Category: 936250-20-3

Huang, Qinhua; Johnson, Ted W.; Bailey, Simon; Brooun, Alexei; Bunker, Kevin D.; Burke, Benjamin J.; Collins, Michael R.; Cook, Andrew S.; Cui, J. Jean; Dack, Kevin N.; Deal, Judith G.; Deng, Ya-Li; Dinh, Dac; Engstrom, Lars D.; He, Mingying; Hoffman, Jacqui; Hoffman, Robert L.; Johnson, Patrick S.; Kania, Robert S.; Lam, Hieu; Lam, Justine L.; Le, Phuong T.; Li, Qiuhua; Lingardo, Laura; Liu, Wei; Lu, Melissa West; McTigue, Michele; Palmer, Cynthia L.; Richardson, Paul F.; Sach, Neal W.; Shen, Hong; Smeal, Tod; Smith, Graham L.; Stewart, Albert E.; Timofeevski, Sergei; Tsaparikos, Konstantinos; Wang, Hui; Zhu, Huichun; Zhu, Jinjiang; Zou, Helen Y.; Edwards, Martin P. published the artcile< Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib>, Electric Literature of 936250-20-3, the main research area is crizotinib resistant lymphoma kinase mutation inhibitor preparation SAR.

Crizotinib, an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS pos. patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine (I), which was potent across a broad panel of engineered ALK mutant cell lines and showed suitable preclin. pharmacokinetics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).

Journal of Medicinal Chemistry published new progress about Antitumor agents. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Electric Literature of 936250-20-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Chowdhury, Sarwat; Chen, Yen Ting; Fang, Xingang; Grant, Wayne; Pocas, Jennifer; Cameron, Michael D.; Ruiz, Claudia; Lin, Li; Park, HaJeung; Schroter, Thomas; Bannister, Thomas D.; LoGrasso, Philip V.; Feng, Yangbo published the artcile< Amino acid derived quinazolines as Rock/PKA inhibitors>, Name: 3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is amino acid derived quinazolinone Rock PKA inhibitor.

SAR and lead optimization studies for Rock inhibitors based on amino acid-derived quinazolines are described. Studies demonstrated that these amino acid derived quinazolinones were mainly puromycin aminonucleoside (PAN)-Rho-associated protein kinase (Rock) (I & II) inhibitors. While selectivity against other kinases could be achieved, selectivity for most of these compounds against PKA was not achieved. This is distinct from Rock inhibitors based on non-amino acid derived quinazolinones, where high selectivity against PKA could be obtained.22 The inhibitors presented here in some cases possessed sub-nanomolar inhibition of Rock, nanomolar potency in ppMLC cell based assays, low to fair cytochrome P 450 inhibition, and good human microsomal stability.

Bioorganic & Medicinal Chemistry Letters published new progress about Heteroarylation (Suzuki). 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Name: 3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Wang, Le; Doherty, George A.; Judd, Andrew S.; Tao, Zhi-Fu; Hansen, T. Matthew; Frey, Robin R.; Song, Xiaohong; Bruncko, Milan; Kunzer, Aaron R.; Wang, Xilu; Wendt, Michael D.; Flygare, John A.; Catron, Nathaniel D.; Judge, Russell A.; Park, Chang H.; Shekhar, Shashank; Phillips, Darren C.; Nimmer, Paul; Smith, Morey L.; Tahir, Stephen K.; Xiao, Yu; Xue, John; Zhang, Haichao; Le, Phuong N.; Mitten, Michael J.; Boghaert, Erwin R.; Gao, Wenqing; Kovar, Peter; Choo, Edna F.; Diaz, Dolores; Fairbrother, Wayne J.; Elmore, Steven W.; Sampath, Deepak; Leverson, Joel D.; Souers, Andrew James published the artcile< Discovery of A-1331852, a First-in-Class, Potent, and Orally-Bioavailable BCL-XL Inhibitor>, HPLC of Formula: 936250-20-3, the main research area is tumor BCLXL BCL2 apoptosis A1155463 structure based drug design.

Herein we describe the discovery of A-1331852(I), a first-in-class orally active BCL-XL inhibitor that selectively and potently induces apoptosis in BCL-XL dependent tumor cells. This mol. was generated by re-engineering our previously reported BCL-XL inhibitor A-1155463 using structure-based drug design. Key design elements included rigidification of the A-1155463 pharmacophore and introduction of sp3-rich moieties capable of generating highly productive interactions within the key P4 pocket of BCL-XL. A-1331852 has since been used as a critical tool mol. for further exploring BCL-2 family protein biol., while also representing an attractive entry into a drug discovery program.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, HPLC of Formula: 936250-20-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Huang, Qinhua; Johnson, Ted W.; Bailey, Simon; Brooun, Alexei; Bunker, Kevin D.; Burke, Benjamin J.; Collins, Michael R.; Cook, Andrew S.; Cui, J. Jean; Dack, Kevin N.; Deal, Judith G.; Deng, Ya-Li; Dinh, Dac; Engstrom, Lars D.; He, Mingying; Hoffman, Jacqui; Hoffman, Robert L.; Johnson, Patrick S.; Kania, Robert S.; Lam, Hieu; Lam, Justine L.; Le, Phuong T.; Li, Qiuhua; Lingardo, Laura; Liu, Wei; Lu, Melissa West; McTigue, Michele; Palmer, Cynthia L.; Richardson, Paul F.; Sach, Neal W.; Shen, Hong; Smeal, Tod; Smith, Graham L.; Stewart, Albert E.; Timofeevski, Sergei; Tsaparikos, Konstantinos; Wang, Hui; Zhu, Huichun; Zhu, Jinjiang; Zou, Helen Y.; Edwards, Martin P. published the artcile< Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib>, Electric Literature of 936250-20-3, the main research area is crizotinib resistant lymphoma kinase mutation inhibitor preparation SAR.

Crizotinib, an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS pos. patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine (I), which was potent across a broad panel of engineered ALK mutant cell lines and showed suitable preclin. pharmacokinetics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).

Journal of Medicinal Chemistry published new progress about Antitumor agents. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Electric Literature of 936250-20-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Chowdhury, Sarwat; Chen, Yen Ting; Fang, Xingang; Grant, Wayne; Pocas, Jennifer; Cameron, Michael D.; Ruiz, Claudia; Lin, Li; Park, HaJeung; Schroter, Thomas; Bannister, Thomas D.; LoGrasso, Philip V.; Feng, Yangbo published the artcile< Amino acid derived quinazolines as Rock/PKA inhibitors>, Name: 3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is amino acid derived quinazolinone Rock PKA inhibitor.

SAR and lead optimization studies for Rock inhibitors based on amino acid-derived quinazolines are described. Studies demonstrated that these amino acid derived quinazolinones were mainly puromycin aminonucleoside (PAN)-Rho-associated protein kinase (Rock) (I & II) inhibitors. While selectivity against other kinases could be achieved, selectivity for most of these compounds against PKA was not achieved. This is distinct from Rock inhibitors based on non-amino acid derived quinazolinones, where high selectivity against PKA could be obtained.22 The inhibitors presented here in some cases possessed sub-nanomolar inhibition of Rock, nanomolar potency in ppMLC cell based assays, low to fair cytochrome P 450 inhibition, and good human microsomal stability.

Bioorganic & Medicinal Chemistry Letters published new progress about Heteroarylation (Suzuki). 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Name: 3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Wang, Le; Doherty, George A.; Judd, Andrew S.; Tao, Zhi-Fu; Hansen, T. Matthew; Frey, Robin R.; Song, Xiaohong; Bruncko, Milan; Kunzer, Aaron R.; Wang, Xilu; Wendt, Michael D.; Flygare, John A.; Catron, Nathaniel D.; Judge, Russell A.; Park, Chang H.; Shekhar, Shashank; Phillips, Darren C.; Nimmer, Paul; Smith, Morey L.; Tahir, Stephen K.; Xiao, Yu; Xue, John; Zhang, Haichao; Le, Phuong N.; Mitten, Michael J.; Boghaert, Erwin R.; Gao, Wenqing; Kovar, Peter; Choo, Edna F.; Diaz, Dolores; Fairbrother, Wayne J.; Elmore, Steven W.; Sampath, Deepak; Leverson, Joel D.; Souers, Andrew James published the artcile< Discovery of A-1331852, a First-in-Class, Potent, and Orally-Bioavailable BCL-XL Inhibitor>, HPLC of Formula: 936250-20-3, the main research area is tumor BCLXL BCL2 apoptosis A1155463 structure based drug design.

Herein we describe the discovery of A-1331852(I), a first-in-class orally active BCL-XL inhibitor that selectively and potently induces apoptosis in BCL-XL dependent tumor cells. This mol. was generated by re-engineering our previously reported BCL-XL inhibitor A-1155463 using structure-based drug design. Key design elements included rigidification of the A-1155463 pharmacophore and introduction of sp3-rich moieties capable of generating highly productive interactions within the key P4 pocket of BCL-XL. A-1331852 has since been used as a critical tool mol. for further exploring BCL-2 family protein biol., while also representing an attractive entry into a drug discovery program.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, HPLC of Formula: 936250-20-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

He, Yuanjun; Duckett, Derek; Chen, Weimin; Ling, Yuan Yuan; Cameron, Michael D.; Lin, Li; Ruiz, Claudia H.; LoGrasso, Philip V.; Kamenecka, Theodore M.; Koenig, Marcel published the artcile< Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors>, Computed Properties of 936250-20-3, the main research area is pyridylisoxazole preparation JNK inhibitor SAR selectivity p38; Isoxazole; JNK; Kinase; c-Jun.

The design and synthesis of isoxazole I is described, a potent JNK inhibitor with two fold selectivity over p38. Optimization of this scaffold led to compounds II and III which showed greatly improved selectivity over p38 by maintaining the JNK3 potency of compound I. Extensive SAR studies will be described as well as preliminary in vivo data of the two lead compounds

Bioorganic & Medicinal Chemistry Letters published new progress about Homo sapiens. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Computed Properties of 936250-20-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Chowdhury, Sarwat; Sessions, E. Hampton; Pocas, Jennifer R.; Grant, Wayne; Schroeter, Thomas; Lin, Li; Ruiz, Claudia; Cameron, Michael D.; Schuerer, Stephan; LoGrasso, Philip; Bannister, Thomas D.; Feng, Yangbo published the artcile< Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I)>, Formula: C10H17BN2O2, the main research area is azaindolecarboxamide aralkyl preparation Rho kinase inhibitor.

Rho kinase (ROCK) inhibitors are potential therapeutic agents to treat disorders such as hypertension, multiple sclerosis, cancers, and glaucoma. The synthesis, optimization, biol. evaluation of potent indole and 7-azaindole based ROCK inhibitors that have high potency on ROCK (IC50 = 1 nM) with 740-fold selectivity over PKA, such as I. Moreover, I showed very good DMPK properties making it a good candidate for further development. Finally, docking studies with a homol. model of ROCK-II were performed to rationalize the binding mode of these compounds and showed the compounds bound in both orientations to take advantage to H-bonds with Lys-121 of ROCK-II.

Bioorganic & Medicinal Chemistry Letters published new progress about 936250-20-3. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Formula: C10H17BN2O2.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Klug, Dana M.; Diaz-Gonzalez, Rosario; DeLano, Travis J.; Mavrogiannaki, Eftychia M.; Buskes, Melissa J.; Dalton, Raeann M.; Fisher, John K.; Schneider, Katherine M.; Hilborne, Vivian; Fritsche, Melanie G.; Simpson, Quillon J.; Tear, Westley F.; Devine, William G.; Perez-Moreno, Guiomar; Ceballos-Perez, Gloria; Garcia-Hernandez, Raquel; Bosch-Navarrete, Cristina; Ruiz-Perez, Luis Miguel; Gamarro, Francisco; Gonzalez-Pacanowska, Dolores; Martinez-Martinez, Maria Santos; Manzano-Chinchon, Pilar; Navarro, Miguel; Pollastri, Michael P.; Ferrins, Lori published the artcile< Structure-property studies of an imidazoquinoline chemotype with antitrypanosomal activity>, Application of C10H17BN2O2, the main research area is imidazoquinoline chemotype antitrypanosomal activity structure activity relationship.

Human African trypanosomiasis is a neglected tropical disease (NTD) that is fatal if left untreated. Although approx. 13 million people live in moderate- to high-risk areas for infection, current treatments are plagued by problems with safety, efficacy, and emerging resistance. In an effort to fill the drug development pipeline for HAT, we have expanded previous work exploring the chemotype represented by the compound NEU-1090, with a particular focus on improvement of absorption, distribution, metabolism and elimination (ADME) properties. These efforts resulted in several compounds with substantially improved aqueous solubility, although these modifications typically resulted in a loss of trypanosomal activity. We herein report the results of our investigation into the antiparasitic activity, toxicity, and ADME properties of this class of compounds in the interest of informing the NTD drug discovery community and avoiding duplication of effort.

RSC Medicinal Chemistry published new progress about Blood. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Application of C10H17BN2O2.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Wang, Dinghai; Wu, Lianqian; Wang, Fei; Wan, Xiaolong; Chen, Pinhong; Lin, Zhenyang; Liu, Guosheng published the artcile< Asymmetric Copper-Catalyzed Intermolecular Aminoarylation of Styrenes: Efficient Access to Optical 2,2-Diarylethylamines>, Synthetic Route of 936250-20-3, the main research area is asym copper catalyzed intermol aminoarylation styrene alkylsulfonamide; diarylethylamine preparation.

We have developed a copper-catalyzed enantioselective intermol. aminoarylation of alkenes using a novel N-fluoro-N-alkylsulfonamide as the amine reagent, which could react with the Cu(I) catalyst to release a related amino radical. After addition to styrene, the generated benzylic radical could couple with a chiral L*CuIIAr complex to achieve enantioselective arylation. Various optical 2,2-diarylethylamines were efficiently synthesized from simple styrenes with high enantioselectivity, and these products can serve as valuable synthons toward bioactive mols.’ synthesis.

Journal of the American Chemical Society published new progress about Alkenes Role: RCT (Reactant), RACT (Reactant or Reagent). 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Synthetic Route of 936250-20-3.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics