Month: October 2022

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

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 2016,Sabat, Nazarii; Postova Slavetinska, Lenka; Klepetarova, Blanka; Hocek, Michal published 《C-H Phosphonation of Pyrrolopyrimidines: Synthesis of Substituted 7- and 9-Deazapurine-8-phosphonate Derivatives》.Journal of Organic Chemistry published the findings.Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The information in the text is summarized as follows:

The Mn(OAc)3-promoted C-H phosphonation of 7-deazapurines (pyrrolo[2,3-d]pyrimidines) and 9-deazapurines (pyrrolo[3,2-d]pyrimidines) with diethylphosphite was developed. The reactions occur regioselectively at position 8 both in 7 and 9-deazapurines, leading to new deazapurine-8-phosphonate derivatives, which can be further modified and transformed to 6-(het)aryl-deazapurine derivatives or deprotected to free phosphonic acids. In addition to this study using 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine, there are many other studies that have used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine) was used in this study.

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineThey have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《An efficient and scalable approach for the synthesis of piperazine based glitazone and its derivatives》 was published in Synthetic Communications in 2020. These research results belong to Sharma, Vijay Kumar; Barde, Anup; Rattan, Sunita. SDS of cas: 3934-20-1 The article mentions the following:

A versatile and efficient synthetic approach has been developed for the synthesis of piperazine based glitazones I (R = Me, propan-2-yl, cyclopropylmethyl, etc.) analogus to Lobeglitazone. Desired compounds I were synthesized with good yields by alkylation of piperazine substrate I (R = H) with various carbonyl compds R1C(O)R2 (R1 = H, Me, Et, cyclopropyl; R2 = H, Me; R1R2 = -(CH2)3-). This substrate has the potential for the construction of novel heterocyclic compounds with medicinal importance. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1SDS of cas: 3934-20-1)

2,4-Dichloropyrimidine(cas: 3934-20-1) 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.SDS of cas: 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Al-Wahaibi, Lamya H.; Bysani, Sai Ramya Sree; Tawfik, Samar S.; Abdelbaky, Mohammed S. M.; Garcia-Granda, Santiago; El-Emam, Ali A.; Percino, M. Judith; Thamotharan, Subbiah published their research in Crystal Growth & Design in 2021. The article was titled 《Invariant and Variable Supramolecular Self-Assembly in 6-Substituted Uracil Derivatives: Insights from X-ray Structures and Quantum Chemical Study》.Product Details of 3764-01-0 The article contains the following contents:

In this study, three new 6-(arylthio)uracil derivatives, namely, 6-(phenylthio)pyrimidine-2,4(1H,3H)-dione (1), C10H8N2O2S; 6-(p-tolylthio)pyrimidine-2,4(1H,3H)-dione (2), C11H10N2O2S; and 6-(3,5-dimethylphenylthio)pyrimidine-2,4(1H,3H)-dione (3), C12H12N2O2S, have been synthesized. Single-crystal structures of these compounds reveal an invariant mol. tape contains alternate R22(8) synthons formed by N-H···O hydrogen bonds in 1 and 3. This alternate hydrogen-bonded pattern disappeared in 2; instead, a new synthon is generated. The lattice energy calculation suggests that the methyl-substituted derivatives (2 and 3) have high stabilization energy than compound 1. The electrostatic potential map reveals the difference in the accepting tendency of the carbonyl oxygen. The Hirshfeld surface and 2D-fingerprint plots analyses demonstrate that the major intermol. interactions come from H···O contacts in 1, and these contacts were reduced due to the presence of Me substitutions in 2 and 3. This reduction is compensated by the increase of the same amount of H···H contacts in these structures. Further, the PIXEL energy and DFT calculations at the M06-2X-D3/ cc-pVTZ level of theory were used to characterize the dimeric topol. formed in structures of 1-3. The intermol. interaction energies of dimers calculated by the PIXEL method were compared with the B97D3/ def2-TZVP level of approximation Although these mols.’ crystal packing is somewhat different, the energy frameworks show similarities on the resp. crystal structure’s shortest axis. Furthermore, the nature and strength of various noncovalent interactions such as N-H···O, C-H···O/ S/π, π···π, and a chalcogen bond of type C-S···O=C were evaluated using the Bader’s quantum theory of atoms-in-mols. framework. In the part of experimental materials, we found many familiar compounds, such as 2,4,6-Trichloropyrimidine(cas: 3764-01-0Product Details 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.Product Details of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Pawara, Rahul; Ahmad, Iqrar; Nayak, Deepika; Belamkar, Sateesh; Surana, Sanjay; Kundu, Chanakya Nath; Patil, Chandragauda; Patel, Harun published an article in Journal of Molecular Structure. The title of the article was 《Design and synthesis of the novel, selective WZ4002 analogue as EGFR-L858R/T790M tyrosine kinase inhibitors for targeted drug therapy in non-small-cell lung cancer (NSCLC)》.Formula: C4H2Cl2N2 The author mentioned the following in the article:

To conquer the drug-resistance of first-generation EGFR (epidermal growth factor receptor) kinase inhibitors and second-generation inhibitors’ non-selective toxicities in Non-Small Cell Lung Cancer (NSCLC) patients, a series of WZ4002 derivatives I [R1 = 4-fluorophenyl, 3,4-dichlorophenyl, 4-bromophenyl, etc.; R2 = 3-CH2=CHC(O)NHC6H4, 4-MeC(O)-N(CH2)2N-C6H4, 3-ClCH2C(O)NHC6H4, etc.] were discovered as novel double mutant EGFR-L858R/T790M TK inhibitors. This objective was attained by employing structure-based drug design and traditional optimization strategies based on the WZ4002 scaffold. Among the synthesized compounds I, representative compounds I [R1 = 4-chloro-3-fluorophenyl, 4-bromophenyl; R2 = 3-CH2=CHC(O)-N(CH2)2N-C6H4] displayed significant anti-proliferative activity on the Gefitinib-resistant cell line NCI-H1975, with an IC50 value of 0.179μM and 0.173μM, resp. Also, these compounds exhibited moderate anti-proliferative activity against the A549 cell, with an IC50 of 0.550μM and 0.528μM resp., suggesting their improved selectivity over the mutant EGFR-L858R/T790M. Excitingly, both these compounds showed significant inhibition of the double mutant EGFR-L858R/T790M TK with an IC50 value of 0.0063μM and 0.0060μM, resp. The IC50 values of both the promising compounds against the HepG2 cell line were more than 1μM, indicating safety for normal cells. Covalent docking and MD simulation further confirm their irreversible binding mode with the target protein. These results demonstrate that compounds I [R1 = 4-chloro-3-fluorophenyl, 4-bromophenyl; R2 = 3-CH2=CHC(O)-N(CH2)2N-C6H4] would be promising lead compound-targeting double mutant EGFR-L858R/T790M TK. The results came from multiple reactions, including the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Formula: C4H2Cl2N2)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Formula: C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

SDS of cas: 90213-66-4In 2021 ,《Structure-Based Design and Discovery of Pyridyl-Bearing Fused Bicyclic HIV-1 Inhibitors: Synthesis, Biological Characterization, and Molecular Modeling Studies》 was published in Journal of Medicinal Chemistry. The article was written by Huang, Boshi; Ginex, Tiziana; Luque, F. Javier; Jiang, Xiangyi; Gao, Ping; Zhang, Jian; Kang, Dongwei; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong. The article contains the following contents:

Tetrahydroquinazolines I [R1 = Me, CN, CHO, CH2=CH2CN; R2 = CN, CH2CN, OCF3, SO2CH3; X = Y = CH, N]/pyrrolopyrimidines II [R3 = CN, CH2=CH2CN, CH2=CH2C(O)NH2; X1 = CH, N; Y1 = CH]/pyrrolotriazines III [R4 = CH2OH, CH2O(CH2)2Si(CH3)3, 2-morpholino-2-oxo-ethyl; X2 = Y2 = CH, N] analogs designed to target the dual-tolerant regions of the non-nucleoside reverse transcriptase inhibitor (NNRTI)-binding pocket were synthesized and evaluated for their anti-HIV activities. Several compounds, such as I [R1 = CN, CH2=CH2CN; R2 = CN; X = Y = CH], compound II [R3 = CN; X1 = N; Y1 = CH] and compounds III [R4 = CH2OH, 2-morpholino-2-oxo-ethyl; X2 = CH, N; Y2 = CH] were found to be potent inhibitors against the wild-type (WT) HIV-1 strain or multiple NNRTI-resistant strains at low nanomolar levels. Detailed structure-activity relationships were obtained by utilizing the variation of moieties within the corresponding pharmacophores. In vitro metabolic stability profiles and some drug-like properties of selected compounds were assessed, furnishing the preliminary structure-metabolic stability relationships. Furthermore, mol. modeling studies elucidated the binding modes of compounds I [R1 = CN, CH2=CH2CN; R2 = CN; X = CH, N; Y = CH], compound II [R3 = CN; X1 = N; Y1 = CH] and compound III [R4 = CH2OH; X2 = CH, N; Y2 = CH] in the binding pocket of WT, E138K, K103N, or Y181C HIV-1 RTs. These promising compounds could be used as lead compounds and warrant further structural optimization to yield more active HIV-1 inhibitors.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4SDS of cas: 90213-66-4) was used in this study.

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. SDS of cas: 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Efficient transformation of thymidine into 2′,3′-didehydro-2′,3′-dideoxythymidine (D4T) involving opening of a 2,3′-anhydro derivative by phenylselenol》 was written by Becouarn, Stefan; Czernecki, Stanislas; Valery, Jean-Marc. Application In Synthesis of ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate And the article was included in Nucleosides & Nucleotides on August 31 ,1995. The article conveys some information:

A high-yielding method for the introduction of the phenylselenyl residue at the 3′-position of thymidine is reported. This reaction avoided any strongly basic or reductive reagent, thus allowing the use of benzoate ester as a protective group at O-5′. Further oxidation-elimination sequence followed by basic deprotection afforded D4T in 67.5% overall yield from thymidine. In the experimental materials used by the author, we found ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9Application In Synthesis of ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate)

((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9) 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.Application In Synthesis of ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Category: pyrimidinesOn March 12, 1982, Barczynski, P.; Van der Plas, H. C. published an article in Journal of Organic Chemistry. The article was 《Ring transformations in reactions of heterocyclic compounds with nucleophiles. Part 24. Pyrimidines. Part 86. Conversion of 5-nitropyrimidine into 2-substituted 5-nitropyrimidine and 2-amino-5-nitropyridines by amidines》. The article mentions the following:

The reaction of 5-nitropyrimidine (I) with benzamidine, pivalamidine, acetamidine, propionamidine, α-phenylacetamidine, O-methylisourea hydrochlorides, and cyanamide in ethanolic solution in the presence of Et3N was investigated. I and alkyl(aryl)amidines, having no active methylene groups attached to the amidine moiety (pivalamidine, benzamidine), gave the corresponding 2-substituted 5-nitropyrimidines in good yields. With acetamidine and propionamidine, 2-amino-5-nitropyridines were also formed; with α-phenylacetamidine a 2-amino-5-nitropyridine derivative was obtained exclusively. The reaction of I with both O-methylisourea and cyanamide leads to 2-amino-5-nitropyrimidine. These reactions provide new examples of degenerate ring transformations of the pyrimidine ring system and of the ring transformation of pyrimidines into pyridines. After reading the article, we found that the author used 2-Methoxy-5-nitropyrimidine(cas: 14001-69-5Category: pyrimidines)

2-Methoxy-5-nitropyrimidine(cas: 14001-69-5) is a member of ether. When aromatic ethers are exposed to halogen in the presence or absence of a catalyst, they undergo halogenation, such as bromination.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

HPLC of Formula: 519032-07-6On May 3, 2007 ,《Dihydroxypyrimidine-4-carboxamides as Novel Potent and Selective HIV Integrase Inhibitors》 appeared in Journal of Medicinal Chemistry. The author of the article were Pace, Paola; Di Francesco, M. Emilia; Gardelli, Cristina; Harper, Steven; Muraglia, Ester; Nizi, Emanuela; Orvieto, Federica; Petrocchi, Alessia; Poma, Marco; Rowley, Michael; Scarpelli, Rita; Laufer, Ralph; Gonzalez Paz, Odalys; Monteagudo, Edith; Bonelli, Fabio; Hazuda, Daria; Stillmock, Kara A.; Summa, Vincenzo. The article conveys some information:

Human immunodeficiency virus type-1 (HIV-1) integrase, one of the three constitutive viral enzymes required for replication, is a rational target for chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clin. setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these mols. were made in order to examine effects on HIV-integrase inhibitory potencies. One of the most interesting compounds for this series is 2-[1-(dimethylamino)-1-methylethyl]-N-(4-fluorobenzyl)-5,6-dihydroxypyrimidine-4-carboxamide, with a CIC95 of 78 nM in the cell-based assay in the presence of serum proteins. The compound has favorable pharmacokinetic properties in preclin. species (rats, dogs, and monkeys) and shows no liabilities in several counterscreening assays, highlighting its potential as a clin. useful antiviral agent. The experimental process involved the reaction of Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6HPLC of Formula: 519032-07-6)

Methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate(cas: 519032-07-6) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. HPLC of Formula: 519032-07-6They have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia