Tag: M.W=150-200

Odell, Luke R. published the artcilePyrimidyn-Based Dynamin Inhibitors as Novel Cytotoxic Agents, COA of Formula: C4H3Cl2N3, the publication is ChemMedChem (2022), 17(1), e202100560, database is CAplus and MEDLINE.

Five focused libraries of pyrimidine-based dynamin GTPase inhibitors, in total 69 compounds were synthesized, and their dynamin inhibition and broad-spectrum cytotoxicity examined Dynamin plays a crucial role in mitosis, and as such inhibition of dynamin was expected to broadly correlate with the observed cytotoxicity. The pyrimidines synthesized ranged from mono-substituted to trisubstituted. The highest levels of dynamin inhibition were noted with di- and tri- substituted pyrimidines, especially those with pendent amino alkyl chains. Short chains and simple heterocyclic rings reduced dynamin activity. There were three levels of dynamin activity noted: 1-10, 10-25 and 25-60 μM. Screening of these compounds in a panel of cancer cell lines: SW480 (colon), HT29 (colon), SMA (spontaneous murine astrocytoma), MCF-7 (breast), BE2-C (glioblastoma), SJ-G2 (neuroblastoma), MIA (pancreas), A2780 (ovarian), A431 (skin), H460 (lung), U87 (glioblastoma) and DU145 (prostate) cell lines reveal a good correlation between the observed dynamin inhibition and the observed cytotoxicity. The most active analogs (31 a,b) developed returned average GI₅₀ values of 1.0 and 0.78 μM across the twelve cell lines examined These active analogs were: N²-(3-dimethylaminopropyl)-N⁴-dodecyl-6-methylpyrimidine-2,4-diamine (31 a) and N⁴-(3-dimethylaminopropyl)-N²-dodecyl-6-methylpyrimidine-2,4-diamine (31 b).

ChemMedChem 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, COA of Formula: C4H3Cl2N3.

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

Cheng, Yuan published the artcileSupramolecular structures constructed by 3-(2-amino-6-chloropyrimidin-4-yl)-1,1-dimethylprop-2-yn-1-ol monohydrate and 3-[2-amino-6-(3-hydroxy-3,3-dimethylprop-1-yn-1-yl)pyrimidin-4-yl]-1,1-dimethylprop-2-yn-1-ol, Safety of 2-Amino-4,6-dichloropyrimidine, the publication is Acta Crystallographica, Section C: Crystal Structure Communications (2011), 67(7), o244-o248, database is CAplus and MEDLINE.

The mol. of 3-(2-amino-6-chloropyrimidin-4-yl)-1,1-dimethylprop-2-yn-1-ol monohydrate, C₉H₁₀ClN₃O·H₂O, (I), shows a very polarized mol.-electronic structure, while the polarization is slight for 3-[2-amino-6-(3-hydroxy-3,3-dimethylprop-1-yn-1-yl)pyrimidin-4-yl]-1,1-dimethylprop-2-yn-1-ol, C₁₄H₁₇N₃O₂, (II). In the supramol. structure of (I), a combination of hard N-H…N H bonds and soft C-H…N H bonds creates a mol. column. Aromatic π-π stackings between the pyrimidine rings stabilize the column with perpendicular and centroid-centroid distances of 3.283(3) and 3.588(1) Å, resp. Short Cl…Cl contacts further link neighboring mol. columns, creating a hydrophilic tube in which H₂O mols. are fixed by various H bonds. In the packing of (II), a 1-dimensional mol. chain is formed through several contacts involving hard N-H…O(N) and O-H…O(N) and soft C-H…O H bonds. Interchain O-H…O H bonds link the chains giving a two-dimensional stepped network. It is anticipated that study of the influence of H bonding on the patterns of base pairing and mol. packing in aminopyrimidine structures will shed significant light on nucleic acid structures as well as their functions. Crystallog. data are given.

Acta Crystallographica, Section C: Crystal Structure Communications 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

Hauke, Sebastian published the artcileTwo-Step Protein Labeling Utilizing Lipoic Acid Ligase and Sonogashira Cross-Coupling, Quality Control of 5738-14-7, the publication is Bioconjugate Chemistry (2014), 25(9), 1632-1637, database is CAplus and MEDLINE.

Labeling proteins in their natural settings with fluorescent proteins or protein tags often leads to problems. Despite the high specificity, these methods influence the natural functions due to the rather large size of the proteins used. Here the authors present a two-step labeling procedure for the attachment of various fluorescent probes to a small peptide sequence (13 amino acids) using enzyme-mediated peptide labeling in combination with palladium-catalyzed Sonogashira cross-coupling. The authors identified p-iodophenyl derivatives from a small library that can be covalently attached to a lysine residue within a specific 13-amino-acid peptide sequence by Escherichia coli lipoic acid ligase A (LplA). The derivatization with p-iodophenyl subsequently served as a reactive handle for bioorthogonal transition metal-catalyzed Sonogashira cross-coupling with alkyne-functionalized fluorophores on both the peptide as well as on the protein level. The authors’ two-step labeling strategy combines high selectivity of enzyme-mediated labeling with the chemoselectivity of palladium-catalyzed Sonogashira cross-coupling.

Bioconjugate Chemistry 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, Quality Control of 5738-14-7.

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

Wang, Li-zhong published the artcileSynthesis of 9-ethylguanine, Related Products of pyrimidines, the publication is Huaxue Shiji (2016), 38(2), 189-192, database is CAplus.

Starting from di-Et malonate and guanidine hydrochloride, condensation in basic conditions gave the intermediate 2-amino-4,6-dihydroxypyrimidine. Then, in the presence of triethylamine as the acid-trapping agent and at a temperature of 80°C, 2-amino-6-chloropyrimidin-4(3H)-one was prepared by an excess of phosphorus oxychloride and the decomposition of sodium hydroxide, and then after ethylamino, nitrosation and cyclization, obtain the target product. Though optimizing the reaction conditions, the optimal parameters are obtained. The reaction route is simple, feasible process routes. The product through the m.p., IR, ¹HNMR and ¹³CNMR was confirmed.

Huaxue Shiji 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 C38H74Cl2N2O4, Related Products of pyrimidines.

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

Grieco, Ilenia published the artcileDeveloping novel classes of protein kinase CK1δ inhibitors by fusing [1,2,4]triazole with different bicyclic heteroaromatic systems, Recommanded Product: 2-Amino-4,6-dichloropyrimidine, the publication is European Journal of Medicinal Chemistry (2021), 113331, database is CAplus and MEDLINE.

New series of [1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-a][1,3,5]triazines was developed. Some crucial interactors have been identified, such as the presence of a free amino group able to interact with the residues of the hinge region at the 5- and 7- positions of the [1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-a][1,3,5]triazine scaffolds, resp.; or the presence of a 3-hydroxyphenyl or 3,5-dihydroxyphenyl moiety at the 2- position of both nuclei. Mol. modeling studies identified the key interactions involved in the inhibitor-protein recognition process that appropriately fit with the outlined structure-activity relationship. Considering the fact that the CK1 protein kinase is involved in various pathologies in particular of the central nervous system, the interest in the development of new inhibitors permeable to the blood-brain barrier represents today an important goal in the pharmaceutical field. The best potent compound of the series is the 5-(7-amino-5-(benzylamino)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-2-yl)benzen-1,3-diol (IC₅₀ = 0.18μM) that was predicted to have an intermediate ability to cross the membrane in vitro assay and represents an optimal starting point to both studies the therapeutic value of protein kinase CK1δ inhibition and to develop new more potent derivatives

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, Recommanded Product: 2-Amino-4,6-dichloropyrimidine.

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

Cao, Jian published the artcileMultiplexed CuAAC Suzuki-Miyaura Labeling for Tandem Activity-Based Chemoproteomic Profiling, Recommanded Product: 2-(Dimethylamino)pyrimidine-4,6-diol, the publication is Analytical Chemistry (Washington, DC, United States) (2021), 93(4), 2610-2618, database is CAplus and MEDLINE.

Mass-spectrometry-based chemoproteomics has enabled the rapid and proteome-wide discovery of functional and potentially ′druggable′ hotspots in proteins. While numerous transformations are now available, chemoproteomic studies still rely overwhelmingly on copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) or ′click′ chem. The absence of bio-orthogonal chemistries that are functionally equivalent and complementary to CuAAC for chemoproteomic applications has hindered the development of multiplexed chemoproteomic platforms capable of assaying multiple amino acid side chains in parallel. Here, we identify and optimize Suzuki-Miyaura cross-coupling conditions for activity-based protein profiling and mass-spectrometry-based chemoproteomics, including for target deconvolution and labeling site identification. Uniquely enabled by the observed orthogonality of palladium-catalyzed cross-coupling and CuAAC, we combine both reactions to achieve dual labeling. Multiplexed targeted deconvolution identified the protein targets of bifunctional cysteine- and lysine-reactive probes.

Analytical Chemistry (Washington, DC, United States) 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, Recommanded Product: 2-(Dimethylamino)pyrimidine-4,6-diol.

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

Volkov, Oleg A. published the artcileSpecies-Selective Pyrimidineamine Inhibitors of Trypanosoma brucei S-Adenosylmethionine Decarboxylase, Computed Properties of 56-05-3, the publication is Journal of Medicinal Chemistry (2018), 61(3), 1182-1203, database is CAplus and MEDLINE.

New therapeutic options are needed for treatment of human African trypanosomiasis (HAT) caused by protozoan parasite Trypanosoma brucei. S-Adenosylmethionine decarboxylase (AdoMetDC) is an essential enzyme in the polyamine pathway of T. brucei. Previous attempts to target this enzyme were thwarted by the lack of brain penetration of the most advanced series. Herein, the authors describe a T. brucei AdoMetDC inhibitor series based on a pyrimidineamine pharmacophore that the authors identified by target-based high-throughput screening. The pyrimidineamines showed selectivity for T. brucei AdoMetDC over the human enzyme, inhibited parasite growth in whole-cell assay, and had good predicted blood-brain barrier penetration. The medicinal chem. program elucidated structure-activity relationships within the series. Features of the series that were required for binding were revealed by determining the x-ray crystal structure of TbAdoMetDC bound to one analog. The pyrimidineamine series provides a novel starting point for an anti-HAT lead optimization.

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 C8H7NO4, Computed Properties of 56-05-3.

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

Noda, Hidetoshi published the artcileA C4N4 Diaminopyrimidine Fluorophore, COA of Formula: C4H3Cl2N3, the publication is Chemistry – A European Journal (2019), 25(17), 4299-4304, database is CAplus and MEDLINE.

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.

Chemistry – A European Journal 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, COA of Formula: C4H3Cl2N3.

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

Murata, Tsuyoshi published the artcileSingle-component organic conductors based on neutral betainic radicals of N-methyl substituted dioxo- and aminooxo-pyrimido-fused TTFs, Related Products of pyrimidines, the publication is Synthetic Metals (2008), 158(12), 497-505, database is CAplus.

New dioxo- and aminooxo-pyrimido-fused tetrathiafulvalene (TTF) derivatives, whose pyrimido-rings are substituted by Me group, were synthesized. In the crystal structures of their tetrabutylammonium salts, complementary hydrogen-bonds inherent in pyrimido-fused TTF derivatives were inhibited by the Me substitution, and the crystals were constructed by the segregated motifs of cations and anions. Betainic radicals prepared by one-electron oxidation of tetrabutylammonium salts exhibited relatively high conductivities (ca. 10^-4 S cm^-1 at room temperature) as single-component organic mols. The optical measurement of betainic radicals showed considerably low-energy charge-transfer absorption between radical mols. compared to those of conventional TTF systems, indicating the reduction of on-site Coulomb repulsion.

Synthetic Metals 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, Related Products of pyrimidines.

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

Norcross, Neil R. published the artcileTrisubstituted Pyrimidines as Efficacious and Fast-Acting Antimalarials, Synthetic Route of 56-05-3, the publication is Journal of Medicinal Chemistry (2016), 59(13), 6101-6120, database is CAplus and MEDLINE.

In this paper we describe the optimization of a phenotypic hit against Plasmodium falciparum, based on a trisubstituted pyrimidine scaffold. This led to compounds with good pharmacokinetics and oral activity in a P. berghei mouse model of malaria. The most promising compound I showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a day for 4 days in the P. berghei mouse model of malaria. It also demonstrated a rapid rate of clearance of the erythrocytic stage of P. falciparum in the SCID mouse model with an ED₉₀ of 11.7 mg/kg when dosed orally. Unfortunately, the compound is a potent inhibitor of cytochrome P 450 enzymes, probably due to a 4-pyridyl substituent. Nevertheless, this is a lead mol. with a potentially useful antimalarial profile, which could either be further optimized or be used for target hunting.

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