Patent TW-375609-B (TW)
Title: 1-benzenesulfonyl-1,3-dihydro-indol-2-one derivatives, their preparation and pharmaceutical compositions in which they are present
Inventor: DI MALTA ALAIN
IPC: A61P1/00
Filed: 1994-07-29
Granted: 1999-12-01
Abstract: The invention relates to 1-benzenesulfonyl-1,3-dihydro-indol-2-one derivatives of the formula (I) and their salts where appropriate, to their preparation and to the pharmaceutical compositions in which they are present. These compounds have an affinity for the vasopressin and/or ocytocin receptors. This compound has the formula (I), wherein R1 is hydrogen, trifluoromethyl or C1-C7-alkoxy; methyltrifluoride, C1-C7 alkoxy group; R3 and -R4 each independently are ω-hydroxyl C2-C7-alkyl, wherein alkyl is in free state or substituted by a group selected from C1-C4 alkyl; tetrahydrofuranyl and tetrahydropyranyl; or R3 and R4 together form -(CH2)pX(CH2)q-; or R3 and R4 plus their bonded carbon to form the desired condensed, saturated or unsaturated C3-C12 hydrocarbon ring, unsubstituted or substituted by one or more C1-C7-alkyl, a ketone, one or two hydroxyl, said hydroxyl is in free state or selected from the following groups: C1-C4-alkyl, C1-C5-alkoxy-alkyl, wherein alkyl is C1-C4, ω-hydroxyl alkyl, wherein alkyl is C1-C4, formyl and (C1-C7) alkyl carbonyl; -R5 is C1-C7-alkoxy; R6 is guanidinyl, unsubstituted or substituted by one or more C1-C7-alkyl; OR7 group; aminoformyl substituted by R'6 and R"6 group; SO2R'7 group, COR'7 group, NR8R9 group; or CO-NH-CR10R'10-COR12 group; R'6 and R"6 each independently are hydrogen; C1-C7 alkyl, unsubstituted or substituted by one or more halogen or R "'6; C3-C7 cycloalkyl; pyrrodinyl-1-yl; or R'6 and R"6 plus their bonded nitrogen form pyrrodinyl, substituted by aminoformyl; R'"6 is C 1-C7-alkoxy; amino formyl, in free state or substituted by one or two C1-C7-alkyl; cyano; phenyl; tetrahydrofuranyl; or adamantane; R7 is C1-C7 alkyl; or ω-aminoformyl C1-C7-alkyl, in free state or substituted by one or two C1-C7-alkyl; R'7 is pyrrodinyl, substituted by R""7 group; R""7 is carboxyl, esterized by C1-C7-alkyl; R8 and R9 are each independently hydrogen; or C1-C7-alkyl; R9 can also be C3-C8-chain alkenyl, aminoformyl, unsubstituted or substituted by R14 and R'14' or thioamino formyl, unsubstituted or substituted by R14 and R'14; or R8 and R9 plus their bonded nitrogen form hydantoin, N-methyl hydantoin, or hetero ring, selected from pyrrolyl-1-yl, Δ3-pyrroline-1-yl, pyrrodinyl-1-yl or isoindoline-2-yl; R10 and R'10 are hydrogen; R12 is amino, unsubstituted or substituted by one or two C1-C7-alkyl; R14 and R'14 are each independently C1-C7-alkyl, unsubstituted or substituted by R15, or C3-C7-cycloalkyl; or R14 and R'14 plus their bonded nitrogen form a hetero ring, selected from morpholine, thiomorpholine, hexahydro pyridazinyl, acridine, pyrrodine, hexahydropyridyl, and panhydronitro heterocyclic ring, unsubstituted or substituted by one or more methyl, a phenyl, or an amino, said amino being in free state or carrying protective group; R15 is pyridyl, hydroxyl, amino, said amino being in free state or substituted by C1-C7-alkyl; or carboxyl which is in free state or esterized by C1-C7-alkyl; p and q are each an integer, whose sum ranges from 3 to 6; X is oxygen or S(O)n group; and n is 0, 1 or 2; with the proviso that when R1 is as defined above; R3 and R4 together form -(CH2)pX(CH2)q-, wherein X is oxygen or sulfur; or R3 and R4 plus their bonded carbon form the desired condensed saturated or unsaturated C3-C10 hydrocarbon ring, unsubstituted or unsubstituted by one or more C1-C7-alkyl; and R6 is guanidinyl, unsubstituted or substituted by one or two C1-C7-alkyl; OR7 group; amino formyl substituted by R'6 and R"6 groups; COR'7 group; or NR8R9 group; R7 is ω-aminoformyl-C1-C7-alkyl, which can be in free state or substituted by one or two C1-C7-alkyl; R'6 and R"6 are each independently C1-C7-alkyl, substituted by one or more halogen or R'"6; C3-C7-cycloalkyl; pyrrodinyl-1-yl; or R'6 and R"6 and their bonded nitrogen form a pyrrodinyl, substituted by aminoformyl; R"'6 is C1-C7-alkoxy; aminoformyl in free state or substituted by one or two C1-C7-alkyl; adamantanyl; or tetrahydrofuranyl; R'7 is pyrrodinyl, substituted by R""7'; R""7 is carboxyl, esterized by C1-C7-alkyl; R8 is hydrogen or C1-C7-alkyl; R9 is C3-C8-chain alkenyl; aminoformyl substituted by R14 and R'14; or thioaminoformyl substituted by R14 and R'14; or R8 and R9 together with their bonded nitrogen form hydantoin, N-methyl hydantoin or heterocyclic ring selected from pyrrolyl-1-yl, Δ3-pyrroline-1-yl, pyrrodinyl-1-yl or isoindoline-2-yl; R14 and R'14 are each independently C1-C7-alkyl, substituted by R15; or C3-C7-cycloalkyl; or R14 and R'14 together with their bonded nitrogen form heterocyclic ring selected from morpholine, thiomorpholine, hexahydro pyridazinyl, acridine, pyrrodine, hexahydropyridyl, and panhydronitro heterocyclic ring, unsubstituted or substituted by one or more methyl, a phenyl, or an amino, said amino being in free state or carrying protective group; R15 is pyridyl, hydroxyl, amino, said amino being in free state or substituted by C1-C7-alkyl; or carboxyl which is in free state or esterized by C1-C7-alkyl; or when R1 is 5-ethoxy, R3 and R4 together with their bonded carbon atom form spirocycloethane, and R is 2-methoxy, R6 can be NR8R9, wherein R8 is hydrogen, and R9 is 3-methylthiophene-2-yl carbonyl, aminoformyl substituted by one methyl or methoxy, or aminoformyl substituted by a methyl and a hydroxyl; and salts thereof (when suitable).