Pharmacologically active substituted benzamides

• US 5,011,992 A
• Filed: 08/22/1989
• Issued: 04/30/1991
• Est. Priority Date: 06/28/1984
• Status: Expired due to Fees

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Willner, David, Monkovic, Ivo
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): Meller, Michael V.
• Application Number:
  US07/397,650
• Time in Patent Office: 616 Days
• Field of Search: 560/251, 564/150, 564/156, 564/162, 564/167, 514/166, 514/546, 514/615, 514/616, 514/618-622
• US Class Current: 564/167
• CPC Class Codes: C07C 243/00 Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
• CPC Class Codes: C07C 255/00 Carboxylic acid nitriles cyanogen or compounds thereof C01C3/00
• CPC Class Codes: C07D 209/48 with oxygen atoms in positions 1 and 3, e.g. phthalimide
• CPC Class Codes: C07D 211/42 attached in position 3 or 5
• CPC Class Codes: C07D 213/30 Oxygen atoms
• CPC Class Codes: C07D 233/22 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 261/08 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 263/24 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
• CPC Class Codes: C07D 295/185 from aliphatic carboxylic acids
• CPC Class Codes: C07D 317/22 etherified
• CPC Class Codes: C07D 333/16 by oxygen atoms

Abstract

Novel substituted benzamides of the formula ##STR1## wherein R¹, R², R³, R⁴, R⁵ and A are as defined herein are useful in the treatment of emesis, and particularly chemotherapy-induced emesis in cancer patients. Some of the compounds are also useful in disorders relating to impaired gastric motility.

Claims

1. A compound having the formula ##STR60## wherein R² is selected from the group consisting of ##STR61## in which R⁹, R¹² and R¹³ are independently selected from hydrogen and (lower) alkyl;

R¹⁴ is selected from hydrogen, (lower) alkyl and hydrazino;

or R¹² and R¹⁴, taken together with the carbon atoms to which they are attached, may form a 5 to 7-membered cycloalkane ring;

R¹⁵ is hydrogen; and

X is oxygen;

or a pharmaceutically acceptable salt, hydrate, solvate or quaternary ammonium salt thereof.

2. The compound of claim 1 which is 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(2-propanon-1-yl)oxybenzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt thereof.

3. The compound of claim 1 which is 4-amino-2-(butan-2-on-3-yl)oxy-5-chloro-N-[2-(diethylamino)ethyl]benzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt thereof.

4. The compound of claim 1 which is 4-amino-5-chloro-2-(cyclohexanon-2-yl)oxy-N-[2-(diethylamino)ethyl]benzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt.

5. The compound of claim 1 which is 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(2-hydroxypropan-1-yl)oxybenzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt thereof.

6. The compound of claim 1 which is 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(pentan-2-on-3yl)oxybenzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt thereof.

7. The compound of claim 1 is 4-amino-2-(2-butanon-1-yl)oxy-5-chloro-N-[2-(diethylamino)ethyl]benzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt thereof.

8. The compound of claim 1 which is 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(pentan-2-on-1-yl)oxybenzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt thereof.

9. The compound of claim 1 which is 4-amino-5-chloro-2-(pentan-3-on-2-yl)oxy-N-(2-diethylaminoethyl)benzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt thereof.

10. The compound of claim 1 which is 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(2-hydrazino-2-oxoethoxy)benzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt thereof.

11. The compound of claim 1 which is threo-4-amino-5-chloro-N-[2-(diethylaminoethyl]-2-(2-hydroxybut-3-yl)oxybenzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt thereof.

12. The compound of claim 1 which is erythro-4-amino-5-chloro-N-[2-(diethylaminoethyl]-2-(2-hydroxybut-3-yl)oxybenzamide, or a nontoxic pharmaceutically acceptable salt, hydrate, ester or quaternary ammonium salt thereof.

13. The compound of claim 1 which is 4-Amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(3-hydroxybut-1-yl)oxybenzamide.

14. A pharmaceutical composition for the alleviation of nausea and vomitting, which comprises an effective antiemetic amount of at least one compound of claim 1, or a salt, hydrate or solvate thereof, plus a pharmaceutically acceptable carrier.

15. A pharmaceutical composition for the treatment of disorders related to impaired gastric motility, which comprises an effective gastric motility facilitating amount of at least one compound of claim 1, or a salt, hydrate or solvate thereof, and a pharmaceutically acceptable carrier.

16. A method of alleviating nausea and vomiting in a warm-blooded mammal in need thereof, which comprises administering to said mammal an effective antiemetic amount of at least one compound of claim 1, or a salt, hydrate or solvate thereof, in a pharmaceutically acceptable carrier.

17. A method of treating disorders related to impaired gastric motility in a warm-blooded mammal, which comprises administering to said mammal an effective gastric motility facilitating amount of at least one compound of claim 1, or a salt, hydrate or solvate thereof, in a pharmaceutically acceptable carrier.