14205-43-7Relevant articles and documents
A new modification of the Bohlmann-Rahtz pyridine synthesis
Bagley,Dale,Bower
, p. 1149 - 1151 (2001)
A range of highly functionalised pyridines is prepared from enamino esters and alkynones in a single synthetic step by the use of acetic acid or amberlyst 15 ion exchange resin at 50°C.
Noncovalently Functionalized Commodity Polymers as Tailor-Made Additives for Stereoselective Crystallization
Wan, Xinhua,Wang, Zhaoxu,Ye, Xichong,Zhang, Jie
supporting information, p. 20243 - 20248 (2021/08/09)
Stereoselective inhibition of the nucleation and crystal growth of one enantiomer aided by “tailor-made” polymeric additives is an efficient method to obtain enantiopure compounds. However, the conventional preparation of polymeric additives from chiral monomers are laborious and limited in structures, which impedes their rapid optimization and applicability. Herein, we report a “plug-and-play” strategy to facilitate synthesis by using commercially available achiral polymers as the platform to attach various chiral small molecules as the recognition side-chains through non-covalent interactions. A library of supramolecular polymers made up of two vinyl polymers and six small molecules were applied with seeds in the selective crystallization of seven racemates in different solvents. They showed good to excellent stereoselectivity in yielding crystals with high enantiomeric purities in conglomerates and racemic compound forming systems. This convenient, low-cost modular synthesis strategy of polymeric additives will allow for high-efficient, economical resolution of various racemates on different scales.
Unsymmetric dihydropyridines bearing 2-pyridyl methyl carboxylate as modulators of P-glycoprotein; Synthesis and biological evaluation in resistant and non-resistant cancer cells
Nejati, Maryam,Sadeghpour, Hossein,Ranjbar, Sara,Javidnia, Katayoun,Edraki, Najmeh,Saso, Luciano,Firuzi, Omidreza,Miri, Ramin
, p. 603 - 614 (2019/08/06)
Multi-drug resistance (MDR) in cancer cells is often associated with overexpression of P-glycoprotein (P-gp or ABCB1 or MDR1); therefore, modulators of this transporter might be helpful in overcoming MDR. In this study, 16 novel unsymmetrical dihydropyridine (DHP) derivatives bearing 2-pyridyl methyl carboxylate at C3 and a nitroimidazole or nitrophenyl ring at C4 positions of the DHP ring were synthesized. Their cytotoxicity was tested against four human cancer cells by MTT assay. The reversal capacity of MDR was examined in P-gp overexpressing cells (MES-SA/DX5) by measuring the alteration of doxorubicin's IC50 and performing flow cytometric determination of intracellular rhodamine 123 accumulation. The calcium channel blocking (CCB) activity, as a side effect of DHPs, was tested on the ileum of a guinea pig. Molecular docking was performed to explain the binding mode of compounds. Two derivatives, 4a and 4c, containing 4-nitrophenyl at C4 and possessing methyl (4a) and iso-propyl (4c) carboxylates at the C5 position of DHP core demonstrated superior cytotoxic and MDR reversal activities and lower CCB effect. Docking analysis confirmed the importance of the 4-nitrophenyl ring for P-gp inhibitory activity. Some of the synthesized DHP derivatives with considerable MDR reversal capacity could be promising compounds for further discovery of useful agents for management of drug resistant cancer.
Cytotoxic and multidrug resistance reversal activities of novel 1,4-dihydropyridines against human cancer cells
Shekari, Farnaz,Sadeghpour, Hossein,Javidnia, Katayoun,Saso, Luciano,Nazari, Farhad,Firuzi, Omidreza,Miri, Ramin
, p. 233 - 244 (2015/04/16)
Multidrug resistance (MDR) caused by P-glycoprotein (P-gp, ABCB1, MDR-1) transporter over-expression in cancer cells substantially limits the effectiveness of chemotherapy. 1,4-Dihydropyridines (DHPs) derivatives possess several pharmacological activities. In this study, 18 novel asymmetrical DHPs bearing 3-pyridyl methyl carboxylate and alkyl carboxylate moieties at C3 and C5 positions, respectively, as well as nitrophenyl or hetero aromatic rings at C4 were synthesized and tested for MDR reversal with the aim of establishing a structure-activity relationship (SAR) for these agents. Effect of these compounds on P-gp mediated MDR was assessed in P-gp over-expressing MES-SA/DX5 doxorubicin resistant cells by flow cytometric detection of rhodamine 123 efflux. MDR reversal was further examined as the alteration of doxorubicin's IC50 in MES-SA/DX5 cells in the presence of DHPs by MTT assay and was compared to nonresistant MES-SA cells. Direct anticancer effect was examined against 4 human cancer cells including HL-60, K562, MCF-7 and LS180. Calcium channel blocking (CCB) activity was also measured as a potential side effect. Most DHPs, particularly compounds bearing 3-nitrophenyl (A2B2 and A3B2) and 4-nitrophenyl (A3B1 and A4B1) moieties at C4 significantly inhibited rhodamine 123 efflux at 5-25 μM, showing that the mechanism of MDR reversal by these agents is P-gp transporter modulation. Same derivatives were also able to selectively lower the resistance of MES-SA/DX5 to doxorubicin. A2B2 bearing ethyl carboxylate at C5 had also high direct antitumoral effect (IC50 range: 3.77-15.60 μM). Our findings suggest that SAR studies of DHPs may lead to the discovery of novel MDR reversal agents.
Discovery and structure-activity relationships of pyrrolone antimalarials
Murugesan, Dinakaran,Mital, Alka,Kaiser, Marcel,Shackleford, David M.,Morizzi, Julia,Katneni, Kasiram,Campbell, Michael,Hudson, Alan,Charman, Susan A.,Yeates, Clive,Gilbert, Ian H.
supporting information, p. 2975 - 2990 (2013/05/23)
In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 ～ 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.
Synthesis of β-amino acid derivatives via copper-catalyzed asymmetric 1,4-reduction of β-(acylamino)acrylates
Wu, Yan,Qi, Shan-Bin,Wu, Fei-Fei,Zhang, Xi-Chang,Li, Min,Wu, Jing,Chan, Albert S. C.
supporting information; experimental part, p. 1754 - 1757 (2011/05/12)
A new set of reaction conditions has been established to facilitate the copper-catalyzed enantioselective 1,4-reduction of β-(acylamino)acrylates toward a selection of β-alkyl-β-amino acid derivatives in high yields and with uniformly high ee values (up to 99%) irrespective of the use of (E)- or (Z)-substrates.
Bohlmann-Rahtz cyclodehydration of aminodienones to pyridines using N-iodosuccinimide
Bagley, Mark C.,Glover, Christian
experimental part, p. 3211 - 3227 (2010/09/04)
Cyclodehydration of Bohlmann-Rahtz aminodienone intermediates using N-iodosuccinimide as a Lewis acid proceeds at low temperature under very mild conditions to give the corresponding 2, 3,6-trisubstituted pyridines in high yield and with total regiocontrol.
One-step continuous flow synthesis of highly substituted pyrrole-3-carboxylic acid derivatives via in situ hydrolysis of tert-butyl esters
Herath, Ananda,Cosford, Nicholas D. P.
body text, p. 5182 - 5185 (2011/02/27)
The first one-step, continuous flow synthesis of pyrrole-3-carboxylic acids directly from tert-butyl acetoacetates, amines, and 2-bromoketones is reported. The HBr generated as a byproduct in the Hantzsch reaction was utilized in the flow method to hydrolyze the t-butyl esters in situ to provide the corresponding acids in a single microreactor. The protocol was used in the multistep synthesis of pyrrole-3-carboxamides, including two CB1 inverse agonists, directly from commercially available starting materials in a single continuous process.
An efficient, metal-free, room temperature aromatization of Hantzsch-1,4-dihydropyridines with urea-hydrogen peroxide adduct, catalyzed by molecular iodine
Filipan-Litvi?, Mirela,Litvi?, Mladen,Vinkovi?, Vladimir
, p. 5649 - 5656 (2008/09/21)
A mild, highly efficient and metal-free synthetic method for aromatization of 1,4-dihydropyridines employing urea-hydrogen peroxide adduct as oxidant catalyzed by 20 mol % of molecular iodine was developed. The reaction was carried out in ethyl acetate at room temperature and the products were isolated in high to excellent yields. A plausible free-radical mechanism is proposed based on results obtained with derivatives having alkyl and aryl substituents in the 1,4-dihydropyridine ring.
PYRIDINE COMPOUNDS AS INHIBITORS OF DIPEPTIDYL PEPTIDASE IV
-
Page/Page column 105-106, (2010/02/11)
A compound represented by the formula wherein R1 and R2 are the same or different and each is an optionally substituted hydrocarbon group or an optionally substituted hydroxy group; R3 is an optionally substituted aromatic group; R4 is an optionally substituted amino group; L is a divalent chain hydrocarbon group; Q is a bond or a divalent chain hydrocarbon group; and X is a hydrogen atom, a cyano group, a nitro group, an acyl group, a substituted hydroxy group, an optionally substituted thiol group, an optionally substituted amino group or an optionally substituted cyclic group; provided that when X is an ethoxycarbonyl group, then Q is a divalent chain hydrocarbon group. The compound has a peptidase inhibitory action, is useful as an agent for the prophylaxis or treatment of diabetes and the like, and is superior in efficacy, duration of action, specificity, lower toxicity and the like.
