Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.

Inhibitors of factor xa

Novel benzamide compounds including their pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives having activity against mammalian factor Xa are described. Compositions containing such compounds are also described. The compounds and compositions are useful in vitro or in vivo for preventing or treating coagulation disorders.

Benzamides and related inhibitors of factor Xa

The invention relates to new disubstituted bicyclic heterocycles of the general formula (I): Ra-A-Het-B-Ar-E, in which A, B, Ar, Het and Ra are defined as in claim 1. The invention also relates to their tautomers, their stereoisomers, their mixtures, and their salts, which have valuable properties. The compounds of the above general formula (I), in which E is a cyano group, thus represent valuable intermediate products for the production of the other compounds of the general formula (I). Furthermore, the compounds of the above general formula (I), in which E stands for a RbNH-C(=NH)-group, have valuable pharmacological properties, in particular in inhibiting thrombin and prolonging thrombin time.

Disubstituted bicyclic heterocycles, their production and use as medicaments

A biphasic controlled release delivery system for pharmaceuticals which have high water solubility, such as the antidiabetic metformin HCl salt, is provided which provides a dosage form that has prolonged gastric residence and includes (1) an inner solid particulate phase formed of substantially uniform granules containing a pharmaceutical having a high water solubility, and one or more hydrophilic polymers, one or more hydrophobic polymers and/or one or more hydrophobic materials such as one or more waxes, fatty alcohols and/or fatty acid esters, and (2) an outer solid continuous phase in which the above granules of inner solid particulate phase are embedded and dispersed throughout, the outer solid continuous phase including one or more hydrophilic polymers, one or more hydrophobic polymers and/or one or more hydrophobic materials such as one or more waxes, fatty alcohols and/or fatty acid esters, which may be compressed into tablets or filled into capsules. Methods for forming the so-described biphasic controlled release delivery system and using such biphasic controlled release delivery system for treating diabetes are also provided.

Biphasic controlled release delivery system for high solubility pharmaceuticals and method

This invention is directed to compounds of formula (III) wherein B, C, D, E, R?1, R2 and R3? are disclosed herein. These compounds are disclosed as being useful as anti-coagulants.

Ortho-anthranilamide derivatives as anti-coagulants

An anticoagulant agent which comprises, as an active ingredient, an aromatic amidine derivative represented by the following general formula (1) or a salt thereof: ##STR1## wherein the group represented by ##STR2## is a group selected from indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, naphthyl, tetrahydronaphthyl and indanyl; X is a single bond, an oxygen atom, a sulfur atom or a carbonyl group; and Y is a saturated or unsaturated 5- or 6-membered heterocyclic moiety or cyclic hydrocarbon moiety optionally having a substituent group, an amino group optionally having a substituent group or an aminoalkyl group optionally having a substituent group. The inventive compound has a high anticoagulant capacity based on its excellent FXa inhibition activity.

Aromatic amidine derivatives and salts thereof

PURPOSE:To obtain a new aromatic amidine derivative capable of exhibiting an anti-blood coagulating action based on its excellent FXa inhibiting action. CONSTITUTION:A compound of formula I [R is H or alkoxy; R is H, alkyl, alkoxy, carboxyl, alkoxylcarbonyl, carbonylalkyl or alkoxycarbonylalkyl; R is H, carboxyl, alkoxycarbonyl, carboxyalkyl, alkoxycarbonylalkyl, carboxyalkoxy, etc.; R is H, OH, alkyl or alkoxy; (n) is 0-4; A is l-4C alkylene which may be substituted; X is single bond, O, S or CO; Y is 5-6 membered heterocyclic group, cyclic hydrocarbon group, amino or aminoalkyl, which may be substituted, respectively; a group of formula II is indolyl, benzofuranyl, benzothienyl, naphthyl, etc.), e.g. 2-[4-[(1-acetoimidoyl-3-pyrrolidinyl) oxy]phenyl]-3-(7-amidino-2-naphthyl)propionic acid. This compound is produced from a nitrile compound of formula III.

Aromatic amidine derivative and its salt

FIELD: organic chemistry, pharmacy. SUBSTANCE: invention describes new aromatic amidine derivatives of the general formula (I) where R 2 means hydrogen atom or lower alkoxy-group; R 2 means hydrogen atom, lower alkyl group, lower alkoxy-group, carboxyl-group, carboxyalkyl-group with 2-5 carbon atoms or alkoxycarbonyl-group with 2-5 carbon atoms; R 3 means hydrogen atom, carboxyl-group, carboxyalkyl-group with 2-5 carbon atoms, alkoxycarbonylalkyl-group with 3-6 carbon atoms, carboxyalkoxyl-group with 2-5 carbon atoms and alkoxycarbonylalkoxyl-group with 3-6 carbon atoms; R 4 means hydrogen atom, hydroxyl group or lower alkoxy-group; n is the whole number from 0 to 2; A is alkylene group with 1-4 carbon atoms that can be substituted with one or two substituents taken among hydroxyalkyl-group with 1-4 carbon atoms, carboxyl, alkoxycarbonyl-group with 2-5 carbon atoms and carboxyalkyl-group with 2-5 carbon atoms; X is a simple bond, oxygen or sulfur atom or carbonyl-group; Y is saturated or unsaturated 5- or 6-membered heterocyclic fragment containing one or two heteroatoms taken among nitrogen, oxygen, sulfur atoms or cyclic hydrocarbon fragment that can be substituted with amino-group, carbamoyl, mono- or dialkylcarbamoyl, alkanoimido-yl, lower alkyl, lower alkanoyl, alkoxycarbonylimine, benzylimidoyl, alkanoylamino-group, alkylamine; saturated or unsaturated 5- or 6-membered cyclic hydrocarbon fragment that can be substituted with aminoalkyl-group or alkanoylamino-alkyl-group; or Y is amino-group that can be substituted with pyrrolidinyl or pyridinyl group; and the group of the formula (II) is taken among indolyl, benzofuranyl, benzothienyl, benzothiazolyl, naphthyl, tetrahydronaphthyl, benzimidazolyl; or its pharmaceutically acceptable salt. The end compounds show the strong anticoagulating effect by reversible inhibition of blood activated clotting factor ("FXA"). Invention describes also an anticoagulating composi

Inamura Kazue

Papers

Aromatic amidine derivatives and salts thereof

Aromatic amidine derivative and its salt

Aromatic amidine derivative and pharmaceutical composition

Process for production of amidinoindole derivs, and salts thereof