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CuI-catalyzed amination of arylhalides with guanidines or amidines: A facile synthesis of 1-H-2-substituted benzimidazoles

(Figure Presented) CuI/L5 (N,N?-dimethylethylenediamine) proves to be an efficient catalyst system for the amination of arylhalides with guanidines. The same catalyst system is then successfully applied to the one-step synthesis of 1-H-2-aminobenzimidazoles through tandem aminations of 1,2-dihaloarenes in modest yields. This methodology is also applicable for the preparation of 1-H or 1-substutituted 2-aryl- or 2-alkyl-benzimidazoles.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N70 – PubChem

 

Simple exploration of 3-Aminopyridazine

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2-Aminoimidazole-based antagonists of the 5-HT6 receptor ? A new concept in aminergic GPCR ligand design

A new strategy in the design of aminergic GPCR ligands is proposed ? the use of aromatic, heterocyclic basic moieties in place of the evergreen piperazine or alicyclic and aliphatic amines. This hypothesis has been tested using a benchmark series of 5-HT6R antagonists obtained by coupling variously substituted 2-aminoimidazole moieties to the well established 1-benzenesulfonyl-1H-indoles, which served as the ligands cores. The crystallographic studies revealed that upon protonation, the 2-aminoimidazole fragment triggers a resonance driven conformational change leading to a form of higher affinity. This molecular switch may be responsible for the observed differences in 5-HT6R activity of the studied chemotypes with different amine-like fragments. Considering the multiple functionalization sites of the embedded guanidine fragment, diverse libraries were constructed, and the relationships between the structure and activity, metabolic stability, and solubility were established. Compounds from the N-(1H-imidazol-2-yl)acylamide chemotype (10a?z) exhibited high affinity for 5-HT6R and very high selectivity over 5-HT1A, 5-HT2A, 5-HT7 and D2 receptors (negligible binding), which was attributed to their very weak basicity. The lead compound in the series 4-methyl-5-[1-(naphthalene-1-sulfonyl)-1H-indol-3-yl]-1H-imidazol-2-amine (9i) was shown to reverse the cognitive impairment caused by the administration of scopolamine in rats indicating procognitive potential.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N76 – PubChem

 

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Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.Synthetic Route of 5469-70-5. In my other articles, you can also check out more blogs about 5469-70-5

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2-AMINO-7,8-DIHYDRO-6H-PYRIDO[4,3-D] PYRIMIDIN-5-ONES

Disclosed are 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, their stereoisomers, tautomers, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, either alone or in combination with at least one additional therapeutic agent. Disclosed also are methods of using the 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of cellular proliferative, viral, autoimmune, cardiovascular, and central nevous system diseases.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N32 – PubChem

 

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1-Pyridylmethyl-3-acyl guanidines

1-Acyl-3-pyridyl guanidine and 1-acyl-3-pyridylalkyl guanidine compounds, methods for the treatment of blood pressure disorders, including hypertension, in humans and other mammals.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N45 – PubChem

 

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Construction of sulfur-containing moieties in the total synthesis of natural products

Covering: January 2013 to September 2018 Sulfur-containing natural products are a large class of significant functional molecules. Many of these compounds exhibit potent biological activities and pharmacological properties; in fact, some of them have been developed into important drugs. The total synthesis of sulfur-containing natural products is a subject that has long attracted significant attention from synthetic organic chemists; to achieve this goal, various methods have been developed over the past years. This review surveys total syntheses of sulfur-containing natural products that introduce sulfur atoms using different sulfurization agents to construct related sulfur-containing moieties.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N99 – PubChem

 

Brief introduction of Pyridazin-4-amine

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Synthesis and evaluation of 2?H-spiro[cyclohexane-1,3?-imidazo[1,5-a]pyridine]-1?,5?-dione derivatives as Mnk inhibitors

Post-translational modulation of eIF4E through phosphorylation by Mnks is highly integral to the pathogenesis of different cancers. Therefore, inhibition of Mnks offers a strategy for cancer treatment. Herein, a series of 2?H-spiro[cyclohexane-1,3?-imidazo[1,5-a]pyridine]-1?,5?-dione derivatives is presented as Mnk inhibitors. Some of them showed sub-micromolar to low nanomolar inhibitory activities against Mnk1/2 with a high level of selectivity for both kinases over CDKs. Biochemical assays revealed that compounds 4c and 4t are non-ATP-competitive inhibitors of Mnks. Lead compound 4t demonstrated a high selectivity for Mnk1/2 over a selection of 51 kinases, and displayed anti-proliferative activities against a panel of cancer cell lines. However, this compound in combination with our in-house CDK4/6 inhibitor 83 did not show a synergistic effect in A2780 ovarian cancer cells, suggesting that caution be exercised in the selection of an agent to be combined with an Mnk inhibitor.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N145 – PubChem

 

Discovery of Pyridazin-4-amine

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Design, synthesis and biological evaluation of pyridone?aminal derivatives as MNK1/2 inhibitors

Excessive phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) plays a major role in the dysregulation of mRNA translation and the activation of tumor cell signaling. eIF4E is exclusively phosphorylated by mitogen-activated protein kinase interacting kinases 1 and 2 (MNK1/2) on Ser209. So, MNK1/2 inhibitors could decrease the level of p-eIF4E and regulate tumor-associated signaling pathways. A series of pyridone?aminal derivatives were synthesized and evaluated as MNK1/2 inhibitors. Several compounds exhibited great inhibitory activity against MNK1/2 and selected compounds showed moderate to excellent anti-proliferative potency against hematologic cancer cell lines. In particular, compound 42i (MNK1 IC50 = 7.0 nM; MNK2 IC50 = 6.1 nM) proved to be the most potent compound against TMD-8 cell line with IC50 value of 0.91 muM. Furthermore, 42i could block the phosphorylation level of eIF4E in CT-26 cell line, and 42i inhibited the tumor growth of CT-26 allograft model significantly. These results indicated that compound 42i was a promising MNK1/2 inhibitor for the potent treatment of colon cancer.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N171 – PubChem

 

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6-Methyl-5-azacytidine – Synthesis, conformational properties and biological activity. A comparison of molecular conformation with 5- azacytidine

The title compound was prepared by the isocyanate procedure and the trimethylsilyl method. The measurement of 1H NMR spectrum of 6-methyl-5- azacytidine (1) revealed a preference of gamma(t) (46%) rotamer around C(5′)- C(4′) bond, a predominance of N conformation of the ribose ring (K(eq) 0.33) and a preference of syn conformation around the C-N glycosyl bond. An analogous measurement of 5-azacytidine has shown a preference of gamma+ (60%) rotamer around the C(5′)-C(4′) bond, a predominance of N conformation of the fibose ring (K(eq) 0.41) and a preference of anti conformation around the C- N glycosyl bond 6-Methyl-5-azacytidine (1) inhibits the growth of bacteria E coli to the extent of 85% at 4000 muM concentration and the growth of LoVo/L, a human colon carcinoma cell line, to the extent of 30% at 100 muM concentration but did not inhibit L1210 cells at ? 100 muM concentration 6- Methyl-5-azacytidine (1) exhibited no in vitro antiviral activity at ? 1 muM concentration.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N75 – PubChem

 

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Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as transforming growth factor-beta type 1 receptor kinase inhibitors

A series of 4(5)-(6-alkylpyridin-2-yl)imidazoles 13a-p, 17a, and 17b have been synthesized and evaluated for ALK5 inhibitory activity in an enzyme assay and in cell-based luciferase reporter assays. The quinoxalinyl analogue 13e inhibited ALK5 phosphorylation with an IC50 of 0.012 muM and showed more than 90% inhibition at 0.05 muM in a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporter construct. The binding mode of 13e generated by flexible docking studies shows that 13e fits well into the active site cavity of ALK5 by forming several tight interactions.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N79 – PubChem

 

Final Thoughts on Chemistry for 3-Aminopyridazine

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IMIDAZOLYL INHIBITORS OF 15-LIPOXYGENASE

The present invention provides imidazolyl inhibitors of 15-LO, pharmaceutical compositions containing such inhibitors and methods for treating diseases related to the 15-LO cascade using such compounds and compositions

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N14 – PubChem