Abstract: The disclosure provides compositions and methods for delaying the onset of delivery in a pregnant subject, such as a pregnant human subject, that is undergoing or at risk of undergoing preterm labor at a gestational age of from about 24 weeks to about 34 weeks. Using the compositions and methods described herein, such subjects may be administered atosiban in combination with a prostaglandin F2? (PGF2?) antagonist. Exemplary PGF2? receptor antagonists that may be used for the treatment or prevention of preterm labor as described herein include 1,3-thiazolidine-2-carboxamide compounds, such as (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate or a pharmaceutically acceptable salt thereof (e.g., (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate hydrochloride). The compositions and methods described herein provide various clinical benefits.

Abstract: The invention provides compositions and methods for reducing the volume of menstrual blood loss in a patient, such as a human patient, for instance, that has uterine fibroids, by administration of a gonadotropin-releasing hormone (GnRH) antagonist. Suitable GnRH antagonists useful in conjunction with the compositions and methods described herein include thieno[3,4d]pyrimidine derivatives, such as 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4d]pyrimidine-5-carboxylic acid and the choline salt thereof.

Abstract: The invention provides compositions and methods for delaying the onset of delivery in a pregnant subject, such as a pregnant human subject, that is undergoing or at risk of undergoing preterm labor at a gestational age of from about 24 weeks to about 34 weeks. Using the compositions and methods described herein, such subjects may be administered nifedipine in combination with a prostaglandin F2? (PGF2?) antagonist. Exemplary PGF2? receptor antagonists that may be used for the treatment or prevention of preterm labor as described herein include 1,3-thiazolidine-2-carboxamide compounds, such as (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate or a pharmaceutically acceptable salt thereof (e.g., (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate hydrochloride.

Abstract: The invention provides ?-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1?-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorphs thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as preterm labor at the early gestational stage by the administration of these substances to a patient in need of treatment.

Abstract: The invention provides compositions and methods for reducing the volume of menstrual blood loss in a patient, such as a human patient, for instance, that has uterine fibroids, by administration of a gonadotropin-releasing hormone (GnRH) antagonist. Suitable GnRH antagonists useful in conjunction with the compositions and methods described herein include thieno[3,4d]pyrimidine derivatives, such as 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxypheny I]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4d]pyrimidine-5-carboxylic acid and the choline salt thereof.

Abstract: The disclosure provides compositions and methods for determining the propensity of a subject (e.g., a female human subject) undergoing embryo transfer therapy to benefit from administration of an oxytocin receptor antagonist, as well as for treating such patients accordingly. Using the compositions and methods of the disclosure, a subject undergoing embryo transfer therapy may be selected for treatment with an oxytocin receptor antagonist on the basis of a pre-treatment gene signature. Additionally or alternatively, a subject that is undergoing embryo transfer therapy and that has been administered an oxytocin receptor antagonist may be monitored following treatment to determine whether the subject is responding to the oxytocin receptor antagonist or if subsequent dosing is desirable.

Abstract: The present disclosure provides compositions and methods for treating estrogen-dependent disorders, such as disorders of the female reproductive system, including uterine fibroids and endometriosis, among others. Compounds described herein that may be used to treat such indications include gonadotropin-releasing hormone (GnRH) antagonists. Suitable GnRH antagonists useful in conjunction with the compositions and methods described herein include thieno[3,4d]pyrimidine derivatives, such as 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno [3,4d]pyrimidine-5-carboxylic acid and the choline salt thereof, among others. Using the compositions and methods described herein, GnRH antagonists may be periodically administered to a patient, such as one or more times per day, week, or month, in combination with periodic add-back therapy, thereby preventing bone mineral density loss that may otherwise accompany estrogen depletion effectuated by GnRH antagonist activity.

Abstract: The invention provides compositions and methods for delaying the onset of delivery in a pregnant subject, such as a pregnant human subject, that is undergoing or at risk of undergoing preterm labor at a gestational age of from about 24 weeks to about 34 weeks. Using the compositions and methods described herein, such subjects may be administered nifedipine in combination with a prostaglandin F2? (PGF2?) antagonist. Exemplary PGF2? receptor antagonists that may be used for the treatment or prevention of preterm labor as described herein include 1,3-thiazolidine-2-carboxamide compounds, such as (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate or a pharmaceutically acceptable salt thereof (e.g., (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate hydrochloride.

Abstract: The invention provides ?-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1?-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorphs thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as preterm labor at the early gestational stage by the administration of these substances to a patient in need of treatment.

Abstract: The disclosure provides compositions and methods for the use of oxytocin antagonists, such as substituted pyrrolidin-3-one oxime derivatives of formula (I), among other compounds, in the treatment of subjects undergoing embryo transfer therapy. The compositions and methods of the disclosure can be used to dose subjects with oxytocin antagonists, including (3Z,5S)-5-(hydroxymethyl)-1-[(2?-methyl-1,1?-biphenyl-4-yl)carbonyl]pyrrolidin-3-one O-methyloxime, among others, so as to improve endometrial receptivity and reduce the likelihood of embryo implantation failure and miscarriage following, for example, in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI) embryo transfer procedures.

Abstract: The present disclosure provides compositions and methods for treating estrogen-dependent disorders, such as disorders of the female reproductive system, including uterine fibroids and endometriosis, among others. Compounds described herein that may be used to treat such indications include gonadotropin-releasing hormone (GnRH) antagonists. Suitable GnRH antagonists useful in conjunction with the compositions and methods described herein include thieno[3,4d]pyrimidine derivatives, such as 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno [3,4d]pyrimidine-5-carboxylic acid and the choline salt thereof, among others. Using the compositions and methods described herein, GnRH antagonists may be periodically administered to a patient, such as one or more times per day, week, or month.

Abstract: The present disclosure provides compositions and methods for treating estrogen-dependent disorders, such as disorders of the female reproductive system, including uterine fibroids and endometriosis, among others. Compounds described herein that may be used to treat such indications include gonadotropin-releasing hormone (GnRH) antagonists. Suitable GnRH antagonists useful in conjunction with the compositions and methods described herein include thieno[3,4d]pyrimidine derivatives, such as 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4d]pyrimidine-5-carboxylic acid and the choline salt thereof, among others. Using the compositions and methods described herein, GnRH antagonists may be periodically administered to a patient, such as one or more times per day, week, or month, over the course of an extended treatment period, such as a treatment period having a duration of multiple years.

Abstract: The present disclosure provides compositions and methods for treating endometrial growth disorders in a patient, such as a human patient, and particularly pre-menopausal female human patients. Exemplary disorders that may be treated using the compounds and therapeutic regimens described herein include adenomyosis and rectovaginal endometriosis. The compounds described herein that may be used to treat such indications include gonadotropin-releasing hormone (GnRH) antagonists. Suitable GnRH antagonists useful in conjunction with the compositions and methods described herein include thieno[3,4d]pyrimidine derivatives, such as 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno [3,4d]pyrimidine-5-carboxylic acid and the choline salt thereof, among others.

Abstract: The invention provides compositions and methods for reducing the volume of menstrual blood loss in a patient, such as a human patient, for instance, that has uterine fibroids, by administration of a gonadotropin-releasing hormone (GnRH) antagonist. Suitable GnRH antagonists useful in conjunction with the compositions and methods described herein include thieno[3,4d]pyrimidine derivatives, such as 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxypheny I]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4d]pyrimidine-5-carboxylic acid and the choline salt thereof.

Abstract: The invention provides ?-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1?-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorphs thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as preterm labor at the early gestational stage by the administration of these substances to a patient in need of treatment.

Abstract: The invention provides methods of treating endometriosis in a patient by administration of a gonadotropin-releasing hormone (GnRH) antagonist, for instance, according to dosing regimens predicated on the patient's level of anti-Müllerian hormone (AMH) or ?17-estradiol (E2).

Abstract: The invention provides pharmaceutical compositions comprising a compound of formula (I) or (II) and an additional therapeutic agent Also provided is the HCI salt and crystalline form of the compound of formula (I). The compounds inhibit the prostaglandin F receptor (PGF2alpha) and thus useful in the treatment of disorders such as preterm labor at the early gestational stage.

Abstract: The present invention relates generally to a combination for use in the treatment of gynaecological diseases and associated disabling symptoms thereof, in a subject in need thereof, said pharmaceutical combination for use comprising co-administering a suitable pharmaceutical composition for oral administration comprising a first progesterone receptor modulator and a pharmaceutical composition suitable for vaginal and/or intrauterine administration comprising a second progesterone receptor modulator.

Abstract: The invention provides compositions and methods for the use of oxytocin antagonists, such as substituted pyrrolidin-3-one oxime derivatives, among other compounds, in the treatment of subjects undergoing embryo transfer therapy. The compositions and methods of the invention can be used to dose subjects with oxytocin antagonists, including (3Z,55)-5-(hydroxymethyl)-1-[(2?-methyl-1,1?-biphenyl-4-yl)carbonyl]pyrrolidin-3-one O-methyloxime, among others, so as to improve endometrial receptivity and reduce the likelihood of embryo implantation failure and miscarriage following, for example, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) embryo transfer procedures.

Abstract: The invention provides pharmaceutical compositions comprising a compound of formula (I) or (II) and an additional therapeutic agent Also provided is the HCI salt and crystalline form of the compound of formula (I). The compounds inhibit the prostaglandin F receptor (PGF2alpha) and thus useful in the treatment of disorders such as preterm labor at the early gestational stage.