Tag: M.W=250-300

Beaufils, Florent published the artcile5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology, Recommanded Product: 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine, the publication is Journal of Medicinal Chemistry (2017), 60(17), 7524-7538, database is CAplus and MEDLINE.

Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). Here we describe the preclin. characterization of compound 1 (PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations No off-target interactions were detected for 1 in a wide panel of protein kinase, enzyme, and receptor ligand assays. Moreover, 1 did not bind tubulin, which was observed for the structurally related 4 (BKM120, buparlisib). Compound 1 is orally available, crosses the blood-brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Compound 1 demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. This, together with the compound’s safety profile, identifies 1 as a clin. candidate with a broad application range in oncol., including treatment of brain tumors or CNS metastasis. Compound 1 is currently in phase II clin. trials for advanced solid tumors and refractory lymphoma.

Journal of Medicinal Chemistry published new progress about 944401-58-5. 944401-58-5 belongs to pyrimidines, auxiliary class Trifluoromethyl,Pyrimidine,Fluoride,Boronic acid and ester,Amine,Boronate Esters,Boronic acid and ester,, name is 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine, and the molecular formula is C11H15BF3N3O2, Recommanded Product: 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine.

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

Chouikhi, Dalila published the artcileExpanding the Scope of PNA-Encoded Synthesis (PES): Mtt-Protected PNA Fully Orthogonal to Fmoc Chemistry and a Broad Array of Robust Diversity-Generating Reactions, Recommanded Product: 2-(4-((tert-Butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid, the publication is Chemistry – A European Journal (2012), 18(40), 12698-12704, database is CAplus and MEDLINE.

Nucleic acid-encoded libraries are emerging as an attractive and highly miniaturized format for the rapid identification of protein ligands. An important criterion in the synthesis of nucleic acid encoded libraries is the scope of reactions that can be used to introduce mol. diversity and devise divergent pathways for diversity-oriented synthesis (DOS). To date, the protecting group strategies that have been used in peptide nucleic acid (PNA) encoded synthesis (PES) have limited the choice of reactions used in the library synthesis to just a few prototypes. Herein, the describe the preparation of PNA monomers with a protecting group combination (Mtt/Boc) that is orthogonal to Fmoc-based synthesis and compatible with a large palette of reactions that have been productively used in DOS (palladium cross-couplings, metathesis, reductive amination, amidation, heterocycle formation, nucleophilic addition, conjugate additions, Pictet-Spengler cyclization). The authors incorporate γ-modifications in the PNA backbone that are known to enhance hybridization and solubility The authors demonstrate the robustness of this strategy with a PNA library synthesis that is characterized by MALDI MS anal. at every step.

Chemistry – A European Journal published new progress about 172405-16-2. 172405-16-2 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide, name is 2-(4-((tert-Butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid, and the molecular formula is C11H15N3O5, Recommanded Product: 2-(4-((tert-Butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid.

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

Hansen, Anna Mette published the artcileMicrowave-assisted solid-phase synthesis of antisense acpP peptide nucleic acid-peptide conjugates active against colistin- and tigecycline-resistant E. coli and K. pneumoniae, SDS of cas: 172405-16-2, the publication is European Journal of Medicinal Chemistry (2019), 134-145, database is CAplus and MEDLINE.

Recent discovery of potent antibacterial antisense PNA-peptide conjugates encouraged development of a fast and efficient synthesis protocol that facilitates structure-activity studies. The use of an Fmoc/Boc protection scheme for both PNA monomers and amino acid building blocks in combination with microwave-assisted solid-phase synthesis proved to be a convenient procedure for continuous assembly of antisense PNA-peptide conjugates. A validated antisense PNA oligomer (CTCATACTCT; targeting mRNA of the acpP gene) was linked to N-terminally modified drosocin (i.e., RXR-PRPYSPRPTSHPRPIRV; X = aminohexanoic acid) or to a truncated Pip1 peptide (i.e., RXRRXR-IKILFQNRRMKWKK; X = aminohexanoic acid), and determination of the antibacterial effects of the resulting conjugates allowed assessment of the influence of different linkers as well as differences between the L– and D-forms of the peptides. The drosocin-derived compound without a linker moiety exhibited highest antibacterial activity against both wild-type Escherichia coli and Klebsiella pneumoniae (MICs in the range 2-4 μg/mL ∼ 0.3-0.7 μM), while analogs displaying an ethylene glycol (eg1) moiety or a polar maleimide linker also possessed activity toward wild-type K. pneumoniae (MICs of 4-8 μg/mL ∼ 0.6-1.3 μM). Against two colistin-resistant E. coli strains the linker-deficient compound proved most potent (with MICs in the range 2-4 μg/mL ∼ 0.3-0.7 μM). The truncated all-L Pip1 peptide had moderate inherent activity against E. coli, and this was unaltered or reduced upon conjugation to the antisense PNA oligomer. By contrast, this peptide was 8-fold less potent against K. pneumoniae, but in this case some PNA-peptide conjugates exhibited potent antisense activity (MICs of 2-8 μg/mL ∼ 0.3-1.2 μM). Most interestingly, the antibacterial activity of the D-form peptide itself was 2- to 16-fold higher than that of the L-form, even for the colistin- and tigecycline-resistant E. coli strains (MIC of 1-2 μg/mL ∼ 0.25-0.5 μM). Low activity was found for conjugates with a two-mismatch PNA sequence corroborating an antisense mode of action. Conjugates containing D-peptide were also significantly less active. In conclusion, we have designed and synthesized antisense PNA-drosocin conjugates with potent antibacterial activity against colistin- and tigecycline-resistant E. coli and K. pneumonia without concomitant hemolytic properties. In addition, a truncated D-form of Pip1 was identified as a peptide exhibiting potent activity against both wild-type and multidrug-resistant E. coli, P. aeruginosa, and A. baumannii (MICs within the range 1-4 μg/mL ∼ 0.25-1 μM) as well as toward wild-type Staphylococcus aureus (MIC of 2-4 μg/mL ∼ 0.5-1.0 μM).

European Journal of Medicinal Chemistry published new progress about 172405-16-2. 172405-16-2 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide, name is 2-(4-((tert-Butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid, and the molecular formula is C11H15N3O5, SDS of cas: 172405-16-2.

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

Rageot, Denise published the artcile(S)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530), a Potent, Orally Bioavailable, and Brain-Penetrable Dual Inhibitor of Class I PI3K and mTOR Kinase, Safety of 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine, the publication is Journal of Medicinal Chemistry (2019), 62(13), 6241-6261, database is CAplus and MEDLINE.

The phosphoinositide 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) pathway is frequently overactivated in cancer, and drives cell growth, proliferation, survival, and metastasis. Here, we report a structure-activity relationship study, which led to the discovery of a drug-like ATP-site PI3K/mTOR kinase inhibitor: (S)-4-(difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530, compound 6), which qualifies as a clin. candidate due to its potency and specificity for PI3K and mTOR kinases, and its pharmacokinetic properties, including brain penetration. Compound 6 showed excellent selectivity over a wide panel of kinases and an excellent selectivity against unrelated receptor enzymes and ion channels. Moreover, compound 6 prevented cell growth in a cancer cell line panel. The preclin. in vivo characterization of compound 6 in an OVCAR-3 xenograft model demonstrated good oral bioavailability, excellent brain penetration, and efficacy. Initial toxicity studies in rats and dogs qualify 6 for further development as a therapeutic agent in oncol.

Journal of Medicinal Chemistry published new progress about 944401-58-5. 944401-58-5 belongs to pyrimidines, auxiliary class Trifluoromethyl,Pyrimidine,Fluoride,Boronic acid and ester,Amine,Boronate Esters,Boronic acid and ester,, name is 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine, and the molecular formula is C11H15BF3N3O2, Safety of 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine.

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

Chouikhi, Dalila published the artcileClickable peptide nucleic acids (cPNA) with tunable affinity, COA of Formula: C11H15N3O5, the publication is Chemical Communications (Cambridge, United Kingdom) (2010), 46(30), 5476-5478, database is CAplus and MEDLINE.

Peptide nucleic acids (PNAs) are functional analogs of natural oligonucleotides. Herein, the authors report the synthesis of PNAs bearing a triazole in lieu of the amide bond assembled using a “click” cycloaddition, their hybridization properties as well as the DNA-templated coupling of the azide and alkyne PNA fragments.

Chemical Communications (Cambridge, United Kingdom) published new progress about 172405-16-2. 172405-16-2 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide, name is 2-(4-((tert-Butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid, and the molecular formula is C11H15N3O5, COA of Formula: C11H15N3O5.

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