Heterocyclic Building Blocks-Pyridazine

Dow, Nathan W. published the artcileDecarboxylative Borylation and Cross-Coupling of (Hetero)aryl Acids Enabled by Copper Charge Transfer Catalysis, SDS of cas: 919197-88-9, the publication is Journal of the American Chemical Society (2022), 144(14), 6163-6172, database is CAplus and MEDLINE.

Authors report a copper-catalyzed strategy for arylboronic ester synthesis that exploits photoinduced ligand-to-metal charge transfer (LMCT) to convert (hetero)aryl acids into aryl radicals amenable to ambient-temperature borylation. This near-UV process occurs under mild conditions, requires no prefunctionalization of the native acid, and operates broadly across diverse aryl, heteroaryl, and pharmaceutical substrates. They also report a one-pot procedure for decarboxylative cross-coupling that merges catalytic LMCT borylation and palladium-catalyzed Suzuki-Miyaura arylation, vinylation, or alkylation with organo bromides to access a range of value-added products. The utility of these protocols is highlighted through the development of a heteroselective double-decarboxylative C(sp²)-C(sp²) coupling sequence, pairing copper-catalyzed LMCT borylation and halogenation processes of two distinct acids (including pharmaceutical substrates) with subsequent Suzuki-Miyaura cross-coupling.

Journal of the American Chemical Society published new progress about 919197-88-9. 919197-88-9 belongs to pyridazine, auxiliary class Pyridazine,Chloride,Boronic acid and ester,Boronate Esters,Boronic Acids,Boronic acid and ester,Boronate Esters,, name is 3,6-Dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridazine, and the molecular formula is C10H13BCl2N2O2, SDS of cas: 919197-88-9.

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

Varney, Michael D. published the artcileSynthesis and Biological Evaluation of Novel 2,6-Diaminobenz[cd]indole Inhibitors of Thymidylate Synthase Using the Protein Structure as a Guide, Recommanded Product: Pyridazine-4-carbaldehyde, the publication is Journal of Medicinal Chemistry (1995), 38(11), 1892-903, database is CAplus and MEDLINE.

The design, synthesis, and biochem. and biol. evaluations of a novel series of 2,6-diaminobenz[cd]indoles I (R¹, R² = H, Me; X = H; N = methine, nitrogen) of were prepared as inhibitors of human thymidylate synthase (TS) are described. The compounds are characterized by having either a pyridine or pyridazine ring in place of the (phenylsulfonyl)morpholinyl group of the known inhibitor N⁶-[4-(morpholinosulfonyl)benzyl]-N⁶-methyl-2,6-diaminobenz[cd]indole glucuronate. Active compounds from this series showed human TS inhibition constants below the 10 nM level and were potent, selective submicromolar antitumor agents in cell culture. The compounds were synthesized by reductive alkylation of a substituted 6-aminobenz[cd]indole or reductive cyclization of a substituted 1-cyano-8-nitronaphthalene.

Journal of Medicinal Chemistry 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 C9H8O4, Recommanded Product: Pyridazine-4-carbaldehyde.

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

Mammoliti, Oscar published the artcileDiscovery of the S1P2 Antagonist GLPG2938 (1-[2-Ethoxy-6-(trifluoromethyl)-4-pyridyl]-3-[[5-methyl-6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]pyridazin-3-yl]methyl]urea), a Preclinical Candidate for the Treatment of Idiopathic Pulmonary Fibrosis, Related Products of pyridazine, the publication is Journal of Medicinal Chemistry (2021), 64(9), 6037-6058, database is CAplus and MEDLINE.

Mounting evidence from the literature suggests that blocking S1P2 receptor (S1PR2) signaling could be effective for the treatment of idiopathic pulmonary fibrosis (IPF). However, only a few antagonists have been so far disclosed. A chem. enablement strategy led to the discovery of a pyridine series with good antagonist activity. A pyridazine series with improved lipophilic efficiency and with no CYP inhibition liability was identified by scaffold hopping. Further optimization led to the discovery of 40 (GLPG2938)(I), a compound with exquisite potency on a phenotypic IL8 release assay, good pharmacokinetics, and good activity in a bleomycin-induced model of pulmonary fibrosis.

Journal of Medicinal 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, Related Products of pyridazine.

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

Yamane, Daiki published the artcileSelective covalent targeting of SARS-CoV-2 main protease by enantiopure chlorofluoroacetamide, Recommanded Product: Pyridazine-4-carbaldehyde, the publication is Chemical Science (2022), 13(10), 3027-3034, database is CAplus and MEDLINE.

An irreversible SARS-CoV-2 M^pro inhibitor possesseschlorofluoroacetamide (CFA) as a warhead for the covalent modification of M^pro. Ugi multicomponent reaction using chlorofluoroacetic acid enabled the rapid synthesis of dipeptidic CFA derivatives RC(O)N(C₆H₅R¹)CH(R²)C(O)NHR³ (R = Ac, ethenyl, difluoroacetyl, furan-2-yl; R¹ = i-Pr, t-Bu, 1-methylcyclohexyl, etc.; R² = pyridin-3-yl, pyridazin-4-yl, pyridazin-3-yl, etc.; R³ = t-Bu, isoquinolin-7-yl, 2-(3-fluorophenyl)ethyl, etc.) that identified (SR)/(RR)/(RS)(SS)-2-chloro-2-fluoro-N-(2-[(3-fluorophenethyl)amino]-2-oxo-1-(pyrimidin-5-yl)ethyl)-N-[4-(pentafluoro-lmbda6-sulfaneyl)phenyl]acetamide as a potent inhibitor of SARS-CoV-2 M^pro. Among the four stereoisomers, (R)-2-chloro-2-fluoro-N-((R)-2-[(3-fluorophenethyl)amino]-2-oxo-1-(pyrimidin-5-yl)ethyl)-N-[4-(pentafluoro-lamda6-sulfaneyl)phenyl]acetamide exhibited a markedly higher inhibitory activity against M^pro than the other isomers. Reaction kinetics and computational docking studies suggest that the R configuration of the CFA warhead is crucial for the rapid covalent inhibition of M^pro. These findings highlight the prominent influence of the CFA chirality on the covalent modification of proteinous cysteines and provide the basis for improving the potency and selectivity of CFA-based covalent inhibitors.

Chemical Science 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 C4H8Cl2S2, Recommanded Product: Pyridazine-4-carbaldehyde.

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

Heinisch, Gottfried published the artcilePyridazines. 7. Preparation of pyridazine-3-carboxaldehyde: synthesis and reactivity studies, Formula: C5H4N2O, the publication is Monatshefte fuer Chemie (1977), 108(1), 213-24, database is CAplus.

MnO2-oxidation of 3-pyridazinemethanol gave 3-pyridazinecarboxaldehyde (I). Properties of I and its reactions with NH compounds and methylpiridazines were studied. Reaction of I with 3-methylpiridazine gave mainly products of aldol addition II and III. Elimination of H2O from II gave the alkene IV. Isolation of dipyridazinylethane V as main product of reaction of I with 4-methylpiperazine however shows, that thermally induced dismutation cannot be excluded also on pyridazinyl-3-carbinols.

Monatshefte fuer Chemie 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, Formula: C5H4N2O.

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

Heinisch, Gottfried published the artcileSyntheses and reactions of pyridazine derivatives, VI. 1,2-Dipyridazinylethene- and -ethane-1,2-diols from pyridazine carboxaldehydes, Safety of Pyridazine-4-carbaldehyde, the publication is Monatshefte fuer Chemie (1976), 107(3), 799-808, database is CAplus.

Treatment of pyridazine-4-carboxaldehyde with catalytic amounts of KCN gave pyridazine-4-carboxylic acid and two stereoisomeric diols I, II. Pyridazine-3-carboxaldehyde reacts with HCN to give III. HCN-elimination from III yields the enediol IV which is oxidized to pyridazine-3-carboxylic acid or its methyl ester.

Monatshefte fuer Chemie 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, Safety of Pyridazine-4-carbaldehyde.

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

Heinisch, G. published the artcileSyntheses and reactions of pyridazine derivatives. 3. Pyridazine-4-carboxaldehyde, Computed Properties of 50901-42-3, the publication is Monatsh. Chem. (1973), 104(5), 1372-82, database is CAplus.

4-Pyridazine-carboxaldehyde (I) was prepared by treating 4-methylpyridazine with PhCHO and OsO4 oxidation of the resulting 4-styrylpyridazine. I underwent a variety of reactions with amines and CH-acids, as well as the Cannizzaro reaction.

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, Computed Properties of 50901-42-3.

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

Heinisch, G. published the artcileSyntheses and reactions of pyridazine derivatives. V. Thermal disproportionation of pyridazinyl-4-carbinols, Safety of Pyridazine-4-carbaldehyde, the publication is Monatshefte fuer Chemie (1974), 105(4), 763-71, database is CAplus.

Pyridazinecarbinols I (R1 = Me, Ph, 4-pyridazinylmethyl) disproportionated at 120° into the ketones II and alkanes III. The mechanism of the disproportionation was discussed. I (R1 = 4-pyridazinylmethyl) was prepared by treating 4-methylpyridazine with Et 4-pyridazinecarboxylate and Me3COK and reducing II (R1 = 4-pyridazinylmethyl). SeO2 oxidation of III (R1 = 4-pyridazinylmethyl) gave trans-1,2-bis(4-pyridazinyl)ethene. Condensation of 4-formylpyridazine with acetone gave 1-(4-pyridazinyl)-1,3-butanedione.

Monatshefte fuer Chemie 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, Safety of Pyridazine-4-carbaldehyde.

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

Piras, Sandra published the artcileSynthesis and evaluation of gastroprotective activity of omeprazole-related benzimidazole, imidazo[4,5-b]pyridine and quinoxaline 2-substituted derivatives, Safety of (6-Methoxypyridazin-3-yl)methanol, the publication is Farmaco (1993), 48(9), 1249-59, database is CAplus and MEDLINE.

Twenty title compounds, bearing either a substituted arylmethylmercapto group or an arylmethylsulfinyl group in position 2, were prepared (general methods given) in order to evaluate their antiulcer and gastroprotective activity in rats with a ligated pylorus, in comparison with omeprazole (50 mg/kg, i.m.). Approx. one-third of these compounds had a moderate activity, being about half as potent as omeprazole. Some structure-activity parameters are briefly discussed.

Farmaco 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, Safety of (6-Methoxypyridazin-3-yl)methanol.

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

Berlin, Michael published the artcileReduction of hERG inhibitory activity in the 4-piperidinyl urea series of H3 antagonists, Application of Pyridazine-4-carbaldehyde, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(7), 2359-2364, database is CAplus and MEDLINE.

Structural features of the substituted 4-piperidinyl urea analogs, e.g., I, responsible for the H3 antagonist activity, have been identified. Structure-activity relationship of the H3 receptor affinity, hERG ion channel inhibitory activity and their separation is described. Preliminary pharmacokinetic evaluation of some of the compounds of the series is addressed.

Bioorganic & Medicinal Chemistry Letters 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, Application of Pyridazine-4-carbaldehyde.

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