Chiral NG-acylated hetarylpropylguanidine-type histamine H2 receptor agonists do not show significant stereoselectivity.
A set of chiral imidazolylpropylguanidines and 2-aminothiazolylpropylguanidines bearing N(G)-3-phenyl- or N(G)-3-cyclohexylbutanoyl residues was synthesized and investigated for histamine H(2) receptor (H(2)R) agonism (guinea pig (gp) right atrium, GTPase assay on recombinant gp and human (h)H(2)R) and for hH(2)R selectivity compared to hH(1)R, hH(3)R and hH(4)R. In contrast to previous studies on arpromidine derivatives, the present investigation of acylguanidine-type compounds revealed only very low eudismic ratios (1.1-3.2), indicating the stereochemistry of the acyl moiety to play only a minor role in this series of H(2)R agonists.
Ghorai
Prasanta
P
Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Regensburg, D-93040 Regensburg, Germany.
Kraus
Anja
A
Birnkammer
Tobias
T
Geyer
Roland
R
Bernhardt
Günther
G
Dove
Stefan
S
Seifert
Roland
R
Elz
Sigurd
S
Buschauer
Armin
A
D000818:Animals; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D017442:Histamine Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D011970:Receptors, Histamine H2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism
D006146:Guanidines; D017442:Histamine Agonists; D011970:Receptors, Histamine H2; D011994:Recombinant Proteins; C031653:propylguanidine