WO2016147205A1 - Nouveaux 3-spirophosphoryl pyrazole-2-oxindoles substitués en tant qu'agents anti-infectieux et procédé de synthèse correspondant - Google Patents

Nouveaux 3-spirophosphoryl pyrazole-2-oxindoles substitués en tant qu'agents anti-infectieux et procédé de synthèse correspondant Download PDF

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Publication number
WO2016147205A1
WO2016147205A1 PCT/IN2016/050085 IN2016050085W WO2016147205A1 WO 2016147205 A1 WO2016147205 A1 WO 2016147205A1 IN 2016050085 W IN2016050085 W IN 2016050085W WO 2016147205 A1 WO2016147205 A1 WO 2016147205A1
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WO
WIPO (PCT)
Prior art keywords
pyrazole
ethyl
oxospiro
diethoxyphosphoryl
indoline
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PCT/IN2016/050085
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English (en)
Inventor
Gurunath Mallappa Suryavanshi
Anil Maruti SHELKE
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Council Of Scientific & Industrial Research
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Publication of WO2016147205A1 publication Critical patent/WO2016147205A1/fr

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    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents

Definitions

  • the present invention relates to novel substituted 3-spirophosphoryl pyrazole-2- oxindoles of Formula (I) or its pharmaceutically acceptable salts, esters, ethers, isomers, stereoisomers, positional isomers and polymorphs thereof.
  • the present invention further relates to one pot, one step process for the synthesis of spirophosphoryl pyrazole oxindoles of Formula (I) with yield ranging from 70-85%.
  • pyrazoles are formed in one pot via spontaneous elimination of the nitro group.
  • nitropyrazoles could be synthesized by the same strategy using a-bromonitroalkenes. The methodology works for the synthesis of phosphonylpyrazoles fused to other carbo- and heterocycles as well.
  • the main objective of the present invention is to provide a novel substituted spirophosphoryl pyrazole oxindoles of Formula (I) or its pharmaceutically acceptable salts, esters, ethers, isomers, stereoisomers, positional isomers and polymorphs thereof.
  • the another objective of the present invention is to provide a pharmaceutical composition comprising compound of Formula (I) and at least one pharmaceutically acceptable carrier for activity against bacteria, fungi, virus and such like.
  • Still another objective of the present invention is to provide one pot, one step process for the synthesis of substituted spirophosphoryl pyrazole oxindoles of Formula (I) or its pharmaceutically acceptable salts, esters, ethers, isomers, stereoisomers, positional isomers and polymorphs thereof.
  • Yet another objective of the present invention is to provide one pot, one step and simple process for the synthesis of substituted spirophosphoryl pyrazole oxindoles of Formula (I) or its pharmaceutically acceptable salts, esters, ethers, isomers, stereoisomers, positional isomers and polymorphs thereof by using mild reaction conditions and short reaction time with high yield.
  • the present invention provides a novel substituted spirophosphoryl pyrazole oxindoles of Formula (I) or its pharmaceutically acceptable salts, esters, ethers, isomers, stereoisomers, positional isomers and polymorphs thereof.
  • Ri H, F, Br, CI, N0 2 , OCF 3
  • R 2 benzyl, i-butyl carbonyl, methyl, acetyl, tert-butyloxy carbonyl and para methoxybenzyl ether
  • R 3 COOEt, COOMe, COPh, COAr, CN and
  • the present invention further relates to a pharmaceutical composition
  • a pharmaceutical composition comprising compound of Formula I and at least one pharmaceutically acceptable carrier for activity against bacteria, fungi, virus and such like.
  • the present invention further relates to one pot, one step process for the synthesis of substituted spirophosphoryl pyrazole oxindoles of Formula (I) including the steps of adding a base to a stirred solution of Bestmann- Ohira Reagent in a solvent at temperature ranging from 20-30°C in air and stirring the resulting mixture for 2-4 mins followed by adding oxindolylidene acetate to the mixture and stirring the resultant solution for 5-6 min to afford substituted 3-spirophosphonyl pyrazole-2- oxindoles of Formula (I).
  • said base is selected from sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, triethyl amine, potassium carbonate, potassium tert. butoxide, diazabicycloundecene and such like.
  • said solvent is selected from methanol, ethanol, acetonitrile, dimethyl sulfoxide, or tetrahydrofuran.
  • the present invention provides a novel substituted spirophosphoryl pyrazole oxindoles of Formula (I) or its pharmaceutically acceptable salts, esters, ethers, isomers, stereoisomers, positional isomers and polymorphs thereof.
  • Ri H, F, Br, CI, N0 2 , OCF 3
  • R 2 benzyl, i-butyl carbonyl, methyl, acetyl, tert-butyloxy carbonyl and para methoxybenzyl ether
  • R 3 COOEt, COOMe, COPh, COAr, CN and
  • the compounds of Formula (I) are selected from compounds 3a-3n.
  • the compound of Formula I may further find use in the therapeutic classes of cancer and cell proliferation.
  • the compound of Formula I is active against Mycobacteria like E.coli, Pseudomonas flurescence, Staphylococcus aureus, Bacillus subtillus.
  • the compound of Formula I is active against HIV.
  • the present invention further relates to a pharmaceutical composition comprising compound of Formula I and at least one pharmaceutically acceptable carrier for activity against bacteria, fungi, virus and such like.
  • the present invention further relates to one pot, one step process for the synthesis of substituted spirophosphoryl pyrazole oxindoles of Formula (I) or its pharmaceutically acceptable salts, esters, ethers, isomers, stereoisomers, positional isomers and polymorphs thereof including the steps of (a) adding a base to a stirred solution of Bestmann- Ohira Reagent in a solvent at temperature ranging from 20-30°C in air and stirring the resulting mixture for 2-4 mins; (b) adding oxindolylidene acetate to the mixture and stirring the resultant solution for 5-6 min to afford substituted 3-spirophosphonyl pyrazole-2-oxindoles of Formula (I).
  • the present invention further relates to one pot, one step process for the synthesis of substituted spirophosphoryl pyrazole oxindoles of Formula (I) or its pharmaceutically acceptable salts, esters, ethers, isomers, stereoisomers, positional isomers and polymorphs thereof comprising adding a base (2.0 equiv.) to a stirred solution of Bestmann- Ohira Reagent (2.0 equiv.) in a solvent at temperature ranging from 20-30°C in air and stirring the resulting mixture for 2-4 mins; adding oxindolylidene acetate (1.0 equiv.) to the mixture and stirring the resultant solution for 5-6 min to afford substituted 3-spirophosphonyl pyrazole-2- oxindoles of Formula (I).
  • said base is selected from sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, triethyl amine, potassium carbonate, potassium tert. butoxide, diazabicycloundecene and such like.
  • said solvent is selected from methanol, ethanol, acetonitrile, dimethyl sulfoxide, tetrahydrofuran and such like.
  • yield of said process is ranging from 70% to
  • the pharmaceutically acceptable salt includes both acid and base addition salts.
  • the acid addition salts are formed with both inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, nitric acid and the like; the organic acids are selected from but not limited to acetic acid, benzenesulfonic acid, benzoic acid, cinnamic acid, citric acid, formic acid, fumaric acid, and the like.
  • the base addition salts are derived from inorganic bases which include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like; from organic bases such as salts of ammonia, primary, secondary, and tertiary amines, cyclic amines etc.
  • compositions of the invention can be prepared by combining a compound of the invention with an appropriate pharmaceutically acceptable carrier, diluent or excipient, and may be Formulated into preparations in solid, semi-solid, liquid or gaseous forms, such as tablets, capsules, powders, granules, ointments, solutions, injections, gels and microspheres,
  • the present invention relates to administering 'an effective amount' of the 'composition of invention ' to the subject suffering from said disease.
  • compound of Formula I and pharmaceutical compositions containing them may be administered using any amount, any form of pharmaceutical composition via any route of administration effective for treating the disease.
  • Typical routes of administering such pharmaceutical compositions include, without limitation, oral, topical, transdermal, inhalation, parenteral, sublingual, buccal, rectal, vaginal, and intranasal.
  • compositions of the invention are Formulated so as to allow the active ingredients contained therein to be bioavailable upon administration of the composition to a patient.
  • Compositions that will be administered to a subject or patient may take the form of one or more dosage units.
  • the dosage forms can also be prepared as sustained, controlled, modified and immediate dosage forms.
  • Example 1 General procedure for the 1,3 dipolar reaction of Bestmann- Ohira Reagent with oxindolylidene acetates:
  • Example 17 A general experimental procedure for sequential multicom nentreaction of isatin 4, phosphonium ylide 5 and BOR reagent:
  • Example 18 Activity testing of substituted 3-spirophosphoryl pyrazole-2- oxindoles:

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne de nouveaux 3-spirophosphoryl, pyrazole-2-oxindoles substitués de Formule (I) et leurs sels, esters, éthers, isomères, stéréoisomères, isomères de position et polymorphes. La présente invention concerne en outre un procédé en un pot unique, en une étape de synthèse des spirophosphoryl pyrazole oxindoles de Formule (I) avec un rendement situé dans la plage de 70 à 85 %.
PCT/IN2016/050085 2015-03-13 2016-03-11 Nouveaux 3-spirophosphoryl pyrazole-2-oxindoles substitués en tant qu'agents anti-infectieux et procédé de synthèse correspondant WO2016147205A1 (fr)

Applications Claiming Priority (2)

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IN677/DEL/2015 2015-03-13
IN677DE2015 2015-03-13

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WO2016147205A1 true WO2016147205A1 (fr) 2016-09-22

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109867678A (zh) * 2019-04-08 2019-06-11 浙江工业大学 一种四环吲哚啉类化合物的制备方法
CN113845524A (zh) * 2021-10-29 2021-12-28 四川农业大学 一种螺吡咯吲哚酮类化合物及其制备方法和应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009132921A1 (fr) * 2008-04-29 2009-11-05 Novartis Ag Dérivés spiro-indoles pour le traitement de maladies parasitaires
US20110112052A1 (en) * 2009-11-12 2011-05-12 The Regents Of The University Of Michigan Spiro-oxindole mdm2 antagonists
WO2014167528A1 (fr) * 2013-04-11 2014-10-16 Novartis Ag Dérivés de spiropyrazolopyridine et leurs utilisations pour le traitement d'infections virales

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009132921A1 (fr) * 2008-04-29 2009-11-05 Novartis Ag Dérivés spiro-indoles pour le traitement de maladies parasitaires
US20110112052A1 (en) * 2009-11-12 2011-05-12 The Regents Of The University Of Michigan Spiro-oxindole mdm2 antagonists
WO2014167528A1 (fr) * 2013-04-11 2014-10-16 Novartis Ag Dérivés de spiropyrazolopyridine et leurs utilisations pour le traitement d'infections virales

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
AHAMAD ET AL., ORGANIC AND BIOMOLECULAR CHEMISTRY, vol. 13, 25 November 2014 (2014-11-25), pages 1492 - 1499
AHMED KAMAL ET AL.: "Design and synthesis of pyrazole-oxindole conjugates targeting tubulin polymerization as new anticancer agents", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 92, 2015, pages 501 - 513
ANIL M. SHELKE ET AL: "An efficient one pot regioselective synthesis of a 3,3'-spiro-phosphonylpyrazole-oxindole framework via base mediated [1,3]-dipolar cycloaddition reaction of the Bestmann-Ohira reagent with methyleneindolinones", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 13, no. 32, 6 July 2015 (2015-07-06) - 6 July 2015 (2015-07-06), GB, pages 8669 - 8675, XP055281002, ISSN: 1477-0520, DOI: 10.1039/C5OB01020A *
ANTHONY R. MARTIN ET AL.: "Regioselective synthesis of 3-Carbo-5-phosphonylpyrazoles through a one-pot. Claisen–Schmidt/1,3-Dipolar Cycloaddition/Oxidation sequence", EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, vol. 17, 2011, pages 3184 - 3190
ASHIS KUMAR GUPTA ET AL: "Substrate-controlled product-selectivity in the reaction of the Bestmann-Ohira reagent with N-unprotected isatin-derived olefins", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 13, no. 38, 5 August 2015 (2015-08-05) - 5 August 2015 (2015-08-05), GB, pages 9783 - 9788, XP055281021, ISSN: 1477-0520, DOI: 10.1039/C5OB01382H *
DAOJUAN CHENG ET AL.: "Organocatalytic asymmetric assembly reactions: Synthesis of spirooxindoles via organocascade strategies", ACS CATALYSIS, vol. 4, 2014, pages 743 - 762
DEEPTI VERMA ET AL.: "Highly selective synthesis of pyrazole and spiropyrazoline phosphonates via base-assisted reaction of the Bestmann-Ohira Reagent with enones", JOURNAL OF ORGANIC CHEMISTRY, vol. 76, no. 11, 2011, pages 4764 - 4770
KISHOR MOHANAN ET AL., ANGEWANDTE CHEMIE, vol. 49, no. 18, 2010, pages 3196 - 3199
MURUGANANTHAM R ET AL: "Base-Mediated Reaction of the Bestmann-Ohira Reagent with Nitroalkenes for the Regioselective Synthesis of Phosphonylpyrazoles", ORGANIC LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 9, no. 6, 15 March 2007 (2007-03-15), pages 1125 - 1128, XP008088078, ISSN: 1523-7060, DOI: 10.1021/OL070107S *
R. MURUGANANTHAM ET AL.: "Base mediated reaction of the Bestmann-Ohira reagent with Nitroalkenes for the regioselective synthesis of phosphonylpyrazoles", ORGANIC LETTER, vol. 9, no. 6, 2007, pages 1125 - 1128, XP008088078, DOI: doi:10.1021/ol070107s
RAJENDRAN MURUGANANTHAM ET AL.: "Phosphonylpyrazoles from Bestmann-Ohira reagent and nitroalkenes: synthesis and dynamic NMR studies", JOURNAL OF ORGANIC CHEMISTRY, vol. 75, no. 7, 2010, pages 2197 - 2205
VARINDER K. AGGARWAL ET AL.: "A novel one-pot method for the preparation of pyrazoles by 1,3-Dipolar cycloadditions of diazo compounds generated in situ", JOURNAL OF ORGANIC CHEMISTRY, vol. 68, no. 13, 2003, pages 5381 - 5383, XP002646754, DOI: doi:10.1021/jo0268409

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109867678A (zh) * 2019-04-08 2019-06-11 浙江工业大学 一种四环吲哚啉类化合物的制备方法
CN113845524A (zh) * 2021-10-29 2021-12-28 四川农业大学 一种螺吡咯吲哚酮类化合物及其制备方法和应用
CN113845524B (zh) * 2021-10-29 2023-11-07 四川农业大学 一种螺吡咯吲哚酮类化合物及其制备方法和应用

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