Tag: M.W=150-200

Li, Nan published the artcileCopper-Free Sonogashira Cross-Coupling for Functionalization of Alkyne-Encoded Proteins in Aqueous Medium and in Bacterial Cells, Synthetic Route of 5738-14-7, the publication is Journal of the American Chemical Society (2011), 133(39), 15316-15319, database is CAplus and MEDLINE.

Bioorthogonal reactions suitable for functionalization of genetically or metabolically encoded alkynes, for example, copper-catalyzed azide-alkyne cycloaddition reaction (“click chem.”), have provided chem. tools to study biomol. dynamics and function in living systems. Despite its prominence in organic synthesis, copper-free Sonogashira cross-coupling reaction suitable for biol. applications has not been reported. In this work, the authors report the discovery of a robust aminopyrimidine-palladium(II) complex for copper-free Sonogashira cross-coupling that enables selective functionalization of a homopropargylglycine (HPG)-encoded ubiquitin protein in aqueous medium. A wide range of aromatic groups including fluorophores and fluorinated aromatic compounds can be readily introduced into the HPG-containing ubiquitin under mild conditions with good to excellent yields. The suitability of this reaction for functionalization of HPG-encoded ubiquitin in Escherichia coli was also demonstrated. The high efficiency of this new catalytic system should greatly enhance the utility of Sonogashira cross-coupling in bioorthogonal chem.

Journal of the American Chemical Society published new progress about 5738-14-7. 5738-14-7 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Alcohol,Pyrimidine, name is 2-(Dimethylamino)pyrimidine-4,6-diol, and the molecular formula is C6H9N3O2, Synthetic Route of 5738-14-7.

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

Lin, Cui-Hua published the artcile2-Amino-4,6-dimethoxypyrimidin-1-ium 2,2-dichloroacetate, Product Details of C4H3Cl2N3, the publication is Acta Crystallographica, Section E: Structure Reports Online (2012), 68(6), o1898, database is CAplus and MEDLINE.

In the title salt, C₆H₁₀N₃O₂⁺·C₂HCl₂O₂^–, two cations and two anions are linked by N-H···O hydrogen bonds, forming chains along the c axis. Crystallog. data are given.

Acta Crystallographica, Section E: Structure Reports Online 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, Product Details of C4H3Cl2N3.

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

Soukarieh, Fadi published the artcileHit identification of new potent PqsR antagonists as inhibitors of quorum sensing in planktonic and biofilm grown Pseudomonas aeruginosa, HPLC of Formula: 105130-26-5, the publication is Frontiers in Chemistry (Lausanne, Switzerland) (2020), 00204, database is CAplus and MEDLINE.

Current treatments for Pseudomonas aeruginosa infections are becoming less effective because of the increasing rates of multi-antibiotic resistance. Pharmacol. targeting of virulence through inhibition of quorum sensing (QS) dependent virulence gene regulation has considerable therapeutic potential. In P. aeruginosa, the pqs QS system regulates the production of multiple virulence factors as well as biofilm maturation and is a promising approach for developing antimicrobial adjuvants for combating drug resistance. In this work, we report the hit optimization for a series of potent novel inhibitors of PqsR, a key regulator of the pqs system, bearing a 2-((5-methyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)thio) acetamide scaffold. The initial hit compound 7 (PAO1-L IC₅₀ 0.98 ± 0.02 μM, PA14 inactive at 10 μM) was obtained through a virtual screening campaign performed on the PqsR ligand binding domain using the University of Nottingham Managed Chem. Compound Collection. Hit optimization gave compounds with enhanced potency against strains PAO1-L and PA14, evaluated using P. aeruginosa pqs-based QS bioreporter assays. Compound 40 (PAO1-L IC₅₀ 0.25 ± 0.12 μM, PA14 IC₅₀ 0.34 ± 0.03 μM) is one of the most potent PqsR antagonists reported showing significant inhibition of P. aeruginosa pyocyanin production and pqs system signaling in both planktonic cultures and biofilms. The co-crystal structure of 40 with the PqsR ligand binding domain revealed the specific binding interactions occurring between inhibitor and this key regulatory protein.

Frontiers in Chemistry (Lausanne, Switzerland) published new progress about 105130-26-5. 105130-26-5 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Benzene,Ether, name is 4-(2-Pyrimidinyloxy)aniline, and the molecular formula is C10H20O2, HPLC of Formula: 105130-26-5.

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

Chen, Xuwang published the artcileNovel piperidinylamino-diarylpyrimidine derivatives with dual structural conformations as potent HIV-1 non-nucleoside reverse transcriptase inhibitors, HPLC of Formula: 56-05-3, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(24), 6593-6597, database is CAplus and MEDLINE.

A series of novel piperidinylamino-diarylpyrimidine (pDAPY) derivatives with dual structural conformations was designed through a mol. hybridization strategy and expected to bind into the non-nucleoside inhibitor binding pocket (NNIBP) of HIV-1 RT in a flexible manner. A cell-based antiviral screening assay showed that some compounds were active against both wild-type and drug-resistant mutant virus strains (K103N+Y181C RT) of HIV-1, (4-(2-(4-cyanophenylamino)-6-(1-(pyridin-4-yl-methyl)piperidin-4-yl-amino)pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile with EC₅₀ = 0.047 and 4.6 μM, selectivity index = 2145 and 22, resp.). Mol. simulation studies indicated that 4-(2-(4-cyanophenylamino)-6-(1-(pyridin-4-yl-methyl)piperidin-4-ylamino)pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile could maintain the key hydrophobic interaction and hydrogen bonds with the NNIBP of two RT/ligand complexes. In particular, it could simultaneously occupy the protein/solvent interface and the entrance channel. Exploring these hybrid mols. with dual binding conformations might provide optional chem. scaffolds as novel HIV-1 reverse transcriptase inhibitors (HIV-1 NNRTIs).

Bioorganic & Medicinal Chemistry Letters 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, HPLC of Formula: 56-05-3.

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

Li, Shasha published the artcileSolubility Measurement and Modeling of 2-Amino-4,6-dichloropyrimidine in Ten Pure Solvents and (Ethyl Acetate + Ethanol) Solvent Mixtures, Synthetic Route of 56-05-3, the publication is Journal of Chemical & Engineering Data (2018), 63(10), 3715-3726, database is CAplus.

The basis of purification and further theor. studies of 2-amino-4,6-dichloropyrimidine is the solubility and solution thermodn. in different solvents. In this paper, the solubility of 2-amino-4,6-dichloropyrimidine in 10 neat solvents (methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, Et acetate, 1,4-dioxane, toluene, and cyclohexane) and binary liquid mixtures (Et acetate + ethanol) was measured by the isothermal saturation method at temperatures range from 278.15 to 318.15 K, at p = 101.2 kPa. High-performance liquid chromatog. (HPLC) was used to analyze the solubility of 2-amino-4,6-dichloropyrimidine in selected solvents. To sum up, the equilibrium mole fraction solubility was highest in 1,4-dioxane (2.619 × 10^-2 at 318.15 K) and lowest in cyclohexane (0.02238 × 10^-2 at 318.15 K), and ranked as 1,4-dioxane (2.619 × 10^-2 at 318.15 K) > acetone (1.630 × 10^-2 at 318.15 K) > Et acetate (1.471 × 10^-2 at 318.15 K) > acetonitrile (0.5048 × 10^-2 at 318.15 K) > methanol (0.3888 × 10^-2 at 318.15 K) > ethanol (0.3391 × 10^-2 at 318.15 K) > n-propanol (0.3133 × 10^-2 at 318.15 K) > toluene (0.2737 × 10^-2 at 318.15 K) > isopropanol (0.2574 × 10^-2 at 318.15 K) > cyclohexane (0.02238 × 10^-2 at 318.15 K). The achieved solubility values in monosolvents were correlated by the modified Apelblat equation, λh equation, Wilson model, and NRTL model and in solvent mixtures by three cosolvency models including Jouyban-Acree model, van’t Hoff-Jouyban-Acree model, and Apelblat-Jouyban-Acree model. Calculated results fitted well with exptl. data. Consequently, for the monosolvents, the values of root-mean-square deviation (RMSD) and relative average deviation (RAD) were less than 0.58 × 10^-4 and 0.80%, resp., and for the binary solvent mixtures were 0.49 × 10^-4 and 0.46%. Furthermore, the Gibbs energy, mixing enthalpy, mixing entropy, activity coefficient at infinitesimal concentration (γ^∞₁) and reduced excess enthalpy (H^E,∞₁) in monosolvents, and dissolution property in mixed solvents were computed. The mixing process of 2-amino-4,6-dichloropyrimidine in the studied solvents was spontaneous and endothermic. The obtained solubility and thermodn. studies would be used to optimize the purification process of 2-amino-4,6-dichloropyrimidine.

Journal of Chemical & Engineering Data 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, Synthetic Route of 56-05-3.

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

Gustin, Darin J. published the artcileIdentification of potent, noncovalent fatty acid amide hydrolase (FAAH) inhibitors, Name: 2-Amino-4,6-dichloropyrimidine, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(8), 2492-2496, database is CAplus and MEDLINE.

Starting from a series of ureas that were determined to be mechanism-based inhibitors of FAAH, several spirocyclic ureas and lactams e. g., I were designed and synthesized. These efforts identified a series of novel, noncovalent FAAH inhibitors with in vitro potency comparable to known covalent FAAH inhibitors. The mechanism of action for these compounds was determined through a combination of SAR and co-crystallog. with rat FAAH.

Bioorganic & Medicinal Chemistry Letters 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, Name: 2-Amino-4,6-dichloropyrimidine.

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

Wei, Xia published the artcileSelectable and releasable noncovalent functionalization of semiconducting SWCNTs by biethynyl-2,5-bis(dodecoxy)benzene unit-containing conjugated copolymers, Computed Properties of 56-05-3, the publication is Macromolecular Chemistry and Physics (2020), 221(13), 2000086, database is CAplus.

A rigid structural unit diethynyl-2,5-bis(dodecoxy)benzene (DDB) is proposed to functionalize single-walled carbon nanotubes (SWCNTs) with the assistance of pyrimidine ring. The effectiveness of conjugated polymer extraction of semiconducting SWCNTs is demonstrated by absorption and Raman spectroscopy. The protonated pyrimidine ring by the trifluoroacetic acid is used to reduce the interaction between polymer and SWCNTs that the bound wrapping polymer can be removed from the sorted SWCNTs, and mol. dynamics simulations of the binding ability of DDB and pyrimidine units to SWCNTs are conducted to further illustrate the strong binding ability of DDB units to SWCNTs. Therefore, this work provides an effective structural and theor. reference for polymer separation or modification of semiconducting SWCNTs.

Macromolecular 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 C8H5F3O3, Computed Properties of 56-05-3.

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

Huang, Pan published the artcileDiscovery of a Dual Tubulin Polymerization and Cell Division Cycle 20 Homologue Inhibitor via Structural Modification on Apcin, Recommanded Product: 2-Amino-4,6-dichloropyrimidine, the publication is Journal of Medicinal Chemistry (2020), 63(9), 4685-4700, database is CAplus and MEDLINE.

Apcin is one of the few compounds that have been previously reported as a Cdc20 specific inhibitor, although Cdc20 is a very promising drug target. We reported here the design, synthesis, and biol. evaluations of 2,2,2-trichloro-1-aryl carbamate derivatives as Cdc20 inhibitors. Among these derivatives, compound 9f(I) was much more efficient than the pos. compound apcin in inhibiting cancer cell growth, but it had approx. the same binding affinity with apcin in SPR assays. It is possible that another mechanism of action might exist. Further evidence demonstrated that compound 9f also inhibited tubulin polymerization, disorganized the microtubule network, and blocked the cell cycle at the M phase with changes in the expression of cyclins. Thus, it induced apoptosis through the activation of caspase-3 and PARP. In addition, compound 9f inhibited cell migration and invasion in a concentration-dependent manner. These results provide guidance for developing the current series as potential new anticancer therapeutics.

Journal of Medicinal 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 C4H3Cl2N3, Recommanded Product: 2-Amino-4,6-dichloropyrimidine.

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

Guz, Nathan R. published the artcileProcess Development and Multikilogram Syntheses of XL228 Utilizing a Regioselective Isoxazole Formation and a Selective S_nAr Reaction to a Pyrimidine Core, Quality Control of 56-05-3, the publication is Organic Process Research & Development (2013), 17(8), 1066-1073, database is CAplus.

Route scouting, process development, and multikilogram syntheses of an IGF-1R/Src/Bcr-Abl inihibitor are reported. Key aspects of the developed route are a regioselective [3 + 2] isoxazole formation on a pyrimidine core and a selective S_nAr addition of an aryl amine to a sym. dichloro substituted pyrimidine. The route contains six synthetic steps and was demonstrated twice on scale, delivering 4.6 and 11.2 kg (25% and 16% overall yield), for Phase I clin. studies.

Organic Process Research & Development 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

Huang, Luyi published the artcileDiscovery of Pyrrolo[3,2-d]pyrimidin-4-one Derivatives as a New Class of Potent and Cell-Active Inhibitors of P300/CBP-Associated Factor Bromodomain, Category: pyrimidines, the publication is Journal of Medicinal Chemistry (2019), 62(9), 4526-4542, database is CAplus and MEDLINE.

Herein, we report the discovery of a series of new P300/CBP-associated factor (PCAF) bromodomain (BRD) inhibitors, which were obtained through a hit discovery process and subsequent structure-based optimization and structure-activity relationship analyses toward a retrieved hit compound (12). Among these inhibitors, (R,R)-36n is the most potent one with an IC₅₀ of 7 nM in homogeneous time-resolved fluorescence assay and a K_D of 78 nM in isothermal titration calorimetry assay. This compound also exhibited activity against GCN5 and FALZ, but weak or no activity against other 29 BRD proteins and 422 kinases, indicating considerable selectivity. X-ray cocrystal structure anal. revealed the mol. interaction mode and the precise stereochem. required for bioactivity. Cellular activity, preliminary RNA-seq anal., and pharmacokinetic properties were also examined for this compound Collectively, this study provides a versatile tool mol. to explore mol. mechanisms of PCAF BRD regulation and also offers a new lead compound for drug discovery targeting PCAF.

Journal of Medicinal Chemistry 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, Category: pyrimidines.

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