Non-steroidal antifertility agents.

PIP: About three decades ago a new era in the control of fertility began with the discovery of the steroidal hormonal contraceptive drugs, including estradiol and progesterone. The oral administration of progesterone inhibited ovulation in women, but heavy bleeding had to be controlled by estrogen. The development of a combination of pills dates back to Inhoffen in Germany, who synthesized ethisterone and ethinyl estradiol. Djerassi synthesized 19-norprogesterone and norethindrone, which were more potent than the naturally occurring progesterone. Subsequently, a large number of steroidal contraceptives were developed, of which, the fluorinated derivatives, 21-fluoroprogesterone (1a) and 21-fluoro-17alpha-acetoxyprogesterone (1b) were 2 to 4 times as active as progesterone; 21-fluoro-6alpha, 16alpha-dimethyl-17alpha-acetoxyprogesterone (1c) was 20 times as active as ethisterone. The effort to overcome heavy bleeding led to the synthesis of non-steroidal antifertility agents; aliphatic and allied derivatives; alicyclic compounds; aromatic and condensed systems; and heterocycles. All possible types of non-steroidal potential antifertility agents are reviewed, covering literature up to Chemical Abstracts (C.A.) volume 115 (1991), with occasional C.A. volume 116 (1992) references. A large number of prostaglandins and their derivatives were found to be useful as contraceptives even in mammals. Cloprosterol induced estrus in murrah and swamp buffalos. The prostaglandins El an PGF2alpha, when injected into rats, decreased sperm count and suppressed sperm motility and fertility. A number of prostaglandins were synthesized for evaluation of biological activity. Fluoroprostaglandins were evaluated for the interruption of pregnancy in hamsters (80-90 g body weight). Gossypol and gossypol acetate showed a high degree of antifertility activity in male and female animals up to mammals. Indomethacin administered up to 4 hours following mating decreased the number of implantations and increased premature resorption and mortality in rats; administered 8 hours after mating, it decreased pregnancies by 40%.^ieng

Changes in nutritional value of guava fruits infected by major post-harvest pathogens.

Post-infection changes in ascorbic acid, sugars, proteins and phenols were studied in guava fruits infected by major post-harvest pathogens which in order of importance were Colletotrichum gloeosporioides, (Penz.), Botryodiplodia theobromae, Pat., Rhizopus arrhizus Fischer., Phomopsis psidii Nag Raj and Ponnappa apud Ponnappa and Nag Raj, and Pestalotiopsis versicolor (Speg.) Steyaert. Contents of ascorbic acid, sugars and proteins declined in the fruits infected by Botryodiplodia theobromae, Colletotrichum gloeosporioides, Pestalotiopsis versicolor, Phomopsis psidii and Rhizopus arrhizus. Total phenols increased in fruits infected by Pestalotiopsis versicolor and Rhizopus arrhizus while reverse was observed in fruits infected by other pathogens.

Synthesis and antifertility activity of some new fluorine containing 2-([2-(fluoroaryl)-1H-indol-3- yl]methylene)hydrazinecarbothioamides and 2-(fluoroaryl)-([5-(substituted benzylidene)-4-oxo-2-thiazolidinylidene]hydrazone)- 1H-indole-3-carboxaldehydes.

New fluorine containing 2-(fluoroaryl)-1H-indole-3-carboxaldehydes have been synthesized and subjected to reaction with thiosemicarbazide to give corresponding 2-([2- (fluoroaryl)-1H-indol-3-yl]methylene)hydrazinecarbothiamides which were cyclized in the presence of chloroacetic acid, sodium acetate and substituted benzaldehydes to 2-(fluoroaryl)-([5- (substituted benzylidene)-4-oxo-2-thiazolidinylidene]hydrazone)- 1H-indole-3-carboxaldehydes as potential antifertility agents. In preliminary screening, 2-(4'-fluorophenyl)- ([5-(methylene-3,4-dioxyphenyl)-4-oxo-2- thiazolidinylidene]hydrazone)-1H-indole-3-carbocaldehyde exhibited pronounced antifertility activity. All these new compounds have been characterized by analytical and spectral (IR, PMR, MS) studies.

A direct titrimetric method for the microdetermination of some phenothiazine derivatives in pharmaceutical preparations.

A micro method has been developed for the determination of some phenothiazine derivatives in pure form and in pharmaceutical preparations, 1-5 mg of sample being titrated directly with 0.02M N-bromosuccinimide, with Methyl Red as indicator. The error does not exceed +/-1%.

Synthesis and biological activities of some new 2-arylamino-4-fluoroarylthiazoles.

Twenty-one new 2-arylamino-4-fluoroarylthiazoles have been synthesized by the condensation of the appropriate arylthiourea with the corresponding fluorophenacylbromide in ethanol. These new compounds have been characterized by elemental analysis and spectral studies. Some representative compounds have been screened for various biological activities viz. insecticidal, virucidal, bactericidal, fungicidal, herbicidal and antiarthritic.

Studies of potential organo-fluorine antibacterial agents. Part 5: Synthesis and antibacterial activity of some new fluorine-containing indole-2,3-dione derivatives.

A series of new 1-dialkylaminoacetyl-5/6-fluoroindole-2,3-diones and 3-arylhydrazino-5/6-fluoro-1-morpholinomethylindol-2-ones have been synthesized; the former by the reaction of different secondary amines with N-chloro-acetyl-5/6-fluoroindole-2,3-diones and the latter, by the condensation of substituted phenylhydrazines with 5/6-fluoro-1-morpholinomethylindole-2,3-diones. All synthesized compounds have been characterized by their IR, 1H-NMR and elemental analysis. These compounds have been screened for their antibacterial activity against the Gram positive bacterium Staphylococcus albus and the Gram negative bacterium Escherichia coli.

Possible psychopharmacological agents. Part 7: Synthesis and CNS activity of some fluorinated 2,4,7/8-trisubstituted-3H-1,5-benzodiazepinium monoperchlorates.

A series of new fluorinated 2,4'7/8-trisubstituted-3H-1,5-benzodiazepinium monoperchlorates have been synthesized and characterized by IR and NMR spectral studies. Representative compounds have been screened for their CNS activity viz., behavioural, analgesic, anticonvulsant and antireserpine. 8-Chloro-2-(4'-fluorophenyl)-4-phenyl-3H-1,5-benzodiazepinium monoperchlorate has shown pronounced antireserpine activity.

Studies in potential organo-fluorine antibacterial agents. Part 2: Synthesis and antibacterial activity of some new fluorine-containing 3.5-disubstituted isoxazoles.

A series of new fluorine-containing 3,5-disubstituted aryl/alkylisoxazoles has been synthesized by the condensation of hydroxylamine with appropriate beta-diketones in the presence of pyridine and characterized by IR and 1H NMR spectral studies. These isoxazoles have been screened for their antibacterial activity against the gram positive bacteria, Staphylococcus albus, Streptococcus nonhemolyticus and the gram negative bacterium Escherichia coli.