Tag: M.W=150-200

Zhao, Matthew M. published the artcileProcess Development of Tryptophan Hydroxylase Inhibitor LX1031, a Drug Candidate for the Treatment of Irritable Bowel Syndrome, Category: pyrimidines, the publication is Organic Process Research & Development (2020), 24(2), 261-273, database is CAplus.

Two process routes for LX1031 (I), a tryptophan hydroxylase inhibitor for the treatment of irritable bowel syndrome, were developed. They shared the same left-hand and right-hand starting materials as well as the penultimate intermediate. The chiral center in the left-hand moiety was established via a Noyori asym. hydrogenation of a trifluoromethyl aryl ketone. The right-hand boronate was prepared via a palladium-catalyzed borylation of L-tyrosine-derived aryl triflate. Union of these two fragments to the pyrimidine core, from the right- or left-hand side, constituted the first- and second-generation routes, resp. Removal of the Boc-protecting group from the penultimate intermediate gave LX1031. The challenges overcome in purification and isolation of the LX1031 zwitterion are also discussed. Both process routes were successfully performed on multikilogram scales to supply LX1031 API for the preclin. and 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 C10H18O4, Category: pyrimidines.

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

Beesu, Mallesh published the artcileHuman Toll-like Receptor (TLR) 8-Specific Agonistic Activity in Substituted Pyrimidine-2,4-diamines, Application In Synthesis of 56-05-3, the publication is Journal of Medicinal Chemistry (2016), 59(17), 8082-8093, database is CAplus and MEDLINE.

Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N⁴-butyl-5-iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed SAR study of this chemotype was undertaken. A Bu substituent at N⁴ was optimal, and replacement of the 5-iodo group with chloro, bromo, or fluoro groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from the previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N⁴-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6 and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favorable than other TLR8 agonists under evaluation.

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, Application In Synthesis of 56-05-3.

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

Patel, Navin B. published the artcileNew 2-benzylsulfanyl-nicotinic acid based 1,3,4-oxadiazoles: Their synthesis and biological evaluation, Synthetic Route of 56-05-3, the publication is European Journal of Medicinal Chemistry (2013), 677-687, database is CAplus and MEDLINE.

A novel series of 5-(2-benzylsulfanyl-pyridin-3-yl)-2-(substituted)-sulfanyl-1,3,4-oxadiazoles were synthesized from key intermediate 5-(2-benzylsulfanyl-pyridin-3-yl)-3H-[1,3,4]oxadiazole-2-thione. Nucleophilic substitution reactions with different electrophiles (E+), such as haloacetate and haloalkyl groups, were performed to get target compounds Compounds were characterized by NMR, mass, IR spectra and C, H, N analyses. All compounds were evaluated for their antimicrobial and antimycobacterial activities; selected analogs were screened for their anticancer activity on 60 tumor cell lines at single dose 1.00^-5 M. Unfortunately, none of the compounds showed a significant antitumor activity on 60 human tumor cell lines. However, compounds I and II with benzothiazole moiety (12.5 and 25 μg/mL) showed promising activity against Escherichia coli compared to ampicillin; compounds III, IV bearing triazole and morpholine, resp., showed promising antitubercular activity (25 μg/mL) compared to rifampicin.

European 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, Synthetic Route of 56-05-3.

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

Willwacher, Jens published the artcileSelective Metal-Site-Guided Arylation of Proteins, Category: pyrimidines, the publication is Journal of the American Chemical Society (2016), 138(28), 8678-8681, database is CAplus and MEDLINE.

We describe palladium-mediated S-arylation that exploits natural metal-binding motifs to ensure high site selectivity for a proximal reactive residue. This allows the chem. identification not only of proteins that bind metals but also the environment of the metal-binding site itself through proteomic anal. of arylation sites. The transformation is easy to perform under standard conditions, does not require the isolation of a reactive Ar-Pd complex, is broad in scope, and is applicable in cell lysates as well as to covalent inhibition/modulation of metal-dependent enzymic activity.

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 C6H13I, Category: pyrimidines.

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

Li, Nan published the artcileA Genetically Encoded Alkyne Directs Palladium-Mediated Protein Labeling on Live Mammalian Cell Surface, Name: 2-(Dimethylamino)pyrimidine-4,6-diol, the publication is ACS Chemical Biology (2015), 10(2), 379-384, database is CAplus and MEDLINE.

The merging of site-specific incorporation of small bioorthogonal functional groups into proteins via amber codon suppression with bioorthogonal chem. has created exciting opportunities to extend the power of organic reactions to living systems. A new alkyne amino acid can be site-selectively incorporated into mammalian proteins via a known orthogonal pyrrolysyl-tRNA synthetase/tRNA_CUA pair and directs an unprecedented, palladium-mediated cross-coupling reaction-driven protein labeling on live mammalian cell surface. A comparison study with the alkyne-encoded proteins in vitro indicated that this terminal alkyne is better suited for the palladium-mediated cross-coupling reaction than the copper-catalyzed click chem.

ACS Chemical Biology 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, Name: 2-(Dimethylamino)pyrimidine-4,6-diol.

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

Rajasekaran, S. published the artcileSynthesis and anti-denaturation activity of some substituted quinazolinone analogs, Safety of 2-Amino-4,6-dichloropyrimidine, the publication is International Journal of ChemTech Research (2012), 4(3), 1207-1211, database is CAplus.

In recent years there is a tremendous increase of inflammatory cases, leading to the design and development of newer anti-inflammatory agents. The reaction of 2-substituted phenyl-3-chloroacetamido quinazolin-4(3H)-ones with various 5-phenyl-1,3,4-oxadiazole-2-thiol and 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-thiol gave N-(4-oxo-2-substituted phenylquinazolin-3(4H)-yl)-2-[(5-aryl-1,3,4-oxadiazol-2-yl)sulfanyl] acetamides derivatives The reaction of 2-phenyl-3-chloroacetamido quinazolinone with various heteroaryl thiols and amines gave N-(4-oxo-2-Ph quinazolin-3(4H)-yl)-2-[(substituted amino/thiol)] acetamide derivatives The structure of all the compounds has been confirmed by IR, ¹HNMR, Mass spectral data and elemental anal. In vitro anti-inflammatory activity was performed by bovine serum albumin method. Some of the compounds have shown good antibacterial activity and few have shown moderate antioxidant activity compared to the standard drug.

International Journal of ChemTech Research 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, Safety of 2-Amino-4,6-dichloropyrimidine.

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

Kheria, Sanjeev published the artcileThree in one: prototropy-free highly stable AADD-type self-complementary quadruple hydrogen-bonded molecular duplexes with a built-in fluorophore, Application In Synthesis of 56-05-3, the publication is Chemical Communications (Cambridge, United Kingdom) (2017), 53(18), 2689-2692, database is CAplus and MEDLINE.

This communication reports an effective approach for addressing the prototropy-related problems in heterocycle-based AADD-type self-assembling systems by freezing their hydrogen-bonding codes, by utilizing intramol. bifurcated hydrogen bonding interactions. Using this strategy, we have also developed a hydroquinone-conjugated AADD-type self-assembling system adorned with three valuable features such as prototropy-free dimerization yielding single duplexes, high duplex stability and a built-in fluorophore, which would augment its application potential. The rational approach used herein to arrest prototropic shift may also find application elsewhere, wherein proton shift-mediated structural changes become a detrimental factor.

Chemical Communications (Cambridge, United Kingdom) 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, Application In Synthesis of 56-05-3.

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

Sana, Sravani published the artcileExploration of carbamide derived pyrimidine-thioindole conjugates as potential VEGFR-2 inhibitors with anti-angiogenesis effect, Synthetic Route of 56-05-3, the publication is European Journal of Medicinal Chemistry (2020), 112457, database is CAplus and MEDLINE.

Here combined the two pharmacophoric units (pyrimidine and thioindole) combined in a single entity via mol. hybridization strategy along with introduction of urea functionality at C2 position of pyrimidine to increase the efficiency of H-bonding interactions. Among the synthesized conjugates I [R¹ = morpholino, piperidin-1-yl, phenylamino, etc.; R² = Ph, 4-methoxyphenyl, 4-chlorophenyl, etc.] compound I [R¹ = pyrrolidin-1-yl; R² = 4-chlorophenyl] was found to exhibited significant IC₅₀ =5.85, 7.87, 6.41 and 10.43μM against MDA-MB-231 (breast), HepG2 (liver), A549 (lung) and PC-3 (prostate) cancer cell lines, resp. All these compounds I were further evaluated for their inhibitory activities against VEGFR-2 protein. The results specified that among the tested compounds, I [R¹ = morpholino, R² = 2-methyl-4-chlorophenyl; R¹ = piperidin-1-yl, R² = 2,5-dimethylphenyl; R¹ = pyrrolidin-1-yl, R² = 4-chlorophenyl; R¹ = pyrrolidin-1-yl, R² = 2-methyl-4-chlorophenyl, R¹ = 4-(pyridin-2-yl)piperazin-1-yl, R² = 2-methyl-4-chlorophenyl; R¹ = 4-benzylpiperazin-1-yl, R² = Ph, 4-methoxyphenyl; R¹ = cyclopropylamino, R² = 2-methyl-4-chlorophenyl] prominently suppressed VEGFR-2, with IC₅₀ values of 310-920 nM in association to the pos. control (210 nM). Angiogenesis inhibition was evident by tube formation assay in HUVECs and cell-invasion by transwell assay. The mechanism of cellular toxicity on MDA-MB-231 was found through depolarization of mitochondrial membrane potential, increased ROS production and subsequent DNA damage resulting in apoptosis induction. Moreover, clonogenic and wound healing assays designated the inhibition of colony formation and cell migration by I [R¹ = pyrrolidin-1-yl; R² = 4-chlorophenyl] in a dose-dependent manner. Mol. docking studies also shown that compound I [R¹ = pyrrolidin-1-yl; R² = 4-chlorophenyl] capably intermingled with catalytically active residues GLU-885, ASP-1046 of the VEGFR-2 through hydrogen-bonding interactions.

European 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, Synthetic Route of 56-05-3.

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

Sana, Sravani published the artcileCinnamide derived pyrimidine-benzimidazole hybrids as tubulin inhibitors: Synthesis, in silico and cell growth inhibition studies, Recommanded Product: 2-Amino-4,6-dichloropyrimidine, the publication is Bioorganic Chemistry (2021), 104765, database is CAplus and MEDLINE.

A new class of piperazine-linked cinnamide derivatives of benzimidazole-pyrimidine hybrids have been synthesized and their in vitro cytotoxicity profiles were explored on selected human cancer cell lines. Specifically, structural comparison of target hybrids with tubulin-DAMA-colchicine and tubulin-nocodazole complexes has exposed a deep position of benzimidazole ring into the αT5 loop. The utmost cytotoxicity has shown with an amine linker of benzimidazole-pyrimidine series, with toward A549 (lung cancer) cell line. The most potent compound in this series was 18i, which inhibited cancer cell growth at micromolar concentrations ranging 2.21-7.29μM. Flow cytometry studies disclosed that compound I inhibited the cells in G2/M phase of cell cycle. The most active compound I also inhibited tubulin polymerization with an IC50 of 5.72 ± 0.51μM. In vitro biol. anal. of compound I presented apoptosis induction on A549 cells with triggering of ROS generation and loss of mitochondrial membrane potential, resulting in DNA injury. In addition, compound I displayed impairment in cellular migration and inhibited the colony formation. Notably, the safety profile of most potent compound 18i was revealed by screening against normal human pulmonary epithelial cells (L132: IC50: 69.25 ± 5.95μM). The detailed binding interactions of compound I with tubulin was investigated by employing mol. docking, superimposition and free energy analyses.

Bioorganic 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

Hinton, Shante published the artcileDeoxy derivatives of L-like 5′-noraristeromycin, Related Products of pyrimidines, the publication is Tetrahedron Letters (2012), 53(14), 1753-1755, database is CAplus and MEDLINE.

Several base variations of 2′- and 3′-deoxy derivatives of (+)-4′-deoxy-5′-noraristeromycin have been prepared from enantiomerically pure precursors following standard purine nucleoside construction. These carbocyclic nucleosides were evaluated against hepatitis B virus (HBV) and found to be inactive. No cytotoxicity to the cell line was observed

Tetrahedron 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, Related Products of pyrimidines.

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