Synthesis of novel 2-chloro-1,4-dihydropyridines by chlorination of 2-hydroxy-1,4-dihydropyridines with phosphorus oxychloride

Novel 2-chloro-1,4-dihydropyridine derivatives were synthesized by chlorination of 2-hydroxy-1,4-dihydropyridines with POCl3. The dihydropyridines chlorinated at position 2 exhibited more potent vasodilative and hypotensive activities than the dihydropyridines (nicardipine and nitrendipine) with a methyl group at position 2.     

Synthesis of novel unsymmetrical coumarinyl-1,4-dihydropyridines

The novel unsymmetrical 3,5-dialkoxycarbonyl-2,6-dimethyl-4-(7′,8′-dimethoxycoumarin-4′-yl)-1,4-dihydropyridines and 5-acetyl-3-alkoxycarbonyl-2,6-dimethyl-4-(7′,8′-dimethoxycoumarin-4′-yl)-1,4-dihydropyridines (coumarinyl-1,4-dihydropyridines) have been synthesized by Knoevenagel condensation of 4-formyl-7,8-dimethoxycoumarin with alkyl acetoacetates in the presence of AlCl₃ followed by cyclization of the resulted Knoevenagel product with other alkyl acetoacetate or acetyl acetone and ammonium acetate. The structure of the intermediate Knoevenagel product and the cyclized unsymmetrical coumarinyl-1,4-dihydropyridines has been established on the basis of their spectral data analysis and single-crystal X-ray diffraction analysis. The observed conformation of the coumarinyl-1,4-dihydropyridines holds the key to promising calcium antagonistic activity of the synthesized coumarinyl-1,4-dihydropyridines.     

Synthesis of 1,4-dihydropyridines having an N-alkylpyridinium substituent at the 4-position and their affinity towards liposomal membranes

There has been synthesized a series of 1,4-dihydropyridines having an N-alkylpyridinium substituent at position 4 with a varying length of hydrocarbon chain. Their affinity to model (liposomal) membranes has been studied. It was found that this affinity increased with lengthening of the hydrocarbon chain on the Npyridinium substituent at the 4-position of the 1,4-dihydropyridine ring. However, lengthening of the hydrocarbon chain in the 3,5-ester groups of the 1, 4-dihydropyridine ring led to a decrease in the binding to the liposome when a 4-(N-hexadecylpyridinium) substituent was present.Latvian Institute of Organic Synthesis, Riga LV-1006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1112–1117, August, 1995. Original article submitted June 6, 1995.     

Renin inhibitors. I. Synthesis and structure-activity relationships of transition-state inhibitors containing homostatine analogues at the scissile bond.

The synthesis and structure-activity relationships of transition-state renin inhibitors containing the homostatine analogues at the scissile bond are described. These inhibitors incorporate the amino acid side chains corresponding to positions 7-12 (P4-P2') of angiotensinogen. Ethyl, 2-hydroxyethyl and 3-hydroxypropyl groups at position 2 of the homostatine analogues (P1') are more effective for increasing potency than the isopropyl group. A combination of residues at P1, P3 and P4 is important for potency and this result suggests that S1, S3 and S4 form a huge hydrophobic core together in renin.     

Synthesis and study of novel fulleropyrrolidines bearing biologically active 1,4-dihydropyridines

New fulleropyrrolidines endowed with chlorine-containing biological active 1,4-dihydropyridines (1,4-DHPs) have been synthesised from the respective formyl substituted 1,4-DHPs by following Prato's procedure. The presence of the chlorine atom on C2 of the 1,4-DHP ring brings about important spectroscopical and structural differences in compounds 10a-f related to the parent hydrogen-containing 11a. The mass spectroscopy study reveals different fragmentation patterns for fulleropyrrolidines 10a-f and their precursors 1,4-DHPs, as well as with 11a. Semiempirical calculations (AM1 and PM3) predict a most stable stereoisomer in all cases (RS for 10a-f) and the same RR for 11a. The presence of chlorine atom in 10a-f is responsible for the higher calculated conformational energy barriers in comparison with 11a. The geometry of the 1,4-DHP shows that the presence of fullerene unit does not significantly alter the required conformation for biological activity.     

Chiral 1,4-dihydropyridines. Synthesis and absolute configuration.

Addition of organometallics to chiral 3-pyridyl oxazolines gave high diastereoselectivity at the 4-position of the pyridine nucleus. Absolute configuration was determined by x-ray analysis.     

Synthesis of chiral 1,3-dihydroisobenzofurans (phthalans) containing functional substituents in the 1-position

Chiral 3-methyl-1,3-dihydroisobenzofurans (phthalans) having a carbonyl or α-hydroxybenzyl group in position 1 were synthesized by cyclization of the corresponding trimethyl[(S)-1-phenylethyl]ammonium iodides. The configuration of the chiral centers in the products was determined by X-ray analysis.     

Regioselective synthesis of novel 2-chloroquinoline derivatives of 1,4-dihydropyridines

Highly regioselective reaction of some substituted 2,4-dichloroquinolines with symmetrical 1,4-dihydropyridines, leading to novel quinoline derivatives of DHPs, has been achieved in the presence of powdered K₂CO₃, as a mild and efficient base, at moderate temperature. All the synthesized compounds were characterized by use of IR, NMR, and mass spectral data.     

A novel TMSI-mediated synthesis of Hantzsch 1,4-dihydropyridines at ambient temperature

The synthesis of various substituted Hantzsch 1,4-dihydropyridines has been achieved using the classical Hantzsch procedure and modified Hantzsch conditions for the first time at room temperature in the presence of iodotrimethylsilane (TMSI) generated in situ in CH₃CN, in excellent yields.     

Synthesis and novel structure-activity relationships of potent sansalvamide A derivatives

Synthesis of twelve Sansalvamide A derivatives and their SAR against colon cancer (HT-29).     

Synthesis of cationic ether lipids of alkyl type with short-chain substituents at the 2-position of the glycerol backbone

A series of cationic ether lipids with short-chain substituents at the 2-position and various cationic groups attached directly or through a spacer group to the glycerol backbone was synthesized.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1826–1830, October, 1994.This work was supported by the Russian Foundation for Basic Research (Project No. 94-03-08-166).     

Synthesis of some 1,4-dihydropyridines under the microwave irradiation

Russian Journal of General Chemistry -     

Synthesis of some benzimidazoles containing 2-perfluoro substituents

A new method is described for the preparation of 2-perfluoroalkylether- benzimidazoles through the N-monoacyl derivatives of o-phenylenediamine. 2-pentafluorophenylbenzimidazole has been obtained by the reaction of o-phenylenediamine and pentafluorobenzoic acid in the presence of polyphosphoric acid. 2-Perfluoroalkylbenzimidazoles have been prepared in excellent yields by direct condensation of o-phenylenediamine with perfluoroalkane- carboxylic acids in the absence of any solvent or added reagent. Some derivatives of these compounds are also described.     

Studies on cardiotonic agents. VI. Synthesis of novel 4,5-dihydro-3(2H)-pyridazinone derivatives carrying some benzoheterocycles at the 6-position

Several benzothiazolyl, imidazobenzothiazolyl, benzothienyl, benzothienopyrimidinyl and quinazolinyl 4,5-dihydro-3(2H)-pyridazinones were synthesized and examined for cardiotonic activity in anesthetized dogs after i.v. administration. Among them, 4-methylamino-7-(2,3,4,5-tetrahydro-5-methyl-3-oxo-6- pyridazinyl)quinazoline (36) showed potent and long-lasting inotropic activity (relative potency = 2.11, milrinone = 1). The activity of 36 was more potent than indolidan (2) (relative potency = 1.53) which is one of the most potent inotropic agents to date.     

Synthesis and Photochemistry of Novel 3,5-Diacetyl-1,4-dihydropyridines

Summary.  Some novel 3,5-diacetyl-1,4-dihydropyridine derivatives were synthesized; their photochemical behaviour was studied under oxygen or argon atmosphere. Irradiation of these compounds resulted in the aromatization of the ring and formation of 3,5-diacetylpyridine derivatives. The presence of oxygen plays an important role in the type, rate, or failure of oxidation. Irradiation of these compounds with of 2-furyl or 5-methyl-2-furyl substituents in position 4 under argon resulted in the formation of a pyridine ring with retention of these substituents, whereas loss of these substituents and ring aromatization was observed upon irradiation under oxygen. Received September 4, 2001. Accepted September 17, 2001     

Synthesis and Photochemistry of Novel 3,5-Diacetyl-1,4-dihydropyridines

 Some novel 3,5-diacetyl-1,4-dihydropyridine derivatives were synthesized; their photochemical behaviour was studied under oxygen or argon atmosphere. Irradiation of these compounds resulted in the aromatization of the ring and formation of 3,5-diacetylpyridine derivatives. The presence of oxygen plays an important role in the type, rate, or failure of oxidation. Irradiation of these compounds with of 2-furyl or 5-methyl-2-furyl substituents in position 4 under argon resulted in the formation of a pyridine ring with retention of these substituents, whereas loss of these substituents and ring aromatization was observed upon irradiation under oxygen.     

Synthesis and biological evaluation of new series 1,4-dihydropyridines

Research on Chemical Intermediates - N,N,N′,N′-Tetrachlorobenzene-1,3-disulfonamide and poly(N,N′-dichloro-N-ethyl-benzene-1,3-disulfonamide) are new catalysts promoted by...     

A molecular graphics study on structure-action relationships of calcium-antagonistic and agonistic 1,4-dihydropyridines

Summary Based on force field and quantum chemical calculations a hypothesis on the molecular mechanism of Ca channel-modulating 1,4-dihydropyridines (DHPs) has been developed. A careful investigation of the molecular electrostatic fields of the compounds led to the discovery of a unique area of the molecular potentials where Ca agonists and antagonists possess potentials with opposite sign. It is further demonstrated that the molecular potential of a simple receptor site model is reduced by interaction with Ca channel-activating DHPs and on the contrary increased by Ca channel-blocking DHPs. It is concluded that these effects could be the basis for opposite actions of 1,4-dihydropyridine enantiomers at the potential-dependent Ca channels.