Tag: M.W=600-700

Tesch, Roberta published the artcileStructure-Based Design of Selective Salt-Inducible Kinase Inhibitors, Safety of 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, the publication is Journal of Medicinal Chemistry (2021), 64(12), 8142-8160, database is CAplus and MEDLINE.

Salt-inducible kinases (SIKs) are key metabolic regulators. The imbalance in SIK function is associated with the development of diverse cancers, including breast, gastric, and ovarian cancers. Chem. tools to clarify the roles of SIK in different diseases are, however, sparse and are generally characterized by poor kinome-wide selectivity. Here, we have adapted the pyrido[2,3-d]pyrimidin-7-one-based p21-activated kinase (PAK) inhibitor G-5555 for the targeting of SIK, by exploiting differences in the back-pocket region of these kinases. Optimization was supported by high-resolution crystal structures of G-5555 bound to the known off-targets, MST3 and MST4, leading to a chem. probe, MRIA9, with dual SIK/PAK activity and excellent selectivity over other kinases. Furthermore, we show that MRIA9 sensitizes ovarian cancer cells to treatment with the mitotic agent paclitaxel, confirming earlier data from genetic knockdown studies and suggesting a combination therapy with SIK inhibitors and paclitaxel for the treatment of paclitaxel-resistant ovarian cancer.

Journal of Medicinal Chemistry published new progress about 1936529-65-5. 1936529-65-5 belongs to piperidines, auxiliary class Immunology/Inflammation,SIK, name is 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, and the molecular formula is C7H14N4, Safety of 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Tarumoto, Yusuke published the artcileChemical inhibition of SIK3 as a therapeutic strategy in acute myeloid leukemia, Product Details of C32H34ClN7O3, the publication is Ketsueki Naika (2020), 81(4), 529-534, database is CAplus.

A review. Acute myeloid leukemia AML, a type of hematopoietic aneurysm, is caused by an excessive increase in undifferentiated bone marrow cells. These results suggest that SIK drugs can selectively suppress AML proliferation, indicating that SIK blockade is a candidate for an effective AML treatment strategy. Results show chem. inhibition of SIK3 as therapeutic strategy in acute myeloid leukemia.

Ketsueki Naika published new progress about 1936529-65-5. 1936529-65-5 belongs to piperidines, auxiliary class Immunology/Inflammation,SIK, name is 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, and the molecular formula is C2H2N3NaS, Product Details of C32H34ClN7O3.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Sundberg, Thomas B. published the artcileDevelopment of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo, Category: piperidines, the publication is ACS Chemical Biology (2016), 11(8), 2105-2111, database is CAplus and MEDLINE.

Salt-inducible kinases (SIKs) are promising therapeutic targets for modulating cytokine responses during innate immune activation. The study of SIK inhibition in animal models of disease has been limited by the lack of selective small-mol. probes suitable for modulating SIK function in vivo. We used the pan-SIK inhibitor HG-9-91-01 as a starting point to develop improved analogs, yielding a novel probe 5 (YKL-05-099) that displays increased selectivity for SIKs vs. other kinases and enhanced pharmacokinetic properties. Well-tolerated doses of YKL-05-099 achieve free serum concentrations above its IC₅₀ for SIK2 inhibition for >16 h and reduce phosphorylation of a known SIK substrate in vivo. While in vivo active doses of YKL-05-099 recapitulate the effects of SIK inhibition on inflammatory cytokine responses, they did not induce metabolic abnormalities observed in Sik2 knockout mice. These results identify YKL-05-099 as a useful probe to investigate SIK function in vivo and further support the development of SIK inhibitors for treatment of inflammatory disorders.

ACS Chemical Biology published new progress about 1936529-65-5. 1936529-65-5 belongs to piperidines, auxiliary class Immunology/Inflammation,SIK, name is 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, and the molecular formula is C6H9N3, Category: piperidines.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Wein, Marc N. published the artcileSIKs control osteocyte responses to parathyroid hormone, Name: 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, the publication is Nature Communications (2016), 13176, database is CAplus and MEDLINE.

Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small mol. SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small mol. SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small mol. SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.

Nature Communications published new progress about 1936529-65-5. 1936529-65-5 belongs to piperidines, auxiliary class Immunology/Inflammation,SIK, name is 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, and the molecular formula is C8H15NO, Name: 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Wein, Marc N. published the artcileCorrigendum: SIKs control osteocyte responses to parathyroid hormone [Erratum to document cited in CA168:468243], Safety of 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, the publication is Nature Communications (2017), 14745, database is CAplus and MEDLINE.

In this article, there are errors in the labeling of the y axis in Fig. 1b, in which the labels â€?0â€? â€?00â€?′and â€?50â€?should have been â€?00â€? â€?,000â€?and â€?,500â€? resp. The corrected version of Figure 1 is provided.

Nature Communications published new progress about 1936529-65-5. 1936529-65-5 belongs to piperidines, auxiliary class Immunology/Inflammation,SIK, name is 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, and the molecular formula is C17H16O2, Safety of 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Tarumoto, Yusuke published the artcileSalt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo, Formula: C32H34ClN7O3, the publication is Blood (2020), 135(1), 56-70, database is CAplus and MEDLINE.

Lineage-defining transcription factors (TFs) are compelling targets for leukemia therapy, yet they are among the most challenging proteins to modulate directly with small mols. We previously used CRISPR screening to identify a salt-inducible kinase 3 (SIK3) requirement for the growth of acute myeloid leukemia (AML) cell lines that overexpress the lineage TF myocyte enhancer factor (MEF2C). In this context, SIK3 maintains MEF2C function by directly phosphorylating histone deacetylase 4 (HDAC4), a repressive cofactor of MEF2C. In this study, we evaluated whether inhibition of SIK3 with the tool compound YKL-05-099 can suppress MEF2C function and attenuate disease progression in animal models of AML. Genetic targeting of SIK3 or MEF2C selectively suppressed the growth of transformed hematopoietic cells under in vitro and in vivo conditions. Similar phenotypes were obtained when cells were exposed to YKL-05-099, which caused cell-cycle arrest and apoptosis in MEF2C-expressing AML cell lines. An epigenomic anal. revealed that YKL-05-099 rapidly suppressed MEF2C function by altering the phosphorylation state and nuclear localization of HDAC4. Using a gatekeeper allele of SIK3, we found that the antiproliferative effects of YKL-05-099 occurred through on-target inhibition of SIK3 kinase activity. Based on these findings, we treated 2 different mouse models of MLL-AF9 AML with YKL-05-099, which attenuated disease progression in vivo and extended animal survival at well-tolerated doses. These findings validate SIK3 as a therapeutic target in MEF2C-addicted AML and provide a rationale for developing druglike inhibitors of SIK3 for definitive preclin. investigation and for studies in human patients.

Blood published new progress about 1936529-65-5. 1936529-65-5 belongs to piperidines, auxiliary class Immunology/Inflammation,SIK, name is 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, and the molecular formula is C2H2N3NaS, Formula: C32H34ClN7O3.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

In organic chemistry, atoms other than carbon and hydrogen are generally referred to as heteroatoms. The most common heteroatoms are nitrogen, oxygen and sulfur. Now I present to you an article called Evaluation of pressure and correlation to reaction rates during homogeneously catalyzed hydroformylation in supercritical carbon dioxide, published in 2008-08-31, which mentions a compound: 175136-62-6, mainly applied to hydroformylation octene supercritical carbon dioxide, Quality Control of Tris(3,5-bis(trifluoromethyl)phenyl)phosphine.

For the hydroformylation of 1-octene in supercritical carbon dioxide the relation between the change in pressure and the change in reaction mixture composition as a function of time was studied. The activity and selectivity was studied for the catalyst based on tris(3,5-bis(trifluoromethyl)phenyl)phosphine and rhodium(I) dicarbonyl acetylacetonate. The influence of the ligand to rhodium ratio on the hydroformylation was used to demonstrate how the pressure can be correlated to the conversion and yield. The initial rate of reaction is in good agreement with the initial pressure change in the batch reactor. Up to an aldehyde yield of 80%, the pressure drop appears to be independent of the reaction rate and selectivity. The highest average reaction rate, 7170 mol1-octeneoctene molRH-1 h-1, was obtained for a ligand to rhodium ratio of 50 and an initial concentration of 1-octene of 0.5 mol L-1. Both the reaction rate and the selectivity increase when the ligand to rhodium ratio is increased. The Peng-Robinson equation of state was used to describe the pressure as a function of the concentration of the reactants and products. The calculated pressure corresponds reasonably well with the observed reactor pressure. Following the progress of the reaction by monitoring the pressure is a good alternative to reaction mixture sampling, especially for fast reactions.

《Evaluation of pressure and correlation to reaction rates during homogeneously catalyzed hydroformylation in supercritical carbon dioxide》 provides a strategy for the preparation of materials with excellent comprehensive properties, which is conducive to broaden the application field of this compound(Tris(3,5-bis(trifluoromethyl)phenyl)phosphine)Quality Control of Tris(3,5-bis(trifluoromethyl)phenyl)phosphine.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Wu, Hai-Chen; Yu, Jin-Quan; Spencer, Jonathan B. published an article about the compound: Tris(3,5-bis(trifluoromethyl)phenyl)phosphine( cas:175136-62-6,SMILESS:FC(C1=CC(C(F)(F)F)=CC(P(C2=CC(C(F)(F)F)=CC(C(F)(F)F)=C2)C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)=C1)(F)F ).Safety of Tris(3,5-bis(trifluoromethyl)phenyl)phosphine. Aromatic heterocyclic compounds can be classified according to the number of heteroatoms or the size of the ring. The authors also want to convey more information about this compound (cas:175136-62-6) through the article.

Electroneg. phosphine oxides were reduced to corresponding phosphines by trichlorosilane-mediated oxygen transfer to sacrificial PPh3 or P(OEt)3 with excellent yields. The diphosphine dioxides 2,2′-(Ar2PO)-1,1′-binaphthalene (1a-e, Ar = 3,5-(CF3)2C6H3, 4-CF3C6H4), Ar2POCH2CH2POAr2 (1g, Ar = C6F5), monophosphine oxides Ar3PO and Ar2PAr1 (1h and 1f, resp.; Ar = 3,5-(CF3)2C6H3, Ar1 = 1,1′-binaphthalene-2-yl) were deoxygenated to the corresponding phosphines (2a-h) by reaction with HSiCl3 in the presence of PPh3 or tri-Et phosphite, acting as sacrificial oxygen acceptors, which shift the deoxygenation reaction equilibrium to the corresponding phosphines. The advantage of the new method includes milder conditions and considerably shortened reaction times. Mechanistic studies about the oxygen transfer between the starting phosphine oxide and the sacrificial triphenylphosphine are also presented.

《Stereospecific Deoxygenation of Phosphine Oxides with Retention of Configuration Using Triphenylphosphine or Triethyl Phosphite as an Oxygen Acceptor》 provides a strategy for the preparation of materials with excellent comprehensive properties, which is conducive to broaden the application field of this compound(Tris(3,5-bis(trifluoromethyl)phenyl)phosphine)Safety of Tris(3,5-bis(trifluoromethyl)phenyl)phosphine.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Fujita, Shin-ichiro; Fujisawa, Shinya; Bhanage, Bhalchandra M.; Ikushima, Yutaka; Arai, Masahiko published an article about the compound: Tris(3,5-bis(trifluoromethyl)phenyl)phosphine( cas:175136-62-6,SMILESS:FC(C1=CC(C(F)(F)F)=CC(P(C2=CC(C(F)(F)F)=CC(C(F)(F)F)=C2)C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)=C1)(F)F ).Computed Properties of C24H9F18P. Aromatic heterocyclic compounds can be classified according to the number of heteroatoms or the size of the ring. The authors also want to convey more information about this compound (cas:175136-62-6) through the article.

Rhodium-catalyzed hydroformylation of 1,5-hexadiene to dialdehydes was investigated in compressed CO2 and in toluene using different fluorinated phosphine compounds as ligands at a temperature of 60 °C. Product yields depend greatly on the ligand used and, of the ligands examined, tris[3,5-bis(trifluoromethyl)phenyl]phosphine is the most effective for the production of dialdehydes both in supercritical CO2 (scCO2) and in toluene. The total yield of the dialdehydes passes through a min. at about 9 MPa as the CO2 pressure is increased and increases appreciably as the H2 pressure in scCO2 increases. The effect of the syngas (H2/CO) and H2 pressures on the reaction in scCO2 is different from that in toluene. It has been suggested that scCO2 promotes the hydroformylation reaction.

This compound(Tris(3,5-bis(trifluoromethyl)phenyl)phosphine)Computed Properties of C24H9F18P was discussed at the molecular level, the effects of temperature and reaction time on the properties of the compound were discussed, and the optimum reaction conditions were selected.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Related Products of 175136-62-6. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: Tris(3,5-bis(trifluoromethyl)phenyl)phosphine, is researched, Molecular C24H9F18P, CAS is 175136-62-6, about Synthesis of Platinum-Ruthenium Nanoparticles under Supercritical CO2 and their Confinement in Carbon Nanotubes: Hydrogenation Applications. Author is Castillejos, Eva; Jahjah, Mohamad; Favier, Isabelle; Orejon, Arantxa; Pradel, Christian; Teuma, Emmanuelle; Masdeu-Bulto, Anna M.; Serp, Philippe; Gomez, Montserrat.

Bimetallic platinum-ruthenium nanoparticles stabilized by pyridine- and monophosphine-based ligands were prepared either in supercritical CO2 or in THF. TEM analyses evidenced a tendency of the nanoparticles prepared in supercritical CO2 to agglomerate. Both types of bimetallic nanoparticles were further confined into functionalized multiwalled carbon nanotubes. Upon confinement, PtRu nanoparticles stabilized by phosphine ligands appeared more agglomerated than those stabilized by the pyridine ligand. These materials were applied to cinnamaldehyde hydrogenation. Confined PtRu nanoparticles showed higher catalytic activity and selectivity than unsupported nanoparticles.

This compound(Tris(3,5-bis(trifluoromethyl)phenyl)phosphine)Related Products of 175136-62-6 was discussed at the molecular level, the effects of temperature and reaction time on the properties of the compound were discussed, and the optimum reaction conditions were selected.

Reference:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem