There are provided, inter alia, methods for decreasing mucus elasticity or decreasing mucus viscosity in a subject in need thereof, the methods including administering to the subject an effective amount of a dithiolsaccharide mucolytic agent, and compounds and pharmaceutical compositions useful for the methods.

There are provided, inter alia, methods for decreasing mucus elasticity or decreasing mucus viscosity in a subject in need thereof, the methods including administering to the subject an effective amount of a dithiolsaccharide mucolytic agent, and compounds and pharmaceutical compositions useful for the methods.

The present invention relates to methods of using compounds of Formula I,

##STR00001## wherein R.sup.1a, R.sup.1b, R.sup.2, R.sup.3, R.sup.4, W, Y, and Z are as described herein, and pharmaceutically acceptable salts thereof. The compounds are potentiators of Cystic Fibrosis Transmembrane conductance Regulator (CFTR). The invention also discloses pharmaceutical compositions comprising the compound, optionally in combination with additional therapeutic agents, and methods of potentiating, in mammals, including humans, CFTR by administration of the compounds. These compounds are useful for the treatment of cystic fibrosis (CF), asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), constipation, Diabetes mellitus, dry eye disease, pancreatitis, rhinosinusitis, Sjögren's Syndrome, and other CFTR associated disorders.

The present invention relates to methods of using compounds of Formula I,

##STR00001## wherein R.sup.1a, R.sup.1b, R.sup.2, R.sup.3, R.sup.4, W, Y, and Z are as described herein, and pharmaceutically acceptable salts thereof. The compounds are potentiators of Cystic Fibrosis Transmembrane conductance Regulator (CFTR). The invention also discloses pharmaceutical compositions comprising the compound, optionally in combination with additional therapeutic agents, and methods of potentiating, in mammals, including humans, CFTR by administration of the compounds. These compounds are useful for the treatment of cystic fibrosis (CF), asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), constipation, Diabetes mellitus, dry eye disease, pancreatitis, rhinosinusitis, Sjögren's Syndrome, and other CFTR associated disorders.

Cystic fibrosis is developed through mutation of Cystic Fibrosis Transmembrane conductance Regulator (CFTR), which is one type of chloride channel. An object of the present invention is to provide compounds effective in the treatment of cystic fibrosis that open a chloride channel different from CFTR, which is the cause of the disease, and do not depend on CFTR. Compounds of the present invention are compounds or pharmaceutically acceptable salts thereof that open calcium dependent chloride channels (CaCCs) via G-protein coupled receptor 39 (GPR39) agonism to have strong chloride ion-secretory action, and are represented by the following general formula (I): General formula (I): ##STR00001##
wherein, X represents a carboxyl group or a tetrazolyl group; Q represents a C.sub.1-C.sub.3 alkylene group, an oxygen atom, a sulfur atom, etc.; G represents a phenyl group where the phenyl group may have 1 to 3 substituents independently selected from the group consisting of a halogen atom, a cyano group, a C.sub.1-C.sub.6 alkyl group, etc.; R.sup.1 represents a C.sub.1-C.sub.6 alkyl group, etc.; R.sup.2 represents a C.sub.1-C.sub.6 alkyl group that may have 1 to 3 substituents independently selected from the following group A, or a group selected from the following group B: Group A: a phenyl group and a pyridyl group, wherein the phenyl group and the pyridyl group may have 1 to 3 substituents independently selected from the following group D; Group B: —OH, —O-M, —SH, —S-M, —NH.sub.2, —NH-M, and —N-M.sub.2, wherein M is a C.sub.1-C.sub.6 alkyl group that may have 1 or 2 substituents independently selected from the following group C, or a C.sub.3-C.sub.6 cycloalkyl group that may have 1 or 2 substituents independently selected from the following group C; Group C: a halogen atom, a cyano group, a phenyl group, a pyridyl group, etc., wherein the phenyl group and the pyridyl group may have 1 to 3 substituents independently selected from the following group D; and Group D: a halogen atom, a cyano group, a C.sub.1-C.sub.6 alkyl group, etc.

Cystic fibrosis is developed through mutation of Cystic Fibrosis Transmembrane conductance Regulator (CFTR), which is one type of chloride channel. An object of the present invention is to provide compounds effective in the treatment of cystic fibrosis that open a chloride channel different from CFTR, which is the cause of the disease, and do not depend on CFTR. Compounds of the present invention are compounds or pharmaceutically acceptable salts thereof that open calcium dependent chloride channels (CaCCs) via G-protein coupled receptor 39 (GPR39) agonism to have strong chloride ion-secretory action, and are represented by the following general formula (I): General formula (I): ##STR00001##
wherein, X represents a carboxyl group or a tetrazolyl group; Q represents a C.sub.1-C.sub.3 alkylene group, an oxygen atom, a sulfur atom, etc.; G represents a phenyl group where the phenyl group may have 1 to 3 substituents independently selected from the group consisting of a halogen atom, a cyano group, a C.sub.1-C.sub.6 alkyl group, etc.; R.sup.1 represents a C.sub.1-C.sub.6 alkyl group, etc.; R.sup.2 represents a C.sub.1-C.sub.6 alkyl group that may have 1 to 3 substituents independently selected from the following group A, or a group selected from the following group B: Group A: a phenyl group and a pyridyl group, wherein the phenyl group and the pyridyl group may have 1 to 3 substituents independently selected from the following group D; Group B: —OH, —O-M, —SH, —S-M, —NH.sub.2, —NH-M, and —N-M.sub.2, wherein M is a C.sub.1-C.sub.6 alkyl group that may have 1 or 2 substituents independently selected from the following group C, or a C.sub.3-C.sub.6 cycloalkyl group that may have 1 or 2 substituents independently selected from the following group C; Group C: a halogen atom, a cyano group, a phenyl group, a pyridyl group, etc., wherein the phenyl group and the pyridyl group may have 1 to 3 substituents independently selected from the following group D; and Group D: a halogen atom, a cyano group, a C.sub.1-C.sub.6 alkyl group, etc.

Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

There are provided, inter alia, methods for decreasing mucus elasticity or decreasing mucus viscosity in a subject in need thereof, the methods including administering to the subject an effective amount of a thiosaccharide mucolytic agent, and compounds and pharmaceutical compositions useful for the methods.

There are provided, inter alia, methods for decreasing mucus elasticity or decreasing mucus viscosity in a subject in need thereof, the methods including administering to the subject an effective amount of a thiosaccharide mucolytic agent, and compounds and pharmaceutical compositions useful for the methods.

Compounds of general formula (I) wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and X are as defined herein are inhibitors of the epithelial sodium channel (ENaC) and are useful for the treatment or prevention respiratory diseases and conditions, skin conditions and ocular conditions.

##STR00001##