Category: 220731-04-4

Zhang, Lin; Fan, Junhua; Chong, Jer-Hong; Cesena, Angela; Tam, Betty Y. Y.; Gilson, Charles; Boykin, Christina; Wang, Deping; Aivazian, Dikran; Marcotte, Doug; Xiao, Guangqing; Le Brazidec, Jean-Yves; Piao, Jinhua; Lundgren, Karen; Hong, Kevin; Vu, Khang; Nguyen, Khanh; Gan, Liang-Shang; Silvian, Laura; Ling, Leona; Teng, Min; Reff, Mitchell; Takeda, Nicole; Timple, Noel; Wang, Qin; Morena, Ron; Khan, Samina; Zhao, Shuo; Li, Tony; Lee, Wen-Cherng; Taveras, Arthur G.; Chao, Jianhua published the artcile< Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I)>, Related Products of 220731-04-4, the main research area is pyrazolopyrimidine sulfonamide preparation multiple mitotic kinase inhibitor.

A novel class of pyrazolopyrimidine-sulfonamides was discovered as selective dual inhibitors of aurora kinase A (AKA) and cyclin-dependent kinase 1 (CDK1). These inhibitors were originally designed based on an early lead (compound I). SAR development has led to the discovery of potent inhibitors with single digit nM IC50s towards both AKA and CDK1. An exemplary compound II has demonstrated good efficacy in an HCT116 colon cancer xenograft model.

Bioorganic & Medicinal Chemistry Letters published new progress about Alkylation. 220731-04-4 belongs to class pyridine-derivatives, and the molecular formula is C10H15N3O2, Related Products of 220731-04-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Rai, Roopa; Kolesnikov, Aleksandr; Sprengeler, Paul A.; Torkelson, Steven; Ton, Tony; Katz, Bradley A.; Yu, Christine; Hendrix, John; Shrader, William D.; Stephens, Robin; Cabuslay, Ronnell; Sanford, Ellen; Young, Wendy B. published the artcile< Discovery of novel heterocyclic factor VIIa inhibitors>, Category: pyridine-derivatives, the main research area is aminopyrrolopyridine preparation factor VIIa inhibitor SAR.

Structure-activity relationships and binding mode of novel heterocyclic factor VIIa inhibitors will be described. In these inhibitors, a highly basic 5-amidinoindole moiety has been successfully replaced with a less basic 5-aminopyrrolo[3,2-b]pyridine scaffold.

Bioorganic & Medicinal Chemistry Letters published new progress about Anticoagulants. 220731-04-4 belongs to class pyridine-derivatives, and the molecular formula is C10H15N3O2, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Khayat, Maan T.; Omar, Abdelsattar M.; Elfaky, Mahmoud A.; Muhammad, Yosra A.; Felemban, Elaf A.; El-Say, Khalid M.; El-Araby, Moustafa E. published the artcile< Reexamining povarov reaction′s scope and limitation in the generation of HCV-NS4A peptidomimetics>, Recommanded Product: tert-Butyl (5-aminopyridin-2-yl)carbamate, the main research area is hepatitis C virus NS4A peptidomimetics.

Chronic Hepatitis C is a global health threat and a silent killer. Regardless of the profound progress in preventing and treating this disease, research continues to discover new direct antiviral agents (DAAs), especially against novel targets. Our research has been directed to leverage the NS4A binding site to develop peptidomimetic inhibitors of the hepatitis C virus (HCV) NS3 protease. In previous reports, we could provide evidence of tunability of this site by peptide and nonpeptide NS3/4A inhibitors. In this report, we used structure-based techniques to design 1,2,3,4-tetrahydro-1,7-naphthyridine derivative as NS4A core mimics that cover the region between residues Ile-25′ to Arg-28′. The synthetic plan featured the Povarov reaction as an efficient strategy to construct the 1,7-naphthyridine core. Although this reaction has been reported in many literatures, critical assessments for its scope and limitations are scarce. In our work, we found that Povarov was extremely sensitive to alkene and aldehyde reactants. Moreover, using pyridine amines was not as successful as anilines. The most striking results were the lack of stability of compounds during purification and storage. The four compounds that survived the stability problems (1a-1d) did not show significant binding potency with NS3, because their structures were too simple to resemble the originally planned compounds

Heteroatom Chemistry published new progress about Aggregation (temperature). 220731-04-4 belongs to class pyridine-derivatives, and the molecular formula is C10H15N3O2, Recommanded Product: tert-Butyl (5-aminopyridin-2-yl)carbamate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Bourbeau, Matthew P.; Ashton, Kate S.; Yan, Jie; St. Jean, David J. published the artcile< Nonracemic Synthesis of GK-GKRP Disruptor AMG-3969>, Recommanded Product: tert-Butyl (5-aminopyridin-2-yl)carbamate, the main research area is AMG3969 nonracemic preparation glucokinase glucokinase regulatory protein disruptor.

A nonracemic synthesis of the glucokinase-glucokinase regulatory protein disruptor AMG-3969 (I) is reported. Key features of the synthetic approach are an asym. synthesis of the 2-alkynyl piperazine core via a base-promoted isomerization and a revised approach to the synthesis of the aminopyridinesulfonamide with an improved safety profile.

Journal of Organic Chemistry published new progress about Isomerization. 220731-04-4 belongs to class pyridine-derivatives, and the molecular formula is C10H15N3O2, Recommanded Product: tert-Butyl (5-aminopyridin-2-yl)carbamate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Huang, Zhi; Zhou, Wei; Li, Yongtao; Cao, Mei; Wang, Tianqi; Ma, Yakun; Guo, Qingxiang; Wang, Xin; Zhang, Chao; Zhang, Chenglan; Shen, Wenzhi; Liu, Yanhua; Chen, Yanan; Zheng, Jianyu; Yang, Shengyong; Fan, Yan; Xiang, Rong published the artcile< Novel hybrid molecule overcomes the limited response of solid tumours to HDAC inhibitors via suppressing JAK1-STAT3-BCL2 signalling>, Reference of 220731-04-4, the main research area is breast ovarian cancer HDAC inhibitor JAK1 STAT3 BCL2 signaling; CDK4/6; HDAC1; JAK1; inhibitor; solid tumour.

Despite initial progress in preclin. models, most known histone deacetylase inhibitors (HDACis) used as a single agent have failed to show clin. benefits in nearly all types of solid tumors. Hence, the efficacy of HDACis in solid tumors remains uncertain. Herein, we developed a hybrid HDAC inhibitor that sensitized solid tumors to HDAC-targeted treatment. Methods: A hybrid mol., Roxyl-zhc-84 was designed and synthesized with novel architecture. The pharmacokinetics and toxicity of Roxyl-zhc-84 were analyzed. Results: Roxyl-zhc-84 showed excellent pharmacokinetics and low toxicity. The novel hybrid inhibitor Roxyl-zhc-84 induced cell apoptosis and G1-phase arrest in breast cancer and ovarian cancer cell lines. In three mouse models, oral administration of Roxyl-zhc-84 led to significant tumor regression without obvious toxicity. Moreover, Roxyl-zhc-84 dramatically improved the limited response of traditional HDAC inhibitors in solid tumors via overcoming JAK1-STAT3-BCL2-mediated drug resistance. Roxyl-zhc-84 treatment exhibited vastly superior efficacy than the combination of HDAC and JAK1 inhibitors both in vitro and in vivo. Conclusion: Concurrent inhibition of HDAC and CDK using Roxyl-zhc-84 with addnl. JAK1 targeting resolved the limited response of traditional HDAC inhibitors in solid tumors via overcoming JAK1-STAT3-BCL2-mediated drug resistance, providing a rational multi-target treatment to sensitize solid tumors to HDACi therapy.

Theranostics published new progress about Acetylated histone H3 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 220731-04-4 belongs to class pyridine-derivatives, and the molecular formula is C10H15N3O2, Reference of 220731-04-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Li, Yongtao; Luo, Xiaohe; Guo, Qingxiang; Nie, Yongwei; Wang, Tianqi; Zhang, Chao; Huang, Zhi; Wang, Xin; Liu, Yanhua; Chen, Yanan; Zheng, Jianyu; Yang, Shengyong; Fan, Yan; Xiang, Rong published the artcile< Discovery of N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)phenyl)-N8-hydroxyoctanediamide as a Novel Inhibitor Targeting Cyclin-dependent Kinase 4/9 (CDK4/9) and Histone Deacetylase 1 (HDAC1) against Malignant Cancer>, Product Details of C10H15N3O2, the main research area is pyrrolopyrimidine preparation CDK4 CDK9 HDAC1 inhibitor treatment malignant cancer.

A series of highly potent, selective inhibitors targeting both CDK4/9 and HDAC1 have been designed and synthesized. N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)phenyl)-N8-hydroxyoctanediamide (I) was discovered. The lead compound I with excellent CDK4/9 and HDAC1 inhibitory activity of IC50 = 8.8, 12, and 2.2 nM, resp., can effectively induce apoptosis of cancer cell lines. The kinase profiling of compound I showed excellent selectivity and specificity. Compound I induces G2/M arrest in high concentration and G0/G1 arrest in low concentration to prevent the proliferation and differentiation of cancer cells. Mice bared-breast cancer treated with I showed significant antitumor efficacy. The insight into mechanisms of I indicated that it could induce cancer cell death via cell apoptosis based on CDK4/9 and HDAC1 repression and phosphorylation of p53. The data demonstrated the compound I could be a promising drug candidate for cancer therapy.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 220731-04-4 belongs to class pyridine-derivatives, and the molecular formula is C10H15N3O2, Product Details of C10H15N3O2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Nishimura, Nobuko; Norman, Mark H.; Liu, Longbin; Yang, Kevin C.; Ashton, Kate S.; Bartberger, Michael D.; Chmait, Samer; Chen, Jie; Cupples, Rod; Fotsch, Christopher; Helmering, Joan; Jordan, Steven R.; Kunz, Roxanne K.; Pennington, Lewis D.; Poon, Steve F.; Siegmund, Aaron; Sivits, Glenn; Lloyd, David J.; Hale, Clarence; St. Jean, David J. published the artcile< Small Molecule Disruptors of the Glucokinase-Glucokinase Regulatory Protein Interaction: 3. Structure-Activity Relationships within the Aryl Carbinol Region of the N-Arylsulfonamido-N'-arylpiperazine Series>, Recommanded Product: tert-Butyl (5-aminopyridin-2-yl)carbamate, the main research area is arylsulfonamido arylpiperazine glucokinase glucokinase regulatory protein disruptor SAR; AMG 3969 glucokinase glucokinase regulatory protein disruptor SAR; glucose blood level reduction arylsulfonamido arylpiperazine.

We have recently reported a novel approach to increase cytosolic glucokinase (GK) levels through the binding of a small mol. to its endogenous inhibitor, glucokinase regulatory protein (GKRP). These initial investigations culminated in the identification of 2-(4-((2S)-4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (I, AMG-3969), a compound that effectively enhanced GK translocation and reduced blood glucose levels in diabetic animals. Herein we report the results of our expanded SAR investigations that focused on modifications to the aryl carbinol group of this series. Guided by the X-ray cocrystal structure of compound I bound to hGKRP, we identified several potent GK-GKRP disruptors bearing a diverse set of functionalities in the aryl carbinol region. Among them, sulfoximine and pyridinyl derivatives II and III possessed excellent potency as well as favorable PK properties. When dosed orally in db/db mice, both compounds significantly lowered fed blood glucose levels (up to 58%).

Journal of Medicinal Chemistry published new progress about Antidiabetic agents. 220731-04-4 belongs to class pyridine-derivatives, and the molecular formula is C10H15N3O2, Recommanded Product: tert-Butyl (5-aminopyridin-2-yl)carbamate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem