UA75121C2 - Acylated indanyl amines, use thereof, pharmaceutical based thereon and a method for synthesis thereof - Google Patents
Acylated indanyl amines, use thereof, pharmaceutical based thereon and a method for synthesis thereof Download PDFInfo
- Publication number
- UA75121C2 UA75121C2 UA2003098452A UA2003098452A UA75121C2 UA 75121 C2 UA75121 C2 UA 75121C2 UA 2003098452 A UA2003098452 A UA 2003098452A UA 2003098452 A UA2003098452 A UA 2003098452A UA 75121 C2 UA75121 C2 UA 75121C2
- Authority
- UA
- Ukraine
- Prior art keywords
- alkyl
- group
- phenyl
- heteroaryl
- substituents
- Prior art date
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- -1 Acylated indanyl amines Chemical class 0.000 title claims abstract description 437
- 238000000034 method Methods 0.000 title claims description 23
- 230000015572 biosynthetic process Effects 0.000 title description 11
- 238000003786 synthesis reaction Methods 0.000 title description 9
- 125000001424 substituent group Chemical group 0.000 claims abstract description 198
- 150000001875 compounds Chemical class 0.000 claims abstract description 125
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 110
- 125000003118 aryl group Chemical group 0.000 claims abstract description 60
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 206010020772 Hypertension Diseases 0.000 claims abstract description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 11
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 10
- 206010019280 Heart failures Diseases 0.000 claims abstract description 8
- 208000029078 coronary artery disease Diseases 0.000 claims abstract description 8
- 206010048554 Endothelial dysfunction Diseases 0.000 claims abstract description 7
- 208000007718 Stable Angina Diseases 0.000 claims abstract description 7
- 210000001367 artery Anatomy 0.000 claims abstract description 7
- 230000006378 damage Effects 0.000 claims abstract description 7
- 230000008694 endothelial dysfunction Effects 0.000 claims abstract description 7
- 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 6
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 6
- 208000007814 Unstable Angina Diseases 0.000 claims abstract description 6
- 208000037803 restenosis Diseases 0.000 claims abstract description 6
- 206010018367 Glomerulonephritis chronic Diseases 0.000 claims abstract description 5
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 5
- 208000017442 Retinal disease Diseases 0.000 claims abstract description 5
- 206010038923 Retinopathy Diseases 0.000 claims abstract description 5
- 208000006673 asthma Diseases 0.000 claims abstract description 5
- 208000020832 chronic kidney disease Diseases 0.000 claims abstract description 5
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims abstract description 5
- 208000019425 cirrhosis of liver Diseases 0.000 claims abstract description 5
- 239000003433 contraceptive agent Substances 0.000 claims abstract description 5
- 208000017169 kidney disease Diseases 0.000 claims abstract description 5
- 208000002815 pulmonary hypertension Diseases 0.000 claims abstract description 5
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 4
- 201000003099 Renovascular Hypertension Diseases 0.000 claims abstract description 4
- 230000007882 cirrhosis Effects 0.000 claims abstract description 4
- 210000004185 liver Anatomy 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract 8
- 230000002093 peripheral effect Effects 0.000 claims abstract 4
- 206010002388 Angina unstable Diseases 0.000 claims abstract 3
- 208000007530 Essential hypertension Diseases 0.000 claims abstract 3
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims abstract 3
- LMHHFZAXSANGGM-UHFFFAOYSA-N 2-aminoindane Chemical compound C1=CC=C2CC(N)CC2=C1 LMHHFZAXSANGGM-UHFFFAOYSA-N 0.000 claims description 163
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 136
- 229910052736 halogen Inorganic materials 0.000 claims description 130
- 150000002367 halogens Chemical class 0.000 claims description 128
- 125000002577 pseudohalo group Chemical group 0.000 claims description 90
- 239000000203 mixture Substances 0.000 claims description 87
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 72
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 42
- 125000005842 heteroatom Chemical group 0.000 claims description 38
- 229910052799 carbon Inorganic materials 0.000 claims description 36
- 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 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 25
- 239000000243 solution Substances 0.000 claims description 23
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 20
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 18
- 125000002950 monocyclic group Chemical group 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 17
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 16
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 15
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 14
- 230000003511 endothelial effect Effects 0.000 claims description 14
- 230000014509 gene expression Effects 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 125000001931 aliphatic group Chemical group 0.000 claims description 11
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 9
- 239000003826 tablet Substances 0.000 claims description 9
- 239000008177 pharmaceutical agent Substances 0.000 claims description 8
- 229910052698 phosphorus Inorganic materials 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 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
- 239000007903 gelatin capsule Substances 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 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
- 238000002347 injection Methods 0.000 claims description 6
- 239000007924 injection Substances 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl 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
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=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
- COWZPSUDTMGBAT-UHFFFAOYSA-N 5-bromothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)S1 COWZPSUDTMGBAT-UHFFFAOYSA-N 0.000 claims description 5
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 5
- 229910052796 boron Inorganic materials 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000000839 emulsion Substances 0.000 claims description 5
- 239000007943 implant Substances 0.000 claims description 5
- 238000001802 infusion Methods 0.000 claims description 5
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 239000003094 microcapsule Substances 0.000 claims description 5
- 208000010125 myocardial infarction Diseases 0.000 claims description 5
- 239000007922 nasal spray Substances 0.000 claims description 5
- 239000006187 pill Substances 0.000 claims description 5
- 239000000829 suppository Substances 0.000 claims description 5
- 239000006188 syrup Substances 0.000 claims description 5
- 235000020357 syrup Nutrition 0.000 claims description 5
- IFLKEBSJTZGCJG-UHFFFAOYSA-N 3-methylthiophene-2-carboxylic acid Chemical compound CC=1C=CSC=1C(O)=O IFLKEBSJTZGCJG-UHFFFAOYSA-N 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
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 4
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
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- 201000001881 impotence Diseases 0.000 claims description 4
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 4
- 239000006210 lotion Substances 0.000 claims description 4
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- 239000007921 spray Substances 0.000 claims description 4
- 239000007940 sugar coated tablet Substances 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims description 3
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 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
- 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
- LIKIMWYKJUFVJP-UHFFFAOYSA-N 5-acetylthiophene-2-carboxylic acid Chemical compound CC(=O)C1=CC=C(C(O)=O)S1 LIKIMWYKJUFVJP-UHFFFAOYSA-N 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 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 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- GXACFEPGNZAIAV-UHFFFAOYSA-N CC1=CC(C(O)=O)=C(C)N1CC1=CC=NC=C1.NC1CC2=CC=CC=C2C1 Chemical compound CC1=CC(C(O)=O)=C(C)N1CC1=CC=NC=C1.NC1CC2=CC=CC=C2C1 GXACFEPGNZAIAV-UHFFFAOYSA-N 0.000 claims description 2
- OPQNGQDYERJVSO-UHFFFAOYSA-N NC1CC2=CC=CC=C2C1.OC(C(C=C1)=CC2=C1OCC2)=O Chemical compound NC1CC2=CC=CC=C2C1.OC(C(C=C1)=CC2=C1OCC2)=O OPQNGQDYERJVSO-UHFFFAOYSA-N 0.000 claims description 2
- 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
- 230000006386 memory function Effects 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 5
- XIZXADDGOCJZAL-UHFFFAOYSA-N 3h-dioxole-5-carboxylic acid Chemical compound OC(=O)C1=CCOO1 XIZXADDGOCJZAL-UHFFFAOYSA-N 0.000 claims 3
- 208000000418 Premature Cardiac Complexes Diseases 0.000 claims 3
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- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 2
- GHTDODSYDCPOCW-UHFFFAOYSA-N 1h-indole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=CNC2=C1 GHTDODSYDCPOCW-UHFFFAOYSA-N 0.000 claims 2
- LHXYXVBCGWGZTD-UHFFFAOYSA-N CC(C)S(C1=CSC(C(O)=O)=C1Cl)(=O)=O.NC1CC2=CC=CC=C2C1 Chemical compound CC(C)S(C1=CSC(C(O)=O)=C1Cl)(=O)=O.NC1CC2=CC=CC=C2C1 LHXYXVBCGWGZTD-UHFFFAOYSA-N 0.000 claims 2
- HXEJFNYNFBZJKG-UHFFFAOYSA-N CC1=CC(C(O)=O)=C(C)N1.NC1CC2=CC=CC=C2C1 Chemical compound CC1=CC(C(O)=O)=C(C)N1.NC1CC2=CC=CC=C2C1 HXEJFNYNFBZJKG-UHFFFAOYSA-N 0.000 claims 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 230000004936 stimulating effect Effects 0.000 claims 2
- RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical class Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 claims 1
- 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 1
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- 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 claims 1
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Classifications
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2444515C2 (ru) * | 2007-09-28 | 2012-03-10 | Мицубиси Танабе Фарма Корпорейшн | Производное амида индазолакриловой кислоты |
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