The invention relates to 1,5-benzothiazepine and 1,2,5-benzothiadiazepine derivatives of formula (I). These compounds are bile acid modulators having apical sodium-dependent bile acid transporter (ASBT) and/or liver bile acid transport (LBAT) inhibitory activity. The invention also relates to pharmaceutical compositions comprising these compounds and to the use of these compounds in the treatment of cardiovascular diseases, fatty acid metabolism and glucose utilization disorders, gastrointestinal diseases and liver diseases.

The invention relates to 1,5-benzothiazepine and 1,2,5-benzothiadiazepine derivatives of formula (I). These compounds are bile acid modulators having apical sodium-dependent bile acid transporter (ASBT) and/or liver bile acid transport (LBAT) inhibitory activity. The invention also relates to pharmaceutical compositions comprising these compounds and to the use of these compounds in the treatment of cardiovascular diseases, fatty acid metabolism and glucose utilization disorders, gastrointestinal diseases and liver diseases.

Provided are compounds represented by Formula (I-A) and the pharmaceutically acceptable salts and solvates thereof, wherein R.sup.8, R.sup.9a, R.sup.9b, R.sup.9c, R.sup.9d, X, Y, Z, Z.sup.1, W, and (aa) are as defined as set forth in the specification. Provided are also compounds of Formula (I-A) for use to treat a condition or disorder responsive to Mcl-1 inhibition such as cancer. ##STR00001##

[Problem]

To provide a compound having a 15-PGDH inhibitory effect.

[Solution]

A compound represented by general formula (1) or a pharmacologically acceptable salt thereof.

Disclosed are a benzonitric heterocyclic compound, a preparation method therefor and the use thereof. Provided in the present invention is a benzonitric heterocyclic compound represented by formula I, or a pharmaceutically acceptable salt thereof, which can be used as a histone deacetylase inhibitor, has a selective inhibitory effect on HDAC6, and has characteristics such as a high efficiency, low toxicity and ideal pharmacokinetic properties.

##STR00001##

Disclosed are a benzonitric heterocyclic compound, a preparation method therefor and the use thereof. Provided in the present invention is a benzonitric heterocyclic compound represented by formula I, or a pharmaceutically acceptable salt thereof, which can be used as a histone deacetylase inhibitor, has a selective inhibitory effect on HDAC6, and has characteristics such as a high efficiency, low toxicity and ideal pharmacokinetic properties.

##STR00001##

The present invention relates to a process for the preparation of a compound of formula (I) comprising: reacting a compound of formula (II) with a compound of formula (III) in the presence of a triazine compound to obtain a compound of formula (IV), and deprotecting said compound of formula (IV) to obtain the compound of formula (I). The compound of formula (I) can be prepared by the process according to the present invention in high yields and high purity. In addition, the process according to the present invention does not use a large amount of solvents or require a purification process of intermediate compounds.

The present invention relates to a process for the preparation of a compound of formula (I) comprising: reacting a compound of formula (II) with a compound of formula (III) in the presence of a triazine compound to obtain a compound of formula (IV), and deprotecting said compound of formula (IV) to obtain the compound of formula (I). The compound of formula (I) can be prepared by the process according to the present invention in high yields and high purity. In addition, the process according to the present invention does not use a large amount of solvents or require a purification process of intermediate compounds.

Provided herein are methods of treating or ameliorating a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a pediatric liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.

Provided herein are methods of treating or ameliorating a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a pediatric liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.