Category: pyrazoles-derivatives

Zhao, Yujun; Zhou, Bing; Bai, Longchuan; Liu, Liu; Yang, Chao-Yie; Meagher, Jennifer L.; Stuckey, Jeanne A.; McEachern, Donna; Przybranowski, Sally; Wang, Mi; Ran, Xu; Aguilar, Angelo; Hu, Yang; Kampf, Jeff W.; Li, Xiaoqin; Zhao, Ting; Li, Siwei; Wen, Bo; Sun, Duxin; Wang, Shaomeng published the artcile< Structure-Based Discovery of CF53 as a Potent and Orally Bioavailable Bromodomain and Extra-Terminal (BET) Bromodomain Inhibitor>, Synthetic Route of 118430-74-3, the main research area is pyrazole pyrimido indole preparation bromodomain inhibitor cancer.

We report the structure-based discovery of CF53 (28) as a highly potent and orally active inhibitor of bromodomain and extra-terminal (BET) proteins. By the incorporation of a NH-pyrazole group into the 9H-pyrimido[4,5-b]indole core, we identified a series of compounds that bind to BRD4 BD1 protein with Ki values of <1 nM and achieve low nanomolar potencies in the cell growth inhibition of leukemia and breast cancer cells. The most-promising compound, CF53, possesses excellent oral pharmacokinetic properties and achieves significant antitumor activity in both triple-neg. breast cancer and acute leukemia xenograft models in mice. Determination of the co-crystal structure of CF53 with the BRD4 BD1 protein provides a structural basis for its high binding affinity to BET proteins. CF53 is very selective over non-BET bromodomain-containing proteins. These data establish CF53 as a potent, selective, and orally active BET inhibitor, which warrants further evaluation for advanced preclin. development. Journal of Medicinal Chemistry published new progress about Antitumor agents. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Synthetic Route of 118430-74-3.

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

Beveridge, Ramsay E.; Wallweber, Heidi Ackerly; Ashkenazi, Avi; Beresini, Maureen; Clark, Kevin R.; Gibbons, Paul; Ghiro, Elise; Kaufman, Susan; Larivee, Alexandre; Leblanc, Melissa; Leclerc, Jean-Philippe; Lemire, Alexandre; Ly, Cuong; Rudolph, Joachim; Schwarz, Jacob B.; Srivastava, Sanjay; Wang, Weiru; Zhao, Liang; Braun, Marie-Gabrielle published the artcile< Identification of BRaf-Sparing Amino-Thienopyrimidines with Potent IRE1α Inhibitory Activity>, Application In Synthesis of 1046832-21-6, the main research area is preparation BRaf amino thieno pyrimidine derivative IRE1 inhibitor cancer.

Amino-quinazoline BRaf kinase inhibitor 2 was identified from a library screen as a modest inhibitor of the unfolded protein response (UPR) regulating potential anticancer target IRE1α. A combination of crystallog. and conformational considerations were used to guide structure-based attenuation of BRaf activity and optimization of IRE1α potency. Quinazoline 6-position modifications were found to provide up to 100-fold improvement in IRE1α cellular potency but were ineffective at reducing BRaf activity. A salt bridge contact with Glu651 in IRE1α was then targeted to build in selectivity over BRaf which instead possesses a histidine in this position (His539). Torsional angle anal. revealed that the quinazoline hinge binder core was ill-suited to accommodate the required conformation to effectively reach Glu651, prompting a change to the thienopyrimidine hinge binder. Resulting analogs such as 25 demonstrated good IRE1α cellular potency and imparted more than 1000-fold decrease in BRaf activity.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Application In Synthesis of 1046832-21-6.

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

Senga, Keitaro; O’Brien, Darrell E.; Scholten, Mieka B.; Novinson, Thomas; Miller, Jon P.; Robins, Roland K. published the artcile< Synthesis and enzymic activity of various substituted pyrazolo[1,5-a]-1,3,5-triazines as adenosine cyclic 3',5'-phosphate phosphodiesterase inhibitors>, COA of Formula: C6H5ClN4S, the main research area is pyrazolotriazine cAMP phosphodiesterase inhibitor preparation; pyrazolylamidine cyclization; amidine pyrazolyl cyclization.

I (R1 = H, Me, Et, SMe; R2 = H, Ph, Pr, SMe, NHEt, NHBu, NEt2 piperidino, OH, NHPr, SH, OCHMe2, Me, SEt, OMe, OPr; R3 = Ph, C6H4OMe-4, H; R4 = H, Br, C6H4Me-3, Ph, cyano, CO2Et, Cl), prepared by cyclizing II with (R2CO)2O or R2C(OEt)3, followed by electrophilic substitution in the pyrazole ring and/or nucleophilic substitution in the 1,3,5-triazine moiety, were studied as inhibitors of cAMP phosphodiesterase (PDE) isolated from bovine brain, bovine heart, and rabbit lung. A number of compounds were superior to theophylline. 2-Ethyl-7-phenylpyrazolo[1,5-a]-1,3,5-triazine was 97 times more potent than theophylline as an inhibitor of bovine brain PDE. 8-Bromo-2,4-dimethyl-7-phenylpyrazolo[1,5-a]-1,3,5-triazine showed αlung = 40 compared to αheart = 3.0. Thus, various substituents could increase or decrease the inhibition relative to the type and source of tissue from which the PDE was isolated. The most active compound was 8-bromo-4-(diethylamino)-7-phenylpyrazolo[1,5-a]-1,3,5-triazine which was 185 times more potent than theophylline as an inhibitor of PDE isolated from rabbit lung. Structure-activity relationships were reviewed.

Journal of Medicinal Chemistry published new progress about Structure-activity relationship. 54346-19-9 belongs to class pyrazoles-derivatives, and the molecular formula is C6H5ClN4S, COA of Formula: C6H5ClN4S.

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

Gutierrez, Corey D.; Bavetsias, Vassilios; McDonald, Edward published the artcile< ClTi(OiPr)3-Promoted Reductive Amination on the Solid Phase: Combinatorial Synthesis of a Biaryl-Based Sulfonamide Library>, Category: pyrazoles-derivatives, the main research area is combinatorial library biarylsulfonamide preparation; titanium promotor reductive amination aldehyde solid support; sulfonylation resin bound amine; sulfonamide biaryl combinatorial library preparation.

A combinatorial library (9 amines × 7 sulfonyl chlorides × 13 boronic acids = 819 compounds) was produced on solid support in a four-step sequence, i.e., ClTi(OiPr)3-promoted reductive amination, sulfonylation of the resin-bound amine, Suzuki cross-coupling, and acid-mediated cleavage. The library members (e.g. I) were obtained in moderate quantity (1-8 mg) with over 70% of the sampled products greater than 90% pure according to LC-MS anal.

Journal of Combinatorial Chemistry published new progress about Aldehydes Role: CMB (Combinatorial Study), RCT (Reactant), RACT (Reactant or Reagent). 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Category: pyrazoles-derivatives.

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

Jiang, Bo; Ning, Yi; Fan, Wei; Tu, Shu-Jiang; Li, Guigen published the artcile< Oxidative Dehydrogenative Couplings of Pyrazol-5-amines Selectively Forming Azopyrroles>, Quality Control of 118430-74-3, the main research area is stereoselective synthesis azopyrrole; oxidative dehydrogenative coupling pyrazolamine copper iodine.

New oxidative dehydrogenative couplings of pyrazol-5-amines for the selective synthesis of azopyrrole derivatives have been described. The reaction simultaneously installs C-I and N-N bonds through iodination and oxidation; a copper-catalyzed oxidative coupling process led to azopyrroles,. E.g., in presence of I2, TBHP, and K2CO3 in EtOH, dehydrogenative coupling of pyrazol-5-amine (I) gave 86% iodinated azopyrrole [(E)-II]. E.g., in presence of CuI, 1,10-phenanthroline, and TBHP in CH2Cl2, dehydrogenative coupling of I gave 56% (E)-III. The resulting iodo-substituted azopyrroles were employed by treatment with various terminal alkynes through Sonogashira cross-coupling leading to new azo compounds

Journal of Organic Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Quality Control of 118430-74-3.

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

Wei, Wen; Yu, Hao; Zangarelli, Agnese; Ackermann, Lutz published the artcile< Deaminative meta-C-H alkylation by ruthenium(II) catalysis>, COA of Formula: C9H7BrN2, the main research area is alkyl arene preparation chemoselective regioselective; heteroarene Katritzky pyridinium salt deaminative alkylation ruthenium catalyst.

A ruthenium-catalyzed meta-C-H deaminative alkylation with easily accessible amino acid-derived Katritzky pyridinium salts I (R = H, CO2Me, N-[(2S)-1-methoxy-1-oxopropan-2-yl]carbamoyl; R1 = CO2CH2CH3, CH2C6H5, 1H-indol-3-ylmethyl, etc.) has been described. Likewise, remote C-H benzylations were accomplished with high levels of chemoselectivity and remarkable functional group tolerance. The meta-C-H activation approach combined with the deaminative strategy represents a rare example of selectively converting C(sp3)-N bonds into C(sp3)-C(sp2) bonds.

Chemical Science published new progress about Alkylation catalysts, regioselective (deaminative, chemoselective). 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, COA of Formula: C9H7BrN2.

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