Benzothiazoles having histamine H3 receptor activity
View Patent ↗Certain novel benzothiazoles and benzoxazoles, e.g., 2-(piperazin-1-yl)benzothiazoles and 2-(piperazin-1-yl)benzoxazoles, optionally substituted in the 3 and/or 4 positions of the piperazine rings,! of the general formula (1): having histamine H3 antagonistic activity can be used in pharmaceutical compositions.
1. A compound of formula I:
wherein R 1 is cyclopentyl, cyclopropyl, or isopropyl;
m is 1
X is —S—;
R 2 , R 3 , and R 4 are hydrogen;
one of R 5 and R 6 is a group of the formula —Y—(CH 2 ) s —(C═O) r —NR 7 R 8 , and the other is hydrogen;
r is 0 or 1;
s is 0 or 1;
Y is a bond; and
R 7 and R 8 independently are hydrogen, C 1-6 -alkyl or C 3-8 -cycloalkyl; or R 7 and R 8 can together with the attached nitrogen form a heterocyclyl group;
or a pharmaceutically acceptable salt thereof.
2. A compound, which is a compound selected from the group consisting of:
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-yl]piperidin-1-ylmethanone,
2-(4-isopropylpiperazin-1-yl)benzothiazole-6-carboxylic acid dimethylamide,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-yl]morpholin-4-ylmethanone,
2-(4-isopropylpiperazin-1-yl)-6-piperidin-1-ylmethylbenzothiazole,
2-(4-isopropylpiperazin-1-yl)-6-(morpholin-4-ylmethyl)benzothiazole,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]dimethylamine,
[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]dimethylamine,
2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole,
2-(4-cyclopropylpiperazin-1-yl)-6-(morpholin-4-ylmethyl)benzothiazole,
2-(4-cyclopropylpiperazin-1-yl)-6-(piperidin-1-ylmethyl)benzothiazole,
cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine,
2-(4-isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole,
[2-(4-isopropylpiperazin-1-yl)benzothiazol-5-ylmethyl]dimethylamine, and
[2-(4-isopropylpiperazin-1-yl)benzothiazol-5-yl]pyrrolidin-1-ylmethanone;
or a pharmaceutically acceptable salt thereof.
3. 2-(4-Cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.
4. Cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine or a pharmaceutically acceptable salt thereof.
5. 2-(4-Isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or excipient.
7. The compound according to claim 3 , wherein the compound is 2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole.
8. The compound according to claim 4 , wherein the compound is cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine.
9. The compound according to claim 5 , wherein the compound is 2-(4-isopropylpiperazin-1-yl)-5 -(pyrrolidin-1-ylmethyl)benzothiazole.
10. A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier or excipient.
11. A pharmaceutical composition comprising a compound of claim 3 and a pharmaceutically acceptable carrier or excipient.
12. A pharmaceutical composition comprising a compound of claim 4 and a pharmaceutically acceptable carrier or excipient.
13. A pharmaceutical composition comprising a compound of claim 5 and a pharmaceutically acceptable carrier or excipient.