- Design, synthesis and biological evaluation of novel inosine 5′-monophosphate dehydrogenase (IMPDH) inhibitors
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This study is based on our attempts to further explore the structure-activity relationship (SAR) of VX-148 (3) in an attempt to identify inosine 5′-mono-phosphate dehydrogenase (IMPDH) inhibitors superior to mycophenolic acid. A five-point pharmacophore developed using structurally diverse, known IMPDH inhibitors guided further design of novel analogs of 3. Several conventional as well as novel medicinal chemistry strategies were tried. The combined structure- and ligand-based approaches culminated in a few analogs with either retained or slightly higher potency. The compounds which retained the potency were also checked for their ability to inhibit human peripheral blood mononuclear cells proliferation. This study illuminates the stringent structural requirements and strict SAR for IMPDH II inhibition.
- Dunkern, Torsten,Chavan, Sunil,Bankar, Digambar,Patil, Anuja,Kulkarni, Pritee,Kharkar, Prashant S.,Prabhu, Arati,Goebel, Heike,Rolser, Edith,Burckhard-Boer, Waltraud,Arumugam, Premkumar,Makhija, Mahindra T.
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p. 408 - 419
(2014/06/09)
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- Discovery of 2-(α-methylbenzylamino) pyrazines as potent Type II inhibitors of FMS
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A series of 2-(α-methylbenzylamino) pyrazines have shown to be potent inhibitors of the FMS tyrosine receptor kinase. Details of SAR studies, modeling and synthesis of compounds within this series are reported.
- Burns, Christopher J.,Harte, Michael F.,Bu, Xianyong,Fantino, Emmanuelle,Giarrusso, Marilena,Joffe, Max,Kurek, Margarita,Legge, Fiona S.,Razzino, Pasquale,Su, Stephen,Treutlein, Herbert,Wan, Soo San,Zeng, Jun,Wilks, Andrew F.
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scheme or table
p. 1206 - 1209
(2009/08/07)
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- INHIBITORS OF KINASE ACTIVITY
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The present invention relates to pyridines or pyrazines that inhibit kinases. In particular the compounds of the invention inhibit members of the class III PTK receptor family such as FMS (CSF-IR), c-KIT, PDGFRβ, PDGFRα or FLT3 and KDR, SRC, EphA2, EphA3, EphA8, FLTl, FLT4, HCK, LCK, PTK5 (FRK), SYK, DDRl and DDR2 and RET. The compounds of the invention are useful in the treatment of kinase associated diseases such as immunological and inflammatory diseases; hyperproliferative diseases including cancer and diseases involving neo-angiogenesis; renal and kidney diseases; bone remodeling diseases; metabolic diseases; and vascular diseases.
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Page/Page column 91
(2008/12/05)
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- Src kinase inhibitor compounds
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Pyrimidine compounds (Formula I), or their pharmaceutically acceptable salts, hydrates, solvates, crystal forms and individual diastereomers, and pharmaceutical compositions including the same, which are inhibitors of tyrosine kinase enzymes, and as such are useful in the prophylaxis and treatment of protein tyrosine kinase-associated disorders, such as immune diseases, hyperproliferative disorders and other diseases in which inappropriate protein kinase action is believed to play a role, such as cancer, angiogensis, atheroscelerosis, graft rejection, rheumatoid arthritis and psoriasis.
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