Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein, R.sup.1, R.sup.2a, R.sup.2b, R.sup.3 and A 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##

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein, R.sup.1, R.sup.2a, R.sup.2b, R.sup.3 and A 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##

The invention provides compounds of general structure I: (Ar.sup.1—Ar.sup.2—Ar.sup.3-E-P(=D)R.sub.2-).sub.nM.sub.mX.sub.nL.sub.n″. In this structure: •Ar.sup.1, Ar.sup.2 and Ar.sup.3 are aromatic groups wherein: —Ar.sup.1 and Ar.sup.3 are in a 1,3 relationship on Ar.sup.2, —each of Ar.sup.1, Ar.sup.2 and Ar.sup.3 optionally comprises one or more ring substituents of formula YR′.sub.r wherein each Y independently is absent or is O, S, B, N or Si and each R′ is independently H, halogen, alkyl, cycloalkyl, aryl or heteroaryl and r is 1, 2 or 3, where r is 1 if Y is absent or is O or S, 2 if Y is B or N and 3 if Y is Si, —Ar.sup.1, Ar.sup.2 and Ar.sup.3 are each independently carbocyclic or heterocyclic and each is independently monocyclic, bicyclic or polycyclic and each ring of each of Ar.sup.1, Ar.sup.2 and Ar.sup.3 independently has 5, 6 or 7 ring atoms; •E is absent or is selected from the group consisting of O, S, NR″, SiR″.sub.2, AsR″.sub.2 and CR″.sub.2; •M is a complexing metal; •X is selected from the group consisting of H, F, Br, CI, I, OTf, dba (dibenzylidene acetone), OC(═O)CF.sub.3 and OAc; •L is selected from the group consisting of PR″.sub.2, NR″.sub.2, OR″, SR″, SiR″.sub.3, AsR″.sub.3, alkene, alkyne, aryl and heteroaryl, each of said alkene, alkyne, aryl and heteroaryl being optionally substituted, for example with one or more halogens and/or with one or more R groups as defined herein; •each R is independently alkyl, cycloalkyl, heterocyclyl, heterocycloalkyl, aryl or -, heteroaryl; •D is absent or is ═S or —O or —Z-linker-Z—, where each Z independently is O or NH or N-alkyl and linker is an alkyl chain of 2-5 carbon atoms in length; •each R″ is independently H, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each other than H being optionally substituted, or R″.sub.2 is —Z-linker-Z— as defined above; and •m is 0 or 1 or 2; wherein if m is 0, n is 1, n′ and n″ are 0 and -- is absent; and if m is 1 or 2, n is 1 or 2 and n′ and n″ are integers such that the coordination sphere of M is filled, and D is absent.

The invention provides compounds of general structure I: (Ar.sup.1—Ar.sup.2—Ar.sup.3-E-P(=D)R.sub.2-).sub.nM.sub.mX.sub.nL.sub.n″. In this structure: •Ar.sup.1, Ar.sup.2 and Ar.sup.3 are aromatic groups wherein: —Ar.sup.1 and Ar.sup.3 are in a 1,3 relationship on Ar.sup.2, —each of Ar.sup.1, Ar.sup.2 and Ar.sup.3 optionally comprises one or more ring substituents of formula YR′.sub.r wherein each Y independently is absent or is O, S, B, N or Si and each R′ is independently H, halogen, alkyl, cycloalkyl, aryl or heteroaryl and r is 1, 2 or 3, where r is 1 if Y is absent or is O or S, 2 if Y is B or N and 3 if Y is Si, —Ar.sup.1, Ar.sup.2 and Ar.sup.3 are each independently carbocyclic or heterocyclic and each is independently monocyclic, bicyclic or polycyclic and each ring of each of Ar.sup.1, Ar.sup.2 and Ar.sup.3 independently has 5, 6 or 7 ring atoms; •E is absent or is selected from the group consisting of O, S, NR″, SiR″.sub.2, AsR″.sub.2 and CR″.sub.2; •M is a complexing metal; •X is selected from the group consisting of H, F, Br, CI, I, OTf, dba (dibenzylidene acetone), OC(═O)CF.sub.3 and OAc; •L is selected from the group consisting of PR″.sub.2, NR″.sub.2, OR″, SR″, SiR″.sub.3, AsR″.sub.3, alkene, alkyne, aryl and heteroaryl, each of said alkene, alkyne, aryl and heteroaryl being optionally substituted, for example with one or more halogens and/or with one or more R groups as defined herein; •each R is independently alkyl, cycloalkyl, heterocyclyl, heterocycloalkyl, aryl or -, heteroaryl; •D is absent or is ═S or —O or —Z-linker-Z—, where each Z independently is O or NH or N-alkyl and linker is an alkyl chain of 2-5 carbon atoms in length; •each R″ is independently H, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each other than H being optionally substituted, or R″.sub.2 is —Z-linker-Z— as defined above; and •m is 0 or 1 or 2; wherein if m is 0, n is 1, n′ and n″ are 0 and -- is absent; and if m is 1 or 2, n is 1 or 2 and n′ and n″ are integers such that the coordination sphere of M is filled, and D is absent.

The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein, R.sup.1, R.sup.2a, R.sup.2b, R.sup.3 and A 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##

The invention relates to a process for the synthesis of Cariprazine, an antipsychotic compound useful in the treatment of positive and negative symptoms associated to schizophrenia, with the following structural formula: (A) The invention further relates to the synthesis of intermediates useful in the preparation of Cariprazine. ##STR00001##

The invention relates to a process for the synthesis of Cariprazine, an antipsychotic compound useful in the treatment of positive and negative symptoms associated to schizophrenia, with the following structural formula: (A) The invention further relates to the synthesis of intermediates useful in the preparation of Cariprazine. ##STR00001##

A process for preparing compounds of formula (I), or a salt or solvate thereof, including Brexpiprazole, which process comprises cyclization of a compound of formula (II) or (III), or a salt or solvate thereof. The invention also refers to intermediates of said process. ##STR00001##