WO2011062765A3 - 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties - Google Patents

1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties Download PDF

Info

Publication number
WO2011062765A3
WO2011062765A3 PCT/US2010/055254 US2010055254W WO2011062765A3 WO 2011062765 A3 WO2011062765 A3 WO 2011062765A3 US 2010055254 W US2010055254 W US 2010055254W WO 2011062765 A3 WO2011062765 A3 WO 2011062765A3
Authority
WO
WIPO (PCT)
Prior art keywords
benzodiazepine
related compounds
diones
compounds
therapeutic properties
Prior art date
Application number
PCT/US2010/055254
Other languages
French (fr)
Other versions
WO2011062765A2 (en
Inventor
Gary D. Glick
Original Assignee
The Regents Of The University Of Michigan
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 The Regents Of The University Of Michigan filed Critical The Regents Of The University Of Michigan
Priority to AU2010322286A priority Critical patent/AU2010322286B2/en
Priority to JP2012539930A priority patent/JP5856063B2/en
Priority to US13/508,256 priority patent/US9126978B2/en
Priority to CA2780333A priority patent/CA2780333C/en
Priority to EP10831981.5A priority patent/EP2501387B1/en
Priority to CN2010800616314A priority patent/CN102753179A/en
Publication of WO2011062765A2 publication Critical patent/WO2011062765A2/en
Publication of WO2011062765A3 publication Critical patent/WO2011062765A3/en
Priority to US14/846,478 priority patent/US9849138B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Abstract

The present invention provides novel chemical compounds characterized as Rho kinase (ROCK) inhibitors, methods for their discovery, and their therapeutic, research, and diagnostic use. In particular, the present invention provides 1,4-benzodiazepine-2,5-dione compounds and related compounds having ROCK inhibitory activity, and methods of using such compounds as therapeutic agents to treat a number of conditions associated with ROCK activity.
PCT/US2010/055254 2009-11-17 2010-11-03 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties WO2011062765A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
AU2010322286A AU2010322286B2 (en) 2009-11-17 2010-11-03 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
JP2012539930A JP5856063B2 (en) 2009-11-17 2010-11-03 1,4-Benzodiazepine-2,5-dione and related compounds having therapeutic properties
US13/508,256 US9126978B2 (en) 2009-11-17 2010-11-03 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
CA2780333A CA2780333C (en) 2009-11-17 2010-11-03 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
EP10831981.5A EP2501387B1 (en) 2009-11-17 2010-11-03 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
CN2010800616314A CN102753179A (en) 2009-11-17 2010-11-03 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
US14/846,478 US9849138B2 (en) 2009-11-17 2015-09-04 1,4-benzodiazepone-2,5-diones and related compounds with therapeutic properties

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US26201009P 2009-11-17 2009-11-17
US61/262,010 2009-11-17

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US13/508,256 A-371-Of-International US9126978B2 (en) 2009-11-17 2010-11-03 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
US14/846,478 Continuation US9849138B2 (en) 2009-11-17 2015-09-04 1,4-benzodiazepone-2,5-diones and related compounds with therapeutic properties

Publications (2)

Publication Number Publication Date
WO2011062765A2 WO2011062765A2 (en) 2011-05-26
WO2011062765A3 true WO2011062765A3 (en) 2011-10-06

Family

ID=44060266

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/055254 WO2011062765A2 (en) 2009-11-17 2010-11-03 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties

Country Status (7)

Country Link
US (2) US9126978B2 (en)
EP (1) EP2501387B1 (en)
JP (2) JP5856063B2 (en)
CN (1) CN102753179A (en)
AU (1) AU2010322286B2 (en)
CA (2) CA2780333C (en)
WO (1) WO2011062765A2 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011062766A2 (en) * 2009-11-17 2011-05-26 The Regents Of The University Of Michigan 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
CA2780333C (en) 2009-11-17 2016-05-24 The Regents Of The University Of Michigan 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
US11311541B2 (en) * 2014-04-09 2022-04-26 Kadmon Corporation, Llc Treatment of GVHD
JP2020514360A (en) * 2017-03-16 2020-05-21 セルジーン シーエーアール エルエルシー Forms and compositions of MK2 inhibitors
EP3596086A4 (en) 2017-03-16 2020-12-16 Celgene CAR LLC Mk2 inhibitors, synthesis thereof, and intermediates thereto
CN110590695B (en) * 2019-10-22 2023-03-21 南华大学 Benzoazaheterocycle compound and application thereof
WO2023093787A1 (en) * 2021-11-24 2023-06-01 成都奥睿药业有限公司 Benzodiazepine compound and application thereof as rho kinase inhibitor

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030125344A1 (en) * 2001-03-23 2003-07-03 Bayer Corporation Rho-kinase inhibitors
US20040102437A1 (en) * 2000-02-01 2004-05-27 Atsuya Takami Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same
WO2007053725A2 (en) * 2005-11-01 2007-05-10 The Regents Of The University Of Michigan Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties
WO2008086047A1 (en) * 2007-01-03 2008-07-17 Boehringer Ingelheim International Gmbh Rho kinase inhibitors

Family Cites Families (118)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3261828A (en) 1962-10-04 1966-07-19 Hoffmann La Roche 3h-1,4-benzodiazepine-2,5(1h,4h)-dione compounds
US3374264A (en) 1962-10-04 1968-03-19 Hoffmann La Roche N-haloacetyl-anthranilic acids and esters
US3415814A (en) 1966-09-28 1968-12-10 Sterling Drug Inc 4-(cyclopropylmethyl)-3h-1,4-benzodiazepine-2,5(1h,4h)-dione
US3384635A (en) 1966-09-28 1968-05-21 Sterling Drug Inc 1, 4-benzodiazepine derivatives
AT280290B (en) 1967-11-24 1970-04-10 Boehringer Sohn Ingelheim Process for the preparation of new 1-phenyl-4-alkyl-3H-1,4-benzodiazepine-2,5- [1H, 4H] -diones
US4108852A (en) 1969-03-18 1978-08-22 Knoll Ag. Process for preparing 1,5-benzodiazepine-2-ones
USRE30293E (en) 1969-03-18 1980-06-03 Knoll A.G. Process for preparing 1,5-benzodiazepine-2-ones
CH559729A5 (en) 1970-10-23 1975-03-14 Hoechst Ag
GB1324469A (en) 1970-10-28 1973-07-25 Knoll Ag Derivatives of benzodiazepines
ZA7469B (en) 1973-01-16 1974-11-27 J Voorhees Compositions and treatment of proliferative skin diseases with-c-amp analogs
IE38931B1 (en) 1973-03-09 1978-07-05 Lipha Triazolobenzodiazepines
US4076823A (en) 1977-08-18 1978-02-28 E. R. Squibb & Sons, Inc. Triazolo-2,4-benzodiazepines
JPS59112984A (en) 1982-12-21 1984-06-29 Shionogi & Co Ltd 1,4-benzodiazepine derivative
US4495101A (en) 1983-04-28 1985-01-22 American Home Products Corporation Antiinflammatory 5H-tetrazolo (5,1-c)(1,4)benzodiazepine derivatives
US4551480A (en) 1983-06-21 1985-11-05 Stiefel Laboratories, Inc. Compositions for the treatment of psoriasis
US4894366A (en) 1984-12-03 1990-01-16 Fujisawa Pharmaceutical Company, Ltd. Tricyclo compounds, a process for their production and a pharmaceutical composition containing the same
US5004741A (en) 1984-06-26 1991-04-02 Merck & Co., Inc. Methods of antagonizing CCK or gastrin with benzodiazepine analogs
US4820834A (en) 1984-06-26 1989-04-11 Merck & Co., Inc. Benzodiazepine analogs
DE3435974A1 (en) 1984-10-01 1986-04-10 Boehringer Ingelheim KG, 6507 Ingelheim PHARMACEUTICAL COMPOSITIONS CONTAINING DIAZEPINE WITH PAF-ANTAGONISTIC EFFECT
FR2591596B1 (en) 1985-12-13 1988-09-09 Roussel Uclaf NOVEL 4H-TRIAZOLO (4,3-A) (1,4) BENZODIAZEPINES, THEIR PREPARATION PROCESS, THEIR APPLICATION AS MEDICAMENTS AND THE COMPOSITIONS CONTAINING THEM
GB8608080D0 (en) 1986-04-02 1986-05-08 Fujisawa Pharmaceutical Co Solid dispersion composition
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
US4751223A (en) 1986-10-14 1988-06-14 Hoechst-Roussel Pharmaceuticals, Inc. Antiinflammatory and analgesic aminoalkyl tetracyclic benzodiazepines
US4898861A (en) 1987-03-26 1990-02-06 Hoffmann-La Roche Inc. Method for inhibiting the proliferation of tumor cells
US5147872A (en) 1987-06-09 1992-09-15 Golwyn Daniel H Treatment of immunologically based disorders, specifically psoriasis
US4970207A (en) 1988-07-07 1990-11-13 Fujisawa Pharmaceutical Company, Ltd. Benzodiazepine derivatives
SE8804074D0 (en) 1988-11-10 1988-11-10 Pharmacia Ab SENSOR UNIT AND ITS USE IN BIOSENSOR SYSTEM
WO1990013332A1 (en) 1989-05-11 1990-11-15 Cedars-Sinai Medical Center Stent with sustained drug delivery
US5258510A (en) 1989-10-20 1993-11-02 Otsuka Pharma Co Ltd Benzoheterocyclic compounds
US5041438A (en) 1989-10-30 1991-08-20 Hoffmann-La Roche Inc. Method for treating retroviral infections with benzodiazepine compounds
US5324726A (en) 1989-12-18 1994-06-28 Merck & Co., Inc. Benzodiazepine analogs
WO1991012779A1 (en) 1990-02-28 1991-09-05 Medtronic, Inc. Intralumenal drug eluting prosthesis
US5217591A (en) 1990-05-14 1993-06-08 Labintelligence, Inc. Gel electrophoresis sample applicator/retriever
DE69123090D1 (en) 1990-07-06 1996-12-19 Yoshitomi Pharmaceutical Condensed thiophene compounds and their use
GB9015879D0 (en) 1990-07-19 1990-09-05 Fujisawa Pharmaceutical Co Benzodiazepine derivatives
BR9200951A (en) 1991-03-21 1992-11-17 Hoffmann La Roche COMPOUNDS, PROCESS FOR ITS PRODUCTION, PHARMACEUTICAL PREPARATIONS AND USE
JPH07504908A (en) 1992-03-16 1995-06-01 メルク　シヤープ　エンド　ドーム　リミテツド Benzodiazepine derivatives, compositions containing them and their use in therapy
US5599352A (en) 1992-03-19 1997-02-04 Medtronic, Inc. Method of making a drug eluting stent
US5288514A (en) 1992-09-14 1994-02-22 The Regents Of The University Of California Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support
GB9307527D0 (en) 1993-04-13 1993-06-02 Fujisawa Pharmaceutical Co New venzamide derivatives,processes for the preparation thereof and pharmaceutical composition comprising the same
US5391566A (en) 1993-07-20 1995-02-21 Merck & Co., Inc. Benzimidazolinones substituted with phenoxyphenylacetic acid derivatives
US6524832B1 (en) 1994-02-04 2003-02-25 Arch Development Corporation DNA damaging agents in combination with tyrosine kinase inhibitors
US5444092A (en) 1994-07-20 1995-08-22 Collins; Jerry Method and composition for treating psoriasis
JPH10504545A (en) 1994-07-29 1998-05-06 藤沢薬品工業株式会社 Benzodiazepine derivatives
CA2195973A1 (en) 1994-08-18 1996-02-29 David A. Claremon N-2,3-dihydro-1-(2-propyl)-2-oxo-5-phenyl-1h-1,4-benzodiazepines
US5618792A (en) 1994-11-21 1997-04-08 Cortech, Inc. Substituted heterocyclic compounds useful as inhibitors of (serine proteases) human neutrophil elastase
AU5752696A (en) 1995-05-18 1996-11-29 Regents Of The University Of Michigan, The Dna binding antibodies
US5677282A (en) 1995-06-07 1997-10-14 Proscript, Inc. Amino acid amides of 1,3,4-thiadiazoles as matrix metalloproteinase
CA2225914A1 (en) 1995-06-29 1997-01-16 Pharmacopeia, Inc. Combinatorial 1,4-benzodiazepin-2,5-dione library
US5962337A (en) 1995-06-29 1999-10-05 Pharmacopeia, Inc. Combinatorial 1,4-benzodiazepin-2,5-dione library
RU2096044C1 (en) 1995-07-19 1997-11-20 Малое предприятие "Ветта" Veterinary implantable preparation for regulation of biological rhythm in animals
US5776946A (en) 1995-08-28 1998-07-07 Mcgeer; Patrick L. Peripheral benzodiazepine receptor ligands as antiinflammatory agents
WO1997007828A1 (en) 1995-08-30 1997-03-06 The Regents Of The University Of California Therapy for cellular accumulation in chronic inflammatory diseases
ATE214055T1 (en) 1995-09-21 2002-03-15 Inst Med Molecular Design Inc RETINOID POTENTIFIING COMPOUNDS
US6011029A (en) 1996-02-26 2000-01-04 Bristol-Myers Squibb Company Inhibitors of farnesyl protein transferase
US6579854B1 (en) 1996-08-14 2003-06-17 Vanderbilt University Diagnosis and management of infection caused by chlamydia
UA60311C2 (en) 1996-10-02 2003-10-15 Смітклайн Бічам Корпорейшн Vitronectin receptor antagonists
US7351421B2 (en) 1996-11-05 2008-04-01 Hsing-Wen Sung Drug-eluting stent having collagen drug carrier chemically treated with genipin
JP3999819B2 (en) 1996-12-10 2007-10-31 ゼリア新薬工業株式会社 1,5-Benzodiacepine derivatives
AU7799598A (en) 1997-06-09 1998-12-30 Hoeffer Pharmacia Biotech, Inc. Device for rehydration and electrophoresis of gel strips and method of using thesame
US6074859A (en) 1997-07-08 2000-06-13 Kikkoman Corporation Mutant-type bioluminescent protein, and process for producing the mutant-type bioluminescent protein
AU750245B2 (en) 1997-10-08 2002-07-11 Aurinia Phamaceuticals Inc. Deuterated cyclosporine analogs and their use as immunomodulating agents
US6100254A (en) 1997-10-10 2000-08-08 Board Of Regents, The University Of Texas System Inhibitors of protein tyrosine kinases
FR2772271B1 (en) 1997-12-11 2000-09-01 Union Pharma Scient Appl NEW PHARMACEUTICAL ASSOCIATION WITH ANALGESIC ACTIVITY
US6206914B1 (en) 1998-04-30 2001-03-27 Medtronic, Inc. Implantable system with drug-eluting cells for on-demand local drug delivery
WO1999058117A1 (en) 1998-05-13 1999-11-18 Sanofi-Synthelabo Use of compounds for reducing apoptosis
FR2779963A1 (en) 1998-06-22 1999-12-24 Centre Nat Rech Scient New composition useful for treat cancer, comprises compound with affinity for mitochondrial benzodiazepine receptors and agent to induce apoptosis
WO1999067220A1 (en) 1998-06-22 1999-12-29 Elan Pharmaceuticals, Inc. Compounds for inhibiting beta-amyloid peptide release and/or its synthesis
US6277844B1 (en) 1998-09-14 2001-08-21 Sydney Spector Compound for selective treatment of malignant cells by inhibiting cell cycle progression, decreasing Bcl2, and increasing apoptosis
US20030044776A1 (en) 1998-09-25 2003-03-06 James A. Dykens Compositions and methods for identifying agents that alter mitochondrial permeability transition pores
FR2785803B1 (en) 1998-11-17 2005-03-25 Sanofi Sa USE OF A SUBSTANCE BINDING TO THE PERIPHERAL RECEPTOR OF BENZODIAZEPINES IN THE TREATMENT OF SKIN STRESS
US7175953B2 (en) 1999-04-09 2007-02-13 Institute Fuer Diagnostik Forschung Short-warp peptide-dye conjugate as contrast agent for optical diagnostic
JP5127096B2 (en) 1999-04-30 2013-01-23 ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン Use of benzodiazepines to treat autoimmune diseases induced by apoptosis
US20050113460A1 (en) 1999-04-30 2005-05-26 The Regents Of The University Of Michigan Compositions and methods relating to novel compounds and targets thereof
US20030119029A1 (en) 1999-04-30 2003-06-26 Regents Of The University Of Michigan Compositions and methods relating to novel benzodiazepine compounds and targets thereof
US7276348B2 (en) 1999-04-30 2007-10-02 Regents Of The University Of Michigan Compositions and methods relating to F1F0-ATPase inhibitors and targets thereof
US20060025388A1 (en) 1999-04-30 2006-02-02 Glick Gary D Compositions and methods relating to novel compounds and targets thereof
US20040176358A1 (en) 1999-04-30 2004-09-09 The Regents Of The University Of Michigan Compositions and methods relating to novel compounds and targets thereof
US7572788B2 (en) 1999-04-30 2009-08-11 The Regents Of The University Of Michigan Compositions and methods relating to novel compounds and targets thereof
AU5826100A (en) 1999-07-13 2001-01-30 F. Hoffmann-La Roche Ag Benzazepinones and quinazolines
US6524623B1 (en) 1999-11-12 2003-02-25 Milton Hodosh Therapeutic compositions and methods of use thereof
WO2001051922A2 (en) 2000-01-14 2001-07-19 Mitokor Identification of peripheral benzodiazepine receptor binding agents
DE60117777T2 (en) 2000-05-11 2006-08-17 Eastman Chemical Co., Kingsport ACYLATED CYCLODEXTRINE GUEST INCLUSION COMPLEX
EP1295607B9 (en) * 2000-06-23 2011-10-05 Mitsubishi Tanabe Pharma Corporation Antitumor effect potentiators
US20020048566A1 (en) 2000-09-14 2002-04-25 El-Deiry Wafik S. Modulation of cellular apoptosis and methods for treating cancer
US20020128208A1 (en) 2000-12-15 2002-09-12 Snyder James P. Nonpeptide agonists and antagonists of vasopressin receptors
GB0104096D0 (en) 2001-02-20 2001-04-04 Synetix Intellectual Property Catalysts
EP1370294A2 (en) 2001-02-27 2003-12-17 The Regents Of The University Of Michigan Use of natural egfr inhibitors to prevent side effects due to retinoid therapy, soaps, and other stimuli that activate the epidermal growth receptor
AU2002317910B2 (en) 2001-06-07 2008-06-19 Via Pharmaceuticals, Inc. Cyclic nucleotide phosphodiesterase inhibitors, preparation and uses thereof
CA2457405A1 (en) 2001-08-15 2003-02-27 The Regents Of The University Of Michigan Compositions and methods relating to benzodiazepine compounds
WO2003041658A2 (en) 2001-11-13 2003-05-22 Bristol-Myers Squibb Company Process for the preparation of 3,7-disubstituted-2,3,4,5- tetrahydro-1h-1,4-benzodiazepine compounds
AU2002357137A1 (en) 2001-12-10 2003-06-23 Bristol-Myers Squibb Company (1-phenyl-2-heteroaryl)ethyl-guanidine compounds as inhibitors of mitochondrial f1f0 atp hydrolase
GB0208224D0 (en) 2002-04-10 2002-05-22 Celltech R&D Ltd Chemical compounds
US20040009972A1 (en) 2002-06-17 2004-01-15 Ding Charles Z. Benzodiazepine inhibitors of mitochondial F1F0 ATP hydrolase and methods of inhibiting F1F0 ATP hydrolase
US7150433B2 (en) 2002-08-16 2006-12-19 Toyota Motor Sales, U.S.A., Inc. Aircraft bolster trays
US7109224B2 (en) 2002-11-06 2006-09-19 Bristol-Myers Squibb Co. Acyl guanidine compounds and use thereof
US20040087489A1 (en) 2002-11-06 2004-05-06 Antonio Ruiz Compositions and methods for the treatment of mycobacterial infections
WO2004050040A2 (en) 2002-12-03 2004-06-17 Vela Pharmaceuticals, Inc. Pharmaceutical composition of 1-(3,4-dimethoxyphenyl)-4-methyl-5-ethyl-7-methoxy-8-hydroxy-5h-2,3-benzodiazepine and uses thereof
DE60329030D1 (en) 2002-12-04 2009-10-08 Ore Pharmaceuticals Inc Melanocortin receptor MODULATORS
MXPA05011741A (en) 2003-05-01 2006-05-12 Univ Michigan Compositions and methods relating to novel compounds and targets thereof.
US20050272723A1 (en) 2004-04-27 2005-12-08 The Regents Of The University Of Michigan Methods and compositions for treating diseases and conditions associated with mitochondrial function
US20090275099A1 (en) 2004-04-27 2009-11-05 Regents Of The University Of Michigan Methods and compositions for treating diseases and conditions associated with mitochondrial function
CA2571178A1 (en) 2004-07-01 2006-01-19 Synta Pharmaceuticals Corp. 2-substituted heteroaryl compounds
DE602005006585D1 (en) 2004-07-06 2008-06-19 Acp Advanced Circuit Pursuit A SYMMETRIC MIXER WITH FETS
US20060052369A1 (en) 2004-09-07 2006-03-09 The Regents Of The University Of Michigan Compositions and methods relating to novel compounds and targets thereof
JP2008516975A (en) * 2004-10-19 2008-05-22 スミスクライン ビーチャム コーポレーション Compound
FR2879753B1 (en) 2004-12-22 2007-04-20 Sagem
AU2006203946B2 (en) 2005-01-03 2009-07-23 The Regents Of The University Of Michigan Compositions and methods relating to novel compounds and targets thereof
EP1893218A4 (en) 2005-06-01 2011-01-12 Univ Michigan Unsolvated benzodiazepine compositions and methods
WO2007050587A2 (en) 2005-10-26 2007-05-03 The Regents Of The University Of Michigan Therapeutic compositions and methods
US20070105844A1 (en) 2005-10-26 2007-05-10 Regents Of The University Of Michigan Therapeutic compositions and methods
US7759338B2 (en) 2006-04-27 2010-07-20 The Regents Of The University Of Michigan Soluble 1,4 benzodiazepine compounds and stable salts thereof
NZ573452A (en) 2006-06-09 2011-09-30 Univ Michigan Compositions and methods relating to novel compounds and targets thereof
NZ579507A (en) 2007-03-09 2011-11-25 Univ Michigan Compositions and methods relating to novel compounds and targets thereof
CN101855203B (en) 2007-09-14 2014-03-19 密执安州立大学董事会 F1F0-ATPase inhibitors and related methods
UA99839C2 (en) 2007-11-06 2012-10-10 Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган Benzodiazepinone compounds useful in the treatment of skin conditions
WO2011062766A2 (en) * 2009-11-17 2011-05-26 The Regents Of The University Of Michigan 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
CA2780333C (en) 2009-11-17 2016-05-24 The Regents Of The University Of Michigan 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040102437A1 (en) * 2000-02-01 2004-05-27 Atsuya Takami Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same
US20030125344A1 (en) * 2001-03-23 2003-07-03 Bayer Corporation Rho-kinase inhibitors
WO2007053725A2 (en) * 2005-11-01 2007-05-10 The Regents Of The University Of Michigan Novel 1,4-benzodiazepine-2,5-diones with therapeutic properties
WO2008086047A1 (en) * 2007-01-03 2008-07-17 Boehringer Ingelheim International Gmbh Rho kinase inhibitors

Also Published As

Publication number Publication date
US9126978B2 (en) 2015-09-08
EP2501387A4 (en) 2014-01-22
AU2010322286A1 (en) 2012-05-31
EP2501387A2 (en) 2012-09-26
JP2013510902A (en) 2013-03-28
CA2915237A1 (en) 2011-05-26
CA2780333C (en) 2016-05-24
AU2010322286B2 (en) 2014-06-05
US9849138B2 (en) 2017-12-26
JP6158892B2 (en) 2017-07-05
WO2011062765A2 (en) 2011-05-26
JP2016065062A (en) 2016-04-28
US20120283229A1 (en) 2012-11-08
CA2780333A1 (en) 2011-05-26
US20160095866A1 (en) 2016-04-07
CA2915237C (en) 2017-10-10
CN102753179A (en) 2012-10-24
JP5856063B2 (en) 2016-02-09
EP2501387B1 (en) 2016-07-27

Similar Documents

Publication Publication Date Title
WO2011062766A3 (en) 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
WO2011062765A3 (en) 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
WO2009129267A3 (en) Small molecule inhibitors of the pleckstrin homology domain and methods for using same
WO2009012280A3 (en) Benzimidazole poly(adp-ribose)polymerase inhibitors
WO2007050587A3 (en) Therapeutic compositions and methods
WO2011032169A3 (en) Pharmaceutical compositions and formulations including inhibitors of the pleckstrin homology domain and methods for using same
WO2008098104A8 (en) Inhibitors of akt activity
WO2007123892A3 (en) Raf inhibitors and their uses
WO2010005876A3 (en) Polycyclic heteroaryl substituted triazoles useful as axl inhibitors
MX2009010728A (en) Imidazo[1,2-a]pyridine compounds as receptor tyrosine kinase inhibitors.
MX2009006535A (en) Indol-4-yl-pyrimidinyl-2-yl-amine derivatives and use thereof as cyclin dependant kinase inhibitors.
MA32272B1 (en) Inhibitors of pyrazole [3,4-b] pyridine raf
WO2008083367A3 (en) Polycyclic heteroaryl substituted triazoles useful as axl inhibitors
WO2010111626A3 (en) Poly (adp-ribose) polymerase (parp) inhibitors
MX2009012066A (en) Substituted imidazopyridazines as pi3k lipid kinase inhibitors.
EA200901486A1 (en) COMPOUNDS AND COMPOSITIONS AS C-KIT AND PDGFR KINASE INHIBITORS
IL202505A (en) 2-oxo-3-benzyl-benzoxazol-2-one derivatives and related compounds as met kinase inhibitors for the treatment of tumors, medicaments comprising them and use thereof
WO2009129335A3 (en) Selective inhibitors of histone deacetylase
MX2010006203A (en) Pyrazole derivatives and use thereof as inhibitors of cyclin dependent kinases.
WO2009036175A3 (en) F1f0-atpase inhibitors and related methods
WO2007059230A3 (en) Substituted 1h-benzimidazole-4-carboxamides are potent parp inhibitors
WO2011138328A3 (en) Use of inhibitory molecules for the treatment of pulmonary hypertension
WO2012046030A3 (en) Phosphodiesterase inhibitors
MX2009006170A (en) Compounds and compositions as kinase inhibitors.
WO2010030891A3 (en) Aryl guanidine f1f0-atpase inhibitors and related methods

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 201080061631.4

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10831981

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2780333

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2010322286

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2012539930

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2010322286

Country of ref document: AU

Date of ref document: 20101103

Kind code of ref document: A

REEP Request for entry into the european phase

Ref document number: 2010831981

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2010831981

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 13508256

Country of ref document: US