US4000302A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Pharmaceutical compositions and methods of inhibiting H-1 and H-2 histamine receptors
Assignee: Smith Kline & French Laboratories Ltd
•
Filing: 1975-04-16
•
Granted: 1976-12-28
•
Expires: 1995-04-16
Abstract
Abstract Pharmaceutical compositions and methods of inhibiting H-1 and H-2 histamine receptors by administering an antihistamine and an H-2 histamine receptor inhibitor. Exemplary of the antihistamine in the compositions and methods of this invention is mepyramine and exemplary of the H-2 histamine receptor inhibitor is N-cyano-N'-methyl-N''-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]gua nidine.
Inventors
- 👤 James Whyte Black
- 👤 Michael Edward Parsons
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 18:45
CPC Classifications
C; C07; C07D; C07D213/00; C07D213/02; C07D213/04; C07D213/24; C07D213/36; C07D213/40; A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/40; A61K31/41; A61K31/415; A61K31/42; A61K31/425; A61K31/435; A61K31/44; A61K31/445; A61K31/495; A61K31/50; A61K31/505; A61K31/54; C07D249/00; C07D249/02; C07D249/08; C07D275/00; C07D275/02
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
155 words
A pharmaceutical composition having H-1 and H-2 histamine receptor inhibiting activity which comprises about 30 mg. to about 250 mg. of an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, about 50 mg. to about 500 mg. of an H-2 histamine receptor inhibitor, H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, and a pharmaceutically acceptable diluent or carrier, wherein said H-2 histamine receptor inhibitor is a compound of the formula: ##STR15## wherein A is such that there is formed together with the carbon atom shown an imidazole ring; X 1 is hydrogen, lower alkyl, halogen, amino or hydroxyl; X 2 is hydrogen; k is 1; m is 2; Y is sulphur; E is NR 2 ; R 1 is hydrogen or lower alkyl; and R 2 is hydrogen, nitro or cyano, or a pharmaceutically acceptable acid addition salt thereof.
Claim 2
Dependent Claim
155 words
A pharmaceutical composition having H-1 and H-2 histamine receptor inhibiting activity which comprises about 30 mg. to about 250 mg. of an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, about 50 mg. to about 500 mg. of an H-2 histamine receptor inhibitor, H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, and a pharmaceutically acceptable diluent or carrier, wherein said H-2 histamine receptor inhibitor is a compound of the formula: ##STR15## wherein A is such that there is formed together with the carbon atom shown an imidazole ring; X 1 is hydrogen, lower alkyl, halogen, amino or hydroxyl; X 2 is hydrogen; k is 1; m is 2; Y is sulphur; E is NR 2 ; R 1 is hydrogen or lower alkyl; and R 2 is hydrogen, nitro or cyano, or a pharmaceutically acceptable acid addition salt thereof.
Claim 3
Dependent Claim
43 words
A pharmaceutical composition according to claim 1 wherein the antihistamine is a compound selected from the group consisting of mepyramine, mebrophenhydramine, promethazine, diphenhydramine, chloropheniramine, triprolidene, antazoline, bromodiphenydramine, parabromdylamine, carbinoxamine, cyproheptadine, chlorcyclizine, dimethindene, diphenylpyraline, dimethothiazine, methdilazine, trimeprazine, mebhydroline, methapyrilene, phenindamine, pheniramine, phenyltoloxamine and pyrrobutamine.
Claim 4
Dependent Claim
26 words
A pharmaceutical composition according to claim 1 wherein the H-2 histamine receptor inhibitor is a compound selected from the group consisting of N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidine, 2-[(4-imidazolyl)methylthio]-ethylguanidine and N-(2-[(4-methyl-5-imidazolyl)methylthio]-ethyl)-N'-nitroguanidine.
Claim 5
Dependent Claim
15 words
A pharmaceutical composition according to claim 1 wherein the H-2 histamine receptor inhibitor is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine
Claim 6
Dependent Claim
19 words
A pharmaceutical composition according to claim 1, wherein the antihistamine is mepyramine and the H-2histamine receptor inhibitor is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine.
Claim 7
Independent Claim
164 words
A method of inhibiting H-1 and H-2 histamine receptors which comprises administering to an animal in need thereof, in amounts sufficient to inhibit both H-1 and H-2 histamine receptors, an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, and an H-2 histamine receptor inhibitor, said H-1 histamine receptors being those histamine receptors which are inhibited by mepyramine and said H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, wherein said H-2 histamine receptor inhibitor is a compound of the formula: ##STR16## wherein A is such that there is formed together with the carbon atom shown an imidazole ring; X 1 is hydrogen, lower alkyl, halogen, amino or hydroxyl; X 2 is hydrogen; k is 1; m is 2; Y is sulphur; E is NR 2 ; R 1 is hydrogen or lower alkyl; and R 2 is hydrogen, nitro or cyano, or a pharmaceutically acceptable acid addition salt thereof.
Claim 8
Independent Claim
164 words
A method of inhibiting H-1 and H-2 histamine receptors which comprises administering to an animal in need thereof, in amounts sufficient to inhibit both H-1 and H-2 histamine receptors, an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, and an H-2 histamine receptor inhibitor, said H-1 histamine receptors being those histamine receptors which are inhibited by mepyramine and said H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, wherein said H-2 histamine receptor inhibitor is a compound of the formula: ##STR16## wherein A is such that there is formed together with the carbon atom shown an imidazole ring; X 1 is hydrogen, lower alkyl, halogen, amino or hydroxyl; X 2 is hydrogen; k is 1; m is 2; Y is sulphur; E is NR 2 ; R 1 is hydrogen or lower alkyl; and R 2 is hydrogen, nitro or cyano, or a pharmaceutically acceptable acid addition salt thereof.
Claim 9
Dependent Claim
41 words
A method of claim 6 wherein the antihistamine is a compound selected from the group consisting of mepyramine, mebrophenhydramine, promethazine, diphenhydramine, chlorpheniramine, triprolidene, antazoline, bromodiphenydramine, parabromdylamine, carbinoxamine, cyproheptadine, chlorcyclizine, dimethindene, diphenylpyraline, dimethothiazine, methdilazine, trimeprazine, mebhydroline, methapyrilene, phenindamine, pheniramine, phenyltoloxamine and pyrrobutamine.
Claim 10
Dependent Claim
22 words
A method of claim 6 wherein the H-2 histamine receptor inhibitor is selected from the group consisting of N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine, 2-[(4-imidazolyl)methylthio]ethylguanidine and N-(2-[(4-methyl-5-imidazolyl)methylthio]ethyl)-N'-nitroguanidine.
Claim 11
Dependent Claim
13 words
A method of claim 6 wherein the H-2 histamine receptor inhibitor is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine.
Claim 12
Dependent Claim
19 words
The method of claim 6 wherein the antihistamine is mepyramine and the H-2 histamine receptor inhibitor is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)methylthio) ethyl]guanidine.
Claim 13
Independent Claim
143 words
A method of producing anti-inflammatory activity which comprises administering to an animal in need thereof, in amounts sufficient to produce said activity, an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, and an H-2 histamine receptor inhibitor, said H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, wherein said H-2 -histamine receptor inhibitor is a compound of the formula: ##STR17## wherein A is such that there is formed together with the carbon atom shown an imidazole ring; X 1 is hydrogen, lower alkyl, halogen, amino or hydroxyl; X 2 is hydrogen; k is 1; m is 2; Y is sulphur; E is NR 2 ; R 1 is hydrogen or lower alkyl; and R 2 is hydrogen, nitro or cyano, or a pharmaceutically acceptable acid addition salt thereof.
Claim 14
Independent Claim
143 words
A method of producing anti-inflammatory activity which comprises administering to an animal in need thereof, in amounts sufficient to produce said activity, an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, and an H-2 histamine receptor inhibitor, said H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, wherein said H-2 -histamine receptor inhibitor is a compound of the formula: ##STR17## wherein A is such that there is formed together with the carbon atom shown an imidazole ring; X 1 is hydrogen, lower alkyl, halogen, amino or hydroxyl; X 2 is hydrogen; k is 1; m is 2; Y is sulphur; E is NR 2 ; R 1 is hydrogen or lower alkyl; and R 2 is hydrogen, nitro or cyano, or a pharmaceutically acceptable acid addition salt thereof.
Claim 15
Dependent Claim
42 words
A method of claim 11 in which the antihistamine is a compound selected from the group consisting of mepyramine, mebrophenhydramine, promethazine, diphenhydramine, chlorpheniramine, triprolidene, antazoline, bromodiphenhydramine, parabromdylamine, carbinoxamine, cyproheptadine, chlorcyclizine, dimethindene, diphenylpyraline, dimethothiazine, methdilazine, trimeprazine, mebhydroline, methapyrilene, phenindamine, pheniramine, phenyltoloxamine and pyrrobutamine.
Claim 16
Dependent Claim
21 words
A method of claim 11 wherein the H-2 histamine receptor inhibitor is selected from the group consisting of N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine,2-[(4-imidazolyl)methylthio]ethylguanidine and N-(2-[(4-methyl-5-imidazolyl)methylthio]ethyl)-N'-nitroguanidine.
Claim 17
Dependent Claim
13 words
A method of claim 11 wherein the H-2 histamine receptor inhibitor is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine.
Claim 18
Dependent Claim
18 words
A method of claim 11 wherein the antihistamine is mepyramine and the H-2 histamine receptor inhibitor is N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)methylthio)-ethyl]guanidine
Claim 19
Dependent Claim
89 words
A pharmaceutical composition having H-1 and H-2 histamine receptor inhibiting activity which comprises about 30 mg. to about 250 mg. of an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, about 50 mg. to about 500 mg. of an H-2 histamine receptor inhibitor, H-2histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, and a pharmaceutically acceptable diluent or carrier, wherein said H-2 histamine receptor inhibitor is 4-(3-guanidinopropyl)imidazole or a pharmaceutically acceptable acid addition salt thereof.
Claim 20
Dependent Claim
89 words
A pharmaceutical composition having H-1 and H-2 histamine receptor inhibiting activity which comprises about 30 mg. to about 250 mg. of an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, about 50 mg. to about 500 mg. of an H-2 histamine receptor inhibitor, H-2histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, and a pharmaceutically acceptable diluent or carrier, wherein said H-2 histamine receptor inhibitor is 4-(3-guanidinopropyl)imidazole or a pharmaceutically acceptable acid addition salt thereof.
Claim 21
Independent Claim
99 words
A method of inhibiting H-1 and H-2 histamine receptors which comprises administering to an animal in need thereof, in amounts sufficient to inhibit both H-1 and H-2 histamine receptors, an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, and an H-2 histamine receptor inhibitor, said H-1 histamine receptors being those histamine receptors which are inhibited by mepyramine and said H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, wherein said H-2 histamine receptor inhibitor is 4-(3-guanidinopropyl)imidazole or a pharmaceutically acceptable acid addition salt thereof.
Claim 22
Independent Claim
99 words
A method of inhibiting H-1 and H-2 histamine receptors which comprises administering to an animal in need thereof, in amounts sufficient to inhibit both H-1 and H-2 histamine receptors, an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, and an H-2 histamine receptor inhibitor, said H-1 histamine receptors being those histamine receptors which are inhibited by mepyramine and said H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, wherein said H-2 histamine receptor inhibitor is 4-(3-guanidinopropyl)imidazole or a pharmaceutically acceptable acid addition salt thereof.
Claim 23
Independent Claim
78 words
A method of producing anti-inflammatory activity which comprises administering to an animal in need thereof, in amounts sufficient to produce said acitivity, an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, and an H-2 histamine receptor inhibitor, said H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, wherein said H-2 histamine receptor inhibitor is 4-(3-guanidinopropyl)imidazole or a pharmaceutically acceptable acid addition salt thereof.
Claim 24
Independent Claim
78 words
A method of producing anti-inflammatory activity which comprises administering to an animal in need thereof, in amounts sufficient to produce said acitivity, an antihistamine, said antihistamine being a compound which inhibits those histamine receptors inhibited by mepyramine, and an H-2 histamine receptor inhibitor, said H-2 histamine receptors being those histamine receptors which are not inhibited by mepyramine but are inhibited by burimamide, wherein said H-2 histamine receptor inhibitor is 4-(3-guanidinopropyl)imidazole or a pharmaceutically acceptable acid addition salt thereof.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1979-12-28 | 1980-06-28 | 1980-12-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1983-12-28 | 1984-06-28 | 1984-12-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1987-12-28 | 1988-06-28 | 1988-12-28 | $7700.00 | Window Closed / Lapsed |