Synthesis and biological evaluation of 16beta pyrrolidinosteroidal derivatives

The synthesis of some steroidal bisquaternary ammonium substances (compounds 10 and 11), and their in vitro and in vivo neuromuscular blocking action are described in this report. The pyrrolidino functionality was incorporated at both the 3-beta and 16-beta positions of the steroid nucleus to study the importance of the interonium distance between the two quaternary ammonium heads. The 16-beta-pyrrolidino monoquaternary derivatives (compounds 14, 15, 16) were also prepared. The 17-beta-acetoxy bisquaternary derivative compound 11 was found to be more potent than d-tubocurarine (CAS 57-94-3) in in vivo studies. The 17-beta-hydroxy bisquaternary derivative, compound 10, and its 16-beta-pyrrolidino monoquaternary partner, compound 15, were found to be less active as compared to d-tubocurarine in in vitro studies. The monoquaternary compounds 14 and 16 were not tested due to their solubility problems. The intermediate substance, compound 12 was selected by the National Cancer Institute (NCI), Bethesda (USA) for investigation for antineoplastic activity but was found to be inactive

Synthesis and neuromuscular blocking activity of 16β-piperidinosteroidal derivatives

The synthesis and pharmacological profiles of some new steroidal mono- and bisquaternary ammonium derivatives have been described. The compounds featured have been conceptually derived structurally from two lead structures: pancuronium bromide 1 and chandonium iodide 2. In vitro and in vivo neuromuscular blocking studies have indicated the monoquaternary compound 15 to be less active than the bisquaternary compounds 10 and 11. The compound 11 has been found to be more active than d-tubocurarine

Synthesis and biological activity of 16β-morpholinosteroid derivatives

363-367Fusion of morpholine at the 16 position of the steroid nucleus has been carried out to prepare monoquaternary 6,7 and 8 and bisquaternary ammonium compounds 13 and 14. Compounds 13 and 14 partly resemble chandonium iodide in structure. All the compounds have been evaluated for their neuromuscular blocking and ganglion blocking activities. The compounds 3, 4 5, 11 and 12 have been screened for antineoplastic activity at NCI, Bethesda