Category: 31784-71-1

Yang, Wu published the artcileDiscovery of 4-Aryl-7-Hydroxyindoline-Based P2Y₁ Antagonists as Novel Antiplatelet Agents, Recommanded Product: 5-Chlorothiazolo[5,4-b]pyridin-2-amine, the publication is Journal of Medicinal Chemistry (2014), 57(14), 6150-6164, database is CAplus and MEDLINE.

ADP (ADP)-mediated platelet aggregation is signaled through two distinct G protein-coupled receptors (GPCR) on the platelet surface: P2Y₁₂ and P2Y₁. Blocking P2Y₁₂ receptor is a clin. well-validated strategy for antithrombotic therapy. P2Y₁ antagonists have been shown to have the potential to provide equivalent antithrombotic efficacy as P2Y₁₂ inhibitors with reduced bleeding in preclin. animal models. Th have previously reported the discovery of a potent and orally bioavailable P2Y₁ antagonist, I. This paper describes further optimization of I by introducing 4-aryl groups at the hydroxylindoline in two series. In the neutral series, II was identified with excellent potency and desirable pharmacokinetic (PK) profile. It also demonstrated similar antithrombotic efficacy with less bleeding compared with the known P2Y₁₂ antagonist prasugrel in rabbit efficacy/bleeding models. In the basic series, III (BMS-884775) was discovered with an improved PK and liability profile over I. These results support P2Y₁ antagonism as a promising new antiplatelet target.

Journal of Medicinal Chemistry published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C9H10O4, Recommanded Product: 5-Chlorothiazolo[5,4-b]pyridin-2-amine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Qiao, Jennifer X. published the artcile4-Benzothiazole-7-hydroxyindolinyl Diaryl Ureas Are Potent P2Y₁ Antagonists with Favorable Pharmacokinetics: Low Clearance and Small Volume of Distribution, Safety of 5-Chlorothiazolo[5,4-b]pyridin-2-amine, the publication is ChemMedChem (2014), 9(10), 2327-2343, database is CAplus and MEDLINE.

Current antithrombotic discovery efforts target compounds that are highly efficacious in thrombus reduction with less bleeding liability than the standard of care. Preclin. data suggest that P2Y₁ antagonists may have lower bleeding liabilities than P2Y₁₂ antagonists while providing similar antithrombotic efficacy. This article describes the continuous SAR efforts in a series of 7-hydroxyindolinyl diaryl ureas. When dosed orally, 4-trifluoromethyl-7-hydroxy-3,3-dimethylindolinyl analog I was highly efficacious in a model of arterial thrombosis in rats with limited bleeding. The chem. labile CF₃ group in I was then transformed to various groups via a novel one-step synthesis, yielding a series of potent P2Y₁ antagonists. Among them, the 4-benzothiazole-substituted indolines had desirable PK properties in rats, specifically, low clearance and small volume of distribution. In addition, compound II had high i.v. exposure and modest bioavailability, giving it the best overall profile.

ChemMedChem published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C6H4ClN3S, Safety of 5-Chlorothiazolo[5,4-b]pyridin-2-amine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Yamamoto, Yuzuru published the artcilePyridine derivatives containing sulfur. XXXI. Synthesis of pyridothiazoles and pyridoxazoles, Application In Synthesis of 31784-71-1, the publication is Yakugaku Zasshi (1951), 169-72, database is CAplus.

cf. C.A. 46, 112h. The following correction is made: 2-Amino-5-bromo- or 2-amino-5-iodopyridine and KCNS or Cu(CNS)₂ do not form a pyridothiazole ring as reported (cf. C.A. 46, 111c, 112ad). To 2-chloro-5-aminopyridine (I) (3 g.) and 9.1 g. KCNS in 47 mL. 95% AcOH at -5 to -10° is added 1.26 g. Br dropwise, the mixture filtered, and 3 volumes H₂O is added to the filtrate, which is again filtered and neutralized with Na₂CO₃ to give crude 2-amino-5-chloropyrido[3,2-d]thiazole (H) (C.A. numbering). Crude II recrystallized from MeOH gives 1.7 g. II, decompose 243-4°. 2-Hydroxy-5-aminopyridine and KCNS and Br in a similar way give the 5-HO analog (III) of II, m. 248-9°; acetate, needles, m. 286°. By using the 2-alkoxy analogs of I the following 5-alkoxy analogs of II are prepared similarly: MeO, needles or plates, m. 191-1.5°; EtO, needles or plates, m. 201-3°; iso-PrO, light yellow plates, m. 191-3°; BuO, plates, m. 139°; and iso-AmO, light orange needles, m. 126.5°. 2,5-Diaminopyridine and KCNS in 95% AcOH similarly give 2,5-diaminopyrido[3,2-d]-thiazole, m. 214-15°. 2,6-Diaminopyridine (3 g.) and 11 g. Cu(CNS)₂ in AcOH after removal of the AcOH, solution of the residue in hot water, and precipitation with Na₂CO₃ give 0.8 g. 2,5-diaminopyrido[2,3-d]thiazole, yellow prisms, m. 137°. Treating 2 g. 2-amino-3-nitro-5-bromopyridine (IV) with 2.8 g. PCl₅ 4 h. at 120-40°, decomposing the excess PCl₅ with ice water, filtering, and recrystallizing from MeOH give 1.4 g. 2-chloro-3-nitro-5-bromopyridine, yellow needles, m. 67-8°. Heating 1.5 g. IV in 6.5 mL. 85% HCl, adding 6.5 g. SnCl₂ at 100° during a period of 3 h., drying in vacuo, making alk. with NaOH, and taking up with ether gives 0.5 g. 2-hydroxy-3-amino-5-bromopyridine (V), m. 182-4°. Boiling 0.5 g. V in 3 mL. Ac₂O 40 min., filtering off the excess Ac₂O, cooling, making alk. with Na₂CO₃, and taking up with AcOEt gives 0.3 g. 6-bromo-2-methyloxazolo[5,4-b]-pyridine, needles, m. 223-5°.

Yakugaku Zasshi published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C28H29NO4, Application In Synthesis of 31784-71-1.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Okafor, C. O. published the artcileStudies in the heterocyclic series. XVI. Open azaphenothiazines as new central nervous system depressants, Formula: C6H4ClN3S, the publication is Chemical & Pharmaceutical Bulletin (1982), 30(1), 302-18, database is CAplus and MEDLINE.

Acid-catalyzed condensation of 2-amino-3-mercapto-6-methylpyridine and 3-aminopyridine-2[1H]-thiones with 4-chloropyrimidines having free 5-carbon centers gave N-(3-mercapto-2-pyridyl)-6-pyrimidinylamines (I; R = H₂N, MeO, Cl, MeS; R¹ = Me, H₂N, HO, Cl) and N-(2-thioxo-3-pyridyl)-6-pyrimidinylamines (II; R² = Cl, MeO), which were described as open 1,3,9-triaza- and 1,3,6-triazaphenothiazines, resp. A newly developed method of reducing nitro groups was used for preparing the aminopyridine precursors. Eight new and five related compounds including an open 1,9-diazaphenoxazine were tested in mice to display central nervous system depressant activities. The most active compound in the series was II (R = R¹ = H₂N, R² = Cl). Structure-activity correlations were discussed.

Chemical & Pharmaceutical Bulletin published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C6H4ClN3S, Formula: C6H4ClN3S.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Takahashi, Torizo published the artcilePyridine derivatives containing sulfur. XVII. Synthesis of pyridothiazoles and pyrimidazoles, Application In Synthesis of 31784-71-1, the publication is Yakugaku Zasshi (1946), 66(No. 7/8A), 26, database is CAplus.

By the use of Cu(SCN)₂ in glacial AcOH solution the following 2-aminopyrido[2,3-d]thiazoles were obtained: 6-nitro, yellow plates, m. 183°, from 2-amino-5-nitropyridine; 6-bromo, yellow plates, m. 135°, from 5-bromo-2-amino-pyridine; and 5-chloro, pale yellow needles, m. 69-71°, from 2-chloro-5-aminopyridine. BrCH₂COMe with 5-bromo- or 5-nitro-2-aminopyridine gave 6-bromo-2-methyl-imidazo[1,2-a]pyridine HCl salt, colorless, efflorescent rhomboprisms, and the 6-nitro analog (I), bright yellow needles, m. 161°. Reduction of I gave the corresponding amino compound, colorless needles, m. 77° (N-Ac derivative), colorless needles, m. 181°.

Yakugaku Zasshi published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C5H6N2O2, Application In Synthesis of 31784-71-1.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Okafor, Charles O. published the artcileThe first branched benzoxazinophenothiazine ring system and its aza analogs, Application of 5-Chlorothiazolo[5,4-b]pyridin-2-amine, the publication is Tetrahedron (1988), 44(4), 1187-94, database is CAplus.

The synthesis of a branched benzoxazinophenothiazine heterocycle is described. The parent compound benzo[a][1,4]-benzoxazino[3,2-c]phenothiazine (I), was obtained from 2,3-dichloro-1,4-naphthoquinone, 2-aminophenol and 2-(amino)thiophenol. Monoaza-, diaza- and triaza- analogs of this novel heterocycle were also synthesized. The parent compounds, 16-oxa-15-thia-4,5,10-triazabenzo[h]pentaphene and 16-oxa-15-thia-4,5,10,14-tetraazabenzo[h]pentaphene were also synthesized as well as 4-amino-16-oxa-15-thia-4,5,10,12,14-pentaazabenzo[h]pentaphene. They are intensely colored high-melting solids suitable for application as pigments. Their ease of reduction with Na₂S₂O₄ and the ready oxidation of the reduced compounds to the quinoid forms by atm. oxygen suggest their applicability also as vat dyes.

Tetrahedron published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C6H4ClN3S, Application of 5-Chlorothiazolo[5,4-b]pyridin-2-amine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Ueda, Kanichi published the artcilePyridine derivatives containing sulfur. L. Mechanism of cleavage of thiazole ring of 2-aminothiazolo[5,4-b]pyridines by means of aqueous alkali, Application In Synthesis of 31784-71-1, the publication is Pharmaceutical Bulletin (1956), 396-401, database is CAplus and MEDLINE.

cf. C.A. 51, 2741i. Determination of the structures of the previously reported (C.A. 48, 5187h) “Substances I (I), II (II), and III (III),” prepared from 6-Cl (IV) and 6-EtO (V) derivatives of 3-amino-2-mercaptopyridine should help clarify the mechanism of the cleavage of the thiazole ring of the title compounds Comparisons of the infrared and ultraviolet absorption spectra of I with those of the 3-amino (VI) and 3-acetamido (VII) derivatives of 6,2-Cl(MeS)C₅H₂N (VIII) led to the conclusion that I was 6,2,3-Cl(MeS)(H₂NCONH)C₅H₂N. This conclusion was supported by heating 0.6 g. I 6 hrs. on a H₂O bath with 40 cc. Ac₂O and evaporating in vacuo to give 0.08 g. 3-AcNHCONH derivative of VIII, m. 209°, and 0.3 g. VII, m. 166° (from the mother liquor chromatographed in CHCl₃ over Al₂O₃). Support also came from the synthesis of I:1.2 g. IV in 170 cc. AcOH treated slowly with 2.5 g. KNCO in 20 cc. H₂O at 40°, stirred 3 hrs., diluted with much H₂O, and kept overnight yielded 0.82 g. 6,2,3-Cl(HS)(H₂NCONH)C₅H₂N (IX), m. 185-90° (effervescence); this gave I, m. 286-95°, methylated with MeI in alk. solution Also, 0.8 g. VI similarly treated with KNCO yielded 0.8 g. I. Likewise treated with KNCO, 2-MeS (X) and 2-EtS derivatives of 3,6-H₂N(EtO)C₅H₃N gave II, m. 200-36°, and III, m. 160-1°, resp.; their ultraviolet spectra confirmed their structures as 6,2,3-EtO(MeS)(H₂NCONH)C₅H₂N and 6,2,3-EtO(EtS)(H₂NCONH)C₅H₂N, resp. The mechanism of cleavage of the thiazole ring in the 5-Cl (XI) and 5-EtO (XII) derivatives of the title compound was studied. XI (0.7 g.) was refluxed 1 hr. in an oil bath at 120-30° with 6 cc. 10% NaOH while NH₃ evolved, the solution neutralized with AcOH, the resulting precipitate methylated with Me₂SO₄, the ether extract of the product evaporated, and the residue fractionally crystallized to give 0.21 g. VI, m. 56° (from petr. ether-ether), and 0.22 g. I, m. 290° (from MeOH). However, refluxing 7 hrs. instead of 1 hr. gave only VI. IX (0.7 g.) similarly hydrolyzed for 1 hr. and methylated yielded 0.15 g. VI and 0.12 g. I, but after 6 hrs. hydrolysis it gave only VI. XII (1 g.) refluxed 6.5 hrs. with 10 cc. 20% NaOH in the presence of 0.2 g. As₂O₃ while NH₃ evolved, the mixture cooled, filtered, and the filtrate neutralized with AcOH yielded 0.7 g. V, m. 150-70° (characterized by methylation to X and acetylation to 3,6,2-AcNH(EtO)(MeS)C₅H₂N, m. 124°), and after standing overnight, 0.1 g. 6,2,3-EtO(HS)(H₂NCONH)C₅H₂N, m. 195-8° (decomposition)(characterized by methylation with Me₂SO₄ to II). Longer hydrolysis (10 hrs.) of XII gave only V. Confirmation of the production of V from XII was obtained by condensing it (0.5 g.) in 1 cc. H₂O and 5 cc. EtOH containing 0.2 g. NaOH with 0.6 g. BzCH₂Br to yield, after standing overnight at room temperature, the expected 6-ethoxy-2-phenylpyrido[2,3-b]1,4-thiazine(0.42 g.), m. 125° (C.A. 50, 10101g). These results of hydrolysis of IX, XI, and XII led to the conclusion that amino-thiazolopyridines were converted to mercaptopyridines through mercaptopyridylureas as intermediates, which were somewhat resistant to the hydrolysis.

Pharmaceutical Bulletin published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C11H10ClNO, Application In Synthesis of 31784-71-1.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Okafor, Charles O. published the artcileHeterocyclic series. VII. Use of Kaufmann’s reaction as a route to o-aminomercaptopyridines, COA of Formula: C6H4ClN3S, the publication is Journal of Organic Chemistry (1973), 38(26), 4383, database is CAplus.

Kaufmann thiocyanation of 6-substituted 2-amino- and 3-aminopyridines gave 6-substituted-2-amino-3-thiocyanatopyridine (I) and 5-substituted-2-aminothiazolo[5,4-b]pyridine (II), resp. The action of 20% NaOH on II led to 6-substituted 3-aminopyridine-2(1H)-thiones. Heating I in Ac2O gave 5-substituted 2-acetamidothiazolo[4,5-b]pyridine.

Journal of Organic Chemistry published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C6H4ClN3S, COA of Formula: C6H4ClN3S.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Okafor, Charles O. published the artcileHeterocyclic series. II. 3,6-Diazaphenothiazine sulfoxides and other potential antiparasitic and pesticidal agents, Application In Synthesis of 31784-71-1, the publication is Journal of Chemical and Engineering Data (1971), 16(2), 244-6, database is CAplus.

New derivatives of thiazolo[5,4-b]pyridine (I) and 3,6-diazaphenothiazine (II) are described. The yields of products spotlight a definite trend in the role of substituents in the conversion of pyridine derivatives to thiazolo[5,4-b]pyridines. Some derivatives of these compounds were hydrolyzed and converted to nitrothienyl pyridyl sulfides of antibacterial and pesticidal interests by reacting with 2-bromo-3,5-dinitrothiophene. The latter similarly reacts with aminopyridines to yield thienyl aminopyridines. In an attempt to convert 7-methoxy- and 7-chloro-1-nitro-3,6-diazaphenothiazines to their dinitro-3,6-diazaphenothiazine derivatives, only 7-methoxy- and 7-chloro-1-nitro-3,6-diazaphenothiazine sulfoxides, identified by their strong sulfoxide band in the 1035-to 1045-cm-1 region, were obtained.

Journal of Chemical and Engineering Data published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C6H4ClN3S, Application In Synthesis of 31784-71-1.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Jeon, Yoon T. published the artcileIdentification of 1-{2-[4-chloro-1′-(2,2-dimethylpropyl)-7-hydroxy-1,2-dihydrospiro[indole-3,4′-piperidine]-1-yl]phenyl}-3-{5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl}urea, a potent, efficacious and orally bioavailable P2Y₁ antagonist as an antiplatelet agent, Synthetic Route of 31784-71-1, the publication is Bioorganic & Medicinal Chemistry Letters (2014), 24(5), 1294-1298, database is CAplus and MEDLINE.

Spiropiperidine indoline-substituted diaryl ureas had been identified as antagonists of the P2Y₁ receptor. Enhancements in potency were realized through the introduction of a 7-hydroxyl substitution on the spiropiperidinylindoline chemotype. SAR studies were conducted to improve PK and potency, resulting in the identification of compound 3e, a potent, orally bioavailable P2Y₁ antagonist with a suitable PK profile in preclin. species. Compound 3e demonstrated a robust antithrombotic effect in vivo and improved bleeding risk profile compared to the P2Y₁₂ antagonist clopidogrel in rat efficacy/bleeding models.

Bioorganic & Medicinal Chemistry Letters published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C6H4ClN3S, Synthetic Route of 31784-71-1.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica