- Pyrido[2,3-d]pyrimidin-7-ones as specific inhibitors of cyclin-dependent kinase 4
-
Inhibition of the cell cycle kinase, cyclin-dependent kinase-4 (Cdk4), is expected to provide an effective method for the treatment of proliferative diseases such as cancer. The pyrido[2,3-d]-pyrimidin-7-one template has been identified previously as a privileged structure for the inhibition of ATP-dependent kinases, and good potency against Cdks has been reported for representative examples. Obtaining selectivity for individual Cdk enzymes, particularly Cdk4, has been challenging. Here, we report that the introduction of a methyl substituent at the C-5 position of the pyrido[2,3-d]pvrimidin-7-one template is sufficient to confer excellent selectivity for Cdk4 vs other Cdks and representative tyrosine kinases. Further optimization led to the identification of highly potent and selective inhibitors of Cdk4 that exhibit potent antiproliferative activity against human tumor cells in vitro. The most selective Cdk4 inhibitors were evaluated for antitumor activity against MDA-MB-435 human breast carcinoma xenografts in mice.
- VanderWel, Scott N.,Harvey, Patricia J.,McNamara, Dennis J.,Repine, Joseph T.,Keller, Paul R.,Quin III, John,Booth, R. John,Elliott, William L.,Dobrusin, Ellen M.,Fry, David W.,Toogood, Peter L.
-
p. 2371 - 2387
(2007/10/03)
-
- Composition for dyeing keratin fibers, comprising at least one para-phenylenediamine derivative comprising a pyrrolidyl group substituted with a silyl radical
-
Disclosed herein are: a composition for dyeing keratin fibers, for example, human keratin fibres such as hair, comprising at least one para-phenylenediamine derivative comprising a pyrrolidyl group substituted with a silyl radical; a process for dyeing ke
- -
-
-
- Non-classical antifolates, 5-(N-phenylpyrrolidin-3-yl)-2,4,6-triaminopyrimidines and 2,4-Diamino-6(5H)-oxopyrimidines, synthesis and antitumor studies
-
A series of non-classical antifolates, namely 5-(N-phenylpyrrolidin-3-yl)-2,4,6-triaminopyrimidines (25a-i) and 2,4-diamino-(N-phenylpyrrolidin-3-yl)-6(5H)-oxopyrimidines (26a,b,c,f,h,i) was synthesized and evaluated for their in vitro cytotoxicity. React
- Huang, Yen-Lin,Lin, Chyun-Feng,Lee, Yi-Jen,Li, Wei-Wei,Chao, Ting-Chou,Bacherikov, Valeriy A.,Chen, Kuo-Tung,Chen, Chin-Ming,Su, Tsann-Long
-
p. 145 - 157
(2007/10/03)
-
- Dyeing compositions for keratinous fibres containing paraphenylenediamine derivatives with pyrrolidinyl group
-
The invention concerns novel dyeing compositions for keratinous fibers comprising at least a paraphenylenediamine derivative with pyrrolidinyl group as oxidation base, a dyeing method and a dyeing kit using said composition.
- -
-
-
- Pyrrolidinyl-substituted para-phenylenediamine derivatives substituted with a cationic radical, and use of these derivatives for dyeing keratin fibres
-
Novel pyrrolidinyl-substituted para-phenylenediamine derivatives comprising a cationic radical, the dye compositions comprising them and the process for dyeing keratin fibers using these compositions, making it possible to obtain a chromatic, powerful, un
- -
-
-