Tag: 200-300

Discovery of 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-[4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl]benzamide (AP24534), a Potent, Orally Active Pan-Inhibitor of Breakpoint Cluster Region-Abelson (BCR-ABL) Kinase Including the T315I Gatekeeper Mutant was written by Huang, Wei-Sheng;Metcalf, Chester A.;Sundaramoorthi, Raji;Wang, Yihan;Zou, Dong;Thomas, R. Mathew;Zhu, Xiaotian;Cai, Lisi;Wen, David;Liu, Shuangying;Romero, Jan;Qi, Jiwei;Chen, Ingrid;Banda, Geetha;Lentini, Scott P.;Das, Sasmita;Xu, Qihong;Keats, Jeff;Wang, Frank;Wardwell, Scott;Ning, Yaoyu;Snodgrass, Joseph T.;Broudy, Marc I.;Russian, Karin;Zhou, Tianjun;Commodore, Lois;Narasimhan, Narayana I.;Mohemmad, Qurish K.;Iuliucci, John;Rivera, Victor M.;Dalgarno, David C.;Sawyer, Tomi K.;Clackson, Tim;Shakespeare, William C.. And the article was included in Journal of Medicinal Chemistry in 2010.Recommanded Product: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline This article mentions the following:

In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of Ile315 side chain. Extensive SAR studies led to the discovery of development candidate benzamide I (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC₅₀s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of I significantly prolonged survival of mice injected i.v. with BCR-ABL^T315I expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of I to be an effective treatment for CML, including patients refractory to all currently approved therapies. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Recommanded Product: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Recommanded Product: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

A Highly Regioselective Amination of 6-Aryl-2,4-dichloropyrimidine was written by Peng, Zhi-Hui;Journet, Michel;Humphrey, Guy. And the article was included in Organic Letters in 2006.Category: piperazines This article mentions the following:

A highly regioselective amination of 6-aryl-2,4-dichloropyrimidines with aliphatic secondary amines and aromatic amines which strongly favors the formation of the C4-substituted product has been developed. The reactions with aliphatic amines are carried out using LiHMDS as the base and are catalyzed by Pd, while the aromatic amines require no catalyst. In the experiment, the researchers used many compounds, for example, (R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5Category: piperazines).

(R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Category: piperazines

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Multistep Continuous-Flow Synthesis in Medicinal Chemistry: Discovery and Preliminary Structure-Activity Relationships of CCR8 Ligands was written by Petersen, Trine P.;Mirsharghi, Sahar;Rummel, Pia C.;Thiele, Stefanie;Rosenkilde, Mette M.;Ritzen, Andreas;Ulven, Trond. And the article was included in Chemistry – A European Journal in 2013.Recommanded Product: 623586-00-5 This article mentions the following:

A three-step continuous-flow synthesis system and its application to the assembly of a new series of chemokine receptor ligands directly from com. building blocks is reported. No scavenger columns or solvent switches are necessary to recover the desired test compounds, which were obtained in overall yields of 49-94%. The system is modular and flexible, and the individual steps of the sequence can be interchanged with similar outcome, extending the scope of the chem. Biol. evaluation confirmed activity on the chemokine CCR8 receptor and provided initial structure-activity-relationship (SAR) information for this new ligand series, with the most potent member displaying full agonist activity with single-digit nanomolar potency. To the best of the knowledge, this represents the first published example of efficient use of multistep flow synthesis combined with biol. testing and SAR studies in medicinal chem. In the experiment, the researchers used many compounds, for example, (R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5Recommanded Product: 623586-00-5).

(R)-1-Cbz-3-methylpiperazine (cas: 623586-00-5) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Recommanded Product: 623586-00-5

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Molecular iodine-catalyzed facile procedure for N-Boc protection of amines was written by Varala, Ravi;Nuvula, Sreelatha;Adapa, Srinivas R.. And the article was included in Journal of Organic Chemistry in 2006.Application of 780705-64-8 This article mentions the following:

An efficient and practical protocol for the protection of various structurally and electronically divergent aryl and aliphatic amines using (Boc)₂O in the presence of a catalytic amount of mol. iodine under solvent-free conditions at ambient temperature is presented. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8Application of 780705-64-8).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Application of 780705-64-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

An improved synthesis of the 5-HT1A receptor agonist Eptapirone free base was written by Peng, Wei;Chen, Jian;Liu, Hui;Li, Xiufang;Deng, Zhiwei;Yuan, Jing;Peng, Yizhou;Yang, Yanjing;Zhong, Shian. And the article was included in Chemical Papers in 2019.HPLC of Formula: 780705-64-8 This article mentions the following:

A method to retro-synthesize eptapirone free base. The compound consists of heterocyclic aromatic portion and aliphatic portion, and the synthetic route consisted of a total of nine steps with an overall yield of 8.8% starting from the com. available materials. The key steps in the synthetic method involved: (1) using sodium hydroxide and ethylene glycol as solvent resulted in a better cyclization and yield (61.6%) of 1,2,4-triazine-3,5(2H,4H)-dione; (2) an acceptable yield (63.1%) of 4-tert-butyl(pyrimidin-2-yl)piperazine-1-carboxylate was obtained under an optimized conditions of using triethylamine as a base, ethanol as a solvent, and a reaction temperature of 50 掳C for 16 h with non-metal catalysis and less byproducts; (3) the reaction step of eptapirone could get a better yield (49.6%) with an optimized condition of potassium carbonate as a base, acetonitrile as a solvent, NaI as a catalyst, and a reaction temperature of 50 掳C for 12 h by nucleophilic substitution reaction. The main advantages of this route were an acceptable product purity, the com. availability of all starting materials and the absence of high temperature, high pressure and noble metal catalysts, which could result in more feasible com. applications. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8HPLC of Formula: 780705-64-8).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.HPLC of Formula: 780705-64-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Structural Mechanisms Determining Inhibition of the Collagen Receptor DDR1 by Selective and Multi-Targeted Type II Kinase Inhibitors was written by Canning, Peter;Tan, Li;Chu, Kiki;Lee, Sam W.;Gray, Nathanael S.;Bullock, Alex N.. And the article was included in Journal of Molecular Biology in 2014.Computed Properties of C14H20F3N3 This article mentions the following:

The discoidin domain receptors (DDRs), DDR1 and DDR2, form a unique subfamily of receptor tyrosine kinases that are activated by the binding of triple-helical collagen. Excessive signaling by DDR1 and DDR2 has been linked to the progression of various human diseases, including fibrosis, atherosclerosis and cancer. The authors report the inhibition of these unusual receptor tyrosine kinases by the multi-targeted cancer drugs imatinib and ponatinib, as well as the selective type II inhibitor DDR1-IN-1. Ponatinib is identified as the more potent mol., which inhibits DDR1 and DDR2 with an IC₅₀ of 9 nM. Co-crystal structures of human DDR1 reveal a DFG-out conformation (DFG, Asp-Phe-Gly) of the kinase domain that is stabilized by an unusual salt bridge between the activation loop and 伪D helix. Differences to Abelson kinase (ABL) are observed in the DDR1 P-loop, where a 尾-hairpin replaces the cage-like structure of ABL. P-loop residues in DDR1 that confer drug resistance in ABL are therefore accommodated outside the ATP pocket. Whereas imatinib and ponatinib bind potently to both the DDR and ABL kinases, the hydrophobic interactions of the ABL P-loop appear poorly satisfied by DDR1-IN-1 suggesting a structural basis for its DDR1 selectivity. Such inhibitors may have applications in clin. indications of DDR1 and DDR2 overexpression or mutation, including lung cancer. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Computed Properties of C14H20F3N3).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Computed Properties of C14H20F3N3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Structure-Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells was written by Cherian, Joseph;Nacro, Kassoum;Poh, Zhi Ying;Guo, Samantha;Jeyaraj, Duraiswamy A.;Wong, Yun Xuan;Ho, Melvyn;Yang, Hai Yan;Joy, Joma Kanikadu;Kwek, Zekui Perlyn;Liu, Boping;Wee, John Liang Kuan;Ong, Esther HQ;Choong, Meng Ling;Poulsen, Anders;Lee, May Ann;Pendharkar, Vishal;Ding, Li Jun;Manoharan, Vithya;Chew, Yun Shan;Sangthongpitag, Kanda;Lim, Sharon;Ong, S. Tiong;Hill, Jeffrey;Keller, Thomas H.. And the article was included in Journal of Medicinal Chemistry in 2016.Name: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline This article mentions the following:

Clin. used BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia do not eliminate leukemic stem cells (LSC). It has been shown that MNK1 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs. Herein, the authors describe the identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor. Initial structure-activity relationship studies resulted in a compound with loss of BCR-ABL1 inhibition. Further modification led to orally bioavailable dual MNK1 and 2 and BCR-ABL1 inhibitors I and II, which are efficacious in a mouse xenograft model and also reduce the level of phosphorylated eukaryotic translation initiation factor 4E in the tumor tissues. Kinase selectivity of these compounds is also presented. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Name: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Name: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

A Putative Single-Photon Emission CT Imaging Tracer for Erythropoietin-Producing Hepatocellular A2 Receptor was written by Furukawa, Takenori;Kimura, Hiroyuki;Torimoto, Hanae;Yagi, Yusuke;Kawashima, Hidekazu;Arimitsu, Kenji;Yasui, Hiroyuki. And the article was included in ACS Medicinal Chemistry Letters in 2021.COA of Formula: C14H20F3N3 This article mentions the following:

Erythropoietin-producing hepatocellular (Eph) receptors are receptor tyrosine kinases involved in cell-cell contact. The EphA2 receptor is associated with cancer proliferation and migration. Therefore, EphA2 receptor imaging has the potential for cancer diagnosis. Here, we synthesized N-(5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)-2-methylphenyl)-5-[¹²³I]iodonicotinamide ([¹²³I]ETB) and evaluated it as an imaging tracer for single-photon emission computed tomog. (SPECT) imaging of the EphA2 receptor. [¹²³I]ETB was designed on the basis of ALW-II-41-27, an inhibitor of EphA2 receptor kinase. Nonradioactive ETB was also synthesized and has been shown to efficiently inhibit EphA2 receptor kinase activity in vitro (IC₅₀: ETB, 90.2 卤 18.9 nM). A cell-binding assay demonstrated that [¹²⁵I]ETB binds specifically to the EphA2 receptor. The ex vivo biodistribution study of [¹²⁵I]ETB in U87MG tumor-bearing mice also revealed tumor uptake (2.2% ID/g at 240 min). In addition, [¹²³I]ETB uptake in tumors was visualized via SPECT/CT imaging. On the basis of the above, [¹²³I]ETB can be considered a potential SPECT imaging tracer for the EphA2 receptor. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6COA of Formula: C14H20F3N3).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 掳C and boils at 125鈥?30 掳C. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. COA of Formula: C14H20F3N3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Iridium-Catalyzed C-H Borylation of Heteroarenes: Scope, Regioselectivity, Application to Late-Stage Functionalization, and Mechanism was written by Larsen, Matthew A.;Hartwig, John F.. And the article was included in Journal of the American Chemical Society in 2014.SDS of cas: 780705-64-8 This article mentions the following:

A study on the iridium-catalyzed C-H borylation of heteroarenes is reported. Several heteroarenes containing multiple heteroatoms were amenable to C-H borylation catalyzed by the combination of an iridium(I) precursor and tetramethylphenanthroline. The investigations of the scope of the reaction led to the development of powerful rules for predicting the regioselectivity of borylation, foremost of which is that borylation occurs distal to nitrogen atoms. One-pot functionalizations are reported of the heteroaryl boronate esters formed in situ, demonstrating the usefulness of the reported methodol. for the synthesis of complex heteroaryl structures. Application of this methodol. to the synthesis and late-stage functionalization of biol. active compounds is also demonstrated. Mechanistic studies show that basic heteroarenes can bind to the catalyst and alter the resting state from the olefin-bound complex observed during arene borylation to a species containing a bound heteroarene, leading to catalyst deactivation. Studies on the origins of the observed regioselectivity show that borylation occurs distal to N-H bonds due to rapid N-H borylation, creating an unfavorable steric environment for borylation adjacent to these bonds. Computational studies and mechanistic studies show that the lack of observable borylation of C-H bonds adjacent to basic nitrogen is not the result of coordination to a bulky Lewis acid prior to C-H activation, but the combination of a higher-energy pathway for the borylation of these bonds relative to other C-H bonds and the instability of the products formed from borylation adjacent to basic nitrogen. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8SDS of cas: 780705-64-8).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.SDS of cas: 780705-64-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Discovery of 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-[4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl]benzamide (AP24534), a Potent, Orally Active Pan-Inhibitor of Breakpoint Cluster Region-Abelson (BCR-ABL) Kinase Including the T315I Gatekeeper Mutant was written by Huang, Wei-Sheng;Metcalf, Chester A.;Sundaramoorthi, Raji;Wang, Yihan;Zou, Dong;Thomas, R. Mathew;Zhu, Xiaotian;Cai, Lisi;Wen, David;Liu, Shuangying;Romero, Jan;Qi, Jiwei;Chen, Ingrid;Banda, Geetha;Lentini, Scott P.;Das, Sasmita;Xu, Qihong;Keats, Jeff;Wang, Frank;Wardwell, Scott;Ning, Yaoyu;Snodgrass, Joseph T.;Broudy, Marc I.;Russian, Karin;Zhou, Tianjun;Commodore, Lois;Narasimhan, Narayana I.;Mohemmad, Qurish K.;Iuliucci, John;Rivera, Victor M.;Dalgarno, David C.;Sawyer, Tomi K.;Clackson, Tim;Shakespeare, William C.. And the article was included in Journal of Medicinal Chemistry in 2010.Recommanded Product: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline This article mentions the following:

In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of Ile315 side chain. Extensive SAR studies led to the discovery of development candidate benzamide I (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC₅₀s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of I significantly prolonged survival of mice injected i.v. with BCR-ABL^T315I expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of I to be an effective treatment for CML, including patients refractory to all currently approved therapies. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Recommanded Product: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline).

4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Recommanded Product: 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics