154229-18-2 Usage
Description
In April 2011, the United States FDA approved abiraterone acetate
(CB7630) in combination with the steroid prednisone for the treatment
of metastatic castration-resistant prostate cancer (mCRPC) for patients
who were previously treated with a docetaxel containing regimen for
late-stage disease. Abiraterone acetate affects prostate, testicular, and adrenal androgens by irreversibly inhibiting
both the lyase and hydroxylase activity of cytochrome P450 17A
(CYP17) signaling pathways (IC50's of 2.9 and 4 nM, respectively) thereby
decreasing testosterone levels.Most common serious adverse events for abiraterone acetate versus placebo included fluid retention (30.5% vs. 22.3%), hypokalemia (17.1% vs. 8.4%), hypertension (9.7% vs. 7.9%), hepatic transaminase abnormalities (10.4% vs. 8.1%), and cardiac abnormalities (13.3% vs. 10.4%).
Chemical Properties
Off-White Solid
Originator
Institute of Cancer Research, London (United Kingdom)
Uses
Different sources of media describe the Uses of 154229-18-2 differently. You can refer to the following data:
1. Abiraterone acetate is a novel steroidal inhibitor of human Cytochrome P450 (17α-Hydroxylase-C17,20-lyase): potential agent for the treatment of prostatic cancer.
2. Abiraterone acetate was approved by the U.S. Food and Drug
Administration (FDA) in April 2011 for the treatment of castrationresistant
prostate cancer. The drug, marketed under the trade name
Zytiga, was originally discovered by researchers at the Cancer Research
UK Centre for Cancer Therapeutics in 1990, developed by Cougar
Biotechnology, and ultimately commercialized by Johnson &
Johnson after its acquisition of Cougar in 2009. Abiraterone acetate
inhibits CYP17A1—an enzyme expressed in testicular, adrenal, and
prostatic tumor tissues—which has been implied in the production of
testosterone and the proliferation of such tumor cell lines.
3. A novel steroidal inhibitor of human Cytochrome P450(17a-Hydroxylase-C17,20-lyase): potential agent for the treatment of prostatic cancer.
Definition
ChEBI: A sterol ester obtained by formal condensation of the 3-hydroxy group of abiraterone with the carboxy group of acetic acid. A prodrug that is converted in vivo to abiraterone. Used for treatment of metastatic castrate-resistant prostate cance
.
Brand name
Zytiga
Biochem/physiol Actions
Abiraterone acetate is a prodrug of abiraterone, which is a potent, selective, and orally bioavailable inhibitor of CYP17A1 (CYP450c17), an enzyme that catalyzes two key serial reactions (17α hydroxylase and 17,20 lyase) in androgen and estrogen biosynthesis resulting in the formation of DHEA and androstenedione, which may ultimately be metabolized into testosterone. CYP17 is the key enzyme for androgen biosynthesis in both the testes and adrenals, so its inhibition should stop the production of androgens in both places. Abiraterone acetate is used for the treatment of metastatic castration-resistant prostate cancer. Abiraterone acetate possesses significant antitumor activity in post-docetaxel patients with CRPC (castration-resistant prostate cancer). It is highly essential for androgen biosynthesis in the testes, adrenal glands, and prostate tissue.
Clinical Use
Hormone antagonist:
Treatment of metastatic prostate cancer
Synthesis
The most convenient synthesis for scale-up will be highlighted
from two published syntheses. Commercially available
androstenolone 1 was acylated with acetic anhydride in the
presence of boron trifluoride-diethyl etherate to give a near quantitative
yield of acetate 2. The conversion of ketone 2 to vinyl triflate
3 involved careful selection of base to prevent elimination of the acetate
group. To this extent, subjection of 2 to triflic anhydride in
dichloromethane at ambient temperature followed by slow addition
of triethylamine minimized undesired side products and delivered
triflate 3 in 60% isolated yield. Subsequent Suzuki coupling with
diethylborane 4 under standard conditions ultimately furnished
abiraterone acetate (I) in 75% yield.
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: concentration possibly reduced by
rifabutin and rifampicin - avoid.
Antidepressants: concentration possibly reduced by
St John’s wort - avoid.
Antiepileptics: concentration possibly reduced
by carbamazepine, fosphenytoin, phenobarbital,
phenytoin and primidone - avoid.
Metabolism
Abiraterone acetate is hydrolysed to abiraterone, which
then undergoes metabolism including sulphation,
hydroxylation and oxidation mainly in the liver to form
inactive metabolites. About 88% of a dose is excreted in
the faeces, of which about 55% is unchanged abiraterone
acetate and about 22% is abiraterone; about 5% of a dose
is excreted in the urine.
Check Digit Verification of cas no
The CAS Registry Mumber 154229-18-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,5,4,2,2 and 9 respectively; the second part has 2 digits, 1 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 154229-18:
(8*1)+(7*5)+(6*4)+(5*2)+(4*2)+(3*9)+(2*1)+(1*8)=122
122 % 10 = 2
So 154229-18-2 is a valid CAS Registry Number.
InChI:InChI=1/C26H33NO2/c1-17(28)29-20-10-12-25(2)19(15-20)6-7-21-23-9-8-22(18-5-4-14-27-16-18)26(23,3)13-11-24(21)25/h4-6,8,14,16,20-21,23-24H,7,9-13,15H2,1-3H3/t20-,21?,23?,24?,25-,26+/m0/s1
154229-18-2Relevant articles and documents
Improved procedure for preparation of abiraterone acetate
Madhra, Mukesh Kumar,Sriram, Hari Mohan,Inamdar, Murad,Sharma, Mukesh Kumar,Prasad, Mohan,Joseph, Sony
, p. 555 - 558 (2014)
An improved procedure for the preparation of abiraterone acetate is described. The present process highlights reduced reaction time, isolation with acid-base treatment without involving column chromatography, multiple crystallization and is amenable to la
Application of trifluoromethanesulfonate in preparation of abiraterone acetate and synthesis method of trifluoromethanesulfonate
-
Paragraph 0036-0045, (2021/06/12)
The invention particularly relates to application of trifluoromethanesulfonate in preparation of abiraterone acetate and a synthesis method. The invention provides a novel method for synthesizing abiraterone acetate. According to the method, a trifluoromethanesulfonate, such as iron trifluoromethanesulfonate and scandium trifluoromethanesulfonate, is adopted as a catalyst, isopropenyl acetate is adopted as an acylation reagent, and acetylation is carried out on the 3-site hydroxyl of abiraterone to synthesize abiraterone acetate. The method is simple to operate and high in product yield, and the use of irritant acetylation reagents such as acetic anhydride and acetyl chloride and chemical amounts of basic groups such as pyridine and triethylamine is avoided.
Method for preparing abiraterone acetate
-
, (2020/07/14)
The invention provides a method for preparing abiraterone acetate. Specifically, the invention relates to an improved method for synthesizing abiraterone or a derivative thereof through a key 3 beta-benzoyloxy intermediate. According to the process, intermediate DHEA 3-benzoyloxy ester is a solid, the intermediate with higher purity can be obtained through a crystallization method, and the processoperability is high. Meanwhile, benzoyl is strong in electric negative force, easy to react with hydroxyl and high in acylation rate, and a six-membered ring structure is twisted in a space structureof a benzoyl functional group, so that elimination reaction is not easy to perform, and generation of process byproducts is effectively avoided.
Synthetic method of abiraterone acetate and intermediate thereof (by machine translation)
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Paragraph 0093; 0100; 0101; 0102-0128, (2021/01/04)
The invention relates to a synthesis method of abiraterone acetate and a dragon intermediate thereof. In the synthesis method of abiraterone acetate intermediate, a compound of formula (I), a chloro reagent and a base are chlorinated to obtain the abiraterone acetate intermediate of formula (II). The mass ratio of the compound of the formula (I) to the base is 1: (1.5 -3). The structure of the compound of formula (I) and abiraterone acetate is as follows. To the synthesis method, the occurrence probability of side reactions in the chlorination reaction process can be reduced while the high reaction activity is maintained, so that the yield and purity of the abiraterone acetate intermediate can be improved, and the process is simple. (by machine translation)
