Category: pyrimidines

Medina, Jesus R. published the artcileStructure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors, Category: pyrimidines, the publication is Journal of Medicinal Chemistry (2011), 54(6), 1871-1895, database is CAplus and MEDLINE.

Phosphoinositide-dependent protein kinase-1 (PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein, the lead optimization of compound I (R¹ = R² = H) toward highly potent and selective PDK1 inhibitors via a structure-based design strategy is described. A series of (amino)(aminopyrimidinyl)indazoles I (R¹ = H, Me, Et; R² = Me, i-Pr, PhNH, 1-piperidinyl, etc.) was synthesized, and the inhibiting activity of the products towards PDK1 was studied. The most potent and selective inhibitors, e.g. I [R¹ = Me; R² = (3S,6R)-3-(cyclohexylaminocarbonyl)-6-methyl-1-piperidinyl], demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these mols. as tools to further delineate the biol. of PDK1 and the potential pharmacol. uses of a PDK1 inhibitor.

Journal of Medicinal Chemistry 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, Category: pyrimidines.

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

Barbieri, Giorgio published the artcileInternal rotation of the NN-dimethylamino-group in aromatic and heteroaromatic systems, Category: pyrimidines, the publication is Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999) (1979), 330-6, database is CAplus.

The title rotation was examined by comparing thermodn. activation parameters obtained exptl. with energy differences between ground and transition state evaluated by semiempirical MO calculations and describing the mol. electronic characteristics which determine the barriers to rotation. The rotational behavior in the N-protonated and N-alkylated forms relative to the free base of some (dimethylamino)pyridines was also examined Semiempirical calculations were used to predict the activation parameters and to describe the rotational path in these systems.

Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999) published new progress about 31401-45-3. 31401-45-3 belongs to pyrimidines, auxiliary class Pyrimidine,Amine, name is N,N-Dimethylpyrimidin-4-amine, and the molecular formula is C6H9N3, Category: pyrimidines.

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

Arasappan, Ashok published the artcile5-Benzothiazole substituted pyrimidine derivatives as HCV replication (replicase) inhibitors, Quality Control of 56-05-3, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(9), 3229-3234, database is CAplus and MEDLINE.

Based on a previously identified HCV replication (replicase) inhibitor I, SAR efforts were conducted around the pyrimidine core to improve the potency and pharmacokinetic profile of the inhibitors. A benzothiazole moiety was found to be the optimal substituent at the pyrimidine 5-position. Due to potential reactivity concern, the 4-chloro residue was replaced by a Me group with some loss in potency and enhanced rat in vivo profile. Extensive investigations at the C-2 position resulted in identification of compound II that demonstrated very good replicon potency, selectivity and rodent plasma/target organ concentration Inhibitor II also demonstrated good plasma levels and oral bioavailability in dogs, while monkey exposure was rather low. Chem. optimization towards a practical route to install the benzothiazole moiety resulted in an efficient direct C-H arylation protocol.

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, Quality Control of 56-05-3.

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

Basavalingappa, Vasantha published the artcileMechanically rigid supramolecular assemblies formed from an Fmoc-guanine conjugated peptide nucleic acid, Computed Properties of 186046-81-1, the publication is Nature Communications (2019), 10(1), 1-11, database is CAplus and MEDLINE.

The variety and complexity of DNA-based structures make them attractive candidates for nanotechnol., yet insufficient stability and mech. rigidity, compared to polyamide-based mols., limit their application. Here, we combine the advantages of polyamide materials and the structural patterns inspired by nucleic-acids to generate a mech. rigid fluorenylmethyloxycarbonyl (Fmoc)-guanine peptide nucleic acid (PNA) conjugate with diverse morphol. and photoluminescent properties. The assembly possesses a unique at. structure, with each guanine head of one mol. hydrogen bonded to the Fmoc carbonyl tail of another mol., generating a non-planar cyclic quartet arrangement. This structure exhibits an average stiffness of 69.6 ± 6.8 N m^-1 and Young’s modulus of 17.8 ± 2.5 GPa, higher than any previously reported nucleic acid derived structure. This data suggests that the unique cation-free “basket” formed by the Fmoc-G-PNA conjugate can serve as an attractive component for the design of new materials based on PNA self-assembly for nanotechnol. applications.

Nature Communications published new progress about 186046-81-1. 186046-81-1 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C39H35N5O8, Computed Properties of 186046-81-1.

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

Barnes, J. published the artcileThe protonation state of one-electron reduced cytosine and adenine. 1. Initial protonation sites at low temperatures in glassy solids, Safety of N,N-Dimethylpyrimidin-4-amine, the publication is Journal of Physical Chemistry (1993), 97(13), 3401-8, database is CAplus.

ESR spectra of cytosine and adenine, one-electron reduced in a 9 M LiCl glass at 4° K, show that in each case protonation occurs at the amino group. In order to understand this, a number of one-electron-reduced cytosine and adenine analogs in different glassy environments were produced, at 4° K, and used Q-band EPR to determine the sites of protonation. That the specific association of Li⁺ with the ring nitrogen blocks protonation at the expected sites, N3 of cytosine and N1 of adenine, diverting protonation to the less basic amino group was concluded.

Journal of Physical Chemistry published new progress about 31401-45-3. 31401-45-3 belongs to pyrimidines, auxiliary class Pyrimidine,Amine, name is N,N-Dimethylpyrimidin-4-amine, and the molecular formula is C6H9N3, Safety of N,N-Dimethylpyrimidin-4-amine.

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

Degorce, Sebastien L. published the artcileImproving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors, Related Products of pyrimidines, the publication is Bioorganic & Medicinal Chemistry (2020), 28(23), 115815, database is CAplus and MEDLINE.

In this article, we report our efforts towards improving in vitro human clearance in a series of 5-azaquinazolines through a series of C4 truncations and C2 expansions. Extensive DMPK studies enabled us to tackle high Aldehyde Oxidase (AO) metabolism and unexpected discrepancies in human hepatocyte and liver microsomal intrinsic clearance. Our efforts culminated with the discovery of 5-azaquinazoline I, which also displayed exquisite selectivity for IRAK4, and showed synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with the covalent BTK inhibitor acalabrutinib.

Bioorganic & Medicinal Chemistry published new progress about 1370001-96-9. 1370001-96-9 belongs to pyrimidines, auxiliary class Boronic acid and ester,Boronic acid and ester, name is 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine, and the molecular formula is C11H17BN2O2, Related Products of pyrimidines.

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

Hodges, Timothy R. published the artcileDiscovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS, Formula: C11H17BN2O2, the publication is Journal of Medicinal Chemistry (2018), 61(19), 8875-8894, database is CAplus and MEDLINE.

Son of sevenless homolog 1 (SOS1) is a guanine nucleotide exchange factor that catalyzes the exchange of GDP for GTP on RAS. In its active form, GTP-bound RAS is responsible for numerous critical cellular processes. Aberrant RAS activity is involved in ∼30% of all human cancers; hence, SOS1 is an attractive therapeutic target for its role in modulating RAS activation. Here, we describe a new series of benzimidazole-derived SOS1 agonists. Using structure-guided design, we discovered small mols. that increase nucleotide exchange on RAS in vitro at submicromolar concentrations, bind to SOS1 with low double-digit nanomolar affinity, rapidly enhance cellular RAS-GTP levels, and invoke biphasic signaling changes in phosphorylation of ERK 1/2. These compounds represent the most potent series of SOS1 agonists reported to date.

Journal of Medicinal Chemistry published new progress about 1370001-96-9. 1370001-96-9 belongs to pyrimidines, auxiliary class Boronic acid and ester,Boronic acid and ester, name is 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine, and the molecular formula is C11H17BN2O2, Formula: C11H17BN2O2.

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

Maimaitiyiming, Xieraili published the artcileSynthesis, characterization and properties of poly(2,5-didodecyloxy-1,4-diethynyl-phenylene-alt-2-N,N-dimethyl amino-4,6-pyrimidine), Safety of 2-Amino-4,6-dichloropyrimidine, the publication is Materials Chemistry and Physics (2020), 122116, database is CAplus.

This study reports the synthesis and characterization of new type π-conjugated poly(2,5-didodecyloxy-1,4- diethynyl-phenylene-alt-2-N,N-dimethyl amino-4,6-pyrimidine) with good acidochromism. This polymer was prepared by polycondensation of Sonogashira. Sonogashira was a general route for the preparation of arylacetylenes by coupling an alkynes with aryl or alkenyl halide (or triflates). There were very well solubility for the derivatized copolymer in general organic solvents and exhibits good thermal stability. The copolymer emits blue light under UV irradiation of the solution phase and when protonated with an organic acid, the copolymer exhibits a red shift. In addition, was detected that the copolymers with good acidochromism with acidic place. It was expected to used for acid recognition.

Materials Chemistry and Physics 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

Avitabile, Concetta published the artcileIncorporation of Naked Peptide Nucleic Acids into Liposomes Leads to Fast and Efficient Delivery, Formula: C26H26N4O7, the publication is Bioconjugate Chemistry (2015), 26(8), 1533-1541, database is CAplus and MEDLINE.

The delivery of peptide nucleic acids (PNAs) to cells is a very challenging task. We report here that a liposomal formulation composed of egg PC/cholesterol/DSPE-PEG2000 can be loaded, according to different encapsulation techniques, with PNA or fluorescent PNA oligomers. PNA loaded liposomes efficiently and quickly promote the uptake of a PNA targeting the microRNA miR-210 in human erythroleukemic K562 cells. By using this innovative delivery system for PNA, down-regulation of miR-210 is achieved at a low PNA concentration

Bioconjugate Chemistry published new progress about 169396-92-3. 169396-92-3 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide,Others,PNA, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C26H26N4O7, Formula: C26H26N4O7.

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

Avitabile, Concetta published the artcileIncorporation of Naked Peptide Nucleic Acids into Liposomes Leads to Fast and Efficient Delivery, Recommanded Product: 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, the publication is Bioconjugate Chemistry (2015), 26(8), 1533-1541, database is CAplus and MEDLINE.

The delivery of peptide nucleic acids (PNAs) to cells is a very challenging task. We report here that a liposomal formulation composed of egg PC/cholesterol/DSPE-PEG2000 can be loaded, according to different encapsulation techniques, with PNA or fluorescent PNA oligomers. PNA loaded liposomes efficiently and quickly promote the uptake of a PNA targeting the microRNA miR-210 in human erythroleukemic K562 cells. By using this innovative delivery system for PNA, down-regulation of miR-210 is achieved at a low PNA concentration

Bioconjugate Chemistry published new progress about 186046-81-1. 186046-81-1 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C39H35N5O8, Recommanded Product: 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid.

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