The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Mar. 26, 2024

Filed:

Feb. 17, 2021
Applicants:

Muhammad Iqbal Choudhary, Karachi, PK;

Atia-tul Wahab, Karachi, PK;

Mahwish Siddiqui, Karachi, PK;

Nimra Naveed Shaikh, Karachi, PK;

Sammer Yousuf, Karachi, PK;

Atta-ur Rahman, Karachi, PK;

Inventors:

Muhammad Iqbal Choudhary, Karachi, PK;

Atia-tul Wahab, Karachi, PK;

Mahwish Siddiqui, Karachi, PK;

Nimra Naveed Shaikh, Karachi, PK;

Sammer Yousuf, Karachi, PK;

Atta-ur Rahman, Karachi, PK;

Assignee:
Attorney:
Primary Examiner:
Int. Cl.
CPC ...
C07D 311/78 (2006.01); A61K 31/366 (2006.01); A61K 31/585 (2006.01); A61P 35/00 (2006.01); C07D 493/04 (2006.01); C07J 73/00 (2006.01);
U.S. Cl.
CPC ...
C07J 73/003 (2013.01); A61P 35/00 (2018.01);
Abstract

Biotransformation of an aromatase inhibitor, testolactone (1), yielded four metabolites, 7β-hydroxy-3-oxo-13,17-seco-5β-androsta-1-eno-17,13α-lactone (2), 3α,11β-dihydroxy-13,17-seco-5β-androsta-17,13α-lactone (3), 4β,5β-epoxy-3β-hydroxy-13,17-secoandrosta-1-eno-17,13α-lactone (4), and 4β,5β-epoxy-3α-hydroxy-13,17-secoandrosta-1-eno-17,13α-lactone (5). Aromatase (estrogen synthase) involves in the synthesis of estrogen, and promotes the growth of breast cancerous cells. It is a key target for the discovery of chemotherapeutic agents against ER+(estrogen-positive) breast-cancers. Metabolites 2 (IC=8.63±0.402 nM), and 3 (IC=9.23±1.31 nM) were identified as potent inhibitors against human aromatase enzyme, in comparison to 1 (IC=0.716±0.031 μM), and the standard aromatase inhibiting drug, exemestane (IC=0.232±0.031 μM). Derivatives 4 (IC=10.37±0.50 μM) and 5 (IC=0.82±0.059 μM) also showed a good inhibition against aromatase enzyme. Therefore, metabolites 2-5 have the potential to serve as therapeutic agents against ER+ (estrogen-positive) breast-cancers.


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