Nonsteroidal androgen receptor agonists

A modified Knorr cyclization has also been reported using ethyl 4,4,4-trifluoroacetoacetate in the synthesis of potent nonsteroidal androgen receptor agonists (Equation 30) <1998JME623, 1999BML1335, 1999BML1009>. 

Hamann, L.G., Mani, N.S., Davis, R.L., Wang, X.N., Marschke, K.B. and Jones, T.K. (1999) Discovery of a potent, orally active, nonsteroidal androgen receptor agonist 4-ethyl-l,2,3,4-tetrahydro-6-(trifluoromethyl)-8-pyridono[5,6-g]-quinoline (LG 121071). Journal of Medicinal Chemistry, 42, 210-212. 

Edwards JP, Higuchi RI, Winn DT, Pooley CLF, Caferro TR, Hamann LG, Zhi L, Marschke KB, Goldman ME, Jones TK (1999) Nonsteroidal androgen receptor agonist based on 4-(trifluoromethyl)-2//-pyrano[3,2-g]quinolin-2-one. Bioorg Med Chem Lett 9 1003-1008... 

Nickel-catalyzed enantioselective cross-couplings of racemic secondary benzylic halides with organozinc reagents have been further extended to the synthesis of chiral indanes. Indanes are useful building blocks for the synthesis of a variety of bioactive substances. For example, (/ )-3-ethylindanone 129 has been used for the preparation of the nonsteroidal androgen receptor agonist LG 121071. Fu and co-workers have reported on the rapid preparation... 

SCHEME 13.35. Nickel-catalyzed enantioselective cross-coupling in the preparation of the nonsteroidal androgen receptor agonist LG 121071. 

The photochemical electrocychzation was also applied as key step in the synthesis of nitrogen-containing heterocycles possessing pharmaceutical activity such as, for example, the 5-HT2Q2b Receptor Antagonist 49- or the nonsteroidal androgen receptor agonist 50 (Scheme 8). ... 

Edwards, J.P., Higuchi, R.I., Winn, D.T., et al. (1999) Nonsteroidal androgen receptor agonists based on 4-(trifluoromethyl)-2FI-pyrano[3,2-g] quinolin-2-one. Bioorganic Medicinal Chemistry Letters, 9,1003-1008. 

---