Tag: M.W=200-250

Zhang, Chao published the artcileRAF inhibitors that evade paradoxical MAPK pathway activation, Application In Synthesis of 1375301-91-9, the publication is Nature (London, United Kingdom) (2015), 526(7574), 583-586, database is CAplus and MEDLINE.

Oncogenic activation of BRAF fuels cancer growth by constitutively promoting RAS-independent mitogen-activated protein kinase (MAPK) pathway signalling. Accordingly, RAF inhibitors have brought substantially improved personalized treatment of metastatic melanoma. However, these targeted agents have also revealed an unexpected consequence: stimulated growth of certain cancers. Structurally diverse ATP-competitive RAF inhibitors can either inhibit or paradoxically activate the MAPK pathway, depending whether activation is by BRAF mutation or by an upstream event, such as RAS mutation or receptor tyrosine kinase activation. Here we have identified next-generation RAF inhibitors (dubbed ‘paradox breakers’) that suppress mutant BRAF cells without activating the MAPK pathway in cells bearing upstream activation. In cells that express the same HRAS mutation prevalent in squamous tumors from patients treated with RAF inhibitors, the first-generation RAF inhibitor vemurafenib stimulated in vitro and in vivo growth and induced expression of MAPK pathway response genes; by contrast the paradox breakers PLX7904 and PLX8394 had no effect. Paradox breakers also overcame several known mechanisms of resistance to first-generation RAF inhibitors. Dissociating MAPK pathway inhibition from paradoxical activation might yield both improved safety and more durable efficacy than first-generation RAF inhibitors, a concept currently undergoing human clin. evaluation with PLX8394.

Nature (London, United Kingdom) published new progress about 1375301-91-9. 1375301-91-9 belongs to pyrimidines, auxiliary class Pyrimidine,Boronic acid and ester,Boronate Esters,Boronic acid and ester, name is 2-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine, and the molecular formula is C10H9NO, Application In Synthesis of 1375301-91-9.

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

Zhang, Hongpeng published the artcileSynthesis of Silicon-Stereogenic Silanols Involving Iridium-Catalyzed Enantioselective C-H Silylation Leading to a New Ligand Scaffold, Synthetic Route of 2634687-67-3, the publication is ACS Catalysis (2021), 11(17), 10748-10753, database is CAplus.

Despite a growing focus on the construction of highly enantioenriched silicon-stereogenic organosilicon compounds, the enantioselective synthesis of silicon-stereogenic silanols through asym. catalysis remains a considerable challenge. Herein, we realized enantioselective construction of silicon-stereogenic diarylsilanols via an Ir-catalyzed C-H silylation of diarylsilanols along with stereospecific substitution or Tamao-Fleming oxidation This strategy gives rise to a class of chiral diol catalyst cores (PSiOLs). Transformation of PSiOLs led to the ligand possessing both Si and P-stereocenters, which is capable of inducing excellent enantioselectivity in the rhodium(I)-catalyzed conjugate 1,4-addition of aryl boronic acids to cyclohexenone.

ACS Catalysis published new progress about 2634687-67-3. 2634687-67-3 belongs to pyrimidines, auxiliary class OX or FeOX Ligands,Mono-oxazoline Ligands, name is (3aS,8aR)-2-(Pyrimidin-2-yl)-8,8a-dihydro-3aH-indeno[1,2-d]oxazole, and the molecular formula is C18H28B2O4, Synthetic Route of 2634687-67-3.

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

Zhao, Jichen published the artcileHighly Selective MERTK Inhibitors Achieved by a Single Methyl Group, HPLC of Formula: 1375301-91-9, the publication is Journal of Medicinal Chemistry (2018), 61(22), 10242-10254, database is CAplus and MEDLINE.

Although all kinases share the same ATP binding pocket, subtle differences in the residues that form the pocket differentiate individual kinases’ affinity for ATP competitive inhibitors. The authors have found that by introducing a single Me group, the selectivity of the MERTK inhibitors over another target, FLT3, was increased up to 1000-fold (compound I). Compound II was identified as an in vivo tool compound with subnanomolar activity against MERTK and 38-fold selectivity over FLT3 in vitro. The potency and selectivity of II for MERTK over FLT3 were confirmed in cell-based assays using human cancer cell lines. Compound II had favorable pharmacokinetic properties in mice. Phosphorylation of MERTK was decreased by 75% in bone marrow leukemia cells from mice treated with II compared to vehicle-treated mice.

Journal of Medicinal Chemistry published new progress about 1375301-91-9. 1375301-91-9 belongs to pyrimidines, auxiliary class Pyrimidine,Boronic acid and ester,Boronate Esters,Boronic acid and ester, name is 2-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine, and the molecular formula is C5H6N2O2, HPLC of Formula: 1375301-91-9.

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

Stoner, Eric J. published the artcileSynthesis of HIV Protease Inhibitor ABT-378 (Lopinavir), HPLC of Formula: 192725-50-1, the main research area is ABT378 lopinavir large scale synthesis; oxopyrimidineacetate large scale synthesis.

A large-scale process for the synthesis of HIV protease inhibitor candidate ABT-378 was developed which utilizes an intermediate common to the synthesis of ritonavir, Abbott’s first generation compound The synthesis relies on the sequential acylation of this intermediate which is carried through as a mixture of diastereomers until the penultimate step. A synthesis of (S)-tetrahydro-α-(1-methylethyl)-2-oxo-1(2H)-pyrimidineacetate, derived from L-valine, is also reported.

Organic Process Research & Development published new progress about ABT378 lopinavir large scale synthesis; oxopyrimidineacetate large scale synthesis. 192725-50-1 belongs to class pyrimidines, name is (S)-3-Methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoic acid, and the molecular formula is C9H16N2O3, HPLC of Formula: 192725-50-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reddy, Ambati V. Raghava published the artcileSynthesis and characterization of impurities in the production process of lopinavir, Quality Control of 192725-50-1, the main research area is lopinavir synthesis impurity; Lopinavir; Related substances; Synthesis and Characterization of impurities.

Lopinavir is an antiretroviral drug used for the inhibition of HIV protease. Four related substances of lopinavir were observed during the manufacturing process of lopinavir in the laboratory and they were identified. The present work describes the origin, synthesis, characterization, and control of these related substances.

Scientia Pharmaceutica published new progress about Impurities. 192725-50-1 belongs to class pyrimidines, name is (S)-3-Methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoic acid, and the molecular formula is C9H16N2O3, Quality Control of 192725-50-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Berhane, Ilyas published the artcileThieno[2,3-d]pyrimidine-Based Positive Allosteric Modulators of Human Mas-Related G Protein-Coupled Receptor X1 (MRGPRX1), Application In Synthesis of 439692-55-4, the main research area is MRGPRX1 pos allosteric modulator neuropathic pain analgesic.

Mas-related G protein-coupled receptor X1 (MRGPRX1) is a human sensory neuron-specific receptor and potential target for the treatment of pain. Pos. allosteric modulators (PAMs) of MRGPRX1 have the potential to preferentially activate the receptors at the central terminals of primary sensory neurons and minimize itch side effects caused by peripheral activation. Using a high-throughput screening (HTS) hit, a series of thieno[2,3-d]pyrimidine-based mols. were synthesized and evaluated as human MRGPRX1 PAMs in HEK293 cells stably transfected with human MrgprX1 gene. An iterative process to improve potency and metabolic stability led to the discovery of orally available 6-(tert-butyl)-5-(3,4-dichlorophenyl)-4-(2-(trifluoromethoxy)phenoxy)thieno[2,3-d]pyrimidine (1t), which can be distributed to the spinal cord, the presumed site of action, following oral administration. In a neuropathic pain model induced by sciatic nerve chronic constriction injury (CCI), compound 1t (100 mg/kg, po) reduced behavioral heat hypersensitivity in humanized MRGPRX1 mice, demonstrating the therapeutic potential of MRGPRX1 PAMs in treating neuropathic pain.

Journal of Medicinal Chemistry published new progress about Analgesics. 439692-55-4 belongs to class pyrimidines, name is Thieno[2,3-d]pyrimidine, 4-chloro-6-(1,1-dimethylethyl)-, and the molecular formula is C10H11ClN2S, Application In Synthesis of 439692-55-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia