Modulator
The present disclosure relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Z is selected from OH, NHCH 2 CH 2 F, NHCH(Me)CH 2 OH and NHCH 2 CH 2 OH; X is an alkylene, alkenylene, or alkynylene group, each of which may be optionally substituted by one or more substituents selected from alkyl, COOH, CO 2 -alkyl, alkenyl, CN, NH 2 , hydroxy, halo, alkoxy, CF 3 and nitro; Y is a polar functional group selected from OH, NO 2 , CN, COR 3 , COOR 3 , NR 3 R 4 , CONR 3 R 4 , SO 3 H, SO 2 —R 3 , SO 2 NR 3 R 4 and CF 3 , where each of R 3 and R 4 is independently H or a hydrocarbyl group; A is phenyl or pyridyl; and B is (CH 2 ) n where n is 0; with the proviso that: (i) when A is phenyl, and Z is OH, X—Y is other than C≡C—(CH 2 ) 2 CO 2 H, C≡C—(CH 2 ) 2 CO 2 Me, (CH 2 ) 4 CO 2 H. Uses of such compounds as medicaments for the treatment of a muscular disorder, a gastrointestinal disorder, or for controlling spasticity or tremors are provided.
1. A compound of formula I, or a pharmaceutically acceptable salt thereof,
wherein
Z is selected from OH, NHCH 2 CH 2 F, NHCH(Me)CH 2 OH and NHCH 2 CH 2 OH;
X is an alkenylene or alkynylene group, each of which may be optionally substituted by one or more substituents selected from alkyl, COOH, CO 2 -alkyl, akenyl, CN, NH 2 , hydroxy, halo, alkoxy, CF 3 , and nitro;
Y is a polar functional group selected from OH, NO 2 , CN, COR 3 , COOR 3 , NR 3 R 4 , CONR 3 R 4 , SO 3 H, SO 2 —R 3 , SO 2 NR 3 R 4 and CF 3 , where each of R 3 and R 4 is independently H or a hydrocarbyl group;
A is phenyl or pyridyl; and
B is (CH 2 ) n where n is 0;
with the proviso that:
when A is phenyl, and Z is OH, X—Y is other than C≡C—(CH 2 ) 2 OH, C≡C—(CH 2 ) 2 OH, C≡C—(CH 2 ) 2 CO 2 Me.
2. A compound according to claim 1 wherein Y is selected from CN, OH, COOR 3 , SO 2 NR 3 R 4 , CONR 3 R 4 , where each of R 3 and R 4 is independently H or a hydrocarbyl group.
3. A compound according to claim 1 wherein each of R 3 and R 4 is independently H, an alkyl group, an aryl group, or a cycloalkyl group, each of which may be optionally substituted.
4. A compound according to claim 1 wherein Y is selected from OH, CN, COOR 3 , CONR 3 R 4 , where each of R 3 and R 4 is independently H or an optionally substituted alkyl group.
5. A compound according to claim 1 wherein Y is selected from OH, CN, COOMe, COOH, CONH 2 , CONHMe and CONMe 2 .
6. A compound according to claim 1 wherein X—Y is selected from
—C≡C—(CH 2 ) p —Y;
and
—C(R 5 )═C(R 6 )—(CH 2 ) q —Y;
wherein each of R 5 and R 6 is independently H or alkyl, and each of p and q is independently 2, 3, or 4.
7. A compound according to claim 1 wherein X—Y is selected from
—C≡C—(CH 2 ) p —Y;
and
—CH═CH—(CH 2 ) q —Y;
wherein each of p and q is independently 2, 3 or 4.
8. A compound according to claim 6 wherein X—Y is
cis-C(R 5 )═C(R 6 )—(CH 2 ) q —Y and q is 2, 3 or 4.
9. A compound according to claim 1 wherein A is phenyl.
10. A compound which is selected from the group consisting of
11. The compound of claim 10 which is
12. The compound of claim 11 which is in the form of a racemic mixture.
13. A compound according to claim 10 selected from the following:
14. The compound according to claim 11 selected from the following:
15. A compound according to claim 13 selected from the following:
16. A compound according to claim 13 selected from the following:
17. A compound according to claim 13 selected from the following: