This invention relates to compounds that are agonists of the muscarinic M.sub.1 and/or M.sub.4 receptor and which are useful in the treatment of diseases mediated by the muscarinic M.sub.1 and M.sub.4 receptors. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula (1) ##STR00001##
wherein X.sup.1; X.sup.2; R.sup.1 and R.sup.4 are as defined herein.

Disclosed are compounds useful, for example, in methods of treating hyperproliferative disorders such as cancer, methods of arresting the cell cycle in cancer cells, methods of inhibiting glutathione synthesis in cancer cells, and associated compounds for use and uses in medicaments. In certain embodiments, the methods, uses and compounds are provided with reference to compounds of the structural formulae (Ia), (Ib), (Ic), (Id) and (Ie), in which R.sup.1, L.sup.1, L.sup.2, Q, L.sup.3, R.sup.3, L.sup.4, R.sup.4, L.sup.5, and R.sup.5 are as described herein. In certain embodiments, compounds disclosed herein are especially active against cancers having a mutant KRAS gene. ##STR00001##

Disclosed are compounds useful, for example, in methods of treating hyperproliferative disorders such as cancer, methods of arresting the cell cycle in cancer cells, methods of inhibiting glutathione synthesis in cancer cells, and associated compounds for use and uses in medicaments. In certain embodiments, the methods, uses and compounds are provided with reference to compounds of the structural formulae (Ia), (Ib), (Ic), (Id) and (Ie), in which R.sup.1, L.sup.1, L.sup.2, Q, L.sup.3, R.sup.3, L.sup.4, R.sup.4, L.sup.5, and R.sup.5 are as described herein. In certain embodiments, compounds disclosed herein are especially active against cancers having a mutant KRAS gene. ##STR00001##

Described herein are small molecule splicing modulator compounds that modulate splicing of mRNA, such as pre-mRNA, encoded by genes, and methods of use of the small molecule splicing modulator compounds for modulating splicing and treating diseases and conditions.

Described herein are small molecule splicing modulator compounds that modulate splicing of mRNA, such as pre-mRNA, encoded by genes, and methods of use of the small molecule splicing modulator compounds for modulating splicing and treating diseases and conditions.

Provided herein are piperidine dione compounds having the following structure: ##STR00001## wherein R.sup.N, R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, L, V, m, and n are as defined herein, compositions comprising an effective amount of a piperidine dione compound, and methods for treating or preventing an androgen receptor mediated disease.

The present invention is relates to a compound of formula (I),

##STR00001##

wherein
X.sup.1, X.sup.2 and X.sup.3 are, independently of each other, N or CH; with the proviso that at least two of X.sup.1, X.sup.2 and X.sup.3 are N;
Y is N or CH;
R.sup.1 and R.sup.2 are independently of each other (iii) a morpholinyl of formula (II)

##STR00002##

wherein the arrow denotes the bond in formula (I); and
wherein R.sup.3 and R.sup.4 are independently of each other H, C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, CN, or C(O)O—C.sub.1-C.sub.2alkyl; or R.sup.3 and R.sup.4 form together a bivalent residue —R.sup.5R.sup.6— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2—O—CH.sub.2—, —CH.sub.2—NH—CH.sub.2—, or any of the structures

##STR00003##

wherein the arrows denote the bonds in formula (II); or (iv) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R.sup.7; wherein R.sup.7 is independently at each occurrence C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, C.sub.3-C.sub.6cycloalkyl; or two R.sup.7 substituents form together a bivalent residue —R.sup.8R.sup.9— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2—O—CH.sub.2— or —O—CH.sub.2CH.sub.2—O—;
with the proviso that at least one of R.sup.1 and R.sup.2 is a morpholinyl of formula II;
and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a neurological disorder in a subject.

The present invention is relates to a compound of formula (I),

##STR00001##

wherein
X.sup.1, X.sup.2 and X.sup.3 are, independently of each other, N or CH; with the proviso that at least two of X.sup.1, X.sup.2 and X.sup.3 are N;
Y is N or CH;
R.sup.1 and R.sup.2 are independently of each other (iii) a morpholinyl of formula (II)

##STR00002##

wherein the arrow denotes the bond in formula (I); and
wherein R.sup.3 and R.sup.4 are independently of each other H, C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, CN, or C(O)O—C.sub.1-C.sub.2alkyl; or R.sup.3 and R.sup.4 form together a bivalent residue —R.sup.5R.sup.6— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2—O—CH.sub.2—, —CH.sub.2—NH—CH.sub.2—, or any of the structures

##STR00003##

wherein the arrows denote the bonds in formula (II); or (iv) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R.sup.7; wherein R.sup.7 is independently at each occurrence C.sub.1-C.sub.3alkyl optionally substituted with one or two OH, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.3alkyl, C.sub.3-C.sub.6cycloalkyl; or two R.sup.7 substituents form together a bivalent residue —R.sup.8R.sup.9— selected from C.sub.1-C.sub.3alkylene optionally substituted with 1 to 4 F, —CH.sub.2—O—CH.sub.2— or —O—CH.sub.2CH.sub.2—O—;
with the proviso that at least one of R.sup.1 and R.sup.2 is a morpholinyl of formula II;
and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a neurological disorder in a subject.

The present invention relates to novel [1,2,4]triazolo[1,5-a]pyrimidin-yl derivatives as inhibitors of phosphodiesterase 2 (PDE2). The invention is also directed to pharmaceutical compositions comprising the compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which PDE2 is involved, such as neurological and psychiatric disorders.

This invention is directed to compounds of formula (I):

##STR00001##

where r, q, R, R.sup.2, R.sup.3, R.sup.4, R.sup.5a, R.sup.5b, R.sup.5c, R.sup.6a, R.sup.6b, R.sup.6c, R.sup.7, R.sup.8, and R.sup.9 are described herein, as single stereoisomers or as mixtures of stereoisomers, or pharmaceutically acceptable salts, solvates, clathrates, polymorphs, ammonium ions, N-oxides or prodrugs thereof; which are leukotriene A.sub.4 hydrolase inhibitors and therefore useful in treating inflammatory disorders. Pharmaceutical compositions comprising the compounds of the invention and methods of preparing the compounds of the invention are also disclosed.