Title:
GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONIST AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2021/213538
Kind Code:
A1
Abstract:
Provided is a compound or a pharmaceutically acceptable salt, isomer, prodrug, polymorph, or solvate thereof, and a preparation method therefor and use thereof. The compound is used as a GnRHR antagonist in a calcium flux detection experiment, has an activity equivalent to or better than that of Elagolix, and has better pharmacokinetic properties.
Inventors:
LIU GUOQIANG (CN)
LIU WEI (CN)
WANG YANDONG (CN)
LIU WEI (CN)
WANG YANDONG (CN)
Application Number:
PCT/CN2021/094748
Publication Date:
October 28, 2021
Filing Date:
May 20, 2021
Export Citation:
Assignee:
SHANGHAI INNOFORTUNE BOITECH CO LTD (CN)
International Classes:
C07D239/54; A61K31/55; A61P5/02
Domestic Patent References:
| WO2018189212A1 | 2018-10-18 | |||
| WO2018224063A2 | 2018-12-13 |
Foreign References:
| CN1819829A | 2006-08-16 | |||
| CN200480019502A | 2004-07-06 |
Other References:
SHEBLEY MOHAMAD, POLEPALLY AKSHANTH R., NADER AHMED, NG JUKI W., WINZENBORG INSA, KLEIN CHERI E., NOERTERSHEUSER PETER, GIBBS MEGA: "Clinical Pharmacology of Elagolix: An Oral Gonadotropin-Releasing Hormone Receptor Antagonist for Endometriosis", CLINICAL PHARMACOKINETICS, vol. 59, no. 3, 1 March 2019 (2019-03-01), NZ, pages 297 - 309, XP055859685, ISSN: 0312-5963, DOI: 10.1007/s40262-019-00840-7
NG JUKI, DUAN W. RACHEL, MARBURY THOMAS, SCHMIDT JEFFREY M., KLEIN CHERI E: "Elagolix Pharmacokinetic Profiles in Women With Renal or Hepatic Impairment", CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT, vol. 8, no. 8, 1 November 2019 (2019-11-01), GB, pages 1053 - 1061, XP055859688, ISSN: 2160-763X, DOI: 10.1002/cpdd.640
CHEN CHEN; DONGPEI WU; ZHIQIANG GUO; QIU XIE; GREG J REINHART; AJAY MADAN; JENNY WEN; TAKUNG CHEN; CHARLES Q HUANG; MI CHEN; YONGS: "“Discovery of Sodium R-(+)-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]-benzyl)-4-methyl-2, 6-dioxo-3, 6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (Elagolix), a Potent and Orally Available Nonpeptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor”", JOURNAL OF MEDICINAL CHEMISTRY, vol. 51, no. 23, 11 December 2008 (2008-12-11), pages 7478 - 7485, XP055377651, ISSN: 0022-2623, DOI: 10.1021/jm8006454
SARMA, PKS ET AL., EXPERT OPINION ON THERAPEUTIC PATENTS, vol. 16, no. 6, 2006, pages 733 - 751
CHEN ET AL.: "Discovery of Sodium R-(+)-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-l-yl]-l-phenylethylamino}butyrate (Elagolix), a Potent and Orally Available Nonpeptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor", J. MED. CHEM., vol. 51, 2008, pages 7478 - 7485
KROGSGAARD-LARSEN ET AL.: "Textbook of Drug design and Discovery", April 2002, TAYLOR & FRANCIS
"Remington's Pharmaceutical Sciences", 1991, MACK PUB. CO.
See also references of EP 4140984A4
NG JUKI, DUAN W. RACHEL, MARBURY THOMAS, SCHMIDT JEFFREY M., KLEIN CHERI E: "Elagolix Pharmacokinetic Profiles in Women With Renal or Hepatic Impairment", CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT, vol. 8, no. 8, 1 November 2019 (2019-11-01), GB, pages 1053 - 1061, XP055859688, ISSN: 2160-763X, DOI: 10.1002/cpdd.640
CHEN CHEN; DONGPEI WU; ZHIQIANG GUO; QIU XIE; GREG J REINHART; AJAY MADAN; JENNY WEN; TAKUNG CHEN; CHARLES Q HUANG; MI CHEN; YONGS: "“Discovery of Sodium R-(+)-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]-benzyl)-4-methyl-2, 6-dioxo-3, 6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (Elagolix), a Potent and Orally Available Nonpeptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor”", JOURNAL OF MEDICINAL CHEMISTRY, vol. 51, no. 23, 11 December 2008 (2008-12-11), pages 7478 - 7485, XP055377651, ISSN: 0022-2623, DOI: 10.1021/jm8006454
SARMA, PKS ET AL., EXPERT OPINION ON THERAPEUTIC PATENTS, vol. 16, no. 6, 2006, pages 733 - 751
CHEN ET AL.: "Discovery of Sodium R-(+)-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-l-yl]-l-phenylethylamino}butyrate (Elagolix), a Potent and Orally Available Nonpeptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor", J. MED. CHEM., vol. 51, 2008, pages 7478 - 7485
KROGSGAARD-LARSEN ET AL.: "Textbook of Drug design and Discovery", April 2002, TAYLOR & FRANCIS
"Remington's Pharmaceutical Sciences", 1991, MACK PUB. CO.
See also references of EP 4140984A4
Attorney, Agent or Firm:
J.Z.M.C. PATENT AND TRADEMARK LAW OFFICE (CN)
Download PDF: