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, having histamine H3 antagonistic activity can be used in pharmaceutical compositions.
1. A method of treating obesity comprising administering to a human subject 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.
2. The method of claim 1 , wherein the compound is 2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the compound is cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the compound is 2-(4-isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.
5. A method of reducing weight comprising administering to a human subject 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.
6. The method of claim 5 , wherein the compound is 2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.
7. The method of claim 5 , wherein the compound is cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine or a pharmaceutically acceptable salt thereof.
8. The method of claim 5 , wherein the compound is 2-(4-isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.
9. A method of suppressing appetite or inducing satiety comprising administering to a human subject 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.
10. The method of claim 9 , wherein the compound is 2-(4-cyclopropylpiperazin-1-yl)-6-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.
11. The method of claim 9 , wherein the compound is cyclopropyl-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-ylmethyl]amine or a pharmaceutically acceptable salt thereof.
12. The method of claim 9 , wherein the compound is 2-(4-isopropylpiperazin-1-yl)-5-(pyrrolidin-1-ylmethyl)benzothiazole or a pharmaceutically acceptable salt thereof.