Novel C-17-heteroaryl steroids as potential inhibitors of CYP17

MEDI 82

Vincent C. O. Njar, vnjar001@umaryland.edu1, Jorge A. R. Salvador, salvador@ci.uc.pt2, Vânia M. A. Moreira, vmam@ci.uc.pt2, and Tadas Sean Vasaitis, sean@sightinsoul.com3. (1) Pharmacology and Experimental Therapeutic, University of Maryland, School of Medicine, 685, West Baltimore street, HSF-I, Room No. 563, Baltimore, MD 21201-1559, (2) Laboratório de Química Farmacêutica, Faculdade de Farmácia da Universidade de Coimbra, Rua do Norte, 3000 295 Coimbra, Portugal, (3) Department of Pharmacology & Experimental Therapeutics, University of Maryland School of Medicine, 685 West Baltimore Street, HSF 1, Room 580 I, Baltimore, MD 21201-1559
Androgens are important in the development, growth, and progression of Prostate Cancer (PC). Androgen ablation therapy has been shown to produce the most beneficial responses in multiple settings in PC patients. In the testes and adrenal glands, the last step in the biosynthesis of testosterone involves two key reactions, which act sequentially, and they are both catalyzed by a single enzyme, the cytochrome P450 monooxygenase 17α-hydroxylase/17,20-lyase (CYP17). Thus, potent and specific compounds that inhibit this enzyme's activity may be effective for the treatment of PC. High yield synthesis of novel steroidal compounds containing the 2-methylimidazole moiety at the C17 position of the androstane backbone has been achieved. Also, Δ16-17-indol, -indazole and -5-azaindole steroid derivatives have been synthesized via the nucleophilic vinylic “addition-elimination” substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene with the corresponding heterocyclic moieties. Their potential as CYP17 inhibitors has been evaluated.
 

General Poster Session
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006