DL-Centchroman (67/20; INN: Ormeloxifene) synthesized at the Central Drug Research Institute, Lucknow, is a nonsteroidal once-a-week oral contraceptive. It was introduced in Delhi in July, 1991, marketed in India in 1992 as Saheli and Choice-7 (Hindustan Latex Ltd., Thiruvananthapuram) and Centron (Torrent Pharmaceuticals India Ltd., Ahmedabad), and included in the National Family Welfare Programme in 1995.5 According to post-marketing surveillance, approximately 100,000 women were using this pill and approximately 1100,000 menstrual cycles were covered until 1996. It is a unique need-oriented contraceptive being effective when taken immediately after coitus or routinely as a weekly pill and has the advantage of less frequent administration. Its contraceptive action is quickly reversible. It has long terminal serum halflife of 168 hr in women and exhibits duration of anti-implantation/estrogen antagonistic action of 120 hr, despite a short (24.1 hr) serum halflife, in the rat. In lactating women, it is excreted in milk in quantities considered unlikely to cause any deleterious effect on suckling babies. In phase II and III multicentric trials as a contraceptive, children born of method-and-user failure pregnancies showed normal milestones, without any congenital anomaly. Reports of its promising action in the management of certain hormone-related clinical disorders are available. It has an excellent therapeutic index and is considered safe for chronic administration.

Centchroman, a selective estrogen receptor modulator, as a contraceptive and for the management of hormone-related clinical disorders.

Hantzsch reaction seems to be one of the earliest procedures for the production of pyridines. Later on, Hantzsch 1,4-dihydropyridines, which mimic NADH reduction process in vitro, have shown promising biological activities. This review presents production procedure, major reactions of current interest, oxidation and reduction of Hantzsch 1,4-dihydropyridines, besides indication of some existing gaps and areas to be developed.

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Hantzsch reaction: Recent advances in Hantzsch 1,4-dihydropyridines

Hantzsch Reaction: Recent Advances in Hantzsch 1,4‐Dihydropyridines

Clinical pharmacokinetics and interaction of centchroman--a mini review.

Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens

A number of 2,6-dimethyl-3,5-bis(methoxycarbonyl)-4-substituted-1,4- dihydropyridines were synthesized and evaluated for pregnancy-interceptive activity in mated hamsters. Out of 24 compounds, 12, 15, 21, 22, 28, and 34 caused a marked reduction in the number of implantations when administered on days 3-8 postcoitum. In an in vitro competition assay, none of the compounds exhibited noticeable binding affinity for uterine progesterone receptors. The results reported here have helped to identify new leads for developing pregnancy-interceptive agents and the active compounds do not seem to elicit their interceptive effect through receptor-mediated inhibition of progesterone action in hamster uterus.

Syntheses and bioevaluation of substituted dihydropyridines for pregnancy-interceptive activity in hamsters.

Centchroman, a non-steroidal antifertility agent showed a low affinity (Kd = 13.19 X 10(-6) M) and nonsaturable binding to human plasma. Centchroman did not compete either with sex hormone binding globulin or corticosteroid binding globulin. Polyacrylamide gel electrophoresis and temperature dependent binding characteristics revealed that the protein responsible for centchroman binding to human plasma resembles albumin.

Binding of centchroman—a nonsteroidal antifertility agent to human plasma proteins

The synthesis of C-nor-9,11-secoestradiol (4) has been achieved from 17 beta-acetoxy-11-chloro-3-methoxy-C-nor-9,11-secoestra-1,3,5(10)-tr ien-9-one (1) through a sequence of reactions without affecting the stereochemistry of estradiol-17 beta. Removal of the 9-keto function of 1 by hydrogenolysis and its subsequent treatment with Na/NH3 gives C-nor-9,11-secoestradiol 3-(methyl ether) (3), which has been demethylated under alkaline conditions to furnish C-nor-9,11-secoestradiol (4). Pyridinium chlorochromate oxidation of 3 gives the corresponding 17-ketone 6. Jones' oxidation of 4 to the ketone 5 and reaction of 5 and 6 with lithium acetylide gives corresponding 17 alpha-ethynyl derivatives 7 and 8. Relative binding affinity to estradiol-17 beta receptors and uterotropic, antiuterotrophic, and antiimplantation activities of compounds 3-8 have been studied. The effect of conformational flexibility on ligand-receptor interaction of these compounds is discussed.

C-nor-9,11-secoestranes as modified estrogens and fertility regulation.

Levonorgestrel as a new radioligand for determination of sex hormone binding globulin in human plasma

Progesterone-receptor binding affinity of some nonsteroidal molecules was assessed by competitive protein binding assay in rabbit as well as human uterine cytosol in vitro. Of 40 compounds belonging to 5 different series tested, 3-(p-anisoyl)-2-chloro-6, 7-dimethoxy-quinoline exhibited around 50% inhibition whereas 2-(p-anisoyl) naphthalene and 3-substituted phenyl-1-(3-(2-chloro-6, 7-dialkoxy) quinolinyl)prop-2-en-1-one showed around 20% inhibition in 3H-progesterone binding for rabbit and human uterine progesterone receptor.

Anila Agnihotri

Papers

Syntheses and bioevaluation of substituted dihydropyridines for pregnancy-interceptive activity in hamsters.

Binding of centchroman—a nonsteroidal antifertility agent to human plasma proteins

C-nor-9,11-secoestranes as modified estrogens and fertility regulation.

Levonorgestrel as a new radioligand for determination of sex hormone binding globulin in human plasma

Molecular Interaction of Nonsteroidal Compounds with Uterine Progesterone Receptor (Part I)1)