Literature DB >> 20101277

PROBES FOR NARCOTIC RECEPTOR MEDIATED PHENOMENA. 38. AN EXPEDITIOUS SYNTHESIS OF RAC-CIS-4a-ETHYL-2-METHYL-1,2,3,4,4a,9a-HEXAHYDROBENZOFURO[2,3-c]PYRIDIN-6-OL AND RAC-CIS-2-METHYL-4a-PHENETHYL-1,2,3,4,4a,9a-HEXAHYDROBENZOFURO[2,3-c]PYRIDIN-6-OL.

Malliga R Iyer1, Jeffrey R Deschamps, Arthur E Jacobson, Kenner C Rice.   

Abstract

A high-yielding five-step synthesis of cis-benzofuropyridin-6-ols provided an improved route to compounds with low to subnanomolar affinity at opioid receptors and high antinociceptive potency. This synthesis provided the known n class="Chemical">rac-cis-4a-ethyl-2-methyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol (1a) in high yield, and the novel rac-cis-2-methyl-4a-phenethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol (1b). It was achieved using NBS to prepare the key intermediate 7. Di-demethylation followed by subsequent displacement of the bromine by the phenolic ion in hot Et(3)N gave the desired 1a. The structure of 1a was confirmed by X-ray crystallography.

Entities:  

Year:  2009        PMID： 20101277      PMCID： PMC2714916          DOI： 10.3987/COM-09-S(D)84

Source DB:  PubMed          Journal:  Heterocycles        ISSN： 0385-5414            Impact factor:   0.831


  8 in total

1.  Probes for narcotic receptor mediated phenomena. 9. Synthesis of (+/-)-(3 alpha,6a alpha,11a beta)-1,3,4,5,6,11a-hexahydro-2-methyl-2H-3,6a- methanobenzofuro[2,3-c]azocin-10-ol, an oxide-bridged 5-(m-hydroxyphenyl)morphan.

Authors:  T R Burke; A E Jacobson; K C Rice; B A Weissman; H C Huang; J V Silverton
Journal:  J Med Chem       Date:  1986-05       Impact factor: 7.446

2.  Benzofuro[2,3-c]pyridin-6-ols: synthesis, affinity for opioid-receptor subtypes, and antinociceptive activity.

Authors:  A J Hutchison; R de Jesus; M Williams; J P Simke; R F Neale; R H Jackson; F Ambrose; B J Barbaz; M A Sills
Journal:  J Med Chem       Date:  1989-09       Impact factor: 7.446

3.  Probes for narcotic receptor mediated phenomena. 37. Synthesis and opioid binding affinity of the final pair of oxide-bridged phenylmorphans, the ortho- and para-b-isomers and their N-phenethyl analogues, and the synthesis of the N-phenethyl analogues of the ortho- and para-d-isomers.

Authors:  Muneaki Kurimura; Hehua Liu; Agnieszka Sulima; Akihiro Hashimoto; Anna K Przybyl; Etsuo Ohshima; Shinichi Kodato; Jeffrey R Deschamps; Christina M Dersch; Richard B Rothman; Yong Sok Lee; Arthur E Jacobson; Kenner C Rice
Journal:  J Med Chem       Date:  2008-12-25       Impact factor: 7.446

4.  Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis.

Authors:  J W Langston; P Ballard; J W Tetrud; I Irwin
Journal:  Science       Date:  1983-02-25       Impact factor: 47.728

5.  Synthesis and pharmacological effects of the enantiomers of the N-phenethyl analogues of the ortho and para e- and f-oxide-bridged phenylmorphans.

Authors:  Josef Zezula; Lisa Singer; Anna K Przybył; Akihiro Hashimoto; Christina M Dersch; Richard B Rothman; Jeffrey Deschamps; Yong Sok Lee; Arthur E Jacobson; Kenner C Rice
Journal:  Org Biomol Chem       Date:  2008-06-13       Impact factor: 3.876

6.  Probes for narcotic receptor-mediated phenomena. 33. Construction of a strained trans-5,6-ring system by displacement of a nitro-activated aromatic fluorine. synthesis of the penultimate oxide-bridged phenylmorphans.

Authors:  Akihiro Hashimoto; Anna K Przybyl; Joannes T M Linders; Shinichi Kodato; Xinrong Tian; Jeffrey R Deschamps; Clifford George; Judith L Flippen-Anderson; Arthur E Jacobson; Kenner C Rice
Journal:  J Org Chem       Date:  2004-08-06       Impact factor: 4.354

7.  A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Authors:  R S Burns; C C Chiueh; S P Markey; M H Ebert; D M Jacobowitz; I J Kopin
Journal:  Proc Natl Acad Sci U S A       Date:  1983-07       Impact factor: 11.205

8.  Probes for narcotic receptor mediated phenomena. 34. Synthesis and structure-activity relationships of a potent mu-agonist delta-antagonist and an exceedingly potent antinociceptive in the enantiomeric C9-substituted 5-(3-hydroxyphenyl)-N-phenylethylmorphan series.

Authors:  Anne-Cécile Hiebel; Yong Sok Lee; Edward Bilsky; Denise Giuvelis; Jeffrey R Deschamps; Damon A Parrish; Mario D Aceto; Everette L May; Louis S Harris; Andrew Coop; Christina M Dersch; John S Partilla; Richard B Rothman; Kejun Cheng; Arthur E Jacobson; Kenner C Rice
Journal:  J Med Chem       Date:  2007-07-11       Impact factor: 7.446
  8 in total
  4 in total

1.  Probes for narcotic receptor mediated phenomena 49. N-substituted rac-cis-4a-arylalkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols.

Authors:  Malliga R Iyer; Richard B Rothman; Christina M Dersch; Arthur E Jacobson; Kenner C Rice
Journal:  Eur J Med Chem       Date:  2015-01-13       Impact factor: 6.514

2.  Probes for narcotic receptor mediated phenomena. 40. N-substituted cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols.

Authors:  Malliga R Iyer; Yong Sok Lee; Jeffrey R Deschamps; Richard B Rothman; Christina M Dersch; Arthur E Jacobson; Kenner C Rice
Journal:  Bioorg Med Chem       Date:  2009-11-18       Impact factor: 3.641

3.  Probes for narcotic receptor mediated phenomena. 47. Novel C4a- and N-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols.

Authors:  Malliga R Iyer; Richard B Rothman; Christina M Dersch; Arthur E Jacobson; Kenner C Rice
Journal:  Bioorg Med Chem       Date:  2013-04-03       Impact factor: 3.641

4.  Probes for narcotic receptor mediated phenomena. 39. Enantiomeric N-substituted benzofuro[2,3-c]pyridin-6-ols: synthesis and topological relationship to oxide-bridged phenylmorphans.

Authors:  Yi Zhang; Yong Sok Lee; Richard B Rothman; Christina M Dersch; Jeffrey R Deschamps; Arthur E Jacobson; Kenner C Rice
Journal:  J Med Chem       Date:  2009-12-10       Impact factor: 7.446
  4 in total

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