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WO2015127941A1 - Relation qualitative structure-activité (rqsa) de nouveaux composés organiques synthétisés par une réaction de couplage croisé de stille présentant une activité antitumorale - Google Patents

Relation qualitative structure-activité (rqsa) de nouveaux composés organiques synthétisés par une réaction de couplage croisé de stille présentant une activité antitumorale Download PDF

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Publication number
WO2015127941A1
WO2015127941A1 PCT/EG2014/000006 EG2014000006W WO2015127941A1 WO 2015127941 A1 WO2015127941 A1 WO 2015127941A1 EG 2014000006 W EG2014000006 W EG 2014000006W WO 2015127941 A1 WO2015127941 A1 WO 2015127941A1
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WIPO (PCT)
Prior art keywords
thiophen
coupling reaction
qsar
organic compounds
cross coupling
Prior art date
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Ceased
Application number
PCT/EG2014/000006
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English (en)
Inventor
Yasmine Mohamed Hashem Ezz El Din ABOU ELSAOUD
Abdel-Sattar S. Hamad ELGAZWY
Ibrahim F. NASSAR
Nasser S.M ISMAIL
Nour A. ABDEL SATTAR
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Individual
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Individual
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Priority to PCT/EG2014/000006 priority Critical patent/WO2015127941A1/fr
Publication of WO2015127941A1 publication Critical patent/WO2015127941A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • Novel Diarylthiophene and Heterothiophene Derivatives with the formula 7,8,9,10 and 11 were designed and synthesized to target cancer cells with high potency and were docked into protein using molecular modeling software to test their interaction energies with the receptor compared to. Their structures were proved using spectral and elemental analysis and they were tested for their activity against three different cancer cell lines.
  • Biphenyl ring system of 8 was perfectly aligned with purine nucleus of ligand 1
  • Benzyloxy group of 8 superimposed with 4-anino substituent of lead compound 1
  • the 2-thiophene part of 8 was aligned with O-pyrrolidin-2-one methyl substituent of ligand 1
  • both the 8 and ligand 1 make the same hydrogen bonding interaction with Asp86 and Lys33.
  • compound 8 makes two hydrophobic interactions with Lys33.
  • compound 9 revealed good alignment with lead compound 1 ( Figure 2 A&B).
  • the high docking results and biological activities can be explained by; first, the thiophene ring in compounds will increase the hydrophobic binding interaction with the deep hydrophobic pocket created by His 84, Phe 82, Glu81 and Ala 31. Second, the hydrogen bonding interactions have been found, between the crucial features of compounds (7-11) with the high docking scores and N-H group of Lys33, N-# of Lys89 and Asp86. The H-bond is displayed as line. Compound 8 and 9 is nicely bound to the CDK2. Oxygen atom of 8 project toward the side chain N-H group of Asp86, forming a more optimal H-bond interaction. Also, the sulfur atom of the thiophene ring of compound 8 forms hydrogen bond with Lys33.

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

Abstract

Selon l'invention, de nouveaux dérivés de diaryldithiophène et d'hétéromonothiophène et/ou d'hétérodithiophène (7-11) ont été conçus, synthétisés dans des réactions de couplage de Stille et évalués en ce qui concerne leur activité antitumorale dans 3 lignées cellulaires différentes : MCF7, HEPG2 et cancer du poumon. Les composés 7, 8, 9, 10 et 11 présentaient une activité cytotoxique hautement puissante avec des valeurs IC50 respectivement dans des plages de 0,042 - 4,09 μΜ. De plus, une étude d'assemblage moléculaire a été effectuée à l'aide du complexe (H10V) comme matrice pour prédire l'affinité de liaison des composés cibles au récepteur.
PCT/EG2014/000006 2014-02-03 2014-02-03 Relation qualitative structure-activité (rqsa) de nouveaux composés organiques synthétisés par une réaction de couplage croisé de stille présentant une activité antitumorale Ceased WO2015127941A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/EG2014/000006 WO2015127941A1 (fr) 2014-02-03 2014-02-03 Relation qualitative structure-activité (rqsa) de nouveaux composés organiques synthétisés par une réaction de couplage croisé de stille présentant une activité antitumorale

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EG2014/000006 WO2015127941A1 (fr) 2014-02-03 2014-02-03 Relation qualitative structure-activité (rqsa) de nouveaux composés organiques synthétisés par une réaction de couplage croisé de stille présentant une activité antitumorale

Publications (1)

Publication Number Publication Date
WO2015127941A1 true WO2015127941A1 (fr) 2015-09-03

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PCT/EG2014/000006 Ceased WO2015127941A1 (fr) 2014-02-03 2014-02-03 Relation qualitative structure-activité (rqsa) de nouveaux composés organiques synthétisés par une réaction de couplage croisé de stille présentant une activité antitumorale

Country Status (1)

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WO (1) WO2015127941A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023036868A1 (fr) * 2021-09-10 2023-03-16 Reuter Chemische Apparatebau E.K. Composés de bisphénol substitués par un groupe (het)aryle et résines thermoplastiques

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007125061A1 (fr) * 2006-04-27 2007-11-08 Glaxo Group Limited Composés spiro utiles en tant que modulateurs de récepteurs de la dopamine d3
WO2009063240A1 (fr) * 2007-11-16 2009-05-22 Arrow Therapeutics Limited Dérivés de 2,4-diaminopyrimidine utiles en tant qu'inhibiteurs de l'aurora kinase

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007125061A1 (fr) * 2006-04-27 2007-11-08 Glaxo Group Limited Composés spiro utiles en tant que modulateurs de récepteurs de la dopamine d3
WO2009063240A1 (fr) * 2007-11-16 2009-05-22 Arrow Therapeutics Limited Dérivés de 2,4-diaminopyrimidine utiles en tant qu'inhibiteurs de l'aurora kinase

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
XINSHUAI ZHANG ET AL: "An Organocatalytic Cascade Approach toward Polysubstituted Quinolines and Chiral 1,4-Dihydroquinolines-Unanticipated Effect of N-Protecting Groups", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, vol. 51, no. 29, 16 July 2012 (2012-07-16), pages 7282 - 7286, XP055108656, ISSN: 1433-7851, DOI: 10.1002/anie.201202161 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023036868A1 (fr) * 2021-09-10 2023-03-16 Reuter Chemische Apparatebau E.K. Composés de bisphénol substitués par un groupe (het)aryle et résines thermoplastiques

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