pyrazoles-derivatives

Saha, Debasmita; Ryan, Katie Rose; Lakkaniga, Naga Rajiv; Smith, Erica Lane; Frett, Brendan published the artcile< Pyrazoloadenine Inhibitors of the RET Lung Cancer Oncoprotein Discovered by a Fragment Optimization Approach>, Safety of 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine, the main research area is pyrazoloadenine inhibitor RET lung cancer oncoprotein fragment optimization; RET inhibitor; fragment-based drug discovery; oncoproteins; pyrazoloadenines.

A fragment-based drug-discovery approach was used on a pyrazoloadenine fragment library to uncover new mols. that target the RET (REarranged during Transfection) oncoprotein, which is a driver oncoprotein in ∼2 % of non-small-cell lung cancers. The fragment library was screened against the RET kinase and LC-2/ad (RET-driven), KM-12 (TRKA-driven matched control) and A549 (cytotoxic control) cells to identify selective scaffolds that could inhibit RET-driven growth. An unsubstituted pyrazoloadenine fragment was found to be active on RET in a biochem. assay, but reduced cell viability in non-RET-driven cell lines (EC50=1 and 3 μM, resp.). To increase selectivity for RET, the pyrazoloadenine was modeled in the RET active site, and two domains were identified that were probed with pyrazoloadenine fragment derivatives to improve RET affinity. Scaffolds at each domain were merged to generate a novel lead compound, 8 p (I), which exhibited improved activity and selectivity for the RET oncoprotein (A549 EC50=5.92 μM, LC-2/ad EC50=0.016 μM, RET IC50=0.000326 μM).

ChemMedChem published new progress about Antitumor agents. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Safety of 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine.

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

Zhang, Shiyan; Huang, Chaoying; Lyu, Xilin; Wang, Peipei; Zang, Yi; Wang, Zengtao; Wang, Huan; Li, Jia; Zhao, Yujun published the artcile< Discovery of a 2-pyridinyl urea-containing compound YD57 as a potent inhibitor of apoptosis signal-regulating kinase 1 (ASK1)>, Name: 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine, the main research area is pyridinyl urea containing compound preparation ASK1 inhibitor cancer; ASK1; ASK2; Apoptosis; Cell cycle arrest; Selectivity.

Inhibition of MAP3K kinase ASK1 has been an attractive strategy for the treatment of nonalcoholic steatohepatitis and multiple sclerosis, among others. Herein, we reported the discovery of 2-pyridinyl urea-containing compound 14l (YD57) as a potent, small-mol. inhibitor of ASK1. 14l was selective against MAP3K kinases ASK2 and TAK1 (>140-fold), while it also inhibited several cell cycle regulating kinases with IC50 values in a range of 90-400 nM (<20-fold selectivity). As a consequence, 14l had stronger apoptosis induction, more potent G1 cell cycle arrest activities, and lower IC50 value of cell growth inhibition than that of GS4997 in HepG2 cancer cell line. On the other hand, 14l did not inhibit ASK1 and p38 phosphorylation in intact cells. We reason that the multi-target effects of 14l likely neutralized the activities caused by inhibition of cellular ASK1. Future studies of these ASK1 inhibitors should pay close attention to their kinome selectivity profile. European Journal of Medicinal Chemistry published new progress about Antitumor agents. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Name: 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine.

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

Vasilevskii, S. F.; Shvartsberg, M. S. published the artcile< Oxidative iodination of substituted N-methylpyrozoles>, Computed Properties of 17827-61-1, the main research area is oxidation iodination methylpyrazole; pyrazole methyl oxidation iodination.

1-Methylpyrazole was iodinated in position 4 with iodine in aqueous KI with a low yield: introduction of an electron donor substituent in position 3 or 5 increased the reactivity of the heterocycle. Iodination of 5-amino-1,3-dimethylpyrazole gave 80% 4-iodide, but its N-acetyl derivative did not react. N-Methylpyrazole-4-carboxylic acids and -4-aldehydes underwent iodination under the same conditions and gave the 4-iodo or polyiodo derivative The presence of moderately strong electro acceptor substituents, e.g., iodo, or CO2Me, in the ring in the 4 position did not exclude the possibility of oxidative iodination at other positions of the ring. Strong electron acceptor groups, e.g., NO2, retard the reaction.

Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya published new progress about Iodination. 17827-61-1 belongs to class pyrazoles-derivatives, and the molecular formula is C6H8N2O2, Computed Properties of 17827-61-1.

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

Kumar, Rahul; Turcaud, Serge; Micouin, Laurent published the artcile< The Reaction of Dimethylalkynylaluminum Reagents with Trimethylsilyldiazomethane: Original Reactivity Leading to New α-Silylated Alkynyl Hydrazones>, Electric Literature of 13808-65-6, the main research area is methylalkynylaluminum reaction silyldiazomethane preparation silylated alkynyl hydrazone.

Trimethylsilyldiazomethane does not react as a homologating reagent but as a C-electrophilic species with dimethylalkynylaluminum reagents. This unprecedented reactivity enables a simple access to unusual α-silylated alkynyl hydrazones.

Organic Letters published new progress about Alkynes Role: RCT (Reactant), RACT (Reactant or Reagent) (aluminated). 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Electric Literature of 13808-65-6.

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

Drew, Samuel L.; Thomas-Tran, Rhiannon; Beatty, Joel W.; Fournier, Jeremy; Lawson, Kenneth V.; Miles, Dillon H.; Mata, Guillaume; Sharif, Ehesan U.; Yan, Xuelei; Mailyan, Artur K.; Ginn, Elaine; Chen, Jie; Wong, Kent; Soni, Divyank; Dhanota, Puja; Chen, Pei-Yu; Shaqfeh, Stefan G.; Meleza, Cesar; Pham, Amber T.; Chen, Ada; Zhao, Xiaoning; Banuelos, Jesus; Jin, Lixia; Schindler, Ulrike; Walters, Matthew J.; Young, Stephen W.; Walker, Nigel P.; Leleti, Manmohan Reddy; Powers, Jay P.; Jeffrey, Jenna L. published the artcile< Discovery of Potent and Selective PI3Kγ Inhibitors>, Name: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is PI3K gamma inhibitors ATP binding site SAR hydrogen bond.

The selective inhibition of the lipid signaling enzyme PI3Kγ constitutes an opportunity to mediate immunosuppression and inflammation within the tumor microenvironment but is difficult to achieve due to the high sequence homol. across the class I PI3K isoforms. Here, we describe the design of a novel series of potent PI3Kγ inhibitors that attain high isoform selectivity through the divergent projection of substituents into both the “”selectivity”” and “”alkyl-induced”” pockets within the ATP (ATP) binding site of PI3Kγ. These efforts have culminated in the discovery of 5-[2-amino-3-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl]-2-[(1S)-1-cyclopropylethyl]-7-(trifluoromethyl)-2,3-dihydro-1H-isoindol-1-one (4(I), IC50 = 0.064 μM, THP-1 cells), which displays >600-fold selectivity for PI3Kγ over the other class I isoforms and is a promising step toward the identification of a clin. development candidate. The structure-activity relationships identified throughout this campaign demonstrate that greater γ-selectivity can be achieved by inhibitors that occupy an “”alkyl-induced”” pocket and possess bicyclic hinge-binding motifs capable of forming more than one hydrogen bond to the hinge region of PI3Kγ.

Journal of Medicinal Chemistry published new progress about Crystal structure (compound 4 bound to hPI3Kγ). 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

Lyalin, Boris V.; Sigacheva, Vera L.; Kokorekin, Vladimir A.; Petrosyan, Vladimir A. published the artcile< A new synthesis of azopyrazoles by oxidation of C-aminopyrazoles on a NiO(OH) electrode>, Application of C7H11N3, the main research area is amino pyrazole electrochem oxidation; azopyrazole diastereoselective preparation.

Oxidation of C-amino-N-alkylpyrazoles on a NiO(OH) electrode in an aqueous alk. medium afforded the corresponding azopyrazoles. The success in implementation of these processes was due to the structure of C-aminopyrazoles.

Mendeleev Communications published new progress about Azo compounds Role: SPN (Synthetic Preparation), PREP (Preparation). 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Application of C7H11N3.

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

Adachi, Ikuo; Yamamori, Teruo; Hiramatsu, Yoshiharu; Sakai, Katsunori; Sato, Hatsuo; Kawakami, Masaru; Uno, Osamu; Ueda, Motohiko published the artcile< Studies on dihydropyridines. II. Synthesis of 4,7-dihydropyrazolo[3,4-b]pyridines with vasodilating and antihypertensive activities>, Formula: C7H11N3, the main research area is coronary vasodilator dihydropyrazolopyridine preparation; structure property relationship dihydropyrazolopyridine antihypertensive; pyrazolopyridine dihydro antihypertensive preparation; aminopyrazole unsaturated ketoester cyclocondensation; calcium channel blocker dihydropyrazolopyridine.

A series of 4-aryl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate derivatives I (R = Me, Ph, cyclopentyl; R1 = Me, Et, CHMe2, cyclohexyl, substituted phenethyl, etc.; R2 = 2-O2NC6H4, 3-O2NC6H4, 2-ClC6H4, 2.8-Cl2C6H4, pyridyl; R3 = H, Me, CHMe2, Ph, cycloalkyl, CO2Et, pyridyl, etc.) was prepared and the compounds were tested for Ca-blocking activity in isolated guinea pig portal vein, antihypertensive activity in spontaneously hypertensive rats, and coronary vasodilating effect in isolated guinea pig heart. A number of derivatives had potent antihypertensive and coronary vasodilating activities. The structure-activity relationships of the series indicated that a 3-cyclopentyl or 3-cyclohexyl substituent and a hydrophobic 5-ester moiety with moderate bulkiness were effective for increasing the pharmacol. potencies.

Chemical & Pharmaceutical Bulletin published new progress about Antihypertensives. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Formula: C7H11N3.

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

Haydl, Alexander M.; Xu, Kun; Breit, Bernhard published the artcile< Regio- and Enantioselective Synthesis of N-Substituted Pyrazoles by Rhodium-Catalyzed Asymmetric Addition to Allenes>, Application In Synthesis of 13808-65-6, the main research area is pyrazole terminal alkene addition rhodium catalyst; allylated pyrazole asym preparation; allenes; allylic compounds; asymmetric catalysis; heterocycles; rhodium.

The rhodium-catalyzed asym. N-selective coupling of pyrazole derivatives with terminal allenes gives access to enantioenriched secondary and tertiary allylic pyrazoles, i.e. I, which can be employed for the synthesis of medicinally important targets. The reaction tolerates a large variety of functional groups and labeling experiments gave insights into the reaction mechanism. This new methodol. was further applied in a highly efficient synthesis of JAK 1/2 inhibitor (R)-ruxolitinib.

Angewandte Chemie, International Edition published new progress about Addition reaction catalysts, stereoselective. 13808-65-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Application In Synthesis of 13808-65-6.

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