Tag: M.W=150-200

Radhakrishnan, K. published the artcileSynthesis of Size-Expanded Nucleobase Analogues for Artificial Base-Pairing Using a Ligand-Free, Microwave-Assisted Copper(I)-Catalyzed Reaction, Safety of 2-Amino-6-chloropyrido[3,2-d]pyrimidin-4(1H)-one, the publication is ChemistrySelect (2018), 3(46), 13098-13102, database is CAplus.

In order to incorporate valuable properties to the size-expanded nucleobases, a new catalog of highly substituted 2-aminoquinazolinone derivatives, e.g., I have been synthesized in a one-pot, microwave-directed reaction. Syntheses were carried out using simple reactants such as ortho-halo aromatic carboxylic acids, e.g., 4-bromo-3-thiophenecarboxylic acid and guanidine hydrochloride, in absence of any addnl. ligand. The usefulness of the methodol. could be justified by the diversity of the compounds synthesized, containing functional groups, natural nucleobases, fluorophores or peptide bonds.

ChemistrySelect published new progress about 897359-74-9. 897359-74-9 belongs to pyrimidines, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine,Amide, name is 2-Amino-6-chloropyrido[3,2-d]pyrimidin-4(1H)-one, and the molecular formula is C7H5ClN4O, Safety of 2-Amino-6-chloropyrido[3,2-d]pyrimidin-4(1H)-one.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Fernandez-Cureses, Gloria published the artcileDesign, Synthesis, and Biological Evaluation of Unconventional Aminopyrimidine, Aminopurine, and Amino-1,3,5-triazine Methyloxynucleosides, Quality Control of 56-05-3, the publication is ChemMedChem (2015), 10(2), 321-335, database is CAplus and MEDLINE.

Herein we describe a class of unconventional nucleosides (methyloxynucleosides) that combine unconventional nucleobases such as substituted aminopyrimidines, aminopurines, or aminotriazines with unusual sugars in their structures. The allitollyl or altritollyl derivatives were pursued as ribonucleoside mimics, whereas the THF analogs were pursued as their dideoxynucleoside analogs. The compounds showed poor, if any, activity against a broad range of RNA and DNA viruses, including human immunodeficiency virus (HIV). This inactivity may be due to lack of an efficient metabolic conversion into their corresponding 5′-triphosphates and poor affinity for their target enzymes (DNA/RNA polymerases). Several compounds showed cytostatic activity against proliferating human CD4⁺ T-lymphocyte CEM cells and against several other tumor cell lines, including murine leukemia L1210 and human prostate PC3, kidney CAKI-1, and cervical carcinoma HeLa cells. A few compounds were inhibitory to Moloney murine sarcoma virus (MSV) in C₃H/3T3 cell cultures, with the 2,6-diaminotri-O-benzyl-D-allitolyl- and -D-altritolyl pyrimidine analogs being the most potent among them. This series of unconventional nucleosides may represent a novel family of potential antiproliferative agents.

ChemMedChem published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Quality Control of 56-05-3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Goldberg, Daniel R. published the artcileOptimization of spirocyclic proline tryptophan hydroxylase-1 inhibitors, Name: 2-Amino-4,6-dichloropyrimidine, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(3), 413-419, database is CAplus and MEDLINE.

As a follow-up to the discovery of our spirocyclic proline-based TPH1 inhibitor lead, we describe the optimization of this scaffold. Through a combination of X-ray co-crystal structure guided design and an in vivo screen, new substitutions in the lipophilic region of the inhibitors were identified. This effort led to new TPH1 inhibitors with in vivo efficacy when dosed as their corresponding Et ester prodrugs. In particular, 15b (KAR5585), the prodrug of the potent TPH1 inhibitor 15a (KAR5417), showed robust reduction of intestinal serotonin (5-HT) levels in mice. Furthermore, oral administration of 15b generated high and sustained systemic exposure of the active parent 15a in rats and dogs. KAR5585 was selected for further pharmacol. evaluation in disease models associated with a dysfunctional peripheral 5-HT system.

Bioorganic & Medicinal Chemistry Letters published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Name: 2-Amino-4,6-dichloropyrimidine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Goldberg, Daniel R. published the artcileDiscovery of spirocyclic proline tryptophan hydroxylase-1 inhibitors, Computed Properties of 56-05-3, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(4), 1124-1129, database is CAplus and MEDLINE.

The central role of the biogenic monoamine serotonin (5-hydroxytryptamine, 5-HT) as a neurotransmitter with important cognitive and behavioral functions is well known. However, 5-HT produced in the brain only accounts for approx. 5% of the total amount of 5-HT generated in the body. At the onset of our work, it appeared that substituted phenylalanine derivatives or related aryl amino acids were required to produce potent inhibitors of TPH1, as significant losses of inhibitory activity were noted in the absence of this structural element. We disclose herein the discovery of a new class of TPH1 inhibitors that significantly lower peripherally 5-HT.

Bioorganic & Medicinal Chemistry Letters published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Computed Properties of 56-05-3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Kaczanowska, Katarzyna published the artcileSubstituted 2-Aminopyrimidines Selective for α7-Nicotinic Acetylcholine Receptor Activation and Association with Acetylcholine Binding Proteins, Name: 2-Amino-4,6-dichloropyrimidine, the publication is Journal of the American Chemical Society (2017), 139(10), 3676-3684, database is CAplus and MEDLINE.

Through studies with ligand binding to the acetylcholine binding protein (AChBP), the authors previously identified a series of 4,6 substituted 2-aminopyrimidines that associate with this soluble surrogate of the nicotinic acetylcholine receptor (nAChR) in a cooperative fashion, not seen for classical nicotinic agonists and antagonists. To examine receptor interactions of this structural family on ligand-gated ion channels, the authors employed HEK cells transfected with cDNA’s encoding three requisite receptor subtypes: α7-nAChR, α4β2-nAChR and a serotonin receptor (5-HT3AR), along with a fluorescent reporter. Initial screening of a series of over 50 newly characterized 2-aminopyrimidines with affinity for AChBP showed only two to be agonists on the α7-nAChR below 10 μM concentration Their unique structural features were incorporated into design of a second subset of 2-aminopyrimidines yielding several congeners that elicited α7 activation with EC₅₀‘s of 70 nM and Kd’s for AChBP in a similar range. Several compounds within this series exhibit specificity for the α7-nAChR, showing no activation or antagonism of α4β2-nAChR or 5-HT3AR at concentrations up to 10 μM, while others were weaker antagonists (or partial agonists) on these receptors. Anal. following cocrystn. of four ligand complexes with AChBP show binding at the subunit interface, but with an orientation or binding pose that differs from classical nicotinic agonists and antagonists and from the previously analyzed set of 2-aminopyrimidines that displayed distinct cooperative interactions with AChBP. Orientations of aromatic side chains of these complexes are distinctive, suggesting new modes of binding at the agonist-antagonist site and perhaps an allosteric action for heteromeric nAChRs.

Journal of the American Chemical Society published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Name: 2-Amino-4,6-dichloropyrimidine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

D’Attoma, Joseph published the artcileEfficient Transposition of the Sandmeyer Reaction from Batch to Continuous Process, Computed Properties of 56-05-3, the publication is Organic Process Research & Development (2017), 21(1), 44-51, database is CAplus.

The transposition of Sandmeyer chlorination from a batch to a safe continuous flow process was investigated. Our initial approach was to develop a cascade method using flow chem. which involved the generation of diazonium salt and its quenching with copper chloride. To achieve this safe diazotation continuous process, a chemometric approach (Simplex method) was used and extrapolated to establish a fully continuous flow method. The reaction scope was also examined via the synthesis of several (het)aryl chlorines. Validation and scale-up of the process were also performed. A higher productivity was obtained under increasingly tight security.

Organic Process Research & Development published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Computed Properties of 56-05-3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Ke, Shaoyong published the artcileSubstituted-nicotinyl thiourea derivatives bearing pyrimidine moiety: synthesis and biological evaluation, Safety of 2-Amino-4,6-dichloropyrimidine, the publication is Research on Chemical Intermediates (2011), 37(6), 627-633, database is CAplus.

Several substituted nicotinyl thiourea derivatives containing a pyrimidine ring were designed and the synthesis of the target compounds was achieved in good to excellent yield using PEG-400 as solid-liquid phase transfer catalyst under ultrasound irradiation conditions. The structures of the new compounds were confirmed by IR, ¹H-NMR and elemental anal. The preliminary biol. tests show that some of the target compounds present good inhibitory activities against the root and stalk of Magnoliopsida (dicotyledon plants) and are safe for Liliopsida (monocotyledon plants).

Research on Chemical Intermediates published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Safety of 2-Amino-4,6-dichloropyrimidine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Myrianthopoulos, Vassilios published the artcileTandem virtual screening targeting the SRA domain of UHRF1 identifies a novel chemical tool modulating DNA methylation, Name: 2-(Dimethylamino)pyrimidine-4,6-diol, the publication is European Journal of Medicinal Chemistry (2016), 390-396, database is CAplus and MEDLINE.

Ubiquitin-like protein UHRF1 that contains PHD and RING finger domain 1 is a key epigenetic protein enabling maintenance of the DNA methylation status through replication. A tandem virtual screening approach was implemented for identifying small mols. able to bind the 5-methylcytosine pocket of UHRF1 and inhibit its functionality. The NCI/DTP small mols. Repository was screened in silico by a combined protocol implementing structure-based and ligand-based methodologies. Consensus ranking was utilized to select a set of 27 top-ranked compounds that were subsequently evaluated exptl. in a stepwise manner for their ability to demethylate DNA in cellulo using PCR-MS and HPLC-MS/MS. The most active mols. were further assessed in a cell-based setting by the Proximity Ligation In Situ Assay and the ApoTome technol. Both evaluations confirmed that the DNMT1/UHRF1 interactions were significantly reduced after 4 h of incubation of U251 glioma cells with the most potent compound NSC232003, showing a 50% interaction inhibition at 15 μM as well as induction of global DNA cytosine demethylation as measured by ELISA. This is the first report of a chem. tool that targets UHRF1 and modulates DNA methylation in a cell context by potentially disrupting DNMT1/UHRF1 interactions. Compound NSC232003, a uracil derivative freely available by the NCI/DTP Repository, provides a versatile lead for developing highly potent and cell-permeable UHRF1 inhibitors that will enable dissection of DNA methylation inheritance.

European Journal of Medicinal Chemistry published new progress about 5738-14-7. 5738-14-7 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Alcohol,Pyrimidine, name is 2-(Dimethylamino)pyrimidine-4,6-diol, and the molecular formula is C6H9N3O2, Name: 2-(Dimethylamino)pyrimidine-4,6-diol.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Tessier, Romain published the artcile“Doubly Orthogonal” Labeling of Peptides and Proteins, Formula: C4H3Cl2N3, the publication is Chem (2019), 5(8), 2243-2263, database is CAplus.

Herein, we report a cysteine bioconjugation methodol. for the introduction of hypervalent iodine compounds onto biomols. Ethynylbenziodoxolones (EBXs) engage thiols in small organic mols. and cysteine-containing peptides and proteins in a fast and selective addition onto the alkynyl triple bond, resulting in stable vinylbenziodoxolone hypervalent iodine conjugates. The conjugation occurs at room temperature in an open flask under physiol. conditions. The use of an azide-bearing EBX reagent enables a “doubly orthogonal” functionalization of the bioconjugate via strain-release-driven cycloaddition and Suzuki-Miyaura cross-coupling of the vinyl hypervalent iodine bond. We successfully applied the methodol. on relevant and complex biomols., such as histone proteins. Through single-mol. experiments, we illustrated the potential of this doubly reactive bioconjugate by introducing a triplet-state quencher close to a fluorophore, which extended its lifetime by suppressing photobleaching. This work is therefore expected to find broad applications for peptide and protein functionalization.

Chem published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C10H2F12NiO4, Formula: C4H3Cl2N3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Tessier, Romain published the artcile“Doubly Orthogonal” Labeling of Peptides and Proteins, Quality Control of 5738-14-7, the publication is Chem (2019), 5(8), 2243-2263, database is CAplus.

Herein, we report a cysteine bioconjugation methodol. for the introduction of hypervalent iodine compounds onto biomols. Ethynylbenziodoxolones (EBXs) engage thiols in small organic mols. and cysteine-containing peptides and proteins in a fast and selective addition onto the alkynyl triple bond, resulting in stable vinylbenziodoxolone hypervalent iodine conjugates. The conjugation occurs at room temperature in an open flask under physiol. conditions. The use of an azide-bearing EBX reagent enables a “doubly orthogonal” functionalization of the bioconjugate via strain-release-driven cycloaddition and Suzuki-Miyaura cross-coupling of the vinyl hypervalent iodine bond. We successfully applied the methodol. on relevant and complex biomols., such as histone proteins. Through single-mol. experiments, we illustrated the potential of this doubly reactive bioconjugate by introducing a triplet-state quencher close to a fluorophore, which extended its lifetime by suppressing photobleaching. This work is therefore expected to find broad applications for peptide and protein functionalization.

Chem published new progress about 5738-14-7. 5738-14-7 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Alcohol,Pyrimidine, name is 2-(Dimethylamino)pyrimidine-4,6-diol, and the molecular formula is C3H6O2, Quality Control of 5738-14-7.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia