Contraceptive compounds and methods
Inventors
Georg, Ingrid Gunda • Cheryala, Narsihmulu
Assignees
University of Minnesota System
Publication Number
US-12281105-B2
Publication Date
2025-04-22
Expiration Date
2042-05-03
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The invention provides a compound of formula (I):or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof, wherein R1-R6 have any of the values described in the specification, as well as compositions comprising a compound of formula (I). The compounds are useful as contraceptive agents.
Core Innovation
The invention provides a novel class of compounds defined by formula (I), which are retinoic acid receptor-α (RARα) antagonists. These compounds, or their pharmaceutically acceptable salts, stereoisomers, solvates, or prodrugs, are described in detail with respect to possible substituent groups (R1–R6). Pharmaceutical compositions containing these compounds are also disclosed.
The compounds are intended for use as non-steroid, hormone-free, reversible male contraceptives by reducing sperm count or inducing reversible infertility through the selective antagonism of RARα. The invention also includes methods for reducing likelihood of conception following intercourse by administering these compounds to a male subject, and methods for selectively antagonizing RARα over RARβ and RARγ both in vivo and in vitro.
The background section identifies a critical need for additional reversible male contraceptive options that do not rely on steroid hormones and exhibit minimal side effects. Current methods for males are limited, and hormonal therapies like testosterone have incomplete efficacy and multiple health risks. The invention addresses this need by presenting a non-hormonal approach specifically targeting RARα, aiming for effective, safe, and reversible male contraception.
Claims Coverage
The patent includes four independent claims, each directed to a distinct inventive feature involving methods for contraception and RARα antagonism using a compound of formula (I).
Reducing sperm count in a male subject using a compound of formula (I)
This feature covers a method to reduce sperm count in a male subject by administering a compound of formula (I), which is defined in the specification and represents a retinoic acid receptor-α antagonist, or its pharmaceutically acceptable salt.
Producing reversible infertility in a male subject using a compound of formula (I)
The method involves administering a compound of formula (I) to a male subject to induce reversible infertility, as exemplified by restored fertility upon cessation of administration.
Selective antagonism of RAR alpha over RAR beta and RAR gamma in a subject
This inventive feature relates to administering a compound of formula (I) to a subject to selectively antagonize RAR alpha, achieving at least a 2, 5, or 10-fold greater antagonist activity at RAR alpha compared to RAR beta or RAR gamma.
Selective antagonism of RAR alpha over RAR beta and RAR gamma in vitro
The feature concerns contacting RAR alpha, RAR beta, and RAR gamma in vitro with a compound of formula (I) or its salt to achieve selective antagonism of RAR alpha.
These inventive features provide methods for non-hormonal male contraception and for selective RAR alpha antagonism, both in vivo and in vitro, using specifically described compounds.
Stated Advantages
The compounds provide an effective, non-steroid hormone-based reversible male contraceptive that exhibits few if any side effects, health risks, or further complications.
The compounds offer a non-hormonal approach by targeting RAR alpha, which is anticipated to result in minimal side effects relative to steroid hormone therapies.
The method and compounds induce reversible infertility in males, enabling restoration of fertility after treatment cessation.
Documented Applications
Use as a contraceptive agent for male subjects by reducing sperm count, producing reversible infertility, or reducing the likelihood of conception following intercourse.
Treatment of a disease or condition associated with RAR alpha activity in a subject wherein antagonism of RAR alpha is indicated, including cancer, metabolic disease, eye diseases, acne, neurodegenerative diseases, renal diseases, aging, depression, hyperlipidemia, vascular trauma, ischemic injury, rheumatoid arthritis, reducing mucin secretion, reducing chemotherapy or radiation therapy side-effects, serving as an antidote for retinoid intoxication, inhibiting viral replication, or antagonizing effects of ATRA.
Selective antagonism of RAR alpha over RAR beta and RAR gamma, either in a subject or in vitro.
Interested in licensing this patent?