Benzothiazines (including Hydrogenated) Patents (Class 544/49)
  • Patent number: 4829062
    Abstract: A series of novel oxyalkyl ether derivatives of various enolic oxicam compounds have been prepared, including certain novel enol oxyalkyl ethers of 4-hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (piroxicam). These particular compounds are useful in theraphy as prodrug forms of the known anti-inflammatory and analgesic oxicams.
    Type: Grant
    Filed: December 22, 1987
    Date of Patent: May 9, 1989
    Assignee: Pfizer Inc.
    Inventors: Joseph G. Lombardino, Anthony Marfat
  • Patent number: 4820842
    Abstract: The present invention provides a process for preparing a 5-cyano-2-substituted-1,4-dihydropyridine compound having cardiovascular activity.
    Type: Grant
    Filed: September 11, 1987
    Date of Patent: April 11, 1989
    Assignee: Warner-Lambert Company
    Inventors: Kevin R. Anderson, Ila Sircar
  • Patent number: 4818756
    Abstract: The invention relates to substituted 2-pyrimidinyl-1-piperazine derivatives defined herein by formula (I), processes for their manufacture, compositions containing said substituted 2-pyrimidinyl-1-piperazine derivatives as active materials and the use of said compounds and compositions as agents effecting the central nervous system. Also included in the invention are intermediates of formula (VIII) for making the active formula (I) compounds.
    Type: Grant
    Filed: March 10, 1986
    Date of Patent: April 4, 1989
    Assignee: Troponwerke GmbH & Co., KG
    Inventors: Peter-Rudolf Seidel, Harald Horstmann, Jorg Traber, Wolfgang Dompert, Thomas Glaser, Teunis Schuurman
  • Patent number: 4797483
    Abstract: A process for obtaining 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, which may be used as a non-steroidal analgesic and anti-inflammatory drug. The process comprises reacting saccharin sodium with isopropyl chloroacetate in dimethylformamide, reacting the resultant isopropyl 3-oxo-1,2-benzoisothiazoline-2-acetate 1,1-dioxide with sodium isopropylate in isopropanol to produce an intermediate which, when methylated in an aqueous-alcoholic basic medium with dimethyl sulfate, gives an intermediate compound which when condensed with 2-aminopyridine in xylene, yields 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazone-3-carboxamide 1,1-dioxide.
    Type: Grant
    Filed: June 24, 1987
    Date of Patent: January 10, 1989
    Assignee: Induspol, S.A.
    Inventors: Jordi Frigola Constansa, Jose M. Ribalta Baro, Julio Campon Pardo
  • Patent number: 4750930
    Abstract: Novel N-hydroxy-N'-sulfonylguanidine compounds are described which possess significant herbicidal and plant growth regulant activity for control of undesired vegetation.
    Type: Grant
    Filed: June 10, 1987
    Date of Patent: June 14, 1988
    Assignee: E. I. Du Pont de Nemours and Company
    Inventor: Rafael Shapiro
  • Patent number: 4748174
    Abstract: The water soluble acid addition salts of an NSAID, such as acetylsalicylic acid, fenbufen, diflunisal, piroxicam, naproxen, or the like, with either glucamine or meglumine (N-methylglucamine) are useful anti-inflammatory and analgesic drugs, well adopted for parenteral, oral, rectal or topical administration.
    Type: Grant
    Filed: January 5, 1987
    Date of Patent: May 31, 1988
    Assignee: Therapicon s.r.l.
    Inventor: Paolo A. Veronesi
  • Patent number: 4746355
    Abstract: Benzylsulfonylureas and arylsulfamoylureas are useful as pre-emergent and post-emergent herbicides and as plant growth regulants.
    Type: Grant
    Filed: July 16, 1986
    Date of Patent: May 24, 1988
    Assignee: E. I. Du Pont De Nemours and Company
    Inventors: Robert J. Pasteris, Mark E. Thompson
  • Patent number: 4746357
    Abstract: Sulfonylureas derived from acetylenic pyrimidines and triazines, useful as pre- and postemergence herbicides. Typical of this group is 2-[[(4-ethynyl-6-methylpyrimidine-2-yl)aminocarbonyl]-aminosulfonyl]-benzo ic acid, methyl ester.
    Type: Grant
    Filed: May 21, 1987
    Date of Patent: May 24, 1988
    Assignee: E. I. Du Pont de Nemours and Company
    Inventor: Steven P. Artz
  • Patent number: 4744816
    Abstract: Herbicidal sulfonamides such as 2-[[[4-(methylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl]aminocar bonyl]aminosulfonyl]benzoic acid, methyl ester are useful as herbicides and plant growth regulants.
    Type: Grant
    Filed: June 11, 1987
    Date of Patent: May 17, 1988
    Assignee: E. I. DuPont de Nemours and Company
    Inventors: Martha M. Bolinski, Donald J. Dumas
  • Patent number: 4732898
    Abstract: The present invention are 2-(2-aryl-2-oxo-alkylidene) analogs of 1,2,3,4-tetrahydropyridine-3,5-pyridinecarboxylic acids and particularly esters thereof having valuable calcium antagonist and positive inotropic activity useful in the treatment of cardiovascular disorders, pharmaceutical compositions and methods of use therefor.
    Type: Grant
    Filed: March 3, 1987
    Date of Patent: March 22, 1988
    Assignee: Warner-Lambert Company
    Inventors: Edward W. Badger, Michael D. Taylor
  • Patent number: 4705555
    Abstract: Aryl and heteroaryl sulfonimidamides which also contain a pyrimidine or triazine heterocycle are useful as general or selective preemergent and postemergent herbicides.
    Type: Grant
    Filed: February 20, 1987
    Date of Patent: November 10, 1987
    Assignee: E. I. Du Pont de Nemours and Company
    Inventor: Craig L. Hillemann
  • Patent number: 4694080
    Abstract: Certain substituted-4-hydroxy-(or 4-acyloxy-)2H-1,2-benzothiazine 1,1-dioxides having at the 3-position a 2-substituted-1,3,4-oxadiazol-5-yl, a 2-substituted-tetrazol-5-yl or a 1-substituted-tetrazol-5-yl group useful as selective 5-lipoxygenase pathway inhibitors; and methods for their preparation.
    Type: Grant
    Filed: March 19, 1986
    Date of Patent: September 15, 1987
    Assignee: Pfizer Inc.
    Inventors: Susumu Nakanishi, Isao Nagakura
  • Patent number: 4689069
    Abstract: Sulfonylureas derived from acetylenic pyrimidines and triazines, useful as pre- and postemergence herbicides. Typical of this group is 2-[[(4-ethynyl-6-methylpyrimidine-2-yl)aminocarbonyl]-aminosulfonyl]-benzo ic acid, methyl ester.
    Type: Grant
    Filed: June 27, 1985
    Date of Patent: August 25, 1987
    Assignee: E. I. Du Pont de Nemours and Company
    Inventor: Steven P. Artz
  • Patent number: 4683306
    Abstract: Process for the preparation of 3,4-dihydro-2-substituted-4(or 3)-oxo-2H-1,2-thiazine-3(or 4)-carboxylic acid 1,1,-dioxide magnesium chelate derivatives and its acids by reacting appropriately 3,4-dihydro-2-substituted-4(or 3)-oxo-2H-1,2-thiazine 1,1-dixoides with alkylmagnesiumcarbonate and then hydrolyzing and its use as intermediates for the preparation of N-substituted-2-substituted-2H-1,2-thiazine-3(or 4)-carboxamide-1,1-dioxide derivatives, effective antiinflammatory agents.
    Type: Grant
    Filed: July 13, 1984
    Date of Patent: July 28, 1987
    Assignee: YuHan Corporation Co., Ltd.
    Inventors: Jung J. Suh, You H. Hong
  • Patent number: 4666506
    Abstract: Aryl and heteroaryl sulfonimidamides which also contain a pyrimidine or triazine heterocycle are useful as general or selective preemergent and postemergent herbicides.
    Type: Grant
    Filed: July 11, 1985
    Date of Patent: May 19, 1987
    Assignee: E. I. Du Pont de Nemours and Company
    Inventor: Craig L. Hillemann
  • Patent number: 4656273
    Abstract: There is described a novel process for producing sulfonylureas of formula I ##STR1## wherein R.sub.1 is hydrogen or alkyl,R.sub.2 is ##STR2## E is .dbd.N-- or .dbd.CH--, R.sub.3 is alkyl, alkoxy or halogen,R.sub.4 is alkyl, cycloalkyl, alkoxy, halogen, alkoxy-alkyl, halo-alkyl or halo-alkoxy,R.sub.5 is hydrogen or alkyl,T is a substituted phenyl group ##STR3## Y is hydrogen or halogen, X is hydrogen, halogen, alkyl, halo-alkyl, alkenyl, halo-alkenyl, alkynyl, alkoxy, halo-alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, halo-alkylthio, alkylsulfonyloxy, phenylsulfonyloxy, phenylsulfonyloxy mono- or polysubstituted by alkyl, or is di-alkylsulfamoyl, andA is a bridge member which has 3 or 4 atoms and which contains 1 or 2 hetero atoms, selected from the group consisting of oxygen, sulfur and nitrogen,the said process comprising reacting a silfonamide of the formula IIT--SO.sub.2 --NH.sub.
    Type: Grant
    Filed: December 16, 1985
    Date of Patent: April 7, 1987
    Assignee: Ciba-Geigy Corporation
    Inventor: Werner Topfl
  • Patent number: 4623486
    Abstract: Certain novel p-aminomethylbenzoyl derivatives of 4-hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide and several other closely-related known oxicams have been prepared. These particular compounds are useful in therapy as prodrug forms of the known anti-inflammatory and analgesic oxicams. Preferred member compounds include 2-methyl-4-[4-(morpholinomethyl)benzoyloxy]-N-(2-pyridinyl)-2H-1,2-benzoth iazine-3-carboxamide 1,1-dioxide, 2-methyl-4-[4-(piperidinomethyl)benzoyloxy]-N-(2-pyridinyl)-2H-1,2-benzoth iazine-3-carboxamide 1,1-dioxide, 2-methyl-N-(6-methyl-2-pyridinyl)-4-[4-(piperidinomethyl)benzoyloxy]-2H-1, 2-benzothiazine-3-carboxamide 1,1-dioxide, 2-methyl-4-[4-(4-methylpiperazinomethyl)benzoyloxy]-N-(2-pyridinyl)-2H-1,2 -benzothiazine-3-carboxamide 1,1-dioxide and 2-methyl-4-[4-(pyridiniummethyl)benzoyloxy]-N-(2-pyridinyl)-2H-1,2-benzoth iazine-3-carboxamide 1,1-dioxide chloride. Methods for preparing these compounds from known starting materials are provided.
    Type: Grant
    Filed: May 29, 1985
    Date of Patent: November 18, 1986
    Assignee: Pfizer Inc.
    Inventor: Joseph G. Lombardino
  • Patent number: 4610982
    Abstract: Certain novel 2-acetoxybenzoyl and ring-substituted .alpha.-arylpropionyl derivatives of 4-hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide and several other closely-related known oxicams have been prepared. These particular compounds are useful in therapy as non-steroidal anti-arthritic agents. Typical member compounds include 4-(2-acetoxybenzoyloxy)-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-ca rboxamide 1,1-dioxide, 4-[.alpha.-(4-isobutylphenyl)propionyloxy]-2-methyl-N-(2-pyridinyl)-2H-1,2 -benzothiazine-3-carboxyamide N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxyamide 1,1-dioxide, 4-[.alpha.-(3-benzoylphenyl)propionyloxy]-2-methyl-N-(2-pyridinyl)-2H-1,2- benzothiazine-3-carboxamide 1,1-dioxide, "d-4-[.alpha.-6-methoxynaphth-2-yl)propionyloxy]-2-methyl-N-(2-pyridinyl)- 2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide" to -- d-4-[.alpha.-(6-methoxynaphth-2-yl)propionyloxy]-2-methyl-N-(2-pyridinyl)- 2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide.
    Type: Grant
    Filed: June 3, 1985
    Date of Patent: September 9, 1986
    Assignee: Pfizer Inc.
    Inventor: Joseph G. Lombardino
  • Patent number: 4599406
    Abstract: The process for the preparation of derivatives of 2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide of the formula ##STR1## wherein R represents hydroxy (Ia) or substituted hydroxy OR.sub.1 in which R.sub.1 is the cinnamoyl radical --CO--CH.dbd.CH--C.sub.6 H.sub.5 (Ib) consists in reacting a strong base salt of 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylic acid 1,1-dioxide with an acyl chloride R.sub.1 Cl, in which R.sub.1 is the cinnamoyl radical, or R.sub.2 Cl, in which R.sub.2 is an aromatic or aliphatic C.sub.2 -C.sub.6 acyl radical to give the corresponding mixed anhydride, optionally esterified at position 4, which is then reacted with 2-aminopyridine to give the desired amide.
    Type: Grant
    Filed: December 13, 1984
    Date of Patent: July 8, 1986
    Assignee: SPA-Societa Prodotti Antibiotici spa
    Inventors: Tiberio Bruzzese, Ernani Dell'Acqua, Franco Ottoni, Holger H. van den Heuvel
  • Patent number: 4589911
    Abstract: Fused N-phenylsulfonyl-N'-triazinylurea of formula I ##STR1## wherein Z is oxygen or sulfur,R.sup.1 is hydrogen, halogen, nitro, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 haloalkyl, cyano, or a --X--R.sup.5, --CO--X--R.sup.6, --CO--NR.sup.7 R.sup.8, --SO--R.sup.9 or --SO.sub.2 --R.sup.10 group,R.sup.2 is hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy,R.sup.3 is C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkoxy or C.sub.3 -C.sub.6 cycloalkyl,R.sup.4 is hydrogen, halogen, C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkoxy, C.sub.2 -C.sub.4 alkoxyalkoxy, C.sub.3 -C.sub.6 cycloalkyl or --NR.sup.11 R.sup.12,R.sup.5 is C.sub.3 -C.sub.5 alkynyl or C.sub.1 -C.sub.4 alkyl which is unsubstituted or substituted by halogen or C.sub.1 -C.sub.4 -alkoxy, or is C.sub.3 -C.sub.5 alkenyl, which is unsubstituted or is substituted by halogen or C.sub.1 -C.sub.4 -alkoxy,R.sup.6 and R.sup.9 are each independently C.sub.1 -C.sub.
    Type: Grant
    Filed: May 1, 1984
    Date of Patent: May 20, 1986
    Assignee: Ciba-Geigy Corporation
    Inventors: Josef Ehrenfreund, Werner Fory
  • Patent number: 4587335
    Abstract: The present invention refers to a new process for preparing 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-[N-(2-pyridinyl)carboxamide]-1,1 -dioxide, its phosphoric ester and the obtained phosphoric ester.
    Type: Grant
    Filed: July 17, 1984
    Date of Patent: May 6, 1986
    Inventor: Vincenzo Iannella
  • Patent number: 4586950
    Abstract: Herbicidal sulfonamides are useful as general or selective herbicides, both pre-emergence and post-emergence.
    Type: Grant
    Filed: September 20, 1983
    Date of Patent: May 6, 1986
    Assignee: E. I. Du Pont de Nemours & Company
    Inventor: Robert J. Pasteris
  • Patent number: 4582831
    Abstract: A novel crystalline form of the monoethanolamine salt of N-(2-pyridyl)-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide has been prepared. This novel crystalline form is designated as polymorph I and is useful in therapy as a non-steroidal anti-arthritic agent. Methods for preparing this polymorph from readily available materials are provided.
    Type: Grant
    Filed: November 16, 1984
    Date of Patent: April 15, 1986
    Assignee: Pfizer Inc.
    Inventor: Robert L. Robertson
  • Patent number: 4581178
    Abstract: Low valent transition metal complexes containing small cone angle phosphine or arsine ligands efficiently catalyze addition of aldehydes to compounds or groups having a C--H bond activated by a nitro or nitrile group, to provide nitroalcohols or cyanohydrins, respectively.
    Type: Grant
    Filed: February 28, 1985
    Date of Patent: April 8, 1986
    Assignee: E. I. Du Pont de Nemours and Company
    Inventor: David Milstein
  • Patent number: 4581356
    Abstract: New triazine derivatives represented by the formula: ##STR1## wherein R.sup.1 is a 1,2,3,4-tetrahydroquinolyl, 2-oxo-1,2,3,4-tetrahydroquinolyl, 2-oxo-1,2-dihydroquinolyl, indolyl, 2-oxoindolinyl, benzothiazolyl, 2-oxobenzothiazolinyl, 3,4-dihydro-1H-2,1-benzothiazinyl in which the S atom being optionally oxidized, or 3-oxo-2,3-dihydro-4H-1,4-benzoxazinyl, each of which may have one or more substituent(s) selected from lower alkyl, hydroxy(lower)alkyl, lower alkylamino, lower alkanoyl, cyclic lower alkanoyl, lower alkoxy(lower)alkyl, lower alkylamino(lower)alkanoyl, benzyl, benzyloxy(lower)alkyl, lower alkoxycarbonyl(lower)alkyl and 4-(2-hydroxyethyl)piperazin-1-yl-carbonylmethyl;R.sup.2 is a hydrogen, lower alkenyl, benzyl, carboxy(lower)alkyl or lower alkoxycarbonyl(lower)alkyl;R.sup.3 and R.sup.4, which may be the same or different, are each hydrogen or lower alkyl or together represent a bond;provided that when R.sup.
    Type: Grant
    Filed: March 12, 1984
    Date of Patent: April 8, 1986
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Tsutomu Teraji, Youichi Shiokawa, Kazuo Okumura, Yoshinari Sato
  • Patent number: 4578460
    Abstract: The invention relates to a derivative of 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide of the formula: ##STR1## in which X is 6-aminopurinyl. The above compound exhibits anti-inflammatory activity.
    Type: Grant
    Filed: October 4, 1983
    Date of Patent: March 25, 1986
    Assignee: Francia Farmaceutici s.r.l.
    Inventor: Giorgio A. Francia
  • Patent number: 4567179
    Abstract: Improved antiinflammatory salts of piroxicam with antidepressant doxepin, with bronchodilator pirbuterol or isoproterenol, with H.sub.2 -antagonist inhibitor 2-guanidino-4-(2-methyl-4-imidazolyl)thiazole, with pyridoxine, a member of the vitamin B.sub.6 complex, or with antihypertensive trimazosin.
    Type: Grant
    Filed: October 11, 1984
    Date of Patent: January 28, 1986
    Assignee: Pfizer, Inc.
    Inventor: Joseph G. Lombardino
  • Patent number: 4563211
    Abstract: Certain sulfonylurea compounds such as 2-[[[4-methoxy-6-(methylselenylmethyl)pyrimidin-2-yl]aminocarbonyl]aminosu lfonyl]benzoic acid, methyl ester and 2-[[[4-methoxy-6-(phenylthiomethyl)pyrimidin-2-yl]-aminocarbonyl]aminosulf onyl]benzoic acid, methyl ester provide herbicidal activity.
    Type: Grant
    Filed: March 19, 1984
    Date of Patent: January 7, 1986
    Assignee: E. I. Du Pont De Nemours and Company
    Inventors: Barry A. Wexler, William T. Zimmerman
  • Patent number: 4551525
    Abstract: A process for preparing N-(2-pyridyl)-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide-1,1-di oxide which comprises reacting an alkyl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide with P-phenyl-N,N'-di-2-pyridylphosphonium diamide.
    Type: Grant
    Filed: October 2, 1984
    Date of Patent: November 5, 1985
    Assignee: KRKA, tovarna zdravil, n.sol.o.
    Inventors: Natasa Zupancic, Boris Sket, Pavel Zupet, Marko Zupan
  • Patent number: 4551452
    Abstract: Certain enol ether derivatives of oxicams (1,1-dioxides of N-heteroaryl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamides and N-heteroaryl-4-hydroxy-2-methyl-2H-thieno[2,3-e]-1,2-thiazine-3-carboxamid es) are useful as prodrugs of these antiinflammatory compounds.
    Type: Grant
    Filed: May 2, 1984
    Date of Patent: November 5, 1985
    Assignee: Pfizer Inc.
    Inventor: Anthony Marfat
  • Patent number: 4540692
    Abstract: The invention relates to novel tropone derivatives, of antiinflammatory, analgesic and antirheumatic activity, of the formula: ##STR1## wherein R.sup.1 is hydrogen or lower alkyl,R.sup.2 is hydrogen, hydroxy, halogen, lower alkyl, or lower alkoxy, andR.sup.3 is hydrogen or acyl,and pharmaceutically acceptable salts thereof.
    Type: Grant
    Filed: March 14, 1984
    Date of Patent: September 10, 1985
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Ikuo Ueda, Masayuki Kato, Yoshiharu Kasai
  • Patent number: 4536573
    Abstract: A novel compound of the formula ##STR1## wherein R is hydrogen, benzyl or (C.sub.1 -C.sub.3)alkyl; R.sup.1 is benzyl or (C.sub.1 -C.sub.4)alkyl and Z.sup.1 taken together with --C.dbd.
    Type: Grant
    Filed: May 11, 1984
    Date of Patent: August 20, 1985
    Assignee: Pfizer Inc.
    Inventor: Joseph A. Kardys
  • Patent number: 4533664
    Abstract: Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, methyl, methoxy, fluorine or chlorine; andR.sub.2 is hydrogen, methyl, ethyl or n-propyl;and non-toxic, pharmacologically acceptable salts thereof formed with an inorganic or organic base. The compounds as well as the salts are useful as antithrombotics.
    Type: Grant
    Filed: September 30, 1983
    Date of Patent: August 6, 1985
    Assignee: Dr. Karl Thomae Gesellschaft mit beschrankter Haftung
    Inventors: Gunter Trummlitz, Wolfhard Engel, Ernst Seeger, Walter Haarmann
  • Patent number: 4506071
    Abstract: A new process for the preparation of microcrystalline isoxicam having a particle size of about 1-30 .mu.m which comprises dissolving isoxicam in a mixture consisting of a solvent miscible with water and of an aqueous base where the resulting basic solution is neutralized with dilute acid to a pH of 4-6 with vigorous agitation precipitating the microcrystalline product is herein described.
    Type: Grant
    Filed: March 12, 1984
    Date of Patent: March 19, 1985
    Assignee: Warner-Lambert Company
    Inventors: Wolfgang Herrmann, Uwe Gebhardt
  • Patent number: 4489077
    Abstract: 4-Hydroxy-N-[5-[(substituted hetero)methyl]-3-isoxazolyl]-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides as agents for treating pain in mammals resulting from inflammation.
    Type: Grant
    Filed: February 2, 1984
    Date of Patent: December 18, 1984
    Assignee: Warner-Lambert Company
    Inventors: Jagadish C. Sircar, Thomas Capiris
  • Patent number: 4483982
    Abstract: Processes for the preparation of the antiinflammatory agent piroxicam and intermediates leading thereto, the first of which comprises reacting N-methylsaccharin with (N-2-pyridyl)haloacetamides and alkyl haloacetates in the presence of an appropriate base to give, respectively, piroxicam and alkyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxides, intermediates which can be converted into piroxicam; and the second of which comprises reacting a novel alkyl 2-(2-methyl-3-hydroxy-2,3-dihydro-1,2-benzisosulfonazol-3-yl)-2-haloacetat e with a metal hydride to give alkyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxides, intermediates leading to piroxicam.
    Type: Grant
    Filed: April 5, 1984
    Date of Patent: November 20, 1984
    Assignee: Pfizer Inc.
    Inventor: Paul D. Weeks
  • Patent number: 4478996
    Abstract: A process for the preparation of 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxides, of the formula: ##STR1## in which R may be phenyl, aryl substituted with halogen (Cl, Br or I) or with C.sub.1 -C.sub.6 alkyl groups, 2, 3 or 4-pyridyl or pyridyls substituted with halogen (Cl, Br or I) or with C.sub.1 -C.sub.6 alkyl groups, 5-methyl-isoxazolyl or 2-thiazolyl.In the process a C.sub.1 -C.sub.6 alkyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide is reacted with a magnesium derivative of formula:R-NH-Mg-Xin which X is halogen, preferably Br and R is the same as defined for formula (I). The compounds produced by the described process have analgesic and antiinflammatory properties.
    Type: Grant
    Filed: March 7, 1983
    Date of Patent: October 23, 1984
    Assignee: Medichem, S.A.
    Inventor: Manuel A. Almenara
  • Patent number: 4477661
    Abstract: The present invention provides a process for the preparation of 4-hydroxy-3-(heterocyclocarbamoyl)-2H-1,2-benzothiazine-1,1-dioxides of the general formula: ##STR1## wherein R.sub.1 is a hydrogen atom or a methyl radical, R.sub.2 is a nitrogen-containing heterocyclic radical and R.sub.3 is a hydrogen or halogen atom or a methyl radical, and of the alkali metal, alkaline earth metal and amine salts thereof, by the reaction of an amine-substituted, nitrogen-containing heterocyclic compound with a halo-acetyl halide, reaction of the intermediate thus obtained with sodium benzoic acid sulphimide, ring expansion of the benzoisothiazole ring to give a benzothiazine ring and, in case R.sub.
    Type: Grant
    Filed: March 25, 1983
    Date of Patent: October 16, 1984
    Assignee: Warner-Lambert Company
    Inventors: Wolfgang Herrmann, Wolfram Geibel, Gerhard Satzinger
  • Patent number: 4474955
    Abstract: The present invention refers to a new process for preparing 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-[N-(2-pyridinyl)carboxamide]-1,1 -dioxide, its phosphoric ester and the obtained phosphoric ester.
    Type: Grant
    Filed: June 4, 1982
    Date of Patent: October 2, 1984
    Inventor: Vincenzo Iannella
  • Patent number: 4474956
    Abstract: In the preparation of 4-hydroxy-2-methyl-N-2-pyridyl-2H-benzothiazine-3-carboxamide 1,1-dioxide by reacting the corresponding 3-methoxycarbonyl compound with 2-aminopyridine, a dramatic increase in the yield is obtained if the reaction is carried out in the presence of 0.1 to 1.5 mole equivalent (based on the 3-methoxycarbonyl compound) of an alkyl- or arylsulfonic acid.
    Type: Grant
    Filed: June 29, 1983
    Date of Patent: October 2, 1984
    Assignee: Siegfried Aktiengesellschaft
    Inventors: Ludwig Zirngibl, Rene Gnehm
  • Patent number: 4469866
    Abstract: A novel compound of the formula ##STR1## wherein R is hydrogen, benzyl or (C.sub.1 -C.sub.3)alkyl; R.sup.1 is benzyl or (C.sub.1 -C.sub.4)alkyl and Z.sup.1 taken together with --C.dbd.
    Type: Grant
    Filed: April 25, 1983
    Date of Patent: September 4, 1984
    Assignee: Pfizer Inc.
    Inventor: Joseph A. Kardys
  • Patent number: 4461768
    Abstract: A new benzothiazine derivative, that is N-(2-pyridyl)-2-methyl-4-cinnamoyloxy-2H-1,2-benzothiazine-3-carboxamido 1,1-dioxide has been prepared. Owing to its peculiar ester structure, obtained by condensation with cinnamic acid, the new product is endowed with so outstanding pharmacological and toxicological activities, particularly with reference to its tolerableness, to make it a therapeutically valuable anti-inflammatory drug.
    Type: Grant
    Filed: November 4, 1982
    Date of Patent: July 24, 1984
    Assignee: SPA Societa Prodotti Antibiotici S.p.A.
    Inventors: Ernani Dell'Acqua, Tiberio Bruzzese, Lorenzo Ferrari
  • Patent number: 4434163
    Abstract: The water-soluble lysine and arginine salts of N-(2-pyridyl)-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide have been prepared. These novel salts are useful in therapy as non-steroidal anti-arthritic agents, especially when administered by the parenteral route. Methods for preparing these salts from the corresponding acidic starting material and the appropriate amine base are provided.
    Type: Grant
    Filed: April 13, 1982
    Date of Patent: February 28, 1984
    Assignee: Pfizer Inc.
    Inventor: Joseph G. Lombardino
  • Patent number: 4434164
    Abstract: The water-soluble ethylenediamine, monoethanolamine and diethanolamine salts of N-(2-pyridyl)-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide have been prepared. These novel crystalline salts are useful in therapy as non-steroidal anti-arthritic agents. Methods for preparing these salts from the corresponding acidic starting material and the appropriate amine base are provided.
    Type: Grant
    Filed: April 13, 1982
    Date of Patent: February 28, 1984
    Assignee: Pfizer Inc.
    Inventor: Joseph G. Lombardino
  • Patent number: 4388105
    Abstract: There are provided herbicidal cyclic sulfonamides of phenoxybenzoic acids.
    Type: Grant
    Filed: July 27, 1981
    Date of Patent: June 14, 1983
    Assignee: Rhone-Poulenc Agrochimie
    Inventor: James T. Bahr
  • Patent number: 4376768
    Abstract: N-(6-chloro-2-pyridyl)-3,4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-ca rboxamide 1,1-dioxide that is a novel benzothiazine derivative. The compound is characterized by a low degree of toxicity and a low incidence of gastric disorders and useful as an anti-inflammatory agent.
    Type: Grant
    Filed: June 16, 1981
    Date of Patent: March 15, 1983
    Assignee: Mitsui Toatsu Chemicals, Inc.
    Inventors: Shoichiro Ozaki, Hideya Kobayashi, Haruki Mori, Takafumi Kitano, Hiroshi Kawazura, Yutaka Okazaki
  • Patent number: 4376119
    Abstract: N-(6-fluoro-2-pyridyl)-3,4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-ca rboxamide 1,1-dioxide that is a novel benzothiazine derivative. The compound is characterized by a low degree of toxicity and a low incidence of gastric disorders and useful as an anti-inflammatory agent.
    Type: Grant
    Filed: June 16, 1981
    Date of Patent: March 8, 1983
    Assignee: Mitsui Toatsu Chemicals, Inc.
    Inventors: Shoichiro Ozaki, Hideya Kobayashi, Haruki Mori, Hiroshi Kawazura, Yutaka Okazaki, Takafumi Kitano, Mikio Kumakura, Takuo Nakano
  • Patent number: 4342761
    Abstract: Compounds having the formula ##STR1## wherein Y represents --CHOH-- or ##STR2## Z and Z.sup.1 independently represent ##STR3## --SO.sub.2 --, --COCH.sub.2 --, or --CO(CH.sub.2).sub.2 --; Z may also represent --CH.sub.2 --, --(CH.sub.2).sub.2, --CHMe--, or --CMe.sub.2 --; R.sup.1 and R.sup.2 independently represent hydrogen or substituents selected from halogen, lower-alkoxy, nitro, amino, lower alkylamino, trifluoromethyl, hydroxy, aryl lower alkoxy and lower alkyl; or R.sup.1 and R.sup.2 when adjacent together with the carbon atoms to which they are attached form a six membered carbocyclic ring; R.sup.3 represents hydrogen, halogen, lower alkyl or lower alkoxy, R.sup.4 represents lower alkyl or hydrogen; .alpha. and .beta. each represent hydrogen or a direct bond between the carbon atoms to which they are attached, and acid addition quaternary ammonium salts thereof, are disclosed which possess antihypertensive activity.
    Type: Grant
    Filed: October 20, 1980
    Date of Patent: August 3, 1982
    Assignee: John Wyeth & Brother Limited
    Inventor: Terence J. Ward
  • Patent number: 4327091
    Abstract: 3,4-Dihydro-2H-1,2-benzothiazine 1,1-dioxides of the formula ##STR1## wherein Ph represents a substituted or unsubstituted 1,2-phenylene radical, R represents a substituted or unsubstituted benzopyrone radical, and R.sub.1 represents hydrogen or a substituted or unsubstituted hydrocarbon radical of aliphatic character, and their salts, possess antiinflammatory properties and are useful as medicaments.
    Type: Grant
    Filed: January 28, 1980
    Date of Patent: April 27, 1982
    Assignee: Ciba-Geigy Corporation
    Inventors: Alex Sele, Pier G. Ferrini, Georges Haas, Knut A. Jaeggi, Alberto Rossi
  • Patent number: 4309427
    Abstract: Certain novel derivatives of N-(2-pyridyl)-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide have been prepared, including N-(2-pyridyl)-2-methyl-4-acetoxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, N-(2-pyridyl)-2-methyl-4-(n-butyryloxy)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, N-(6-methyl-2-pyridyl)-2-methyl-4-acetoxy-2H-1,2-benzothiazine-3-carboxami de 1,1-dioxide, N-(2-pyridyl)-2-methyl-4-benzoyloxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, N-(6-methyl-2-pyridyl)-2-methyl-4-benzoyloxy-2H-1,2-benzothiazine-3-carbox amide 1,1-dioxide, N-(2-pyridyl)-2-methyl-4-methanesulfonyloxy-2H-1,2-benzothiazine-3-carboxa mide 1,1-dioxide and N-(6-methyl-2-pyridyl)-2-methyl-4-methanesulfonyloxy-2H-1,2-benzothiazine- 3-carboxamide 1,1-dioxide. All these compounds are useful in therapy as non-steroidal anti-inflammatory agents, especially when administered by the topical route of administration. Methods for preparing these compounds from known starting materials are provided.
    Type: Grant
    Filed: January 15, 1981
    Date of Patent: January 5, 1982
    Assignee: Pfizer Inc.
    Inventor: Joseph G. Lombardino