pyrazoles-derivatives

The author of 《Discovery of pyrazole-thiophene derivatives as highly Potent, orally active Akt inhibitors》 were Zhan, Wenhu; Che, Jinxin; Xu, Lei; Wu, Yizhe; Hu, Xiaobei; Zhou, Yubo; Cheng, Gang; Hu, Yongzhou; Dong, Xiaowu; Li, Jia. And the article was published in European Journal of Medicinal Chemistry in 2019. Safety of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole The author mentioned the following in the article:

A series of pyrazole-thiophene derivatives exhibiting good Akt inhibitory activities were obtained on the basis of conformational restriction strategy, leading to the discovery of compound 1d(I) and 1o(II) which showed excellent in vitro antitumor effect against a variety of hematol. cancer cells and their potential of inducing apoptosis, blocking the cell cycles at S phase and significantly inhibiting the phosphorylation of downstream biomarkers of Akt kinase of cancer cells. Amongst, II also exhibited good PK profiles and inhibited about 40% tumor growth in MM1S xenograft model. II might be a potential candidate for further development. The experimental part of the paper was very detailed, including the reaction process of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Safety of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole)

1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. Safety of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

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

SDS of cas: 847818-74-0In 2016 ,《Design, synthesis and biological evaluation of pyrazol-furan carboxamide analogues as novel Akt kinase inhibitors》 appeared in European Journal of Medicinal Chemistry. The author of the article were Zhan, Wenhu; Xu, Lei; Dong, Xiaowu; Dong, Jun; Yi, Xiao; Ma, Xiaodong; Qiu, Ni; Li, Jia; Yang, Bo; Zhou, Yubo; Hu, Yongzhou. The article conveys some information:

A series of novel pyrazolylfuran carboxamides I (24a-d; X = S, R2 = R3 = H; R1, R4: a, H, 4-F; b, Cl, 4-F; c, Br, 4-F; d, H, 3,4-Cl2; 25a-e, X = O, R3 = H, R1, R2, R4: a, Cl, H, 4-F; b, Br, H, 4-F; c, Br, H, 3,4-Cl2; d, Cl, Cl, 4-F; e, Cl, Cl, 3,4-Cl2; 27a-c, X = NMe, R1, R2, R3, R4: a, Br, H, H, 3,4-Cl2; b, Br, Br, H, 3,4-Cl2; c, Cl, Cl, Cl, 3,4-Cl2) and II (26a-c; R1, R2, R4: a, H, Br, 3,4-Cl2; b, Cl, Br, 3,4-Cl2; c, Br, Br, 3,4-Cl2) were designed, synthesized and biol. evaluated for their Akt1 inhibitory activities, as well as anti-proliferative efficacies against HCT116 and OVCAR-8 cell lines. Most compounds exhibited moderate to excellent Akt1 inhibitory activities, together with favorable cytotoxicities. Further kinase selectivity assay of the most promising compound 25e illustrated that it was also potent against the structurally related AGC kinases, including Akt2, Akt3, ROCK1 and PKA, but was specific over kinases from other subfamilies. In addition, the Western blot anal. indicated that 25e could significantly suppress the phosphorylation level of Akt substrate GSK3β in PC-3 cell. Moreover, 25e demonstrated a concentration-dependent inhibition of phosphorylation of PRAS40 in LNCaP cell, with IC50 value of 30.4 nM. In the experiment, the researchers used many compounds, for example, 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0SDS of cas: 847818-74-0)

1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. SDS of cas: 847818-74-0

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

《Fused pyrazolopyrimidines. I. Pyrazolo[4,3-e]-v-triazolo[1,5-a]pyrimidine. A new heterocyclic system》 was published in Journal of Heterocyclic Chemistry in 1980. These research results belong to Khan, Misbahul Ain; Freitas, Antonio Carlos Carreira. COA of Formula: C10H6BrN3 The article mentions the following:

5-Azido-4-cyano-1-phenylpyrazole reacts with benzyl cyanide in the presence of MeONa to give the title ring derivative I. The results came from multiple reactions, including the reaction of 5-Bromo-1-phenyl-1H-pyrazole-4-carbonitrile(cas: 76767-44-7COA of Formula: C10H6BrN3)

5-Bromo-1-phenyl-1H-pyrazole-4-carbonitrile(cas: 76767-44-7) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. COA of Formula: C10H6BrN3

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

Category: pyrazoles-derivativesOn November 25, 2020 ,《Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases》 appeared in Journal of Medicinal Chemistry. The author of the article were Gerstenberger, Brian S.; Ambler, Catherine; Arnold, Eric P.; Banker, Mary-Ellen; Brown, Matthew F.; Clark, James D.; Dermenci, Alpay; Dowty, Martin E.; Fensome, Andrew; Fish, Susan; Hayward, Matthew M.; Hegen, Martin; Hollingshead, Brett D.; Knafels, John D.; Lin, David W.; Lin, Tsung H.; Owen, Dafydd R.; Saiah, Eddine; Sharma, Raman; Vajdos, Felix F.; Xing, Li; Yang, Xiaojing; Yang, Xin; Wright, Stephen W.. The article conveys some information:

Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family that regulates signal transduction downstream of receptors for the IL-23/IL-12 pathways and type I interferon family, where it pairs with JAK2 or JAK1, resp. On the basis of human genetic and emerging clin. data, a selective TYK2 inhibitor provides an opportunity to treat autoimmune diseases delivering a potentially differentiated clin. profile compared to currently approved JAK inhibitors. The discovery of an ATP-competitive pyrazolopyrazinyl series of TYK2 inhibitors was accomplished through computational and structurally enabled design starting from a known kinase hinge binding motif. With understanding of PK/PD relationships, a target profile balancing TYK2 potency and selectivity over off-target JAK2 was established. Lead optimization involved modulating potency, selectivity, and ADME properties which led to the identification of the clin. candidate PF-06826647 (22). The experimental process involved the reaction of 1-Methylpyrazole(cas: 930-36-9Category: pyrazoles-derivatives)

1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Category: pyrazoles-derivatives

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

Safronov, Sergey P.; Nagrimanov, Ruslan N.; Samatov, Aizat A.; Emel’yanenko, Vladimir N.; Zaitsau, Dzmitry H.; Pimerzin, Andrey A.; Skrzypczak, Andrzej; Verevkin, Sergey P. published an article on January 31 ,2019. The article was titled 《Benchmark properties of pyrazole derivatives as a potential liquid organic hydrogen carrier: Evaluation of thermochemical data with complementary experimental and computational methods》, and you may find the article in Journal of Chemical Thermodynamics.Reference of 1-Methylpyrazole The information in the text is summarized as follows:

The standard molar enthalpies of vaporization of alkyl-pyrazoles were derived from their vapor pressure-temperature dependence measured by the transpiration method as well as indirectly using solution calorimetry. Thermodn. data on vaporization processes available in the literature were collected, evaluated, and combined with our own exptl. results. Addnl. combustion experiments on the highly pure 1-methyl-pyrazoles helped to resolve ambiguity in the enthalpy of formation for this compound We have evaluated and recommended a set of vaporization and formation enthalpies for the alkyl-pyrazoles at 298.15 K as the reliable benchmark properties for further thermochem. calculations Gas phase molar enthalpies of formation of alkyl-pyrazoles calculated by the high-level quantum-chem. G4 and G3MP2 methods were in an excellent agreement with the recommended exptl. data. The hydrogenation/dehydrogenation reaction enthalpies of alkyl-pyrazoles were calculated and compared with the data for other potential liquid organic hydrogen carriers. In addition to this study using 1-Methylpyrazole, there are many other studies that have used 1-Methylpyrazole(cas: 930-36-9Reference of 1-Methylpyrazole) was used in this study.

1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Reference of 1-Methylpyrazole

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

The author of 《Inhibition of fatty acid release by pyrazole derivatives》 were Bizzi, Adalgisa. And the article was published in Progress in Biochemical Pharmacology in 1968. Recommanded Product: (3-methyl-1H-pyrazol-5-yl)methanol The author mentioned the following in the article:

In rats, 3,5-dimethylpyrazole (I) is quiet active in decreasing free fatty acid (FFA) and glycerol in adipose tissue as well as in plasma with doses as low as 50 μg/kg, i.p. In plasma after 2 hr, I and 5-carboxyl-3-methylpyrazole (II) appear more active than 3-methylpyrazole. When tested in vitro on the release of FFA from adipose tissue, II appeared to be the most active. The 3 compounds when given orally in doses of 0.75-30 mg/kg also produce up to a 50% decrease in plasma triglycerides. This effect is proportional to the dose used. The experimental part of the paper was very detailed, including the reaction process of (3-methyl-1H-pyrazol-5-yl)methanol(cas: 29004-73-7Recommanded Product: (3-methyl-1H-pyrazol-5-yl)methanol)

(3-methyl-1H-pyrazol-5-yl)methanol(cas: 29004-73-7) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Recommanded Product: (3-methyl-1H-pyrazol-5-yl)methanol

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

Xie, Jizhao; Xu, Huanji; Wu, Xinduo; Xie, Yunfeng; Lu, Xiuhong; Wang, Lisheng published their research in Bioorganic & Medicinal Chemistry Letters in 2021. The article was titled 《Design, synthesis and anti-TNBC activity of Azeliragon triazole analogues》.Application of 847818-74-0 The article contains the following contents:

Triple-neg. breast cancer (TNBC) is the most aggressive subtype of breast cancer. Many studies have shown a significant increase in the marker signal of the receptor for advanced glycation end-products (RAGE) with the malignant progression of tumor growth, metastasis and recurrence of breast cancer, including TNBC of primary tumors and lymph node metastases. Azeliragon is a RAGE inhibitor and it has been shown to actively inhibit the TNBC cell line, SUM149 (IC50 = 5.292 ± 0.310 μM). In order to develop a new anti-TNBC agent, we designed, synthesized and screened 26 Azeliragon triazole analogs to determine their anti-TNBC activities in vitro. The most active compound was KC-10 (3-(4-(5-butyl-1-(4′-chloro-[1,1′-biphenyl]-4-yl)-1H-1,2,4-triazol-3-yl)phenoxy)-N, N-diethylpropan-1-amine) with an IC50 value of 0.220 ± 0.034 μM. The experimental part of the paper was very detailed, including the reaction process of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Application of 847818-74-0)

1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. Application of 847818-74-0

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

In 2022,Bin, Huachao; Chen, Pei; Wu, Ming; Wang, Falu; Lin, Guifeng; Pan, Shulei; Liu, Jingming; Mu, Bo; Nan, Jinshan; Huang, Qiao; Li, Linli; Yang, Shengyong published an article in European Journal of Medicinal Chemistry. The title of the article was 《Discovery of a potent and highly selective inhibitor of ataxia telangiectasia mutated and Rad3-Related (ATR) kinase: Structural activity relationship and antitumor activity both in vitro and in vivo》.COA of Formula: C10H17BN2O2 The author mentioned the following in the article:

Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is an important regulator of the DNA damage response (DDR), especially in response to replication stress (RS). Tumor cells with ataxia-telangiectasia mutated (ATM) kinase loss of function or DDR defects that promote replicative stress are often more reliant on ATR for survival, highlighting ATR as a good antitumor target under the principle of synthetic lethality. Herein we report the discovery of a potent and highly selective ATR inhibitor, SKLB-197, which was obtained through structural optimization and structure-activity relationship (SAR) studies towards a hit compound (Cpd-1). SKLB-197 showed an IC50 value of 0.013 μM against ATR but very weak or no activity against other 402 protein kinases. It displayed potent antitumor activity against ATM-deficent tumors both in vitro and in vivo. In addition, this compound exhibited good pharmacokinetic properties. Overall, SKLB-197 could be a promising lead compound for drug discovery targeting ATR and deserves further in-depth studies. In the experiment, the researchers used many compounds, for example, 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0COA of Formula: C10H17BN2O2)

1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. COA of Formula: C10H17BN2O2

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

Reference of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleIn 2022 ,《Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted Cancers》 appeared in Journal of Medicinal Chemistry. The author of the article were Smith, Christopher R.; Aranda, Ruth; Bobinski, Thomas P.; Briere, David M.; Burns, Aaron C.; Christensen, James G.; Clarine, Jeffery; Engstrom, Lars D.; Gunn, Robin J.; Ivetac, Anthony; Jean-Baptiste, Ronald; Ketcham, John M.; Kobayashi, Masakazu; Kuehler, Jon; Kulyk, Svitlana; Lawson, J. David; Moya, Krystal; Olson, Peter; Rahbaek, Lisa; Thomas, Nicole C.; Wang, Xiaolun; Waters, Laura M.; Marx, Matthew A.. The article conveys some information:

The PRMT5•MTA complex has recently emerged as a new synthetically lethal drug target for the treatment of MTAP-deleted cancers. Here, we report the discovery of development candidate MRTX1719. MRTX1719 is a potent and selective binder to the PRMT5•MTA complex and selectively inhibits PRMT5 activity in MTAP-deleted cells compared to MTAP-wild-type cells. Daily oral administration of MRTX1719 to tumor xenograft-bearing mice demonstrated dose-dependent inhibition of PRMT5-dependent sym. dimethylarginine protein modification in MTAP-deleted tumors that correlated with antitumor activity. A 4-(aminomethyl)phthalazin-1(2H)-one hit was identified through a fragment-based screen, followed by x-ray crystallog., to confirm binding to the PRMT5•MTA complex. Fragment growth supported by structural insights from x-ray crystallog. coupled with optimization of pharmacokinetic properties aided the discovery of development candidate MRTX1719. In the experiment, the researchers used many compounds, for example, 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Reference of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole)

1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Reference of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

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

Computed Properties of C5H6N2O2In 1976 ,《Unusual reaction of 3-carbomethoxy-Δ2-pyrazoline in the presence of lead tetraacetate》 appeared in Khimiya Geterotsiklicheskikh Soedinenii. The author of the article were Akhrem, A. A.; Kvasyuk, E. I.; Mikhailopulo, I. A.. The article conveys some information:

Treatment of pyrazolinecarboxylate I with Pb(OAc)4 in dry C6H6 30 min at 70° gave 71% II and 14% III whose structures were confirmed by ir, uv, and NMR spectra. In the experiment, the researchers used many compounds, for example, Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Computed Properties of C5H6N2O2)

Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4) belongs to pyrazoles. Pyrazole derivatives have been reported to exhibit a wide range of applications in medicinal chemistry and pharmacology. A large number of drugs incorporating pyrazole structure have been utilized as partial agonists for nicotinic acid receptors, antidepressants, antimicrobial agents, antiviral agents, and antifungal agents solely or along with the combination of other structural motifs.Computed Properties of C5H6N2O2

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