Patent EA-001084-B1 (EA)
Title: Prokinetic oxadiazoles
Inventor: BOSMANS JEAN-PAUL RENE MARIE A
IPC: A61K31/445
Filed: 1996-02-21
Abstract: 1. A derivative of oxadiazole with general formula   and a N-oxide form, a pharmaceutically acceptable acid addition form or a stereochemically isomeric form, wherein: R<1> is hydrogen or halo; R<2> is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; R<3> is hydrogen; or R<2> and R<3> taken together may form a C2-3 alkanediyl radical wherein one or two hydrogen atoms may be replaced by C1-4 alkyl; R<4> is hydrogen, hydroxy or C1-6 alkyloxy; X is a bivalent radical of the formula   L is a radical of formula: -Alk-R<5> (b), -Alk-O-R<6> (c), Alk is C1-12 alkanediyl; R<5> is hydrogen, cyano, C1-6 alkylcarbonyl, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, aryl, arylcarbonyl, tetrahydrofuran, dioxolane, dioxolane substituted with C1-6 alkyl, dioxane, dioxane substituted with C1-6 alkyl; R<6> is hydrogen, aryl, C1-6 alkyl, hydroxy-C1-6 alkyl, C1-6 alkylcarbonyl; aryl is defined as phenyl or phenyl substituted with up to three substituents selected from halo, C1-6 alkyl or C1-6 alkyloxy with proviso that L is not a methyl when R<3> and R<4> are hydrogen; X is a heterocycle of formula (a-2), R<1> is chloro, R<2> is methyl. 2. A compound according to claim 1 wherein R<1> is chloro. 3. A compound according to claim 1 wherein R<4> is hydrogen. 4. A compound according to claim 1 wherein R<1> is chloro; R<2> is methyl, R<3> and R<4> are hydrogen; and L is a radical of formula (b) wherein R<5> is tetrahydrofuran, or a radical of formula (c) wherein R<6> is 4-fluorophenyl. 5. A compound according to claim 1 wherein R<1> is chloro; R<2> and R<3> taken together form an ethanediyl radical; R<4> is hydrogen; and L is a radical of formula (c) wherein R<6> is methyl. 6. A compound according to claim 1, wherein the compound is selected from 2-chloro-5-methoxy-4-[3-[1-(tetrahydro-2-furanyl)methyl]-4-piperidinyl]-1,2,4-oxadiazol-5-yl]benzenamine; 5-chloro-2,3-dihydro-7-[3-[1-(3-methoxypropyl)-4-piperidinyl]-1,2,4-oxadiazol-5-yl]-4-benzofuranamine; 5-chloro-2,3-dihydro-7-[5-[1(3-methoxy-propyl)-4-piperidinyl]-1,2,4-oxadiazol-3-yl]-4-benzofuranamine; the N-oxide forms, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof. 7. A composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in any one of claims 1 to 6. 8. A process for preparing a composition as claimed in claim 7, wherein a pharmaceutically acceptable carrier is intimately mixed with a therapeutically effective amount of a compound as claimed in any one of claims 1 to 6. 9. Use of a compound as claimed in any one of claims 1 to 6 as a medicine. 10. An intermediate compound of formula   a stereochemically isomeric form, or a pharmaceutically acceptable acid addition salt thereof wherein R<1>, R<2>, R<3>, R<4> and X are as defined in claim 1. 11. A process for preparing a compound as claimed in claim 1 characterised in that an intermediate of formula (II)   wherein meanings of R<1>-R<4> are determined in claim 1, N- is alkylated by intermediate of formula L-W<1> (III), W<1> is a leaving group, and L is as defined in claim 1 and further optionally converting the compounds of formula (I) into each other by a functional group transformation reaction; and, optionally converting a compound of formula (I) into a pharmaceutically acceptable acid addition salt or converting an acid addition salt into a free base form with alkali; and/or preparing stereochemically isomeric forms thereof. The eurasian patent is valid in all contracting states except for AM and MD.