The present invention relates to a novel serotonin reuptake inhibitor which also exhibits 5-HT.sub.2C antagonistic action (antidepressive and anxiolytic effects), in particular, 5-HT.sub.2C inverse agonistic action comprising Compound (1): ##STR00001## or a pharmaceutically acceptable salt thereof wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently hydrogen or C.sub.1-6 alkyl etc.; R.sup.5 is C.sub.4-7 alkyl or —(CR.sup.8R.sup.9).sub.r-E; R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are independently hydrogen, fluorine or C.sub.1-6 alkyl; A is C.sub.6-10 aryl or heteroaryl etc.; r is 1, 2, 3 or 4; E is C.sub.3-8 cycloalkyl or C.sub.6-10 aryl etc.; L is oxygen, sulfur or —NR.sup.10—; n is 1, 2 or 3; R.sup.10 is hydrogen or C.sub.1-6 alkyl etc.; and X is hydrogen or halogen etc.

The invention relates to N-hydroxysulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia/reperfusion injury. Novel N-hydroxysulfonamide derivatives release HNO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxysulfonamide derivatives.

The invention relates to N-hydroxysulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia/reperfusion injury. Novel N-hydroxysulfonamide derivatives release HNO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxysulfonamide derivatives.

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided.

##STR00001##

In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and

##STR00002##

in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided.

##STR00001##

In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and

##STR00002##

in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided. ##STR00001## In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and ##STR00002## in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.

A compound represented by Formula (I), or a salt or N-oxide compound thereof is provided. ##STR00001## In Formula (I), A.sup.1 to A.sup.4 each independently represents a carbon atom or nitrogen atom, X.sup.1 represents a C1-6 alkyl group or the like, n represents the number of X.sup.1 groups, R.sup.1 represents a C1-6 alkylthio group or the like, and D is a group represented by Formula (D-1) or (D-2), and ##STR00002## in Formula (D-1) and (D-2), * represents a binding position, Q represents a C1-6 alkyl group or the like, B.sup.1 and B.sup.2 each independently represents a nitrogen atom or the like, R.sup.2 represents a C1-6 alkyl group or the like that is bound to one of the nitrogen atoms in Formula (D-1), B.sup.3 and B.sup.4 each independently represents a nitrogen atom or carbon atom, R.sup.4 represents a C1-6 alkyl group or the like, and m represents the number of R.sup.4 groups.

In one aspect, the invention relates to compounds having the formula XII: ##STR00001##
where R.sup.a, R.sup.b, R.sup.2, R.sup.7, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds described herein are prodrugs of compounds having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.

In one aspect, the invention relates to compounds having the formula XII: ##STR00001##
where R.sup.a, R.sup.b, R.sup.2, R.sup.7, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds described herein are prodrugs of compounds having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.

The present invention relates to sulfonylureas and sulfonylthioureas of formula (I) comprising a 5-membered heteroaryl ring attached to the sulfonyl group, wherein the heteroaryl ring is di-substituted at the 3- and 4-positions relative to the point of attachment of the sulfonyl group, and wherein the group attached to the terminal nitrogen atom of the urea group is either a 1,2, 3,5,6, 7-hexahydro-s-indacen-4-yl group substituted at the 8-position, or a heteroaryl group substituted at the alpha and alpha′ positions. The present invention further relates to salts, solvates and prodrugs of such compounds, to pharmaceutical compositions comprising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by NLRP3 inhibition.

##STR00001##