100303-76-2Relevant articles and documents
Spirolactones from Dirhodium(II)-Catalyzed Diazo Decomposition with Regioselective Carbon-Hydrogen Insertion
Doyle, Michael P.,Dyatkin, Alexey B.
, p. 3035 - 3038 (1995)
Dirhodium(II) caprolactamate, Rh2(cap)4, catalyzes diazo decomposition of cycloalkylmethyl diazoacetates which form spirolactones in moderate to high yield by insertion into a tertiary carbon-hydrogen bond.Similar results are obtained with diazoacetates derived from tetrahydropyran-2-methanol and tetrahydrofurfuryl alcohol but not from cyclopropylmethanol.With tetrahydrofuran-3-ylmethyl diazoacetate, Rh2(cap)4 catalysis promotes δ-lactone formation via insertion into the oxygen-activated secondary C-H bond instead of γ-lactone formation by carbene insertion into the unactivated tertiary C-H bond.However, when both 1,5- and 1,6-positions are activated for insertion by adjacent oxygen atoms, as in (2,2-dimethyl-1,3-dioxolan-4-yl)methyl diazoacetate, five-membered ring formation occurs exclusively in Rh2(cap)4-catalyzed reactions, whereas use of dirhodium(II) acetate leads to both insertion products.
Design and synthesis of new 1,4-dihydropyridines containing 4(5)-chloro-5(4)-imidazolyl substituent as a novel calcium channel blocker
Iman, Maryam,Davood, Asghar,Nematollahi, Ali Reza,Dehpoor, Ahmad Rerza,Shafiee, Abbas
experimental part, p. 1417 - 1426 (2012/05/04)
New analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 has been replaced by 4(5)-chloro-5(4)-imidazolyl substituent and which are able to interact with the receptor by hydrogen binding were designed, synthesized, and evaluated as calcium channel antagonists. The designed dihydropyridines were synthesized using the Hantzsch condensation and evaluated as calcium channel antagonists using the high K+ contraction of guineapig ileal longitudinal smooth muscle. A docking study was performed using the AutoDock4 program, and QSAR equations were obtained using multilinear regression. Our computational studies indicated that the oxygen of the ester (O10) and the N3′ of the imidazole ring form a hydrogen bonding interaction with the NH of HIS 363 and NH of LYS354, respectively, and that the sum of the BEHp5 and RDF075p are the most significant descriptors. The results of calcium channel antagonist evaluation demonstrated that increasing the chain length in C3 and C5 ester substituents increased activity. The most potent compound was the bis-phenylpropyl ester (5l) derivative, in that it was more active than the reference drug nifedipine and that the bis-phenylethyl ester (5k) derivative had comparable activity with nifedipine. The present research revealed that the 4(5)-chloro-5(4)-imidazolyl moiety is a bioisoster of o-nitrophenyl in nifedipine and provided novel dihydropyridines with more activity as calcium channel antagonists.
Synthesis and calcium-channel antagonist activity of 4-imidazolyl-1,4-dihydropyridines
Pourmorad,Hadizadeh,Shafiee
, p. 165 - 168 (2007/10/03)
The o-nitrophenyl group at position 4 of dihydropyridine of nifedipine analogues was replaced by 1-methylimidazole. These compounds were evaluated as calcium-channel antagonists using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle. The results for the symmetrical esters showed that increasing the length of methylene chain of ester more than 3 units decreases activity. For cyclic esters, cyclopropylmethyl ester was more active than cyclohexylmethyl ester. Our results revealed two compounds with activities similar to the reference drug nifedipine; the symmetrical cyclopropylmethyl ester, and the asymmetrical phenethyl ethyl derivatives were the most potent antagonists tested.