Category: 18437-58-6

Hameed P., Shahul published the artcileTriaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate, Product Details of C6H8N2, the publication is Nature Communications (2015), 6715, database is CAplus and MEDLINE.

The widespread emergence of Plasmodium falciparum (Pf) strains resistant to frontline agents has fuelled the search for fast-acting agents with novel mechanism of action. Here, we report the discovery and optimization of novel antimalarial compounds, the triaminopyrimidines (TAPs), which emerged from a phenotypic screen against the blood stages of Pf. The clin. candidate (compound 12) is efficacious in a mouse model of Pf malaria with an ED₉₉ <30 mg kg^-1 and displays good in vivo safety margins in guinea pigs and rats. With a predicted half-life of 36 h in humans, a single dose of 260 mg might be sufficient to maintain therapeutic blood concentration for 4-5 days. Whole-genome sequencing of resistant mutants implicates the vacuolar ATP synthase as a genetic determinant of resistance to TAPs. Our studies highlight the potential of TAPs for single-dose treatment of Pf malaria in combination with other agents in clin. development.

Nature Communications published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Product Details of C6H8N2.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Chae, Eunhee published the artcileDiscovery of biological evaluation of pyrazole/imidazole amides as mGlu5 receptor negative allosteric modulators, Application In Synthesis of 18437-58-6, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(7), 2134-2139, database is CAplus and MEDLINE.

Development of SAR in a 5-aryl-3-acylpyridinyl-pyrazoles and 1-aryl-4-acylpyridinyl imidazoles series of mGlu5 receptor neg. allosteric modulators (mGluR5 NAMs) using a functional cell-based assay is described in this Letter. Anal. of the Ligand-lipophilic efficiency (LipE) of compounds provided new insight for the design of potent mGluR5 neg. allosteric modulators with anti-depressant activities.

Bioorganic & Medicinal Chemistry Letters published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Application In Synthesis of 18437-58-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Dabholkar, Vijay V. published the artcileChemistry of novel biphenyl cyclic 3,5-disubstituted 1,2,4-oxadiazole derivatives – their synthesis and microbial evaluation, COA of Formula: C6H8N2, the publication is Heterocyclic Letters (2013), 3(4), 525-531, database is CAplus.

2′-Cyano-4-bromomethyl biphenyl was reacted with hydroxylamine hydrochloride in the presence of sodium carbonate and on further treatment with 2-methyl-4-aminopyridine yielded 3,5-disubstituted 1,2,4-oxadiazole I. 3,5-Di(4-bromomethyl-biphenyl-6′,6”-yl)-1,2,4-oxadiazole was condensed with L-valine Me ester and further cyclized with aliphatic dibromo alkanes Br₂(CH₂)_n to yield the resp. cyclic 3,5-disubstituted 1,2,4-oxadiazoles II [n = 2, 3, 4]. Compounds I and II were evaluated for their antimicrobial activity against Gram pos. and Gram neg. bacteria.

Heterocyclic Letters published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, COA of Formula: C6H8N2.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Cumper, C. W. N. published the artcileThe ultraviolet spectra of aniline, 2-, 3-, and 4-aminopyridines, and of some of their derivatives in n-hexane, 1,4-dioxane, ethanol, and water solutions, Category: pyridine-derivatives, the publication is Journal of the Chemical Society [Section] B: Physical Organic (1968), 649-51, database is CAplus.

The uv spectra of aniline, 2-, 3-, and 4-aminopyridines, and certain of their derivatives have been determined in hexane, 1,4-dioxane, EtOH, and water solutions N-Methylation of the amino group increases its electron-donating ability and the introduction of a Me group or halogen atom into the Ph or pyridyl ring also produces a bathochromic shift. In dioxane and EtOH solutions the amine forms H bonds to the solvent; this also occurs with 4-aminopyridines in water; with the other solutes H bonding by the water predominates.

Journal of the Chemical Society [Section] B: Physical Organic published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Category: pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Cumper, Charles W. N. published the artcileElectric dipole moments of toluidines and some aminopicolines in benzene and 1,4-dioxane solution, Formula: C6H8N2, the publication is Journal of the Chemical Society [Section] B: Physical Organic (1967), 1100-3, database is CAplus.

The elec. dipole moments of the three toluidines and seven aminopicolines were calculated from measurements of the dielec. constants, sp. volumes, and refractive indexes of their solutions in benzene and in 1,4-dioxane at 25.00°. In o-toluidine, 4-amino-3-methylpyridine, and 2-amino-3-methylpyridine there is an interaction between the adjacent substituents but this is somewhat less in 3-amino-4-methylpyridine. Mesomeric moments are present in 2- and 4-aminopyridines and in the former direct interaction occurs between the amino-group and heterocyclic N atom.

Journal of the Chemical Society [Section] B: Physical Organic published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Formula: C6H8N2.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Terashima, Masanao published the artcilePhotoinduced reactions. XXVII. Photochemistry of the phthalimide system. XIV. Photochemical synthesis of a pyridopyrrolo[2,1-a]isoindole system by cyclization of N-methylpyridylphthalimides, HPLC of Formula: 18437-58-6, the publication is Chemical & Pharmaceutical Bulletin (1977), 25(7), 1591-5, database is CAplus.

Photochem. reactions of N-(3-methyl-2-pyridyl)-(I), N-(4-methyl-3-pyridyl)-(II), and N-(3-methyl-4-pyridyl)phthalimide (III) were investigated. Although irradiation of II in an acetone solution gave only the dihydro product, 3-hydroxy-2-(3-methyl-2-pyridyl)phthalimidine, III afforded the expected cyclized product, 10b,11-dihydro-10b-hydroxy-6H-pyrido[4′,3′:4,5]pyrrolo[2,1-a]isoindol-6-one (IV) and dihydro product, 3-hydroxy-2-(4-methyl-3-pyridyl)phthalimidine. Under similar conditions, the cyclized product, 10b,11-dihydro-10b-hydroxy-6H-pyrido[3′,4′:4,5]pyrrolo[2,1-a]isoindol-6-one was obtained from the photolysis of III and none of the reduced product was isolated.

Chemical & Pharmaceutical Bulletin published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C15H14O3, HPLC of Formula: 18437-58-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Ceccarelli, Simona M. published the artcileMetabolite identification via LC-SPE-NMR-MS of the in vitro biooxidation products of a lead mGlu5 allosteric antagonist and impact on the improvement of metabolic stability in the series, Name: 4-Amino-2-picoline, the publication is ChemMedChem (2008), 3(1), 136-144, database is CAplus and MEDLINE.

Detailed information on the metabolic fate of lead compounds can be a powerful tool for an informed approach to the stabilization of metabolically labile compounds in the lead optimization phase. The combination of high performance liquid chromatog. (HPLC) with NMR spectroscopy and mass spectrometry (MS) has been used to give comprehensive structural data on metabolites of novel drugs in development. Recently, increased automation and the embedding of online solid-phase extraction (SPE) into a integrated LC-SPE-NMR-MS system have improved enormously the detection limits of this approach. The new technol. platform allows the anal. of complex mixtures from microsome incubations, combining low material requirements with relatively high throughput. Such characteristics make it possible to thoroughly characterize metabolites of selected compounds at earlier phases along the path to lead identification and clin. candidate selection, thus providing outstanding guidance in the process of eliminating undesired metabolism and detecting active or potentially toxic metabolites. Such an approach was applied at the lead identification stage of a backup program on metabotropic glutamate receptor 5 (mGlu5) allosteric inhibition. The major metabolites of a lead (I) were synthesized and screened, revealing significant in vitro activity and possible involvement in the overall pharmacodynamic behavior of I. The information collected on the metabolism of the highly active compound I was pivotal to the synthesis of related compounds with improved microsomal stability.

ChemMedChem published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Name: 4-Amino-2-picoline.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Urban, R. published the artcileAminomethoxypyridines and corresponding sulfanilamides, Application of 4-Amino-2-picoline, the publication is Helvetica Chimica Acta (1964), 47(2), 363-79, database is CAplus.

A number of 2-, 3-, and 4-sulfanilamidopyridines containing substituents in the pyridine ring, particularly all still unknown monomethoxy derivatives, were prepared for pharmacol. evaluation. To 10 g. Na in 185 mL. absolute MeOH was added 20 g. 2-amino-4-chloropyridine and a little Cu powder, the whole heated 12 h. at 150° in a sealed tube, cooled, diluted with H₂O, filtered, and evaporated, the residue dissolved in H₂O, and the product extracted with Et₂O to give 10.6 g. 2-amino-4-methoxypyridine, m. 115-16° (C₆H₆). 2-Chloro-4-nitropyridine (16 g.), 32 g. Fe powder, and 500 mL. AcOH heated gradually with stirring until the reaction became brisk, when the reaction subsided the mixture heated 1 h. at 100°, cooled, and worked up gave 10.4 g. 4-amino-2-chloropyridine (I), m. 87-9° (C₆H₆-petr. ether). To 5.0 g. Na in 90 mL. absolute MeOH was added 10 g. I and a little Cu powder and the mixture heated 10 h. at 150° in a sealed tube, and worked up to give 5.4 g. 4-amino-2-methoxypyridine, m. 88-9° (C₆H₆-petr. ether, sublimation at 60°/0.1 mm.); Ac derivative m. 96-7° (C₆H₆). 5-Hydroxy-2-phenylazopyridine (II) in 400 mL. tert-BuOH added dropwise during 4 h. to 11 g. CH₂N₂ in 1.7 l. Et₂O at – 15 to -10° with stirring, the solution allowed to reach room temperature and evaporated, the residue dissolved in C₆H₆, the solution worked up, and the partially crystalline product chromatographed on Al₂O₃ (activity II) with C₆H₆ gave 14.8 g. 5-MeO analog (III) of II, m. 72-3° (petr. ether). III (10 g.) in 220 mL. MeOH and 55 mL. 3N HCl hydrogenated over 10 g. 10% Pd-C (the calculated amount H was absorbed in 8 h.) and the solution filtered, concentrated, and worked up gave 4.1 g. 2-amino-5-methoxypyridine, b₁₀ 128-30°, m. 36-8°; Ac derivative (IV) m. 102-3° (C₆H₆-petr. ether); HCl salt m. 145-6° (MeOH-Et₂O). Ac₂O (2.9 mL.) added dropwise to 2.5 g. 2-amino-3-methoxypyridine (V) in 5.0 mL. anhydrous C₅H₅N at below 0° with stirring and worked up gave 2.9 g. Ac derivative of V, m. 102-3° (C₆H₆-petr. ether, C₆H₆ or EtOAc), mixed m.p. (with IV) 70°. 5-Bromonicotinic acid NH₄ salt (270 g.) in 2 1. 25% aqueous NH₃ heated 10 h. at 180° with 100 g. CuO in an autoclave, the filtered solution concentrated and treated with aqueous Cu(OAc)₂, the precipitated Cu salt filtered and dissolved in dilute HCl, the solution treated with H₂S, filtered, and evaporated, the residue dissolved in dilute aqueous NaOH, and the solution neutralized with dilute HCl gave 104 g. 5-aminonicotinic acid (VI), m. 295-6° (decomposition) (H₂O). VI (20 g.) suspended in 400 mL. absolute MeOH saturated with HCl with ice-cooling, and the resulting solution refluxed 0.5 h. while continuously introducing HCl and cooled gave (in 2 crops) 23.8 g. Me 5-hydroxynicotinate-HCl (VII.-HCl), m. 194-6° (decomposition); 73% VII m. 192-3° (H₂O). VII (8.0 g.) in 200 mL. tert-BuOH added dropwise during 6 h. to 3.5 g. CH₂N₂ in 350 mL. Et₂O at – 15 to – 10° with stirring, the solution stirred several hrs. with cooling, allowed to reach room temperature, filtered, and concentrated, the residue dissolved in alc.-HCl, and the solution evaporated gave, after crystallization from MeOH-Et₂O, 9.5 g. Me 5-methoxynicotinate-HCl (VIII.HCl), which in aqueous solution passed through a column of Amberlite IR-45 and the effluent evaporated gave 5.0 g. VIII, m. 61-2° (sublimation at 40°/0.1 mm.), saponification giving 5-methoxynicotinic acid (IX), m. 228-9°. VIII (8.0 g.), 18 mL. 100% N₂H₄.H₂O, and 25 mL. MeOH refluxed 6 h. and cooled gave 6.8 g. hydrazide (X) of IX, m. 157-8° (MeOH). X (19.4 g.) in 125 mL. N HCl treated dropwise with 12 g. KNO₂ in 40 mL. H₂O at 5° with stirring and ice-cooling, the precipitated azide filtered off, washed with a little H₂O, dried over P₂O₅, and refluxed 1 h. in 200 mL. absolute EtOH, and the solution evaporated gave 20.8 g. 5-methoxy-3-pyridinecarbamic acid Me ester, m. 139-41°, which refluxed with 40 g. Ba(OH)₂ in 400 mL. H₂O, the solution cooled, saturated with CO₂, filtered, and worked up gave 8.0 g. 3-amino-5-methoxypyridine, b₁₅ 166-8°, m. 64-5° (C₆H₆); Ac derivative m. 133-4° (C₆H₆, EtOAc); HCl salt m. 205-7° (decomposition). Nicotinic acid-HCl (280 g.) and 500 mL. SOCl₂ refluxed 6 days and then heated 12 h. at 180° in an autoclave, the mixture added to H₂O, heated to boiling, and filtered hot, the filtrate cooled, and the precipitate recrystallized from H₂O with C gave 130 g. mixture of 5-chloro- (XI) and 5,6-dichloronicotinic acid, which refluxed 4 h. with 52 g. red P and 130 g. KI in 800 mL. 57% HI, the solution cooled, diluted with H₂O, filtered, concentrated to small volume, and treated with an appropriate amount aqueous Na₂CO₃ gave 78 g. XI, m. 167-8° (H₂O); Me ester m. 87-8°; hydrazide (XII) m. 176-8°. XII (20 g.) dissolved in 120 mL. N HCl by heating, the solution cooled in ice, treated dropwise with 12 g. KNO₂ in 40 mL. H₂O at 5° with stirring, the precipitated azide filtered off, washed with H₂O, heated 0.5 h. on a water bath in 220 mL. 50% AcOH, cooled, made alk. with aqueous NaOH, and cooled, and the product isolated with Et₂O gave 6.0 g. 3-amino-5-chloropyridine, m. 78-9° (sublimation at 60°/0.1 mm., C₆H₆-petr. ether). The above azide dried over P₂O₅ and refluxed 1 h. with 10 volumes absolute EtOH gave 5-chloro-3-pyridinecarbamic acid Et ester, m. 149-51° (MeOH, sublimation at 70°/0.1 mm.). Na (5 g.) in 60 mL. MeOH and 16.2 g. 4,6-dichloro-2-picoline heated 12 h. at 130-40° in a sealed tube, cooled, and diluted with Et₂O, and the solution filtered and fractionated gave 11.8 g. 4,6-dimethoxy-2-picoline (XIII), b₁₇ 87-8°, n²³_D 1.5076, m. 19-20°. XIII (11.7 g.) in 350 mL. H₂O heated on a water bath, 13 g. finely powd. KMnO₄ added with stirring, when the violet color disappeared 12.5 g. KMnO₄ and 70 mh H₂O added, the mixture heated 2.5 h., cooled a little, the MnO₂ filtered off and washed with hot H₂O, the combined cooled filtrates extracted with Et₂O (6 g. XIII recovered), acidified with HCl, and evaporated, the residue (XIV) extracted (Soxhlet) exhaustively with C₆H₆, and the extract evaporated gave 1.2 g. 4,6-dimethoxypicolinic acid (XV), m. 145-7° (C₆H₆, sublimation at 90°/0.1 mm.). It was preferable not to isolate XV, but to convert XIV directly into the Me ester (XVI) of XV (20% yield). XV (1.2 g.) in 40 mL. absolute MeOH saturated with HCl with ice-cooling, the solution evaporated, the residue extracted with Et₂O, and the extract worked up gave 1.1 g. XVI, m. 108-9° (C₆H₆, sublimation at 60°/0.1 mm.). Na (3.3 g.) in 50 mL. absolute MeOH refluxed 8 h. with 10.0 g. Me 4,6-dichloropicolinate and a little Cu powder, the filtered solution evaporated, and the residue extracted with Et₂O gave 4.8 g. XVI, m. 106-8°. XVI (18 g.) in 100 mL. MeOH treated with 33 mL. 100% N₂H₄.H₂O gave 17 g. hydrazide (XVII) of XV, m. 156-7° (MeOH). H₂O (35 mL.) containing 8.0 g.

Helvetica Chimica Acta published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C15H20O6, Application of 4-Amino-2-picoline.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Malarski, Z. published the artcileDielectric and spectroscopic studies of pentachlorophenol-amine complexes, Recommanded Product: 4-Amino-2-picoline, the publication is Journal of Physical Chemistry (1982), 86(3), 401-6, database is CAplus.

Dipole moments in CCl₄, IR absorption spectra under various conditions, and UV spectra of a number of pentachlorophenol (PCP) complexes with N bases were measured over a broad ΔpK_a range. From the dipole moment measurements an inversion region of ΔpK_a was found for which a 50% proton transfer can be expected. The complexes from this region exhibit certain anomalies in their IR spectra, in particular a broad continuous absorption, a strong temperature effect on the absorption in the far-IR, and particular sensitivity to changes in solvent polarity. The UV spectra revealed proton-transfer equilibrium for a number of complexes, both in solutions and in the solid state.

Journal of Physical Chemistry published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Recommanded Product: 4-Amino-2-picoline.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Profft, E. published the artcileThe preparation of 4-halo-2-methylpyridines, SDS of cas: 18437-58-6, the publication is Journal fuer Praktische Chemie (Leipzig) (1959), 164-72, database is CAplus.

Diazotization of 2-methyl-4-aminopyridine (I) (Boekelheide, C.A. 49, 5256f) with HBr and NaNO₂ at -15°, decomposition of the diazonium salt by bringing slowly to room temperature, addition of aqueous NaOH, and steam distillation gave 72% 2-methyl-4-bromopyridine (II), b. 184°, b₁₄74-6°, n²⁰_D 1.5542. II treated with MeI in C₆H₆ 10 hrs. at room temperature gave the methiodide, m. 214° (decomposition); II picrate m. 186°. II, AcOH, and H₂O₂ gave 55% 2-methyl-4-bromopyridine N-oxide (III), b₁₄ 178°, also prepared from 2-methyl-4-nitropyridine N-oxide and HBr in an autoclave at 160° (Suzuki, C.A. 47, 8074b). III was reduced to II by powd. Fe in AcOH at 100°. II.HCl and Reinecke salt in H₂O gave on standing II reineckate, m. 152-3°. From I, dilute H₂SO₄, and NaNO₂ at -15°, followed by addition of cold aqueous KI, warming to room temperature, addition of NaOH, and extraction with Et₂O was obtained 52% 2-methyl-4-iodopyridine (IV), b₁₄ 84-6°, m. 42°; picrate, yellow, decomposed 209°; reineckate m. 156-7°; methiodide m. 238° (decomposition). IV, AcOH, and H₂O₂ gave 2-methyl-4-iodopyridine N-oxide, b₁₄ 192-4°. I with HBF₄ and NaNO₂ at -15° followed by warming, NaOH addition, and steam distillation gave 43% 2-methyl-4-fluoropyridine (V), b. 128-32°, n²⁰_D 1.4713, more easily soluble in H₂O than the Br and iodo analogs; V picrate m. 152°; reineckate m. 158-9°; methiodide m. 191°; N-oxide (made by both methods shown for III) b₁₄ 136-8°. IV (5 g.) refluxed at 210° with 10 g. powd. Cu gave a solid mass, which ground in a mortar, extracted with 2N HCl, the solution neutralized with NaOH, extracted with Et₂O, and the extract evaporated gave 52% 2,2′-dimethyl-4,4′-bipyridyl, yellowish, m. 83°; picrate, yellow, decompose 237°.

Journal fuer Praktische Chemie (Leipzig) published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, SDS of cas: 18437-58-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem