Tag: 100-200

In Vivo Phenotypic Screening for Treating Chronic Neuropathic Pain: Modification of C2-Arylethynyl Group of Conformationally Constrained A₃ Adenosine Receptor Agonists was written by Tosh, Dilip K.;Finley, Amanda;Paoletta, Silvia;Moss, Steven M.;Gao, Zhan-Guo;Gizewski, Elizabeth T.;Auchampach, John A.;Salvemini, Daniela;Jacobson, Kenneth A.. And the article was included in Journal of Medicinal Chemistry in 2014.Synthetic Route of C6H4N2 This article mentions the following:

(N)-Methanocarba adenosine 5′-methyluronamides containing 2-arylethynyl groups were synthesized as A₃ adenosine receptor (AR) agonists and screened in vivo (po) for reduction of neuropathic pain. A small N⁶-Me group maintained binding affinity, with human > mouse A₃AR and MW < 500 and other favorable physicochem. properties. E_max (maximal efficacy in a mouse chronic constriction injury pain model) of previously characterized A₃AR agonist, 2-(3,4-difluorophenylethynyl)-N⁶-(3-chlorobenzyl) derivative 6a, MRS5698, was surpassed. More efficacious analogs (in vivo) contained the following C2-arylethynyl groups: pyrazin-2-yl 23 (binding K_i, hA₃AR, nM 1.8), fur-2-yl 27 (0.6), thien-2-yl 32 (0.6) and its 5-chloro 33, MRS5980 (0.7) and 5-bromo 34 (0.4) equivalent, and physiol. unstable ferrocene 36, MRS5979 (2.7). 33 and 36 displayed particularly long in vivo duration (>3 h). Selected analogs were docked to an A₃AR homol. model to explore the environment of receptor-bound C2 and N⁶ groups. Various analogs bound with μM affinity at off-target biogenic amine (M₂, 5HT_2A, β₃, 5HT_2B, 5HT_2C, and α_2C) or other receptors. Thus, we have expanded the structural range of orally active A₃AR agonists for chronic pain treatment. In the experiment, the researchers used many compounds, for example, 2-Ethynylpyrimidine (cas: 37972-24-0Synthetic Route of C6H4N2).

2-Ethynylpyrimidine (cas: 37972-24-0) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Synthetic Route of C6H4N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ab Initio EOM-CCSD Investigation of One-Bond C-C, N-C, and N-N Spin-Spin Coupling Constants in Fluoroazines was written by Del Bene, Janet E.;Alkorta, Ibon;Elguero, Jose. And the article was included in Journal of Physical Chemistry A in 2010.Synthetic Route of C4HF3N2 This article mentions the following:

Ab initio EOM-CCSD calculations were carried out to examine one-bond ¹J (C-C), ¹J(N-C), and ¹J(N-N) spin-spin coupling constants in benzene, pyridine, the diazines, and selected triazines, tetrazines, and pentazine and their fluoro-substituted derivatives Relative to benzene, ¹J(C-C) decreases in the azines as N atoms are introduced into the ring, but this decrease does not exceed 5 Hz. In the fluoro-substituted derivatives, ¹J(C-C) may increase only slightly if the coupled carbon atoms form C-H bonds, or increase dramatically if either or both of the coupled atoms participate in C-F bonds. The value of ¹J(C-C) also depends on the nature of the bonding of the coupled atoms in the ring. The largest increase is found when both carbons participate in C-F bonds, and both are ortho to N atoms. Relative to pyridine, ¹J(N-C) increases as N atoms are introduced into the ring, with the magnitude of the increase depending on the bonding of the coupled atoms. It is negligible if neither atom is bonded to another N, increases if one of the coupled atoms is bonded to another N atom, and increases further if both are bonded to other N atoms. Fluoro-substitution has an opposing effect on ¹J(N-C), making this coupling constant less pos. or neg. when the coupled C participates in a C-F bond. The decrease in ¹J(N-C) relative to the parent mol. is enhanced if either of the coupled atoms is bonded to another N atom or to another C-F group. A further enhancement occurs if both coupled atoms are so bonded, with the largest increases associated with the bonding scheme in which the coupled C is bonded to another N and the coupled N to another C-F. Fluoro-substitution has a small effect on ¹J(N-C) if the coupled C forms a C-H bond, and on ¹J(N-N). Thus, the effects of fluoro-substitution on one-bond couplings tend to be localized. In the experiment, the researchers used many compounds, for example, 4,5,6-Trifluoropyrimidine (cas: 17573-78-3Synthetic Route of C4HF3N2).

4,5,6-Trifluoropyrimidine (cas: 17573-78-3) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Synthetic Route of C4HF3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Design, Synthesis, and Biological Evaluation of Quinazolin-4-one-Based Hydroxamic Acids as Dual PI3K/HDAC Inhibitors was written by Thakur, Ashish;Tawa, Gregory J.;Henderson, Mark J.;Danchik, Carina;Liu, Suiyang;Shah, Pranav;Wang, Amy Q.;Dunn, Garrett;Kabir, Md.;Padilha, Elias C.;Xu, Xin;Simeonov, Anton;Kharbanda, Surender;Stone, Richard;Grewal, Gurmit. And the article was included in Journal of Medicinal Chemistry in 2020.Application of 20090-58-8 This article mentions the following:

A series of quinazolin-4-one based hydroxamic acids was rationally designed and synthesized as novel dual PI3K/HDAC inhibitors by incorporating an HDAC pharmacophore into a PI3K inhibitor (Idelalisib) via an optimized linker. Several of these dual inhibitors were highly potent (IC₅₀ < 10 nM) and selective against PI3Kγ, δ and HDAC6 enzymes and exhibited good antiproliferative activity against multiple cancer cell lines. The lead compound 48c, induced necrosis in several mutant and FLT3-resistant AML cell lines and primary blasts from AML patients, while showing no cytotoxicity against normal PBMCs, NIH3T3, and HEK293 cells. Target engagement of PI3Kδ and HDAC6 by 48c was demonstrated in MV411 cells using the cellular thermal shift assay (CETSA). Compound 48c showed good pharmacokinetics properties in mice via i.p. administration and provides a means to examine the biol. effects of inhibiting these two important enzymes with a single mol., either in vitro or in vivo. In the experiment, the researchers used many compounds, for example, 4-Chloro-5-methylpyrimidin-2-amine (cas: 20090-58-8Application of 20090-58-8).

4-Chloro-5-methylpyrimidin-2-amine (cas: 20090-58-8) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Application of 20090-58-8

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Three Efficient Methods for Preparation of Coelenterazine Analogues was written by Shakhmin, Anton;Hall, Mary P.;Walker, Joel R.;Machleidt, Thomas;Binkowski, Brock F.;Wood, Keith V.;Kirkland, Thomas A.. And the article was included in Chemistry – A European Journal in 2016.Reference of 90905-32-1 This article mentions the following:

The growing popularity of bioluminescent assays has highlighted the need for coelenterazine analogs possessing properties tuned for specific applications. However, the structural diversity of known coelenterazine analogs has been limited by current syntheses. Known routes for the preparation of coelenterazine analogs employ harsh reaction conditions that limit access to many substituents and functional groups. Novel synthetic routes reported here establish simple and robust methods for synthesis and investigation of structurally diverse marine luciferase substrates. Specifically, these new routes allow synthesis of coelenterazine analogs containing various heterocyclic motifs and substituted aromatic groups with diverse electronic substituents at the R² position. Interesting analogs described herein were characterized by their physicochem. properties, bioluminescent half-life, light output, polarity and cytotoxicity. Some of the analogs represent leads that can be utilized in the development of improved bioluminescent systems. In the experiment, the researchers used many compounds, for example, 2-Methoxypyrimidine-5-carbaldehyde (cas: 90905-32-1Reference of 90905-32-1).

2-Methoxypyrimidine-5-carbaldehyde (cas: 90905-32-1) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Reference of 90905-32-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Regioselectivity studies of sydnone cycloaddition reactions of azine-substituted alkynes was written by Foster, Robert S.;Jakobi, Harald;Harrity, Joseph P. A.. And the article was included in Tetrahedron Letters in 2011.Synthetic Route of C6H4N2 This article mentions the following:

The synthesis of azine-substituted pyrazoles by a sydnone cycloaddition strategy is described. Incorporation of a 3-pyridyl moiety at the sydnone N-atom has little effect on either reactivity or regioselectivity, however, 2-ethynyl-pyridine and -pyrimidine undergo cycloaddition with surprisingly poor levels of regiocontrol. A rationale for the observed regiochem. trends and potential routes for improving selectivities are discussed. In the experiment, the researchers used many compounds, for example, 2-Ethynylpyrimidine (cas: 37972-24-0Synthetic Route of C6H4N2).

2-Ethynylpyrimidine (cas: 37972-24-0) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Synthetic Route of C6H4N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthesis and biological research of 2-aryl-4-morpholino-6-triazolylpyrimidine derivatives as antitumor PI3K inhibitors was written by Yang, Xiu-li;Wang, Tian-cai;Lin, Sen;Fan, Hou-xing. And the article was included in Jingxi Huagong in 2014.Recommanded Product: 4-(2-Chloropyrimidin-4-yl)morpholine This article mentions the following:

In order to find more active antitumor PI3K inhibitors, pyrimidine-2,4-diol was used as raw material to go through chlorination by POCl₃, coupling with morpholine, then iodine generation, which was followed by Sonogashira coupling to remove the trimethylsilyl in order to get the triazolyl intermediate. Finally, the intermediate went through Suzuki coupling to give 2-aryl-4-morpholino-6-triazolylpyrimidine 14-27. Their structures were confirmed by ¹HNMR and LC-MS. The in vitro anti-proliferative activity assay against A2780 was carried out by MTT detection method, and the results showed that, at the test concentration of 10μmol/L, the compounds 14 and 25 were more potent than clin. candidates GDC-0941 and BEZ-235, the inhibition rate of which reached 76.7% and 77.2%, resp. Furthermore, the results of pharmacokinetic study suggested that compound 25 was desirable: t_1/2 = 3.2 h, and AUC_0-∞ was 34,193 (ng·h)/mL. In the experiment, the researchers used many compounds, for example, 4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0Recommanded Product: 4-(2-Chloropyrimidin-4-yl)morpholine).

4-(2-Chloropyrimidin-4-yl)morpholine (cas: 62968-37-0) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. For example, the neurotoxin tetrodotoxin is a pyrimidine derivative. It is found in a number of species including the Japanese puffer fish, the blue-ringed octopus, and the orange-bellied newt. Tetrodotoxin prevents the transmission of nerve signals and can result in paralysis and death.Recommanded Product: 4-(2-Chloropyrimidin-4-yl)morpholine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthesis of pyrido[2,3-d]pyrimidinones by the reaction of aminopyrimidin-4-ones with benzylidene Meldrum’s acid derivatives was written by Quiroga, Jairo;Hormaza, Angelina;Insuasty, Braulio;Nogueras, Manuel;Sanchez, Adolfo;Hanold, Norbert;Meier, Herbert. And the article was included in Journal of Heterocyclic Chemistry in 1997.Quality Control of 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one This article mentions the following:

A series of pyrido[2,3-d]pyrimidine-4,7-diones I (R¹ = MeS, MeO; R² = H, Me; R³ = H, Cl, NO₂) were prepared from 6-amino-4-pyrimidinones (II) and benzylidene Meldrum’s acid derivatives (III) by cyclization reactions in boiling nitrobenzene. The structure of I, determined by NMR measurements, reveals a selective orientation of II and III in the addition step. In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7Quality Control of 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) belongs to pyrimidine derivatives. Heterocyclic compounds bearing the pyrimidine core are of tremendous interest as they constitute an important class of natural and synthetic compounds exhibiting diverse useful biological activities that hold attractive potential for clinical translation as therapeutic agents in alleviation of a myriad of diseases. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Quality Control of 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electro-organic synthesis of new pyrimidine and uracil derivatives was written by Davarani, Saied Saeed Hosseiny;Fumani, Neda Sheijooni;Vahidi, Siavash;Tabatabaei, Mohammad-Ali;Arvin-Nezhad, Hamid. And the article was included in Journal of Heterocyclic Chemistry in 2010.Application of 54030-56-7 This article mentions the following:

Electrochem. oxidation of catechols was studied in the presence of 6-aminopyrimidine derivatives as nucleophiles in aqueous solution using cyclic voltammetry. This efficient electro-organic synthesis was successfully performed at carbon rod electrodes in an undivided cell under controlled potential conditions to give dihydroxyaryl-substituted aminopyrimidinones and dihydroxypyrimido[4,5-b]indolones in good yields and purity. In the experiment, the researchers used many compounds, for example, 6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7Application of 54030-56-7).

6-Amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one (cas: 54030-56-7) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Application of 54030-56-7

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Two-, three-, and four-bond N-F spin-spin coupling constants in fluoroazines was written by Del Bene, Janet E.;Alkorta, Ibon;Elguero, Jose. And the article was included in Molecular Physics in 2010.Formula: C4HF3N2 This article mentions the following:

Ab initio EOM-CCSD calculations were performed to investigate 2-, 3- and 4-bond ¹⁵N-¹⁹F coupling constants in mono-, di-, and trifluoroazines. ²J(N-F) values are neg. and are dominated by the Fermi-contact (FC) term. Absolute values of ²J(N-F) tend to decrease as the number of N atoms in the ring increases, and may also be influenced by the number and positions of C-F bonds. ³J(N-F) values are pos. with three exceptions, are usually dominated by the FC term, and also tend to decrease as the number of N atoms increases. The three mols. which have neg. values of ³J(N-F) have dominant neg. paramagnetic-spin orbit (PSO) terms, and are structurally similar insofar as they have an intervening C-F bond between the N and the coupled F. ⁴J(N-F) values are neg. because the PSO, FC, and spin-dipole (SD) terms are neg., with only one exception. Four mols. have significantly greater values of ⁴J(N-F). These are structurally similar with the coupled N bonded to two other N atoms. The computed EOM-CCSD ⁿJ(N-F) coupling constants are in good agreement with the few exptl. values that are available. In the experiment, the researchers used many compounds, for example, 4,5,6-Trifluoropyrimidine (cas: 17573-78-3Formula: C4HF3N2).

4,5,6-Trifluoropyrimidine (cas: 17573-78-3) belongs to pyrimidine derivatives. The pyrimidine derivatives can easily interact with enzymes, genetic materials, and bio components within the cell. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Formula: C4HF3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Pyrimidines. XIII. 2- and 6-Substituted 4-pyrimidinecarboxylic acids was written by Daves, G. Doyle Jr.;O’Brien, Darrell E.;Lewis, Leland R.;Cheng, C. C.. And the article was included in Journal of Heterocyclic Chemistry in 1964.Application In Synthesis of 2-Chloropyrimidine-4-carbonitrile This article mentions the following:

The abnormal behavior of 4,6-dimethyl-2-pyrimidinol towards HONO has been clarified. The reaction between 4-methyl-2-pyrimidinol and HONO has been utilized as a new synthetic procedure for the preparation of several 2-substituted 4-pyrimidinecarboxylic acids. 2-Hydroxy-4-pyrimidinecarboxylic acid has also been prepared from 4-chloro-2-methylthiopyrimidine via the trimethylammonium intermediate. 6-Amino-and 6-thio-4-pyrimidinecarboxylic acids have been readily prepared from the previously reported 6-hydroxy-4-pyrimidinecarboxylic acid. In the experiment, the researchers used many compounds, for example, 2-Chloropyrimidine-4-carbonitrile (cas: 75833-38-4Application In Synthesis of 2-Chloropyrimidine-4-carbonitrile).

2-Chloropyrimidine-4-carbonitrile (cas: 75833-38-4) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Application In Synthesis of 2-Chloropyrimidine-4-carbonitrile

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia