Pfizer CONTRAST

Pfizer s tenidap (CP-66,248) (157), another enolic compound, was also more potent (500-fold) toward CO over 5-LO inhibition in human ISN (0.032 /iM and 18 /iM, respectively) [379-381]. Efficacy in rheumatoid arthritis clinical trials has been reported [380,382] in patients, serum levels of acute phase proteins and synovial fluid levels of IL-1 were reduced by tenidap, in contrast to the lack of this effect with NSAIDs. Besides CO/5-LO inhibition, a variety of in vitro activities have been reported, including a number of effects on monocyte functions and differentiation [379], inhibition of neutrophil degranulation [382], inhibition of the activation of neutrophil collagenase [383], inhibition of leukocyte-endothelial cell adhesion [384], and inhibition of LTB4-induced neutrophil chemotaxis [385]. Al-... 

Amlodipine shows a preference for binding vascular smooth muscle cells over cardiac muscle cells, thus acting as a peripheral arterial vasodilator (Pfizer, Inc. 2005). Like most other CCB dihydropyridines, amlodipine is highly protein bound and heavily metabolized. In contrast to felodipine, this compound is not influenced by grapefruit juice and appears to show fewer drug-drug interactions. 

In-house chemical information management systems began to emerge at some of the larger chemical and pharmaceutical firms. These included CONTRAST and SOCRATES at Pfizer, SYNLIB at SmithKline, COUSIN at Upjohn, MSDRL/CSIS at Merck, and CROSSBOW at ICI (27). The Chemical Abstracts database was made available online in 1967 (28). In 1980 this became CAS ONLINE. A compre-... 

For example, in one 30-day period in the late summer of 2006 no fewer than four small companies, Icagen, Corcept, SGX, and Adolor, lost 73%, 56%, 41%, and 45% of their stock values, respectively, in one single day because of bad news on late-stage clinical trials. In contrast, Pfizer stock lost 10.6% of its value (still about 19 billion ) after the company announced that it was discontinuing clinical trials on its most promising candidate, torcetrapib, for safety reasons. 

In contrast, a second Pfizer group found that the pyrimidinol 870 was the major, if not exclusive, product from reaction of 2-amino-5-aroyloxazoles 868 and dimethylamine (Scheme 1.233). In this case, the authors found that electron-withdrawing substituents favored cyclization to yield 870. A similar mechanistic rationale (vide supra) was proposed to explain the product distribution. Selected examples are shown in Table 1.61. 

The major commercially available reaction indexing programs are REACCS (Molecular Design Limited), SYNLIB (started by Clark Still, developed by Smith, Kline and French and now sold by Dan Chodosh), ORAC (developed at the University of Leeds) and DARC-RMS (Telelsystemes). Pfizer s in-house system CONTRAST is noteworthy but is not available outside Pfizer. The release of CASREACT by Chemical Abstracts is awaited with interest. 

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