C07J3/005

METHODS TO INDUCE TARGETED PROTEIN DEGRADATION THROUGH BIFUNCTIONAL MOLECULES

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.

NEUROACTIVE STEROIDS AND THEIR METHODS OF USE

Provided herein is a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein R.sup.2a, R.sup.2b, R.sup.3, R.sup.4a, R.sup.4b, R.sup.5, R.sup.6a, R.sup.6b, R.sup.11a, R.sup.11b, R.sup.15a, R.sup.15b, R.sup.16a, R.sup.16b, R.sup.18, R.sup.19, R.sup.20a, R.sup.20b, X, A, Z, q, u, r, s, t, m, and n are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) and methods of using the compounds, e.g., in the treatment of CNS-related disorders.

##STR00001##

Preparations of hydrophobic therapeutic agents, methods of manufacture and use thereof

The present invention further provides method of preparing nanocrystals of a hydrophobic therapeutic agent such as fluticasone or triamcinolone, pharmaceutical compositions (e.g., topical or intranasal compositions) thereof and methods for treating and/or preventing the signs and/or symptoms of disorders such as blepharitis, meibomian gland dysfunction or skin inflammation or a respiratory disease (e.g., asthma).

Compositions and methods for treating CNS disorders

Described herein are neuroactive steroids of the Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof, wherein custom character, A, R.sup.1, R.sup.2, R.sup.3a, R.sup.4a, R.sup.4b, R.sup.5, R.sup.7a, and R.sup.7b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

19-NOR C3, 3-DISUBSTITUTED C21-C-BOUND HETEROARYL STEROIDS AND METHODS OF USE THEREOF

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I):

##STR00001##

and pharmaceutically acceptable salts thereof; wherein custom-character, R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4a, and R.sup.4b are as defined herein, and A is a carbon bound substituted or unsubstituted 5- to 6-membered heteroaryl ring as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

Highly potent glucocorticoids

The present invention relates to novel glucocorticoid compounds. The invention also relates to methods of using these compounds, the synthesis of these compounds, and to compositions and formulations comprising the glucocorticoid compounds, and uses thereof.

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein (II), A, R.sup.1, R.sup.2, R.sup.3a, R.sup.4a, R.sup.4b, R.sup.5, R.sup.7a, and R.sup.7b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

##STR00001##

custom-character

METHODS TO INDUCE TARGETED PROTEIN DEGRADATION THROUGH BIFUNCTIONAL MOLECULES
20180085465 · 2018-03-29 ·

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.

PREPARATIONS OF HYDROPHOBIC THERAPEUTIC AGENTS, METHODS OF MANUFACTURE AND USE THEREOF

The present invention further provides method of preparing nanocrystals of a hydrophobic therapeutic agent such as fluticasone or triamcinolone, pharmaceutical compositions (e.g., topical or intranasal compositions) thereof and methods for treating and/or preventing the signs and/or symptoms of disorders such as blepharitis, meibomian gland dysfunction or skin inflammation or a respiratory disease (e.g., asthma).

Methods to induce targeted protein degradation through bifunctional molecules

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.