Tag: M.W=200-250

Saal, Christoph; Becker, Axel; Krier, Mireille; Fuchss, Thomas published the artcile< Atropisomerism - A Neglected Way to Escape Out of Solubility Flatlands>, Name: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is atropisomer aqueous solubility enantiomers; ATM; ATM-inhibitor; Ataxia-telangiectasia mutated kinase; Atropisomerism; Chirality; Crystal structure; Dissolution; Kinase inhibitor; M4076; Solubility.

Low solubility of drugs represents a major challenge during research and development. Ways to overcome this are either focused on formulation development or optimization of the mol. structure of the drug. The latter is not only governed by the constitution of the mol. but also by its stereochem. Development of enantiomers in contrast to racemic mixtures has become the state of the art over the last decades as this leads to higher potency and selectivity. Thus, enantiopure drugs require lower doses compared to their racemates. Addnl., selecting one enantiomer also leads to improved solubility of the drug compared to its racemic compound While this effect is well known for enantiomers and racemic compounds where chirality is introduced via a chiral central atom, here we describe the first case where improved solubility is realized by selecting an axially chiral atropisomer.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Atropisomers. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Name: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

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

Hilpert, Lukas J.; Sieger, Simon V.; Haydl, Alexander M.; Breit, Bernhard published the artcile< Palladium- and Rhodium-Catalyzed Dynamic Kinetic Resolution of Racemic Internal Allenes Towards Chiral Pyrazoles>, Synthetic Route of 13808-65-6, the main research area is pyrazole allene palladium rhodium catalyst chemoselective regioselective enantioselective hydroamination; alkenylpyrazole preparation; asymmetric catalysis; dynamic kinetic resolution; internal allenes; palladium; rhodium.

A complementing Pd- and Rh-catalyzed dynamic kinetic resolution (DKR) of racemic allenes leading to N-allylated pyrazoles was described. Such compounds are of enormous interest in medicinal chem. as certified drugs and potential drug candidates. The new methods feature high chemo-, regio- and enantioselectivities aside from displaying a broad substrate scope and functional group compatibility. A mechanistic rational accounting for allene racemization and trans-alkene selectivity was discussed.

Angewandte Chemie, International Edition published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Synthetic Route of 13808-65-6.

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

Dong, Xinrui; Jiang, Wenhua; Hua, Dexiang; Wang, Xiaohui; Xu, Liang; Wu, Xiaoxing published the artcile< Radical-mediated vicinal addition of alkoxysulfonyl/fluorosulfonyl and trifluoromethyl groups to aryl alkyl alkynes>, Safety of 1-(4-Bromophenyl)-1H-pyrazole, the main research area is trifluoromethylalkenylsulfonate ester sulfonyl fluoride preparation diastereoselective; aryl alkyl alkyne alkoxy fluorosulfonyl trifluoromethylation radical mediator.

The addition of sulfonyl radicals to alkenes and alkynes is a valuable method for constructing useful highly functionalized sulfonyl compounds The underexplored alkoxy- and fluorosulfonyl radicals are easily accessed by CF3 radical addition to readily available allylsulfonic acid derivatives and then β-fragmentation. These substituted sulfonyl radicals add to aryl alkyl alkynes to give vinyl radicals that are trapped by trifluoromethyl transfer to provide tetra-substituted alkenes bearing the privileged alkoxy- or fluorosulfonyl group on one carbon and a trifluoromethyl group on the other. This process exhibits broad functional group compatibility and allows for the late-stage functionalization of drug mols., demonstrating its potential in drug discovery and chem. biol. And alkyl allylsulfonates/allylsulfonyl fluoride.

Chemical Science published new progress about Alkynes, aryl Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation) (alkyl). 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Safety of 1-(4-Bromophenyl)-1H-pyrazole.

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

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

Milner, Phillip J.; Yang, Yang; Buchwald, Stephen L. published the artcile< In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides>, Safety of 4-Bromo-3-phenyl-1H-pyrazole, the main research area is palladium catalyzed fluorination five membered heteroaryl bromide; bromoazole palladium catalyzed fluorination theor.

A thorough investigation of the challenging Pd-catalyzed fluorination of five-membered heteroaryl bromides is presented. Crystallog. studies and d. functional theory (DFT) calculations suggest that the challenging step of this transformation is C-F reductive elimination of five-membered heteroaryl fluorides from Pd(II) complexes. On the basis of these studies, we have found that various heteroaryl bromides bearing Ph groups in the ortho position can be effectively fluorinated under catalytic conditions. Highly activated 2-bromoazoles, such as 8-bromocaffeine, are also viable substrates for this reaction.

Organometallics published new progress about Crystal structure. 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Safety of 4-Bromo-3-phenyl-1H-pyrazole.

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

Bellenie, Benjamin R.; Hall, Edward; Bruce, Ian; Spendiff, Matthew; Culshaw, Andrew; McDonald, Sarah; Ambarkhane, Ameet; Chinn, Colin; Thomas, Matthew; Rosner, Elisabeth; Bracher, Marguerite; Nicklin, Paul; Marshall, Stephen; Coote, Julie; Cullen, Eva; Tessier, Clemence; Wuersch, Kuno; Lal, Ajay; Wallis, Gillian; Hollingworth, Gregory J.; Neef, James published the artcile< Discovery and Toxicological Profiling of Aminopyridines as Orally Bioavailable Selective Inhibitors of PI3-Kinase γ>, Quality Control of 1046832-21-6, the main research area is pharmacokinetic aminopyridine oral inhibitor PI3K gamma airway inflammation toxicol.

Using a novel physiol. relevant in vitro human whole blood neutrophil shape change assay, an aminopyrazine series of selective PI3Kγ inhibitors was identified and prioritized for further optimization. Severe solubility limitations associated with the series leading to low oral bioavailability and poor exposures, especially at higher doses, were overcome by moving to an aminopyridine core. Compound 33, with the optimal balance of on-target activity, selectivity, and pharmacokinetic parameters, progressed into in vivo studies and demonstrated good efficacy (10 mg/kg) in a rat model of airway inflammation. Sufficient exposures were achieved at high doses to support toxicol. studies, where unexpected inflammatory cell infiltrates in cardiovascular tissue prevented further compound development.

Journal of Medicinal Chemistry published new progress about Aminopyridines Role: PAC (Pharmacological Activity), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Quality Control of 1046832-21-6.

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

Khan, M. A.; Mustafa, A. published the artcile< Ipso substitution in heterocyclic compounds. Bromination of pyrazole-4-carboxaldehydes>, Recommanded Product: 4-Bromo-3-phenyl-1H-pyrazole, the main research area is pyrazolecarboxaldehyde bromination.

Bromination of pyrazolecarboxaldehydes I (R1 = H, Me; R2 = H, NO2) with Br in AcOH at room temperature for 30 min gave 46-66% bromopyrazolecarboxaldehydes II.

Pharmazie published new progress about Bromination. 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Recommanded Product: 4-Bromo-3-phenyl-1H-pyrazole.

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