Day: November 9, 2022

Finzi, Paola Vita published an article in 1965, the title of the article was Reactions between sulfone azides and arylacetylenes.Quality Control of 4-(p-Tolyl)-1H-1,2,3-triazole And the article contains the following content:

cf. CA 60, 5479g; 62, 13078d. Sulfone azides react with PhCCH (I) and some p-substituted phenylacetylenes yielding the corresponding 5-phenyltriazole sulfonates instead of the 1-sulfonyl-5-phenyltriazole monohydrates (Boyer, et al., CA 53, 15065e). Equimol. amounts are boiled for 12-16-hrs. to give low yields (2-30%) of pure crystalline products. PhSO2N3 (II), p-MeC6H4SO2N3 (III), p-BrC6H4SO2N3(IV), and MeSO2N3 (V) react with I to yield 5-phenyltriazole benzenesulfonate (m. 164-5°), tosylate(m. 170-1°), p-bromobenzenesulfonate (m. 160-1°), and methanesulfonate (m. 143.5-4.5°), resp. By a similar process III reacts with p-BrC6H4CCH, with p-ClC6H4CCH, and with β-C10H7CCH to yield the corresponding tosylates, m. 185-6.5°, 182.5-3.5°, and 174-5.5°, resp. As a confirmation of the proposed structure the corresponding 4-phenyltriazoles were treated in the cold with p-MeC6H4SO3H in iso-Pr2O and the same results as above were obtained except in the case of II with p-MeC6H4CCH, of II with p-MeOC6H4CCH, and of III with V where 5-tolyl-1-tosyl-1,2,3-triazole (m. 161-2°), 5-(p-methoxyphenyl)-1-tosyl-1,2,3-triazole (m. 133.5-4.5°), and 5-phenyl-1-(p-bromophenylsulfonyl)-1,2,3-triazole (m. 132.5-33°), were obtained, resp. The experimental process involved the reaction of 4-(p-Tolyl)-1H-1,2,3-triazole(cas: 5301-96-2).Quality Control of 4-(p-Tolyl)-1H-1,2,3-triazole

The Article related to , azides, sulfonyl azides role: uses (uses), ir spectra, nmr (nuclear magnetic resonance), sulfonyl compounds, sulfonyl azides and other aspects.Quality Control of 4-(p-Tolyl)-1H-1,2,3-triazole

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

On February 11, 2021, Duncan, James S. published a patent.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 title of the patent was Combination therapy for treatment of cancer. And the patent contained the following:

Pharmaceutical compositions comprising: one or more bromodomain and extra terminal domain (BET) proteolysis targeting chimera (PROTAC) (BET-PROTAC) therapeutic agents or one or more cyclin-dependent kinase 9 (CDK9) PROTAC (CDK9-PROTAC) therapeutic agents; and one or more kinase inhibitors, one or more KRAS inhibitors, or one or more autophagy inhibitors; and methods of treating cancer in a human patient by administering such pharmaceutical compositions are described herein. 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 cancer drug combination therapy cdk9 inhibitor, Pharmaceuticals: General 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 October 22, 2020, Goracci, Laura; Desantis, Jenny; Valeri, Aurora; Castellani, Beatrice; Eleuteri, Michela; Cruciani, Gabriele published an article.Product Details of 1949837-12-0 The title of the article was Understanding the Metabolism of Proteolysis Targeting Chimeras (PROTACs): The Next Step toward Pharmaceutical Applications. And the article contained the following:

Hetero-bifunctional PROteolysis TArgeting Chimeras (PROTACs) represent a new emerging class of small mols. designed to induce polyubiquitylation and proteasomal-dependent degradation of a target protein. Despite the increasing number of publications about the synthesis, biol. evaluation, and mechanism of action of PROTACs, the characterization of the pharmacokinetic properties of this class of compounds is still minimal. Here, we report a study on the metabolism of a series of 40 PROTACs in cryopreserved human hepatocytes at multiple time points. Our results indicated that the metabolism of PROTACs could not be predicted from that of their constituent ligands. Their linkers’ chem. nature and length resulted in playing a major role in the PROTACs’ liability. A subset of compounds was also tested for metabolism by human cytochrome P 450 3A4 (CYP3A4) and human aldehyde oxidase (hAOX) for more in-depth data interpretation, and both enzymes resulted in active PROTAC metabolism 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 protac metabolism human hepatocytes ligands linkers cyp3a4 haox, Pharmacology: Drug Metabolism and other aspects.Product Details of 1949837-12-0

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

On May 5, 2022, Xu, Qiaobing; Chen, Jinjin published a patent.COA of Formula: C49H60ClN9O7S2 The title of the patent was Enhanced hydrophobic tag-induced protein degradation using lipid nanoparticle delivery. And the patent contained the following:

Disclosed are conjugates, comprising a PROTAC and a protein. Also disclosed are nanoparticles, comprising the conjugates disclosed herein and a membrane. The present disclosure further relates to therapeutic methods of using the conjugates and nanoparticles. 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).COA of Formula: C49H60ClN9O7S2

The Article related to cancer antitumor lipid nanoparticle protac protein degradation, Pharmaceuticals: Pharmaceutics and other aspects.COA of Formula: C49H60ClN9O7S2

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

Jensen, Stephanie M.; Potts, Gregory K.; Ready, Damien B.; Patterson, Melanie J. published an article in 2018, the title of the article was Specific MHC-I peptides are induced using PROTACs.Name: (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:

Peptides presented by the class-I major histocompatibility complex (MHC-I) are important targets for immunotherapy. The identification of these peptide targets greatly facilitates the generation of T-cell-based therapeutics. Herein, we report the capability of proteolysis targeting chimera (PROTAC) compounds to induce the presentation of specific MHC class-I peptides derived from endogenous cellular proteins. Using LC-MS/MS, we identified several BET-derived MHC-I peptides induced by treatment with three BET-directed PROTAC compounds To understand our ability to tune this process, we measured the relative rate of presentation of these peptides under varying treatment conditions using label-free mass spectrometry quantification. We found that the rate of peptide presentation reflected the rate of protein degradation, indicating a direct relationship between PROTAC treatment and peptide presentation.We addnl. analyzed the effect of PROTAC treatment on the entire immunopeptidome and found many new peptides that were displayed in a PROTAC-specific fashion: we determined that these identifications map to the BET pathway, as well as, potential off-target or unique-to-PROTAC pathways. This work represents the first evidence of the use of PROTAC compounds to induce the presentation of MHC-I peptides from endogenous cellular proteins, highlighting the capability of PROTAC compounds for the discovery and generation of new targets for immunotherapy. 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).Name: (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 mhci peptide proteolysis targeting chimera, bet, hla, mhc-i, protac, immunopeptides, Biochemical Methods: Synthesis and other aspects.Name: (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 25, 2018, Zhou, Bing; Hu, Jiantao; Xu, Fuming; Chen, Zhuo; Bai, Longchuan; Fernandez-Salas, Ester; Lin, Mei; Liu, Liu; Yang, Chao-Yie; Zhao, Yujun; McEachern, Donna; Przybranowski, Sally; Wen, Bo; Sun, Duxin; Wang, Shaomeng published an article.Product Details of 1949837-12-0 The title of the article was Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. And the article contained the following:

The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT members, are epigenetic “readers” and play a key role in the regulation of gene transcription. BET proteins are considered to be attractive therapeutic targets for cancer and other human diseases. Recently, heterobifunctional small-mol. BET degraders have been designed based upon the proteolysis targeting chimera (PROTAC) concept to induce BET protein degradation Herein, we present our design, synthesis, and evaluation of a new class of PROTAC BET degraders. One of the most promising compounds, 23, effectively degrades BRD4 protein at concentrations as low as 30 pM in the RS4;11 leukemia cell line, achieves an IC50 value of 51 pM in inhibition of RS4;11 cell growth and induces rapid tumor regression in vivo against RS4;11 xenograft tumors. These data establish that compound 23 (BETd-260/ZBC260) is a highly potent and efficacious BET degrader. 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 preparation degrader bromodomain extra terminal protein cancer, Pharmacology: Structure-Activity and other aspects.Product Details of 1949837-12-0

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

On June 14, 2012, Rohrig, Ute F.; Majjigapu, Somi Reddy; Grosdidier, Aurelien; Bron, Sylvian; Stroobant, Vincent; Pilotte, Luc; Colau, Didier; Vogel, Pierre; Van den Eynde, Benoit J.; Zoete, Vincent; Michielin, Olivier published an article.Application of 5301-96-2 The title of the article was Rational Design of 4-Aryl-1,2,3-Triazoles for Indoleamine 2,3-Dioxygenase 1 Inhibition. And the article contained the following:

Indoleamine 2,3-dioxygenase 1 (IDO1) is an important therapeutic target for the treatment of diseases such as cancer that involve pathol. immune escape. Starting from the scaffold of our previously discovered IDO1 inhibitor 4-phenyl-1,2,3-triazole, we used computational structure-based methods to design more potent ligands. This approach yielded highly efficient low mol. weight inhibitors, the most active being of nanomolar potency both in an enzymic and in a cellular assay, while showing no cellular toxicity and a high selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO). A quant. structure-activity relationship based on the electrostatic ligand-protein interactions in the docked binding modes and on the quantum chem. derived charges of the triazole ring demonstrated a good explanatory power for the observed activities. The experimental process involved the reaction of 4-(p-Tolyl)-1H-1,2,3-triazole(cas: 5301-96-2).Application of 5301-96-2

The Article related to aryl triazole preparation indoleamine dioxygenase inhibition sar, Pharmacology: Structure-Activity and other aspects.Application of 5301-96-2

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

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