FIELD: chemistry.
SUBSTANCE: invention relates to a novel sulfonamide derivative of general formula (1) and a pharmaceutically acceptable salt thereof. Compounds have an inhibitory effect on α4-integrin with high selectivity with a weak effect on α4β1 and a strong effect on α4β7. In general formula (1) A represents a group represented by the general formula (2-1), (2-2) or (2-4)
,
, where Arm is a phenyl group, a pyridyl group or a pyrimidyl group, R11 is a lower alkyl group, R12, R13 and R14 each independently represents any of the following fragments: a hydrogen atom, a lower alkoxy group and a lower alkylamino-lower alkyl group, and when A represents a group represented by the general formula (2-1) or (2-4), R1, R2, R3, R51, R52 and R53 each independently represents any of the following fragments: a hydrogen atom, a lower alkyl group and a halo-lower alkyl group, B is any of the following: (a) a hydroxyl group, (b) -O-Rx, wherein Rx is a 6-membered heterocyclic group containing an oxygen atom or a nitrogen atom, optionally substituted with a lower alkyl group, (c) a hydroxyamino group, (d) C1-C10alkoxyamino group or (e) an alkoxy group having from 1 to 10 carbon atoms, optionally substituted with a substituent selected from the group consisting of (e-1) alkyl group having from 1 to 10 carbon atoms, (e-2) halogen atom, (e-3) 6-membered heterocyclic group containing an oxygen atom or a nitrogen atom as a heteroatom, and (e-4) a lower alkoxy group, R41 represents a hydrogen atom,a, b, c and d are independently C-R31, C-R32, C-R33 or C-R34 respectively, where R31, R32, R33 and R34 each independently represents any of the following fragments: a hydrogen atom, a halogen atom, one of g and e is N and the other is CH, or both g and e are CH, f and h are independently C-R36 or C-R38 respectively, where R36 and R38 each independently represents any of the following fragments: a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group and a nitro group, D represents a phenyl group, optionally having a substituent selected from the group consisting of the following substituents: a lower alkyl group, or D is a 6-membered heterocyclic group containing 1 to 2 ring heteroatoms selected from a nitrogen atom, and optionally substituted with a substituent selected from the group consisting of a lower alkyl group, when A represents a group represented by general formula (2-1) or (2-2), E represents a 5- or 6-membered heterocyclic group containing 1 to 3 nitrogen atoms or an oxygen atom, wherein the 5- or 6-membered heterocyclic group containing 1 to 3 nitrogen atoms is substituted with a substituent selected from the group consisting of a lower alkoxy-lower alkylene group, (mono- or di-lower alkyl) amino-lower alkylene group, and a 5- or 6-membered heterocyclic group containing an oxygen atom; or E represents a 6-membered cyclic group containing a ketone group and containing 2 nitrogen atoms as ring atoms, wherein the cyclic group is substituted with a lower alkyl group or a lower alkenyl group, and when A represents a group represented by general formula (2-4), E is a 5- or 6-membered aromatic heterocyclic group containing 1 to 3 heteroatoms selected from nitrogen, and optionally having a substituent selected from the group consisting of a lower alkyl group, a lower alkoxy group, a lower alkoxy-lower alkylene group, and a 4-6 membered heterocyclic group containing an oxygen atom or a nitrogen atom.
EFFECT: compounds can be used in the treatment of inflammatory diseases.
22 cl, 2 tbl, 104 ex
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Authors
Dates
2018-09-21—Published
2014-10-28—Filed