Month: November 2022

On September 8, 2005, Kallander, Lara S.; Lu, Qing; Chen, Wenfang; Tomaszek, Thaddeus; Yang, Guang; Tew, David; Meek, Thomas D.; Hofmann, Glenn A.; Schulz-Pritchard, Christina K.; Smith, Ward W.; Janson, Cheryl A.; Ryan, M. Dominic; Zhang, Gui-Feng; Johanson, Kyung O.; Kirkpatrick, Robert B.; Ho, Thau F.; Fisher, Paul W.; Mattern, Michael R.; Johnson, Randall K.; Hansbury, Michael J.; Winkler, James D.; Ward, Keith W.; Veber, Daniel F.; Thompson, Scott K. published an article.Category: triazoles The title of the article was 4-Aryl-1,2,3-triazole: A Novel Template for a Reversible Methionine Aminopeptidase 2 Inhibitor, Optimized To Inhibit Angiogenesis in Vivo. And the article contained the following:

Inhibitors of human methionine aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for cancer. A new class of small mol. reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound (I), a potent inhibitor of cobalt-activated hMetAP2, also inhibits human and mouse endothelial cell growth. Using a mouse matrigel model, this reversible hMetAP2 inhibitor was also shown to inhibit angiogenesis in vivo. The experimental process involved the reaction of 4-(p-Tolyl)-1H-1,2,3-triazole(cas: 5301-96-2).Category: triazoles

The Article related to aryltriazole derivative preparation methionine aminopeptidase inhibitor angiogenesis, Pharmacology: Structure-Activity and other aspects.Category: triazoles

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Huang, Qiang; Zheng, Maofa; Yang, Shuangshuang; Kuang, Chunxiang; Yu, Cunjing; Yang, Qing published an article in 2011, the title of the article was Structure-activity relationship and enzyme kinetic studies on 4-aryl-1H-1,2,3-triazoles as indoleamine 2,3-dioxygenase (IDO) inhibitors.HPLC of Formula: 5301-96-2 And the article contains the following content:

Previously, we have reported the design and synthesis of 4-aryl-1H-1,2,3-triazoles as inhibitors of indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target of cancer. Here, we present the structure-activity relationship and enzyme kinetic studies on a series of 4-aryl-1H-1,2,3-triazoles. Three compounds (1, 6, 8) were found to possess more IDO inhibitory potency than the most commonly used 1-methyltryptophan. The results from the structure-activity relationship and mol. docking studies indicated that an electron-withdrawing group with low steric hindrance near the NH group of triazoles was necessary for the IDO inhibition. The experimental process involved the reaction of 4-(p-Tolyl)-1H-1,2,3-triazole(cas: 5301-96-2).HPLC of Formula: 5301-96-2

The Article related to structure preparation aryl triazole derivative indoleamine dioxygenase inhibitor cancer, Pharmacology: Structure-Activity and other aspects.HPLC of Formula: 5301-96-2

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Tian, Ruilin; Samelson, Avi J.; Rezelj, Veronica V.; Chen, Merissa; Ramadoss, Gokul N.; Guo, Xiaoyan; Kain, Alice Mac; Tran, Quang Dinh; Lim, Shion A.; Lui, Irene; Nunez, James; Rockwood, Sarah J.; Liu, Na; Carlson-Stevermer, Jared; Oki, Jennifer; Maures, Travis; Holden, Kevin; Weissman, Jonathan S.; Wells, James A.; Conklin, Bruce; Vignuzzi, Marco; Kampmann, Martin published an article in 2021, the title of the article was BRD2 inhibition blocks SARS-CoV-2 infection in vitro by reducing transcription of the host cell receptor ACE2.Reference of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide And the article contains the following content:

SARS-CoV-2 infection of human cells is initiated by the binding of the viral Spike protein to its cell-surface receptor ACE2. We conducted an unbiased CRISPRi screen to uncover druggable pathways controlling Spike protein binding to human cells. We found that the protein BRD2 is an essential node in the cellular response to SARS-CoV-2 infection. BRD2 is required for ACE2 transcription in human lung epithelial cells and cardiomyocytes, and BRD2 inhibitors currently evaluated in clin. trials potently block endogenous ACE2 expression and SARS-CoV-2 infection of human cells. BRD2 also controls transcription of several other genes induced upon SARS-CoV-2 infection, including the interferon response, which in turn regulates ACE2 levels. It is possible that the previously reported interaction between the viral E protein and BRD2 evolved to manipulate the transcriptional host response during SARS-CoV-2 infection. Together, our results pinpoint BRD2 as a potent and essential regulator of the host response to SARS-CoV-2 infection and highlight the potential of BRD2 as a novel therapeutic target for COVID-19. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Reference of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide

The Article related to brd2 inhibitor ace2 transcription regulation sars cov2 coronavirus covid19, Biochemical Genetics: Genomic Processes and other aspects.Reference of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On December 23, 2021, Klein, Victoria G.; Bond, Adam G.; Craigon, Conner; Lokey, R. Scott; Ciulli, Alessio published an article.SDS of cas: 1949837-12-0 The title of the article was Amide-to-Ester Substitution as a Strategy for Optimizing PROTAC Permeability and Cellular Activity. And the article contained the following:

Criteria for predicting the druglike properties of “beyond Rule of 5” Proteolysis Targeting Chimeras (PROTAC) degraders are underdeveloped. PROTAC components are often combined via amide couplings due to their reliability. Amides, however, can give rise to poor absorption, distribution, metabolism, and excretion (ADME) properties. We hypothesized that a bioisosteric amide-to-ester substitution could lead to improvements in both physicochem. properties and bioactivity. Using model compounds, bearing either amides or esters, we identify parameters for optimal lipophilicity and permeability. We applied these learnings to design a set of novel amide-to-ester-substituted, VHL-based BET degraders with the goal to increase permeability. Our ester PROTACs retained intracellular stability, were overall more potent degraders than their amide counterparts, and showed an earlier onset of the hook effect. These enhancements were driven by greater cell permeability rather than improvements in ternary complex formation. This largely unexplored amide-to-ester substitution provides a simple strategy to enhance PROTAC permeability and bioactivity and may prove beneficial to other beyond Ro5 mols. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).SDS of cas: 1949837-12-0

The Article related to amide ester substitution optimizing protac permeability cell, Placeholder for records without volume info and other aspects.SDS of cas: 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Deng, Yuanfei; Yu, Cuifu; Chen, Lushi; Zhang, Xin; Lei, Qiucheng; Liu, Qing; Cai, Gengxi; Liu, Fang published an article in 2022, the title of the article was ARV-771 acts as an inducer of cell cycle arrest and apoptosis to suppress hepatocellular carcinoma progression.Quality Control of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide And the article contains the following content:

Hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer with limited treatment options and extremely poor prognosis worldwide. Recently, the proteolysis targeting chimeras (PROTACs), which aim to induce proteasome-mediated degradation of interesting proteins via recruiting E3 ligases, have become the advanced tools and attractive mols. for cancer treatment. However, the anticancer effects of PROTACs in HCC remain to be clarified. Here, we evaluate the anticancer activity of ARV-771, a previously reported PROTAC compound designed for bromodomain and extra-terminal domain (BET) proteins, in HCC. We show that ARV-771 suppresses the cell viability and colony formation of HCC cells via arresting cell cycle progression and triggering apoptosis. Further investigations reveal that ARV-771 notably downregulates multiple non-proteasomal deubiquitinases which are critical to the development of cancers. Addnl., HCC cells can decrease their sensitivity to ARV-771 via activating the MEK/ERK and p38 MAPKs. ARV-771 also inhibits HCC progression in vivo. Moreover, we show that ARV-771 and sorafenib, a Raf inhibitor that clin. used for targeted therapy of liver cancer, can synergistically inhibit the growth of HCC cells. Overall, this study not only explores the anticancer activity of ARV-771 and its underlying mechanisms in HCC, but also deepens our understanding of deubiquitinases, MAPKs, cell cycle, and apoptosis induction in cancer therapy. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Quality Control of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide

The Article related to hepatocellular carcinoma sorafenib krk mapk cell cycle arrest apoptosis, arv-771, mapks, protacs, deubiquitinases, hepatocellular carcinoma, Placeholder for records without volume info and other aspects.Quality Control of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On August 6, 2020, Zhao, Chuanwu; Jiang, Chunhua; Zhang, Yan; Zhang, Xuejiao; Yang, Jinlu; Kang, Jieqiong; Zhao, Peipei published a patent.Application In Synthesis of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide The title of the patent was Targeted ubiquitination degradation brd4 protein compound, preparation method therefor and application thereof. And the patent contained the following:

The present invention relates to a compound represented by formula (I) or a tautomer, optical isomer, deuterated substance, oxynitride, solvate, pharmaceutically acceptable salt or prodrug thereof, a preparation method for the compound, a pharmaceutical composition containing same and a use of the compound or the pharmaceutical composition in the preparation of a drug for the prevention and/or treatment of cancer, tumors, viral infections, depression, neurol. disorders, trauma, age-related cataracts, organ transplant rejection or autoimmune diseases. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Application In Synthesis of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide

The Article related to targeted ubiquitination brd4 protein, Pharmaceuticals: Formulation and Compounding and other aspects.Application In Synthesis of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On January 30, 2020, Raheja, Raj; Jackman, Robin M.; Kahana, Jason A. published a patent.Computed Properties of 1949837-12-0 The title of the patent was Nanoparticle compositions. And the patent contained the following:

Provided herein are nanoparticle compositions comprising a pharmaceutically acceptable carrier and a compound of Formula: A-L-B. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Computed Properties of 1949837-12-0

The Article related to nanoparticle lyophilized formulation, Pharmaceuticals: Formulation and Compounding and other aspects.Computed Properties of 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On July 22, 2021, Raheja, Raj; Jackman, Robin M.; Kahana, Jason A. published a patent.Synthetic Route of 1949837-12-0 The title of the patent was Nanoparticle compositions. And the patent contained the following:

Provided herein are nanoparticle compositions comprising a pharmaceutically acceptable carrier and a therapeutic compound useful for treating. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Synthetic Route of 1949837-12-0

The Article related to pharmaceutical nanoparticle preparation formulation disease therapy, Pharmaceuticals: Formulation and Compounding and other aspects.Synthetic Route of 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Wu, Zijun; Jiang, Di; Wang, Jian published an article in 2019, the title of the article was Carbene-catalyzed oxidative acylation promoted by an unprecedented oxidant CCl3CN.Application In Synthesis of (R)-5-Benzyl-2-mesityl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate And the article contains the following content:

An unprecedented example of a NHC-catalyzed acylation reaction promoted by an oxidant CCl3CN is described. This protocol features several advantages, including mild reaction conditions, broad substrate scope, and easy operation. In addition, low cost, low b.p., and small mol. weight allow CCl3CN to be an attractive and amenable oxidant. Meanwhile, this formal dehydrogenative coupling reaction of aldehydes RCHO (R = 4-chlorophenyl, quinolin-2-yl, naphthalen-2-yl, etc.) and alcs. R1OH (R1 = Benzyl, 2-methylpiperidin-1-yl, diethylaminyl, etc.) involves a hydride transfer process. The experimental process involved the reaction of (R)-5-Benzyl-2-mesityl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate(cas: 1469801-67-9).Application In Synthesis of (R)-5-Benzyl-2-mesityl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate

The Article related to ester preparation, aldehyde alc oxidative acylation carbene catalyst, General Organic Chemistry: Synthetic Methods and other aspects.Application In Synthesis of (R)-5-Benzyl-2-mesityl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On June 19, 2019, Jain, Neeraj; Hartert, Keenan; Tadros, Saber; Fiskus, Warren; Havranek, Ondrej; Ma, Man Chun John; Bouska, Alyssa; Heavican, Tayla; Kumar, Dhiraj; Deng, Qing; Moore, Dalia; Pak, Christine; Liu, Chih Long; Gentles, Andrew J.; Hartmann, Elena; Kridel, Robert; Smedby, Karin Ekstrom; Juliusson, Gunnar; Rosenquist, Richard; Gascoyne, Randy D.; Rosenwald, Andreas; Giancotti, Filippo; Neelapu, Sattva S.; Westin, Jason; Vose, Julie M.; Lunning, Matthew A.; Greiner, Timothy; Rodig, Scott; Iqbal, Javeed; Alizadeh, Ash A.; Davis, R. Eric; Bhalla, Kapil; Green, Michael R. published an article.Product Details of 1949837-12-0 The title of the article was Targetable genetic alterations of TCF4 (E2-2) drive immunoglobulin expression in diffuse large B cell lymphoma. And the article contained the following:

The activated B cell (ABC-like) subtype of diffuse large B cell lymphoma (DLBCL) is characterized by chronic activation of signaling initiated by Ig μ (IgM). By analyzing the DNA copy number profiles of 1000 DLBCL tumors, we identified gains of 18q21.2 as the most frequent genetic alteration in ABC-like DLBCL. Using integrative anal. of matched gene expression profiling data, we found that the TCF4 (E2-2) transcription factor gene was the target of these alterations. Overexpression of TCF4 in ABC-like DLBCL cell lines led to its occupancy on Ig (IGHM) and MYC gene enhancers and increased expression of these genes at the transcript and protein levels. Inhibition of TCF4 activity with dominant-neg. constructs was synthetically lethal to ABC-like DLBCL cell lines harboring TCF4 DNA copy gains, highlighting these gains as an attractive potential therapeutic target. Furthermore, the TCF4 gene was one of the top BRD4-regulated genes in DLBCL cell lines. BET proteolysis-targeting chimera (PROTAC) ARV771 extinguished TCF4, MYC, and IgM expression and killed ABC-like DLBCL cells in vitro. In DLBCL xenograft models, ARV771 treatment reduced tumor growth and prolonged survival. This work highlights a genetic mechanism for promoting Ig signaling in ABC-like DLBCL and provides a functional rationale for the use of BET inhibitors in this disease. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Product Details of 1949837-12-0

The Article related to tcf4 mutation diffuse large b cell lymphoma copy number, Mammalian Pathological Biochemistry: Oncology and other aspects.Product Details of 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics