US 7,022,860 B2 · Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic agents

Abstract

A process for preparing a compound represented by formula (IIa′) wherein Q represents group (i) as defined in the specification and R2 to R5, R31, R32, and R52 are as defined in the specification, by (1) reacting a compound represented by formula (V) wherein R2 to R5 and R52 are as defined in the specification. with a compound represented by R31R32C═O wherein R31 and R32 are as defined in the specification; (2) reacting the compound prepared in (1) with a compound represented by R71—C(═O)—R72 wherein R71 and R72 each independently represent a chlorine atom, 4-nitrophenyl, or 1-imidazolyl; and (3) reacting the compound prepared in (2) with a compound represented by R33OH wherein R33 is as defined in the specification.

A compound represented by formula (II) or a salt or solvate thereof:

wherein
R2, R3, R4, and R5, which may be the same or different, represent any of the following (a) to (n):
(a) a hydrogen atom;
(b) a halogen atom;
(c) a hydroxyl group optionally protected by acetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, benzoyl, 4-nitrobenzoyl, 3-oxobutyryl, benzyl, diphenylmethyl, triphenylmethyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, methoxymethyl, methoxyethoxymethyl, benzyloxymethyl, trimethylsilyl, tert-butyldimethylsilyl, triphenysilyl, 2-tetrahydropyranyl, or trimethylsilylethoxymethoxy;
(d) formyl;
(e) C1-12 alkyl which may be substituted by a halogen atom;
(f) C2-12 alkenyl which has one or more carbon-carbon double bonds and may be substituted by
(1) a halogen atom,
(2) cyano,
(3) —COR9 wherein R9 represents a hydrogen atom or C1-6 alkyl,
(4) —COOR10 wherein R10 represents a hydrogen atom or C1-6 alkyl,
(5) —CONR11R12 wherein R11 and R12, which may be the same or different, represent
(i) a hydrogen atom,
(ii) C1-6 alkyl which may be substituted by amino optionally substituted by C1-4 alkyl, phenyl optionally substituted by C1-4 alkyl which may be substituted by a saturated five- to seven-membered heterocyclic ring containing one or two nitrogen atoms (the nitrogen atoms may be substituted by C1-4 alkyl), or a saturated or unsaturated five- to seven-membered heterocyclic ring,
(iii) phenyl which may be substituted by carboxyl, or
(iv) a saturated or unsaturated five to seven-membered heterocyclic ring,
(6) a saturated or unsaturated five- to seven-membered heterocyclic ring which may be substituted by C1-4 alkyl or may form a bicyclic ring fused with another ring;
(g) C1-12, alkoxy which may be substituted by
(1) a halogen atom,
(2) a hydroxyl group,
(3) cyano,
(4) C3-7 cycloalkyl,
(5) phenyl,
(6) C1-4 alkoxy,
(7) phenoxy,
(8) amino which may be substituted by C1-4 alkyl,
(9) —COR13 wherein R13 represents a hydrogen atom, C1-6 alkyl, phenyl optionally substituted by halogen or C1-4 alkoxy, or phenyl C1-4 alkyl,
(10) —COOR14 wherein R14 represents a hydrogen atom or C1-6 alkyl,
(11) —CONR15R15 wherein R15 and R16, which may be the same or different, represent a hydrogen atom or C1-6 alkyl which may be substituted by a saturated or unsaturated five to seven-membered heterocyclic ring, or
(12) a saturated or unsaturated five- to seven-membered heterocyclic ring which may be substituted by C1-4 alkyl or phenyl C1-4 alkyl;
(h) —CH═N—OR16a wherein R16a represents a hydrogen atom, C1-6 alkyl, phenyl C1-4 alkyl, or phenyl;
(i) —(CH2)mOR17 wherein m is an integer of 0 to 4, and R17 represents a hydrogen atom, C1-6 alkyl, or phenyl C1-4 alkyl of which one or more hydrogen atoms on the benzene ring may be substituted by C1-4 alkyl;
(j) —(CH2)kCOR18 wherein k is an integer of 1 to 4, and R18 represents a hydrogen atom or C1-4 alkyl;
(k) —(CH2)jCOOR19 wherein j is an integer of 0 to 4, and R19 represents a hydrogen atom or C1-6 alkyl;
(l) —(CH2)p—NR20R21 wherein p is an integer of 1 to 4, and R20 and R21 which may be the same or different, represent
(1) a hydrogen atom,
(2) C1-6 alkyl which may be substituted by amino optionally substituted by C1-4 alkyl,
(3) phenyl C1-4 alkyl,
(4) —COR22 wherein R22 represents a hydrogen atom or C1-4 alkyl which may be substituted by carboxyl, or
(5) —SO2R23 wherein R23 represents C1-4alkyl or phenyl which may be substituted by a halogen atom;
(m) —(CH2)q—CONR24R25 wherein q is an integer of 0 to 4, and R24 and R25, which may be the same or different, represent a hydrogen atom, a saturated or unsaturated five to seven-membered heterocyclic ring, or C1-6 alkyl which may be substituted by a saturated or unsaturated five to seven-membered heterocyclic ring, or alternatively R24 and R25 may form a saturated or unsaturated five to seven-membered heterocyclic ring together with a nitrogen atom to which they are attached (the heterocyclic ring may further contain at least one oxygen, nitrogen, or sulfur atom, may form a bicyclic ring fused with another ring, or may be substituted by C1-4 alkyl);
and
(n) —NR26R27 wherein R26 and R27, which may be the same or different, represent a hydrogen atom or —COR28 wherein R28 represents a hydrogen atom, C1-6 alkyl, or phenyl which may be substituted by C1-4 alkyl or C1-6 alkoxy optionally substituted by phenyl;
R31 and R32, which may be the same or different, represent a hydrogen atom or C1-6 alkyl which may be substituted by a halogen atom;
and
Q represents a group selected from the following groups (i) to (iv) or a halogen atom or C1-6 alkoxy:
wherein
R33 represents
C1-6 alkyl which may be substituted by C1-6 alkoxy optionally substituted by C1-6 alkoxy, phenyl optionally substituted by C1-6 alkoxy, amino, or nitro, or a saturated or unsaturated five to seven-membered heterocyclic ring optionally substituted by C1-6 alkoxy, amino, or nitro,
phenyl which may be substituted by C1-6 alkoxy, amino, or nitro, or
a saturated or unsaturated five- to seven-membered heterocyclic ring which may be substituted by C1-6 alkoxy, amino, or nitro, or
R33 may form C1-4 alkylene together with R31 or R32,
R34 represents
C1-16 alkyl which may be substituted by a halogen atom, carboxyl, phenyl optionally substituted by C1-6 alkoxy, amino, or nitro, or a saturated or unsaturated five- to seven-membered heterocyclic ring optionally substituted by C1-6 alkoxy, amino, or nitro,
phenyl which may be substituted by C1-6 alkoxy, amino, or nitro, or
a saturated or unsaturated five- to seven-membered heterocyclic ring which may be. substituted by C1-6 alkoxy, amino, or nitro,
R35 and R36, which may be the same or different, represent a hydrogen atom or C1-6 alkyl which may be substituted by amino optionally substituted by C1-4 alkyl or
R35 and R36 may form a saturated or unsaturated five- to seven-membered heterocyclic ring together with a nitrogen atom to which they are attached, and
R37 and R38, which may be the same or different, represent C1-6 alkyl,
R51 represents nitro or amino, and
R52 represents a hydrogen atom or a protective group for carboxyl selected from the group consisting of methyl, ethyl, tert-butyl, benzyl, 4-methoxybenzyl, diphenylmethyl, 4-nitrobenzyl, tert-butyldimethylsilyl, triphenylsilyl, 2-phenylsulfonylethyl, 2-methoxycarbonylethyl, 2-cyanoethyl, and 2-trimethylsilylethyl,
provided that the group —CR31R32Q does not represent C1-6 alkyl substituted by a halogen atom or C1-6 alkoxy.

60 more elements

Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic agents

Life of this patent

Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic agents

Life of this patent

Abstract

Claims5