Alma Fejzic

Publications (2)9.6 Total impact

• Article: Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators.

  Nathalie Schlienger, Birgitte W Lund, Jan Pawlas, Fabrizio Badalassi, Fabio Bertozzi, Rasmus Lewinsky, Alma Fejzic, Mikkel B Thygesen, Ali Tabatabaei, Stefania Risso Bradley, Luis R Gardell, Fabrice Piu, Roger Olsson
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  ABSTRACT: Herein we describe the discovery of ACP-105 (1), a novel and potent nonsteroidal selective androgen receptor modulator (SARM) with partial agonist activity relative to the natural androgen testosterone. Compound 1 was developed from a series of compounds found in a HTS screen using the receptor selection and amplification technology (R-SAT). In vivo, 1 improved anabolic parameters in a 2-week chronic study in castrated male rats. In addition to compound 1, a number of potent antiandrogens were discovered from the same series of compounds whereof one compound, 13, had antagonist activity at the AR T877A mutant involved in prostate cancer.
  Journal of Medicinal Chemistry 10/2009; 52(22):7186-91. · 4.80 Impact Factor
• Article: Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists.

  Hanna Pettersson, Anne Bülow, Fredrik Ek, Jacob Jensen, Lars K Ottesen, Alma Fejzic, Jian-Nong Ma, Andria L Del Tredici, Erika A Currier, Luis R Gardell, Ali Tabatabaei, Darren Craig, Krista McFarland, Thomas R Ott, Fabrice Piu, Ethan S Burstein, Roger Olsson
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  ABSTRACT: A novel class of CB1 inverse agonists was discovered. To efficiently establish structure-activity relationships (SARs), new synthetic methodologies amenable for parallel synthesis were developed. The compounds were evaluated in a mammalian cell-based functional assay and in radioligand binding assays expressing recombinant human cannabinoid receptors (CB1 and CB2). In general, all of the compounds exhibited high binding selectivity at CB1 vs CB2 and the general SAR revealed a lead compound 11-(4-chlorophenyl)dibenzo[b,f][1,4]thiazepine-8-carboxylic acid butylamide (12e) which showed excellent in vivo activity in pharmacodynamic models related to CB1 receptor activity. The low solubility that hampered the development of 12e was solved leading to a potential preclinical candidate 11-(3-chloro-4-fluorophenyl)dibenzo[b,f][1,4]thiazepine-8-carboxylic acid butylamide (12h).
  Journal of Medicinal Chemistry 05/2009; 52(7):1975-82. · 4.80 Impact Factor