1045-29-0Relevant academic research and scientific papers
Pharmacokinetics and pharmacodynamics of anordrin (2α,17α-diethynyl-A-nor-5α-androstane-2β,17β-diol diproprionate)
Chatterton, Robert T.,Kowalski, Wlodzimierz,Lu, Yu-cai,Peters, Albert J.
, p. 217 - 223 (1994)
In order to determine the pharmacokinetics of anordrin a dose of 0.2 mg/kg of anordrin was administered i.v. to 5-cynomolgus monkeys; the same monkeys received the same dose i.m. at a later date.An additional 3 monkeys received 1.0 mg/kg of anordrin i.m.After administration of the compound, the dipropionate esters of anordrin were rapidly hydrolyzed to the dihydroxy parent compound, anordiol.After i.v. administration, anordin had a mean residence time (MRT) of 5.0 +/- (SE) min. Anordiol formed from anordrin had an MRT of 139 +/- 27 (SE) min.The metabolic clearance rates (MCR) of anordin and anordiol were 55 and 34 mL/min*kg, respectively.The apparent volume of distribution at steady state (Vss) for anordrin was 276 mL/kg, 7.5percent of body weight of the animals; anordrin had a much larger Vss of 4460 mL/kg.The MRT of anordiol after i.m. administration of 1.0 mg/kg of anordrin was 26.3 days.An average of 44percent of the dose appeared in urine regardless of the route of administration or dose.The MRT values of total radioactivity were the same when calculated from serum or urine after an i.v. dose, but after i.m. administration, values from urine were approximately 60percent of that calculated from serum, indicating that products appearing in urine had a shorter MRT than products appearing primarily in feces.A separate group of monkeys was given anordrin i.m. in doses ranging from 0.1 to 0.4 mg/kg on the first day of menses.The regression of length of menstrual cycle on dose was significant (P=0.004).Control cycle length was 30 days and the response was linear to 76 days with the maximum dose given. Keywords: anordrin, contraceptive; pharmacokinetics; pharmacodynamics; monkey
Predominant contributions of carboxylesterase 1 and 2 in hydrolysis of anordrin in humans
Jiang, Jinfang,Chen, Xiaoyan,Zhong, Dafang
, p. 533 - 540 (2018)
1.Anordrin (2α, 17α-diethynyl-A-nor-5α-androstane-2β, 17β-diol diproprionate) is post-coital contraceptive drug that is on the market in China for more than 30 years. This study aims to elucidate enzymes involved in anordrin hydrolysis, and to evaluate the significant role of carboxylesterases in anordrin hydrolysis in humans. 2.Human liver and intestinal microsomes, recombinant human carboxylesterase were selected as enzyme sources. In human liver microsomes, intrinsic clearance was 684 ± 83 μL/min/mg protein, which was considerably higher than the value of intestine microsomes (94.6 ± 13.3 μL/min/mg protein). Carboxylesterase (CES) 1 has more contribution than CES2 in human liver. 3.Inhibition studies were performed using representative esterase inhibitors to confirm esterase isoforms involved in anordrin hydrolysis. Simvastatin strongly inhibited hydrolytic process of anordrin in liver and intestine microsomes, with IC50 values of 10.9 ± 0.1 and 6.94 ± 0.03 μM, respectively. 4.The present study investigated for the first time hydrolytic enzyme phenotypes of anordrin. Anordrin is predominantly catalyzed by CES1 and CES2 to generate the main active metabolite, anordiol. Moreover, anordrin and its metabolite anordiol can be altered by esterase inhibitors, such as simvastatin, upon exposure in vivo.
ASYMMETRIC SYNTHESIS AND USES OF COMPOUNDS IN DISEASE TREATMENTS
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, (2019/03/17)
The present application discloses, among other things, asymmetric synthesis a diastereomeric compound of formula (I) (e.g., α-anordrin) or salt thereof. Also provided are methods and compositions for treatment of estrogen deficiency as well as preventing or reducing an estrogen deficiency symptom using a diastereomeric compound of formula (I) (e.g., α-anordrin) or salt thereof alone or in combination with at least one additional agent. Further provided are methods and compositions for reducing a side effect of an additional agent in the context of combination therapy with a diastereomeric compound of formula (I) (e.g., α-anordrin) or salt thereof.
