US 6,221,907 B1 · Tricyclic compounds having activity specific for integrins, particularly alphanubeta3 integrins, method for preparing same, intermediates therefor, use of said compounds as drugs, and pharmaceutical compositions containing same

Abstract

The subject of the invention is the products of formula (I): in which R1, R2, R3, R4, R5 and G are as defined in the description, the dotted lines represent an optional second bond, as well as the addition salts with acids and bases and the esters, their preparation process and the intermediates of this process, their use as medicines and the pharmaceutical compositions containing them.

A compound selected from the group consisting of a compound of the formula

wherein R1 is selected from the group consisting of
—C≡C—A—B—COR6, —CH═CH—A—B—COR6,
—CH2—CH2—A—B—COR6, —O—A—B—COR6 and
—CH2—CO—A—B—COR6, A is selected from the group consisting of a) optionally unsaturated bivalent hydrocarbyl of 1 to 12 carbon atoms and 1 to 6 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen and b) optionally unsaturated bivalent hydrocarbyl of 1 to 12 carbon atoms, B is selected from the group consisting of phenyl, —CH—Z and a single bond, Z is selected from the group consisting of hydrogen,
—D0-6—NHSO2RC, —D0-6—NH—CO2RC, —D0-6—NH—CORC, —D0-6—NH—SO2—NH—RC, —D0-6—NH—CO—NHRC, —D0-6—COORC, —D0-6—SO2—RC, —D0-6—CORC and —D0-6—RC, D0-6— is optionally unsaturated bivalent acyclic hydrocarbon of 0 to 6 carbon atoms, Ra, Rb and Rc are individually selected from the group consisting of hydrogen, —(CH2)0-3-Ar, —(CH2)0-3-Het and —(CH2)0-3-Alk, Ar1 is carbocyclic aryl of 6 to 18 carbon atoms, Het is optionally unsaturated aromatic and non-aromatic heterocycle of 1 to 9 carbon atoims and 1 to 5 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, Alk is selected from the group consisting of optionally unsaturated alkyl of up to 12 carbon atoms and optionally unsaturated cycloalkyl of up to 12 carbon atoms, both optionally substituted or Ra and Rb taken with the nitrogen form an optionally unsaturated and optionally substituted aromatic or non-aromatic nitrogen heterocycle optionally containing at least one heteroaton selected from the group consisting of oxygen, sulfur and nitrogen, R6 is selected from the group —OH, —OAlk, —OAr, —NH2, —NH Alk, —N(Alk)2 and Z- or D-amino acyl, Alk and Ar are defined as above, R2 and R3 are individually selected from the group consisting of hydrogen, —OH, —OAlk and —O—(CH2)0-3-Ar, Alk and Ar defined as above or R2 and R3 together form a ring —O—(CRdRc)n—, n is an integer of 1 to 5, Rd and Rc are individually selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms and phenyl, Rd is selected from the group consisting of hydrogen, halogen, —OH, —NH2, —NO2, —CN, —CF3, acyl and acyloxy of an organic carboxylic acid of 1 to 12 carbon atoms, and alkyl, alkenyl, alkynyl, alkylthio, alkoxy, alkylamino, dialkylamino, dialkylaminoalkyl and dialkylaminoalkoxy of up to 6 carbon atoms, R5 is selected from the group consisting of hydrogen, —OH, halogen, —OAlk and —O(CH2)0-3-Ar, Alk and Ar defined as above, G is selected from the group consisting of
Rm is hydrogen or Alk as defined above, Het′ is a heterocycle of the formula
H forms the remainder of an optionally unsaturated, mono- or bicyclic aromatic or non-aromatic heterocycle of up to 9 carbon atoms and 2 to 5 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, the dotted lines are an optional second bond and their salts with non-toxic, pharmaceutically acceptable acids and bases and their esters.

4 more elements

Tricyclic compounds having activity specific for integrins, particularly alphanubeta3 integrins, method for preparing same, intermediates therefor, use of said compounds as drugs, and pharmaceutical compositions containing same

Life of this patent

Tricyclic compounds having activity specific for integrins, particularly alphanubeta3 integrins, method for preparing same, intermediates therefor, use of said compounds as drugs, and pharmaceutical compositions containing same

Life of this patent

Abstract

Claims12