Month: February 2023

Biaryl substituted hydantoin compounds as TACE inhibitors was written by Yu, Wensheng;Tong, Ling;Kim, Seong Heon;Wong, Michael K. C.;Chen, Lei;Yang, De-Yi;Shankar, Bandarpalle B.;Lavey, Brian J.;Zhou, Guowei;Kosinski, Aneta;Rizvi, Razia;Li, Dansu;Feltz, Robert J.;Piwinski, John J.;Rosner, Kristin E.;Shih, Neng-Yang;Siddiqui, M. Arshad;Guo, Zhuyan;Orth, Peter;Shah, Himanshu;Sun, Jing;Umland, Shelby;Lundell, Daniel J.;Niu, Xiaoda;Kozlowski, Joseph A.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2010.Related Products of 73387-46-9 This article mentions the following:

We disclose further optimization of hydantoin TNF-α convertase enzyme (TACE) inhibitors. SAR with respect to the non-prime region of TACE active site was explored. A series of biaryl substituted hydantoin compounds was shown to have sub-nanomolar K _i, good rat PK, and good selectivity vs. MMP-1, -2, -3, -7, -9, and -13. In the experiment, the researchers used many compounds, for example, 3-(4-Bromophenyl)-1H-pyrazole (cas: 73387-46-9Related Products of 73387-46-9).

3-(4-Bromophenyl)-1H-pyrazole (cas: 73387-46-9) belongs to pyrazole derivatives. As is the case with imidazoles, the pyrazole ring offers many opportunities to create new multiring systems that incorporate this heterocycle. Pyrazoles and pyrimidines have diverse biological and pharmacological activities. There are a number of antimicrobial compounds containing pyrazole moiety as the core unit. Pyrazofurin is important antimicrobial drug and 2-methylpyrimidine-4-ylamine derivatives I and II were found to be effective inhibitors of Escherichia coli PDHc-E1 with antibacterial and antifungal activity.Related Products of 73387-46-9

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

Discovery of a Teraryl Oxazolidinone Compound (S)-N-((3-(3-Fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide Phosphate as a Novel Antimicrobial Agent with Enhanced Safety Profile and Efficacies was written by Yang, Tao;Chen, Gong;Sang, Zitai;Liu, Yuanyuan;Yang, Xiaoyan;Chang, Ying;Long, Haiyue;Wei, Ang;Tang, Jianying;Wang, Zhenling;Li, Guobo;Yang, Shengyong;Zhang, Jingren;Wei, Yuquan;Luo, Youfu. And the article was included in Journal of Medicinal Chemistry in 2015.Synthetic Route of C8H7N3 This article mentions the following:

A series of novel teraryl oxazolidinone compounds was designed, synthesized, and evaluated for their antimicrobial activity and toxicities. The compounds with aromatic N-heterocyclic substituents at the 4-position of pyrazolyl ring showed better antibacterial activity against the tested bacteria than other compounds with different patterns of substitution. Among all potent compounds, I exhibited promising safety profile in MTT assays and in hERG K⁺ channel inhibition test. Furthermore, its phosphate was found to be highly soluble in water (47.1 mg/mL), which is beneficial for the subsequent in vivo test. In MRSA systemic infection mice models, I phosphate exerted significantly improved survival protection compared with linezolid. The compound also demonstrated high oral bioavailability (F = 99.1%). Moreover, from the results of in vivo toxicol. experiments, I phosphate would be predicted to have less bone marrow suppression. In the experiment, the researchers used many compounds, for example, 3-(1H-Pyrazol-3-yl)pyridine (cas: 45887-08-9Synthetic Route of C8H7N3).

3-(1H-Pyrazol-3-yl)pyridine (cas: 45887-08-9) belongs to pyrazole derivatives. Pyrazole has two ring nitrogen atoms in which N1 is pyrrolic and N2 is pyridine-like. The N1 nitrogen is not reactive but is deprotonated in the presence of a base-forming anion. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Synthetic Route of C8H7N3

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

Substituent-oriented C-N bond formation via N-H insertion or Wolff rearrangement of 5-aryl-1H-pyrazoles and diazo compounds was written by Zuo, Youpeng;He, Xinwei;Ning, Yi;Tang, Qiang;Xie, Mengqing;Hu, Wangcheng;Shang, Yongjia. And the article was included in Organic & Biomolecular Chemistry in 2019.Formula: C9H7BrN2 This article mentions the following:

A facile and efficient synthetic strategy for the chemoselective synthesis of N-substituted 3-aryl-1H-pyrazole derivatives was developed and it was oriented by different 2-diazo compounds Both N-H insertion and Wolff-rearrangement products were obtained selectively by the opportune choice of diazo compounds N-Cyclohexenone 3-aryl-1H-pyrazoles were formed using cyclic 2-diazo-1,3-diketones via N-H insertion in the presence of a copper catalyst and α-carbonyl 3-aryl-1H-pyrazoles were be synthesized through a Wolff-rearrangement process without any catalyst under thermal conditions. Moreover, both reactions were carried out in moderate to excellent yields (58-93%) and showed good functional group tolerance. In the experiment, the researchers used many compounds, for example, 3-(4-Bromophenyl)-1H-pyrazole (cas: 73387-46-9Formula: C9H7BrN2).

3-(4-Bromophenyl)-1H-pyrazole (cas: 73387-46-9) belongs to pyrazole derivatives. Pyrazoles, a five-membered heterocycle containing two adjacent nitrogen atoms, are the core structures found in a number of molecules that possess a wide range of pharmaceutical and agricultural activities. Pyrazoles can be selectively lithiated at different carbons and subsequently react with electrophiles depending on the substitution patterns.Formula: C9H7BrN2

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

The N-alkylation and N-arylation of unsymmetrical pyrazoles was written by Grimmett, M. Ross;Lim, K. H. Richard;Weavers, Rex T.. And the article was included in Australian Journal of Chemistry in 1979.Synthetic Route of C4H5N3O2 This article mentions the following:

Unsym. pyrazoles with alkyl, aryl, nitro and carboxyl substituents at C-3 or C-5 were methylated with Me₂SO₄-MeOH, Me₂SO₂ in basic medium, and with CH₂N₂. The ratios of the isomeric N-methylpyrazoles were determined by NMR and gas liquid chromatog. The modified Ullmann phenylation was also applied to these pyrazoles. Product orientations involve considerations of electronic and steric effects, the possible intermediacy of quaternary salts, and the likelihood that the dominant tautomer is reacting. In the experiment, the researchers used many compounds, for example, 1-Methyl-3-nitro-1H-pyrazole (cas: 54210-32-1Synthetic Route of C4H5N3O2).

1-Methyl-3-nitro-1H-pyrazole (cas: 54210-32-1) belongs to pyrazole derivatives. Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Synthetic Route of C4H5N3O2

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

Potent and Selective Ketoamide-Based Inhibitors of Cysteine Protease, Cathepsin K was written by Tavares, Francis X.;Deaton, David N.;Miller, Aaron B.;Miller, Larry R.;Wright, Lois L.;Zhou, Hui-Qiang. And the article was included in Journal of Medicinal Chemistry in 2004.Application In Synthesis of 1-Ethyl-1H-pyrazol-5-amine This article mentions the following:

Cathepsin K, a lysosomal cysteine protease of the papain superfamily, is abundantly and selectively expressed in osteoclasts, suggesting that this enzyme is crucial for bone resorption. Prevention of osteoclast-mediated bone resorption via inhibition of cathepsin K could be an effective approach to prevent osteoporosis. Potent and selective reversible ketoamide-based inhibitors have been identified in the present study. Using a known crystal structure of a ketoamide-based inhibitor, information from residues that form the P2/P3 pocket was used in the design of inhibitors that could allow for gains in selectivity and potency. Further, incorporation of P’ selective heterocycles, along with the P2/P3 modifications, is also described. These modifications have resulted in potent and selective cathepsin K inhibitors that allow for improvements in their physiochem. properties and represent a viable lead series for the discovery of new therapies for the prevention and treatment of osteoporosis. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Application In Synthesis of 1-Ethyl-1H-pyrazol-5-amine).

1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) belongs to pyrazole derivatives. Pyrazoles, a five-membered heterocycle containing two adjacent nitrogen atoms, are the core structures found in a number of molecules that possess a wide range of pharmaceutical and agricultural activities. Pyrazoles and pyrimidines have diverse biological and pharmacological activities. There are a number of antimicrobial compounds containing pyrazole moiety as the core unit. Pyrazofurin is important antimicrobial drug and 2-methylpyrimidine-4-ylamine derivatives I and II were found to be effective inhibitors of Escherichia coli PDHc-E1 with antibacterial and antifungal activity.Application In Synthesis of 1-Ethyl-1H-pyrazol-5-amine

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

Structure-Based Discovery of CF53 as a Potent and Orally Bioavailable Bromodomain and Extra-Terminal (BET) Bromodomain Inhibitor was written by 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. And the article was included in Journal of Medicinal Chemistry in 2018.Quality Control of 1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine This article mentions the following:

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 K_i 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. In the experiment, the researchers used many compounds, for example, 1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine (cas: 141459-53-2Quality Control of 1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine).

1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine (cas: 141459-53-2) belongs to pyrazole derivatives. The 1H-pyrazole provides an excellent means by which to provide the requisite hydrogen bond acceptor–donor motifs, whether as a monocyclic ring or as a fused indazole ring. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Quality Control of 1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine

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

Platinum(II) and palladium(II) complexes with 3,5-dimethyl-1-pyrazolylcarbamide was written by Safronova, L. A.;Shebaldova, A. D.. And the article was included in Koordinatsionnaya Khimiya in 1989.Recommanded Product: 3,5-Dimethyl-1H-pyrazole-1-carboxamide This article mentions the following:

MLCl₂ (M = Pd, Pt; L = 3,5-dimethyl-1-pyrazolylcarbamide) were prepared and characterized by IR and ¹H NMR spectra and colorimetry with SnCl₂. L coordinates through the pyridine N atom and the amino N atom. In the experiment, the researchers used many compounds, for example, 3,5-Dimethyl-1H-pyrazole-1-carboxamide (cas: 934-48-5Recommanded Product: 3,5-Dimethyl-1H-pyrazole-1-carboxamide).

3,5-Dimethyl-1H-pyrazole-1-carboxamide (cas: 934-48-5) belongs to pyrazole derivatives. Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. Pyrazoles and pyrimidines have diverse biological and pharmacological activities. There are a number of antimicrobial compounds containing pyrazole moiety as the core unit. Pyrazofurin is important antimicrobial drug and 2-methylpyrimidine-4-ylamine derivatives I and II were found to be effective inhibitors of Escherichia coli PDHc-E1 with antibacterial and antifungal activity.Recommanded Product: 3,5-Dimethyl-1H-pyrazole-1-carboxamide

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

Identification of ring-fused pyrazolo pyridin-2-ones as novel poly(ADP-ribose)polymerase-1 inhibitors was written by Moree, Wilna J.;Goldman, Phyllis;Demaggio, Anthony J.;Christenson, Erik;Herendeen, Dan;Eksterowicz, John;Kesicki, Edward A.;McElligott, David L.;Beaton, Graham. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2008.Name: 1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine This article mentions the following:

A novel class of PARP-1 inhibitors was identified containing a non-aromatic heterocycle or carbocycle fused to a pyrazolo pyridin-2-one. Compounds displayed low nanomolar binding activity in the PARP-1 binding assay and submicromolar activity in a cell based chemosensitization assay. In the experiment, the researchers used many compounds, for example, 1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine (cas: 141459-53-2Name: 1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine).

1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine (cas: 141459-53-2) belongs to pyrazole derivatives. An alternative way to synthesize multisubstituted pyrazoles is the Csingle bondH arylation of simple pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities.Name: 1-(tert-Butyl)-3-methyl-1H-pyrazol-5-amine

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