C07J21/00

Benzoic acid derivatives of bile acid as FXR/TGR5 agonists and methods of use thereof

The present invention provides compounds of Formula I: ##STR00001##
pharmaceutical compositions comprising these compounds and methods of using these compounds to treat or prevent a disease or disorder mediated by FXR and/or TGR5.

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.

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Described herein are steroids of Formula (I):

##STR00001##

and pharmaceutically acceptable salts thereof; wherein R.sup.1, R.sup.2a, R.sup.2b, R.sup.3, R.sup.4, R.sup.5a, R.sup.5b, R.sup.6, and Z are 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.

COMPLEX AND STRUCTURALLY DIVERSE COMPOUNDS

The invention provides a novel, general, and facile strategy for the creation of small molecules with high structural and stereochemical complexity. Aspects of the methods include ring system distortion reactions that are systematically applied to rapidly convert readily available natural products to structurally complex compounds with diverse molecular architectures. Through evaluation of chemical properties including fraction of sp.sup.3 carbons, ClogP, and the number of stereogenic centers, these compounds are shown to be significantly more complex and diverse than those in standard screening collections. This approach is demonstrated with natural products (gibberellic acid, adrenosterone, and quinine) from three different structural classes, and methods are described for the application of this strategy to any suitable natural product.

SMALL MOLECULES ACTIVE AGAINST GRAM-NEGATIVE BACTERIA

Disclosed are compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I):

##STR00001##

and pharmaceutical compositions thereof. 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, 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, tinnitus, status epilepticus.

Neuroactive steroids, compositions, and uses thereof

Described herein are steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein R.sup.1, R.sup.2a, R.sup.2b, R.sup.3, R.sup.4, R.sup.5a, R.sup.5b, R.sup.6, and Z are 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. ##STR00001##

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein -----, R.sup.1, R.sup.2, R.sup.5, A and L 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##

METHODS FOR PREPARING DEOXYCHOLIC ACID

The present invention discloses method for preparing deoxycholic acid (DCA) or an ester thereof or a pharmaceutically acceptable salt thereof. Said compounds may be applied to remove a fat deposition.

PROCESS AND INTERMEDIATES FOR THE PRODUCTION OF 17(20)-ENE B-SECO STEROIDS

##STR00001##

The invention pertains to a process for producing a compound of formula (11) wherein R.sup.7 and R.sup.8 are each independently selected from H, halogen, alkyl, aryl, or alkylaryl, R.sup.42 is H or a protective group, R.sup.43 is H or R.sup.3, wherein R.sup.3 is a protective group, by contacting a compound of formula (10) with an olefmation reagent, wherein compound of formula (10) comprises a counter acid X.sup.1 when R.sup.42H and R.sup.43H.