1.
J Med Chem
; 25(1): 12-8, 1982 Jan.
Article
in English
| MEDLINE
| ID: mdl-7086815
ABSTRACT
A novel series of antiinflammatory agents, N-isoxazolyl-3-carboxamides of 4-hydroxy-2H-1,2-benzothiazine 1,1-dioxide, was synthesized and evaluated as antiinflammatory agents in the carrageenin-induced rat paw edema (CIRPE) assay and adjuvant-induced polyarthritis (AIP) assay. Several analogues were found to be equipotent or more potent than aspirin and phenylbutazone. Structure-activity relationships are discussed. One of the compounds, 4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-1,2-benzothiazine 3-carboxamide 1,1-dioxide (3a; isoxicam), was found to be 3 times as potent as phenylbutazone in the CIRPE and in the therapeutic AIP assays. Isoxicam (3a) is presently undergoing phase III clinical trial as an antiarthritic drug.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Isoxazoles/pharmacology , Oxazoles/pharmacology , Piroxicam/analogs & derivatives , Thiazines/pharmacology , Animals , Anti-Inflammatory Agents/chemical synthesis , Isoxazoles/chemical synthesis , Male , Rats , Rats, Inbred Strains , Structure-Activity Relationship , Thiazines/chemical synthesis
2.
J Med Chem
; 18(2): 211-3, 1975 Feb.
Article
in English
| MEDLINE
| ID: mdl-235645
Subject(s)
Adrenergic beta-Antagonists/chemical synthesis , Anti-Arrhythmia Agents/chemical synthesis , Propanolamines/chemical synthesis , Adrenergic beta-Antagonists/pharmacology , Animals , Anti-Arrhythmia Agents/pharmacology , Benzyl Compounds/chemical synthesis , Benzyl Compounds/pharmacology , Blood Pressure/drug effects , Dogs , Heart Rate/drug effects , Ouabain/antagonists & inhibitors , Propanolamines/pharmacology , Vagotomy
3.
3-(Alpha-(tert-butylamino)methyl)-5-hydroxy-m-xylene-alpha, alpha'-diol, a selective bronchodilator.
J Med Chem
; 17(10): 1112-5, 1974 Oct.
Article
in English
| MEDLINE
| ID: mdl-4153860
Subject(s)
Bronchodilator Agents/chemical synthesis , Ethanolamines/chemical synthesis , Phenethylamines/chemical synthesis , Administration, Oral , Aerosols , Airway Resistance/drug effects , Albuterol/pharmacology , Animals , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/pharmacology , Dogs , Dose-Response Relationship, Drug , Ethanolamines/administration & dosage , Ethanolamines/pharmacology , Guinea Pigs , Heart Atria/drug effects , Heart Rate/drug effects , Histamine H1 Antagonists/administration & dosage , In Vitro Techniques , Isoproterenol/pharmacology , Levobunolol/pharmacology , Male , Phenethylamines/administration & dosage , Phenethylamines/pharmacology , Spirometry , Terbutaline/pharmacology , Trachea/drug effects , Xylenes/administration & dosage , Xylenes/chemical synthesis , Xylenes/pharmacology
4.
J Med Chem
; 16(5): 585-8, 1973 May.
Article
in English
| MEDLINE
| ID: mdl-4146254
Subject(s)
Adrenergic beta-Antagonists/chemical synthesis , Levobunolol/chemical synthesis , Naphthalenes/chemical synthesis , Adrenergic beta-Antagonists/pharmacology , Animals , Blood Pressure/drug effects , Dogs , Heart Rate/drug effects , Isoproterenol/pharmacology , Levobunolol/pharmacology , Naphthalenes/pharmacology , Structure-Activity Relationship
5.
J Med Chem
; 16(3): 254-7, 1973 Mar.
Article
in English
| MEDLINE
| ID: mdl-4147388
Subject(s)
Adrenergic beta-Antagonists/chemical synthesis , Levobunolol/chemical synthesis , Adrenergic beta-Antagonists/pharmacology , Animals , Anti-Arrhythmia Agents/chemical synthesis , Anti-Arrhythmia Agents/pharmacology , Blood Pressure/drug effects , Dogs , Heart Rate/drug effects , Isoproterenol/antagonists & inhibitors , Levobunolol/pharmacology , Magnetic Resonance Spectroscopy , Ouabain/pharmacology , Receptors, Adrenergic/drug effects , Spectrophotometry, Ultraviolet , Structure-Activity Relationship , Vascular Resistance/drug effects
6.
J Med Chem
; 16(1): 44-8, 1973 Jan.
Article
in English
| MEDLINE
| ID: mdl-4682200
Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Thiazines/chemical synthesis , Animals , Anti-Inflammatory Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Carbamates/chemical synthesis , Carbamates/therapeutic use , Carrageenan , Disease Models, Animal , Dose-Response Relationship, Drug , Edema/chemically induced , Edema/drug therapy , Foot , Freund's Adjuvant , Male , Rats , Structure-Activity Relationship , Sulfoxides/chemical synthesis , Sulfoxides/therapeutic use , Thiazines/therapeutic use
7.
Proc Soc Exp Biol Med
; 139(3): 909-12, 1972 Mar.
Article
in English
| MEDLINE
| ID: mdl-4554135
Subject(s)
Immunity, Cellular/drug effects , Immunosuppressive Agents/pharmacology , Pyridines/pharmacology , Acetates/pharmacology , Animals , Antibody Formation , Erythrocytes/immunology , Female , Graft Rejection , Hypersensitivity, Delayed/prevention & control , Immunity, Active , Mercaptopurine/pharmacology , Mice , Mice, Inbred Strains , Models, Biological , Sheep , Skin Transplantation , Sulfenic Acids/pharmacology , Transplantation Immunology , Transplantation, Homologous
8.
J Med Chem
; 13(4): 684-8, 1970 Jul.
Article
in English
| MEDLINE
| ID: mdl-4393796
9.
J Org Chem
; 33(4): 1663-4, 1968 Apr.
Article
in English
| MEDLINE
| ID: mdl-5641032
10.
J Org Chem
; 32(12): 4089-91, 1967 Dec.
Article
in English
| MEDLINE
| ID: mdl-5622479
11.
J Med Chem
; 10(6): 1063-5, 1967 Nov.
Article
in English
| MEDLINE
| ID: mdl-6069772
12.
J Org Chem
; 32(11): 3691-3, 1967 Nov.
Article
in English
| MEDLINE
| ID: mdl-5622462
13.
J Med Chem
; 10(5): 888-90, 1967 Sep.
Article
in English
| MEDLINE
| ID: mdl-6057836
14.
J Med Chem
; 10(2): 223-7, 1967 Mar.
Article
in English
| MEDLINE
| ID: mdl-5342286
15.
J Org Chem
; 31(6): 1765-71, 1966 Jun.
Article
in English
| MEDLINE
| ID: mdl-5940658