PT1373191E - Indanilaminas aciladas e sua utilização como fármacos - Google Patents
Indanilaminas aciladas e sua utilização como fármacos Download PDFInfo
- Publication number
- PT1373191E PT1373191E PT2722067T PT02722067T PT1373191E PT 1373191 E PT1373191 E PT 1373191E PT 2722067 T PT2722067 T PT 2722067T PT 02722067 T PT02722067 T PT 02722067T PT 1373191 E PT1373191 E PT 1373191E
- Authority
- PT
- Portugal
- Prior art keywords
- indan
- phenyl
- methyl
- chloro
- alkyl
- Prior art date
Links
- -1 Acylated indanyl amines Chemical class 0.000 title claims description 331
- 239000003814 drug Substances 0.000 title claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 111
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 43
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 36
- 239000000243 solution Substances 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical class C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 230000014509 gene expression Effects 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 16
- 230000003511 endothelial effect Effects 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 13
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 13
- 125000000335 thiazolyl group Chemical group 0.000 claims description 13
- 125000001544 thienyl group Chemical group 0.000 claims description 13
- 125000002883 imidazolyl group Chemical group 0.000 claims description 12
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 11
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 11
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 10
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 10
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 201000001320 Atherosclerosis Diseases 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- 206010020772 Hypertension Diseases 0.000 claims description 6
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 6
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 208000029078 coronary artery disease Diseases 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 238000001802 infusion Methods 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 239000003826 tablet Substances 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 4
- IGQDZYVWSOKCCO-UHFFFAOYSA-N 2-chloro-n-(2,3-dihydro-1h-inden-2-yl)-6-methylpyridine-3-carboxamide Chemical compound ClC1=NC(C)=CC=C1C(=O)NC1CC2=CC=CC=C2C1 IGQDZYVWSOKCCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 206010002383 Angina Pectoris Diseases 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 206010048554 Endothelial dysfunction Diseases 0.000 claims description 4
- 206010047281 Ventricular arrhythmia 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
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000008694 endothelial dysfunction Effects 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- NIXQKUWFMQZTOS-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)NC1CC2=CC=CC=C2C1 NIXQKUWFMQZTOS-UHFFFAOYSA-N 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 4
- 230000000638 stimulation Effects 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 4
- YXYOLVAXVPOIMA-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2OCCC2=C1 YXYOLVAXVPOIMA-UHFFFAOYSA-N 0.000 claims description 3
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 3
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
- QRENWBKXNZJPCB-UHFFFAOYSA-N 5-bromo-n-(2,3-dihydro-1h-inden-2-yl)thiophene-2-carboxamide Chemical compound S1C(Br)=CC=C1C(=O)NC1CC2=CC=CC=C2C1 QRENWBKXNZJPCB-UHFFFAOYSA-N 0.000 claims description 3
- KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 claims description 3
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 3
- 208000007718 Stable Angina Diseases 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 239000008298 dragée Substances 0.000 claims description 3
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- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- QNKGSVMHFYKXMY-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-1h-indole-6-carboxamide Chemical compound C1=C2C=CNC2=CC(C(NC2CC3=CC=CC=C3C2)=O)=C1 QNKGSVMHFYKXMY-UHFFFAOYSA-N 0.000 claims description 3
- OKCJNSDIVCXYAL-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-2,2-difluoro-1,3-benzodioxole-5-carboxamide Chemical compound C1C2=CC=CC=C2CC1NC(=O)C1=CC=C2OC(F)(F)OC2=C1 OKCJNSDIVCXYAL-UHFFFAOYSA-N 0.000 claims description 3
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
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- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- 230000007334 memory performance Effects 0.000 claims description 2
- LDRDLYITKGCQQZ-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-4-(methylamino)benzamide Chemical compound C1=CC(NC)=CC=C1C(=O)NC1CC2=CC=CC=C2C1 LDRDLYITKGCQQZ-UHFFFAOYSA-N 0.000 claims description 2
- KJRZWIKUHMWWFM-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-4-methylsulfanylbenzamide Chemical compound C1=CC(SC)=CC=C1C(=O)NC1CC2=CC=CC=C2C1 KJRZWIKUHMWWFM-UHFFFAOYSA-N 0.000 claims description 2
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- KPVOHHOWYRESDB-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-2,5-dimethyl-1h-pyrrole-3-carboxamide Chemical compound N1C(C)=CC(C(=O)NC2CC3=CC=CC=C3C2)=C1C KPVOHHOWYRESDB-UHFFFAOYSA-N 0.000 claims 2
- MPXUHFXUIZRORK-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-4-ethylsulfanylbenzamide Chemical compound C1=CC(SCC)=CC=C1C(=O)NC1CC2=CC=CC=C2C1 MPXUHFXUIZRORK-UHFFFAOYSA-N 0.000 claims 2
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Classifications
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| TWI241190B (en) * | 2001-02-13 | 2005-10-11 | Aventis Pharma Gmbh | 4-Fluoro-N-indan-2-yl benzamide and its use as pharmaceutical |
| TWI243164B (en) * | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
| SE0102764D0 (sv) | 2001-08-17 | 2001-08-17 | Astrazeneca Ab | Compounds |
| US7338956B2 (en) | 2002-08-07 | 2008-03-04 | Sanofi-Aventis Deutschland Gmbh | Acylamino-substituted heteroaromatic compounds and their use as pharmaceuticals |
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| US7105513B2 (en) * | 2002-08-07 | 2006-09-12 | Sanofi-Avertis Deutschland Gmbh | Acylated, heteroaryl-condensed cycloalkenylamines and their use as pharmaceuticals |
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| KR20060025132A (ko) * | 2003-04-11 | 2006-03-20 | 더 유니버시티 오브 테네시 리서치 파운데이션 | 리소포스파티드산 유사체 및 신생내막 형성의 저해 |
| US7132536B2 (en) * | 2003-04-24 | 2006-11-07 | Sanofi-Aventis Deutschland Gmbh | Triaza- and tetraaza-anthracenedione derivatives, their preparation and their use as pharmaceuticals |
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| EP1529525A1 (en) * | 2003-11-06 | 2005-05-11 | Aventis Pharma Deutschland GmbH | ENOS transcription enhancers for use in the cell therapy of ischemic heart diseases |
| US8309608B2 (en) * | 2003-11-06 | 2012-11-13 | Sanofi-Aventis Deutschland Gmbh | Use of eNOS transcription enhancers in the cell therapy of ischemic heart diseases |
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| JP2008500358A (ja) * | 2004-05-25 | 2008-01-10 | メタボレックス インコーポレーティッド | Pparのモジュレーターとしての、二環式の置換されたトリアゾール、およびこれらの調製方法 |
| PL2489659T3 (pl) | 2004-06-24 | 2018-06-29 | Vertex Pharma | Modulatory transporterów posiadających kasetę wiążącą atp |
| US8354427B2 (en) * | 2004-06-24 | 2013-01-15 | Vertex Pharmaceutical Incorporated | Modulators of ATP-binding cassette transporters |
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| JP2007277096A (ja) * | 2004-07-15 | 2007-10-25 | Astellas Pharma Inc | フェネチルニコチンアミド誘導体含有医薬 |
| WO2006040645A1 (en) * | 2004-10-11 | 2006-04-20 | Ranbaxy Laboratories Limited | N-(3,5-dichloropyridin-4-yl)-2,4,5-alkoxy and 2,3,4-alkoxy benzamide derivatives as pde-iv (phophodiesterase type-iv) inhibitors for the treatment of inflammatory diseases such as asthma |
| NZ555121A (en) * | 2004-10-14 | 2011-01-28 | Abbott Gmbh & Co Kg | 6-amino(aza)indane compounds suitable for treating disorders that respond to modulation of the dopamine d3 recptor |
| ZA200800191B (en) * | 2005-06-09 | 2009-04-29 | Vertex Pharmaceuicals Inc | Indane derivatives as modulators of ion channels |
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| KR101346902B1 (ko) | 2005-07-09 | 2014-01-02 | 아스트라제네카 아베 | 당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한헤테로아릴 벤즈아미드 유도체 |
| GT200600429A (es) * | 2005-09-30 | 2007-04-30 | Compuestos organicos | |
| US7592461B2 (en) * | 2005-12-21 | 2009-09-22 | Bristol-Myers Squibb Company | Indane modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| EP1979367A2 (en) * | 2005-12-24 | 2008-10-15 | Vertex Pharmaceuticals Incorporated | Quinolin-4-one derivatives as modulators of abc transporters |
| US7906508B2 (en) | 2005-12-28 | 2011-03-15 | Japan Tobacco Inc. | 3,4-dihydrobenzoxazine compounds and inhibitors of vanilloid receptor subtype 1 (VRI) activity |
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2010
- 2010-03-29 US US12/748,951 patent/US8163751B2/en not_active Expired - Fee Related
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