Advances in the stereoselective synthesis of antifungal agents and ...

Chapter 1 28NCCNNN16NFigure 1.17: CGS 20267 16It is important to note that, in this case the heterocyclic moiety isdirectly linked to benzhydrilic position.1.5.2. Vorazole 17.Vorazole, 6-[(4-chlorophenil)(1H-1,2,4-triazole-1-yl)]-1-methyl-1Hbenzotriazole]17 has been recently developed 136 as a non steroidalaromatase inhibitor, (Fig. 1.18).ClNNNNN17NFigure 1.18: Vorazole 17.In vitro and in vivo studies with animal models demonstrated highpotency and specificity and thus its potential clinical usefulness in humans.It has also been demonstrated that almost all aromatase activity resides inthe dextroenantiomer (R83842). The (+)-and (-)-enantiomers were separatedby chiral semipreparative HPLC column. Studies both in animals andhumans showed an almost complete inhibition of in vivo human aromataseactivity 138 .In May 1994, Janssen Pharmaceuticals patented the synthesis of bothenantiomers 139 . The procedure is based on the classical resolution of17a 139 (±)-6- [(4-chlorophenyl- hydrazinomethyl) -1-methyl- 1,4-benzotriazole] using a chiral acid (Scheme 1.5) and subsequent