COMPOUND HAVING ERK KINASE INHIBITORY ACTIVITY AND USE THEREOF
The invention relates to a compound of formula (I): wherein variables are as defined in the specification. The compound is an inhibitor of an ERK kinase, e.g. ERK1 and/or ERK2 kinase. The invention also relates to the use of the compound and a method for preparing the compound, and a pharmaceutical composition containing the compound.
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(2020/08/20)
Potent, orally active heterocycle-based combretastatin A-4 analogues: Synthesis, structure - Activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation
The synthesis and structure - activity relationship study of a series of compounds with heterocycles in place of the cis double bond in combretastatin A-4 (CA-4) are described. Substituted tosylmethyl isocyanides were found to be the key intermediates in construction of the heterocycles. Cytotoxicities of the heterocycle-based CA-4 analogues were evaluated against NCI-H460 and HCT-15 cancer cell lines. 3-Amino-4-methoxyphenyl and N-methyl-indol-5-yl were the best replacements for the 3-hydroxy-4-methoxyphenyl in CA-4. 4,5-Disubstituted imidazole was found to be the best for the replacement of the cis double bond in CA-4. Medicinal chemistry efforts led to the discovery of compounds 24h and 25f that were found to be 32 and 82% bioavailable, respectively, in rat. Evaluation of 24h and 25f against murine M5076 reticulum sarcoma in mice revealed that both compounds were orally efficacious with an increase in life span of 38.5 and 40.5%, respectively.
Wang, Le,Woods, Keith W.,Li, Qun,Barr, Kenneth J.,McCroskey, Richard W.,Hannick, Steven M.,Gherke, Laura,Credo, R. Bruce,Hui, Yu-Hua,Marsh, Kennan,Warner, Robert,Lee, Jang Y.,Zielinski-Mozng, Nicolette,Frost, David,Rosenberg, Saul H.,Sham, Hing L.
p. 1697 - 1711
(2007/10/03)
Oxazoline antiproliferative agents
Compounds having Formula I are useful for treating cancer. Also disclosed are pharmaceutical compositions comprising compounds of Formula I, and methods of treating cancer in a mammal.
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(2008/06/13)
Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone(CRH) antagonists, useful for treating CNS and stress-related disorders
Corticotropin releasing factor (CRF) antagonists of Formula (I): and their use in treating psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.
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(2008/06/13)
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