Disclosed is a compound of formula (I)

##STR00001## or a stereoisomer thereof, or a salt of any of the foregoing and to processes for its preparation. The compounds of formula (I) are useful in the treatment TRPML1-mediated disorders or diseases.

A compound of formula (I):

##STR00001##

wherein: R.sup.1 is selected from (i) H, (ii) C.sub.3-6cycloalkyl, (iii) C.sub.3-7heterocyclyl optionally substituted with a group selected from: methyl and ester, and (iv) linear or branched C.sub.1-4alkyl optionally substituted with a group selected from: alkoxy, amino, amido, acylamido, acyloxy, alkyl carboxyl ester, alkyl carbamoyl, alkyl carbamoyl ester, phenyl, phosphonate ester, C.sub.3-7heterocyclyl optionally substituted with a group selected from methyl and oxo, and a naturally occurring amino acid, optionally N-substituted with a group selected from methyl, acetyl and boc; A.sup.1 is CR.sup.A or N; A.sup.2 is CR.sup.B or N; A.sup.3 is CR.sup.C or N; A.sup.4 is CR.sup.D or N; where no more than two of A.sup.1, A.sup.2, A.sup.3, and A.sup.4 may be N; one or two of R.sup.A, R.sup.B, R.sup.C, and R.sup.D, (if present) are selected from H, F, Cl, Br, Me, CF.sub.3, cyclopropyl, cyano, OMe, OEt, CH.sub.2OH, CH.sub.2OMe and CH.sub.2NMe.sub.2; the remainder of R.sup.A, R.sup.B, R.sup.C, and R.sup.D, (if present) are H; Y is O, NH or CH.sub.2; R.sup.Y is selected from: (RYA) and (RYB).

A compound of formula (I):

##STR00001##

wherein: R.sup.1 is selected from (i) H, (ii) C.sub.3-6cycloalkyl, (iii) C.sub.3-7heterocyclyl optionally substituted with a group selected from: methyl and ester, and (iv) linear or branched C.sub.1-4alkyl optionally substituted with a group selected from: alkoxy, amino, amido, acylamido, acyloxy, alkyl carboxyl ester, alkyl carbamoyl, alkyl carbamoyl ester, phenyl, phosphonate ester, C.sub.3-7heterocyclyl optionally substituted with a group selected from methyl and oxo, and a naturally occurring amino acid, optionally N-substituted with a group selected from methyl, acetyl and boc; A.sup.1 is CR.sup.A or N; A.sup.2 is CR.sup.B or N; A.sup.3 is CR.sup.C or N; A.sup.4 is CR.sup.D or N; where no more than two of A.sup.1, A.sup.2, A.sup.3, and A.sup.4 may be N; one or two of R.sup.A, R.sup.B, R.sup.C, and R.sup.D, (if present) are selected from H, F, Cl, Br, Me, CF.sub.3, cyclopropyl, cyano, OMe, OEt, CH.sub.2OH, CH.sub.2OMe and CH.sub.2NMe.sub.2; the remainder of R.sup.A, R.sup.B, R.sup.C, and R.sup.D, (if present) are H; Y is O, NH or CH.sub.2; R.sup.Y is selected from: (RYA) and (RYB).

The present invention provides compounds useful as inhibitors of ATP citrate lyase (ACLY), compositions thereof, and methods of using the same.

The invention relates to compounds as described herein and pharmaceutical compositions containing them. Also, the invention relates to methods for expanding stem cells and/or progenitor cells and methods for treating a hematopoietic disorder/malignancy, an autoimmune disease and/or an inherited immunodeficient disease.

A compound of formula (I), wherein R.sup.1 is selected from (i) H, (ii) C.sub.3-6cycloalkyl, (iii) C.sub.3-7heterocyclyl optionally substituted with a group selected from: methyl and ester, and (iv) linear or branched C.sub.1-4alkyl optionally substituted with a group selected from: alkoxy, amino, amido, acylamido, acyloxy, alkyl carboxyl ester, alkyl carbamoyl, alkyl carbamoyl ester, phenyl, phosphonate ester, C.sub.3-7heterocyclyl optionally substituted with a group selected from methyl and oxo, and a naturally occurring amino acid, optionally N-substituted with a group selected from methyl, acetyl and boc; A.sup.1 is CR.sup.A or N; A.sup.2 is CR.sup.B or N; A.sup.3 is CR.sup.C or N; A.sup.4 is CR.sup.D or N; where no more than two of A.sup.1, A.sup.2, A.sup.3, and A.sup.4 may be N; one or two of R.sup.A, R.sup.B, R.sup.C, and R.sup.D, (if present) are selected from H, F, Cl, Br, Me, CF.sub.3, cyclopropyl, cyano, OMe, OEt, CH.sub.2OH, CH.sub.2OMe and CH.sub.2NMe.sub.2; the remainder of R.sup.A, R.sup.B, R.sup.C, and R.sup.D, (if present) are H; Y is O, NH or CH.sub.2; R.sup.Y is selected from: (RYA) and (RYB).

A compound of formula (I), wherein R.sup.1 is selected from (i) H, (ii) C.sub.3-6cycloalkyl, (iii) C.sub.3-7heterocyclyl optionally substituted with a group selected from: methyl and ester, and (iv) linear or branched C.sub.1-4alkyl optionally substituted with a group selected from: alkoxy, amino, amido, acylamido, acyloxy, alkyl carboxyl ester, alkyl carbamoyl, alkyl carbamoyl ester, phenyl, phosphonate ester, C.sub.3-7heterocyclyl optionally substituted with a group selected from methyl and oxo, and a naturally occurring amino acid, optionally N-substituted with a group selected from methyl, acetyl and boc; A.sup.1 is CR.sup.A or N; A.sup.2 is CR.sup.B or N; A.sup.3 is CR.sup.C or N; A.sup.4 is CR.sup.D or N; where no more than two of A.sup.1, A.sup.2, A.sup.3, and A.sup.4 may be N; one or two of R.sup.A, R.sup.B, R.sup.C, and R.sup.D, (if present) are selected from H, F, Cl, Br, Me, CF.sub.3, cyclopropyl, cyano, OMe, OEt, CH.sub.2OH, CH.sub.2OMe and CH.sub.2NMe.sub.2; the remainder of R.sup.A, R.sup.B, R.sup.C, and R.sup.D, (if present) are H; Y is O, NH or CH.sub.2; R.sup.Y is selected from: (RYA) and (RYB).

The disclosure of a compound of Formula (I) or a pharmaceutically acceptable salt thereof (I) The variables W, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are defined in the disclosure. The disclosure provides a compound or salt of Formula (I) together with a pharmaceutically acceptable carrier. The disclosure also provides methods of treating a patient for Parkinson's disease and related syndromes, dyskinesia, especially dyskinesias secondary to treating Parkinson's disease with L-DOPA, neurodegenerative disorders such as Alzheimer's disease and dementia, Huntington's disease, restless legs syndrome, bipolar disorder and depression, schizophrenia, cognitive dysfunction, or substance use disorders, the methods comprising administering a compound of Formula I or salt thereof to the patient. The disclosure provides combination methods of treatment in which the compound of Formula (I) is administered to the patient together with one or more additional active agents.

The disclosure of a compound of Formula (I) or a pharmaceutically acceptable salt thereof (I) The variables W, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are defined in the disclosure. The disclosure provides a compound or salt of Formula (I) together with a pharmaceutically acceptable carrier. The disclosure also provides methods of treating a patient for Parkinson's disease and related syndromes, dyskinesia, especially dyskinesias secondary to treating Parkinson's disease with L-DOPA, neurodegenerative disorders such as Alzheimer's disease and dementia, Huntington's disease, restless legs syndrome, bipolar disorder and depression, schizophrenia, cognitive dysfunction, or substance use disorders, the methods comprising administering a compound of Formula I or salt thereof to the patient. The disclosure provides combination methods of treatment in which the compound of Formula (I) is administered to the patient together with one or more additional active agents.

The present disclosure relates to heterocyclic compounds, pharmaceutically acceptable salts thereof, and pharmaceutical preparations thereof. Also described herein are compositions and the use of such compounds in methods of treating diseases and conditions mediated by deficient CFTR activity, in particular cystic fibrosis.