC1 ORZRHMRDNOCKDU-UHFFFAOYSA-N 0.000 claims description 4
- NUPAMNLYORQZRV-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]cyclopropanamine Chemical compound COC1=CC=CC(CNC2CC2)=C1 NUPAMNLYORQZRV-UHFFFAOYSA-N 0.000 claims description 4
- LJBFNXZKZYKGFY-UHFFFAOYSA-N n-[(3-methylphenyl)methyl]cyclopropanamine Chemical compound CC1=CC=CC(CNC2CC2)=C1 LJBFNXZKZYKGFY-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 238000002054 transplantation Methods 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- 238000007631 vascular surgery Methods 0.000 claims description 4
- LXYQIBRUJZBFFC-UHFFFAOYSA-N 4-[4-[2-(2-chloro-4,5-dimethylphenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxylic acid Chemical compound C1=C(C)C(C)=CC(Cl)=C1OCCOC1=CC=C(C=2CCNCC=2C(O)=O)C=C1 LXYQIBRUJZBFFC-UHFFFAOYSA-N 0.000 claims description 3
- OUZFDZJXZYVMMY-UHFFFAOYSA-N 4-[4-[2-[2-chloro-4-(trifluoromethyl)phenoxy]ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxylic acid Chemical compound C1CNCC(C(=O)O)=C1C(C=C1)=CC=C1OCCOC1=CC=C(C(F)(F)F)C=C1Cl OUZFDZJXZYVMMY-UHFFFAOYSA-N 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
- YQZBGRHQOOLPMJ-UHFFFAOYSA-N N-[(2-bromophenyl)methyl]-N-cyclopropylpyridine-3-carboxamide Chemical compound BrC1=C(CN(C(=O)C=2C=NC=CC2)C2CC2)C=CC=C1 YQZBGRHQOOLPMJ-UHFFFAOYSA-N 0.000 claims description 3
- 201000001881 impotence Diseases 0.000 claims description 3
- ILHIZUJWNGLALK-UHFFFAOYSA-N n-(2-phenylethyl)cyclopropanamine Chemical compound C1CC1NCCC1=CC=CC=C1 ILHIZUJWNGLALK-UHFFFAOYSA-N 0.000 claims description 3
- INJAMPFEUYMVHZ-UHFFFAOYSA-N n-[(2,3-difluorophenyl)methyl]cyclopropanamine Chemical compound FC1=CC=CC(CNC2CC2)=C1F INJAMPFEUYMVHZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 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
- 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 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
- 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 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
- 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
- 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 description 2
- 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 description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 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 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
- VNFABSKAJCALBZ-UHFFFAOYSA-N n-[(2-chloro-6-fluorophenyl)methyl]cyclopropanamine Chemical compound FC1=CC=CC(Cl)=C1CNC1CC1 VNFABSKAJCALBZ-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 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
- NTIIWMOYVFPRJN-UHFFFAOYSA-N n-[(3-fluoro-2-methylphenyl)methyl]cyclopropanamine Chemical compound CC1=C(F)C=CC=C1CNC1CC1 NTIIWMOYVFPRJN-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
- 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
- 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 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- CKJMNMSAMKXMGW-UHFFFAOYSA-N 4-[4-[3-(2-bromo-5-fluorophenoxy)propyl]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxylic acid Chemical compound C1CNCC(C(=O)O)=C1C(C=C1)=CC=C1CCCOC1=CC(F)=CC=C1Br CKJMNMSAMKXMGW-UHFFFAOYSA-N 0.000 claims 5
- 230000001506 immunosuppresive effect Effects 0.000 claims 3
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- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims 2
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- ZEIBSIUXWIZWFG-UHFFFAOYSA-N 4-[4-[2-(2,3,6-trifluorophenoxy)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(F)=C1F ZEIBSIUXWIZWFG-UHFFFAOYSA-N 0.000 claims 1
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- JOYRYOBNNYDUMR-UHFFFAOYSA-N 4-[4-[2-(2,4,6-trifluorophenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxylic acid Chemical compound C1CNCC(C(=O)O)=C1C(C=C1)=CC=C1OCCOC1=C(F)C=C(F)C=C1F JOYRYOBNNYDUMR-UHFFFAOYSA-N 0.000 claims 1
- FZHYIKABBMEJMA-UHFFFAOYSA-N 4-[4-[2-(2,6-difluoro-3-methylphenoxy)ethoxy]phenyl]-1,2,3,6-tetrahydropyridine-5-carboxylic acid Chemical compound CC1=CC=C(F)C(OCCOC=2C=CC(=CC=2)C=2CCNCC=2C(O)=O)=C1F FZHYIKABBMEJMA-UHFFFAOYSA-N 0.000 claims 1
- 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 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
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- 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
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP0207102 | 2002-06-27 | ||
| AU2002321123 | 2002-06-27 | ||
| PCT/EP2003/004445 WO2004002957A1 (en) | 2002-06-27 | 2003-04-29 | Novel tetrahydropyridine derivatives as renin inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2003229746A1 true AU2003229746A1 (en) | 2004-01-19 |
Family
ID=29797098
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003229746A Abandoned AU2003229746A1 (en) | 2002-06-27 | 2003-04-29 | Novel tetrahydropyridine derivatives as renin inhibitors |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20060009497A1 (enExample) |
| EP (1) | EP1519920A1 (enExample) |
| JP (1) | JP2005532371A (enExample) |
| CN (1) | CN1662498A (enExample) |
| AU (1) | AU2003229746A1 (enExample) |
| BR (1) | BR0312000A (enExample) |
| CA (1) | CA2490138A1 (enExample) |
| CL (1) | CL2003002043A1 (enExample) |
| IL (1) | IL165887A0 (enExample) |
| MX (1) | MXPA04012136A (enExample) |
| NO (1) | NO20050290L (enExample) |
| PL (1) | PL375214A1 (enExample) |
| RU (1) | RU2005102002A (enExample) |
| TW (1) | TW200514772A (enExample) |
| WO (1) | WO2004002957A1 (enExample) |
| ZA (1) | ZA200408423B (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060217371A1 (en) * | 2003-04-28 | 2006-09-28 | Olivier Bezencon | Diazabicyclononene and tetrahydropyriddine derivatives as renin inhibitors |
| BRPI0409881A (pt) * | 2003-04-29 | 2006-05-23 | Actelion Pharmaceuticals Ltd | compostos, composições farmacêuticas, método para o tratamento ou profilaxia de doenças, e, usos de compostos e de um ou mais compostos em combinação com outros compostos farmacologicamente ativos |
| AU2004233575A1 (en) * | 2003-04-30 | 2004-11-11 | Actelion Pharmaceuticals Ltd | 9-azabicyclo'3.3.1!non-6-ee derivatives with a heteroatom at the 3-position as renin inhibitors |
| RU2005137571A (ru) * | 2003-05-02 | 2006-05-10 | Актелион Фармасьютикалз Лтд. (Ch) | Новые производные диазабициклононена |
| WO2004105738A2 (en) * | 2003-05-30 | 2004-12-09 | Actelion Pharmaceuticals Ltd | Use of tetrahydropyridine derivatives |
| CN1863773A (zh) * | 2003-10-09 | 2006-11-15 | 埃科特莱茵药品有限公司 | 四氢吡啶衍生物 |
| US20070142363A1 (en) * | 2003-10-13 | 2007-06-21 | Actelion Pharmaceuticals Ltd | Novel diazabicyclonene derivatives and use thereof |
| WO2005054243A1 (en) * | 2003-12-05 | 2005-06-16 | Actelion Pharmaceuticals Ltd | Diazabicyclononene derivatives and their use as renin inhibitors |
| CA2552965A1 (en) * | 2004-01-14 | 2005-07-28 | Takeda Pharmaceutical Company Limited | Carboxamide derivative and use thereof |
| NZ586285A (en) * | 2004-03-17 | 2011-12-22 | Novartis Ag | Use of aliskiren in monotherapy for treating diabetes and metabolic disorder (syndrome X) |
| JP2008510755A (ja) | 2004-08-25 | 2008-04-10 | アクテリオン ファーマシューティカルズ リミテッド | ビシクロノネン誘導体 |
| GB0428526D0 (en) * | 2004-12-30 | 2005-02-09 | Novartis Ag | Organic compounds |
| GB0500784D0 (en) * | 2005-01-14 | 2005-02-23 | Novartis Ag | Organic compounds |
| GB0504850D0 (en) * | 2005-03-09 | 2005-04-13 | Novartis Ag | Organic compounds |
| GB0510810D0 (en) * | 2005-05-26 | 2005-06-29 | Novartis Ag | Organic compounds |
| KR100963455B1 (ko) * | 2005-05-27 | 2010-06-18 | 액테리온 파마슈티칼 리미티드 | 신규한 피페리딘 카르복실산 아미드 유도체 |
| GB0514203D0 (en) | 2005-07-11 | 2005-08-17 | Novartis Ag | Organic compounds |
| WO2007049224A1 (en) * | 2005-10-25 | 2007-05-03 | Actelion Pharmaceuticals Ltd | Novel hexahydro- or octahydro-cyclopenta[c]pyrrole derivatives |
| JP2009526767A (ja) | 2006-02-02 | 2009-07-23 | アクテリオン ファーマシューティカルズ リミテッド | 新規二級アミン |
| AU2007220149A1 (en) * | 2006-03-03 | 2007-09-07 | Actelion Pharmaceuticals Ltd | Primary amines as renin inhibitors |
| TW200800897A (en) * | 2006-03-08 | 2008-01-01 | Actelion Pharmaceuticals Ltd | New amines |
| EP1908471A1 (en) * | 2006-10-04 | 2008-04-09 | Speedel Experimenta AG | Tetrahydropyridines as renin inhibitors |
| EP2162436A4 (en) | 2007-05-24 | 2010-08-04 | Merck Frosst Canada Ltd | NEW CASE OF RENININHIBITORS |
| CA2696689A1 (en) | 2007-08-20 | 2009-02-26 | Merck Frosst Canada Ltd. | Renin inhibitors |
| CN102015682B (zh) | 2008-05-05 | 2014-07-16 | 埃科特莱茵药品有限公司 | 作为肾素抑制剂的3,4-取代的哌啶衍生物 |
| ES2645725T3 (es) | 2010-06-11 | 2017-12-07 | Rhodes Technologies | Procesos catalizados por metales de transición para la preparación de compuestos de N-alilo y uso de los mismos |
| WO2011154826A1 (en) | 2010-06-11 | 2011-12-15 | Rhodes Technologies | Process for n-dealkylation of tertiary amines |
| CN117865941B (zh) * | 2024-03-13 | 2024-06-28 | 上海方予健康医药科技有限公司 | 取代哌啶化合物及其制备方法和应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5376666A (en) * | 1992-11-30 | 1994-12-27 | The Du Pont Merck Pharmaceutical Company | Angiotension-II receptor blocking, azacycloalkyl or azacycloalkenyl |
| KR100384979B1 (ko) * | 1995-09-07 | 2003-10-17 | 에프. 호프만-라 로슈 아게 | 심부전증및신부전증치료용의신규한4-(옥시알콕시페닐)-3-옥시-피페리딘 |
| US6376672B1 (en) * | 1999-04-27 | 2002-04-23 | Hoffmann-La Roche Inc. | Naphthalenylmethoxypiperidines as renin inhibitors |
-
2003
- 2003-04-29 JP JP2004516551A patent/JP2005532371A/ja active Pending
- 2003-04-29 EP EP03722566A patent/EP1519920A1/en not_active Withdrawn
- 2003-04-29 AU AU2003229746A patent/AU2003229746A1/en not_active Abandoned
- 2003-04-29 BR BR0312000-7A patent/BR0312000A/pt not_active IP Right Cessation
- 2003-04-29 MX MXPA04012136A patent/MXPA04012136A/es unknown
- 2003-04-29 CA CA002490138A patent/CA2490138A1/en not_active Abandoned
- 2003-04-29 RU RU2005102002/04A patent/RU2005102002A/ru not_active Application Discontinuation
- 2003-04-29 PL PL03375214A patent/PL375214A1/xx not_active Application Discontinuation
- 2003-04-29 CN CN038138875A patent/CN1662498A/zh active Pending
- 2003-04-29 WO PCT/EP2003/004445 patent/WO2004002957A1/en not_active Ceased
- 2003-04-29 US US10/514,164 patent/US20060009497A1/en not_active Abandoned
- 2003-10-10 CL CL200302043A patent/CL2003002043A1/es unknown
- 2003-10-28 TW TW092129927A patent/TW200514772A/zh unknown
-
2004
- 2004-10-18 ZA ZA200408423A patent/ZA200408423B/xx unknown
- 2004-12-21 IL IL16588704A patent/IL165887A0/xx unknown
-
2005
- 2005-01-19 NO NO20050290A patent/NO20050290L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2490138A1 (en) | 2004-01-08 |
| CN1662498A (zh) | 2005-08-31 |
| MXPA04012136A (es) | 2005-04-19 |
| TW200514772A (en) | 2005-05-01 |
| PL375214A1 (en) | 2005-11-28 |
| ZA200408423B (en) | 2005-10-11 |
| NO20050290L (no) | 2005-01-19 |
| US20060009497A1 (en) | 2006-01-12 |
| EP1519920A1 (en) | 2005-04-06 |
| WO2004002957A1 (en) | 2004-01-08 |
| RU2005102002A (ru) | 2005-09-20 |
| JP2005532371A (ja) | 2005-10-27 |
| BR0312000A (pt) | 2005-03-22 |
| CL2003002043A1 (es) | 2005-01-28 |
| IL165887A0 (en) | 2006-01-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |