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Volumn 40, Issue 23, 1997, Pages 3804-3819

Antimuscarinic 3-(2-Furanyl)quinuclidin-2-ene derivatives: Synthesis and structure-activity relationships

Author keywords

[No Author keywords available]

Indexed keywords

3 (2 FURANYL)QUINUCLIDIN 2 ENE; 3 [3 (3 HYDROXYPHENYL)FURAN 2 YL]QUINUCLIDIN 2 ENE; MUSCARINIC RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

EID: 0030813612     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970346t     Document Type: Article
Times cited : (26)

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    • The PLS equation for the model is pKi(cortex) = 6.3938 -0.17612T - 1.0582MR - 0.77751o(para).
    • The PLS equation for the model is pKi(cortex) = 6.3938 -0.17612 - 1.0582MR - 0.77751o(para).
  • 51
    • 85069085567 scopus 로고    scopus 로고
    • note
    • In order to explore this possibility, we docked 68 into a homologybased model of the muscarinic ml receptor (see ref 44). During the docking the protonated quinuclidin-2-ene nitrogen was kept interacting via a hydrogen bond reinforced ionic interaction with AsplOS in transmembrane region (TM) 3.The 3-phenyl group could interact with Trpl64. We also identified a possible hydrogen bond interaction with Ser388 in TM6. This is a variable residue between the subtypes (Ser in ml and m5, Asn in m2, m3 and m4). The lack of subtype selectivity exhibited by 68 may be rationalized as both serine and aspargine residues can accept and donate hydrogen bonds to the ligand.
  • 52
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    • Binding-site Modelling of the Muscarinic ml Receptor: A Combination of Homology-Based and Indirect Approaches
    • Nordvall, G.; Hacksell, U.Binding-site Modelling of the Muscarinic ml Receptor: A Combination of Homology-Based and Indirect Approaches. J. Med. Chem. 1993, 36, 967-976.
    • (1993) J. Med. Chem , vol.36 , pp. 967-976
    • Nordvall, G.1    Hacksell, U.2
  • 53
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    • Comparative Molecular Field Analysis (CoMFA). 1. Effect of Shape on Binding of Steroids to Carrier Proteins
    • (b) Cramer, R. D., III; Depriest, S. A.; Patterson, D. E.; Hecht, P. In The Developing Practise of Comparative Molecular Field Analysis. In 3d QSAR in Drug Design: Theory, Methods and Applications; Kubinyi, H., Ed.; ESCOM: Leiden, 1993; pp 443-485. (c) Van Steen, B. J.; Van Wijngaarden, I.; Tulp, M. T.; Soujdin, W. Structure-affinity relationship studies on 5-HTiA receptor ligands. 2. Heterobicyclic phenylpiperazines with N4-aralkyl substituents. J. Med. Chem. 1994, 37, 2761-2773.
    • (a) Gramer, R. D., Ill; Patterson, D.E.; Bunce, J. D. Comparative Molecular Field Analysis (CoMFA). 1. Effect of Shape on Binding of Steroids to Carrier Proteins. J. Am. Chem. Soc. 1988, 110, 5959-5967. (b) Cramer, R. D., III; Depriest, S. A.; Patterson, D. E.; Hecht, P. In The Developing Practise of Comparative Molecular Field Analysis. In 3d QSAR in Drug Design: Theory, Methods and Applications; Kubinyi, H., Ed.; ESCOM: Leiden, 1993; pp 443-485. (c) Van Steen, B. J.; Van Wijngaarden, I.; Tulp, M. T.; Soujdin, W. Structure-affinity relationship studies on 5-HTiA receptor ligands. 2. Heterobicyclic phenylpiperazines with N4-aralkyl substituents. J. Med. Chem. 1994, 37, 2761-2773.
    • (1988) J. Am. Chem. Soc. , vol.110 , pp. 5959-5967
    • Ill, G.R.D.1    Patterson, D.E.2    Bunce, J.D.3
  • 54
    • 85069084668 scopus 로고    scopus 로고
    • However, the methyl esters 66 and 67 were not included because they may have been partially hydrolyzed during the binding experiments.
    • However, the methyl esters 66 and 67 were not included because they may have been partially hydrolyzed during the binding experiments.
  • 55
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    • Phenothiazines: Preparation of 2- And 3-Tertiary Aminophenothiazines
    • Jones, D. H.Phenothiazines: Preparation of 2- and 3-Tertiary Aminophenothiazines. J. Chem. Soc. C 1971, 132-137.
    • (1971) J. Chem. Soc. C , pp. 132-137
    • Jones, D.H.1
  • 57
    • 85069061853 scopus 로고    scopus 로고
    • Cul was purified by extraction with CH2C12 using a Soxhlet apparatus.
    • Cul was purified by extraction with CH2C12 using a Soxhlet apparatus.
  • 58
    • 85069068900 scopus 로고    scopus 로고
    • Umetri AB, Box 1456, S-901 24 Urnea, Sweden.
    • Umetri AB, Box 1456, S-901 24 Urnea, Sweden.
  • 59
    • 85069072209 scopus 로고    scopus 로고
    • Wavefunction, Inc., 18401Von Karman Ave., No. 370, Irvine, CA
    • Wavefunction, Inc., 18401Von Karman Ave., No. 370, Irvine, CA 92715.
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    • Estimation of Hormone Receptor Affinity by Competitive Displacement of Labelled Ligand. Effects of Concentration of Receptor and Labelled Ligand
    • Jacobs, S.; Chang, K.-J.; Cuatrecasas, P.Estimation of Hormone Receptor Affinity by Competitive Displacement of Labelled Ligand. Effects of Concentration of Receptor and Labelled Ligand. Biophys. Res. Commun. 1975, 66, 687-692.
    • (1975) Biophys. Res. Commun. , vol.66 , pp. 687-692
    • Jacobs, S.1    Chang, K.-J.2    Cuatrecasas, P.3
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    • Schild, H.I.1


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.