- Reversible covalent Bruton's tyrosine kinase inhibitor, pharmaceutical composition and application thereof
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The invention discloses a reversible covalent Bruton's tyrosine kinase (BTK) inhibitor compound, a pharmaceutical composition and application of the compound and the pharmaceutical composition in preparation of drugs for treating diseases, disorders or symptoms benefitting from inhibition of Bruton's tyrosine kinase activity. The compound provided by the invention has strong in-vitro BTK kinase inhibition activity, and can be applied to treatment of diseases, disorders or symptoms, including B-cell lymphoma, autoimmune diseases, inflammatory diseases and the like, which benefit from inhibitionof Bruton's tyrosine kinase activity, alone or in combination with other drugs.
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- Selective Bruton's tyrosine kinase inhibitor and application thereof
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The invention discloses a selective Bruton's tyrosine kinase (BTK) inhibitor compound, a pharmaceutical composition, preparation and application thereof to preparation of medicines for treating diseases, disorders or symptoms obtained from inhibition of Bruton's tyrosine kinase activity. The compound disclosed by the invention has anti-proliferation and inhibition effects on tumor cell lines including A549, MINO, OCI-LY10, TMD-8 and the like, has good anti-tumor activity in tumor models including Mino subcutaneous xenoplastic transplantation and the like and can be applied to medicines for treating solid tumors or leukemia related to human or animal cell proliferation; the compound disclosed by the invention has relatively good pharmacokinetic performance and can be orally taken to treat the solid tumors or the leukemia related to the human or animal cell proliferation or autoimmune diseases; the compound disclosed by the invention has a low hERG channel blocking property.
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- Bruton's tyrosine kinase inhibitor intermediates and preparation method thereof
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The invention relates to Bruton's tyrosine kinase inhibitor intermediates which are compounds shown in I, II, III, IV and IV or their pharmaceutically acceptable salt, and structural formulas of I, II, III, IV and V are shown as below. The novel Bruton's tyrosine kinase inhibitor intermediates are provided, a preparation method of these intermediates is convenient and efficient and is helpful for the preparation of novel BTK inhibitors and deep research and even marketing thereof.
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- Boronic species as promising inhibitors of the Staphylococcus aureus NorA efflux pump: Study of 6-substituted pyridine-3-boronic acid derivatives
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In response to the extensive use of antibiotics, bacteria have evolved numerous mechanisms of defense against antimicrobial agents. Among them, extrusion of the antimicrobial agents outside the bacterial cell through efflux pumps is a major cause of concern. At first limited to one or few structurally-related antibiotics, bacterial resistance have then progressed towards cross-resistance between different classes of antibiotics, leading to multidrug-resistant microorganisms. Emergence of these pathogens requires development of novel therapeutic strategies and inhibition of efflux pumps appears to be a promising strategy that could restore the potency of existing antibiotics. NorA is the most studied chromosomal efflux pump of Staphylococcus aureus; it is known to be implied in resistance of Methicillin-resistant S. aureus (MRSA) strains against a wide range of unrelated substrates, including hydrophilic fluoroquinolones. Starting from 6-benzyloxypyridine-3-boronic acid I that we previously identified as a potential inhibitor of the NorA efflux pump against the NorA-overexpressing S. aureus 1199B strain (SA1199B), we describe here the synthesis and biological evaluation of a series of 6-(aryl)alkoxypyridine-3-boronic acids. 6-(3-Phenylpropoxy)pyridine-3-boronic acid 3i and 6-(4-phenylbutoxy)pyridine-3-boronic acid 3j were found to potentiate ciprofloxacin activity by a 4-fold increase compared to the parent compound I. In addition, it has been shown that both compounds promote Ethidium Bromide (EtBr) accumulation in SA1199B, thus corroborating their potential mode of action as NorA inhibitors.
- Fontaine, Fanny,Héquet, Arnaud,Voisin-Chiret, Anne-Sophie,Bouillon, Alexandre,Lesnard, Aurélien,Cresteil, Thierry,Jolivalt, Claude,Rault, Sylvain
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p. 185 - 198
(2015/04/14)
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- PURINONE COMPOUNDS AS KINASE INHIBITORS
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Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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Paragraph 00459
(2015/01/16)
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