Synthesis and biological evaluation of 16beta pyrrolidinosteroidal derivatives

D.P. Jindal, P. Piplani, H. Fajrak, C.B. Prior, I.G. Marshall

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalArzneimittel Forschung
Volume53
Issue number2
DOIs
Publication statusPublished - 2003

Fingerprint

Tubocurarine
Ammonium Compounds
National Cancer Institute (U.S.)
Antineoplastic Agents
Solubility
Steroids
In Vitro Techniques

Keywords

  • biological evaluation
  • 16beta pyrrolidinosteroidal derivatives
  • ammonium substances
  • antineoplastic activity

Cite this

Jindal, D.P. ; Piplani, P. ; Fajrak, H. ; Prior, C.B. ; Marshall, I.G. / Synthesis and biological evaluation of 16beta pyrrolidinosteroidal derivatives. In: Arzneimittel Forschung. 2003 ; Vol. 53, No. 2. pp. 73-79.
@article{2c70f2b0aeb84118a47a7799d66217d9,
title = "Synthesis and biological evaluation of 16beta pyrrolidinosteroidal derivatives",
abstract = "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.",
keywords = "biological evaluation , 16beta pyrrolidinosteroidal derivatives , ammonium substances , antineoplastic activity",
author = "D.P. Jindal and P. Piplani and H. Fajrak and C.B. Prior and I.G. Marshall",
year = "2003",
doi = "10.1002/chin.200321166",
language = "English",
volume = "53",
pages = "73--79",
journal = "Arzneimittel Forschung",
issn = "0004-4172",
number = "2",

}

Synthesis and biological evaluation of 16beta pyrrolidinosteroidal derivatives. / Jindal, D.P.; Piplani, P.; Fajrak, H.; Prior, C.B.; Marshall, I.G.

In: Arzneimittel Forschung, Vol. 53, No. 2, 2003, p. 73-79.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis and biological evaluation of 16beta pyrrolidinosteroidal derivatives

AU - Jindal, D.P.

AU - Piplani, P.

AU - Fajrak, H.

AU - Prior, C.B.

AU - Marshall, I.G.

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

KW - biological evaluation

KW - 16beta pyrrolidinosteroidal derivatives

KW - ammonium substances

KW - antineoplastic activity

U2 - 10.1002/chin.200321166

DO - 10.1002/chin.200321166

M3 - Article

VL - 53

SP - 73

EP - 79

JO - Arzneimittel Forschung

JF - Arzneimittel Forschung

SN - 0004-4172

IS - 2

ER -