Category: pyrimidines

The author of 《Protonation of 2,4-diaminopyrimidines. I. Dissociation constants and substituent effects》 were Roth, Barbara; Strelitz, Justina Z.. And the article was published in Journal of Organic Chemistry in 1969. Computed Properties of C7H10N4O2 The author mentioned the following in the article:

The basic dissociation constant of a series of approx. 70 2,4-diaminopyrimidines and condensed pyrimidine derivatives were obtained. The major effect of 5 substitution is inductive, but there is a greater resonance component than can be accounted for by correlation with Hammett σm constant The effect of 6 substitution, on the other hand, is almost completely inductive. Similar relations were found with 4-amino-6-substituted pyrimidines. In some cases H bonding renders such correlations imprecise. Dissociation constant of 4-substituted pyrimidines can be correlated with σp constant, but 2-substituted derivatives appear to have a considerately greater inductive component. The shifts in uv maximum of 2,4-diamino-6-substituted, but not 5-substituted, pyrimidines had a dependence on the + R or -R character of the substituents. Ion pair formation between certain diaminopyrimidines and divalent ions in aqueous solution was postulated on the basis of uv studies. After reading the article, we found that the author used Ethyl 2,4-diaminopyrimidine-5-carboxylate(cas: 15400-54-1Computed Properties of C7H10N4O2)

Ethyl 2,4-diaminopyrimidine-5-carboxylate(cas: 15400-54-1) belongs to anime. The reaction of alkyl halides, R―X, where X is a halogen, or analogous reagents with ammonia (or amines) is useful with certain compounds. Not all alkyl halides are effective reagents; the reaction is sluggish with secondary alkyl groups and fails with tertiary ones. Its usefulness is largely confined to primary alkyl halides (those having two hydrogen atoms on the reacting site).Computed Properties of C7H10N4O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2013,Nature Communications included an article by Srinivasan, Prakash; Yasgar, Adam; Luci, Diane K.; Beatty, Wandy L.; Hu, Xin; Andersen, John; Narum, David L.; Moch, J. Kathleen; Sun, Hongmao; Haynes, J. David; Maloney, David J.; Jadhav, Ajit; Simeonov, Anton; Miller, Louis H.. Computed Properties of C23H22N4O. The article was titled 《Disrupting malaria parasite AMA1-RON2 interaction with a small molecule preventserythrocyte invasion》. The information in the text is summarized as follows:

Plasmodium falciparum resistance to artemisinin derivatives, the first-line antimalarial drug, drives the search for new classes of chemotherapeutic agents. Current discovery is primarily directed against the intracellular forms of the parasite. However, late schizont-infected red blood cells (RBCs) may still rupture and cause disease by sequestration; consequently targeting invasion may reduce disease severity. Merozoite invasion of RBCs requires interaction between two parasite proteins AMA1 and RON2. Here we identify the first inhibitor of this interaction that also blocks merozoite invasion in genetically distinct parasites by screening a library of over 21,000 compounds We demonstrate that this inhibition is mediated by the small mol. binding to AMA1 and blocking the formation of AMA1-RON complex. Electron microscopy confirms that the inhibitor prevents junction formation, a critical step in invasion that results from AMA1-RON2 binding. This study uncovers a strategy that will allow for highly effective combination therapies alongside existing antimalarial drugs. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8Computed Properties of C23H22N4O)

7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Computed Properties of C23H22N4O

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Quality Control of Ethyl 2-cyano-2-(pyrimidin-2-yl)acetateOn March 31, 1994, Oleinik, Irina V.; Zagulyaeva, Olga A. published an article in Mendeleev Communications. The article was 《Reaction of dihydroazinylidene cyanoacetic esters with nitric acid: a new method for the synthesis of dihydroazinylidene nitroacetonitriles》. The article mentions the following:

An approach to the synthesis of previously unknown dihydroazinylidene nitroacetonitriles (derivatives of pyridine, pyrimidine, pyrazine and pyridazine) has been developed involving nitration of the corresponding dihydroazinylidene cyanoacetic esters at the side chain α-C-atom and dealkoxycarbonylation of the resulting products. In the experimental materials used by the author, we found Ethyl 2-cyano-2-(pyrimidin-2-yl)acetate(cas: 65364-63-8Quality Control of Ethyl 2-cyano-2-(pyrimidin-2-yl)acetate)

Ethyl 2-cyano-2-(pyrimidin-2-yl)acetate(cas: 65364-63-8) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.Quality Control of Ethyl 2-cyano-2-(pyrimidin-2-yl)acetate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 519032-07-6On November 21, 2018 ,《Discovery and Structure-Activity-Relationship Study of N-Alkyl-5-hydroxypyrimidinone Carboxamides as Novel Antitubercular Agents Targeting Decaprenylphosphoryl-β-D-ribose 2′-Oxidase》 appeared in Journal of Medicinal Chemistry. The author of the article were Oh, Sangmi; Park, Yumi; Engelhart, Curtis A.; Wallach, Joshua B.; Schnappinger, Dirk; Arora, Kriti; Manikkam, Michelle; Gac, Brian; Wang, Hongwu; Murgolo, Nicholas; Olsen, David B.; Goodwin, Michael; Sutphin, Michelle; Weiner, Danielle M.; Via, Laura E.; Boshoff, Helena I. M.; Barry, Clifton E.. The article conveys some information:

Magnesium plays an important role in infection with Mycobacterium tuberculosis (Mtb) as a signal of the extracellular environment, as a cofactor for many enzymes, and as a structural element in important macromols. Raltegravir, an antiretroviral drug that inhibits HIV-1 integrase is known to derive its potency from selective sequestration of active-site magnesium ions in addition to binding to a hydrophobic pocket. In order to determine if essential Mtb-related phosphoryl transfers could be disrupted in a similar manner, a directed screen of known mols. with integrase inhibitor-like pharmacophores (N-alkyl-5-hydroxypyrimidinone carboxamides) was performed. Initial hits afforded compounds with low-micromolar potency against Mtb, acceptable cytotoxicity and PK characteristics, and robust SAR. Elucidation of the target of these compounds revealed that they lacked magnesium dependence and instead disappointingly inhibited a known promiscuous target in Mtb, decaprenylphosphoryl-β-D-ribose 2′-oxidase (DprE1, Rv3790).Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6Related Products of 519032-07-6) was used in this study.

Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Related Products of 519032-07-6

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Tozasertib Analogues as Inhibitors of Necroptotic Cell Death》 was written by Hofmans, Sam; Devisscher, Lars; Martens, Sofie; Van Rompaey, Dries; Goossens, Kenneth; Divert, Tatyana; Nerinckx, Wim; Takahashi, Nozomi; De Winter, Hans; Van Der Veken, Pieter; Goossens, Vera; Vandenabeele, Peter; Augustyns, Koen. Recommanded Product: 3764-01-0This research focused ontozasertib analog preparation necroptosis inhibitor antiinflammatory SIRS. The article conveys some information:

Receptor interacting protein kinase 1 (RIPK1) plays a crucial role in tumor necrosis factor (TNF)-induced necroptosis, suggesting that this pathway might be druggable. Most inhibitors of RIPK1 are classified as either type II or type III kinase inhibitors. This opened up some interesting perspectives for the discovery of novel inhibitors that target the active site of RIPK1. Tozasertib, a type I pan-aurora kinase (AurK) inhibitor, was found to show a very high affinity for RIPK1. Because tozasertib presents the typical structural elements of a type I kinase inhibitor, the development of structural analogs of tozasertib is a good starting point for identifying novel type I RIPK1 inhibitors. In this paper, we identified interesting inhibitors of mTNF-induced necroptosis with no significant effect on AurK A and B, resulting in no nuclear abnormalities as is the case for tozasertib. Compounds 71 and 72 outperformed tozasertib in an in vivo TNF-induced systemic inflammatory response syndrome (SIRS) mouse model. The experimental part of the paper was very detailed, including the reaction process of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Recommanded Product: 3764-01-0)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Recommanded Product: 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,Chemistry – A European Journal included an article by Noda, Hidetoshi; Asada, Yasuko; Maruyama, Tatsuro; Takizawa, Naoki; Noda, Nobuo N.; Shibasaki, Masakatsu; Kumagai, Naoya. Reference of 4,6-Dichloropyrimidine. The article was titled 《A C4N4 Diaminopyrimidine Fluorophore》. The information in the text is summarized as follows:

A new scaffold for producing efficient organic fluorescent materials was identified: 2,5-diamino-4,6-diarylpyrimidine featuring a C4N4 elemental composition Single-step installation of two aryl groups at the 4,6-positions of the pyrimidine core delivered fluorescent organic materials in a modular fashion. A range of fluorescent compounds with distinct absorption/emission properties was readily accessed by changing the aromatic attachments. A generally high absorption coefficient and quantum yield were observed, including C4N4 derivatives that could fluoresce even in the solid state. The two amino groups at the 2,5-positions of the pyrimidine were essential for intense fluorescence with a large Stokes shift, which was corroborated by structural relaxation to a p-iminoquinone-like structure in the excited state. Besides live-cell imaging capabilities, fluorescent labeling of a protein involved in autophagy elucidated a new protein-protein interaction, supporting potential utility in bioimaging applications. The experimental process involved the reaction of 4,6-Dichloropyrimidine(cas: 1193-21-1Reference of 4,6-Dichloropyrimidine)

4,6-Dichloropyrimidine(cas: 1193-21-1) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Reference of 4,6-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,Journal of Medicinal Chemistry included an article by Wu, Tsung-Sheng; Lin, Wen-Hsing; Tsai, Hui-Jen; Hsueh, Ching-Cheng; Hsu, Tsu; Wang, Pei-Chen; Lin, Hui-You; Peng, Yi-Hui; Lu, Cheng-Tai; Lee, Lung-Chun; Tu, Chih-Hsiang; Kung, Fang-Chun; Shiao, Hui-Yi; Yeh, Teng-Kuang; Song, Jen-Shin; Chang, Jia-Yu; Su, Yu-Chieh; Chen, Li-Tzong; Chen, Chiung-Tong; Jiaang, Weir-Torn; Wu, Su-Ying. Synthetic Route of C4H2Cl2N2. The article was titled 《Discovery of Conformational Control Inhibitors Switching off the Activated c-KIT and Targeting a Broad Range of Clinically Relevant c-KIT Mutants》. The information in the text is summarized as follows:

Drug resistance due to acquired mutations that constitutively activate c-KIT is a significant challenge in the treatment of patients with gastrointestinal stromal tumors (GISTs). Herein, we identified 1-(5-ethyl-isoxazol-3-yl)-3-(4-{2-[6-(4-ethylpiperazin-1-yl)pyrimidin-4-ylamino]-thiazol-5-yl}phenyl)urea (10a) as a potent inhibitor against unactivated and activated c-KIT. The binding of 10a induced rearrangements of the DFG motif, αC-helix, juxtamembrane domain, and the activation loop to switch the activated c-KIT back to its structurally inactive state. To the best of our knowledge, it is the first structural evidence demonstrating how a compound can inhibit the activated c-KIT by switching back to its inactive state through a sequence of conformational changes. Moreover, 10a can effectively inhibit various c-KIT mutants and the proliferation of several GIST cell lines. The distinct binding features and superior inhibitory potency of 10a, together with its excellent efficacy in the xenograft model, establish 10a as worthy of further clin. evaluation in the advanced GISTs.4,6-Dichloropyrimidine(cas: 1193-21-1Synthetic Route of C4H2Cl2N2) was used in this study.

4,6-Dichloropyrimidine(cas: 1193-21-1) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Synthetic Route of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Bioorganic & Medicinal Chemistry included an article by Fuerst, Rita; Yong Choi, Jun; Knapinska, Anna M.; Smith, Lyndsay; Cameron, Michael D.; Ruiz, Claudia; Fields, Gregg B.; Roush, William R.. Product Details of 90213-66-4. The article was titled 《Development of matrix metalloproteinase-13 inhibitors – A structure-activity/structure-property relationship study》. The information in the text is summarized as follows:

A structure-activity/structure-property relationship study based on the physicochem. as well as in vitro pharmacokinetic properties of a first generation matrix metalloproteinase (MMP)-13 inhibitor (2) was undertaken. After systematic variation of inhibitor 2, compound 31 was identified which exhibited microsomal half-life higher than 20 min, kinetic solubility higher than 20 μM, and a permeability coefficient greater than 20 × 10-6 cm/s. Compound 31 also showed excellent in vivo PK properties after IV dosing (Cmax = 56.8 μM, T1/2 (plasma) = 3.0 h, Cl = 0.23 mL/min/kg) and thus is a suitable candidate for in vivo efficacy studies in an OA animal model. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Product Details of 90213-66-4)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Product Details of 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Li, Shu-Wei; Yu, Cheng-Hung; Ko, Chang-Lun; Chatterjee, Tanmay; Hung, Wen-Yi; Wong, Ken-Tsung published 《Cyanopyrimidine-Carbazole Hybrid Host Materials for High-Efficiency and Low-Efficiency Roll-Off TADF OLEDs》.ACS Applied Materials & Interfaces published the findings.Application of 3764-01-0 The information in the text is summarized as follows:

Two isomeric host materials (Sy and Asy) comprising carbazole (donor) and CN-substituted pyrimidine (acceptor) were synthesized, characterized, and utilized as host materials for green and blue thermally activated delayed fluorescence (TADF) organic light emitting diodes (OLEDs). Both mols. have high triplet energy and small energy difference between singlet and triplet states, leading to feasible TADF. The different linking topologies of carbazole and CN groups on the pyrimidine core provide distinct photophys. properties and mol. packing manners, which further influence the efficiency as they served as hosts in TADF OLEDs. As compared to Asy-based cases, the Sy-hosted TADF OLED device gave higher maximum external quantum efficiencies (EQE) of 24.0% (vs 22.5%) for green (4CzIPN as a dopant) and 20.4% (vs 15.0%) for blue (2CzTPN as a dopant) and low efficiency roll-off. The high horizontal dipole ratio (Θ ≈ 88%) for both emitters dispersed in Sy and Asy hosts accounts for the high device efficiency. A clear mol. structure-phys. property-device performance relationship has been established to highlight the importance of sym. structure in TADF host material design. After reading the article, we found that the author used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Application of 3764-01-0)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Application of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Wu, Chien-Huang; Song, Jen-Shin; Kuan, Hsuan-Hao; Wu, Szu-Huei; Chou, Ming-Chen; Jan, Jiing-Jyh; Tsou, Lun K.; Ke, Yi-Yu; Chen, Chiung-Tong; Yeh, Kai-Chia; Wang, Sing-Yi; Yeh, Teng-Kuang; Tseng, Chen-Tso; Huang, Chen-Lung; Wu, Mine-Hsine; Kuo, Po-Chu; Lee, Chia-Jui; Shia, Kak-Shan published 《Development of Stem-Cell-Mobilizing Agents Targeting CXCR4 Receptor for Peripheral Blood Stem Cell Transplantation and Beyond》.Journal of Medicinal Chemistry published the findings.Related Products of 3764-01-0 The information in the text is summarized as follows:

The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4+ cell types from bone marrow to peripheral circulation. We have discovered a novel series of pyrimidine-based CXCR4 antagonists, a representative (i.e., 16) of which was tolerated at a higher dose and showed better HSC-mobilizing ability at the maximal response dose relative to the approved drug 1 (AMD3100), and thus considered a potential drug candidate for PBSCT indication. Docking compound 16 into the X-ray crystal structure of CXCR4 receptor revealed that it adopted a spider-like conformation striding over both major and minor subpockets. This putative binding mode provides a new insight into CXCR4 receptor-ligand interactions for further structural modifications. The experimental process involved the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Related Products of 3764-01-0)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Related Products of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia