52 results about "Progesterone receptor modulators" patented technology

Compounds of formula I are provided, wherein R₁-R₉ and n are defined herein, and pharmaceutical compositions and kits containing these compounds.

Also provided are methods of inducing contraception, providing hormone replacement therapy, treating cycle-related symptoms, or treating or preventing benign or malignant neoplastic disease using the compounds of formula I or formula II, wherein R₃-R₅, R₁₀, and R₁₁ are defined herein.

A progesterone receptor modulator of the structure

is provided. Use of compositions containing this compound for contraception, hormone replacement therapy, treating hormone-dependent disease, synchronizing estrus, treating dysmenorrhea, treating dysfunctional uterine bleeding, inducing amenorrhea, or treating symptoms of premenstrual syndrome and premenstrual dysphoric disorder in a mammal are described.

Compounds of formula I, wherein R₁-R₉ and n are defined herein, and pharmaceutical compositions and kits containing these compounds are provided.

Also provided are methods of inducing contraception, providing hormone replacement therapy, treating cycle-related symptoms, or treating or preventing benign or malignant neoplastic disease using the compounds of formula I or formula II, wherein R₃-R₅, R₁₀, and R₁₁ are defined herein.

Compounds of formula I or II are provided, wherein R₁—R₈ are defined herein, and pharmaceutical compositions and kits containing these compounds.

Also provides are methods of inducing contraception, providing hormone replacement therapy, treating cycle-related symptoms, or treating or preventing benign or malignant neoplastic disease using the compounds of formula I, formula II, or formula III, wherein R₂—R₄ and R₉ are defined herein.

The present invention provides methods of treating skin disorders includes delivering to a mammal a composition containing a compound of formula I, or tautomers thereof, in a regimen, wherein formula I is:

and wherein R¹-R⁵ and Q¹ are defined as described herein. Specifically, methods for treating acne, hirsutism, and conditioning the skin are described. Also provided are novel PR modulators of formula II.

Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure:

wherein R¹, R², R³, R⁴, R⁵, and Q¹ are defined herein.

Compounds having the structure of formula I are provided. In formula I, R₁ is H, OH, substituted or unsubstituted C₁ to C₃ alkyl, C₁ to C₃ perfluoroalkyl, or COR₆; R₆ is H, substituted or unsubstituted C₁ to C₄ alkyl, aryl, substituted or unsubstituted C₁ to C₄ alkoxy, substituted or unsubstituted C₁ to C₃ aminoalkyl; R₂ and R₃ are H, substituted or unsubstituted C₁ to C₆ alkyl, C₁ to C₆ perfluoroalkyl, substituted or unsubstituted C₂ to C₆ alkenyl, substituted or unsubstituted C₂ to C₆ alkynyl, substituted or unsubstituted C₃ to C₆ cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic; or R₂ and R₃ are fused to form spirocyclic rings; R₄ is NHR₇, OR₇, NHSO₂R₇, or OSO₂R₇; Q is O, S, NR₈, or CR₉R₁₀; or a pharmaceutically acceptable salt, ester, or prodrug thereof. Such compounds are useful as progesterone receptor modulators and for treating progesterone receptor related conditions.

Processes are provided for purifying a compound of the structure:

wherein, A, B, T, Q and R¹ are defined herein, and wherein the process includes dissolving the compound of formula I in a solution containing acetone, water and a base at about 30° C.; filtering the solution containing the compound of formula I at about 30° C.; and precipitating the purified compound of formula I by adjusting the filtered solution to an acidic pH. Desirably, the compound of formula I is 5-(2-thioxospiro[cyclohexane-1,3-[3H]indol]-5-yl)-1-methylpyrrole-2-carbonitrile or tanaproget.

Processes for preparing oxindoles, which can be utilized in the preparation of a variety of useful compounds, and methods for minimizing or preventing N-alkylation of amide containing compounds, including oxindoles, are provided. Also provided is a compound of the following structure:

Processes for preparing substituted oxindole-2-ones, and specifically the following, are described, wherein R¹-R⁴, R⁶, and n are defined herein. The processes include reacting a first alkali metal hydroxide, a tetraalkyl ammonium salt, a benzonitrile, and R⁶X or XCH₂(CH₂)_nX′, wherein R⁶ is C₁ to C₆ alkyl, substituted C₁ to C₆ alkyl, C₃ to C₈ cycloalkyl, substituted C₃ to C₈ cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, or substituted heterocyclic, X and X′ are, independently, leaving groups, and n is 1 to 5; (ii) reacting the product of step (i) with a second alkali metal hydroxide at a temperature of at least about 60° C.; (iii) reacting the product of step (ii) with an alkali alkoxide at a temperature of at least about 140° C. to form an oxindol-2-one; (iv) brominating the oxindol-2-one; and (v) coupling the brominated oxindol-2-one with a coupling reagent.

The present invention relates to a compound represented by the following formula:

or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a combination thereof, wherein R¹, R², and X are as defined herein. Compounds of the present invention are useful as progesterone receptor modulators.

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.

The invention relates to a modulator of nonsteroidal progesterone receptor with a structure of the general formula I or an acceptable salt on pharmacy and a preparation method thereof. The invention also relates to drug combination including compounds of the general formula I or an acceptable salt on pharmacy thereof and the antagonist activity of progesterone receptor which is provided by the compounds of the general formula I or the acceptable salt on pharmacy thereof; therefore, the invention can be used for preparing nonsteroidal drugs to prevent and (or) or treat symptoms or diseases such as secondary amenorrhea, functional bleeding disorder, uterine fibroids, endometriosis, polycystic ovary syndrome, breast cancer, contraceptive, induced labor, and termination of pregnancy, etc.

Retrosteroidal compounds corresponding to formula I, representing progesterone receptor modulators, and their production, and pharmaceutical preparations containing these compounds. These compounds are useful in the treatment of benign gynecological disorders such as endometriosis and uterine fibroids, as well as for female birth control and for hormone replacement therapy.

The present invention is directed to novel heteroatom containing tetracyclic derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders mediated by one or more estrogen receptors. The compounds of the invention are useful in the treatment of disorders associated with the depletion of estrogen such as hot flashes, vaginal dryness, osteopenia and osteoporosis; hormone sensitive cancers and hyperplasia of the breast, endometrium, cervix and prostate; endometriosis, uterine fibroids, osteoarthritis and as contraceptive agents, alone or in combination with a progestogen or progestogen antagonist.