Title:
MONOMERIC AND OLIGOMERIC COMPOUND EMBODIMENTS AS CONTRACEPTIVES AND THERAPIES AND METHODS OF MAKING AND USING THE SAME
Document Type and Number:
WIPO Patent Application WO/2021/252761
Kind Code:
A3
Abstract:
Disclosed herein are monomeric and oligomeric compound embodiments for use as contraceptive agents. Monomeric compound embodiments disclosed herein comprise substituents that facilitate the ability of the compounds to exhibit progestogenic, androgenic, and estrogenic activity, which can prevent or inhibit bone density loss in subjects. Oligomeric compound embodiments disclosed herein provide the ability to control receptor activation and/or treatment by incorporating a tunable linker group which couples steroidal-based compounds to one another or with therapeutic agents and facilitates selective cleavage of the monomeric components of the oligomeric compound.
Inventors:
KASKAR BASHIR (US)
LIN MING-TEH (US)
LEE MIN (US)
BLITHE DIANA (US)
GUPTA PRANAB (US)
LIN MING-TEH (US)
LEE MIN (US)
BLITHE DIANA (US)
GUPTA PRANAB (US)
Application Number:
PCT/US2021/036809
Publication Date:
February 10, 2022
Filing Date:
June 10, 2021
Export Citation:
Assignee:
US HEALTH (US)
ASH STEVENS LLC (US)
ASH STEVENS LLC (US)
International Classes:
A61P1/00; A61P3/00; A61P7/06; A61P9/00; A61P11/00; A61P15/00; A61P15/08; A61P21/06; A61P31/04; A61P31/10; A61P31/12; A61P35/00; A61P35/02; A61P37/00; C07J1/00; C07J3/00; C07J5/00; C07J31/00; C07J41/00; C07J43/00
Domestic Patent References:
| WO2001074839A2 | 2001-10-11 | |||
| WO2006083618A1 | 2006-08-10 | |||
| WO2003101374A2 | 2003-12-11 | |||
| WO1999026962A1 | 1999-06-03 |
Foreign References:
| DE2150534A1 | 1973-04-12 | |||
| GB1041276A | 1966-09-01 | |||
| EP1457208A1 | 2004-09-15 | |||
| DD109621A1 | 1974-11-12 | |||
| US2173423A | 1939-09-19 | |||
| US3338892A | 1967-08-29 | |||
| JPS433107B1 | 1968-02-05 |
Other References:
BURSI R ET AL: "Structure-activity relationship study of human liver microsomes-catalyzed hydrolysis rate of ester prodrugs of MENT by comparative molecular field analysis (CoMFA)", STEROIDS, ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY, US, vol. 68, no. 3, 1 March 2003 (2003-03-01), pages 213 - 220, XP004414163, ISSN: 0039-128X, DOI: 10.1016/S0039-128X(02)00186-1
NADERI S ET AL: "Long-acting contraceptive agents: In vitro hydrolysis of esters of norethisterone and levonorgestrel", STEROIDS, ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY, US, vol. 41, no. 3, 1 March 1983 (1983-03-01), pages 397 - 417, XP023430093, ISSN: 0039-128X, [retrieved on 19830301], DOI: 10.1016/0039-128X(83)90110-1
HUMPEL M ET AL: "A new principle of injectable depot contraceptives I. Drug selection and studies in monkeys", CONTRACEPTION, GERON-X, INC., LOS ALTOS, CA, US, vol. 19, no. 4, 1 April 1979 (1979-04-01), pages 411 - 419, XP023168192, ISSN: 0010-7824, [retrieved on 19790401], DOI: 10.1016/0010-7824(79)90035-0
CUNNINGHAM G R ET AL: "Steroid structural requirements for high affinity binding to human sex steroid binding protein (SBP)", STEROIDS, ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY, US, vol. 38, no. 3, 1 September 1981 (1981-09-01), pages 243 - 262, XP025206042, ISSN: 0039-128X, [retrieved on 19810901], DOI: 10.1016/0039-128X(81)90061-1
BOROWIECKI PAWEL ET AL: "Highly efficient, solvent-free esterification of testosterone promoted by a recyclable polymer-supported tosylic acid catalyst under microwave irradiation", ARKIVOC, vol. 2019, no. 6, 1 January 2019 (2019-01-01), pages 288 - 305, XP055865916, Retrieved from the Internet
LI C ET AL: "Stereoselective synthesis of some methyl-substituted steroid hormones and their in vitro cytotoxic activity against human gastric cancer cell line MGC-803", STEROIDS, ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY, US, vol. 75, no. 12, 1 December 2010 (2010-12-01), pages 859 - 869, XP027221102, ISSN: 0039-128X, [retrieved on 20100521]
DATABASE Chemical Abstracts [online] ACS; 1 January 1964 (1964-01-01), CAMPBELL J. A. ET AL: "7.alpha.-Methyltestosterones, a new class of potent anabolic agents", XP055866249, retrieved from STN Database accession no. 64:106570
DATABASE Chemical Abstracts [online] ACS; 1 January 1972 (1972-01-01), PHELAN RICHARD ET AL: "Preclinical toxicological evaluation of intramuscular administration of 7--- methyltestosterone propionate (NSC-136 020E) in dogs,rats, and rabbits", XP055866241, retrieved from STN Database accession no. 79:13780
MODI S P ET AL: "Conjugate addition of Grignard reagents to enones and dienones", THE JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY, vol. 54, 1 January 1989 (1989-01-01), pages 2317 - 2321, XP002242748, ISSN: 0022-3263, DOI: 10.1021/JO00271A014
MIESCHER K ET AL: "WEITERE UNTERSUCHUNGEN ÜBER DIE WIRKUNGSVERSTÄNNLICHER SEXUALHORMONE DURCH VERESTERUNG", BIOCHEMISCHE ZEITSCHRIFT, SPRINGER, BERLIN, DE, vol. 294, 1 January 1937 (1937-01-01), pages 39 - 60, XP008076314, ISSN: 0366-0753
KAUFMANN G ET AL: "Inhibition of 16-androstene biosynthesis in boar testis preparations by known and new steroids", JOURNAL OF STEROID BIOCHEMISTRY, PERGAMON PRESS PLC, GB, vol. 13, no. 3, 1 March 1980 (1980-03-01), pages 351 - 358, XP023415195, ISSN: 0022-4731, [retrieved on 19800301], DOI: 10.1016/0022-4731(80)90015-1
FARKAS EUGENE ET AL: "Steroidal Carbamic Acid gamma-Lactones", JOURNAL OF MEDICINAL CHEMISTRY, vol. 7, 1 January 1964 (1964-01-01), pages 739 - 741, XP055866349, Retrieved from the Internet DOI: 10.1021/jm00336a013
ARTH G E ET AL: "STEROIDAL ANDROGEN BIOSYNTHESIS INHIBITORS", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 14, no. 8, 1 January 1971 (1971-01-01), pages 675 - 679, XP001172875, ISSN: 0022-2623, DOI: 10.1021/JM00290A003
DATABASE Chemical Abstracts [online] ASC; 1 January 1984 (1984-01-01), SMITH WALTER T ET AL: "An improved method for the preparation of steryl N-methylcarbamates", XP055866512, retrieved from STN Database accession no. DN 101:192287
MOERSCH G W ET AL: "Steroidal 4-Methylene-2-oxoazolidinones", JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 2, 1 June 1965 (1965-06-01), pages 207 - 208, XP055866344
KUSAKABE TAICHI ET AL: "Carbonylation of Propargyl Carbamates with Palladium(II) Bisoxazoline Catalysts: Efficient Synthesis of 5-Methoxy-3(2 H )-furanones", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, vol. 52, no. 30, 20 June 2013 (2013-06-20), pages 7845 - 7849, XP055866419, ISSN: 1433-7851, DOI: 10.1002/anie.201303684
NADERI S ET AL: "Long-acting contraceptive agents: In vitro hydrolysis of esters of norethisterone and levonorgestrel", STEROIDS, ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY, US, vol. 41, no. 3, 1 March 1983 (1983-03-01), pages 397 - 417, XP023430093, ISSN: 0039-128X, [retrieved on 19830301], DOI: 10.1016/0039-128X(83)90110-1
HUMPEL M ET AL: "A new principle of injectable depot contraceptives I. Drug selection and studies in monkeys", CONTRACEPTION, GERON-X, INC., LOS ALTOS, CA, US, vol. 19, no. 4, 1 April 1979 (1979-04-01), pages 411 - 419, XP023168192, ISSN: 0010-7824, [retrieved on 19790401], DOI: 10.1016/0010-7824(79)90035-0
CUNNINGHAM G R ET AL: "Steroid structural requirements for high affinity binding to human sex steroid binding protein (SBP)", STEROIDS, ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY, US, vol. 38, no. 3, 1 September 1981 (1981-09-01), pages 243 - 262, XP025206042, ISSN: 0039-128X, [retrieved on 19810901], DOI: 10.1016/0039-128X(81)90061-1
BOROWIECKI PAWEL ET AL: "Highly efficient, solvent-free esterification of testosterone promoted by a recyclable polymer-supported tosylic acid catalyst under microwave irradiation", ARKIVOC, vol. 2019, no. 6, 1 January 2019 (2019-01-01), pages 288 - 305, XP055865916, Retrieved from the Internet
LI C ET AL: "Stereoselective synthesis of some methyl-substituted steroid hormones and their in vitro cytotoxic activity against human gastric cancer cell line MGC-803", STEROIDS, ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY, US, vol. 75, no. 12, 1 December 2010 (2010-12-01), pages 859 - 869, XP027221102, ISSN: 0039-128X, [retrieved on 20100521]
DATABASE Chemical Abstracts [online] ACS; 1 January 1964 (1964-01-01), CAMPBELL J. A. ET AL: "7.alpha.-Methyltestosterones, a new class of potent anabolic agents", XP055866249, retrieved from STN Database accession no. 64:106570
DATABASE Chemical Abstracts [online] ACS; 1 January 1972 (1972-01-01), PHELAN RICHARD ET AL: "Preclinical toxicological evaluation of intramuscular administration of 7--- methyltestosterone propionate (NSC-136 020E) in dogs,rats, and rabbits", XP055866241, retrieved from STN Database accession no. 79:13780
MODI S P ET AL: "Conjugate addition of Grignard reagents to enones and dienones", THE JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY, vol. 54, 1 January 1989 (1989-01-01), pages 2317 - 2321, XP002242748, ISSN: 0022-3263, DOI: 10.1021/JO00271A014
MIESCHER K ET AL: "WEITERE UNTERSUCHUNGEN ÜBER DIE WIRKUNGSVERSTÄNNLICHER SEXUALHORMONE DURCH VERESTERUNG", BIOCHEMISCHE ZEITSCHRIFT, SPRINGER, BERLIN, DE, vol. 294, 1 January 1937 (1937-01-01), pages 39 - 60, XP008076314, ISSN: 0366-0753
KAUFMANN G ET AL: "Inhibition of 16-androstene biosynthesis in boar testis preparations by known and new steroids", JOURNAL OF STEROID BIOCHEMISTRY, PERGAMON PRESS PLC, GB, vol. 13, no. 3, 1 March 1980 (1980-03-01), pages 351 - 358, XP023415195, ISSN: 0022-4731, [retrieved on 19800301], DOI: 10.1016/0022-4731(80)90015-1
FARKAS EUGENE ET AL: "Steroidal Carbamic Acid gamma-Lactones", JOURNAL OF MEDICINAL CHEMISTRY, vol. 7, 1 January 1964 (1964-01-01), pages 739 - 741, XP055866349, Retrieved from the Internet
ARTH G E ET AL: "STEROIDAL ANDROGEN BIOSYNTHESIS INHIBITORS", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 14, no. 8, 1 January 1971 (1971-01-01), pages 675 - 679, XP001172875, ISSN: 0022-2623, DOI: 10.1021/JM00290A003
DATABASE Chemical Abstracts [online] ASC; 1 January 1984 (1984-01-01), SMITH WALTER T ET AL: "An improved method for the preparation of steryl N-methylcarbamates", XP055866512, retrieved from STN Database accession no. DN 101:192287
MOERSCH G W ET AL: "Steroidal 4-Methylene-2-oxoazolidinones", JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 2, 1 June 1965 (1965-06-01), pages 207 - 208, XP055866344
KUSAKABE TAICHI ET AL: "Carbonylation of Propargyl Carbamates with Palladium(II) Bisoxazoline Catalysts: Efficient Synthesis of 5-Methoxy-3(2 H )-furanones", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, vol. 52, no. 30, 20 June 2013 (2013-06-20), pages 7845 - 7849, XP055866419, ISSN: 1433-7851, DOI: 10.1002/anie.201303684
Attorney, Agent or Firm:
SCHWARTZ, Johanna P. et al. (US)
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