GB1447032A - Tricyclic sulphones and pharmaceutical compositions containing them - Google Patents

Tricyclic sulphones and pharmaceutical compositions containing them

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Publication number
GB1447032A
GB1447032A GB1955276A GB1955276A GB1447032A GB 1447032 A GB1447032 A GB 1447032A GB 1955276 A GB1955276 A GB 1955276A GB 1955276 A GB1955276 A GB 1955276A GB 1447032 A GB1447032 A GB 1447032A
Authority
GB
United Kingdom
Prior art keywords
dioxide
prep
acid
formula
compound
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
GB1955276A
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.)
Wellcome Foundation Ltd
Original Assignee
Wellcome Foundation Ltd
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 Wellcome Foundation Ltd filed Critical Wellcome Foundation Ltd
Priority to GB1955276A priority Critical patent/GB1447032A/en
Priority claimed from GB2117473*[A external-priority patent/GB1447031A/en
Publication of GB1447032A publication Critical patent/GB1447032A/en
Expired legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/382—Heterocyclic compounds having sulfur as a ring hetero atom having six-membered rings, e.g. thioxanthenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/12—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/257—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings
    • C07C43/263—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings the aromatic rings being non-condensed
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
    • C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
    • C07D327/06—Six-membered rings
    • C07D327/08—[b,e]-condensed with two six-membered carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/76—Dibenzothiophenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/10—Dibenzothiopyrans; Hydrogenated dibenzothiopyrans
    • C07D335/12—Thioxanthenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/10—Dibenzothiopyrans; Hydrogenated dibenzothiopyrans
    • C07D335/12—Thioxanthenes
    • C07D335/14—Thioxanthenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 9
    • C07D335/16—Oxygen atoms, e.g. thioxanthones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
    • C07D339/08—Six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
    • C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic Table without C-Metal linkages

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

1447032 Tricyclic sulphones WELLCOME FOUNDATION Ltd 17 Aug 1973 [19 May 1972 6 Sept 1972 4 May 1973] 19552/76 and 19553/76 Divided out of 1447031 Heading C2C The invention comprises compounds of the formula wherein Z<SP>1</SP> is carboxyl, a carboxylate salt a (C 1 -C 6 ) -alkylcarboxylate or a carboxamide optionally substituted by (C 1 -C 6 )-alkyl, Z<SP>3</SP> is a bond, -CO-, -O-, -S-, -SO-, or -CH 2 - and Z<SP>2</SP> is H, a carboxylate salt, (C 1 - C 6 )-alkylsulphonyl, alkylsulphinyl, alkylthio, alkyl or alkoxy, (C 2 -C 7 )-alkanoyl or alkanoylamino, amino, NO 2 , CN or halogen, with the proviso that (1) when Z<SP>2</SP> is H or a carboxylate salt then Z<SP>1</SP> is a carboxylate salt, and (2) when Z<SP>3</SP> is -CO- and Z<SP>1</SP> is in the 2-position then Z<SP>2</SP> when in the 5-, 6- or 7-position, is other than halogen, alkanoyl, alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl; and except for 7 - nitro - 2 - carboxythioxanthone - 10,10- dioxide and its amide, 9-nitro-4-carboxyphenoxathiin - 10,10 - dioxide, 8 - chloro - 2 - carboxyphenoxathiin - 10,10 - dioxide and its methyl ester, 4,6-dicarboxydibenzothiophene- 5,5-dioxide disodium salt, and 8-chloro-2- carboxythioxanthone-10,10-dioxide. They may be obtained by (a) when Z<SP>1</SP> is carboxyl or a carboxylate salt, or both Z<SP>1</SP> and Z<SP>2</SP> are carboxylate salts, hydrolysing a compound of the formula wherein Y<SP>1</SP> is a carboxyl group precursor or is the same as Z<SP>1</SP> and Y<SP>2</SP> is carboxyl group precursor or is the same as Z<SP>2</SP>, with a base or with a dilute aqueous mineral acid optionally in the presence of an organic acid; (b) oxidizing a compound of the formula wherein Y<SP>5</SP> is alkyl, alkanoyl or is the same as Z<SP>1</SP>, Y<SP>3</SP> is the same as Z<SP>3</SP>, Y<SP>4</SP> is -S-, -SO-, or -SO 2 -, and Y<SP>6</SP> is alkyl, alkanoyl or is the same as Z<SP>2</SP>, provided that when Y<SP>5</SP> is the same as Z<SP>1</SP> and Y<SP>6</SP> is the same as Z<SP>2</SP> then at least Y<SP>4</SP> is - or Y<SP>3</SP> is -CH 2 - or -S-,-S-or-SO with an appropriate oxidizing agent; (c) when Z<SP>3</SP> is -O- or -S-, cyclizing a compound of the formula wherein one of R<SP>2</SP> and R<SP>3</SP> is SH, OH or an ester thereof and the other is a leaving group, with a base; (d) cyclizing a compound of the formula using a Lewis acid; (e) cyclizing a compound of the formula with C1SO 3 H; (f) when Z<SP>3</SP> is -S- or -CH 2 -, reducing the corresponding compound of Formula I wherein Z<SP>3</SP> is -SO- or -CO-, with an appropriate reducing agent; (g) when Z<SP>3</SP> is -S-, reacting a compound of the formula wherein R<SP>5</SP> and R<SP>6</SP> are each leaving groups, with sodium sulphide; or (h) when Z<SP>3</SP> is -CO-, cyclizing a compound of the formula wherein R<SP>1</SP> is -COOH or a derivative thereof or is -CHO, in the presence of a Lewis or protonic acid; and when a salt, an amide or an alkyl ester is required converting the products obtained above by appropriate reactions. Pharmaceutical compositions comprise the compounds of Formula I and in addition the compounds excluded by proviso (1) and those compounds specifically named, in association with an acceptable carrier. They are useful as inhibitors of allergic reactions associated with asthma, hay fever, conjunctivitis, urticaria and eczema and may be applied orally, rectally, ophthalmically, pulmonarily, nasally, dermally, topically or parenterally. The preparation of the following intermediates and other products is described: Prep. (1) 2-carboxydibenzothiophene-5,5-dioxide from dibenzothiophene via 2-acetyldibenzothiophene and dibenzothiophene-2-carboxylic acid; Prep. (2) 2,8-dicarboxyphenoxathiin-10,10-dioxide from 2,8-diacetylphenoxathiin via its 10,10-dioxide; Prep. (3) 2-methoxycarbonylphenoxathiin-1.0,10-dioxide from the corresponding free acid; Prep. (4) 3-carboxythioxanthone- 10,10-dioxide from benzene sulphonyl chloride and p-xylene via 2,5-dimethyldiphenyl sulphone and diphenyl sulphone-2,5-dicarboxylic acid; Prep. (5) 2-carbozyphenozathiin-10,10-dioxide by a route analogous to prep. (1); Preps. (6) and (7) 2-carboxythioxanthone-10,10-dioxide by a route analogous to prep. (4) or from toluene and omercaptobenzoic acid via methylthioxanthone and its 10,10-dioxide; Prep. (9) 3-carboxythioxanthone-10,10-dioxide from 3-carboxy-thioxanthone-10,10-dioxide; Prep. (10) 2,6-dicarboxythioxanthone - 10,10 - dioxide from diphenylsulphone 2,4<SP>1</SP>,5- tricarboxylic acid; Prep. (11) 2,7 - dicarboxythioxanthone - 10,10 - dioxide by a route analogous to prep. (4); Prep. (12) 3- methoxycarbonylthioxanthone - 10,10 - dioxide from the corresponding free acid; Example (1) 7 - ethylthioxanthone - 3 - carboxylic acid from ethylbenzene via p-ethylthiophenol, and 2-(pethylphenylthio) terephthalic acid; Example (2) 7 - t - butylthioxanthone - 3 - carboxylic acid from p - t - butylthiophenol and nitroterephthalonitrile via 2 - (p - t - butylphenylthio) terephthalic acid; Example (3) 2,8 - dimethylphenoxathiin - 10,10 - dioxide from p - bromotoluene and p-cresol via 4,4<SP>1</SP>-dimethyldiphenyl ether and 2,8-dimethylphenoxathiin; Example (4) p - chlorophenylsulphonyl terephthalic acid from p-chlorothiophenol and nitroterephthalonitrile via p-chlorophenylthioterephthalonitrile and the corresponding free acid; Example (5) 7 - methoxythioxanthone - 3 - carboxylic acid by a route analogous to Example (2); Prep. (15) 3- carboxydibenzothiophene - 5,5 - dioxide from dibenzothiophene - 5,5 - dioxide via 3 - nitro- and 3 - amino - dibenzothiophene - 5,5 - dioxide; Prep. (16) 3-carboxythioxanthene-10,10-dioxide from 3 - carboxythioxanthone - 10,10 - dioxide; Example (6) 7-methylthioxanthone-3-carboxylic acid by a route analogous to Example (2); Example (10) 7-Nitrothioxanthone- 3-carboxylic acid from sodium 4-nitrothiophenoxide and 2,5- dicyanonitrobenzene via 2,5-dicyano- 4<SP>1</SP>-nitrodiphenylsulphide and p - nitrothiophenoxy terephthalic acid; Prep. (17) 2,5-dicarboxythioxanthone-10,10-dioxide from thioxanthone-2,5-dicarboxylic acid which is itself obtained by a route analogous to Example (10); Prep. (18) 1-carboxythioxanthone-10,10-dioxide by a route analogous to Prep. (17); Prep. (19) 3-carboxythianthrene-5,5,10-trioxide from 3-carboxythianthrene-5,5-dioxide; and Prep. (20) 4,5-dicarboxythioxanthone-10,10-dioxide by a route analogous to Prep. (17). Other intermediates are described in Specification 1,447,031.
GB1955276A 1972-05-19 1972-05-19 Tricyclic sulphones and pharmaceutical compositions containing them Expired GB1447032A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB1955276A GB1447032A (en) 1972-05-19 1972-05-19 Tricyclic sulphones and pharmaceutical compositions containing them

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB1955276A GB1447032A (en) 1972-05-19 1972-05-19 Tricyclic sulphones and pharmaceutical compositions containing them
GB2380572 1972-05-19
GB4142972 1972-09-06
GB1955376 1972-09-06
GB2117473*[A GB1447031A (en) 1972-05-19 1973-05-04 Tricyclic sulphones and pharmaceutical compositions containing them
GB1955476 1973-05-04

Publications (1)

Publication Number Publication Date
GB1447032A true GB1447032A (en) 1976-08-25

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0004257A1 (en) * 1978-03-09 1979-09-19 Sanofi S.A. Benzonitrile derivative, process for its preparation and its application
US4505794A (en) * 1979-05-18 1985-03-19 Ciba-Geigy Corporation Thioxanthonecarboxylic acid esters, thioesters and amides
EP0419157A2 (en) * 1989-09-18 1991-03-27 The Wellcome Foundation Limited Pharmacologically active compound., preparation and use
WO1992004897A1 (en) * 1990-09-17 1992-04-02 The Wellcome Foundation Limited 1-substituted phenoxathiin derivatives as antidepressants
EP1380580A1 (en) * 2002-07-13 2004-01-14 Great Lakes (UK) Limited An improved process for the production of subsituted thioxanthones
WO2008151719A2 (en) * 2007-06-11 2008-12-18 Bayer Cropscience Ag 3-cyclopropyl-4-(3-thiobenzoyl)pyrazoles and their use as herbicides

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0004257A1 (en) * 1978-03-09 1979-09-19 Sanofi S.A. Benzonitrile derivative, process for its preparation and its application
US4505794A (en) * 1979-05-18 1985-03-19 Ciba-Geigy Corporation Thioxanthonecarboxylic acid esters, thioesters and amides
US4506083A (en) * 1979-05-18 1985-03-19 Ciba-Geigy Corporation Thioxanthonecarboxylic acid esters, thioesters and amides
EP0419157A2 (en) * 1989-09-18 1991-03-27 The Wellcome Foundation Limited Pharmacologically active compound., preparation and use
EP0419157A3 (en) * 1989-09-18 1991-08-28 The Wellcome Foundation Limited Pharmacologically active compound., preparation and use
WO1992004897A1 (en) * 1990-09-17 1992-04-02 The Wellcome Foundation Limited 1-substituted phenoxathiin derivatives as antidepressants
EP1380580A1 (en) * 2002-07-13 2004-01-14 Great Lakes (UK) Limited An improved process for the production of subsituted thioxanthones
US6960668B2 (en) 2002-07-13 2005-11-01 Great Lakes (Uk) Limited Process for the production of substituted thioxanthones
WO2008151719A2 (en) * 2007-06-11 2008-12-18 Bayer Cropscience Ag 3-cyclopropyl-4-(3-thiobenzoyl)pyrazoles and their use as herbicides
WO2008151719A3 (en) * 2007-06-11 2009-08-06 Bayer Cropscience Ag 3-cyclopropyl-4-(3-thiobenzoyl)pyrazoles and their use as herbicides
US7943551B2 (en) 2007-06-11 2011-05-17 Bayer Cropscience Ag 3-cyclopropyl-4-(3-thiobenzoyl) pyrazoles and their use as herbicides
CN101679285B (en) * 2007-06-11 2013-07-24 拜尔农作物科学股份公司 3-cyclopropyl-4-(3-thiobenzoyl)pyrazoles and their use as herbicides

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PCNP Patent ceased through non-payment of renewal fee