76132-63-3Relevant academic research and scientific papers
Acylguanidines as bioisosteres of guanidines: NG-acylated imidazolylpropylguanidines, a new class of histamine h2 receptor agonists
Ghorai, Prasanta,Kraus, Anja,Keller, Max,G?tte, Carsten,Igel, Patrick,Schneider, Erich,Schnell, David,Bernhardt, Günther,Dove, Stefan,Zabel, Manfred,Elz, Sigurd,Seifert, Roland,Buschauer, Armin
supporting information; experimental part, p. 7193 - 7204 (2009/10/02)
N1-Aryl(heteroaryl)alkyl-N2-[3-(1H-imidazol-4-yl) propyl]guanidines are potent histamine H2-receptor (H2R) agonists, but their applicability is compromised by the lack of oral bioavailability and CNS penetration. To improve pharmacokinetics, we introduced carbonyl instead of methylene adjacent to the guanidine moiety, decreasing the basicity of the novel H2R agonists by 4-5 orders of magnitude. Some acylguanidines with one phenyl ring were even more potent than their diaryl analogues. As demonstrated by HPLC-MS, the acylguanidines (bioisosteres of the alkylguanidines) were absorbed from the gut of mice and detected in brain. In GTPase assays using recombinant receptors, acylguanidines were more potent at the guinea pig than at the human H2R. At the hH1R and hH3R, the compounds were weak to moderate antagonists or partial agonists. Moreover, potent partial hH4R agonists were identified. Receptor subtype selectivity depends on the imidazolylpropylguanidine moiety (privileged structure), opening an avenue to distinct pharmacological tools including potent H4R agonists.
Conjugate addition of 2- and 4-pyridylcuprates: An expeditious asymmetric synthesis of natural (-)-evoninic acid
Spivey, Alan C.,Shukla, Lena,Hayler, Judy F.
, p. 891 - 894 (2007/10/03)
(Chemical Equation Presented) The scope and limitations of the conjugate addition of 2- and the first 4-pyridyl Gilman homocuprates to various α,β-unsaturated Michael acceptors are delineated. The conjugate addition of the cuprate of 2-bromo-3-methylpyridine to (E)-methyl crotonate then diastereoselective enolate alkylation and lipase-mediated enantioselective ester hydrolysis have enabled an efficient four-step first asymmetric synthesis of the Celastraceae sesquiterpenoid esterifying ligand (-)-(1′S,2′S) -evoninic acid.
Synthesis of a series of potent and orally bioavailable thrombin inhibitors that utilize 3,3-disubstituted propionic acid derivatives in the P3 position
Tucker, Thomas J.,Lumma, William C.,Dale Lewis,Gardell, Stephen J.,Lucas, Bobby J.,Sisko, Jack T.,Lynch, Joseph J.,Lyle, Elizabeth A.,Baskin, Elizabeth P.,Woltmann, Richard F.,Appleby, Sandra D.,Chen, I.-Wu,Dancheck, Kimberley B.,Naylor-Olsen, Adel M.,Krueger, Julie A.,Cooper, Carolyn M.,Vacca, Joseph P.
, p. 3687 - 3693 (2007/10/03)
As part of an effort to prepare efficacious and orally bioavailable analogs of the previously reported thrombin inhibitors 1a,b, we have synthesized a series of compounds that utilize 3,3-disubstituted propionic acid derivatives as P3 ligands.
CONJUGATE ADDITIONS WITH CHIRAL LITHIUM (2-PYRIDYL)-CUPRATE
Malmberg, Hans,Nilsson, Martin
, p. 241 - 244 (2007/10/02)
The cuprate (LiPyR*Cu) transfers its pyridyl group to 4-phenyl-3-buten-2-one at -60 deg C in ether to give (+)-4-phenyl-4-(2-pyridyl)-2-butanone in good yield with some enantioselectivity (23percent e.e.).Additions to ethyl 3-phenyl-propenoate and to 5-phenyl-2,2-dimethyl-4-penten-3-one give good yields but low inductions.Induction is also low on transfer of a phenyl group from LiPhR*Cu to 4-(2-pyridyl)-buten-2-one.
CONJUGATE ADDITION WITH 2-PYRIDYLCOPPER AND LITHIUM 2-PYRIDYLCUPRATES
Malmberg, H.,Nilsson, M.
, p. 1509 - 1510 (2007/10/02)
2-Pyridylcopper/dibutyl sulfide, 2-pyridylcopper/tributylphosphine, lithium di(2-pyridyl)cuprate and lithium (2-pyridyl)(phenyl)cuprate all add the 2-pyridyl group to 4-phenyl-3-buten-2-one in good yields.The cuprates also add the 2-pyridyl group to ethyl 3-phenypropenoate.
