[go: up one dir, main page]

AU2001274009A1 - Substituted indoles as parp inhibitors - Google Patents

Substituted indoles as parp inhibitors

Info

Publication number
AU2001274009A1
AU2001274009A1 AU2001274009A AU7400901A AU2001274009A1 AU 2001274009 A1 AU2001274009 A1 AU 2001274009A1 AU 2001274009 A AU2001274009 A AU 2001274009A AU 7400901 A AU7400901 A AU 7400901A AU 2001274009 A1 AU2001274009 A1 AU 2001274009A1
Authority
AU
Australia
Prior art keywords
parp inhibitors
substituted indoles
indoles
substituted
parp
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
Application number
AU2001274009A
Inventor
Roland Grandel
Thomas Hoger
Uta Holzenkamp
Michael Kock
Wilfried Lubisch
Reinhold Muller
Sabine Schult
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
B A S F A G
BASF SE
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by B A S F A G, BASF SE filed Critical B A S F A G
Publication of AU2001274009A1 publication Critical patent/AU2001274009A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/08Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Pain & Pain Management (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Psychology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Vascular Medicine (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Indole Compounds (AREA)
AU2001274009A 2000-05-11 2001-05-09 Substituted indoles as parp inhibitors Abandoned AU2001274009A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10022925A DE10022925A1 (en) 2000-05-11 2000-05-11 New indole-carboxamide or azepino-indole derivatives and analogs, are poly-ADP ribose polymerase inhibitors useful e.g. for treating neurodegenerative disease, ischemia, epilepsy, tumors, sepsis or diabetes mellitus
DE10022925 2000-05-11
PCT/EP2001/005278 WO2001085687A1 (en) 2000-05-11 2001-05-09 Substituted indoles as parp inhibitors

Publications (1)

Publication Number Publication Date
AU2001274009A1 true AU2001274009A1 (en) 2001-11-20

Family

ID=7641548

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2001274009A Abandoned AU2001274009A1 (en) 2000-05-11 2001-05-09 Substituted indoles as parp inhibitors

Country Status (8)

Country Link
US (1) US7087637B2 (en)
EP (1) EP1280774A1 (en)
JP (1) JP2003532709A (en)
AU (1) AU2001274009A1 (en)
CA (1) CA2408369A1 (en)
DE (1) DE10022925A1 (en)
MX (1) MXPA02010985A (en)
WO (1) WO2001085687A1 (en)

Families Citing this family (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10022925A1 (en) 2000-05-11 2001-11-15 Basf Ag New indole-carboxamide or azepino-indole derivatives and analogs, are poly-ADP ribose polymerase inhibitors useful e.g. for treating neurodegenerative disease, ischemia, epilepsy, tumors, sepsis or diabetes mellitus
US7151102B2 (en) 2000-10-30 2006-12-19 Kudos Pharmaceuticals Limited Phthalazinone derivatives
JPWO2003062234A1 (en) * 2002-01-23 2005-05-19 山之内製薬株式会社 Quinoxaline compounds
DE60335359D1 (en) 2002-04-30 2011-01-27 Kudos Pharm Ltd phthalazinone
GB0305681D0 (en) 2003-03-12 2003-04-16 Kudos Pharm Ltd Phthalazinone derivatives
US7449464B2 (en) 2003-03-12 2008-11-11 Kudos Pharmaceuticals Limited Phthalazinone derivatives
GB0317466D0 (en) * 2003-07-25 2003-08-27 Univ Sheffield Use
US7405300B2 (en) 2003-09-04 2008-07-29 Aventis Pharmaveuticals Inc. Substituted indoles as inhibitors of poly (ADP-ribose) polymerase (PARP)
US8060112B2 (en) 2003-11-20 2011-11-15 Intellient Spatial Technologies, Inc. Mobile device and geographic information system background and summary of the related art
DK2305221T3 (en) * 2003-12-01 2015-08-24 Kudos Pharm Ltd DNA damage repair inhibitors for the treatment of cancer
US7868037B2 (en) 2004-07-14 2011-01-11 Ptc Therapeutics, Inc. Methods for treating hepatitis C
US7781478B2 (en) 2004-07-14 2010-08-24 Ptc Therapeutics, Inc. Methods for treating hepatitis C
MX2007000481A (en) 2004-07-14 2007-03-29 Ptc Therapeutics Inc Methods for treating hepatitis c.
US7772271B2 (en) 2004-07-14 2010-08-10 Ptc Therapeutics, Inc. Methods for treating hepatitis C
JP2008507518A (en) 2004-07-22 2008-03-13 ピーティーシー セラピューティクス,インコーポレーテッド Thienopyridine for treating hepatitis C
GB0419072D0 (en) 2004-08-26 2004-09-29 Kudos Pharm Ltd Phthalazinone derivatives
CA2595290C (en) 2005-01-19 2013-06-25 Mgi Gp, Inc. Diazabenzo[de]anthracen-3-one compounds and methods for inhibiting parp
GB0521373D0 (en) 2005-10-20 2005-11-30 Kudos Pharm Ltd Pthalazinone derivatives
EP2007733B1 (en) * 2006-04-03 2016-05-25 MSD Italia S.r.l. Amide substituted indazole and benzotriazole derivatives as poly(adp-ribose)polymerase (parp) inhibitors
TWI404716B (en) 2006-10-17 2013-08-11 Kudos Pharm Ltd Phthalazinone derivative
EP2805945B1 (en) 2007-01-10 2019-04-03 MSD Italia S.r.l. Amide substituted indazoles as poly(ADP-ribose)polymerase (PARP) inhibitors
WO2008154129A1 (en) * 2007-06-08 2008-12-18 Bausch & Lomb Incorporated Pharmaceutical compositions and method for treating, reducing, ameliorating, alleviating, or preventing dry eye
US20090023727A1 (en) * 2007-07-05 2009-01-22 Muhammad Hashim Javaid Phthalazinone derivatives
EP2188278A1 (en) 2007-09-14 2010-05-26 AstraZeneca AB Phthalazinone derivatives
JP5439380B2 (en) 2007-10-03 2014-03-12 エーザイ インク. PARP inhibiting compounds, compositions and methods of use
JP5989965B2 (en) * 2008-01-08 2016-09-07 メルク シャープ エンド ドーム リミテッド Pharmaceutically acceptable salt of 2- {4-[(3S) -piperidin-3-yl] phenyl} -2H-indazole-7-carboxamide
AR070221A1 (en) 2008-01-23 2010-03-25 Astrazeneca Ab DERIVATIVES OF FTALAZINONA POLYMERASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM AND USES OF THE SAME TO PREVENT AND / OR TREAT CANCERIGENE TUMORS, ISCHEMICAL INJURIES AND OTHER ASSOCIATED DISEASES.
ME02640B (en) 2008-10-07 2017-06-20 Kudos Pharm Ltd PHARMACEUTICAL FORMULATION 514
MY205872A (en) 2009-04-29 2024-11-18 Amarin Pharmaceuticals Ie Ltd Pharmaceutical compositions comprising omega-3 fatty acids
WO2011058367A2 (en) 2009-11-13 2011-05-19 Astrazeneca Ab Diagnostic test for predicting responsiveness to treatment with poly(adp-ribose) polymerase (parp) inhibitor
NZ603454A (en) 2010-05-07 2014-06-27 Glaxosmithkline Llc Indoles useful for treating cellular proliferation diseases such as cancer
US8765792B2 (en) 2010-12-01 2014-07-01 Glaxosmithkline Llc Indoles
WO2012071684A1 (en) 2010-12-02 2012-06-07 Shanghai De Novo Pharmatech Co Ltd. Heterocyclic derivates,preparation processes and medical uses thereof
JP6005753B2 (en) 2011-11-04 2016-10-12 グラクソスミスクライン、インテレクチュアル、プロパティー、(ナンバー2)、リミテッドGlaxosmithkline Intellectual Property (No.2) Limited Method of treatment
KR101827444B1 (en) * 2012-02-01 2018-02-08 제일약품주식회사 Crystalline acid-added salt of tircyclo derivatives compound or hydrate thereof and preparation thereof
CN103242273B (en) * 2012-02-09 2015-06-03 中国科学院上海药物研究所 2-arylbenzofuran-7-methanamide compound, preparation method and application thereof
CN102627620B (en) * 2012-04-10 2015-12-16 江苏先声药物研究有限公司 One class benzofuran derivative and medical applications thereof
WO2014210255A1 (en) 2013-06-26 2014-12-31 Abbvie Inc. Primary carboxamides as btk inhibitors
EP3265560B1 (en) 2015-03-02 2021-12-08 Sinai Health System Homologous recombination factors
PL3325623T6 (en) 2015-07-23 2022-05-30 Institut Curie Use of a combination of dbait molecule and parp inhibitors to treat cancer
GB201519573D0 (en) 2015-11-05 2015-12-23 King S College London Combination
WO2018162439A1 (en) 2017-03-08 2018-09-13 Onxeo New predictive biomarker for the sensitivity to a treatment of cancer with a dbait molecule
US20200129476A1 (en) 2017-04-28 2020-04-30 Akribes Biomedical Gmbh PARP Inhibitor in Combination with a Glucocorticoid and/or Ascorbic Acid and/or a Protein Growth Factor for the Treatment of Impaired Wound Healing
WO2019175132A1 (en) 2018-03-13 2019-09-19 Onxeo A dbait molecule against acquired resistance in the treatment of cancer
US20210347758A1 (en) 2018-10-03 2021-11-11 Tesaro, Inc. Crystalline Forms of Niraparib Freebase
CN109574986B (en) * 2019-01-23 2020-10-27 聊城大学 6-Aminobenzo[b]thiophene-2-carboxylic acid derivatives and their application in antiepileptic
GB201913030D0 (en) 2019-09-10 2019-10-23 Francis Crick Institute Ltd Treatment of hr deficient cancer
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
WO2024233875A2 (en) * 2023-05-11 2024-11-14 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Heterocyclic compounds for imaging aggregated tau in tauopathies
WO2024261243A1 (en) 2023-06-21 2024-12-26 Hemispherian As Combination comprising a deoxycytidine derivative and a parp inhibitor for use in a method of treating hr proficient cancer

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TR199800127T1 (en) 1995-08-02 1998-04-21 Newcastle University Ventures Limited Benzimidazole bile�ikleri.
ES2229375T3 (en) * 1996-07-09 2005-04-16 Nikem Research S.R.L. DERIVATIVES OF INDOL FOR THE TREATMENT OF OSTEOPOROSIS.
EP0927167A1 (en) 1996-08-14 1999-07-07 Warner-Lambert Company 2-phenyl benzimidazole derivatives as mcp-1 antagonists
DE19636150A1 (en) * 1996-09-06 1998-03-12 Asta Medica Ag N-substituted indole-3-glyoxylamides with antiasthmatic, antiallergic and immunosuppressive / immunomodulating effects
US6916841B2 (en) * 1998-02-25 2005-07-12 Genetics Institute, Llc Inhibitors of phospholipase enzymes
IL143102A0 (en) 1998-11-17 2002-04-21 Basf Ag 2-phenylbenzimidazoles and 2-phenylindoles, and production and use thereof
GB9902459D0 (en) * 1999-02-05 1999-03-24 Zeneca Ltd Chemical compounds
US6831095B1 (en) * 1999-09-20 2004-12-14 Eli Lilly And Company Hydroxyfunctional amide 1h-indole derivatives active as sPLA2 inhibitors
GB0000625D0 (en) * 2000-01-13 2000-03-01 Zeneca Ltd Chemical compounds
DE10009000A1 (en) * 2000-02-25 2001-08-30 Basf Ag Process for the preparation of substituted indoles
DE10022925A1 (en) 2000-05-11 2001-11-15 Basf Ag New indole-carboxamide or azepino-indole derivatives and analogs, are poly-ADP ribose polymerase inhibitors useful e.g. for treating neurodegenerative disease, ischemia, epilepsy, tumors, sepsis or diabetes mellitus
IT1318641B1 (en) * 2000-07-25 2003-08-27 Novuspharma Spa AMID ACIDS 2- (1H-INDOL-3-IL) -2-OXO-ACETICS WITH ANTI-TUMOR ACTIVITY.
CA2460347A1 (en) * 2001-09-13 2003-03-20 Synta Pharmaceuticals Corp. 3-glyoxlylamideindoles for treating cancer
US6951849B2 (en) * 2001-10-02 2005-10-04 Acadia Pharmaceuticals Inc. Benzimidazolidinone derivatives as muscarinic agents
US6933316B2 (en) * 2001-12-13 2005-08-23 National Health Research Institutes Indole compounds
JP2003300382A (en) * 2002-04-08 2003-10-21 Konica Minolta Holdings Inc Imaging method using heat-transfer intermediate transfer medium
ES2275105T3 (en) * 2002-09-12 2007-06-01 F. Hoffmann-La Roche Ag ACID COMPOUNDS 1-H-INDOL-5-PROPIONIC N-SUBSTITUTED AS USEFUL PPAR AGONISTS FOR THE TREATMENT OF DIABETES.

Also Published As

Publication number Publication date
CA2408369A1 (en) 2002-11-07
DE10022925A1 (en) 2001-11-15
MXPA02010985A (en) 2003-04-25
US20040067949A1 (en) 2004-04-08
EP1280774A1 (en) 2003-02-05
WO2001085687A1 (en) 2001-11-15
JP2003532709A (en) 2003-11-05
US7087637B2 (en) 2006-08-08

Similar Documents

Publication Publication Date Title
AU2001274009A1 (en) Substituted indoles as parp inhibitors
AU2001258771A1 (en) -secretase inhibitors
SI1686119T1 (en) Pyrimidine-5-one derivatives as LDL-PLA2 inhibitors
AU2002303892A1 (en) 5-aralkylsulfonyl-3- (pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors
AU2002357003A1 (en) Indoles as naaladase inhibitors
AU3770000A (en) Indolinone compounds as kinase inhibitors
AU2001288374A1 (en) Substituted oxindole derivatives as tyrosine kinase inhibitors
AU2001231664A1 (en) Indol-3-yl derivatives
IL151154A0 (en) Indol-3-yl derivatives
AU2002213100A1 (en) Indole compounds as minimally physiologial function monitioring agents
AU2003277674A1 (en) Novel parp inhibitors
AU8664701A (en) Oxindole derivatives
AU2002213978A1 (en) Substituted C-cyclohexylmethylamine derivatives
AU5215700A (en) Substituted indolinone as tyrosine kinase inhibitors
AU2001241917A1 (en) Myt1 kinase inhibitors
AU2002222627A1 (en) Tak1 inhibitors
AU5331499A (en) Indole spla2 inhibitors
AU2001244562A1 (en) Neovascularization inhibitors
AU3703499A (en) Substituted indolinones as kinase inhibitors
AU2001289937A1 (en) Substituted 1-aminobutan-3-ol derivatives
AU2001292241A1 (en) Benzodiazepine derivative
AU2001295455A1 (en) Indoline derivatives as 5ht2c antagonists
AU3235100A (en) Prothease inhibitors
AU2002239263A1 (en) Tetracyclic carbazole derivates and their use as spla2 inhibitors
AU2001255408A1 (en) Tetrahydro-azepinone derivatives as thrombin inhibitors