Selective androgen receptor modulators

Structural modifications of bicalutamide led to the discovery of the first generation of selective androgen receptor modulators (SARMs). These compounds not only bind to the AR with an affinity in the nanomolar range, but they also show tissue selectivity in animal models [206]. 

Title N-Bridged Selective Androgen Receptor Modulators and Methods of Use Thereof... 

J.T. Dalton et al., US Patent 7,022,870 (April 4, 2006) Assignee University of Tennessee Research Foundation Utility Nonsteroidal Selective Androgen Receptor Modulators Useful for Treating Androgen-related Disorders... 

Table 1 Evaluation of selected experimental agents as selective androgen receptor modulators. Entry 16 had a moderate androgen receptor affinity while entry 17 displayed a very high propensity as an androgen selective receptor binding agent. H NMR data supplied by author...

Brown TR. Nonsteroidal selective androgen receptors modulators (SARMs) designer androgens with flexible structures provide clinical promise. Endocrinology 2004 145 5417-5419. 

Several CoMFA and CoMSIA studies were performed, both for optimizing selective androgen receptor modulators and for toxicity predictions. An early AR CoMFA model was reported by Waller et al. [118]. It was based on 28 structurally diverse chemicals from which 21 served as training set and yielded a cross-validated q2 value of 0.792. From the seven test compounds six were predicted within one order of magnitude to the experiment, the remaining deviated by 1.8 log units in K, from the experimental value. 

Salvati ME. Synthesis of selective androgen receptor modulators and methods for their identification, design and use. Ed. (Bristol-Myers Squibb Co. U. 2001-US19665[2002000617], 140. 20020103. WO. 20-6-2001. 

Wu, D., Wu, Z., Yang, J., Nair, V. A., Miller, D. D., Dalton, J. T. Pharmacokinetics and metaboUsm of a selective androgen receptor modulator in rats implication of molecular properties and intensive metabolic profile to investigate ideal pharmacokinetic characteristics of a propanamide in preclinical study. Drug Metab. Dispos. 2006, 34(3), 483-494. 

Rosen, J. and Negro-Vilar, A. (2002) Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile. Journal of Musculoskeletal and Neuronal Interactions, 32, 222-224. 

Nonsteroidal Tissue-selective Androgen Receptor Modulators... 

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