GB861367A - 3:4-dihydro-1:2:4-benzothiadiazine-1:1-dioxides - Google Patents

3:4-dihydro-1:2:4-benzothiadiazine-1:1-dioxides

Info

Publication number
GB861367A
GB861367A GB7209/59A GB720959A GB861367A GB 861367 A GB861367 A GB 861367A GB 7209/59 A GB7209/59 A GB 7209/59A GB 720959 A GB720959 A GB 720959A GB 861367 A GB861367 A GB 861367A
Authority
GB
United Kingdom
Prior art keywords
alkyl
benzothiadiazine
carbon atoms
hydrogen
dihydro
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB7209/59A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF Schweiz AG
Original Assignee
Ciba AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ciba AG filed Critical Ciba AG
Publication of GB861367A publication Critical patent/GB861367A/en
Expired legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/15—Six-membered rings
    • C07D285/16—Thiadiazines; Hydrogenated thiadiazines
    • C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
    • C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
    • C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
    • C07D285/26—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals
    • C07D285/28—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/15—Six-membered rings
    • C07D285/16—Thiadiazines; Hydrogenated thiadiazines
    • C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
    • C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
    • C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
    • C07D285/26—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals
    • C07D285/30—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals with hydrocarbon radicals, substituted by hetero atoms, attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention comprises 3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxides of the formula <FORM:0861367/IV (b)/1> and N-acyl derivatives and salts of these compounds, in which R1, R3, R5 and R6 are eac hydrogen or alkyl, R2 is hydrogen, an aliphatic hydrocarbon radical of 1-8 carbon atoms, a cycloalkyl, cycloalkenyl, phenyl or phenylalkyl radical or a monocyclic heterocyclic or heterocyclic-alkyl radical containing one oxygen, nitrogen or sulphur atom in the ring, e.g. furan, pyridine or thiophene, all these radicals being optionally substituted by halogen atoms, free, esterified or etherified hydroxyl or mercapto groups, nitro, acylamino, mono-alkyl-, di-alkyl-or N : N-alkylene-amino groups wherein the alkylene group has 4 or 5 carbon atoms and may be interrupted by a hetero-atom, carboxyl groups or alkyl groups of 1-5 carbon atoms, R4 is a halogen atom or an alkoxy, alkyl or haloalkyl group of 1-5 carbon atoms and when R2, R3, R5 and R6 are hydrogen and R4\t is chlorine, R1 may be an alkyl or acyl group. The compounds are prepared either by reacting a 2-sulphamoyl aniline of the formula <FORM:0861367/IV (b)/2> p in which R11 and R31 stand for hydrogen or alkyl with an aldehyde R2CHO or a functional derivative thereof, preferably in the presence of a mineral acid, and, if desired, alkylating or acylating the product, or by hydrogenating the 3,4-positions of the corresponding benzothiadiazine 1,1-dioxides preferably by means of a di-metal hydride such as an alkali metal borohydride, and if desired alkylating or acylating the product. The compounds are used pharmaceutically as diuretics and natriuretics. Preferred products include the 3-propyl-, 3-butyl-, 3-chloromethyl-, 3-ethoxymethyl-, 3-phenoxymethyl-, 3-benzyl-, 3-b -phenethyl-, 3-cyclohexen-31-yl-, 2-methyl- and 4-methyl-6-chloro - 7 - sulphamoyl - 3,4 - dihydro - 1,2,4-benzothiadiazine - 1,1 - dioxide, 6 - trifluoromethyl - 7 - sulphamoyl - 3,4 - dihydro - 1,2,4-benzothiadiazine-1,1-dioxide and 2-methyl-6-chloro - 7 - methylsulphamoyl - 3,4 - dihydro-1,2,4 - benzothiadiazine - 1,1 - dioxide. Many other products are specified. 2-Sulphamoyl anilines of the formula given above, which are used as starting materials are made by the reacting aniline or an N-alkyl aniline, bearing a substituent R4 in the m-position with a halogenosulphonic acid, e.g. chlorosulphonic acid and treating the resulting disulphonyl chloride chloride with ammonia or an amine.ALSO:Diuretic and natriuretic preparations comprise benzothiadiazine compounds of the formula <FORM:0861367/VI/1> or salts or N-acyl derivatives thereof, wherein R1, R3, R5 and R6 are hydrogen or alkyl, R2 is hydrogen, an aliphatic hydrocarbon radical of 1-8 carbon atoms, a cycloalkyl, cycloalkenyl, phenyl or phenylalkyl radical or a monocyclic heterocyclic or heterocyclic-alkyl radical containing one oxygen, nitrogen or sulphur atom in the ring, e.g. furan, pyridine or thiophene, all these radicals being optionally substituted by halogen atoms, free, esterified or etherified hydroxyl or mercapto groups, nitro, acyl-amino, mono-alkyl-, di-alkyl- or N : N-alkylene-amino groups, wherein the alkylene group has 4 or 5 carbon atoms and may be interrupted by a hetero atom, carboxyl groups or alkyl groups of 1-5 carbon atoms, R4 is a halogen atom or an alkoxy, alkyl or haloalkyl group of 1-5 carbon atoms, and when R2, R3, R5 and R6 are hydrogen and R4 is chlorine, R1 may be an alkyl or acyl group (see Group IV (b)), in admixture or conjunction with a pharmaceutical carrier for oral or parenteral administration. The preparations may take the form of tablets, dragees, capsules, solutions, suspensions or emulsions and may contain other therapeutic substances, for example, hypotensive agents such as Rauwolfia or Veratrum alkaloids, e.g. reserpine, rescinnamine, deserpidine, germine or protoveratrine, or hydralazine or ganglionic blockers such as chlorisondamine. An example describes the preparation of tablets containing 3 - butyl - 6 - chloro - 7 - sulphamoyl - 3,4 - dihydro - 1,2,4 - benzothiadiazine - 1,1 - dioxide.
GB7209/59A 1958-03-03 1959-03-02 3:4-dihydro-1:2:4-benzothiadiazine-1:1-dioxides Expired GB861367A (en)

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
US71845258A 1958-03-03 1958-03-03
US72724258A 1958-04-09 1958-04-09
US74058258A 1958-06-09 1958-06-09
US75162058A 1958-07-29 1958-07-29
US76448258A 1958-09-29 1958-09-29
DEC0024177 1959-02-27
DEC0024178 1959-02-27
DEC0024176 1959-02-27
DEC0028408 1959-02-27
DEC0028409 1959-02-27

Publications (1)

Publication Number Publication Date
GB861367A true GB861367A (en) 1961-02-22

Family

ID=27579177

Family Applications (1)

Application Number Title Priority Date Filing Date
GB7209/59A Expired GB861367A (en) 1958-03-03 1959-03-02 3:4-dihydro-1:2:4-benzothiadiazine-1:1-dioxides

Country Status (6)

Country Link
CH (4) CH371454A (en)
DE (4) DE1112079B (en)
FR (2) FR1217929A (en)
GB (1) GB861367A (en)
MY (1) MY6200051A (en)
OA (2) OA01178A (en)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3200117A (en) * 1962-10-03 1965-08-10 Hoffmann La Roche Derivatives of 1, 2, 4-benzothiadiazine-7-sulfonamide-1, 1-dioxide
WO1999042456A2 (en) * 1998-02-18 1999-08-26 Neurosearch A/S Novel compounds and their use as positive ampa receptor modulators
WO2004017964A1 (en) 2002-08-19 2004-03-04 Pfizer Products Inc. Combination therapy for hyperproliferative diseases
US6943159B1 (en) 1998-02-18 2005-09-13 Neurosearch A/S Compounds and their use as positive AMPA receptor modulators
WO2007062314A2 (en) 2005-11-23 2007-05-31 Bristol-Myers Squibb Company Heterocyclic cetp inhibitors
WO2008070496A2 (en) 2006-12-01 2008-06-12 Bristol-Myers Squibb Company N- ( (3-benzyl) -2, 2- (bis-phenyl) -propan-1-amine derivatives as cetp inhibitors for the treatment of atherosclerosis and cardiovascular diseases
US7732413B2 (en) 2003-03-07 2010-06-08 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7741289B2 (en) 2003-03-07 2010-06-22 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
WO2011069038A2 (en) 2009-12-03 2011-06-09 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
EP2392567A1 (en) 2005-10-21 2011-12-07 Bristol-Myers Squibb Company Benzothiazine derivatives and their use as lxr modulators
WO2013138352A1 (en) 2012-03-15 2013-09-19 Synergy Pharmaceuticals Inc. Formulations of guanylate cyclase c agonists and methods of use
WO2014151200A2 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Compositions useful for the treatment of gastrointestinal disorders
WO2014151206A1 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
WO2014170786A1 (en) 2013-04-17 2014-10-23 Pfizer Inc. N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases
EP2810951A2 (en) 2008-06-04 2014-12-10 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
WO2014197720A2 (en) 2013-06-05 2014-12-11 Synergy Pharmaceuticals, Inc. Ultra-pure agonists of guanylate cyclase c, method of making and using same
EP2998314A1 (en) 2007-06-04 2016-03-23 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
WO2016055901A1 (en) 2014-10-08 2016-04-14 Pfizer Inc. Substituted amide compounds
EP3241839A1 (en) 2008-07-16 2017-11-08 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
WO2020150473A2 (en) 2019-01-18 2020-07-23 Dogma Therapeutics, Inc. Pcsk9 inhibitors and methods of use thereof

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2642140C2 (en) * 1976-09-20 1982-10-28 Degussa Ag, 6000 Frankfurt Process for the production of benzoyl cyanide
DE8700284U1 (en) * 1987-01-07 1987-04-30 Ernst Reiner GmbH & Co KG, 7743 Furtwangen Post date stamp

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3200117A (en) * 1962-10-03 1965-08-10 Hoffmann La Roche Derivatives of 1, 2, 4-benzothiadiazine-7-sulfonamide-1, 1-dioxide
US7235548B2 (en) 1998-02-18 2007-06-26 Neurosearch A/S Compounds and their use as positive AMPA receptor modulators
WO1999042456A2 (en) * 1998-02-18 1999-08-26 Neurosearch A/S Novel compounds and their use as positive ampa receptor modulators
WO1999042456A3 (en) * 1998-02-18 1999-10-07 Neurosearch As Novel compounds and their use as positive ampa receptor modulators
US6943159B1 (en) 1998-02-18 2005-09-13 Neurosearch A/S Compounds and their use as positive AMPA receptor modulators
WO2004017964A1 (en) 2002-08-19 2004-03-04 Pfizer Products Inc. Combination therapy for hyperproliferative diseases
US7732413B2 (en) 2003-03-07 2010-06-08 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
US7741289B2 (en) 2003-03-07 2010-06-22 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
EP2392567A1 (en) 2005-10-21 2011-12-07 Bristol-Myers Squibb Company Benzothiazine derivatives and their use as lxr modulators
WO2007062314A2 (en) 2005-11-23 2007-05-31 Bristol-Myers Squibb Company Heterocyclic cetp inhibitors
WO2008070496A2 (en) 2006-12-01 2008-06-12 Bristol-Myers Squibb Company N- ( (3-benzyl) -2, 2- (bis-phenyl) -propan-1-amine derivatives as cetp inhibitors for the treatment of atherosclerosis and cardiovascular diseases
EP2998314A1 (en) 2007-06-04 2016-03-23 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
EP2810951A2 (en) 2008-06-04 2014-12-10 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
EP3241839A1 (en) 2008-07-16 2017-11-08 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
EP2923706A1 (en) 2009-12-03 2015-09-30 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia
WO2011069038A2 (en) 2009-12-03 2011-06-09 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
WO2013138352A1 (en) 2012-03-15 2013-09-19 Synergy Pharmaceuticals Inc. Formulations of guanylate cyclase c agonists and methods of use
EP3708179A1 (en) 2012-03-15 2020-09-16 Bausch Health Ireland Limited Formulations of guanylate cyclase c agonists and methods of use
EP4309673A2 (en) 2012-03-15 2024-01-24 Bausch Health Ireland Limited Formulations of guanylate cyclase c agonists and methods of use
WO2014151206A1 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
WO2014151200A2 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Compositions useful for the treatment of gastrointestinal disorders
WO2014170786A1 (en) 2013-04-17 2014-10-23 Pfizer Inc. N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases
WO2014197720A2 (en) 2013-06-05 2014-12-11 Synergy Pharmaceuticals, Inc. Ultra-pure agonists of guanylate cyclase c, method of making and using same
WO2016055901A1 (en) 2014-10-08 2016-04-14 Pfizer Inc. Substituted amide compounds
WO2020150473A2 (en) 2019-01-18 2020-07-23 Dogma Therapeutics, Inc. Pcsk9 inhibitors and methods of use thereof

Also Published As

Publication number Publication date
CH377365A (en) 1964-05-15
CH376514A (en) 1964-04-15
CH371454A (en) 1963-08-31
DE1445006B2 (en) 1975-05-07
DE1445008A1 (en) 1968-10-24
OA03826A (en) 1971-12-24
DE1445007A1 (en) 1968-10-24
FR1217929A (en) 1960-05-06
CH387642A (en) 1965-02-15
MY6200051A (en) 1962-12-31
OA01178A (en) 1969-01-25
DE1112079B (en) 1961-08-03
DE1445574A1 (en) 1969-01-16
DE1445005A1 (en) 1968-10-24
FR1264468A (en) 1961-06-23
DE1445006A1 (en) 1968-10-24

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