33016-47-6Relevant academic research and scientific papers
Efficient molar-scale synthesis of 1-methyl-5-acylimidazole triflic acid salts
Chen, Bang-Chi,Skoumbourdis, Amanda P.,Sundeen, Joseph E.,Rovnyak, George C.,Traeger, Sarah C.
, p. 613 - 614 (2000)
A new process for the molar-scale preparation of 1-methyl-5-acylimidazole triflic acid salts was developed. The new process consists of: (i) regioselective 3N-tritylation of 5-acylimidazole to give 3-trityl-5-acylimidazoles, (ii) 1N-methylation of 3-trityl-5-acylimidazoles, and (iii) hydrolysis of the resulting quaternary ammonium salts to afford 1-methyl-5-acylimidazole triflic acid salts. This process is highly efficient, affording 1-methyl-5-acylimidazole triflic acid salts in 86-88% overall yield in three steps without chromatographic separation of products.
Synthesis and Biological Evaluation of Imidazole-Bearing α-Phosphonocarboxylates as Inhibitors of Rab Geranylgeranyl Transferase (RGGT)
Joachimiak, ?ukasz,Marchwicka, Aleksandra,Gendaszewska-Darmach, Edyta,B?a?ewska, Katarzyna M.
, p. 842 - 851 (2018)
Rab geranylgeranyl transferase (RGGT) is an interesting therapeutic target, as it ensures proper functioning of Rab GTPases, a class of enzymes responsible for the regulation of vesicle trafficking. Relying on our previous studies, we synthesized a set of new α-phosphonocarboxylic acids as potential RGGT inhibitors, with emphasis on the elaboration of imidazole-containing analogues. We identified two compounds with activity similar to that of previously reported RGGT inhibitors, showing structural similarity to imidazo[1,2-a]pyridine-containing analogues in terms of their substitution pattern. Interestingly, analogues of the N-series, derived from another phosphonocarboxylate RGGT inhibitor, 2-fluoro-3-(1H-imidazol-1-yl)-2-phosphonopropanoic acid, turned out to be inactive in our model, indicating that an additional substituent localized at positions C2 or C4 of the imidazole ring, may adversely affect the potency against the targeted enzyme.
Functionalization of the Imidazole Backbone by Means of a Tailored and Optimized Oxidative Heck Cross-Coupling
Cirillo, Davide,Angelucci, Francesco,Bj?rsvik, Hans-René
, p. 5079 - 5092 (2020/09/23)
A general and selective Pd-catalyzed cross-coupling of aromatic boronic acids with vinyl-imidazoles is disclosed. Unlike most cross-coupling reactions, this method operates well in absence of bases avoiding the formation of by-products. The reactivity is highly enhanced by the presence of nitrogen-based ligands, in particular bathocuproine. The method involves MnO2 as oxidant for the oxidation Pd (0)→Pd (II), a much weaker oxidant than previously reported in the literature. This allows for the use of reactants that possess a multitude of functional groups. A scope and limitation study involving a series of 24 boronic acids, whereof 18 afforded TMs in yields in the range 41–95%. The disclosed method constitutes the first general method for the oxidative Heck cross-coupling on the imidazole scaffold, which moreover operates with a selection of other heterocycles. (Figure presented.).
PURIFIED CRYSTALLINE DETOMIDINE HYDROCHLORIDE MONOHYDRATE, ANHYDRATE AND FREE BASE WITH LOW AMOUNTS OF ISO-DETOMIDINE AND OTHER IMPURITIES BY RECRYSTALLISATION IN WATER
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Page/Page column 26; 27, (2020/02/14)
The present disclosure relates to crystalline detomidine hydrochloride monohydrate, anhydrous detomidine hydrochloride and detomidine free base (4-[(2,3-dimethylphenyl)methyl]-1H-lmidazole ), purified by recrystallisation in water, with a low amount (total amount of impurities is not more than 0.1% area relative to detomidine based on HPLC, UV detection at 220 nm) of the impurities iso-detomidine (4-[(3,4-dimethylphenyl)methyl]-1H-lmidazole ), iso-impurity A (((RS)-(3,4-dimethylphenyl)(1H-imidazol-4-yl)methanol)), impurity A ((RS)-(2,3-dimethylphenyl)(1H-imidazol-4-yl)methanol), "ketone impurity" (2,3-dimethylphenyl)(1H-imidazol-4-yl) methanone, impurity B ((RS)-(1-benzyl-1H-imidazol-5-yl)(2, 3-dimethyl phenyl) methanol) and impurity C (4-[(2,3-dimethylcyclohexyl)methyl]-1H-imidazole). Also disclosed are processes for recrystallising detomidine hydrochloride monohydrate from commercially available anhydrous detomidine hydrochloride in water, pharmaceutical compositions comprising detomidine hydrochloride in purified form for use as an analgesic in methods of treating human subjects, a process for validating a batch of detomidine hydrochloride drug substance by determining the content of impurities iso-detomidine and iso- impurity A by HPLC, as well as XRPD, DSC and TGA data of crystalline detomidine free base.
Discovery and Lead-Optimization of 4,5-Dihydropyrazoles as Mono-Kinase Selective, Orally Bioavailable and Efficacious Inhibitors of Receptor Interacting Protein 1 (RIP1) Kinase
Harris, Philip A.,Faucher, Nicolas,George, Nicolas,Eidam, Patrick M.,King, Bryan W.,White, Gemma V.,Anderson, Niall A.,Bandyopadhyay, Deepak,Beal, Allison M.,Beneton, Veronique,Berger, Scott B.,Campobasso, Nino,Campos, Sebastien,Capriotti, Carol A.,Cox, Julie A.,Daugan, Alain,Donche, Frederic,Fouchet, Marie-Hélène,Finger, Joshua N.,Geddes, Brad,Gough, Peter J.,Grondin, Pascal,Hoffman, Bonnie L.,Hoffman, Sandra J.,Hutchinson, Susan E.,Jeong, Jae U.,Jigorel, Emilie,Lamoureux, Pauline,Leister, Lara K.,Lich, John D.,Mahajan, Mukesh K.,Meslamani, Jamel,Mosley, Julie E.,Nagilla, Rakesh,Nassau, Pamela M.,Ng, Sze-Ling,Ouellette, Michael T.,Pasikanti, Kishore K.,Potvain, Florent,Reilly, Michael A.,Rivera, Elizabeth J.,Sautet, Stéphane,Schaeffer, Michelle C.,Sehon, Clark A.,Sun, Helen,Thorpe, James H.,Totoritis, Rachel D.,Ward, Paris,Wellaway, Natalie,Wisnoski, David D.,Woolven, James M.,Bertin, John,Marquis, Robert W.
supporting information, p. 5096 - 5110 (2019/05/22)
RIP1 kinase regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including inflammatory and neurological diseases. Currently, RIP1 kinase inhibitors have advanced into early clinical trials for evaluation in inflammatory diseases such as psoriasis, rheumatoid arthritis, and ulcerative colitis and neurological diseases such as amyotrophic lateral sclerosis and Alzheimer's disease. In this paper, we report on the design of potent and highly selective dihydropyrazole (DHP) RIP1 kinase inhibitors starting from a high-throughput screen and the lead-optimization of this series from a lead with minimal rat oral exposure to the identification of dihydropyrazole 77 with good pharmacokinetic profiles in multiple species. Additionally, we identified a potent murine RIP1 kinase inhibitor 76 as a valuable in vivo tool molecule suitable for evaluating the role of RIP1 kinase in chronic models of disease. DHP 76 showed efficacy in mouse models of both multiple sclerosis and human retinitis pigmentosa.
Concise Synthesis of Anserine: Efficient Solvent Tuning in Asymmetric Hydrogenation Reaction
Yamashita, Megumi,Shimizu, Keita,Koizumi, Yasuaki,Wakimoto, Toshiyuki,Hamashima, Yoshitaka,Asakawa, Tomohiro,Inai, Makoto,Kan, Toshiyuki
supporting information, p. 2734 - 2736 (2016/11/30)
A concise synthesis of anserine and related compounds was accomplished by Et-DuPhos-Rh-catalyzed asymmetric hydrogenation of dehydrohistidine derivatives in 2,2,2-trifluoroethanol, which played a key role in improving the yield and selectivity.
Diversity-Oriented Synthesis of β-Lactams and γ-Lactams by Post-Ugi Nucleophilic Cyclization: Lewis Acids as Regioselective Switch
Li, Zhenghua,Sharma, Upendra Kumar,Liu, Zhen,Sharma, Nandini,Harvey, Jeremy N.,Van Der Eycken, Erik V.
supporting information, p. 3957 - 3962 (2015/06/30)
Heterocyclic fused α-methylene β-lactams were successfully synthesized by a post-Ugi InIII-catalyzed intramolecular addition reaction. Switching from InCl3 to AlCl3 led to the regioselective synthesis of α,β-unsaturated γ-lactams. Moreover, replacing terminal alkynes by substituted alkynes in the Ugi adducts resulted in the exclusive formation of γ-lactams with both catalytic systems. A regioselective approach for the synthesis of heterocyclic fused α-methylene β-lactams and α,β-unsaturated γ-lactams by employing a Ugi reaction followed by InIII- or AlIII-catalyzed intramolecular nucleophilic addition is reported.
NITROGENATED HETEROCYCLIC COMPOUND
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Paragraph 0816, (2015/03/28)
The present invention provides a compound having a PDE2A selective inhibitory action, which is useful as an agent for the prophylaxis or treatment of schizophrenia, Alzheimer's disease and the like. The present invention is a compound represented by the formula (1): wherein each symbol is as described in the specification, or a salt thereof.
Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14α-demethylase as anti-Chagas disease agents
Suryadevara, Praveen Kumar,Racherla, Kishore Kumar,Olepu, Srinivas,Norcross, Neil R.,Tatipaka, Hari Babu,Arif, Jennifer A.,Planer, Joseph D.,Lepesheva, Galina I.,Verlinde, Christophe L.M.J.,Buckner, Frederick S.,Gelb, Michael H.
supporting information, p. 6492 - 6499 (2013/11/19)
New dialkylimidazole based sterol 14α-demethylase inhibitors were prepared and tested as potential anti-Trypanosoma cruzi agents. Previous studies had identified compound 2 as the most potent and selective inhibitor against parasite cultures. In addition, animal studies had demonstrated that compound 2 is highly efficacious in the acute model of the disease. However, compound 2 has a high molecular weight and high hydrophobicity, issues addressed here. Systematic modifications were carried out at four positions on the scaffold and several inhibitors were identified which are highly potent (EC50 1 nM) against T. cruzi in culture. The halogenated derivatives 36j, 36k, and 36p, display excellent activity against T. cruzi amastigotes, with reduced molecular weight and lipophilicity, and exhibit suitable physicochemical properties for an oral drug candidate.
PRODUCTION METHOD OF IMIDAZOLE DERIVATIVES
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Page/Page column 35-36, (2013/02/28)
The present invention provides an advantageous production method of an imidazole derivative, which is suitable for industrial production. Compound (VI) is produced by reacting compound (I) with a Grignard reagent or a magnesium reagent, and a lithium reagent, and then reacting the resulting compound with compound (V).
