Month: November 2022

Floyd, David M. published the artcileHit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides, Application In Synthesis of 50901-42-3, the publication is Journal of Medicinal Chemistry (2016), 59(17), 7950-7962, database is CAplus and MEDLINE.

Phenotypic whole-cell screening in erythrocytic co-cultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent anti-malarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity studies revealed relationships between potency and modifications at N-2, C-3 and C-4. Careful structure-property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicol. effects, inherent in the more potent primary screening hits such as (I). Analogs (II) and (+)-SJ733 (13i), with structural modifications at each site, were shown to possess excellent anti-malarial activity in vivo. The (+)-(3S,4S) enantiomer of 13i and similar analogs were identified as the more potent. Based on these studies, the authors have selected (+)-13i for further study as a preclin. candidate.

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 C5H4N2O, Application In Synthesis of 50901-42-3.

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

Cacciari, Barbara published the artcileFacile and versatile route to the synthesis of fused 2-pyridones: useful intermediates for polycyclic systems, Safety of 3-Aminopyridazine-4-carbonitrile, the publication is Synthetic Communications (2006), 36(9), 1177-1183, database is CAplus.

The reaction of various heteroaromatic amino nitriles with di-Et malonate under basic conditions is reported. This reaction affords a series of different highly functionalized 2-pyridone condensed systems, which can be suitable intermediates in the construction of polyheterocyclic structures.

Synthetic Communications published new progress about 119581-52-1. 119581-52-1 belongs to pyridazine, auxiliary class Pyridazine,Nitrile,Amine, name is 3-Aminopyridazine-4-carbonitrile, and the molecular formula is C5H4N4, Safety of 3-Aminopyridazine-4-carbonitrile.

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

Vetrichelvan, Muthalagu published the artcileDevelopment of a Scalable Synthesis of the Small Molecule TGFβR1 Inhibitor BMS-986260, Product Details of C18H12ClFN6O, the publication is Organic Process Research & Development (2020), 24(7), 1310-1320, database is CAplus.

A scalable route to the small mol. TGFβR1 inhibitor BMS-986260 I was developed. This alternative approach circumvented the purification of intermediates by column chromatog. and provided access to multikilogram quantities of the key intermediate, 6-formylimidazo[1,2-b]pyridazine-3-carbonitrile. The safety aspects of the synthetic approach to the other fragment of the API (TosMIC) were critically evaluated, and a robust process for its large-scale synthesis was successfully demonstrated.

Organic Process Research & Development 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 C10H10O6, Product Details of C18H12ClFN6O.

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

Liu, Yuji published the artcileConstruction of Bicyclic 1,2,3-Triazine N-Oxides from Aminocyanides, HPLC of Formula: 119581-52-1, the publication is Organic Letters (2021), 23(3), 734-738, database is CAplus and MEDLINE.

Using a facile and cost-effective method, nine bicyclic 1,2,3-triazine 2-oxides were synthesized from o-aminocyanide substrates through an unusual nitration cyclization. The reaction mechanism was studied exptl. and theor. Moreover, nine 1,2,3-triazine 3-oxides were also obtained in good yields.

Organic Letters published new progress about 119581-52-1. 119581-52-1 belongs to pyridazine, auxiliary class Pyridazine,Nitrile,Amine, name is 3-Aminopyridazine-4-carbonitrile, and the molecular formula is C5H4N4, HPLC of Formula: 119581-52-1.

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

Helm, Matthew D. published the artcileA novel approach to functionalized pyridazinone arrays, Quality Control of 919197-88-9, the publication is Organic & Biomolecular Chemistry (2006), 4(23), 4278-4280, database is CAplus and MEDLINE.

A series of 3,6-dichloro-1H-pyridazin-4-ones have been prepared via the cycloaddition of 3,6-dichlorotetrazine with alkynylboronates, and their employment as useful synthetic intermediates was highlighted through a selection of highly regioselective C-O, C-S and C-C bond forming reactions.

Organic & Biomolecular Chemistry 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, Quality Control of 919197-88-9.

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

Heinisch, G. published the artcilePyridazines. Part 55. Electron-ionization mass spectrometry of selected monosubstituted pyridazines, Category: pyridazine, the publication is Scientia Pharmaceutica (1991), 59(2), 111-13, database is CAplus.

The electron-ionization mass spectrometric fragmentations of 20 3- or 4-substituted pyridazines (I, R or R¹ = H, CH₂OH, CH:NOH, CN, COOH, CONH₂, COOMe, COOEt, CHO, COMe, COEt) are given.

Scientia Pharmaceutica 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

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