Title:
CONDENSED PYRIDOINDOLE DERIVATIVES
Document Type and Number:
WIPO Patent Application WO2002028865
Kind Code:
A3
Abstract:
Compounds of general structural formula (I) and use of the compounds and salts and solvates thereof, as therapeutic agents._In particular, the invention relates to compounds that are potent and selective inhibitors of cyclic guanosine 3', 5' -monophosphate specific phosphodiesterase (cGMP-specific PDE), in particular PDE5, and have utilisty in a variety of therapeutic areas wherein such inhibition is considered beneficial, including the treatment of cardiovascular disorders and erectile dysfunction.
Inventors:
ORME MARK W (US)
SAWYER JASON SCOTT (US)
DAUGAN ALAIN CLAUDE-MARIE (FR)
GOSIMINI ROMAIN LUC MARIE (FR)
SCHULTZE LISA M (US)
SAWYER JASON SCOTT (US)
DAUGAN ALAIN CLAUDE-MARIE (FR)
GOSIMINI ROMAIN LUC MARIE (FR)
SCHULTZE LISA M (US)
Application Number:
PCT/US2001/042175
Publication Date:
February 27, 2003
Filing Date:
September 17, 2001
Export Citation:
Assignee:
LILLY ICOS LLC (US)
ORME MARK W (US)
SAWYER JASON SCOTT (US)
DAUGAN ALAIN CLAUDE-MARIE (FR)
GOSIMINI ROMAIN LUC MARIE (FR)
SCHULTZE LISA M (US)
ORME MARK W (US)
SAWYER JASON SCOTT (US)
DAUGAN ALAIN CLAUDE-MARIE (FR)
GOSIMINI ROMAIN LUC MARIE (FR)
SCHULTZE LISA M (US)
International Classes:
A61K31/437; A61P1/00; A61P1/04; A61P7/04; A61P9/00; A61P9/04; A61P9/08; A61P9/10; A61P9/12; A61P11/00; A61P11/02; A61P11/06; A61P13/08; A61P13/12; A61P15/06; A61P15/10; A61P19/10; A61P25/26; A61P27/06; A61P29/00; A61P35/00; A61P37/08; A61P43/00; C07D471/14; C07D498/04; C07D498/14; C07D513/04; C07D513/14; C07D515/14; (IPC1-7): C07D498/14; A61K31/437; A61P9/00; A61P15/10; C07D513/14; C07D471/14; C07D515/14
Domestic Patent References:
| WO1994010175A1 | 1994-05-11 | |||
| WO1996032003A2 | 1996-10-17 |
Foreign References:
| EP0357122A2 | 1990-03-07 |
Other References:
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; TANABE SIYAKU: "Tetrahydro-.beta.-carboline derivatives", XP002204315, retrieved from STN Database accession no. 1986:608864
KUMAR, N. ET AL.: "Agents acting on CNS: Part XXXI-Synthesis of 2-substituted 1,2,3,5,11,11a-hexahydro-6H-imidazo [5,1:6,1] pyrido [3,4-b] indoles", INDIAN JOURNAL OF CHEMISTRY, SECTION B: ORGANIC, INCL. MEDICINAL., vol. 19B, no. 12, 1980, PUBLICATIONS & INFORMATIONS DIRECTORATE, NEW DELHI., IN, pages 1087 - 1088, XP008004701, ISSN: 0019-5103
MADALENGOITIA, J.S. ET AL.: "Structure-activity relationship for DNA topiisomerase II-induced DNA clevage by azatoxin analogues", BIOORGANIC & MEDICINAL CHEMISTRY., vol. 5, no. 9, 1997, ELSEVIER SCIENCE LTD., GB, pages 1807 - 1815, XP002204309, ISSN: 0968-0896
LETEURTRE, F. ET AL.: "Azatoxin derivatives with potent and selective action on topoisomerase II", BIOCHEMICAL PHARMACOLOGY, vol. 49, no. 9, 1995, PERGAMON, OXFORD, GB, pages 1283 - 1290, XP002204310, ISSN: 0006-2952
LOPEZ RODRIGUEZ M L ET AL: "REACTION OF 6-HYDROXYTETRAHYDRO-BETA-CARBOLINE-3-CARBOXYLIC ACIDS WITH ISOCYANATES AND ISOTHIOCYANATES", CHEMICAL AND PHARMACEUTICAL BULLETIN, PHARMACEUTICAL SOCIETY OF JAPAN. TOKYO, JP, vol. 42, no. 10, 1 October 1994 (1994-10-01), pages 2108 - 2112, XP000608286, ISSN: 0009-2363
BRAÑA M F ET AL: "SYNTHESIS AND REACTIVITY OF BETA-CARBOLINE-HYDANTOIN SYSTEMS", SYNTHETIC COMMUNICATIONS, MARCEL DEKKER, INC., BASEL, CH, vol. 20, no. 12, 1990, pages 1793 - 1810, XP000196528, ISSN: 0039-7911
DEL GIUFICE, M.R. ET AL.: "New tetracyclic compounds containing the beta-carboline moiety", JOURNAL OF HETEROCYCLIC CHEMISTRY., vol. 27, 1990, HETEROCORPORATION. PROVO., US, pages 967 - 973, XP002204311, ISSN: 0022-152X
SAIGA, Y. ET AL.: "Synthesis of 1,2,3,4-tetrahydro-beta-carboline derivatives as hepatoprotective agents. III. Introduction of substituents onto methyl 1,2,3,4-tetrahydro-beta-carboline-2-carbodithioate", CHEMICAL AND PHARMACEUTICAL BULLETIN., vol. 35, no. 8, 1987, PHARMACEUTICAL SOCIETY OF JAPAN. TOKYO., JP, pages 3284 - 3291, XP002204312, ISSN: 0009-2363
HINO T ET AL: "RADIATION-PROTECTIVE AGENTS. IV. SYNTHESIS OF TETRAHYDRO-BETA-CARBOLINES AND 2-AMINOTHIAZOLINE DERIVATIVE FROM TRYPTOPHANOLS", CHEMICAL AND PHARMACEUTICAL BULLETIN, TOKYO, JP, vol. 2, no. 18, 1970, pages 384 - 388, XP008004700, ISSN: 0009-2363
FALTZ ET A.: "Synthesis of optically active, condensed tetrahydropyridin-3-ones as precursors of alkaloid analogs", SYNLETT., no. 9, 1997, THIEME VERLAG, STUTTGART., DE, pages 1071 - 1072, XP002204313, ISSN: 0936-5214
LOPEZ-RODRIGUEZ, M.L. ET AL.: "Stereospecificity in the reaction of tetrahydro-beta-carboline-3-carboxylic acids with isocyanates. Kinetic vs thermodynamic control", JOURNAL OF ORGANIC CHEMISTRY., vol. 59, no. 6, 1994, AMERICAN CHEMICAL SOCIETY. EASTON., US, pages 1583 - 1585, XP002204314, ISSN: 0022-3263
KUMAR, N. ET AL.: "Agents acting on CNS: Part XXXI-Synthesis of 2-substituted 1,2,3,5,11,11a-hexahydro-6H-imidazo [5,1:6,1] pyrido [3,4-b] indoles", INDIAN JOURNAL OF CHEMISTRY, SECTION B: ORGANIC, INCL. MEDICINAL., vol. 19B, no. 12, 1980, PUBLICATIONS & INFORMATIONS DIRECTORATE, NEW DELHI., IN, pages 1087 - 1088, XP008004701, ISSN: 0019-5103
MADALENGOITIA, J.S. ET AL.: "Structure-activity relationship for DNA topiisomerase II-induced DNA clevage by azatoxin analogues", BIOORGANIC & MEDICINAL CHEMISTRY., vol. 5, no. 9, 1997, ELSEVIER SCIENCE LTD., GB, pages 1807 - 1815, XP002204309, ISSN: 0968-0896
LETEURTRE, F. ET AL.: "Azatoxin derivatives with potent and selective action on topoisomerase II", BIOCHEMICAL PHARMACOLOGY, vol. 49, no. 9, 1995, PERGAMON, OXFORD, GB, pages 1283 - 1290, XP002204310, ISSN: 0006-2952
LOPEZ RODRIGUEZ M L ET AL: "REACTION OF 6-HYDROXYTETRAHYDRO-BETA-CARBOLINE-3-CARBOXYLIC ACIDS WITH ISOCYANATES AND ISOTHIOCYANATES", CHEMICAL AND PHARMACEUTICAL BULLETIN, PHARMACEUTICAL SOCIETY OF JAPAN. TOKYO, JP, vol. 42, no. 10, 1 October 1994 (1994-10-01), pages 2108 - 2112, XP000608286, ISSN: 0009-2363
BRAÑA M F ET AL: "SYNTHESIS AND REACTIVITY OF BETA-CARBOLINE-HYDANTOIN SYSTEMS", SYNTHETIC COMMUNICATIONS, MARCEL DEKKER, INC., BASEL, CH, vol. 20, no. 12, 1990, pages 1793 - 1810, XP000196528, ISSN: 0039-7911
DEL GIUFICE, M.R. ET AL.: "New tetracyclic compounds containing the beta-carboline moiety", JOURNAL OF HETEROCYCLIC CHEMISTRY., vol. 27, 1990, HETEROCORPORATION. PROVO., US, pages 967 - 973, XP002204311, ISSN: 0022-152X
SAIGA, Y. ET AL.: "Synthesis of 1,2,3,4-tetrahydro-beta-carboline derivatives as hepatoprotective agents. III. Introduction of substituents onto methyl 1,2,3,4-tetrahydro-beta-carboline-2-carbodithioate", CHEMICAL AND PHARMACEUTICAL BULLETIN., vol. 35, no. 8, 1987, PHARMACEUTICAL SOCIETY OF JAPAN. TOKYO., JP, pages 3284 - 3291, XP002204312, ISSN: 0009-2363
HINO T ET AL: "RADIATION-PROTECTIVE AGENTS. IV. SYNTHESIS OF TETRAHYDRO-BETA-CARBOLINES AND 2-AMINOTHIAZOLINE DERIVATIVE FROM TRYPTOPHANOLS", CHEMICAL AND PHARMACEUTICAL BULLETIN, TOKYO, JP, vol. 2, no. 18, 1970, pages 384 - 388, XP008004700, ISSN: 0009-2363
FALTZ ET A.: "Synthesis of optically active, condensed tetrahydropyridin-3-ones as precursors of alkaloid analogs", SYNLETT., no. 9, 1997, THIEME VERLAG, STUTTGART., DE, pages 1071 - 1072, XP002204313, ISSN: 0936-5214
LOPEZ-RODRIGUEZ, M.L. ET AL.: "Stereospecificity in the reaction of tetrahydro-beta-carboline-3-carboxylic acids with isocyanates. Kinetic vs thermodynamic control", JOURNAL OF ORGANIC CHEMISTRY., vol. 59, no. 6, 1994, AMERICAN CHEMICAL SOCIETY. EASTON., US, pages 1583 - 1585, XP002204314, ISSN: 0022-3263
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