Tag: M.W=150-200

Peng, Cheng published the artcileInhibitor development of MTH1 via high-throughput screening with fragment based library and MTH1 substrate binding cavity, Product Details of C4H3Cl2N3, the publication is Bioorganic Chemistry (2021), 104813, database is CAplus and MEDLINE.

MutT Homolog 1 (MTH1) has been proven to hydrolyze oxidized nucleotide triphosphates during DNA repair. It can prevent the incorporation of wrong nucleotides during DNA replication and mitigate cell apoptosis. In a cancer cell, abundant reactive oxygen species can lead to substantial DNA damage and DNA mutations by base-pairing mismatch. MTH1 could eliminate oxidized dNTP and prevent cancer cells from entering cell death. Therefore, inhibition of MTH1 activity is considered to be an anti-cancer therapeutic target. In this study, high-throughput screening techniques were combined with a fragment-based library containing 2,313 compounds, which were used to screen for lead compounds with MTH1 inhibitor activity. Four compounds with MTH1 inhibitor ability were selected, and compound MI0639 was found to have the highest effective inhibition. To discover the selectivity and specificity of this action, several derivatives based on the MTH1 and MI0639 complex structure were synthesized. We compared 14 complex structures of MTH1 and the various compounds in combination with enzymic inhibition and thermodn. anal. Nanomolar-range IC50 inhibition abilities by enzyme kinetics and Kd values by thermodn. anal. were obtained for two compounds, named MI1020 and MI1024. Based on structural information and compound optimization, we aim to provide a strategy for the development of MTH1 inhibitors with high selectivity and specificity.

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, Product Details of C4H3Cl2N3.

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

Li, Nan published the artcileCopper-Free Sonogashira Cross-Coupling for Functionalization of Alkyne-Encoded Proteins in Aqueous Medium and in Bacterial Cells, Safety of 2-Amino-4,6-dichloropyrimidine, 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 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

Gad, Helge published the artcileMTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool, Name: 2-Amino-4,6-dichloropyrimidine, the publication is Nature (London, United Kingdom) (2014), 508(7495), 215-221, database is CAplus and MEDLINE.

Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, the authors show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. The authors validate MTH1 as an anticancer target in vivo and describe small mols. TH287 (I) and TH588 (II) as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.

Nature (London, 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, Name: 2-Amino-4,6-dichloropyrimidine.

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

Suda, Atsushi published the artcileDesign and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors, Quality Control of 56-05-3, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(2), 1136-1141, database is CAplus and MEDLINE.

Macrocyclic compounds bearing a 2-amino-6-arylpyrimidine moiety were identified as potent heat shock protein 90 (Hsp90) inhibitors by modification of 2-amino-6-aryltriazine derivative (CH5015765). We employed a macrocyclic structure as a skeleton of new inhibitors to mimic the geldanamycin-Hsp90 interactions. Among the identified inhibitors, CH5164840 showed high binding affinity for N-terminal Hsp90α (K _d = 0.52 nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC₅₀ = 0.15 μM, NCI-N87 IC₅₀ = 0.066 μM). CH5164840 displayed high oral bioavailability in mice (F = 70.8%) and potent antitumor efficacy in a HCT116 human colorectal cancer xenograft model (tumor growth inhibition = 83%).

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 C20H28BNO5, Quality Control of 56-05-3.

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

Farand, Julie published the artcileDiscovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation, Related Products of pyrimidines, the publication is ACS Medicinal Chemistry Letters (2020), 11(3), 358-364, database is CAplus and MEDLINE.

We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncol. target, culminating in target (in)validation. Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC₅₀ = 0.043 nM). Cocrystn. of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramol. hydrogen bond and polar interactions with residues Gly34 and Asp120. Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC₅₀ = 0.49 nM). Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat. Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small mol. inhibition was studied. Based on our findings, we were unable to provide evidence to further pursue MTH1 as an oncol. target.

ACS 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, Related Products of pyrimidines.

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

Zidek, Zdenek published the artcileDual inhibition of nitric oxide and prostaglandin E₂ production by polysubstituted 2-aminopyrimidines, HPLC of Formula: 56-05-3, the publication is Nitric Oxide (2016), 48-56, database is CAplus and MEDLINE.

The present in vitro experiments demonstrate inhibitory effects of polysubstituted 2-aminopyrimidines on high output production of nitric oxide (NO) and prostaglandin E₂ (PGE₂) stimulated by interferon-γ and lipopolysaccharide (LPS) in peritoneal macrophages of mouse and rat origin. PGE₂ production was inhibited also in LPS-activated human peripheral blood mononuclear cells. A tight dependence of the suppressive activities on chem. structure of pyrimidines was observed Derivatives containing hydroxyl groups at the C-4 and C-6 positions of pyrimidine ring were devoid of any influence on NO and PGE₂. Remarkable inhibitory potential was acquired by the replacement of hydroxyl groups with chlorine, the 4,6-dichloro derivatives being more effective than the monochloro analogs. The effects were further intensified by modification of the amino group at the C-2 position, changing it to the (N,N-dimethylamino)methyleneamino or the formamido ones. There was no substantial difference in the expression of NO-inhibitory effects among derivatives containing distinct types of substituents at the C-5 position (hydrogen, Me, Et, Pr, Bu, Ph, and benzyl). In contrast to NO, larger substituents then Me were required to inhibit PGE₂ production Overall, no significant correlation between the extent of NO and PGE₂ suppression was observed The IC₅₀s of derivatives with the strongest effects on both NO and PGE₂ were within the range of 2-10 μM. Their NO-inhibitory potential of pyrimidines was stronger than that of non-steroidal anti-inflammatory drugs (NSAIDs) aspirin and indomethacin. The PGE₂-inhibitory effectiveness of pyrimidines was about the same as that of aspirin, but weaker as compared to indomethacin. The NO- and PGE₂-inhibitory activity of tested pyrimidines has been found associated with decreased expression of iNOS mRNA and COX-2 mRNA, resp., and with post-translation interactions. Selected NO-/PGE₂-inhibitory derivatives decreased severity of intestinal inflammation in murine model of ulcerative colitis.

Nitric Oxide 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 C50H65O4P, HPLC of Formula: 56-05-3.

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

Yi, Wonhui published the artcileSynthesis and inhibitory activity on NF-κB activation of chroman-2-carboxylic acid N-heteroarylamide derivatives, HPLC of Formula: 56-05-3, the publication is Yakhak Hoechi (2012), 56(3), 186-190, database is CAplus.

Nuclear factor-κB (NF-κB) has been considered as one of the major targets for therapeutic agents of diverse human diseases. In the previous studies, 6-hydroxy-7-methoxychroman-2-carboxylic acid N-phenylamide (KL-1156) and chroman-2-carboxylic acid N-(4-chlorophenyl)amide were identified as good inhibitors of NF-κB activation. In this continuous study, we describe the synthesis and NF-κB inhibitory activities of chroman derivatives containing N-heteroaryl groups for exploration of SAR (structure-activity relationship). In addition, inhibitory effects of cell proliferation are evaluated against human cancer cell lines (NCI-H23 and PC-3).

Yakhak Hoechi 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 C15H10O2, HPLC of Formula: 56-05-3.

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

Bennett, Frank published the artcilePyridofuran substituted pyrimidine derivatives as HCV replication (replicase) inhibitors, Related Products of pyrimidines, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(15), 5144-5149, database is CAplus and MEDLINE.

Introduction of nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzofuran inhibitor I (X = CH), resulted in the discovery of the more potent pyridofuran analog I (X = N). Subsequent introduction of small alkyl and alkoxy ligands into the pyridine ring resulted in further improvements in replicon potency. Replacement of the 4-chloro moiety on the pyrimidine core with a Me group, and concomitant mono-alkylation of the C-2 amino moiety resulted in the identification of several inhibitors with desirable characteristics. Nucleoside inhibitor II (R = CF₃, R¹ = Et, R² = H; R = cyclopropyl, R¹ = OEt, R² = Me), from the mono-substituted pyridofuran and inhibitor 50 from the disubstituted series displayed excellent potency, selectivity (GAPDH/MTS CC₅₀) and PK parameters in all species studied, while the selectivity in the thymidine incorporation assay (DNA·CC₅₀) was low.

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, Related Products of pyrimidines.

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

Patel, Navin B. published the artcileSynthesis of newer 5-benzylidene-2,4-thiazolidinediones as potential antimicrobials, Name: 2-Amino-4,6-dichloropyrimidine, the publication is Indian Journal of Research in Pharmacy and Biotechnology (2014), 2(1), 993-1001, 9 pp., database is CAplus.

A series of 5-benzylidene-2,4-thiazolidinediones I (R = 5-methylthiazol-2-ylamino, 6-fluorobenzothiazol-2-ylamino, 6-nitrobenzothiazol-2-ylamino, etc.) were synthesized and evaluated for antimycobacterial and antimicrobial activity. In vitro antimycobacterial activity was carried out against (M. tuberculosis) H₃₇Rv strain using Lowenstein-Jensen medium and antimicrobial activity against two Gram pos. bacteria (S. aureus, S. pyogenes), two Gram neg. bacteria (E. coli, P. aeruginosa) and three fungal species (C. albicans, A. niger, A. clavatus) using the broth microdilution method. The compounds I (R = 5-methylthiazol-2-amino, 6-fluorobenzothiazol-2-ylamino, 4-nitrobenzothiazol-2-ylamino, 5-nitrobenzothiazol-2-ylamino, 6-methylbenzothiazol-2-ylamino, 4,6-dimethoxypyrimidin-2-ylamino) exhibited promising antimicrobial activity, whereas compounds I (R = 6-methylbenzothiazol-2-ylamino) showed very good antimycobacterial activity.

Indian Journal of Research in Pharmacy and Biotechnology 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

Rayavarapu, Suresh published the artcileA modular approach towards functionalized highly stable self-complementary quadruple hydrogen bonded systems, Product Details of C4H3Cl2N3, the publication is Organic & Biomolecular Chemistry (2017), 15(47), 10087-10094, database is CAplus and MEDLINE.

Self-complementary quadruple hydrogen bonded systems have shown potential as key building blocks for developing various supramol. polymers. Opportunities for the introduction of multiple functionalities would further augment, in principle, their application potential. Herein, we report a novel modular approach to simultaneously introduce two closely aligned side chains into AADD-type self-complementary quadruple hydrogen-bonding systems. Dithiane-tethered ureidopyrimidinone has been used as a reactive intermediate to efficiently attach closely aligned side chains by simply reacting with amines to form highly stable mol. duplexes. These duplexes featuring AADD-type arrays of hydrogen bonding codes are highly stable in non-polar solvents (K_dim > 1.9 x 10⁷ M^-1 in CDCl₃) as well as in polar solvents (K_dim > 10⁵ in 10% DMSO-d₆/CDCl₃). Another notable feature of these self-assembling systems is their insensitivity to prototropy-related issues owing to their prototropic degeneracy, which will enhance their application potential in supramol. chem.

Organic & Biomolecular 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, Product Details of C4H3Cl2N3.

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