Day: November 21, 2022

Wang, Xiaolun published the artcileIdentification of MRTX1133, a Noncovalent, Potent, and Selective KRAS^G12D Inhibitor, Category: pyrimidines, the publication is Journal of Medicinal Chemistry (2022), 65(4), 3123-3133, database is CAplus and MEDLINE.

KRAS^G12D, the most common oncogenic KRAS mutation, is a promising target for the treatment of solid tumors. However, when compared to KRAS^G12C, selective inhibition of KRAS^G12D presents a significant challenge due to the requirement of inhibitors to bind KRAS^G12D with high enough affinity to obviate the need for covalent interactions with the mutant KRAS protein. Here, we report the discovery and characterization of the first noncovalent, potent, and selective KRAS^G12D inhibitor, MRTX1133, which was discovered through an extensive structure-based activity improvement and shown to be efficacious in a KRAS^G12D mutant xenograft mouse tumor model.

Journal of Medicinal Chemistry published new progress about 2454397-75-0. 2454397-75-0 belongs to pyrimidines, auxiliary class Aromatic Fluorinated Building Blocks, name is 7-Chloro-8-fluoropyrido[4,3-d]pyrimidine-2,4(1H,3H)-dione, and the molecular formula is C19H10Br2N2, Category: pyrimidines.

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

Sreenivas, B. published the artcileSynthesis and biological evaluation of pyrimidine analogs as potential antimicrobial agents, Category: pyrimidines, the publication is International Journal of Pharmacy and Pharmaceutical Sciences (2012), 4(2), 306-310, database is CAplus.

Amino and halogenated pyrimidines were synthesized and screened for biol. activity. All the compounds showed broad spectrum of activity against Staphylococcus epidermidis, tested fungal species and moderate activity towards other tested species. The compound 2-amino-4-bromopyrimidine was the most potent with good efficacy against S. epidermidis and 4-chloropyrimidine-5-carboxylic acid against fungal species.

International Journal of Pharmacy and Pharmaceutical Sciences 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 C12H9N3O4, Category: pyrimidines.

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

Mamtimin, Xirali published the artcileSynthesis, characterization and acidochromism of Poly(2-N,N-dimethylamino-4,6-Bis(2-thienyl)-pyrimidine), SDS of cas: 56-05-3, the publication is Journal of Polymer Research (2011), 18(1), 105-109, database is CAplus.

A new monomer (2-N,N-dimethylamino-4,6-bis(2-thienyl)-pyrimidine) was synthesized and its homopolymer was successfully prepared by using Ferric trichloride (FeCl₃) as an oxidant. The structure of the polymer and monomer was fully characterized by ¹H-NMR, FTIR, UV-vis, Fluorescent spectroscopy and X-ray diffraction pattern. The polymer gives rise to a band at λ _max = 391 nm. The polymer showed the PL spectrum, gave a peak at 507 nm. We have observed that the polymer was sensitive to inorganic acids and the acidochromism behavior was investigated applying organic acid such as CF₃COOH. The corresponding UV-Vis peaks were observed at 464 nm and 357 nm resp. X-ray diffraction data shows that polymer has a certain crystallinity. The polymer exhibited an [η] value of 0.26 dLg^-1 at 25° in H₂SO₄ (w = 98%).

Journal of Polymer Research 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, SDS of cas: 56-05-3.

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

Brun, Omar published the artcileSelective derivatization of N-terminal cysteines using cyclopentenediones, COA of Formula: C39H35N5O8, the publication is Organic Letters (2016), 18(19), 4836-4839, database is CAplus and MEDLINE.

The outcome of the Michael-type reaction between thiols and 2,2-disubstituted cyclopentenediones (CPDs) varies depending on the thiol. Stable compounds with two fused rings were formed upon reaction with 1,2-aminothiols (such as N-terminal cysteines in peptides). Other thiols gave reversibly Michael-type adducts that were in equilibrium with the starting materials. This differential reactivity allows differently placed cysteines to be distinguished and has been exploited to prepare bioconjugates incorporating two or three different moieties.

Organic Letters 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, COA of Formula: C39H35N5O8.

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

Brun, Omar published the artcileSelective derivatization of N-terminal cysteines using cyclopentenediones, Name: 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, the publication is Organic Letters (2016), 18(19), 4836-4839, database is CAplus and MEDLINE.

The outcome of the Michael-type reaction between thiols and 2,2-disubstituted cyclopentenediones (CPDs) varies depending on the thiol. Stable compounds with two fused rings were formed upon reaction with 1,2-aminothiols (such as N-terminal cysteines in peptides). Other thiols gave reversibly Michael-type adducts that were in equilibrium with the starting materials. This differential reactivity allows differently placed cysteines to be distinguished and has been exploited to prepare bioconjugates incorporating two or three different moieties.

Organic Letters 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, Name: 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.

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

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

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

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

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