Patent EA-003252-B1 (EA)
Title: Cyclopentene derivatives useful as antagonists of the motilin receptor
Inventor: CHEN ROBERT
IPC: C07C233/41
Filed: 1998-10-27
Abstract: 1. A compound of the Formula 1: wherein R1 is selected from hydrogen, C1-5alkyl, substituted C1-5alkyl (where the substituents are one or more halogens), aminoC1-5alkyl, C1-5alkylaminoC1-5alkyl; di-C1-5alkylaminoC1-5alkyl, RaRbN-C1-5alkyl (where the Ra and Rb are independently selected from hydrogen and C1-5alkyl, or are taken together to farm a morpholine, piperazine, piperidine, or N-substituted piperidine where the N- substitutent is C1-5alkyl or phenylC1-5alkyl), C1-5alkylcarbonyl, C1-5 alkoxycarbonyl, aminocarbonyl, C1-9alkylaminocarbonyl, cycloC3-9alkylaminocarbonyl, pyridinylcarbonyl, substituted pyridinylcarbonyl (where the pyridinyl substituents are selected from the group consisting of one or more halogens and C1-5alky), thiophenecarbonyl, substituted thiophenecarbonyl (where the thiophene substituents are selected from the group consisting of one or more halogens and C1-5alkyl), phenyl, phenylC1-5alkyl, phenoxycarbonyl, phenylcarbonyl, diphenylmethylcarbonyl, phenylaminocarbonyl, phenylthiocarbonyl, phenylaminothiocarbonyl, substituted phenyl, substituted phenylC1-5alkyl, substituted phenoxycarbonyl, substituted phenylcarbonyl, substituted phenylaminocarbonyl, substituted diphenylmethylcarbonyl, substituted phenylthiocarbonyl, and substituted phenylaminothiocarbonyl (where the phenyl substituents are selected from the group consisting of one or more of halogen, C1-5alkyl, trihalomethyl, C1-5alkoxy, amino, nitrile, nitro, C1-5 alkylamino, di-C1-5alkylamino, if there are more than one substitutents they may be taken together with the phenyl ring to form a fused bicyclic 7-10 membered heterocyclic ring having one to two heteroatoms selected from oxygen, sulfur or nitrogen or the substituents may be taken together to form a fused bicyclic 7-10 membered aromatic ring; R2 is selected from hydrogen, C1-5alkyl, C1-5alkoxy, phenyl, substituted phenyl (where the phenyl substituents are selected from one or more of the group consisting of halogen and C1-5 alkyl), phenylC1-5alkyl, substituted phenylC1-5alkyl (where the phenyl substituents are selected from one or more of the group consisting of halogen, C1-5alkyl, C1-5alkoxy, halo and di-C1-5 alkylamino) R3 is selected from hydrogen, C1-5alkylcarbonyl, substituted C1-5alkylcarbonyl (where the alkyl substituents are selected from one or more halogens), phenylcarbonyl, and substituted phenylcarbonyl (where the phenyl substituents are selected from one or more of the group consisting of halogen, C1-5alkyl, C1-5alkoxy, amino, C1-5alkylamino, and di-C1-5alkylamino) R4 is selected from hydrogen, C1-5alkylcarbonyl, substituted C1-5alkylcarbonyl (where the alkyl substituents are selected from one or more halogens), phenylcarbonyl, and substituted phenylcarbonyl (where the phenyl substituents are selected from one or more of the group consisting of halogen, C1-5alkyl, C1-5alkoxy, amino, C1-5alkylamino, and di-C1-5alkylamino) n is 0-3; m is 1-5 R5 is where: q is 0-2; t is 0-1; X is oxygen, CH2, sulfur, or NRc where Rc is hydrogen, C1-5alkyl, morpholinoC1-5alkyl, piperidinylC1-5alkyl, N-phenylmethylpiperidinyl or piperazinylC1-5alkyl, with the proviso that if q and t are 0, then X is hydroxy, thiol, or amino, A is C1-5alkoxycarbonyl, phenylcarbonyl, or R7R8N- where R7 is independently selected from hydrogen, C1-5alkyl, cycloC1-9alkyl, or R7 is taken together with R8 to form a 5 or 6 membered heterocyclic ring with one or more heteroatoms selected from the group consisting of oxygen, nitrogen or sulfur and N-oxides thereof; R8 is independently selected from hydrogen, C1-5alkyl, cycloC1-5alkyl or taken together with R7 to form a 5 or 6 membered heterocyclic ring with one or more heteroatoms selected from the group consisting of oxygen, nitrogen or sulfur, and N-oxides thereof; R6 is selected from hydrogen, halogen, C1-5alkoxy, C1-5alkylamino, or di-C1-5alkylamino ; and the pharmaceutically acceptable salts thereof. 2. The compound of claim 1 wherein: R1 is selected from phenylaminocarbonyl, phenylcarbonyl, substituted phenylaminocarbonyl, substituted phenylcarbonyl, and hydrogen; R2 is phenylC1-5alkyl; R3 is hydrogen; R4 is trifluoromethylacetyl; R5 is O-(CH2)2-morpholin-1-yl; R6 is hydrogen; n is 0; and m is 1. 3. The compound according to claim 1 of the formula: 4. The compound according to claim 1 of the formula: 5. The compound according to claim 1 of the formula: 6. The compound according to claim 1 of the formula: 7. The compound according to claim 1 of the formula: 8. A pharmaceutical composition for treating disorders associated with the motilin receptor comprising an effective amount of a compound of claim 1 in association with one or more pharmaceutically acceptable carriers. 9. A method of treating disorders associated with the motilin receptor in humans comprising administering to a human in need of such treatment an effective amount of a compound of claim 1.