184948-24-1Relevant articles and documents
Synthesis of an inhibitor-tethered resin for detection of active matrix metalloproteinases involved in disease
Hesek, Dusan,Toth, Marta,Krchnak, Viktor,Fridman, Rafael,Mobashery, Shahriar
, p. 5848 - 5854 (2007/10/03)
Matrix metalloproteinases (MMPs), of which 26 members are known in humans, are implicated in a number of diseases. Their activity is strictly controlled, but when the biological control over the activity is lost, disease processes set in. In an attempt to delineate what MMP activity has gone awry in what diseases, including metastatic cancers that are of special interest to our laboratories, we conceived and synthesized two chromatographic resins incorporated with a multifunctional broad-spectrum inhibitor for MMPs. The broad-spectrum inhibitor contains three sterogentic centers and was synthesized in 13 steps. Two structural variants of the inhibitors were linked to the polymer support via disulfide moieties. These resins are intended for use in cellular systems to selectively fish out from a complex mixture of all cellular proteins the active MMP forms important for the specific disease for identification.
Highly water-soluble matrix metalloproteinases inhibitors and their effects in a rat adjuvant-induced arthritis model.
Fujisawa, Tetsunori,Igeta, Katsuhiro,Odake, Shinjiro,Morita, Yasuo,Yasuda, Junko,Morikawa, Tadanori
, p. 2569 - 2581 (2007/10/03)
A new series of succinate-based dual inhibitors against matrix metalloproteinases (MMPs) and tumor necrosis factor alpha converting enzyme (TACE) possessing highly-water solubility was designed, synthesized, and evaluated for enzyme inhibition. Incorporat
NOVEL HYDROXAMIC ACID DERIVATIVES
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Page 41, (2010/01/31)
Disclosed are compounds which have not only potent metalloproteinase-inhibiting activity but also amazingly excellent bioavailability and biological activity invivo, including the property of being well absorbed via oral routes, thereby serving as useful pharmaceuticals, intermediates and processes for the production thereof. The disclosed compounds of the formula (I): wherein R1 is hydrogen, or a hydroxy-protecting group; R2 is hydrogen, or an amino-protecting group; R3, R7, and R8, which may be identical or different, are each independently hydrogen, hydroxy, unsubstituted or optionally substituted (C1-C6) alkyl, or unsubstituted or optionally substituted aryl-(C1-C6) alkyl; R4 is unsubstituted or optionally substituted (C1-C6) alkyl, or unsubstituted or optionally substituted aryl-(C1-C6) alkyl; R5 is hydrogen, unsubstituted or optionally substituted alkyl, unsubstituted or optionally substituted aralkyl, or a carboxy-protecting group; R6 is hydrogen, hydroxy, amino, and a group of the formula: -X-Y wherein X is oxygen, (C1-C6) alkylene or phenylene, Y is a group of the formula: -A-B or -B, wherein A is (C1-C6) alkylene, imino, and (C1-C6) alkyleneimino, and B is hydrogen, amino, amidino, sulfonyl, acylimidoyl, unsubstituted or optionally substituted imidazolyl, unprotected or optionally protected bis(phosphono)methyl or unprotected or optionally protected bis(phosphono)hydroxymethyl; or salts thereof are useful for pharmaceutical and/or veterinary compositions, particularly as metalloproteinase inhibitors which inhibit matrix metalloproteinases or tumor necrosis factor-α-converting enzymes (TNF-α convertases).
NOVEL REMEDIES FOR ALLERGIC DISEASES
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, (2008/06/13)
Disclosed are anti-inflammatory agents, antiallergic agents, particularly prophylactically and/or therapeutically effective drugs for type I and/or IV allergic conditions, and further pharmaceutical drugs for prophylactically and/or therapeutically treating bronchial asthma, atopic diseases, etc. The inventive drugs comprising a prophylactically and/or therapeutically effective amount of a hydroxamic acid derivative are active in the prophylaxis and/or therapy of allergy, especially type I and/or IV allergy, etc. The drugs are active in prophylactically and/or therapeutically treating inflammation, rhinitis, conjunctivitis, bronchial asthma, atopic diseases (including dermatitis, enteritis, etc.), or allergic gastroenterocolitis (allergic inflammation in digestive tract). The application of such drugs leads to (A) reduction of cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages and monocytes) at a diseased site, and/or (B) alleviation of inflammatory symptoms caused by migration, infiltration or accumulation of cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages and monocytes) to (or at) the diseased site, (C) inhibition of pathophysiological functions in cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages, monocytes, Langerhans cell and dendritic cells), and/or (D) reducing the blood level or inhibiting the production, of antibodies, especially IgE. Accordingly, the drugs are useful in the prophylaxis and/or therapy of diseases, disorders or ill conditions at the site.
Design and synthesis of the cartilage protective agent (CPA, Ro32-3555)
Broadhurst,Brown,Lawton,Ballantyne,Borkakoti,Bottomley,Cooper,Eatherton,Kilford,Malsher,Nixon,Lewis,Sutton,Johnson
, p. 2299 - 2302 (2007/10/03)
A novel series of MMP inhibitors has been identified. The compounds are potent selective inhibitors of collagenase with good solubility and oral bioavailability. One compound, designated Ro32-3555, has been selected for development as a cartilage protective agent for use in the treatment of rheumatoid- and osteoarthritis.