INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
The present invention aims to provide a compound having H-PGDS inhibitory activity. The present invention relates to a compound of the formula [I]: wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof.
1 : A compound of the formula [I]:
wherein
X 1 , Y 1 , Y 2 , Y 3 and Y 4 are each independently a carbon or a nitrogen atom (wherein the total number of the nitrogen atoms for Y 1 , Y 2 , Y 3 and Y 4 is 0, 1 or 2),
m is 0, 1 or 2,
n is 0, 1 or 2,
R 1 is
(1) hydroxy,
(2) cyano,
(3) C 1-4 alkyl (wherein the alkyl is optionally substituted by hydroxy or C 1-4 alkoxy),
(4) C 1-4 alkoxy,
(5) halogen,
(6) C 1-4 haloalkyl, or
(7) C 3-6 cycloalkyl,
R 2 in the number of m are each independently
(1) cyano,
(2) C 1-4 alkyl,
(3) C 1-4 alkoxy,
(4) halogen, or
(5) C 1-4 haloalkyl,
R 3 in the number of n are each independently
(1) C 1-4 alkyl,
(2) C 1-4 alkoxy, or
(3) halogen, and
R 4 is
(1) ring Cy [wherein the ring Cy is
(a) C 4-6 cycloalkyl (wherein the cycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(I) hydroxy,
(II) cyano,
(III) oxo,
(IV) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(i) hydroxy,
(ii) carboxy,
(iii) —CONH 2 ,
(iv) —CO—C 1-4 alkoxy,
(v) —SO 2 —C 1-4 alkyl, or
(vi) a group represented by the formula:
(V) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(VI) carboxy,
(VII) —CO—NR 5 R 6 [wherein R 5 and R 6 are each independently C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy), or R 5 and R 6 optionally form, together with the nitrogen atom bonded thereto, 4- to 6-membered heterocycloalkyl containing 1 or 2 hetero atoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the heterocycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(i) hydroxy, and
(ii) C 1-6 alkyl (wherein the alkyl is optionally substituted by hydroxy)}],
(VIII) —NR 7 R 8 {wherein R 7 and R 8 are each independently C 1-4 alkyl or —CO—C 1-6 alkyl (wherein the alkyl is optionally substituted by cyano)},
(IX) —O—C 1-6 haloalkyl,
(X) a group represented by the formula:
(XI) a group represented by the formula:
{wherein R 9 is C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy)}, and
(XII) a group represented by the formula:
wherein R 10 is C 1-4 alkyl)),
(b) C 5-8 bridged cycloalkyl {wherein the bridged cycloalkyl is optionally substituted by
(I) hydroxy,
(II) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(i) hydroxy,
(ii) carboxy,
(iii) —CONH 2 ,
(iv) —CO—C 1-4 alkoxy,
(v) —SO 2 —C 1-4 alkyl, or
(vi) a group represented by the formula:
(III) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(IV) carboxy,
(V) —CO—C 1-4 alkoxy,
(VI) —O—C 1-6 haloalkyl, or
(VII) a group represented by the formula:
(c) 5- or 6-membered heterocycloalkyl containing one nitrogen atom [wherein the heterocycloalkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of
(I) oxo,
(II) C 1-6 alkyl,
(III) —CO—R 11 {wherein R 11 is
(i) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(A) hydroxy,
(B) cyano, or
(C) C 1-4 alkoxy),
(ii) C 1-6 alkoxy,
(iii) C 1-6 haloalkyl,
(iv) C 3-6 cycloalkyl (wherein the cycloalkyl is optionally substituted by halogen), or
(v) 4- to 6-membered heterocycloalkyl containing one oxygen atom (wherein the heterocycloalkyl is optionally substituted by halogen)}, and
(IV) a group represented by the formula:
(d) 8-membered bridged heterocycloalkyl containing one nitrogen atom {wherein the bridged heterocycloalkyl is optionally substituted by —CO—R 11 ),
(e) 7- to 11-membered spiro heterocycloalkyl containing one nitrogen atom {wherein the spiro heterocycloalkyl is optionally substituted by —CO—R 11 ),
(f) 5- to 9-membered saturated or partially unsaturated fused ring group containing 1 or 2 nitrogen atoms (wherein the fused ring group is optionally substituted by —CO—R 11 ),
(g) a group represented by the formula:
(h) a group represented by the formula:
(i) a group represented by the formula:
(2) C 1-4 alkyl {wherein the alkyl is optionally substituted by
(a) C 3-4 cycloalkyl (wherein the cycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of hydroxy and C 1-4 alkyl optionally substituted by hydroxy), or
(b) phenyl}, or
(3) C 1-4 haloalkyl (wherein the haloalkyl is optionally substituted by C 3-4 cycloalkyl optionally substituted by hydroxy)],
or a pharmaceutically acceptable salt thereof.
2 : The compound of claim 1 , wherein the total number of the nitrogen atoms for Y 1 , Y 2 , Y 3 and Y 4 is 1 or 2, or a pharmaceutically acceptable salt thereof.
3 : The compound of claim 1 , which is represented by the formula [IA]:
(wherein each symbol is as defined for claim 1 ), or a pharmaceutically acceptable salt thereof.
4 : The compound of claim 1 , wherein R 3 is halogen, or a pharmaceutically acceptable salt thereof.
5 : The compound of claim 1 , wherein R 4 is ring Cy, or a pharmaceutically acceptable salt thereof.
6 : The compound of claim 1 , which is represented by the formula [IB]:
(wherein each symbol is as defined for claim 1 ), or a pharmaceutically acceptable salt thereof.
7 : The compound of claim 1 , wherein R 1 is
(1) C 1-4 alkyl (wherein the alkyl is optionally substituted by hydroxy or C 1-4 alkoxy),
(2) C 1-4 alkoxy,
(3) halogen, or
(4) C 1-4 haloalkyl,
or a pharmaceutically acceptable salt thereof.
8 : The compound of claim 1 , wherein R 2 is halogen, or a pharmaceutically acceptable salt thereof.
9 : The compound of claim 1 , wherein ring Cy is
(1) C 4-6 cycloalkyl (wherein the cycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(a) hydroxy,
(b) cyano,
(c) oxo,
(d) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(e) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(f) carboxy,
(g) —CO—NR 5 R 6 [wherein R 5 and R 6 are each independently C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy), or R 5 and R 6 optionally form, together with the nitrogen atom bonded thereto, 4- to 6-membered heterocycloalkyl containing 1 or 2 hetero atoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the heterocycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(I) hydroxy, and
(II) C 1-6 alkyl (wherein the alkyl is optionally substituted by hydroxy)}],
(h) —NR 7 R 8 {wherein R 7 and R 8 are each independently C 1-4 alkyl, or —CO—C 1-6 alkyl (wherein the alkyl is optionally substituted by cyano)},
(i) —O—C 1-6 haloalkyl,
(j) a group represented by the formula:
(k) a group represented by the formula:
{wherein R 9 is C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy)}, and
(m) a group represented by the formula:
wherein R 10 is C 1-4 alkyl)),
(2) C 5-8 bridged cycloalkyl {wherein the bridged cycloalkyl is optionally substituted by
(a) hydroxy,
(b) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(c) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(d) carboxy,
(e) —CO—C 1-4 alkoxy,
(f) —O—C 1-6 haloalkyl, or
(g) a group represented by the formula:
(3) 5- or 6-membered heterocycloalkyl containing one nitrogen atom [wherein the heterocycloalkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of
(a) oxo,
(b) C 1-6 alkyl,
(c) —CO—R 11 {wherein R 11 is
(I) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(i) hydroxy,
(ii) cyano, or
(iii) C 1-4 alkoxy),
(II) C 1-6 alkoxy,
(III) C 1-4 haloalkyl,
(IV) C 3-4 cycloalkyl (wherein the cycloalkyl is optionally substituted by halogen), or
(V) 4- to 6-membered heterocycloalkyl containing one oxygen atom (wherein the heterocycloalkyl is optionally substituted by halogen)}, and
(d) a group represented by the formula:
(4) 8-membered bridged heterocycloalkyl containing one nitrogen atom {wherein the bridged heterocycloalkyl is optionally substituted by —CO—R 11 ),
(5) 7- to 11-membered spiro heterocycloalkyl containing one nitrogen atom {wherein the spiro heterocycloalkyl is optionally substituted by —CO—R 11 }, or
(6) a 6- to 9-membered saturated or partially unsaturated fused ring group containing 1 or 2 nitrogen atoms (wherein the fused ring group is optionally substituted by —CO—R 11 ), or a pharmaceutically acceptable salt thereof.
10 : The compound of claim 1 , wherein ring Cy is
(1) C 4-6 cycloalkyl (wherein the cycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(a) hydroxy,
(b) cyano,
(c) oxo,
(d) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(e) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(f) carboxy,
(g) —CO—NR 5 R 6 [wherein R 5 and R 6 are each independently C 1-6 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy), or R 5 and R 6 optionally form, together with the nitrogen atom bonded thereto, 4- to 6-membered heterocycloalkyl containing 1 or 2 hetero atoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the heterocycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(I) hydroxy, and
(II) C 1-6 alkyl (wherein the alkyl is optionally substituted by hydroxy)}],
(h) —NR 7 R 8 {wherein R 7 and R 8 are each independently C 1-4 alkyl, or —CO—C 1-6 alkyl (wherein the alkyl is optionally substituted by cyano)},
(i) —O—C 1-6 haloalkyl,
(j) a group represented by the formula:
(k) a group represented by the formula:
{wherein R 9 is C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy)}, and (m) a group represented by the formula:
wherein R 10 is C 1-4 alkyl)),
(2) C 5-8 bridged cycloalkyl {wherein the bridged cycloalkyl is optionally substituted by
(a) hydroxy,
(b) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(c) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(d) carboxy,
(e) —CO—C 1-4 alkoxy,
(f) —O—C 1-6 haloalkyl, or
(g) a group represented by the formula:
(3) 5- or 6-membered heterocycloalkyl containing one nitrogen atom [wherein the heterocycloalkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of
(a) oxo,
(b) C 1-6 alkyl,
(c) —CO—R 11 {wherein R 11 is
(I) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(i) hydroxy,
(ii) cyano, or
(iii) C 1-4 alkoxy),
(II) C 1-6 alkoxy,
(III) C 1-6 haloalkyl,
(IV) C 3-6 cycloalkyl (wherein the cycloalkyl is optionally substituted by halogen), or
(V) 4- to 6-membered heterocycloalkyl containing one oxygen atom (wherein the heterocycloalkyl is optionally substituted by halogen)}, and
(d) a group represented by the formula:
or
(4) 8-membered bridged heterocycloalkyl containing one nitrogen atom {wherein the bridged heterocycloalkyl is optionally substituted by —CO—R 11 },
or a pharmaceutically acceptable salt thereof.
11 : The compound of claim 1 , wherein ring Cy is
(1) C 4-6 cycloalkyl (wherein the cycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(a) hydroxy,
(b) cyano,
(c) oxo,
(d) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(e) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(f) carboxy,
(g) —CO—NR 5 R 6 [wherein R 5 and R 6 are each independently C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy), or R 5 and R 6 optionally form, together with the nitrogen atom bonded thereto, 4- to 6-membered heterocycloalkyl containing 1 or 2 hetero atoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the heterocycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(I) hydroxy, and
(II) C 1-6 alkyl (wherein the alkyl is optionally substituted by hydroxy)}],
(h) —NR 7 R 8 {wherein R 7 and R 8 are each independently C 1-4 alkyl, or —CO—C 1-6 alkyl (wherein the alkyl is optionally substituted by cyano)},
(i) —O—C 1-6 haloalkyl,
(j) a group represented by the formula:
(k) a group represented by the formula:
{wherein R 9 is C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy)}, and
(m) a group represented by the formula:
wherein R 10 is C 1-4 alkyl)), or
(2) C 5 -s bridged cycloalkyl {wherein the bridged cycloalkyl is optionally substituted by
(a) hydroxy,
(b) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(c) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(d) carboxy,
(e) —CO—C 1-4 alkoxy,
(f) —O—C 1-6 haloalkyl, or
(g) a group represented by the formula:
or a pharmaceutically acceptable salt thereof.
12 : The compound of claim 1 , wherein ring Cy is
(1)cyclohexyl (wherein the cyclohexyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(a) hydroxy,
(b) cyano,
(c) oxo,
(d) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(e) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(f) carboxy,
(g) —CO—NR 5 R 6 [wherein R 5 and R 6 are each independently C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy), or R 5 and R 6 optionally form, together with the nitrogen atom bonded thereto, 4- to 6-membered heterocycloalkyl containing 1 or 2 hetero atoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the heterocycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(I) hydroxy, and
(II) C 1-6 alkyl (wherein the alkyl is optionally substituted by hydroxy)}],
(h) —NR 7 R 8 {wherein R 7 and R 8 are each independently C 1-4 alkyl, or —CO—C 1-6 alkyl (wherein the alkyl is optionally substituted by cyano)},
(i) —O—C 1-6 haloalkyl,
(j) a group represented by the formula:
(k) a group represented by the formula:
{wherein R 9 is C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy)}, and
(m) a group represented by the formula:
wherein R 10 is C 1-4 alkyl)), or
(2) a group represented by the formula:
{wherein the group represented by the formula is optionally substituted by
(a) hydroxy,
(b) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(c) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(d) carboxy,
(e) —CO—C 1-4 alkoxy,
(f) —O—C 1-6 haloalkyl, or
(g) a group represented by the formula:
or a pharmaceutically acceptable salt thereof.
13 : The compound of claim 1 , wherein ring Cy is
(1) a group represented by the formula:
wherein R 12 and R 13 are each independently
(a) hydrogen,
(b) hydroxy,
(c) cyano,
(d) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(e) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(f) carboxy,
(g) —CO—NR 5 R 6 [wherein R 5 and R 6 are each independently C 1-6 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy), or R 5 and R 6 optionally form, together with the nitrogen atom bonded thereto, 4- to 6-membered heterocycloalkyl containing 1 or 2 hetero atoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the heterocycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(I) hydroxy, and
(II) C 1-6 alkyl (wherein the alkyl is optionally substituted by hydroxy)}],
(h) —NR 7 R 8 {wherein R 7 and R 8 are each independently C 1-4 alkyl or —CO—C 1-6 alkyl (wherein the alkyl is optionally substituted by cyano)},
(i) —O—C 1-6 haloalkyl,
(j) a group represented by the formula:
(k) a group represented by the formula:
{wherein R 9 is C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy)}, or
(m) a group represented by the formula:
wherein R 10 is C 1-6 alkyl), or R 12 and R 13 are optionally joined to form oxo), or
(2) a group represented by the formula:
wherein R 14 is
(a) hydrogen,
(b) hydroxy,
(c) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(d) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(e) carboxy,
(f) —CO—C 1-4 alkoxy,
(g) —O—C 1-6 haloalkyl, or
(h) a group represented by the formula:
or a pharmaceutically acceptable salt thereof.
14 : The compound of claim 1 , which is represented by the formula [IC]:
wherein
X 1 , R 1 , R 2 and m are as defined for claim 1 , and
R 12 is
(a) hydrogen,
(b) hydroxy,
(c) cyano,
(d) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(e) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(f) carboxy,
(g) —CO—NR 5 R 6 [wherein R 5 and R 6 are each independently C 1-4 alkyl (wherein the alkyl is optionally substituted by C 4 alkoxy), or R 5 and R 6 optionally form, together with the nitrogen atom bonded thereto, 4- to 6-membered heterocycloalkyl containing 1 or 2 hetero atoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the heterocycloalkyl is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
(I) hydroxy, and
(II) C 1-6 alkyl (wherein the alkyl is optionally substituted by hydroxy)}],
(h) —NR 7 R 8 {wherein R 7 and R 8 are each independently C 1-6 alkyl or —CO—C 1-6 alkyl (wherein the alkyl is optionally substituted by cyano)}.
(i) —O—C 1-6 haloalkyl,
(j) a group represented by the formula:
(k) a group represented by the formula:
{wherein R 9 is C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy)}, or
(m) a group represented by the formula:
wherein R 10 is C 1-4 alkyl),
or a pharmaceutically acceptable salt thereof.
15 : The compound of claim 14 , wherein
R 12 is
(1) hydroxy,
(2) cyano,
(3) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(a) hydroxy,
(b) carboxy,
(c) —CONH 2 ,
(d) —CO—C 1-4 alkoxy,
(e) —SO 2 —C 1-4 alkyl, or
(f) a group represented by the formula:
(4) C 1-6 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(5) —CO—NR 5 R 6 [wherein R 5 and R 6 form, together with the nitrogen atom bonded thereto, 4- to 6-membered heterocycloalkyl containing 1 or 2 hetero atoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the heterocycloalkyl is optionally substituted by C 1-6 alkyl (wherein the alkyl is optionally substituted by hydroxy)}],
(6) —NR 7 R 8 {wherein R 7 and R 8 are each independently C 1-4 alkyl or —CO—C 1-6 alkyl (wherein the alkyl is optionally substituted by cyano)},
(7) a group represented by the formula:
(8) a group represented by the formula:
{wherein R 9 is C 1-4 alkyl (wherein the alkyl is optionally substituted by C 1-4 alkoxy)}, or
(9) a group represented by the formula:
wherein R 10 is C 1-4 alkyl,
or a pharmaceutically acceptable salt thereof.
16 : The compound of claim 1 , which is represented by the formula [ID]:
wherein
X 1 , R 1 , R 2 and m are as defined for claim 1 , and
R 14 is
(a) hydrogen,
(b) hydroxy,
(c) C 1-6 alkyl (wherein the alkyl is optionally substituted by
(I) hydroxy,
(II) carboxy,
(III) —CONH 2 ,
(IV) —CO—C 1-4 alkoxy,
(V) —SO 2 —C 1-4 alkyl, or
(VI) a group represented by the formula:
(d) C 1 alkoxy (wherein the alkoxy is optionally substituted by hydroxy or —SO 2 —C 1-4 alkyl),
(e) carboxy,
(f) —CO—C 1-4 alkoxy,
(g) —O—C 1-6 haloalkyl, or
(h) a group represented by the formula:
or a pharmaceutically acceptable salt thereof.
17 : The compound of claim 16 , wherein R 14 is C 1-6 alkyl (wherein the alkyl is optionally substituted by hydroxy), or a pharmaceutically acceptable salt thereof.
18 : A compound selected from the group consisting of the following structural formulas:
or a pharmaceutically acceptable salt thereof.
19 : A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
20 - 22 . (canceled)
23 : A method for inhibiting H-PGDS in a mammal, comprising administering a pharmaceutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to the mammal.
24 : A method for treating or preventing a disease selected from the group consisting of peripheral arterial diseases, cardiovascular diseases, allergic asthma, chronic obstructive pulmonary diseases, allergic rhinitis, sarcopenia, and Duchenne muscular dystrophy in a mammal, comprising administering a pharmaceutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to the mammal.
25 : The method of claim 24 , wherein the peripheral arterial disease is intermittent claudication or comprehensive severe chronic lower extremity ischemia based on PAD.
26 - 31 . (canceled)