Category: 1003-21-0

Butler, Richard Noel published the artcile< Proton nuclear magnetic resonance spectra of aryl and mono- and disubstituted N-methylazoles>, Synthetic Route of 1003-21-0, the main research area is NMR methylazole; pyrazole tetrazole imidazole NMR.

Proton NMR spectra of substituted azoles, e.g., methylpyrrole, imidazoles, pyrazoles, etc., are compared. The influence of the azole ring on the chem. shifts of phenyl protons is discussed. A correlation between N-Me chem. shifts and the structural characteristics of the N-Me group in mono- and disubstituted azoles is noted.

Canadian Journal of Chemistry published new progress about Molecular structure-property relationship. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Synthetic Route of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Amaudrut, Jerome; Argiriadi, Maria A.; Barth, Martine; Breinlinger, Eric C.; Bressac, Didier; Broqua, Pierre; Calderwood, David J.; Chatar, Mohamed; Cusack, Kevin P.; Gauld, Stephen B.; Jacquet, Sebastien; Kamath, Rajesh V.; Kort, Michael E.; Lepais, Valerie; Luccarini, Jean-Michel; Masson, Philippe; Montalbetti, Christian; Mounier, Laurent; Potin, Dominique; Poupardin, Olivia; Rouaud, Sylvie; Spitzer, Luc; Wallace, Craig D. published the artcile< Discovery of novel quinoline sulphonamide derivatives as potent, selective and orally active RORγ inverse agonists>, Category: imidazoles-derivatives, the main research area is RORgamma agonist IL17 nuclear hormone receptor SAR; IL-17; Nuclear hormone receptor; RORγt inverse agonist; SAR; Th17 cells.

A high-throughput screen against Inventiva’s compound library using a Gal4/RORγ-LBD luciferase reporter gene assay led to the discovery of a new series of quinoline sulfonamides as RORγ inhibitors, eventually giving rise to a lead compound having an interesting in vivo profile after oral administration. This lead was evaluated in a target engagement model in mouse, where it reduced IL-17 cytokine production after immune challenge. It also proved to be active in a multiple sclerosis model (EAE) where it reduced the disease score. The synthesis, structure activity relationship (SAR) and biol. activity of these derivatives is described herein.

Bioorganic & Medicinal Chemistry Letters published new progress about Autoimmune disease. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Linciano, Pasquale; Sorbi, Claudia; Comitato, Antonella; Lesniak, Anna; Bujalska-Zadrozny, Magdalena; Pawlowska, Agata; Bielenica, Anna; Orzelska-Gorka, Jolanta; Kedzierska, Ewa; Biala, Grazyna; Ronsisvalle, Simone; Limoncella, Silvia; Casarini, Livio; Cichero, Elena; Fossa, Paola; Satala, Grzegorz; Bojarski, Andrzej J.; Brasili, Livio; Bardoni, Rita; Franchini, Silvia published the artcile< Identification of a Potent and Selective 5-HT1A Receptor Agonist with In Vitro and In Vivo Antinociceptive Activity>, Safety of 5-Bromo-1-methyl-1H-imidazole, the main research area is pain 5HT1A receptor agonist preparation analgesic; 5-HT1AR agonists; Serotonin receptors; behavioral profiling; mice; pain.

Opioids are the gold standard drugs for the treatment of acute and chronic severe pain, although their serious side effects constitute a big limitation. In the search for new and safer drugs, 5-HT1AR agonists are emerging as potential candidates in pain relief therapy. In this work, we evaluated the affinity and activity of enantiomers of the two newly synthesized, potent 5-HT1AR agonists N-[(2,2-diphenyl-1,3-dioxolan-4-yl)methyl]-2-[2-(pyridin-4-yl)phenoxy]ethan-1-ammonium hydrogenoxalate (rac-1) and N-((2,2-diphenyl-1,3-dioxolan-4-yl)methyl)-2-(2-(1-methyl-1H-imidazol-5-yl)phenoxy)ethan-1-ammonium hydrogenoxalate (rac-2) in vitro and in vivo. The role of chirality in the interaction with 5-HT1AR was evaluated by mol. docking. The activity of the rac-1 was tested in mouse models of acute pain (hot plate) and severe tonic nociceptive stimulation (intraplantar formalin test). Rac-1 was active in the formalin test with a reduction in paw licking in both phases at 10 mg/kg, and its effect was abolished by the selective 5-HT1AR antagonist, WAY-100635. The eutomer (S)-1, but not the racemate, was active during the hot plate test at 10 and 20 mg/kg, and this effect was abolished by 30 min treatment with WAY-100635 at 30 min. Similarly to 8-OH-DPAT, (S)-1 evoked a slow outward current and depressed spontaneous glutamatergic transmission in superficial dorsal horn neurons, more effectively than rac-1. The eutomer (S)-1 showed promising developability properties, such as high selectivity over 5-HT subtypes, no interaction with the μ receptors, and low hepato- and cardiotoxicity. Therefore, (S)-1 may represent a potential candidate for the treatment of acute and chronic pain without having the adverse effects that are commonly associated with the classic opioid drugs.

ACS Chemical Neuroscience published new progress about 5-HT1A agonists. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Safety of 5-Bromo-1-methyl-1H-imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Inoue, Hiroo; Hayashi, Shigeki; Imoto, Eiji published the artcile< Electrical conductivity of heterocyclic compounds. Molecular complexes of phenazine>, Application In Synthesis of 1003-21-0, the main research area is .

The composition, color, and m.p. of mol. complexes of the salt type prepared from phenazine hydro-chloride (I) or methosulfate and pyrene (II) or p-hydroquinone (III) varied with drying conditions. Thus, the N content and resistivity increased and the Cl content and m.p. decreased with increased drying times over P2O5 at reduced pressure. The ultraviolet spectra of I-II in a KBr pellet showed an absorption band at ∼620 mμ. The electron spin resonance spectra showed an unpaired electron localized on the N atom of II. The salt-type mol. complexes had a lower resistivity than the non-salt type. Thus, the sp. resistivities of I-III and II-III were 3 × 1011 and 3 × 1015 ohm-cm., res.

Bulletin of the Chemical Society of Japan published new progress about Heterocyclic compounds. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Application In Synthesis of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ohba, Masashi; Mukaihira, Takafumi; Fujii, Tozo published the artcile< Preparatory study for the synthesis of the starfish alkaloid imbricatine. Syntheses of 5-arylthio-3-methyl-L-histidines>, HPLC of Formula: 1003-21-0, the main research area is asym synthesis arylthiomethylhistidine; histidine arylthio asym synthesis; formal synthesis starfish alkaloid imbricatine; ovothiol A C formal synthesis.

Chiral syntheses of 3-methyl-5-(arylthio)-L-histidines I (R = Ph, 1-naphthyl), selected as models for the asteroid alkaloid imbricatine, have been accomplished through a 10-step route starting from 4(5)-bromoimidazole (II). The key steps involved were methylation of II, hydroxymethylation of 4-bromo-1-methyl-1H-imidazole, replacement of the 4-bromo group by an arylthio group, and introduction of a chiral α-amino acid moiety into the chlorides III by the bislactim ether method. The synthesis of 4-(4-methoxybenzyl)thio analog III (R = 4-MeOC6H4CH2), carried out in a similar manner, concluded formal syntheses of ovothiols A and C.

Chemical & Pharmaceutical Bulletin published new progress about Stereoselective synthesis. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, HPLC of Formula: 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Li, Na; Yang, Hong; Liu, Ke; Zhou, Liwei; Huang, Yuting; Cao, Danyan; Li, Yanlian; Sun, Yaoliang; Yu, Aisong; Du, Zhiyan; Yu, Feng; Zhang, Ying; Wang, Bingyang; Geng, Meiyu; Li, Jian; Xiong, Bing; Xu, Shilin; Huang, Xun; Liu, Tongchao published the artcile< Structure-Based Discovery of a Series of NSD2-PWWP1 Inhibitors>, Category: imidazoles-derivatives, the main research area is imidazole preparation SAR antitumor activity inhibitor.

A series of NSD2-PWWP1 inhibitors I (R = 4-cyanophenyl, 4-cyanonaphthalen-1-yl, 8-cyanoquinolin-5-yl, etc.; R1 = H, OMe, F, Cl, CF3; R2 = H, Me, OMe; R3 = aminomethyl, CHO, 4-aminopiperidin-1-yl, etc.), and further structure-based optimization resulted in a potent inhibitor compound I (R = 4-cyanonaphthalen-1-yl; R1 = R2 = Me; R3 = 4-aminopiperidin-1-yl) (II), that has high selectivity toward the NSD2-PWWP1 domain were reported. The detailed biol. evaluation revealed that compound II can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. The current discovery will provide a useful chem. probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition and pave the way to develop potential drugs targeting NSD2 protein.

Journal of Medicinal Chemistry published new progress about Amines Role: PAC (Pharmacological Activity), PKT (Pharmacokinetics), PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Kauffmann, Thomas; Nuernberg, Reinhard; Schulz, Jutta; Stabba, R. published the artcile< Hetarynes. X. Detection of a 5-membered ring aryne (1-methyl-4,5-dehydroimidazole)>, Application In Synthesis of 1003-21-0, the main research area is IMIDAZOLES ARYNE; DEHYDROIMIDAZOLES; ARYNE IMIDAZOLES.

Treating 5-chloro-1-methylimidazole (I) and 5-bromol-1-methylimidazole (II) with Li piperidide/piperidine (III) in boiling ether gave a mixture of 4-piperidino-1-methylimidazole (IV) and 5-piperidino-1-methylimidazole (V). Analogous results using Li pyrrolidide (VI)/pyrrolidine (VII) base pair suggested that IV and V were formed through an elimination-addition mechanism on the title compound (VIII). The mechanism was elucidated by competing reactions of I and II with varying ratios of VII-III base pairs which resulted in IV, V, 5-pyrrolidinyl-1-methylimidazole, and 4-pyrrolidinyl-1-methylimidazole (IX). Anal. of product distribution indicated that the rearranged substitution products IV and IX were prepared through the elimination-addition mechanism, whereas the non-rearranged substitution products resulted from an overlap of the elimination-addition and the normal addition-elimination mechanism, in each case confirming the presence of VIII. Study on competitive reaction of 3-chloropyridine and 4-chloropyridine with the base-pair diethylamine/diisopropylamine confirmed the conclusion that all reactions with II follow the elimination-addition mechanism over the poorly selective intermediate VIII. With chloro compounds such as I, the normal addition-elimination mechanism becomes more important.

Tetrahedron Letters published new progress about 1003-21-0. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Application In Synthesis of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Li, Peng; Herrmann, Wolfgang A.; Kuehn, Fritz E. published the artcile< Unsaturated NHC Complexes Immobilized by the Backbone: Synthesis and Application>, Application In Synthesis of 1003-21-0, the main research area is silica rhodium heterocyclic carbene complex catalyst styrene hydrogenation ethylbenzene.

The synthesis and an exemplary catalytic application of a SBA-15-supported rhodium-N-heterocyclic carbene (NHC) complex is reported. In contrast to the conventional method of immobilization of unsaturated NHC complexes, the rhodium-NHC compound described here is connected to the SBA-15 surface by a linker originating from the backbone of the unsaturated NHC ligand. The unique characteristics of the new immobilization mode enable the supported NHC complexes to maintain two unchanged “”wing-tip”” ligands. This method of immobilization of unsaturated NHC complexes provides a new way to maintain the original configuration of homogeneous NHC complexes in the heterogenized catalytic system. The immobilized rhodium-NHC catalyst is used in a hydrogenation reaction with styrene as substrate.

ChemCatChem published new progress about Catalyst supports. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Application In Synthesis of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Xu, Guozhang; Liu, Zhijie; Wang, Xinkang; Lu, Tianbao; DesJarlais, Renee L.; Thieu, Tho; Zhang, Jing; Devine, Zheng Huang; Du, Fuyong; Li, Qiu; Milligan, Cynthia M.; Shaffer, Paul; Cedervall, Peder E.; Spurlino, John C.; Stratton, Christopher F.; Pietrak, Beth; Szewczuk, Lawrence M.; Wong, Victoria; Steele, Ruth A.; Bruinzeel, Wouter; Chintala, Madhu; Silva, Jose; Gaul, Michael D.; Macielag, Mark J.; Nargund, Ravi published the artcile< Discovery of Potent and Orally Bioavailable Pyridine N-Oxide-Based Factor XIa Inhibitors through Exploiting Nonclassical Interactions>, Formula: C4H5BrN2, the main research area is cyclopropylpyrazolyl pyridine oxide preparation anticoagulation docking SAR.

Herein, activated factor XI (FXIa) inhibitors novel anticoagulants, discovery effort, utilizing nonclassical interactions to improve potency, cellular permeability, and oral bioavailability by enhancing the binding while reducing polar atoms was described. Beginning with literature-inspired pyridine N-oxide-based FXIa inhibitor 1, the imidazole linker was first replaced with a pyrazole moiety to establish a polar C-H···water hydrogen-bonding interaction. Then, structure-based drug design was employed to modify lead mol. I in the P1′ and P2′ regions, with substituents interacting with key residues through various nonclassical interactions. As a result, a potent FXIa inhibitor II (Ki = 0.17 nM) was discovered. This compound demonstrated oral bioavailability in preclin. species (rat 36.4%, dog 80.5%, and monkey 43.0%) and displayed a dose-dependent antithrombotic effect in a rabbit arteriovenous shunt model of thrombosis.

Journal of Medicinal Chemistry published new progress about Anticoagulants, oral. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Formula: C4H5BrN2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Iddon, Brian; Lim, Bee Lan published the artcile< Metal-halogen exchange reactions of mono- and polyhaloimidazoles>, Application In Synthesis of 1003-21-0, the main research area is exchange lithium halogen haloimidazole; haloimidazole lithiation alkylation; imidazole halo lithiation alkylation; ethoxymethylation lithiation haloimidazole; sulfuration lithiation haloimidazole; alkylhaloimidazole; methylthiophenylthioimidazole; phenylthioimidazole.

Treatment of 4(5)-bromoimidazole with 1-2 equiv BuLi in Et2O or THF followed by reaction with Me2SO4 gave 46-63% of a 1:1-3 mixture of 4- and 5-bromo-1-methylimidazole, resp. 5-Iodo- and 2,4,5-tribromo-1-methylimidazole were similarly prepared N-1-alkylation of tribromoimidazole with ClCH2OEt in C6H6 containing Et3N gave 2,4,5-tribromo-1-(ethoxymethyl)imidazole (I). Similar reaction of 2,4,5-triiodoimidazole required NaOMe in dioxane and gave mainly 1-ethoxymethyl-4,5-diiodoimidazole. Treatment of I with BuLi followed by (PhS)2 gave 67% 4,5-dibromo-1-(ethoxymethyl)-2-phenylthioimidazole, which on further treatment with BuLi followed by (MeS)2 gave 63% 4-bromo-1-(ethoxymethyl)-5-methylthio-2-phenylthioimidazole.

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) published new progress about Alkylation. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Application In Synthesis of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem