- Synthesis and Antihypertensive Activities of New 1,4-Dihydropyridine Containing Nitroimidazolyl Substituent with a Nitrooxy Group at the 3-Ester Position
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New analogues of nifedipine, in which the ortho nitrophenyl group of position 4 is replaced by 1-methyl-4-nitro-5-imidazolyl or 1-methyl-5-imidazolyl with a nitrooxy group at the 3-ester position were synthesized, and the antihypertensive activity of the compounds was examined by the tail-cuff method and compared with TNG and nifedipine. Compounds 11g, 11i-m, 11o, 11r, and 11v showed activity similar to nifedipine and TNG.
- Shafiee, Abbas,Rastkary, Noushin,Jorjani, Masoumeh,Shafaghi, Bijan
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Read Online
- 4,5-Disubstituted N-Methylimidazoles as Versatile Building Blocks for Defined Side-Chain Introduction
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Fungerin is a 1,4,5-trisubstituted imidazole natural product characterised by a broad spectrum of antifungal activities. We planned to develop flexible strategies to access to such compounds. Imidazoles bearing suitable anchor groups at C-4 and C-5 allow the introduction of various substituted side-chains, generating libraries of fungerin derivatives for biological tests. Starting from commercially available reactants, two N-methyl 4,5-substituted imidazole core units were synthesised. Derivatives of type 1 contained two orthogonally protected C-1 anchors. Selective side-chain introduction was achieved through a sequence of Grignard coupling at C-5 to replace a tosylate and a Horner olefination through an aldehyde attached to C-4. Two target fungerin derivatives were synthesised. Since the organometallic substitution of the C-5-CH2-positioned leaving group proved to suffer from limitations concerning potential competing side-reactions, a type 2 imidazole core was built up. These structures had a halogen centre at C-4 and a hydroxyethyl anchor at C-5. Now, selective side-chain introduction allowed us to use Julia olefination to form the allyl side-chain at C-5 and Heck reactions to introduce the C-4 acryl substituents. Eight derivatives, including fungerin, were synthesised by this latter strategy, without producing any regioisomers. The second approach had the advantage that various side-chains could be coupled at C-4 and C-5 in two final steps. Thus, this strategy represents a versatile way to build up libraries of fungerin derivatives for biological testing.
- Przybyla, Daniel,Nubbemeyer, Udo
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supporting information
p. 695 - 703
(2017/02/05)
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- Synthesis and antiproliferative activity evaluation of imidazole-based indeno[1,2-b]quinoline-9,11-dione derivatives
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A series of new imidazole substituted indeno[1,2-b]quinoline-9,11-dione derivatives were synthesized and evaluated for their antiproliferative effects on HeLa, LS180, MCF-7 and Jurkat human cancer cell lines. Antiproliferative effects were evaluated using MTT assay. Prepared compounds exhibited weak to good antiproliferative activity in evaluated cell lines. Prepared compounds were more potent in Jurkat cell line when compared to LS180, HeLa and MCF-7 cell lines. Compounds 29 (IC16 = 0.7 μM) and 31 (IC16 = 1.7 μM) and 33 (IC16 = 1.7 μM) were found to be the most potent molecules on Jurkat cell lines. Moreover; it was found that some of the tested compounds bearing imidazole-2-yl moiety on the C11-position of dihydropyridine ring exhibited superior antiproliferative activity in comparison to cis-platin especially in Jurkat cell line (compounds 29, 31, and 33). It seemed that the introduction of electron-withdrawing groups on the imidazole ring enhanced the antiproliferative potential of these compounds (compounds 27, 29 and 31). The results of this study proposed that some of the imidazole substituted indeno[1,2-b]quinoline-9,11-dione compounds may act as efficient anticancer agents in vitro, emphasizing their potential role as a source for rational design of potent antiproliferative agents.
- Sarkarzadeh, Hasti,Miri, Ramin,Firuzi, Omidreza,Amini, Mohsen,Razzaghi-Asl, Nima,Edraki, Najmeh,Shafiee, Abbas
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p. 436 - 447
(2013/07/28)
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- Development of a regioselective N-methylation of (benz)imidazoles providing the more sterically hindered isomer
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An efficient and highly regioselective N-methylation of (NH)-(benz)imidazoles furnishing the sterically more hindered, less stable, and usually minor regioisomer has been developed. The methodology involves very mild reaction conditions and tolerates a wide range of functional groups.
- Van Den Berge, Emilie,Robiette, Raphael
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p. 12220 - 12223
(2014/01/06)
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- PH-dependent optical properties of synthetic fluorescent imidazoles
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An imidazole moiety is often found as an integral part of fluorophores in a variety of fluorescent proteins and many such proteins display pH-dependent light emission. In contrast, synthetic fluorescent compounds with incorporated imidazoles are rare and
- Berezin, Mikhail Y.,Kao, Jeff,Achilefu, Samuel
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supporting information; experimental part
p. 3560 - 3566
(2010/02/16)
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- Regiochemistry of N-substitution of some 4(5)-substituted imidazoles under solvent-free conditions
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(Chemical Equation Presented) Imidazole-4(5)-carboxaldehyde and 4(5)-cyanoimidazole were N-benzylated and N-methylated using benzyl chloride and methyl iodide on zinc oxide (ZnO), alumina, and KF/alumina under basic conditions without solvent. Triethylamine (Et3N) or potassium carbonate was added as base in the reactions on ZnO and alumina. Imidazole-4(5)-carboxaldehyde was also benzylated on silica and carbon nanotubes. The effect of bases and solids on the product distribution of 1,4- and 1,5-substituted compounds was investigated. In some cases, the product ratios were different for imidazole-4(5)-carboxaldehyde and 4(5)-cyanoimidazole. In the reactions on KF/alumina the 1,4-product was favored for both compounds. The combination of Et3N and ZnO favored the 1,5-product, however for the nitrile effect was not so pronounced. When N-benzylation and methylation of the aldehyde were performed in the presence of catalytic amount of zinc chloride with Et3N as base, the product distributions were the same as in the reactions on ZnO. Nitrile gave different product ratios on ZnO and in the presence of ZnCl2. In addition, a mixture of N-benzylimidazole and 1,3-dibenzylimidazolium was produced when imidazole was benzylated on KF/alumina. Only the latter product was afforded when two equivalents of benzyl chloride were used.
- Oresmaa, Larisa,Taberman, Helena,Haukka, Matti,Vainiotalo, Pirjo,Aulaskari, Paula
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p. 1445 - 1451
(2008/09/18)
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- (+)-Echinobetaine B: Isolation, structure elucidation, synthesis and preliminary SAR studies on a new nematocidal betaine from a southern Australian marine sponge, Echinodictyum sp
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The principle nematocidal agent present in a southern Australian marine sponge of the genus Echinodictyum has been isolated and identified as the novel betaine (+)-echinobetaine B (6), and the structure assigned by spectroscopic analysis has been confirmed by total synthesis. Preliminary SAR conclusions are drawn from analysis of synthetic intermediates and the known marine metabolites zooanemonin (12) and norzooanemonin (13), and the new sponge metabolite norzooanemonin methyl ester (14). The latter compound is reported for the first time from a selection of Australian sponges, including an Axinyssa sp., a Niphates sp., an Axinella sp. and a Ptilocaulis sp.
- Capon, Robert J.,Vuong, Dat,McNally, Michelle,Peterle, Torsten,Trotter, Nicholas,Lacey, Ernest,Gill, Jennifer H.
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p. 118 - 122
(2007/10/03)
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- Dynamic equilibrium of self-assembled cyclic trimer and tetramer of 1-methyl-5-imidazolylcobalt(III)porhyrin
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Dynamic equilibrium of self-assembled multi-porphyrin systems is of interest in obtaining switchable photoresponsive material, but rarely reported. 1-methyl-5-imidazolylcobalt(III)porphyrin (1Co) synthesized here assembled automatically into cyclic trimer and tetramer by intermolecular imidazolyl-cobalt(III) coordination. The trimer-tetramer equilibrium was dependent on concentration and solvent, as examined by NMR spectrometry. In CDCl3, the tetramer formation was favored at high concentrations, as the ratio of the trimer to the tetramer was 1:2 at 14.8 mM 1Co, and shifted to 1:8 at 74 mM. Further, when the sample was concentrated from a CHCl3 solution to dryness, the ratio increased to 1:24 on dissolution. In CD 3OD, on the other hand, only the trimer was observed in the wide concentration range. Accordingly, both the trimeric and the tetrameric structures could be prepared selectively by the choice of concentration and solvent.
- Tanaka, Akira,Ryuno, Aya,Okada, Saori,Satake, Akiharu,Kobuke, Yoshiaki
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p. 281 - 291
(2007/10/03)
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- Novel benzothienyl or indole derivatives, preparation and use thereof as inhibitors of prenyl transferase proteins
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The invention concerns compounds of general formula (1), wherein, in particular; W represents H, SO2R5. CO(CH2)nR5, (CH2)nR6, CS(CH2)nR5; X represents S or NH; Y represents (CH2)p, CO, (CH2)pCO, CH═CH—CO; Z represents a hetcrocycle, imidazole, benzimidazole, isoxazole, tetrazole, oxadiazole, thiadazole, pyridine, quinazoline, quinoxaline, quinoline, thiophene; R1 represents COOR6, CONR6R7, CO—NH—CH(R6)—COOR7, CH2NR6R7, CH2OR6, (CH2)pR6, CH═CHR6; R2 represents in particular hydrogen, C1-C10 alkyl, a substituted or unsubstituted phenyl; R5 and R6 represents hydrogen, C1—C6 alkyl; R5 represents a substituted or unsubstituted phenyl or naphthyl; R6 and R7, identical or different, represent hydrogen, C1—C15 alkyl, a hetcrocycle. an aryl; n represents 0 to 10; p represents 1 to 6.
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- Synthesis and anti-inflammatory activity of new 1-methyl-4-(4-X-benzenesulfonyl)pyrrolo[2,3-d] imidazole-5-carboxylates
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A series of 1-methyl-4-(4-X-arylsulfonyl)pyrrolo[2,3-d]imidazole-5-carboxylates were synthesized and tested as anti-inflammatory agents. Indomethacin was used as reference drug. Two of the synthesized compounds 7a and 7b had an effect equal to 0.1 of indomethacin. Our result showed that the electron-withdrawing substituents in the para position of the benzensulfonyl moiety increase activity.
- Zarghi,Ebrahimabadi,Hassanzadeh,Heydari,Shafiee
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p. 251 - 254
(2007/10/03)
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- Substituted phenyl farnesyltransferase inhibitors
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Compounds of formula (I) or pharmaceutically acceptable salts thereof, inhibit farnesyltransferase. Methods for making the compounds, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds are disclosed.
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- Synthesis of chiral pilocarpine analogues via a C-8 ketone intermediate.
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The synthesis of a chiral pilocarpine analogue 3 in which the lactone ring is replaced by an oxazolidinone and the bridging methylene group is in the ketone oxidation state has been accomplished. The utility of this compound as a key intermediate for the preparation of more complex structures was demonstrated by its reduction to two alcohol epimers and its reaction with a methylene ylide.
- Holden, Kenneth G,Mattson, Matthew N,Cha, Kyung Hoi,Rapoport, Henry
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p. 5913 - 5918
(2007/10/03)
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- Inhibitors of farnesyl protein transferase
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The present invention comprises benzodiazepine compounds having farnesyl transferase inhibitory activity.
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- Synthesis of marine 2-aminoimidazole metabolites: Hymenidin, oroidin and keramadine
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Through a general synthetic scheme, hymenidin, oroidin and keramadine, all marine 2-aminoimidazole metabolites were prepared. Seven steps from imidazolemethanol provided an improved synthesis of oroidin and the first synthesis of hymenidin and keramadine.
- Daninos-Zeghal, Sophie,Al Mourabit, Ali,Ahond, Alain,Poupat, Christiane,Potier, Pierre
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p. 7605 - 7614
(2007/10/03)
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- Preparation and structure determination of 1-benzyl-, 1-methyl- and 1H-5-[(2-nitro-2-phenyl)ethenyl]imidazoles
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1-R-5-[(2-Nitro-2-phenyl)ethenyl]imidazoles (R = Bn, Me, H) 6a,b,c were synthesized by the Knoevenagel reaction of the corresponding aldehydes 4a,b,c with phenylnitromethane 5. The E-isomers 6a,b,c were precipitated from the reaction mixture as crystalline compounds in 89, 81 and 60% yields, respectively. Traces of the Z-isomers 6a'b',c' were found in the reaction mixtures but could be obtained in a ratio of 4:3 from the E-form with UV irradiation. The E-forms were more stable and the Z-isomers changed again to the E-isomers in several weeks.
- Aulaskari, Paula,Ahlgren, Markku,Rouvinen, Juha,Vainiotalo, Pirjo,Pohjala, Esko,Vepsaelaeinen, Jouko
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p. 1345 - 1354
(2007/10/03)
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- New synthesis of 1,5-disubstituted imidazoles
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A new synthesis of 1-alkylimidazole-5-carbaldehydes starting from [3- (dimethylamino)-2-azaprop-2-enylidene]dimethylammonium chloride and alkyl N- alkylglycinate is described.
- Kirchlechner,Casutt,Heywang,Schwarz
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p. 247 - 248
(2007/10/02)
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- The use of vinyl imidazoles as Diels-Alder dienes
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The first use of a vinylimidazole as a Diels-Alder diene is reported. Semiempirical calculations are used to characterize 1-methyl-5-vinylimidazole as an electron-rich diene
- Walters, Michael A.,Lee, Melissa D.
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p. 8307 - 8310
(2007/10/02)
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- Carboxylate protection for the synthesis of 4,5-disubstituted 1-methylimidazoles
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Using the carboxylate function as a readily removed blocking group for the 2-position, a regioselective synthesis of diverse 4,5-disubstituted 1-methylimidazoles has been developed starting from 1-methyltribromoimidazole, 5.
- Shapiro,Gomez-Lor
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p. 5524 - 5526
(2007/10/02)
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- Imidazolyl-alkenoic acids useful as angiotensin II receptor antagonists
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Angiotensin II receptor antagonists having the formula: STR1 which are useful in regulating hypertension and in the treatment of congestive heart failure, renal failure, and glaucoma, pharmaceutical compositions including these antagonists, and methods of using these compounds to produce angiotensin II receptor antagonism in mammals.
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- SYNTHESIS OF 2,5-DILITHIO-1-METHYLIMIDAZOLE
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C5 to C2 position migrations of 2-trialkylsilyl and thiophenyl groups have been observed upon lithiation at the C5-position of corresponding C2-substituted 1-methylimidazoles.Double bromine-lithium exchange of 1-methyl-2,5-dibromoimidazole (5) affords a facile, quantitative and unequivocal synthesis of 2,5-dilithio-1-methyl-imidazole (4).Reaction of 4 with one equivalent of DMF occurs selectively at the C5 position to give 1-methylimidazole-5-carboxaldehyde.
- Shapiro, Gideon,Marzi, Martin
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p. 3401 - 3404
(2007/10/02)
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- An Effective Chirospecific Synthesis of (+)-Pilocarpine from L-Aspartic Acid
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A short and efficient synthesis of (+)-pilocarpine (1) has been accomplished in 10 steps and 51percent overall yield from L-aspartic acid.The synthesis features a diastereoselective alkylation of a protected aspartic acid diester derivative and a selective hydrolysis of the α-methyl ester to give the corresponding amino acid.Subsequent replacement of the amino group with bromo, esterification, and a modified Reformatsky reaction with 1-methylimidazole-5-carboxaldehyde (8) afforded imidazole-substituted lactone 28.Details concerning this novel lactone synthesis are also described.Finally, hydrogenolysis of the lactone carbon-oxygen bond and selective reduction of the resulting monoester afforded pure (+)-pilocarpine (1).
- Dener, Jeffrey M.,Zhang, Lin-Hua,Rapoport, Henry
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p. 1159 - 1166
(2007/10/02)
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