Bibenzyls/*chemical synthesis ; Bibenzyls/therapeutic use ; Imidazoles/*chemical synthesis ; Imidazoles/therapeutic use ; Pyrimidines/*chemical synthesis ; Pyrimidines/therapeutic use ; Sarcoma 180/drug therapy

Acyltransferases ; antagonists & inhibitors ; chemistry ; Animals ; Antifungal Agents ; chemical synthesis ; pharmacology ; Benzofurans ; chemical synthesis ; pharmacology ; Benzothiazoles ; chemical synthesis ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; pharmacology ; Fungi ; drug effects ; enzymology ; Imidazoles ; chemical synthesis ; pharmacology ; Molecular Structure

Animals ; Bibenzyls ; chemical synthesis ; therapeutic use ; Imidazoles ; chemical synthesis ; therapeutic use ; Mice ; Pyrimidines ; chemical synthesis ; therapeutic use ; Sarcoma 180 ; drug therapy

AIMTo develop a new synthetic route for olmesartan medoxomil.

METHODSOlmesartan medoxomil was prepared from ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate via hydrolysis and lactonization to afford 4,4- dimethyl-2-propyl-4,6-dihydrofuro [3,4-d]-1H-imidazole-6-one which was condensed with 2-(triphenylmethyl)-5-[4'-(bromomethylbiphenyl)-2-yl] tetrazole, followed by esterification with 4-chloromethyl-5-methyl-1,3-dioxol-2-one, and deprotection. The chemical structure of the major impurity in condensation reaction is the regio-isomer in the imidazole moiety, and confirmed by single crystal X-ray diffraction. The corresponding regio-isomer of olmesartan medoxomil was synthesized from the impurity by similar method. Optimization of the condensation conditions reduced the impurity to a negligible quantity.

RESULTSSynthesis of olmesartan medoxomil by the new route gave a product of 60% yield and above 99.0% purity. The content of olmesartan medoxomil regio-isomer was effectively controlled to less than 0.1%.

CONCLUSIONA novel synthetic route for olmesartan medoxomil was developed successfully. The olmesartan medoxomil regio-isomer is reported for the first time.

Angiotensin II Type 1 Receptor Blockers ; chemical synthesis ; chemistry ; Animals ; Antihypertensive Agents ; chemical synthesis ; chemistry ; pharmacology ; Blood Pressure ; drug effects ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Olmesartan Medoxomil ; Rats ; Stereoisomerism ; Tetrazoles ; chemical synthesis ; chemistry ; pharmacology

AIMTo design and synthesize new arylsubstituted imidazolin-2-one analogues as antitumor compounds.

METHODSArylsubstituted imidazolin-2-ones were prepared by condensation the appropriate omega-amino-acetophenone hydrochloride with arylisocyanate in toluene. The target compounds prepared in this study were tested for cytotoxicity against PC-3, A549, HO-8910, Hela, HL60, K562 and HL60R cancer cell lines, and mechanism of one of the products 4y was further evaluated with its mechanium.

RESULTSThirty-six new compounds were synthesized and confirmed by 1H NMR, MS and elemental analysis. One of the synthesized products, compound 4y, displayed an encouraging selective activity against HL60 cells, and it was partlydue to the cell cycle arrest and cell apoptosis.

CONCLUSIONCompound 4y is worthy to be intensively studied.

Amides ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; HL-60 Cells ; Humans ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Imidazolines ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure

AIMDesign, synthesis and evaluation of a series of 7-imidazolylalkanamido-1-carboxylalkylbenzodiazepine farnesyltransferase (FTase) inhibitors.

METHODS AND RESULTSCoupling of imidazolylalkylcarboxylic acids and 1-substituted 7-aminobenzodiazepines (5a-5c) yielded 10 new compounds (6-12, 16-18) which were biologically tested against FTase using scintillation proximity assay method.

CONCLUSIONFive target compounds were found to be potential farnesyltransferase inhibitors.

Alkyl and Aryl Transferases ; antagonists & inhibitors ; drug effects ; Benzodiazepines ; chemical synthesis ; chemistry ; pharmacology ; Farnesyltranstransferase ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Inhibitory Concentration 50 ; Molecular Conformation ; Molecular Structure ; Structure-Activity Relationship

Polyamides, containing N-methylpyrrole (Py) and N-methyl-imidazole (Im) amino acids, are synthetic oligomers programmed to read the DNA double helix in the minor groove with high affinities and sequence specificities resulting in modulation of gene expression. They are cell permeable, stable and have no cytotoxicity, which provide a promising tool of gene regulation. We describe here recent advances in the field of DNA binding polyamides, including pairing rules, specifities and affinities to DNA, synthesis methods, cellular and nuclear uptake properties, gene regulation and effectiveness in vivo. The potential problems and difficulties in future research are also discussed.
Animals ; Base Pairing ; DNA ; chemistry ; genetics ; DNA Footprinting ; Gene Expression Regulation ; drug effects ; Imidazoles ; chemical synthesis ; chemistry ; metabolism ; pharmacology ; Nylons ; chemical synthesis ; chemistry ; metabolism ; pharmacology ; Pyrroles ; chemical synthesis ; chemistry ; metabolism ; pharmacology

Tepoxalin is a potent inhibitor of both the cyclooxygenase and lipoxygenase pathways of the arachidonic acid cascade, as well as a potent anti-inflammatory and control-pain (postoperation, arthritis et. al.) agent. The new method about the use of novel synthesis reagents and the first using ionic liquid as reactive solvent to synthesize tepoxalin were presented in this paper. The ionic liquid can be easily recycled and reused for several runs efficiently. The analgesic activity of tepoxalin was detected by acetic acid test on mice. The analysis of variance showed that oral administration of tepoxalin could significantly inhibit the number of writhing response within 1 hour and prolong the latent time in a dose dependent manner as compared with CMC control group (P < 0.05). At the same time, tepoxalin had the same analgesic activity as diclofenac sodium.
Administration, Oral ; Analgesics ; administration & dosage ; chemical synthesis ; pharmacology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; chemical synthesis ; pharmacology ; Cyclooxygenase Inhibitors ; administration & dosage ; chemical synthesis ; pharmacology ; Diclofenac ; pharmacology ; Imidazoles ; chemistry ; Ionic Liquids ; chemistry ; Lipoxygenase Inhibitors ; administration & dosage ; chemical synthesis ; pharmacology ; Mice ; Pain Measurement ; drug effects ; Pyrazoles ; administration & dosage ; chemical synthesis ; pharmacology ; Random Allocation

To optimize the synthetic method and antibacterial activity of fused heterocyclic thiadiazole compounds, cyclocondensation of 2-(4-methoxyphenyl)-5-amino-1,3,4-thiadiazole (2) with alpha-chloro-4-chloro acetophenone (3) resulted in a key intermediate (4), 6 -(4-chlorophenyl)-2-(4-methoxyphenyl)-imidazo-[2,1-b][1,3,4]thiadiazole, which was carried out an nucleophilic substitution with substituted piperazine to give the corresponding free bases of piperazine (5a-5c), then followed by Mannich reaction with heterocyclicamines and formaldehyde to yield the corresponding Mannich bases, (1a-11) as respective hydrochloride salts. The structures were confirmed by IR, 1H NMR, MS and elemental analysis and the antibacterial activities in vitro of fifteen newly synthesized compounds were also tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method. The antibacterial results showed that the introduction of a polar group resulted in the enhancement of antibacterial activity in vitro. Thus, the structures of these fused compounds could further be investigated.
Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Bacillus subtilis ; drug effects ; Escherichia coli ; drug effects ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Mannich Bases ; chemistry ; Microbial Sensitivity Tests ; Molecular Structure ; Pseudomonas aeruginosa ; drug effects ; Staphylococcus aureus ; drug effects ; Thiadiazoles ; chemical synthesis ; chemistry ; pharmacology