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Orally active PDE4 inhibitor with therapeutic potential.
Eur J Med Chem 2004; 39(7):555-71EJ

Abstract

Based on the promising results obtained by the clinical trial of Ariflo, further optimization of the spatial arrangement of the three pharmacophores (the carboxylic acid moiety, nitrile moiety and 3-cyclopentyloxy-4-methoxyphenyl moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3 ?3 ?0]octane template with more stereochemical diversity than the cyclohexane template of Ariflo 1. Biological evaluation of the decyanated analogs and further optimization of the cyclopentyloxy moiety of 2a-b were also performed. Among the compounds tested, 2a, 7a-b and 12a were found to be orally active and were estimated to have therapeutic potential based on cross-species and same-species comparisons. The structure-activity relationships (SARs) of these compounds were investigated and pharmacokinetic data for 2a and 7b were also obtained by single-dose studies in rats.

Authors+Show Affiliations

Medicinal Chemistry Research Laboratories, Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15236836

Citation

Ochiai, Hiroshi, et al. "Orally Active PDE4 Inhibitor With Therapeutic Potential." European Journal of Medicinal Chemistry, vol. 39, no. 7, 2004, pp. 555-71.
Ochiai H, Ohtani T, Ishida A, et al. Orally active PDE4 inhibitor with therapeutic potential. Eur J Med Chem. 2004;39(7):555-71.
Ochiai, H., Ohtani, T., Ishida, A., Kishikawa, K., Yamamoto, S., Takeda, H., ... Toda, M. (2004). Orally active PDE4 inhibitor with therapeutic potential. European Journal of Medicinal Chemistry, 39(7), pp. 555-71.
Ochiai H, et al. Orally Active PDE4 Inhibitor With Therapeutic Potential. Eur J Med Chem. 2004;39(7):555-71. PubMed PMID: 15236836.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Orally active PDE4 inhibitor with therapeutic potential. AU - Ochiai,Hiroshi, AU - Ohtani,Tazumi, AU - Ishida,Akiharu, AU - Kishikawa,Katuya, AU - Yamamoto,Susumu, AU - Takeda,Hiroshi, AU - Obata,Takaaki, AU - Nakai,Hisao, AU - Toda,Masaaki, PY - 2003/09/02/received PY - 2004/01/29/revised PY - 2004/02/12/accepted PY - 2004/7/9/pubmed PY - 2005/2/24/medline PY - 2004/7/9/entrez SP - 555 EP - 71 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 39 IS - 7 N2 - Based on the promising results obtained by the clinical trial of Ariflo, further optimization of the spatial arrangement of the three pharmacophores (the carboxylic acid moiety, nitrile moiety and 3-cyclopentyloxy-4-methoxyphenyl moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3 ?3 ?0]octane template with more stereochemical diversity than the cyclohexane template of Ariflo 1. Biological evaluation of the decyanated analogs and further optimization of the cyclopentyloxy moiety of 2a-b were also performed. Among the compounds tested, 2a, 7a-b and 12a were found to be orally active and were estimated to have therapeutic potential based on cross-species and same-species comparisons. The structure-activity relationships (SARs) of these compounds were investigated and pharmacokinetic data for 2a and 7b were also obtained by single-dose studies in rats. SN - 0223-5234 UR - https://www.unboundmedicine.com/medline/citation/15236836/Orally_active_PDE4_inhibitor_with_therapeutic_potential_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223523404000509 DB - PRIME DP - Unbound Medicine ER -