35189-28-7 Usage
Description
Norgestimate, also known as (17α)-17-acetyloxy-13-ethyl-18,19-dinor-pregn-4-en-20yn-3-one oxime, is a 19-nortestosterone, 3-oxime prodrug that is orally active. It is a white crystalline solid with minimal androgenic action and is metabolized to 17-deacetylnorgestimate (norelgestromin) and norgestrel, which provide the progestational action. Norgestimate is used in combination with estrogen as an oral contraceptive and is also known for its antifungal properties.
Uses
Used in Pharmaceutical Industry:
Norgestimate is used as a progestogen in combination with estrogen for oral contraceptive products. It provides effective birth control by working together with estrogen to prevent ovulation, thicken cervical mucus, and thin the uterine lining.
Used in Antifungal Applications:
Norgestimate is used as an antifungal agent, helping to treat and prevent fungal infections by inhibiting the growth and reproduction of fungi.
Used in Hormonal Regulation:
Norgestimate is used as a hormonal regulator, particularly in the treatment of conditions related to hormonal imbalances, such as menstrual disorders and endometriosis. It helps to regulate the menstrual cycle and reduce symptoms associated with hormonal imbalances.
Brand Name:
CILEST is a brand name under which Norgestimate is marketed, in combination with ethinyl estradiol, as an oral contraceptive.
Manufacturing Process
A solution of 4.5 g of D-17β-acetoxy-13β-ethyl-17α-ethynyl-gon-4-en-3-one in 15 ml of pyridine and 2.0 g of hydroxylamine hydrochloride hydroxylamine hydrochloride is heated on a steam bath for 45 min. It is then cooled and poured into a large amount of ice-water, after which the solid which is thus produced is filtered off and air dried. Recrystallization from methylene chloride-ethanol gives D-17β-acetoxy-13α-ethyl-17α-ethynyl-gon-4-en-one oxime, m.p. 214-218°C; [α]D25 = +41°.
Therapeutic Function
Progestin
in vitro
norgestimate was found that, unlike other 19-nortestosterone derivatives, showed high selectivity for the progesterone receptor and low androgenic activity. moreover, norgestimate and its main active metabolite norelgestromin could not bind to or occupy sex hormone-binding globulin [1].
in vivo
the androgenic and the progestational activity of norgestimate were compared in two animal studies. it was found the difference in the pharmacological response in norgestimate treated rats was equivalent to the difference in the exposure of the animals to either directly administered or metabolically derived levonorgestrel [2].
Metabolism
Norgestimate is considered to be a pro-proges tin (prodrug), because it rapidly undergoes a two-s tep m etabolic transformation to form two active products, norelgestromine (levonorgestrel 3-oxime) and levonorgestrel. Deacetylation occurs in the intestine and liver, whereas convers ion of the 3-oxime to the corresponding ketone occurs primarily in the liver. Unlike the other progestins mentioned, norgestimate and its metabolites are not bound to SHBG.
references
[1] thomas l. lemke; david a. williams (2008). foye's principles of medicinal chemistry. lippincott williams & wilkins. pp. 1316–. isbn 978-0-7817-6879-5.[2] kuhnz w, beier s. comparative progestational and androgenic activity of norgestimate and levonorgestrel in the rat. contraception. 1994 mar;49(3):275-89.[3] https://en. wikipedia.org/wiki/norgestimate
Check Digit Verification of cas no
The CAS Registry Mumber 35189-28-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,5,1,8 and 9 respectively; the second part has 2 digits, 2 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 35189-28:
(7*3)+(6*5)+(5*1)+(4*8)+(3*9)+(2*2)+(1*8)=127
127 % 10 = 7
So 35189-28-7 is a valid CAS Registry Number.
InChI:InChI=1/C23H31NO3/c1-4-22-12-10-19-18-9-7-17(24-26)14-16(18)6-8-20(19)21(22)11-13-23(22,5-2)27-15(3)25/h2,14,18-21,26H,4,6-13H2,1,3H3/b24-17+/t18?,19?,20?,21?,22-,23-/m0/s1
35189-28-7Relevant articles and documents
PROCESS FOR THE SYNTHESIS OF HIGH PURITY D-(17ALPHA)-13-ETHYL-17-HYDROXY-18,19-DINORPRE:GN-4-ENE-20-YNE-3-ONE-OXIME
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Page/Page column 5, (2008/06/13)
The invention relates to a process for the synthesis of high purity d-(17α)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yne-3-one-oxime (further on norelgestromine) via acetylation of d-norgestrel at position 17, oximation of the oxo group at position 3 of the obtained 17-acetoxy derivative, and finally hydrolyzing the acetoxy group at position 17 of the obtained 3-oxime derivative. The process according to our invention is as follows: the starting material, d-(17α-17-hydroxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one (d-norgestrel) - purity 93-94 % - is acetylated with acetic anhydride in acetic acid, in the presence of zinc chloride and hydrogen chloride, or 70 % perchloric acid in an inert gas atmosphere, and after completion of the reaction the excess of acetic anhydride and the "enol acetate" by-product are decomposed with aqueous hydrochioric acid, then the formed d-(17α)-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one is isolated from the reaction mixture by addition of ice-water, the precipitated product is filtered off, washed with water, dried, dissolved in dichloromethane or acetone and clarified with silica gel or aluminum oxide and charcoal, after filtration of the clarifier the resulted solution is concentrated and the residue is recrystallized, the obtained d-(17α)-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one is reacted either with hydroxylammonium acetate or with hydroxylammonium chloride in the presence of sodium acetate, in acetic acid in nitrogen atmosphere under vigorous stirring for about 1 hour, after completion of the reaction water is added, the precipitated product is filtered off, washed with water, dried and recrystallized, the obtained d-(17α-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one-oxime is hydrolyzed with an equivalent amount of an alkali metal hydroxide in a C1-C4 alkanol solution, in nitrogen atmosphere between a temperature of about 5-38 °C, under vigorous stirring, after completion of the reaction the mixture is diluted with water and the pH of the resulted suspension is adjusted to 7,5-9 with acetic acid, the precipitated product is filtered off, washed with water, dried, the crude product is dissolved in ethanol, clarified with charcoal, and after filtration of the clarifier water is added to the obtained solution, the precipitated high purity d-(17α)-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one-oxime is filtered off, washed with water and in given case recrystallized from ethanol.
