The present invention relates to crystal modifications of N-{(2R)-2-[({[3,3-dibutyl-7-(methyl-thio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,5-benzothiazepin-8-yl]oxy}acetyl)amino]-2-phenylethanolyl}glycine (elobixibat), more specifically crystal modifications I, IV, MeOH-1, EtOH-1, 1-PrOH-1 and 2-PrOH-1. The invention also relates to a process for the preparation of these crystal modifications and to a pharmaceutical composition comprising crystal modification IV.

The present invention relates to crystal modifications of N-{(2R)-2-[({[3,3-dibutyl-7-(methyl-thio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,5-benzothiazepin-8-yl]oxy}acetyl)amino]-2-phenylethanolyl}glycine (elobixibat), more specifically crystal modifications I, IV, MeOH-1, EtOH-1, 1-PrOH-1 and 2-PrOH-1. The invention also relates to a process for the preparation of these crystal modifications and to a pharmaceutical composition comprising crystal modification IV.

The present invention relates to crystal modifications of N-{(2R)-2-[({[3,3-dibutyl-7-(methyl-thio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,5-benzothiazepin-8-yl]oxy}acetyl)amino]-2-phenylethanolyl}glycine (elobixibat), more specifically crystal modifications I, IV, MeOH-1, EtOH-1, 1-PrOH-1 and 2-PrOH-1. The invention also relates to a process for the preparation of these crystal modifications and to a pharmaceutical composition comprising crystal modification IV.

Tricyclic dibenzothiazepine compounds for use in the treatment of respiratory depression.

A compound with the following general formula (I) and a general method for making this compound are provided, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15 and R.sup.16 are each independently selected from the group that includes H, halogen, nitro, cyano, alkyl, aryl, alkoxy, cycloalkyl, heteroalkyl, heterocyclyl, aralkyl, heteroaryl and heteroaralkyl. ##STR00001##

A compound with the following general formula (I) and a general method for making this compound are provided, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15 and R.sup.16 are each independently selected from the group that includes H, halogen, nitro, cyano, alkyl, aryl, alkoxy, cycloalkyl, heteroalkyl, heterocyclyl, aralkyl, heteroaryl and heteroaralkyl. ##STR00001##

The invention provides a process for preparing a 2,3,4,5-tetrahydro[1,4]benzothiazepine of formula: ##STR00001##
by reacting a [2-(acylaminoethyl)thio]arene of formula ##STR00002##
with an aldehyde or a multimer thereof, and with an acid. The invention also provides for first reacting the [2-(acylaminoethyl)thio]arene with the aldehyde or multimer thereof and a base to form an [N-hydroxymethyl-2-[acylaminoethyl)thio]arene of formula ##STR00003##
then treating the [N-hydroxymethyl-2-(acylaminoethyl)thio]arene with the acid to form the 2,3,4,5-tetrahydro[1,4]benzothiazepine.

The invention provides a process for preparing a 2,3,4,5-tetrahydro[1,4]benzothiazepine of formula: ##STR00001##
by reacting a [2-(acylaminoethyl)thio]arene of formula ##STR00002##
with an aldehyde or a multimer thereof, and with an acid. The invention also provides for first reacting the [2-(acylaminoethyl)thio]arene with the aldehyde or multimer thereof and a base to form an [N-hydroxymethyl-2-[acylaminoethyl)thio]arene of formula ##STR00003##
then treating the [N-hydroxymethyl-2-(acylaminoethyl)thio]arene with the acid to form the 2,3,4,5-tetrahydro[1,4]benzothiazepine.

Provided herein are compounds that modulate the activity of inhibitor of apoptosis proteins (IAPs), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

The disclosure pertains to chemical entities such as a compound or a pharmaceutically acceptable salt that inhibit inflammatory responses by, for example, inhibiting the oligomerization of Apoptosis-associated speck-like protein containing a C-terminal caspase-recruitment domain (ASC). Also provided are methods of treating various disease states using compounds that inhibit oligomerization of ASC protein.