US 8,008,292 B2 · Condensed benzamide compounds and inhibitors of vanilloid receptor subtype 1 (VR1) activity

Abstract

To provide a compound having an excellent inhibitory effect on vanilloid receptor subtype 1 (VR1) activity which is effective in treating diseases to which the vanilloid receptor subtype 1 (VR1) activity is involved, such as pain, acute pain, chronic pain, neuropathic pain, rheumatoid arthritis pain, neuralgia, etc. and a pharmaceutical composition containing the compound. The object has been attained by a condensed benzamide compound represented by the following formula (the symbols in the formula have the same meanings defined in the specification) or its salt:

A condensed benzamide compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof:

[wherein Z is
(1) —O—,
(2) —NR5— (wherein R5 is a hydrogen atom or a C1-6 alkyl group),
(3) —S—,
(4) —SO— or
(5) —SO2—;
1 is 0, 1 or 2;
m is 0, 1 or 2;
R1 is
(1) a hydrogen atom or
(2) a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the following Group A:
Group A:
(a) a halogen atom,
(b) a hydroxyl group,
(c) a C1-6 alkoxy group,
(d) a carboxyl group,
(e) a C1-6 alkoxycarbonyl group,
(f) —CONR6R7 (wherein R6 and R7 are the same or different and each represents a hydrogen atom, a C1-6 alkyl group or an acyl group and said alkyl group may be substituted with a hydroxyl group or an acyloxy group),
(g) —NR6R7 (wherein R6 and R7 are the same as above),
(h) —NR6COR7 (wherein R6 and R7 are the same as above),
(i) —NR8CONR6R7 (wherein R6 and R7 are the same as above, and R8 is a hydrogen atom or a C1-6 alkyl group);
and
(j) —NR6SO2R9 (wherein R6 is the same as above, and R9 is a C1-6 alkyl group);
R2 is
(1) a hydrogen atom,
(2) a hydroxyl group,
(3) a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the Group A (wherein the Group A is the same as above),
(4) a carboxyl group,
(5) a C1-6 alkoxycarbonyl group or
(6) —CONR10R11 (wherein R10 and R11 are the same or different and each represents a hydrogen atom or a C1-6 alkyl group);
or R2 together with R1 forms ═O;
R3 is
(1) a hydrogen atom, or
(2) a C1-6 alkyl group;
R4 is
(1) a hydrogen atom,
(2) a halogen atom
(3) a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the following Group B,
(4) a C1-6 alkoxy group which may be substituted with 1 to 5 substituents selected from the following Group B,
(5) a cycloalkyl group which may be substituted with 1 to 5 substituents selected from the following Group B,
(6) an aralkyl group which may be substituted with 1 to 5 substituents selected from the following Group B,
(7) an aralkoxy group which may be substituted with 1 to 5 substituents selected from the following Group B, or
(8) a cycloalkylalkoxy group which may be substituted with 1 to 5 substituents selected from the following Group B,
Group B:
(a) a halogen atom,
(b) a halo C1-6 alkyl group,
(c) a hydroxyl group,
(d) a halo C1-6 alkoxy group,
(e) a C1-6 alkoxycarbonyl group,
(f) a C1-6 alkoxy group,
(g) a carboxyl group,
(h) —CONR12R13 (wherein R12 and R13 are the same or different and each represents a hydrogen atom or a C1-6 alkyl group);
(i) —NR12R13 (wherein R12 and R13 are the same as above),
(j) —NR12COR13 (wherein R12 and R13 are the same as above),
(k) —NR14CONR12R13 (wherein R12 and R13 are the same as above, and R14 is a hydrogen atom or a C1-6 alkyl group),
(l) —SO2R15 (wherein R15 is a C1-6 alkyl group), and
(m) —NR12SO2R15 (wherein R12 and R15 are the same as above);
(9) a hydroxyl group,
(10) —NR16R17 (wherein R16 and R17 are the same or different and each represents a hydrogen atom or a C1-6 alkyl group)
(11) —COR18 (wherein R18 is a C1-6 alkyl group, a C1-6 alkoxy group, a cycloalkyl group, an aralkyl group, an aralkoxy group, a cycloalkylalkoxy group or a hydroxyl group),
(12) —CONR16R17 (wherein R16 and R17 are the same as above),
(13) —NR19CONR16R17 (wherein R16 and R17 are the same as above, and R19 is a hydrogen atom or a C1-6 alkyl group),
(14) —NR16COOR20 (wherein R16 is the same as above, and R20 is a C1-6 alkyl group or a cycloalkyl group),
(15) —SR20 (wherein R20 is the same as above),
(16) —SOR20 (wherein R20 is the same as above),
(17) —SO2R20 (wherein R20 is the same as above),
(18) —SO2NR16R17 (wherein R16 and R17 are the same as above) or
(19) —NR16COR18 (wherein R16 and R18 are the same as above);
V is
(1) a single bond or
(2) —(CR21R22)n— (wherein R21 and R22 are the same or different and each represents a hydrogen atom or a C1-6 alkyl group, and n is 1 or 2);
P1 and P2 rings are the same or different and each represents
(1) a carbocyclic group which may be substituted with 1 to 5 substituents selected from the following group C or
(2) a heterocyclic group which may be substituted with 1 to 5 substituents selected from the following group
Group C:
(a) a halogen atom,
(b) a hydroxyl group,
(c) a C1-6 alkoxy group which may be substituted with 1 to 5 substituents selected from the Group A,
(d) an C1-6 alkylthio group,
(e) a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the Group A,
(f) —CONR23R24 (wherein R23 and R24 are the same or different and each represents a hydrogen atom or a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the Group A),
(g) —NR123R124 (wherein R123 and R124 are the same or different and each represents a hydrogen atom or a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the Group A),
(h) —NR223COR224 (wherein R223 and R224 are the same or different and each represents a hydrogen atom or a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the Group A),
(i) —NR25CONR323R324 (wherein R323 and R324 are the same or different and each represents a hydrogen atom or a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the Group A),
(j) —SR26 (wherein R26 is a C1-6 alkyl group),
(k) —SOR126 (wherein R126 is a C1-6 alkyl group),
(l) —SO2R226 (wherein R226 is a C1-6 alkyl group),
(m) —NR423SO2R326 (wherein R423 is a hydrogen atom or a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the Group A, and R326 is a C1-6 alkyl group),
(n) —SO2NR523R524 (wherein R523 and R524 are the same or different and each represents a hydrogen atom or a C1-6 alkyl group which may be substituted with 1 to 5 substituents selected from the Group A),
(o) —COR27 (wherein R27 is a C1-6 alkyl group, C1-6 alkoxy group, a cycloalkyl group, an aralkyl group, an aralkoxy group, a cycloalkylalkoxy group or a hydroxyl group),
(p) a carbocyclic group which may be substituted with 1 to 5 substituents selected from (a) to (o) of the Group C,
(q) a heterocyclic group which may be substituted with 1 to 5 substituents selected from (a) to (o) of the Group C,
(r) —O—R28 (wherein R28 is an acyl group, a carbocyclic group which may be substituted with 1 to 5 substituents selected from (a) to (o) of the Group C or a heterocyclic group which may be substituted with 1 to 5 substituents selected from (a) to (o) of the Group C),
(s) —O—(CR121R122)n—R128 (wherein R121 and R122 are the same or different and each represents a hydrogen atom or a C1-6 alkyl group, n is 1 or 2, and R128 is an acyl group, a carbocyclic group which may be substituted with 1 to 5 substituents selected from (a) to (i) of the Group C or a heterocyclic group which may be substituted with 1 to 5 substituents selected from (a) to (l) of the Group C),
(t) a nitro group, and
(u) a cyano group.

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Condensed benzamide compounds and inhibitors of vanilloid receptor subtype 1 (VR1) activity

Life of this patent

Condensed benzamide compounds and inhibitors of vanilloid receptor subtype 1 (VR1) activity

Life of this patent

Abstract

Claims6