TW378210B - Tetracyclic derivatives; process of preparation and use - Google Patents
Tetracyclic derivatives; process of preparation and use Download PDFInfo
- Publication number
- TW378210B TW378210B TW084100415A TW84100415A TW378210B TW 378210 B TW378210 B TW 378210B TW 084100415 A TW084100415 A TW 084100415A TW 84100415 A TW84100415 A TW 84100415A TW 378210 B TW378210 B TW 378210B
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- Taiwan
- Prior art keywords
- alkyl
- compound
- pyridyl
- formula
- patent application
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 147
- 230000008569 process Effects 0.000 title description 7
- 238000002360 preparation method Methods 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 225
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 100
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 62
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 36
- 239000001257 hydrogen Substances 0.000 claims abstract description 33
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 18
- 150000002367 halogens Chemical class 0.000 claims abstract description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 16
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims abstract description 9
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 5
- 229930192474 thiophene Natural products 0.000 claims abstract description 5
- 238000011049 filling Methods 0.000 claims description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 51
- -1 3,4- ethylenedioxy group Chemical group 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 47
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 43
- 125000004076 pyridyl group Chemical group 0.000 claims description 40
- 230000002079 cooperative effect Effects 0.000 claims description 39
- 239000002904 solvent Substances 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000003983 fluorenyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 8
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- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
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- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- BFAKENXZKHGIGE-UHFFFAOYSA-N bis(2,3,5,6-tetrafluoro-4-iodophenyl)diazene Chemical compound FC1=C(C(=C(C(=C1F)I)F)F)N=NC1=C(C(=C(C(=C1F)F)I)F)F BFAKENXZKHGIGE-UHFFFAOYSA-N 0.000 claims description 4
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
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- 229940079593 drug Drugs 0.000 claims description 3
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
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- 150000003141 primary amines Chemical class 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 5
- 125000004175 fluorobenzyl group Chemical group 0.000 claims 3
- 125000001712 tetrahydronaphthyl group Chemical class C1(CCCC2=CC=CC=C12)* 0.000 claims 3
- 125000001544 thienyl group Chemical class 0.000 claims 3
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- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 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 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
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- 125000001475 halogen functional group Chemical group 0.000 claims 1
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- 230000004054 inflammatory process Effects 0.000 claims 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 230000035479 physiological effects, processes and functions Effects 0.000 claims 1
- 125000004149 thio group Chemical group *S* 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 14
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- 229920006395 saturated elastomer Polymers 0.000 abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 8
- 239000012453 solvate Substances 0.000 abstract description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 6
- 230000009286 beneficial effect Effects 0.000 abstract description 5
- 125000002619 bicyclic group Chemical group 0.000 abstract description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract description 4
- 229940124639 Selective inhibitor Drugs 0.000 abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 3
- 125000005842 heteroatom Chemical group 0.000 abstract description 3
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
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| GB9514465D0 (en) * | 1995-07-14 | 1995-09-13 | Glaxo Lab Sa | Chemical compounds |
| US6143746A (en) * | 1994-01-21 | 2000-11-07 | Icos Corporation | Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use |
| GB9511220D0 (en) * | 1995-06-02 | 1995-07-26 | Glaxo Group Ltd | Solid dispersions |
| US6232312B1 (en) | 1995-06-07 | 2001-05-15 | Cell Pathways, Inc. | Method for treating patient having precancerous lesions with a combination of pyrimidopyrimidine derivatives and esters and amides of substituted indenyl acetic acides |
| US5874440A (en) | 1995-06-07 | 1999-02-23 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl pyrimidinone derivatives |
| US6200980B1 (en) | 1995-06-07 | 2001-03-13 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl purinone derivatives |
| US6046216A (en) | 1995-06-07 | 2000-04-04 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl pyridinone derivatives |
| US6262059B1 (en) | 1995-06-07 | 2001-07-17 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with quinazoline derivatives |
| US6060477A (en) | 1995-06-07 | 2000-05-09 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl cycloamino pyrimidinone derivatives |
| GB9514464D0 (en) * | 1995-07-14 | 1995-09-13 | Glaxo Lab Sa | Medicaments |
| GB9514473D0 (en) * | 1995-07-14 | 1995-09-13 | Glaxo Lab Sa | Chemical compounds |
| EE9800390A (et) | 1996-05-10 | 1999-06-15 | Icos Corporation | Karboliini derivaadid |
| US5958926A (en) * | 1996-11-01 | 1999-09-28 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses |
| US6331543B1 (en) | 1996-11-01 | 2001-12-18 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use |
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| DE69833254T2 (de) * | 1997-06-23 | 2006-11-02 | Cellegy Pharmaceuticals, Inc., Brisbane | Microdosistherapie von gefässbedingten erscheinungen durch no-donoren |
| US6403597B1 (en) * | 1997-10-28 | 2002-06-11 | Vivus, Inc. | Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation |
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| US6348032B1 (en) | 1998-11-23 | 2002-02-19 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with benzimidazole derivatives |
| US6486155B1 (en) | 1998-11-24 | 2002-11-26 | Cell Pathways Inc | Method of inhibiting neoplastic cells with isoquinoline derivatives |
| US6420410B1 (en) | 1998-11-24 | 2002-07-16 | Cell Pathways, Inc. | Method for treating neoplasia by exposure to N,N′-substituted benzimidazol-2-ones |
| US6211177B1 (en) | 1998-11-24 | 2001-04-03 | Cell Pathways, Inc. | Method for treating neoplasia by exposure to substituted 2-aryl-benzimidazole derivatives |
| US6358992B1 (en) | 1998-11-25 | 2002-03-19 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with indole derivatives |
| JP2002539247A (ja) | 1999-03-24 | 2002-11-19 | ハーバー ブランチ オーシャノグラフィック インスティテューション インク． | マンズアミンの抗炎症作用の使用 |
| HUP0001632A3 (en) * | 1999-04-30 | 2001-12-28 | Lilly Icos Llc Wilmington | Pharmaceutical compositions comprising selective phosphodiestherase inhibitors |
| US6943166B1 (en) | 1999-04-30 | 2005-09-13 | Lilly Icos Llc. | Compositions comprising phosphodiesterase inhabitors for the treatment of sexual disfunction |
| US6451807B1 (en) | 1999-04-30 | 2002-09-17 | Lilly Icos, Llc. | Methods of treating sexual dysfunction in an individual suffering from a retinal disease, class 1 congestive heart failure, or myocardial infarction using a PDE5 inhibitor |
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| UA72922C2 (uk) | 1999-08-03 | 2005-05-16 | Ліллі Айкос Ллк | ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ З <font face="Symbol">b</font>-КАРБОЛІНОМ (ВАРІАНТИ) ТА СПОСІБ ЛІКУВАННЯ СЕКСУАЛЬНОЇ ДИСФУНКЦІЇ |
| US6821975B1 (en) | 1999-08-03 | 2004-11-23 | Lilly Icos Llc | Beta-carboline drug products |
| KR20020038941A (ko) | 1999-10-11 | 2002-05-24 | 디. 제이. 우드, 스피겔 알렌 제이 | 포스포디에스테라아제 억제제로서의5-(2-치환된-5-헤테로사이클릴설포닐피리드-3-일)-디하이드로피라졸로[4,3-ｄ]피리미딘-7-온 |
| TWI224966B (en) * | 1999-11-02 | 2004-12-11 | Pfizer | Pharmaceutical composition (I) useful for treating or preventing pulmonary hypertension in a patient |
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| US20020013327A1 (en) * | 2000-04-18 | 2002-01-31 | Lee Andrew G. | Compositions and methods for treating female sexual dysfunction |
| AU2001255849B8 (en) | 2000-04-19 | 2006-04-27 | Lilly Icos, Llc. | PDE-V inhibitors for treatment of Parkinson's Disease |
| UA74826C2 (en) | 2000-05-17 | 2006-02-15 | Ortho Mcneil Pharm Inc | ?-carboline derivatives as phosphodiesterase inhibitors |
| UA72611C2 (uk) * | 2000-05-17 | 2005-03-15 | Орто-Макнейл Фармацевтикал, Інк. | Похідні заміщеного піролопіридинону, корисні як інгібітори фосфодіестерази |
| EP1289989A2 (en) | 2000-06-07 | 2003-03-12 | Lilly Icos LLC | Derivatives of 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione |
| JP4169149B2 (ja) | 2000-06-23 | 2008-10-22 | リリー アイコス リミテッド ライアビリティ カンパニー | 化学的化合物 |
| JP2004501920A (ja) * | 2000-06-23 | 2004-01-22 | リリー アイコス リミテッド ライアビリティ カンパニー | 環状ｇｍｐ特異的ホスホジエステラーゼ阻害剤 |
| WO2002000657A2 (en) * | 2000-06-26 | 2002-01-03 | Lilly Icos Llc | Condensed pyrazindione derivatives |
| AU2001278480A1 (en) * | 2000-07-24 | 2002-02-05 | Bayer Crop Science Ag | Biphenyl carboxamides |
| CA2423357C (en) * | 2000-08-02 | 2008-05-27 | Lilly Icos Llc | Fused heterocyclic derivatives as phosphodiesterase inhibitors |
| US20040092494A9 (en) * | 2000-08-30 | 2004-05-13 | Dudley Robert E. | Method of increasing testosterone and related steroid concentrations in women |
| US6503894B1 (en) | 2000-08-30 | 2003-01-07 | Unimed Pharmaceuticals, Inc. | Pharmaceutical composition and method for treating hypogonadism |
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| AU2002213419A1 (en) | 2000-10-02 | 2002-04-15 | Lilly Icos Llc | Condensed pyridoindole derivatives |
| ATE297926T1 (de) * | 2000-10-02 | 2005-07-15 | Lilly Icos Llc | Hexahydropyrazino(1'2':1,6)-pyrido(3,4-b)indole 1,4-dion-derivate zur behandlung von cardiovaskulären erkrankungen und erektionsstörungen |
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| DE60122559T2 (de) * | 2000-11-06 | 2006-12-07 | Lilly Icos Llc, Wilmington | Indolderivate als pde5-inhibitoren |
| CA2441792C (en) * | 2001-04-25 | 2010-08-03 | Lilly Icos Llc | Carboline derivatives as inhibitors of phosphodiesterase 5 (pdes) for the treatment of cardiovascular diseases and erectile dysfunction |
| FR2824829B1 (fr) * | 2001-05-16 | 2005-06-03 | Macef | Nouveaux derives de dihydroimidazo [5,1-a]-beta-carboline, leur procede de preparation et leur application a titre de medicament |
| DE60226970D1 (de) | 2001-06-05 | 2008-07-17 | Lilly Icos Llc | Pyrazinoä1',2':1,6ü-pyridoä3,4-bü indole-1,4-dionderivate |
| ES2286291T3 (es) * | 2001-06-05 | 2007-12-01 | Lilly Icos Llc | Compustos tetraciclicos como inhibidores de pde5. |
| WO2002098875A1 (en) * | 2001-06-05 | 2002-12-12 | Lilly Icos Llc | Carboline derivatives as pde-5 inhibitors |
| US6984641B2 (en) | 2001-06-21 | 2006-01-10 | Lilly Icos Llc. | Carboline derivatives as PDE5 inhibitors |
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| UA78974C2 (en) | 2001-10-20 | 2007-05-10 | Boehringer Ingelheim Pharma | Use of flibanserin for treating disorders of sexual desire |
| CA2465893A1 (en) * | 2001-11-09 | 2003-05-22 | Schering Corporation | Polycyclic guanine derivative phosphodiesterase v inhibitors |
| PT1448562E (pt) | 2001-11-14 | 2007-08-31 | Ortho Mcneil Pharm Inc | Derivados da pirroloquinolona tetracíclica substituídos, úteis como inibidores da fosfodiesterase |
| US6962940B2 (en) | 2002-03-20 | 2005-11-08 | Celgene Corporation | (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof |
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| US12569493B2 (en) | 2020-03-24 | 2026-03-10 | Cyrano Therapeutics Inc. | Treatment of chemosensory dysfunction from a coronavirus infection |
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| WO2024158189A1 (ko) | 2023-01-25 | 2024-08-02 | 주식회사 아리바이오 | 포스포디에스테라제 타입 ５ 저해제를 유효성분으로 포함하는 외상 후 스트레스 장애의 예방 또는 치료용 조성물 |
| EP4665351A1 (en) | 2023-02-16 | 2025-12-24 | University of Rochester | Improving glymphatic-lymphatic efflux |
| CN116715667A (zh) * | 2023-06-20 | 2023-09-08 | 常州制药厂有限公司 | 一种他达拉非新晶型b及其制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US3644384A (en) * | 1969-06-09 | 1972-02-22 | Sterling Drug Inc | Certain 2-(alpha-haloacetyl) - 1 2 3 4-tetrahydro - 9h - pyrido(3 4-b)indole-3-carboxylates and derivatives |
| US3717638A (en) * | 1971-03-11 | 1973-02-20 | Sterling Drug Inc | 1,2,3,4,6,7,12,12A-OCTAHYDRO-2-PHENYLPYRAZINO[2',1':6,1]PYRIDO[3,4-b]INDOLES AND INTERMEDIATES THEREFOR |
| US3917599A (en) * | 1973-03-30 | 1975-11-04 | Council Scient Ind Res | 2-Substituted-1,2,3,4,6,7,12,12A-octahydropyrazino(2{40 ,1{40 :6,1)pyrido(3,4-B)indoles |
| GB1454171A (en) * | 1973-10-19 | 1976-10-27 | Council Scient Ind Res | Tetracyclic compounds |
| US4273773A (en) * | 1979-09-24 | 1981-06-16 | American Home Products Corporation | Antihypertensive tricyclic isoindole derivatives |
| EP0357122A3 (en) * | 1988-08-29 | 1991-10-23 | Duphar International Research B.V | Use of beta-carbolines, their bio-isosteric benzofuran and benzothiophene analogues for the manufacture of a medicament having cytostatic properties |
| DE3830096A1 (de) * | 1988-09-03 | 1990-03-15 | Hoechst Ag | Piperazindione mit psychotroper wirkung |
| GB9514465D0 (en) * | 1995-07-14 | 1995-09-13 | Glaxo Lab Sa | Chemical compounds |
| US6046199A (en) * | 1998-01-14 | 2000-04-04 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with tetracyclic pyrido[3,4-B]indole derivatives |
| US6225315B1 (en) * | 1998-11-30 | 2001-05-01 | Pfizer Inc | Method of treating nitrate-induced tolerance |
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