Category: 92276-38-5

Timmis, G. M.; Epstein, S. S. published the artcile< New antimetabolites of vitamin B12>, Electric Literature of 92276-38-5, the main research area is ANTIMETABOLITES/pharmacology; VITAMIN B 12/antagonists.

Of some 100 compounds tested as inhibitors of vitamin B12 in a microbiol. system using Euglena gracilis var. z as the test organism, the following possessed antimetabolite activity: 4-nitro-6-chlorobenzimidazole, 5,6-dichlorobenzimidazole, 4,5,6-trichlorobenzimidazole, 5-bromo-2,7-diazabenzimidazole, purine, purine riboside, and 5-fluorouracil. Seven others, while inhibitory, were not antimetabolites.

Nature (London, United Kingdom) published new progress about 92276-38-5. 92276-38-5 belongs to class triazoles, and the molecular formula is C5H3BrN4, Electric Literature of 92276-38-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Graboyes, Harold; Day, Allan R. published the artcile< Metabolite analogs. VIII. Syntheses of some imidazopyridines and pyridotriazoles>, Application of C5H3BrN4, the main research area is .

2-Amino-5-bromopyridine (I), m. 136-7° (H2O or C6H6), was prepared by the method of Case (C.A. 41, 1672b). The 3-NO2 derivative (22.8 g.) of I added in portions to 76 g. SnCl2 in 200 cc. concentrated HCl with cooling, and the mixture heated 0.5 hr. on the steam bath, cooled, basified strongly with 40% aqueous NaOH, and filtered yielded 68% 3-NH2 derivative (II) of I, m. 163-4° (H2O), also obtained in 34% yield by reduction with Na2S2O4. II (5 g.) in 25 cc. 98-100% HCO2H refluxed 1 hr. and evaporated to dryness on the steam bath gave 57% 6-bromoimidazo[b]pyridine (III), m. 227-8° (H2O). Similarly were prepared: the 5-Me derivative (IV) of III, m. 204-5°; 7-Me derivative (V) of III, 262-3°; 5,7-di-Me derivative (VI) of III, 279-80° (decomposition); all in 100% yield. VI gave 75% VI.HCl, m. 308-9° (decomposition). II (5.64 g.) in 150 cc. warm H2O containing 5 cc. concentrated H2SO4 cooled below 10°, treated dropwise with stirring with 2.3 g. NaNO2 in 25 cc. H2O, stirred 1 hr., filtered, and the solid recrystallized from a large excess of 2N HCl yielded 83% 6-bromopyrido[2,3-d]-v-triazole (VI), m. 208-9°. The 6-Me derivative (VII) (93.5 g.) of I added with stirring to 400 cc. cold concentrated H2SO4, and the mixture warmed to 55°, treated dropwise at 55-60°, with 32 cc. concentrated HNO3 during 3 hrs., stirred 1 hr., poured into 1 kg. crushed ice, treated with 40% aqueous NaOH, and filtered gave 82% 3-NO2 derivative (VIII) of VII, yellow needles, m. 210-11° (BuOH), converted by the method described for II to 88% 6-Me derivative (IX) of II, m. 136-7° (H2O). IV (3.8 g.) in 150 cc. 1% aqueous NaOH hydrogenated 0.5 hr. at 50 lb. over 2 g. 5% Pd-C and 0.2 g. PtO2, filtered, neutralized with HCl, evaporated, the residue extracted with boiling PhMe, and the extract cooled yielded 36% 5-methylimidazo[b]pyridine (X), m. 218-19°. VI yielded similarly 43% 7-Me derivative of X, m. 217-18°. IX (4.04 g.) in 100 cc. 5% HCl treated dropwise with stirring at 5-10° with 1.73 g. NaNO2 in 25 cc. H2O, stirred 1 hr., and filtered gave 71% 5-Me derivative (XI) of VI, m. 201.5-202° (decomposition). Similarly were prepared from the corresponding diamines the following substituted pyrido[2,3-d]-v-triazoles (substituents, % yield, and m.p. given): 5,6-MeBr (XII), 74, 229-30° (decomposition); 5,7,6-Me2Br (XIII), 71, 190-1°; 5-SO2NH2, 85, 249° (decomposition). 2-Amino-4-methylpyridine (XIV) brominated by the method of Case (loc. cit.) yielded 69% 5-Br derivative (XV), m. 147-7.5° (cyclohexane). XV nitrated in the usual manner, poured onto crushed ice, adjusted with NH4OH to pH 5, and filtered yielded 75% 3-NO2 derivative (XVI) of XV, m. 168-9° (aqueous EtOH). XVI (23.2 g.) added gradually to 76 g. SnCl2 in 200 cc. concentrated HCl and worked up in the usual manner gave 73% 3-N2 analog of XVI, m. 161-2°, also obtained in 42% yield by reduction with Na2S2O4. V debrominated by hydrogenation during 7 hrs. yielded 100% 7-isomer of X, m. 146-7° (H2O or PhMe). 2-Acetamido-4,6-dimethyl-5-bromopyridine prepared by the method of Mariella and Belcher (C.A. 48, 2063a), hydrolyzed, and the resulting 2-amino-4,6-dimethyl-5-bromopyridine (XVII) nitrated, poured onto 1 kg. crushed ice, diluted with 1 l. H2O, and filtered 72% 3-NO2 derivative (XVIII) of XVII, m. 169-70°. XVIII reduced with SnCl2 and HCl 92% 3-H2 analog of XVIII, m. 183-4°. The 5,7-di-Me derivative of VI debrominated in the usual manner by hydrogenation yeilded 33% 5,7-dimethylpyrido[2,3-d]-v-triazole, m. 213-14°. 2-Amino-5-pyridinesulfonic acid (XIX) (54.2 g.) in 200 cc. concentrated H2SO4 treated dropwise at 50-5° with 16.4 cc. fuming HNO3, stirred 1 hr. at 50°, then until cooled to room temperature, poured onto 600 g. crushed ice, and filtered yielded 27-32% 3-;N2 derivative (XX) of XIX, decompose above 300°. XX (21.9 g.) added in small portions to 76 g. SnCl2 in 200 cc. concentrated HCl, heated 0.5 hr. on the steam bath, cooled, filtered, the residue suspended in 150 cc. 0.3N HCl, treated with H2S, filtered, and the hot filtrate cooled yielded 70% 3-NH2 analog (XXI) of XX, m. 308-9° (decomposition) (H2O). XXI (3.78 g.) in 25 cc. HCONH2 heated 2 hrs. with stirring, cooled, diluted with 50 cc. absolute EtOH and excess dry Et2O, filtered, and the residue refluxed 0.5 hr. with 50 cc. 2N HCl and cooled gave 62% imidazo[b]pyridine-6-sulfonic acid; m. above 360° (H2O). XXI (4.04 g.) in 100 cc. 5% HCl treated at 5-10° with 1.73 g. NaNO2 in 25 cc. H2O, stirred 2 hrs., evaporated in vacuo, the residue extracted with EtOH, and the extract diluted with dry Et2O yielded 67% pyrido[2,3-d]-v-triazole-6-sulfonic acid, decompose above 200°. XX (21.9 g.) and 41.9 g. PCl5 heated 3 hrs. at 170-80°, cooled, diluted with 150 cc. dry C6H6, filtered, evaporated, the residual brown oil in 100 cc. di-oxane and 100 cc. H2O cooled, treated dropwise with stirring with 150 cc. concentrated NH4OH, stirred 2 hrs., diluted with 200 cc. H2O, acidified with concentrated HCl, filtered, and the precipitate reprecipitated from dilute aqueous NaOH with concentrated HCl 51% 2-amino-3-nitro-5-pyridinesulfonamide, yellow platelets, m. 287-9° (decomposition), which, reduced in the usual manner gave 61% 3-NH2 analog HCl salt (XXII), m. 231-2° (decomposition) (MeOH). XXII (2.5 g.) refluxed 2 hrs., with 50 cc. HC(OEt)3 and cooled gave 83% imidazo[b]pyridine-6-sulfonamide, m. 289-90° (H2O). 2,6-Diamino-3-nitrosopyridine in H2O hydrogenated over Pt, filtered into concentrated HCl, and evaporated in vacuo 84% 2,3,6-triaminopyridine (XXIII).2HCl, m. 270-1° (H2O); the solution from a similar hydrogenation filtered into concentrated H2SO4 gave the sulfate of XXIII, m. 242-3° (decomposition). XXIII.2HCl (9.85 g.) refluxed 8 hrs. with 75 cc. 98-100% HCO2H, evaporated in vacuo and the oily residue dissolved in 50 cc. 2N H2SO4, refluxed 0.5 hr., and diluted with 50 cc. MeOH and excess Et2O precipitated 72% bis(5-aminoimidazo[b]pyridine)sulfate (XXIV), m. 259-60° (decomposition) (aqueous EtOH). XXIV (7.32 g.) in 150 cc. H2O containing 5 cc. concentrated H2SO4 treated at 5-10° with 2.76 g. NaNO2 in 25 cc. H2O with stirring, stirred 2 hrs., neutralized with 2N NaOH, and filtered gave 37% 5-hydroxyimidazo[b]pyridine, m. 311-13° (decomposition). XXIII sulfate (11.1 g.), 100 cc. H2O, and 50 cc. concentrated HCl treated at 5-10° with 13.8 g. NaNO2 in 75 cc. H2O and processed in the usual manner gave 16% 5-hydroxypyrido[2,3-d]-v-triazole, m. 280-2° (decomposition). 4-Aminopyridine (47 g.) added gradually below 10° to 200 cc. cold concentrated H2SO4, treated dropwise during 0.5 hr. with 27 cc. fuming HNO3, warmed during about 1 hr. to room temperature, treated with stirring with 27 cc. fuming HNO3 at 85-90° during 0.5 hr., stirred until room temperature was reached, poured onto 1 kg. crushed ice, neutralized partially with 40% aqueous NaOH, filtered, the filtrate basified strongly with concentrated NH4OH, filtered, and the combined filter cakes (60-5%) recrystallized from H2O gave 4-amino-3,5-dinitropyridine (XXV), bright yellow plates, m. 168-9°. XXV (36.8 g.) added gradually with stirring to 200 cc. 2 NH4OH previously saturated at 0-5° with H2S, stirred 1 hr., and filtered yielded 47% di-NH2 analog (XXVI) of XXV, ruby-red needles, m. 239° (H2O), converted by the method described for XI in quant. yields to 7-nitroimidazo[c]pyridine (XXVIa), m. 275-6°, and to 7-nitropyrido[3,4-d]-v-triazole (XXVII), m. 266-8° (decomposition). XXVI in EtOH hydrogenated over Pt and filtered into concentrated HCl gave 3,4,5-triaminopyridine (XXVIII).3HCl, m. 275-8° (decomposition). Similarly was prepared XXVIII.2H2SO4, m. 252-3° (decomposition), in 100% yield. XXVIII.2H2SO4 (6.4 g.) in 50 cc. 98-100% HCO2H refluxed 4 hrs., evaporated, the residual oil refluxed 0.5 hr. with 50 cc. 2N H2SO4, and the solution concentrated to half the original volume and diluted with 100 cc. MeOH and excess Et2O gave 7-aminoimidazo[c]pyridine sulfate, m. 240-1° (decomposition), also obtained from XXVIa with SnCl2 and HCl. XXVII (6.25 g.) added gradually to 30 g. SnCl2 in 100 cc. concentrated HCl, heated 0.5 hr. on the steam bath, cooled, filtered, the residue decomposed in 0.3N HCl with H2S, filtered, the filtrate evaporated, and the residue dissolved in 50 cc. 2N NaOH, refluxed 0.5 hr., and partially neutralized with HCl precipitated 38% 7-NH2 analog of XXVII, decompose above 300° (H2O). XX (21.9 g.) and 41.9 g. PCl5 heated to solution at 178-80°, then 2 hrs. longer, cooled, mixed with 150 cc. C6H6, filtered, the filtrate evaporated in vacuo, the residual brown oil added gradually with stirring and cooling, to 152 g. SnCl2 in 300 cc. concentrated HCl, heated 1 hr. on the steam bath, cooled, filtered, a 5-g. portion of the residue (34 g.) treated at 5-10° in 50 cc. 2N HCl with 1.38 g. NaNO2 in 25 cc. H2O with stirring, the mixture stirred 2 hrs., and the red precipitate recrystallized from aqueous HCONMe2 81% 6-mercaptopyrido[2,3-d]-v-triazole, m. 234-5° (decomposition). XI debrominated in the usual manner by hydrogenation yielded 71% 5-methylpyrido[2,3-d]-v-triazole, m. 249-51° (decomposition). XII was converted similarly in quant. yield to 5-methylpyrido[2,3-d]-v-triazole, m. 219-20°.

Journal of the American Chemical Society published new progress about Metabolism, animal. 92276-38-5 belongs to class triazoles, and the molecular formula is C5H3BrN4, Application of C5H3BrN4.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Mayer, Ursula published the artcile< Catalase activity and resistance of Salmonella typhimurium against spiramycin>, Reference of 92276-38-5, the main research area is .

Of 11 strains of S. typhimurium, of known catalase activity and virulence, those rich in catalase were resistant or only moderately sensitive to spiramycin while those with low catalase content were all sensitive.

Zeitschrift fuer Hygiene und Infektionskrankheiten published new progress about Salmonella typhimurium. 92276-38-5 belongs to class triazoles, and the molecular formula is C5H3BrN4, Reference of 92276-38-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Chojnacki, K.; Lindenblatt, D.; Winska, P.; Wielechowska, M.; Toelzer, C.; Niefind, K.; Bretner, M. published the artcile< Synthesis, biological properties and structural study of new halogenated azolo[4,5-b]pyridines as inhibitors of CK2 kinase>, SDS of cas: 92276-38-5, the main research area is halogenated azolopyridine synthesis anticancer CK2 kinase inhibition; ATP-Competitive inhibitors; Casein Kinase CK2; Protein Kinase PIM1; Structural study.

The new halogenated 1H-triazolo[4,5-b]pyridines and 1H-imidazo[4,5-b]pyridines were synthesized as analogs of known CK2 inhibitors: 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) and 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi). Their influence on the activity of recombinant human CK2α, CK2α’ and PIM1 kinases was determined The most active inhibitors were di- and trihalogenated 1H-triazolo[4,5-b]pyridines I-III with IC50 values 2.56, 3.82 and 3.26μM resp. for CK2α. Furthermore, effect on viability of cancer cell lines MCF-7 (human breast adenocarcinoma) and CCRF-CEM (T lymphoblast leukemia) of all final compounds was evaluated. Finally, three crystal structures of complexes of CK2α1-335 with inhibitors I-III were obtained. In addition, new protocol was used to obtain high-resolution crystal structures of CK2α’Cys336Ser in complex with four inhibitors I-IV.

Bioorganic Chemistry published new progress about Crystal structure. 92276-38-5 belongs to class triazoles, and the molecular formula is C5H3BrN4, SDS of cas: 92276-38-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Epstein, Samuel S.; Timmis, Geoffrey M. published the artcile< Simple antimetabolites of vitamin B12>, COA of Formula: C5H3BrN4, the main research area is .

Nearly 300 compounds (mostly benzimidazoles, diazabenzimidazoles, purines, azapurines, pteridines, azapteridines, pyrimidines, nicotinamide and p-aminobenzoic acid derivatives, imidazoles, and alloxans) which bear no structural analogy to vitamin B12 (I), were tried as antimetabolites for the I on Euglena gracilis. For 43 compds, less than 500 γ/ml. produced a 50% inhibition of growth when the I concentration was 10-11 g./ml.; 10 of these compounds produced competitive antagonism as evidenced by the reversibility of their inhibition by higher (10-10-10-9 g./ml.) concentration of I. It is suggested that such simple metabolites as above may act indirectly by interfering with cofactors concerned with the utilization of I.

Journal of Protozoology published new progress about 92276-38-5. 92276-38-5 belongs to class triazoles, and the molecular formula is C5H3BrN4, COA of Formula: C5H3BrN4.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Miles, Dillon H.; Yan, Xuelei; Thomas-Tran, Rhiannon; Fournier, Jeremy; Sharif, Ehesan U.; Drew, Samuel L.; Mata, Guillaume; Lawson, Kenneth V.; Ginn, Elaine; Wong, Kent; Soni, Divyank; Dhanota, Puja; Shaqfeh, Stefan G.; Meleza, Cesar; Chen, Ada; Pham, Amber T.; Park, Timothy; Swinarski, Debbie; Banuelos, Jesus; Schindler, Ulrike; Walters, Matthew J.; Walker, Nigel P.; Zhao, Xiaoning; Young, Stephen W.; Chen, Jie; Jin, Lixia; Leleti, Manmohan Reddy; Powers, Jay P.; Jeffrey, Jenna L. published the artcile< Discovery of Potent and Selective 7-Azaindole Isoindolinone-Based PI3Kγ Inhibitors>, Recommanded Product: 6-Bromo-3H-[1,2,3]triazolo[4,5-b]pyridine, the main research area is cancer immunotherapy immunomodulation PI3K gamma inhibitor azaindole selective.

The successful application of immunotherapy in the treatment of cancer relies on effective engagement of immune cells in the tumor microenvironment. Phosphoinositide 3-kinase γ (PI3Kγ) is highly expressed in tumor-associated macrophages, and its expression levels are associated with tumor immunosuppression and growth. Selective inhibition of PI3Kγ offers a promising strategy in immuno-oncol., which has led to the development of numerous potent PI3Kγ inhibitors with variable selectivity profiles. To facilitate further investigation of the therapeutic potential of PI3Kγ inhibition, we required a potent and PI3Kγ-selective tool compound with sufficient metabolic stability for use in future in vivo studies. Herein, we describe some of our efforts to realize this goal through the systematic study of SARs within a series of 7-azaindole-based PI3Kγ inhibitors. The large volume of data generated from this study helped guide our subsequent lead optimization efforts and will inform further development of PI3Kγ-selective inhibitors for use in immunomodulation.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 92276-38-5 belongs to class triazoles, and the molecular formula is C5H3BrN4, Recommanded Product: 6-Bromo-3H-[1,2,3]triazolo[4,5-b]pyridine.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Bookser, Brett C.; Weinhouse, Michael I.; Burns, Aaron C.; Valiere, Andrew N.; Valdez, Lino J.; Stanczak, Pawel; Na, Jim; Rheingold, Arnold L.; Moore, Curtis E.; Dyck, Brian published the artcile< Solvent-Controlled, Site-Selective N-Alkylation Reactions of Azolo-Fused Ring Heterocycles at N1-, N2-, and N3-Positions, Including Pyrazolo[3,4-d]pyrimidines, Purines, [1,2,3]Triazolo[4,5]pyridines, and Related Deaza-Compounds>, Application In Synthesis of 92276-38-5, the main research area is solvent effect alkylation azolo fused ring heterocycle; pyrazolo pyrimidine purine triazolo pyridine alkylation deaza compound preparation; mol crystal structure triazolopyrimidine pyrazolopyrimidine related compound.

Alkylation of 4-methoxy-1H-pyrazolo[3,4-d]pyrimidine (1b) with iodomethane in THF using NaHMDS as base selectively provided N2-Me product 4-methoxy-2-methyl-2H-pyrazolo[3,4-d]pyrimidine (3b) in an 8/1 ratio over N1-Me product (2b). Interestingly, conducting the reaction in DMSO reversed selectivity to provide a 4/1 ratio of N1/N2 methylated products. Crystal structures of product 3b with N1 and N7 coordinated to sodium indicated a potential role for the latter reinforcing the N2-selectivity. Limits of selectivity were tested with 26 heterocycles which revealed that N7 was a controlling element directing alkylations to favor N2 for pyrazolo- and N3 for imidazo- and triazolo-fused ring heterocycles when conducted in THF. Use of 1H-detected pulsed field gradient-stimulated echo (PFG-STE) NMR defined the mol. weights of ionic reactive complexes. This data and DFT charge distribution calculations suggest close ion pairs (CIPs) or tight ion pairs (TIPs) control alkylation selectivity in THF and solvent-separated ion pairs (SIPs) are the reactive species in DMSO.

Journal of Organic Chemistry published new progress about Alkylation. 92276-38-5 belongs to class triazoles, and the molecular formula is C5H3BrN4, Application In Synthesis of 92276-38-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Yokoi, Masateru published the artcile< Catalase, activity of isoniazid-resistant tubercle bacilli>, Name: 6-Bromo-3H-[1,2,3]triazolo[4,5-b]pyridine, the main research area is .

Isonicotinic acid hydrazide-resistant strains of Mycobacterium tuberculosis var. hominis showed a decreased catalase activity. Addition of heroin and coenzyme A to the homogenate of the resistant strains failed to increase catalase activity. However, porphyrin synthesis from δ-aminolevulinic acid showed little or no difference from that of non-resistant strains. Incubation of the resistant strains with this acid, yeast extract, lysine, glycine, alanine, γ-aminobutyric, aspartic, and glutamic acids, proline, histidine, and phenylalanine markedly increased catalase activity. The potentiating effect of these reagents was inhibited by chloramphenicol, dihydrostreptomycin, and 8-azaguanine. Deficiency of the apoprotein may be responsible for the low catalase activity of resistant strains.

Osaka Daigaku Igaku Zasshi published new progress about Mycobacterium tuberculosis. 92276-38-5 belongs to class triazoles, and the molecular formula is C5H3BrN4, Name: 6-Bromo-3H-[1,2,3]triazolo[4,5-b]pyridine.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Kozlova, Arina; Thabault, Leopold; Liberelle, Maxime; Klaessens, Simon; Prevost, Julien R. C.; Mathieu, Caroline; Pilotte, Luc; Stroobant, Vincent; Van den Eynde, Benoit; Frederick, Raphael published the artcile< Rational Design of Original Fused-Cycle Selective Inhibitors of Tryptophan 2,3-Dioxygenase>, Recommanded Product: 6-Bromo-3H-[1,2,3]triazolo[4,5-b]pyridine, the main research area is tumor rejection TDO2 inhibitor rational design scaffold structural modulations.

Tryptophan 2,3-dioxygenase (TDO2) is a heme-containing enzyme constitutively expressed at high concentrations in the liver and responsible for L-tryptophan (L-Trp) homeostasis. Expression of TDO2 in cancer cells results in the inhibition of immune-mediated tumor rejection due to an enhancement of L-Trp catabolism via the kynurenine pathway. In the study herein, we disclose a new 6-(1H-indol-3-yl)-benzotriazole scaffold of TDO2 inhibitors developed through rational design, starting from existing inhibitors. Rigidification of the initial scaffold led to the synthesis of stable compounds displaying a nanomolar cellular potency and a better understanding of the structural modulations that can be accommodated inside the active site of hTDO2.

Journal of Medicinal Chemistry published new progress about Catabolism (L-Trp). 92276-38-5 belongs to class triazoles, and the molecular formula is C5H3BrN4, Recommanded Product: 6-Bromo-3H-[1,2,3]triazolo[4,5-b]pyridine.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics