Category: pyrimidines

Jagadeesha, Gullahalli S. published the artcileMicrowave-Assisted, Metal-Free, Chemoselective N -Formylation of Amines using 2-Formyl-3-methyl-1H-imidazol-3-ium Iodide and In Situ Synthesis of Benzimidazole and Isocyanides, SDS of cas: 56-05-3, the publication is SynOpen (2022), 6(2), 132-140, database is CAplus.

An efficient, environmentally benign, chemoselective, microwave-assisted N-formylation protocol of aromatic, aliphatic, alicyclic, benzylic amines, inactivated aromatic amines and sterically demanding heterocyclic amines using 2-formyl-1,3-dimethyl-1H-imidazol-3-ium iodide were developed. This afforded a series of N-substituted formamides RR¹NCHO [R = H, Me, Bn, R¹ = Me, t-Bu, Bn, etc., RR¹ = (CH₂)₄, (CH₂)₅; R = H, R¹ = Ph, 4-MeC₆H₄, 4-BrC₆H₄, etc.] with good to excellent yields (23 examples, 53-96% yield) and was readily scaled. The methodol. were further extended to synthesize benzimidazole and isocyanide derivatives

SynOpen 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

Guo, Yinping published the artcileStructure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain, COA of Formula: C7H6ClN3O, the publication is Angewandte Chemie, International Edition (2021), 60(16), 8760-8765, database is CAplus and MEDLINE.

SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumor suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1, I), we discovered the first potent and selective small mol. SETDB1-TTD inhibitor (R,R)-59 (II) through stepwise structure-guided optimization. (R,R)-59 showed a K_D value of 0.088±0.045μM in the ITC assay. The high potency of (R,R)-59 was well explained by the cocrystal structure of the (R,R)-59-TTD complex. (R,R)-59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)-59 did not show activity in all the assays, highlighting the potential of (R,R)-59 as a tool compound in exploring the biol. functions of SETDB1-TTD.

Angewandte Chemie, International Edition published new progress about 2351929-82-1. 2351929-82-1 belongs to pyrimidines, auxiliary class Pyrroles, name is 2-Chloro-3-methyl-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, and the molecular formula is C7H6ClN3O, COA of Formula: C7H6ClN3O.

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

Bolli, Martin H. published the artcileNovel Benzo[1,4]diazepin-2-one Derivatives as Endothelin Receptor Antagonists, Computed Properties of 321565-33-7, the publication is Journal of Medicinal Chemistry (2004), 47(11), 2776-2795, database is CAplus and MEDLINE.

Since its discovery in 1988 by Yanagisawa et al., endothelin (ET), a potent vasoconstrictor, has been widely implicated in the pathophysiol. of cardiovascular, cerebrovascular, and renal diseases. Many research groups have embarked on the discovery and development of ET receptor antagonists for the treatment of such diseases. While several compounds, e.g., ambrisentan, are in late clin. trials for various indications, one compound (bosentan, Tracleer) is being marketed to treat pulmonary arterial hypertension. Inspired by the structure of ambrisentan, a novel class of ET receptor antagonists based on a 1,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-2-one scaffold was designed. The preparation as well as the in vitro and in vivo structure-activity relationships of these derivatives are reported. Potent dual ET_A/ET_B receptor antagonists with affinities in the low nanomolar range have been identified. In addition, several compounds efficiently reduced arterial blood pressure after oral administration to Dahl salt-sensitive rats. In this animal model, the efficacy of (αR,5R)-rel-α-[(4,6-dimethyl-2-pyrimidinyl)oxy]-2,3,4,5-tetrahydro-2-oxo-5-phenyl-1-[(2,4,6-trifluorophenyl)methyl]-1H-1,4-benzodiazepine-5-acetic acid (I) was superior to that of racemic ambrisentan.

Journal of Medicinal Chemistry published new progress about 321565-33-7. 321565-33-7 belongs to pyrimidines, auxiliary class Pyrimidine, name is 2-Chloro-5-methanesulfonylpyrimidine, and the molecular formula is C5H5ClN2O2S, Computed Properties of 321565-33-7.

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

Etinski, Mihajlo published the artcileAb initio investigation of the methylation and hydration effects on the electronic spectra of uracil and thymine, Product Details of C5H6N2O2, the publication is Physical Chemistry Chemical Physics (2010), 12(19), 4915-4923, database is CAplus and MEDLINE.

In this work, we investigated the lowest-lying electronic excitations for a series of methyl-substituted uracil derivatives, i.e., uracil, 1-methyluracil, 3-methyluracil, thymine, 1-methylthymine, 1,3-dimethyluracil, 3-methylthymine, 1,3-dimethylthymine, and their microhydrated complexes by means of coupled cluster singles and approx. doubles (CC2) and d. functional theory (DFT) methods. The bulk water environment was mimicked by a combination of microhydration and the conductor-like screening model (COSMO). We find that the shift of the electronic excitation energies due to methylation and hydration depend on the character of the wave function and on the position of the Me substituent. The lowest-lying singlet and triplet n → π^* states are insensitive to methylation but are strongly blue-shifted by microhydration and bulk water solvation. The largest red-shift of the first ¹(π → π^*) excitation occurs upon methylation at N₁ followed by substitution at C₅ whereas no effect is obtained for a methylation at N₃. For this state, the effects of methylation and hydrogen bonding partially cancel. Upon microhydration with six water mols., the order of the ¹(n → π^*) and ¹(π → π^*) states is reversed in the vertical spectrum. Electrostatic solute-solvent interaction in bulk water leads to a further increase of their energy separation The n → π^* states are important intermediates for the triplet formation. Shifting them energetically above the primarily excited ¹(π → π^*) state will considerably decrease the triplet quantum yield and thus increase the photostability of the compounds, in agreement with exptl. observations.

Physical Chemistry Chemical Physics published new progress about 608-34-4. 608-34-4 belongs to pyrimidines, auxiliary class Pyrimidine,Amide, name is 3-Methylpyrimidine-2,4(1H,3H)-dione, and the molecular formula is C5H6N2O2, Product Details of C5H6N2O2.

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

Almeida, D. published the artcileDemethylation enhancement of 3-methyl-uracil and 1-methyl-thymine in atom-molecule collisions, Computed Properties of 608-34-4, the publication is Journal of Physics: Conference Series (2012), 388(Part 10), 102031/1, database is CAplus.

The authors report the formation of demethylation in 3-methyl-uracil (3meU) and 1-methyl-thymine (1meT), i.e. (3meU-CH3)- and (1meT-CH3)-, through potassium-mol. collisions at different potassium kinetic energies. Study of the threshold of formation of this fragment can provide a value of threshold energy that can be compared with DEA studies.

Journal of Physics: Conference Series published new progress about 608-34-4. 608-34-4 belongs to pyrimidines, auxiliary class Pyrimidine,Amide, name is 3-Methylpyrimidine-2,4(1H,3H)-dione, and the molecular formula is C5H6N2O2, Computed Properties of 608-34-4.

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

Ferreira da Silva, Filipe published the artcileNCO^–, a Key Fragment Upon Dissociative Electron Attachment and Electron Transfer to Pyrimidine Bases: Site Selectivity for a Slow Decay Process, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Journal of the American Society for Mass Spectrometry (2013), 24(11), 1787-1797, database is CAplus and MEDLINE.

We report gas phase studies on NCO^– fragment formation from the nucleobases thymine and uracil and their N-site methylated derivatives upon dissociative electron attachment (DEA) and through electron transfer in potassium collisions. For comparison, the NCO^– production in metastable decay of the nucleobases after deprotonation in matrix assisted laser desorption/ionization (MALDI) is also reported. We show that the delayed fragmentation of the dehydrogenated closed-shell anion into NCO^– upon DEA proceeds few microseconds after the electron attachment process, indicating a rather slow unimol. decomposition Utilizing partially methylated thymine, we demonstrate that the remarkable site selectivity of the initial hydrogen loss as a function of the electron energy is preserved in the prompt as well as the metastable NCO^– formation in DEA. Site selectivity in the NCO^– yield is also pronounced after deprotonation in MALDI, though distinctly different from that observed in DEA. This is discussed in terms of the different electronic states subjected to metastable decay in these experiments In potassium collisions with 1- and 3-methylthymine and 1- and 3-methyluracil, the dominant fragment is the NCO^– ion and the branching ratios as a function of the collision energy show evidence of extraordinary site-selectivity in the reactions yielding its formation.

Journal of the American Society for Mass Spectrometry published new progress about 608-34-4. 608-34-4 belongs to pyrimidines, auxiliary class Pyrimidine,Amide, name is 3-Methylpyrimidine-2,4(1H,3H)-dione, and the molecular formula is C5H6N2O2, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione.

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

Schaefer, Gabriel published the artcileFacile Synthesis of Sterically Hindered and Electron-Deficient Secondary Amides from Isocyanates, Quality Control of 56-05-3, the publication is Angewandte Chemie, International Edition (2012), 51(36), 9173-9175, S9173/1-S9173/52, database is CAplus and MEDLINE.

The authors report a convenient and rapid approach to the synthesis of hindered and electron-deficient amides by the direct coupling of isocyanates with Grignard reagents. The hindered isocyanates are readily prepared from either amines or carboxylic acids using well-established methods. The isocyanates are easily handled compounds that can be stored for months without any sign of decomposition, and many of them are com. available. The Grignard reagents used in this study are either com. obtained or are readily prepared from the corresponding organo halide and magnesium metal.

Angewandte Chemie, International Edition 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

Larsen, Aaron T. published the artcilePredictable stereoselective and chemoselective hydroxylations and epoxidations with P450 3A4, Formula: C6H9N3, the publication is Journal of the American Chemical Society (2011), 133(20), 7853-7858, database is CAplus and MEDLINE.

Enantioselective hydroxylation of one specific methylene in the presence of many similar groups is debatably the most challenging chem. transformation. Although chemists have recently made progress toward the hydroxylation of inactivated C-H bonds, enzymes such as P 450s (CYPs) remain unsurpassed in specificity and scope. The substrate promiscuity of many P 450s is desirable for synthetic applications; however, the inability to predict the products of these enzymic reactions is impeding advancement. We demonstrate here the utility of a chem. auxiliary to control the selectivity of CYP3A4 reactions. When linked to substrates, inexpensive, achiral theobromine directs the reaction to produce hydroxylation or epoxidation at the fourth carbon from the auxiliary with pro-R facial selectivity. This strategy provides a versatile yet controllable system for regio-, chemo-, and stereoselective oxidations at inactivated C-H bonds and demonstrates the utility of chem. auxiliaries to mediate the activity of highly promiscuous enzymes.

Journal of the American Chemical Society 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, Formula: C6H9N3.

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

Zhao, Y. published the artcileSynthesis and In Vitro Evaluation of Bis-intercalators with Varied Linkers between Aminochloropyrimidine Rings, Application of 2-Amino-4,6-dichloropyrimidine, the publication is Journal of Heterocyclic Chemistry (2014), 51(5), 1327-1332, database is CAplus.

The synthesis of two groups of aminochloropyrimidine bis-intercalators with different lipophilicity or limited flexibility of linkers as potential DNA intercalators is described. The lipophilic linkers in the synthesized bis-intercalators are represented by alternating methylene groups and oxygen atoms in a chain, with a pyrimidine ring containing an amino group and a chloro group at each end I [X = (CH₂)₂O(CH₂)₂O(CH₂)₂, (CH₂)₃O(CH₂)₂O(CH₂)₃, (CH₂)₃O(CH₂)₄O(CH₂)₃, (CH₂)₃O(CH₂)₂O(CH₂)₂O(CH₂)₃]. The bis-intercalators with limited flexibility contain chains with two benzene rings II [Y = CH₂C₆H₄CH₂, C₆H₄CH₂C₆H₄, C₆H₄(CH₂)₂C₆H₄, C₆H₄OC₆H₄, C₆H₄SC₆H₄]. All compounds I, II were obtained by nucleophilic substitution of 2-amino-4,6-dichloropyrimidine. The anticancer activity of these newly synthesized compounds I, II is also reported. The compounds III (n = 10, 12) described in one of our previous publications display good anticancer activity against murine lymphoma.

Journal of Heterocyclic 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 C3H5BN2O2, Application of 2-Amino-4,6-dichloropyrimidine.

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

Koripelly, Girish published the artcileDual sensing of hairpin and quadruplex DNA structures using multicolored peptide nucleic acid fluorescent probes, Recommanded Product: 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 Bioconjugate Chemistry (2010), 21(11), 2103-2109, database is CAplus and MEDLINE.

Synthesis of water-soluble 5-mer peptide nucleic acids (PNAs) functionalized at their 5′- and 3′-ends with two original precursors of pentamethine cyanine dye synthesis is reported. The successful use of these PNA probes for sensing DNA hairpin structures in vitro was also demonstrated where specific hairpin formation was associated with the appearance of a characteristic fluorescence signal at 660 nm. A comparative study between three different strategies where PNAs were targeting either the stem or the loop of the hairpin was carried out. Best sensitivity was obtained using PNA sequences complementary to the loop sequence and directing both functional moieties toward the base of loop. Unprecedented proof-of-concept for the simultaneous sensing of hairpin and quadruplex DNAs with a nonoverlapping two-color system (C3 and C5) is also demonstrated.

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, Recommanded Product: 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