Biological profile

Steroidal and Nonsteroidal Estrogens. Modification of the basic steroid skeleton and the nature of the functional groups in the B, C, and D rings while maintaining the phenoHc A-ring has continued to be a primary approach in the development of new estrogens with unique biological profiles. 

One of the two carbon atoms of the ethylene bridge of the antidepressants may be replaced by oxygen. Attachment of the side chain via the olefinic linkage found in amytriptyline affords antidepressants with a biologic profile similar to the carbocy-clic prototype. 

In recent years, a wealth of information has accumulated on RCM reactions leading to 5-, 6-, and 7-membered carbocycles and heterocycles, so that it is impossible to refer to all the new, natural product-directed work. Therefore, we will concentrate here on a few selected examples that can illustrate (1) the progress made by the advent of the second-generation ruthenium catalysts C-E, (2) the use of RCM in concert with other innovative methodology, and (3) the use of RCM in total syntheses of newly discovered natural products which, due to an outstanding biological profile, have attracted specific interest by the synthetic community. 

Cases M, Garcia-Serna R, Hettne K, Weeber M, van der Lei J, Boyer S, Mestres J. Chemical and biological profiling of an annotated compound library directed to the nuclear receptor family. Curr Top Med Chem 2005 5 763-72. 

The fundamental problem is to discover which substituents produce the most advantageous effects in the biological profile of a series. Normally, the purpose of introducing a substituent is to alter the physicochemical... 

The biological profile of the optimized lead structure emerging from these studies, compound (15a), was extensively investigated both in vitro and in vivo. The in vitro pattern of activity was in general excellent inasmuch... 

Use of Broad Biological Profiling as a Relevant Descriptor to Describe and Differentiate Compounds Structure-/ Vitro (Pharmacology-ADME)-/n Vivo (Safety) Relationships... 

Biological Profiling/Fingerprints and Drug Discovery Applications... 

An early identification of the best leads is critical, and systematic biological profiling, as with Cerep BioPrint , enables this progress to a great extent. Experience with using this approach in a major pharmaceutical company (Pfizer) has confirmed this. One component of the issue can be stated that it is better to identify the best (not just potency) lead series than to try and find the best candidate from a possibly suboptimal series, which can happen at late stages of lead optimization, where it is very difficult to make major changes to the lead series chemistry. 

Giardina, D., Crucianelli, M., Romanelli, R., Leonardi, A., Poggesi, E. and Melchiorre, C. (1996) Synthesis and biological profile of the enantiomers of [4-(4-amino-6,7-dimethoxyquinazolin-2-... 

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