Month: November 2022

Haider, N. et al. published their research in Science of Synthesis in 2004 | CAS: 105537-97-1

5-Phenylpyridazin-3-amine (cas: 105537-97-1) belongs to pyridazine derivatives. Pyridazines are rare in nature, possibly reflecting the scarcity of naturally occurring hydrazines, common building blocks for the synthesis of these heterocycles. Pyridazine is bioavailable (especially in the CNS) and can reduce toxicity. Pyridazine is a component of several drug molecules, and the pyridazine pharmacophore has contributed to a variety of pharmacologically active compounds.Quality Control of 5-Phenylpyridazin-3-amine

Product class 8: pyridazines was written by Haider, N.;Holzer, W.. And the article was included in Science of Synthesis in 2004.Quality Control of 5-Phenylpyridazin-3-amine The following contents are mentioned in the article:

A review. Methods of preparing pyridazines are reviewed including cyclization, ring transformation, aromatization, and substituent modification. This study involved multiple reactions and reactants, such as 5-Phenylpyridazin-3-amine (cas: 105537-97-1Quality Control of 5-Phenylpyridazin-3-amine).

5-Phenylpyridazin-3-amine (cas: 105537-97-1) belongs to pyridazine derivatives. Pyridazines are rare in nature, possibly reflecting the scarcity of naturally occurring hydrazines, common building blocks for the synthesis of these heterocycles. Pyridazine is bioavailable (especially in the CNS) and can reduce toxicity. Pyridazine is a component of several drug molecules, and the pyridazine pharmacophore has contributed to a variety of pharmacologically active compounds.Quality Control of 5-Phenylpyridazin-3-amine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Sitamze, Jean Marie et al. published their research in Journal of Organic Chemistry in 1992 | CAS: 105537-97-1

5-Phenylpyridazin-3-amine (cas: 105537-97-1) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. Pyridazine can act as a hydrogen bond acceptor to improve the physicochemical properties of drug molecules by increasing their water solubility, and has a high affinity for complexing with targets due to its dipole moment.Category: pyridazine

A general and convenient synthesis of 3-aminopyridazines was written by Sitamze, Jean Marie;Schmitt, Martine;Wermuth, Camille Georges. And the article was included in Journal of Organic Chemistry in 1992.Category: pyridazine The following contents are mentioned in the article:

Hydrogenolysis of 3-hydrazinopyridazines I (R = H, Ph, 4-MeOC6H4; R1 = H, Me, Pr, Ph; R2 = H, Me, Et, CHMe2, CH2Ph, CH2CH2Ph; R3 = NHNH2) by means of nickel-aluminum alloy in alk. medium yield the corresponding 3-aminopyridazines I (R3 = NH2) in approx. 80 % yield. This study involved multiple reactions and reactants, such as 5-Phenylpyridazin-3-amine (cas: 105537-97-1Category: pyridazine).

5-Phenylpyridazin-3-amine (cas: 105537-97-1) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. Pyridazine can act as a hydrogen bond acceptor to improve the physicochemical properties of drug molecules by increasing their water solubility, and has a high affinity for complexing with targets due to its dipole moment.Category: pyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Chen, Zhao et al. published their research in Journal of Medicinal Chemistry in 2019 | CAS: 1439400-46-0

N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide (cas: 1439400-46-0) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. The activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.Application In Synthesis of N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide

Novel 1,3,4-Selenadiazole-Containing Kidney-Type Glutaminase Inhibitors Showed Improved Cellular Uptake and Antitumor Activity was written by Chen, Zhao;Li, Di;Xu, Ning;Fang, Jinzhang;Yu, Yan;Hou, Wei;Ruan, Haoqiang;Zhu, Panpan;Ma, Renchao;Lu, Shiying;Cao, Danhui;Wu, Rui;Ni, Mowei;Zhang, Wei;Su, Weike;Ruan, Benfang Helen. And the article was included in Journal of Medicinal Chemistry in 2019.Application In Synthesis of N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide The following contents are mentioned in the article:

Kidney-type glutaminase [KGA/isoenzyme glutaminase C (GAC)] is becoming an important tumor metabolism target in cancer chemotherapy. Its allosteric inhibitor, CB839, showed early promise in cancer therapeutics but limited efficacy in in vivo cancer models. To improve the in vivo activity, the authors explored a bioisostere replacement of the sulfur atom in bis-2-(5-phenylacetamido-1,2,4-thiadiazol)ethyl sulfide and CB839 analogs with selenium using a novel synthesis of the selenadiazole moiety from carboxylic acids or nitriles. The resulting selenadiazole compounds showed enhanced KGA inhibition, more potent induction of reactive oxygen species, improved inhibition of cancer cells, and higher cellular and tumor accumulation than the corresponding sulfur-containing mols. However, both CB839 and its selenium analogs show incomplete inhibition of the tested cancer cells, and a partial reduction in tumor size was observed in both the glutamine-dependent HCT116 and aggressive H22 liver cancer xenograft models. Despite this, tumor tissue damage and prolonged survival were observed in animals treated with the selenium analog of CB839. This study involved multiple reactions and reactants, such as N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide (cas: 1439400-46-0Application In Synthesis of N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide).

N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide (cas: 1439400-46-0) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. The activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.Application In Synthesis of N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Wermuth, Camille Georges et al. published their research in Journal of Medicinal Chemistry in 1987 | CAS: 105537-97-1

5-Phenylpyridazin-3-amine (cas: 105537-97-1) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. Specifically, the pyridazine moiety is an important structural feature of various pharmacologically important compounds with activities like antimicrobial, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, cardiotonic, vasodilator, antiarrhythmic, and hypocholesterolaemic.Quality Control of 5-Phenylpyridazin-3-amine

Synthesis and structure-activity relationships of a series of aminopyridazine derivatives of γ-aminobutyric acid acting as selective GABA-A antagonists was written by Wermuth, Camille Georges;Bourguignon, Jean Jacques;Schlewer, Gilbert;Gies, Jean Pierre;Schoenfelder, Angele;Melikian, Anita;Bouchet, Marie Jeanne;Chantreux, Dominique;Molimard, Jean Charles. And the article was included in Journal of Medicinal Chemistry in 1987.Quality Control of 5-Phenylpyridazin-3-amine The following contents are mentioned in the article:

Thirty-eight title compounds, e.g., I, were prepared by attaching various pyridazinic structures to GABA or GABA-like side chains. Thus, aminopyridazine II was treated with BrCH2CH2CO2Et, followed by K2CO3 and then HCl-AcOH to give I. Most of the compounds displaced [3H]GABA from rat brain membranes. All the active compounds antagonized the GABA-elicited enhancement of [3H]diazepam binding, strongly suggesting that all these compounds are GABA-A receptor antagonists. None of the compounds that displaced [3H]GABA from rat brain membranes interacted with other GABA recognition sites (GABA-B receptor, GABA uptake binding site, glutamate decarboxylase, GABA-transaminase). They did not interact with the Cl– ionophore associated with the GABA-A receptor and did not interact with the benzodiazepine, strychnine, and glutamate binding sites. Thus, these compounds appear to be specific GABA-A receptor antagonists. In terms of structure-activity, it is concluded that a GABA moiety bearing a pos. charge is necessary for optimal GABA-A receptor recognition. Addnl. binding sites are tolerated only if they are part of a charge-delocalized amidinic or guanidinic system. If this delocalization is achieved by linking a butyric acid moiety to the N(2) nitrogen of a 3-aminopyridazine, GABA-antagonistic character is produced. The highest potency (≃250 times bicuculline) was observed when an aromatic π system, bearing electron-donating substituents, was present on the 6-position of the pyridazine ring. This study involved multiple reactions and reactants, such as 5-Phenylpyridazin-3-amine (cas: 105537-97-1Quality Control of 5-Phenylpyridazin-3-amine).

5-Phenylpyridazin-3-amine (cas: 105537-97-1) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. Specifically, the pyridazine moiety is an important structural feature of various pharmacologically important compounds with activities like antimicrobial, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, cardiotonic, vasodilator, antiarrhythmic, and hypocholesterolaemic.Quality Control of 5-Phenylpyridazin-3-amine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Nakagome, Takenari’s team published research in Yakugaku Zasshi in 82 | CAS: 89532-79-6

Yakugaku Zasshi published new progress about 89532-79-6. 89532-79-6 belongs to pyridazine, auxiliary class Pyridazine,Alcohol,Ether, name is (6-Methoxypyridazin-3-yl)methanol, and the molecular formula is C6H8N2O2, Computed Properties of 89532-79-6.

Nakagome, Takenari published the artcileSyntheses of pyridazine derivatives. III. Structure of 3-substituted 6-methylpyridazine N-oxides., Computed Properties of 89532-79-6, the publication is Yakugaku Zasshi (1962), 249-53, database is CAplus and MEDLINE.

3-Methylpyridazine (I) (9.7 g.) in 140 ml. AcOH, 14 ml. H2O, and 14 ml. 30% H2O2 heated 8 hrs. at 80°, the AcOH removed, the residue in H2O made alk. with Na2CO3, and the product extracted with CHCl3 gave 9.3 g. liquid, b0.5 110-13°; this in 1:1 C6H6CHCl3 chromatographed through Al2O3 and the first eluate concentrated gave 3.9 g. I 2-oxide (II) m. 85-6° and the last effluent gave 4 g. I 1-oxide (III), m. 68-9°. Catalytic reduction of 0.1 g. II in 30 ml. MeOH with 0.5 g. 5% Pd-C absorbed 22 ml. H and gave 0.2 g. I (picrate m. 148-9°). Similarly, III yielded I. 3-Methyl-6-chloropyridazine (IV) (30 g.) and 420 ml. CHCl3 containing 30 g. BzO2H kept 3 days at room temperature, the solution concentrated and the residue washed with Et2O gave 29 g. 3-chloro-6-methylpyridazine 1-oxide (V), m. 160-1°. Catalytic reduction of 2 g. V in 2 ml. 28% NH4OH and 20 ml. H2O at room temperature absorbed 1 mole H in 50 min. and gave 1.2 g. II, m. 85-6°; picrate m. 103-4°. 3-Methoxy-O-methylpyridazine (VI) (44 g.), 350 ml. AcOH, and 50 ml. 30% H2O2 kept 1 week at 40-5°, the AcOH removed, the residue in H2O made alk. with Na2CO3 and the product extracted with CHCl3 gave 41 g. VI 1-oxide (Via) m. 98-9° (AcOEt). VIa (0.7 g.) in 20 ml. 5% NaOH heated 1 hr., the solution acidified with HCl, evaporated to dryness, and the product extracted with EtOH gave 0.3 g. 6-methyl-3-pyridazinol 1-oxide, m. 201-2°. VIa (9 g.) and 60 ml. Ac2O heated 2 hrs. at 100°, the Ac2O removed, the residue made alk. with Na2CO3 and the product extracted with CHCl3 gave 9 g. 6-methoxy-3-pyridazinemethyl acetate (VII), m. 59-61°. VI (8 g.) and 60 ml. 10% HCl refluxed 30 min. and the product treated as usual gave 4 g. 6-methoxy-3-pyridazinemethanol (VIII), m. 55-6.5°. VIII (1.6 g.), 0.8 g. SeO2 and 25 ml. dioxane stirred 4 hrs. at 70-5°, the solution concentrated, and the residue treated with NH2CONHNH2 gave 6-methoxy-3-pyridazinealdehyde semicarbazone, m. 248° (decomposition).

Yakugaku Zasshi published new progress about 89532-79-6. 89532-79-6 belongs to pyridazine, auxiliary class Pyridazine,Alcohol,Ether, name is (6-Methoxypyridazin-3-yl)methanol, and the molecular formula is C6H8N2O2, Computed Properties of 89532-79-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

 

Nakagome, Takenari’s team published research in Yakugaku Zasshi in 82 | CAS: 89532-79-6

Yakugaku Zasshi published new progress about 89532-79-6. 89532-79-6 belongs to pyridazine, auxiliary class Pyridazine,Alcohol,Ether, name is (6-Methoxypyridazin-3-yl)methanol, and the molecular formula is C6H8N2O2, Recommanded Product: (6-Methoxypyridazin-3-yl)methanol.

Nakagome, Takenari published the artcileSyntheses of pyridazine derivatives. II. 3-Methoxy-6-pyridazinol 1-oxide, Recommanded Product: (6-Methoxypyridazin-3-yl)methanol, the publication is Yakugaku Zasshi (1962), 244-8, database is CAplus and MEDLINE.

cf. CA 55, 21134c. 3-Chloro-6-methoxypyridazine (I) (7.3 g.) in 50 mL. AcOH treated with 24 mL. 30% H2O2, kept 5 h. at 70°, the solution concentrated in vacuo, the residue made alk. with Na2CO3 and the product extracted with CHCl3 gave 1.4 g. 3-methoxy-6-chloropyridazine 1-oxide (II), m. 157-8° (C6H6). The mother liquor from washing II with 2N NaOH gave 0.4 g. 3-methoxy-6(1H)-pyridazinone (III), plates, m. 162-3° (AcOEt). A solution of 18 g. BzO2H in 337 mL. CHCI3 treated with 14.5 g. I, kept 3 days at room temperature and the product treated as above gave 14.3 g. II, m. 157-8°. I (3 g.), 20 mL. AcOH, and 3.4 g. AcOK in a sealed tube heated 1.5 h. at 140-50° and the AcOH removed gave 3.6 g. III, m. 162-3°. III (4 g.) and 30 mL. POCl3 heated 30 min. at 100° the product poured into ice-H2O and extracted with Et2O gave 1.5 g. 3,6-dichloropyridazine (IV), m. 68-9°. Catalytic reduction of 0.5 g. II in 3 mL. 28% NH4OH and 30 mL. MeOH with 0.05 g. 10% Pd-C absorbed 77 mL. H and gave 0.35 g. 3-methoxypyridazine 1-oxide (V), m. 79-80°. Catalytic reduction of 0.5 g. II in 3 mL. 28% NH4OH and 30 mL. MeOH with Pd-C (from 10 mL. 1% PdCl2 and 0.5 g. C) absorbed 160 mL. H in 15 min. and gave 0.5 g. 3-methoxypyridazine; picrate m. 111°. II (3.2 g.), 12 mL. AcOH, and 1.64 g. AcONa in a sealed tube heated 1 h. at 150-60° and the product concentrated gave 1.64 g. 1-hydroxy-3-methoxy-5(1H)-pyridazinone (VI), m. 178-9°. A solution of 29.5 g. 3,6-dimethoxypyridazine I-oxide in 400 mL. 2N HCl heated 20 min. at 80-90° and the solution concentrated gave 25.3 g. VI, m. 178-9°. VI (2.8 g.), 2.54 g. BzCl, 0.46 g. Na and 30 mL. MeOH in a sealed tube heated 2 h. at 100° the solution concentrated and the residue extracted with CHCl3 gave 3.1 g. 1-benzoyloxy-3-methoxy-6(1H)pyridazinone (VII), m. 86.5-87°. VI (2 g.), 2.5 g. MeI, Ag2O (from 3 g. AgNO3), and 20 mL. MeOH in a sealed tube heated 2 h. at 100° and the solution concentrated gave 100% 1,3-dimethoxy-6(1H)-pyridazinone, m. 66-7°. A solution of 250 mL. dry C6H6, 20.6 g. PhCH2OH, and 4.4 g. Na, refluxed 1 h., after disappearance of Na, with 20 g. 3-chloropyridazine, and the product distilled gave 18 g. 3-benzyloxypyridazine (VIII), b0.15 120-5°, m. 49-50°. VIII (6 g) and 84.5 mL. CHCl3 containing 4.46 g. BzO2H kept 2 days at room temperature gave 100% VIII I-oxide (VIIIa), m. 118-18.5°. Catalytic reduction of 0.5 g. VIIIa in 30 mL. MeOH with 0.05 g. 10% Pd-C absorbed 64 mL. H in 5 min.and gave 3-pyridazinol 1-oxide, m. 201-2° (decomposition). Catalytic reduction of 0.5 g. VIIIa in 30 mL. MeOH with 0.2 g. 10% Pd-C absorbed 128 mL. H in 15 min. and gave 0.25 g. 3(2H)-pyridazinone-H2O, m. 74°. IV (21 g.) and 240 mL. CHCl3 containing 18.7 g. BzO2H kept 2 days at room temperature and the product concentrated gave 10.4 g. IV 1-oxide, m. 110-12°. IV 1-oxide (1 g.) and 0.33 g. 22.6% MeONa-MeOH heated several min. on a water bath, the solution acidified with AcOH and the product extracted with CHCl3 gave 0.6 g. II, m. 155-7°.

Yakugaku Zasshi published new progress about 89532-79-6. 89532-79-6 belongs to pyridazine, auxiliary class Pyridazine,Alcohol,Ether, name is (6-Methoxypyridazin-3-yl)methanol, and the molecular formula is C6H8N2O2, Recommanded Product: (6-Methoxypyridazin-3-yl)methanol.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

 

Heinisch, G.’s team published research in Monatsh. Chem. in 104 | CAS: 50901-42-3

Monatsh. Chem. published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C5H4N2O, Category: pyridazine.

Heinisch, G. published the artcileSynthesis and reactions of pyridazine derivatives. II. 4-Hydroxymethylpyridazine, Category: pyridazine, the publication is Monatsh. Chem. (1973), 104(5), 1354-9, database is CAplus.

4-(Hydroxymethyl)pyridazine (I) was obtained together with Et 2,5-dihydropyridazine-4-carboxylate by LiAlH4 or NaBH4 reduction of Et 4-pyridazinecarboxylate, the ratios depending on the reaction conditions. Reduction of 4-pyridazinecarboxaldehyde or 4-acetylpyridazine with NaBH4 gave I or 4-(1-hydroxyethyl)pyridazine, resp., in quant. yield. Treatment of I with SOCl2 gave 4-(chloromethyl)pyridazine.

Monatsh. Chem. published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C5H4N2O, Category: pyridazine.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

 

Rak, Gregory D.’s team published research in Journal of Applied Toxicology in 40 | CAS: 2001559-19-7

Journal of Applied Toxicology published new progress about 2001559-19-7. 2001559-19-7 belongs to pyridazine, auxiliary class TGF-beta/Smad,TGF-beta Receptor, name is 6-(4-(3-Chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile, and the molecular formula is C18H12ClFN6O, COA of Formula: C18H12ClFN6O.

Rak, Gregory D. published the artcileIntermittent dosing of the transforming growth factor beta receptor 1 inhibitor, BMS-986260, mitigates class-based cardiovascular toxicity in dogs but not rats, COA of Formula: C18H12ClFN6O, the publication is Journal of Applied Toxicology (2020), 40(7), 931-946, database is CAplus and MEDLINE.

Small-mol. inhibitors of transforming growth factor beta receptor 1 (TGFβRI) have a history of significant class-based toxicities (eg, cardiac valvulopathy) in preclin. species that have limited their development as new medicines. Nevertheless, some TGFβRI inhibitors have entered into clin. trials using intermittent-dosing schedules and exposure limits in an attempt to avoid these toxicities. This report describes the toxicity profile of the small-mol. TGFβRI inhibitor, BMS-986260, in rats and dogs. Daily oral dosing for 10 days resulted in valvulopathy and/or aortic pathol. at systemic exposures that would have been targeted clin., preventing further development with this dosing schedule. These toxicities were not observed in either species in 1-mo studies using the same doses on an intermittent-dosing schedule of 3 days on and 4 days off (QDx3 once weekly). Subsequently, 3-mo studies were conducted (QDx3 once weekly), and while there were no cardiovascular findings in dogs, valvulopathy and mortality occurred early in rats. The only difference compared to the 1-mo study was that the rats in the 3-mo study were 2 wk younger at the start of dosing. Therefore, a follow-up 1-mo study was conducted to evaluate whether the age of rats influences sensitivity to target-mediated toxicity. Using the same dosing schedule and similar doses as in the 3-mo study, there was no difference in the toxicity of BMS-986260 in young (8 wk) or adult (8 mo) rats. In summary, an intermittent-dosing schedule mitigated target-based cardiovascular toxicity in dogs but did not prevent valvulopathy in rats, and thus the development of BMS-986260 was terminated.

Journal of Applied Toxicology published new progress about 2001559-19-7. 2001559-19-7 belongs to pyridazine, auxiliary class TGF-beta/Smad,TGF-beta Receptor, name is 6-(4-(3-Chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile, and the molecular formula is C18H12ClFN6O, COA of Formula: C18H12ClFN6O.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

 

Sadler, Scott A.’s team published research in Organic & Biomolecular Chemistry in 12 | CAS: 1350543-95-1

Organic & Biomolecular Chemistry published new progress about 1350543-95-1. 1350543-95-1 belongs to pyridazine, auxiliary class Pyridazine,Boronic acid and ester,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 3-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridazine, and the molecular formula is C11H17BN2O2, Application In Synthesis of 1350543-95-1.

Sadler, Scott A. published the artcileIridium-catalyzed C-H borylation of pyridines, Application In Synthesis of 1350543-95-1, the publication is Organic & Biomolecular Chemistry (2014), 12(37), 7318-7327, database is CAplus and MEDLINE.

The iridium-catalyzed C-H borylation is a valuable and attractive method for the preparation of aryl and heteroaryl boronates. However, application of this methodol. for the preparation of pyridyl and related azinyl boronates can be challenged by low reactivity and propensity for rapid protodeborylation, particularly for a boronate ester ortho to the azinyl nitrogen. Competition experiments have revealed that the low reactivity is due to inhibition of the active catalyst through coordination of the azinyl nitrogen lone pair at the vacant site on the iridium. This effect can be overcome through the incorporation of a substituent at C-2. Moreover, when this is sufficiently electron-withdrawing protodeborylation is sufficiently slowed to permit isolation and purification of the C-6 boronate ester. Following functionalization, reduction of the directing C-2 substituent provides the product arising from formal ortho borylation of an unhindered pyridine ring.

Organic & Biomolecular Chemistry published new progress about 1350543-95-1. 1350543-95-1 belongs to pyridazine, auxiliary class Pyridazine,Boronic acid and ester,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 3-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridazine, and the molecular formula is C11H17BN2O2, Application In Synthesis of 1350543-95-1.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

 

Parrish, Karen E.’s team published research in Biopharmaceutics & Drug Disposition in 42 | CAS: 2001559-19-7

Biopharmaceutics & Drug Disposition published new progress about 2001559-19-7. 2001559-19-7 belongs to pyridazine, auxiliary class TGF-beta/Smad,TGF-beta Receptor, name is 6-(4-(3-Chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile, and the molecular formula is C18H12ClFN6O, HPLC of Formula: 2001559-19-7.

Parrish, Karen E. published the artcilePharmacodynamics-based approach for efficacious human dose projection of BMS-986260, a small molecule transforming growth factor beta receptor 1 inhibitor, HPLC of Formula: 2001559-19-7, the publication is Biopharmaceutics & Drug Disposition (2021), 42(4), 137-149, database is CAplus and MEDLINE.

For decades, tumor biol. implicated TGF-β as an attractive therapeutic target due to its immunosuppressive effects. Toward this end, multiple pharmaceutical companies developed a number of drug modalities that specifically target the TGF-β pathway. BMS-986260 is a small mol., selective TGF-βR1 kinase inhibitor that was under preclin. development for oncol. In vivo studies across mouse, rat, dog, and monkey and cryopreserved hepatocytes predicted human pharmacokinetics (PK) and distribution of BMS-986260. Efficacy studies of BMS-986260 were undertaken in the MC38 murine colon cancer model, and target engagement, as measured by phosphorylation of SMAD2/3, was assessed in whole blood to predict the clin. efficacious dose. The human clearance is predicted to be low, 4.25 mL/min/kg. BMS-986260 provided a durable and robust antitumor response at 3.75 mg/kg daily and 1.88 mg/kg twice-daily dosing regimens. Phosphorylation of SMAD2/3 was 3.5-fold less potent in human monocytes than other preclin. species. Taken together, the projected clin. efficacious dose was 600 mg QD or 210 mg BID for 3 days followed by a 4-day drug holiday. Mechanism-based cardiovascular findings in the rat ultimately led to the termination of BMS-986260. This study describes the preclin. PK characterization and pharmacodynamics-based efficacious dose projection of a novel small mol. TGF-βR1 inhibitor.

Biopharmaceutics & Drug Disposition published new progress about 2001559-19-7. 2001559-19-7 belongs to pyridazine, auxiliary class TGF-beta/Smad,TGF-beta Receptor, name is 6-(4-(3-Chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile, and the molecular formula is C18H12ClFN6O, HPLC of Formula: 2001559-19-7.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem