CAS: 13425-31-5; (2α,5α,8ξ,9ξ,14ξ,17β)-2-Methyl-3-Oxoandrostan-17-Yl Heptanoate

专利信息

专利号:US-2021308144-A1
优先权日:2021-03-12
标 题:Synthesis of New Potent Aromatase Inhibitors Through Biocatalysis of Anti-Cancer Drugs, Atamestane, Drostanolone Enanthate, and Exemestane
发明人：WAHAB ATIA-TUL-; CHOUDHARY MUHAMMAD IQBAL; SIDDIQUI MAHWISH; SHAIKH NIMRA NAVEED; KHAN NISHA; RAHMAN ATTA-UR-
权利人:WAHAB ATIA TUL; CHOUDHARY MUHAMMAD IQBAL; SIDDIQUI MAHWISH; SHAIKH NIMRA NAVEED; KHAN NISHA; RAHMAN ATTA UR
摘要:New analogues of anti-cancer drugs atamestane (1), drostanolone enanthate ((3), and exemestane (6) were synthesized through biotransformation. New derivatives, 14α-hydroxy-1-methylandrosta-1,4-diene-3,17-dione ((2) (IC50, 9.7±0.72 nM) of 1 (IC50, 13.8±0.2 nM), and 2-methylandrosta-12β,17β-dihydroxy-1,4-diene-3-one (4) (IC50, 4.23±0.133 nM) of 3 (IC50, 6.4±0.06 nM) showed a potent inhibition against human aromatase enzyme and thus have the potential to treat ER+ breast-cancers and other related diseases. New metabolites, 2α-methyl-9α,17β-dihydroxy-5α-androstan-3-one ((5) (IC50=793.0±29.9 nM) of 3, 6-methylene-3α,7β,17β-trihydroxy-5β-androstane (7) (IC50, 46.1±0.81 nM), and 11α,17β-dihydroxy-6-methylene-androsta-1,4-diene-3-one (8) (IC5O=12797.0±844 nM) of exemestane (6) (IC50=232.0±31 nM) also showed a remarkable anti-aromatase activity. Aromatase is an enzyme, involves in the synthesis of estrogen (ER). Increased amount of ER due to overexpression of aromatase in the body, promotes cancerous cells growth in breast. Therefore, aromatase enzyme is a key target for the discovery of chemotherapeutic agents against ER+ breast-cancers.