title: Rationally designed benzopyran fused isoxazolidines and derived β2,3,3-amino alcohols as potent analgesics: Synthesis, biological evaluation and molecular docking analysis.
abstract: Based on structure activity analysis of morphine related opiates, we have synthesized some novel benzopyran fused isoxazolidines (2a-e) and derived conformationally constrained β2,3,3-amino alcohols (3a-e), which were evaluated in vivo for their anti-nociceptive activity through acetic acid induced writhing test (peripheral) and formalin induced algesia (central). Results showed that, compound 2a possesses significant opioid agonist activity. Further, molecular docking analysis reveals that compound 2a binds to δ-opioid receptor (DOR) with comparatively better D-score than to μ (MOR) and κ (KOR) receptors. Compound 2a did not show any toxicity up to a 2000 mg kg-1dose.
authors.affiliation: Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143 005, Punjab, India.
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Singh
authors.affiliation: Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143 005, Punjab, India.
authors.forename: Gurjit
authors.initials: G
authors.lastname: Singh
authors.affiliation: Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143 005, Punjab, India.
authors.forename: Rajbir
authors.initials: R
authors.lastname: Bhatti
authors.affiliation: Post-Graduate Department of Physics & Electronics, University of Jammu, Jammu Tawi, 180 006, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Cancer Pharmacology Division, Indian Institute of Integrative Medicine (CSIR), Jammu, 180001, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Mahajan
authors.affiliation: Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, 143 005, Punjab, India.
authors.forename: Palwinder
authors.initials: P
authors.lastname: Singh
authors.affiliation: Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143 005, Punjab, India. Electronic address: mpsishar@yahoo.com.
authors.forename: Mohan Paul
authors.initials: MP
authors.lastname: Singh Ishar
mesh_terms: D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001578:Benzopyrans / Q000737:chemistry*; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry*; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D010146:Pain / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011487:Protein Conformation; D011957:Receptors, Opioid / Q000737:chemistry / Q000378:metabolism
chemical_list: D000605:Amino Alcohols; D000700:Analgesics; D001578:Benzopyrans; D007555:Isoxazoles; D011957:Receptors, Opioid; D011451:Prostaglandin-Endoperoxide Synthases
keywords: Antinociceptive activity; Benzopyran fused isoxazolidines; Intramolecular 1,3-dipolar cycloaddition; Opioid receptor; Reductive cleavage