188697-89-4Relevant academic research and scientific papers
A chemical switch for the modulation of the functional activity of higher homologues of histamine on the human histamine H3 receptor: Effect of various substitutions at the primary amino function
Govoni, Marinella,Lim, Herman D.,El-Atmioui, Dris,Menge, Wiro M. P. B.,Timmerman, Henk,Bakker, Remko A.,Leurs, Rob,De Esch, Iwan J. P.
, p. 2549 - 2557 (2007/10/03)
In an effort to establish the structural requirements for agonism, neutral antagonism, and inverse agonism at the human histamine H3 receptor (H3R) we have prepared a series of higher homologues of histamine in which the terminal nitrogen of the side chain has been either mono- or disubstituted with several aliphatic, alicyclic, and aromatic moieties or incorporated in cyclic systems. The novel ligands have been pharmacologically investigated in vitro for their affinities on the human H3R and H4R subtypes by radioligand displacement experiments and for their intrinsic H3R activities via a CRE-mediated β-galactosidase reporter gene assay. Subtle changes of the substitution pattern at the side chain nitrogen alter enormously the pharmacological activity of the ligands, resulting in a series of compounds with a wide spectrum of pharmacological activities. Among the several neutral H3R antagonists identified within this series, compounds 2b and 2h display an H3R affinity in the low nanomolar concentration range (pKi values of 8.1 and 8.4, respectively). A very potent and selective H3R agonist (11, pEC 50 = 8.9, α = 0.94) and a very potent, though not highly selective, H3R inverse agonist (2k, pIC50 = 8.9, α = -0.97) have been identified as well.
New high affinity H3 receptor agonists without a basic side chain
Kitbunnadaj, Ruengwit,Hoffmann, Marcel,Fratantoni, Silvina A.,Bongers, Gerold,Bakker, Remko A.,Wieland, Kerstin,El Jilali, Ahmed,De Esch, Iwan J. P.,Menge, Wiro M. P. B.,Timmerman, Henk,Leurs, Rob
, p. 6309 - 6323 (2007/10/03)
In this study, we replaced the basic amine function of the known histamine H3 receptor agonists imbutamine or immepip with non-basic alcohol or hydrocarbon moieties. All compounds in this study show a moderate to high affinity for the cloned human H3 receptor and, unexpectedly, almost all of them act as potent agonists. Moreover, in the alcohol series, we consistently observed an increased selectivity for the human H3 receptor over the human H4 receptor, but none of the compounds in this series possess increased affinity and functional activity compared to their alkylamine congeners. In this new series of compounds VUF5657, 5-(1H-imidazol-4-yl)-pentan-1-ol, is the most potent histamine H3 receptor agonist (pKi = 8.0 and pEC50 = 8.1) with a 320-fold selectivity at the human H3 receptor over the human H 4 receptor.
Substituted imidazoles as dual histamine H1 and H3 agonists or antagonists
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, (2008/06/13)
The present invention discloses novel substituted imidazole compounds which have H3 receptor antagonist or dual histamine-H1 and H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, nasal congestion, inflammatory and CNS-related diseases and others.
Substituted imidazoles as dual histamine H1 and H3 agonists or antagonists
-
, (2008/06/13)
The present invention discloses novel substituted imidazole compounds which have dual histamine-H1 and H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, inflammatory and CNS-related diseases and others.
Substituted imidazoles as dual histamine H1 and H3 agonists or antagonists
-
, (2008/06/13)
The present invention discloses novel substituted imidazole compounds which have H3 receptor antagonist activity or dual histamine-H1 and H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such imidazoles as well as methods of using them to treat allergy, congestion, inflammatory and CNS-related diseases and others.
Sulfonamides and sulfamides as H3 receptor antagonists
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, (2008/06/13)
PCT No. PCT/GB97/00358 Sec. 371 Date Oct. 6, 1998 Sec. 102(e) Date Oct. 6, 1998 PCT Filed Feb. 10, 1997 PCT Pub. No. WO97/29092 PCT Pub. Date Aug. 14, 1997Compounds of formula (I) or (II) wherein R1 is C4 to C20 hydrocarbyl (in which one or more hydrogen atoms may be replaced by halogen, and up to three carbon atoms may be replaced by oxygen, nitrogen or sulphur atoms, provided that R1 does not contain an -O-O- group), R2 is H or C1 to C3 alkyl, m is from 1 to 15, n is from 2 to 6, each X group is independently (a), or one X group is -N(R4)-, -O- or -S- and the remaining X groups are independently (a), wherein R3 is H, C1 to C6 alkyl, -CO2R5, -CONR52, -CR52OR6 or -OR5 (in which R5 and R6 are H or C1 to C3 alkyl), and R4 is H or C1 to C6 alkyl, each Y group is independently -C(R3)R4-, or up to two Y groups are -N(R4)-, -O- or -S- and the remaining Y groups are independently -C(R3)R4-, wherein R3 is as defined above, one R4 group in the structure is imidazoyl or imidazoylalkyl and the remaining R4 groups are H or C1 to C6 alkyl, and Z is >C(R7)NR2- or >N-, wherein R7 is any of the groups recited above for R3, and pharmaceutically acceptable salts thereof are ligands at histamine H3 receptors.
