2. Academic Validation
  3. Role of hydrophobic substituents on the terminal nitrogen of histamine in receptor binding and agonist activity: development of an orally active histamine type 3 receptor agonist and evaluation of its antistress activity in mice

Role of hydrophobic substituents on the terminal nitrogen of histamine in receptor binding and agonist activity: development of an orally active histamine type 3 receptor agonist and evaluation of its antistress activity in mice

  • J Med Chem. 2010 May 13;53(9):3840-4. doi: 10.1021/jm901890s.
Makoto Ishikawa 1,  Rie Shinei,  Fumikazu Yokoyama,  Miki Yamauchi,  Masayo Oyama,  Kunihiro Okuma,  Takako Nagayama,  Kazuhiko Kato,  Nobukazu Kakui,  Yasuo Sato
Affiliations

Affiliation

  • 1 Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan.
PMID: 20384344 DOI: 10.1021/jm901890s
Abstract

The terminal nitrogen atom of histamine was modified with lipophilic substituents to investigate the structure-activity relationship of histamine type 3 receptor (H3R) agonists. The introduction of an alkylated benzene rings maintained or increased the H3R binding affinity. The most potent compound, 4-(2-(4-tert-butylphenylthio)ethyl)-1H-imidazole, possessed in vivo agonistic activity, decreasing brain N(tau)-methylhistamine levels in mice after oral administration. It also exhibited antistress activity in the mouse resident-intruder test.

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