Tag: 300-400

Discovery of Potent and Orally Effective Dual Janus Kinase 2/FLT3 Inhibitors for the Treatment of Acute Myelogenous Leukemia and Myeloproliferative Neoplasms was written by Yang, Tao;Hu, Mengshi;Qi, Wenyan;Yang, Zhuang;Tang, Minghai;He, Jun;Chen, Yong;Bai, Peng;Yuan, Xue;Zhang, Chufeng;Liu, Kongjun;Lu, Yulin;Xiang, Mingli;Chen, Lijuan. And the article was included in Journal of Medicinal Chemistry in 2019.Formula: C15H21N3O4 This article mentions the following:

Herein, the design, synthesis, and structure-activity relationships of a series of unique 4-(1H-pyrazol-4-yl)-pyrimidin-2-amine derivatives that selectively inhibit Janus kinase 2 (JAK2) and FLT3 kinases is described. These screening cascades revealed that I was a preferred compound with IC₅₀ values of 0.7 and 4 nM for JAK2 and FLT3, resp. Moreover, I was a potent JAK2 inhibitor with 37-fold and 56-fold selectivity over JAK1 and JAK3, resp., and possessed an excellent selectivity profile over the other 100 representative kinases. In a series of cytokine-stimulated cell-based assays, I exhibited a higher JAK2 selectivity over other JAK isoforms. The oral administration of 60 mg/kg of I could significantly inhibit tumor growth, with a tumor growth inhibition rate of 93 and 85% in MV4-11 and SET-2 xenograft models, resp. Addnl., I showed an excellent bioavailability (F = 58%), a suitable half-life time (T_1/2 = 4.1 h), a satisfactory metabolic stability, and a weak CYP3A4 inhibitory activity, suggesting that I might be a potential drug candidate for JAK2-driven myeloproliferative neoplasms and FLT3-internal tandem duplication-driven acute myelogenous leukemia. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Formula: C15H21N3O4).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. 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.Formula: C15H21N3O4

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

SAR studies on a series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides: Potent inhibitors of the polymerase enzyme (NS5B) of the hepatitis C virus was written by Gentles, Robert G.;Ding, Min;Zheng, Xiaofan;Chupak, Louis;Poss, Michael A.;Beno, Brett R.;Pelosi, Lenore;Liu, Mengping;Lemm, Julie;Wang, Ying-Kai;Roberts, Susan;Gao, Min;Kadow, John. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2011.Name: 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid This article mentions the following:

Described herein is the initial optimization of (+/-) N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide (1)(I), a hit discovered in a high throughput screen run against the NS5B polymerase enzyme of the hepatitis C virus. This effort resulted in the identification of (S)-N-sec-butyl-6-((R)-3-(4-(trifluoromethoxy)benzylcarbamoyl)-4-(4-(trifluoromethoxy)phenylsulfonyl)piperazin-1-yl)pyridazine-3-carboxamide (2)(II), that displayed potent replicon activities against HCV genotypes 1b and 1a (EC₅₀ 1b/1a = 7/89 nM). In the experiment, the researchers used many compounds, for example, 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2Name: 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid).

4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Name: 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid

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

Expanding Reactivity in DNA-Encoded Library Synthesis via Reversible Binding of DNA to an Inert Quaternary Ammonium Support was written by Flood, Dillon T.;Asai, Shota;Zhang, Xuejing;Wang, Jie;Yoon, Leonard;Adams, Zoe C.;Dillingham, Blythe C.;Sanchez, Brittany B.;Vantourout, Julien C.;Flanagan, Mark E.;Piotrowski, David W.;Richardson, Paul;Green, Samantha A.;Shenvi, Ryan A.;Chen, Jason S.;Baran, Phil S.;Dawson, Philip E.. And the article was included in Journal of the American Chemical Society in 2019.Electric Literature of C16H22N2O4 This article mentions the following:

DNA Encoded Libraries have proven immensely powerful tools for lead identification. The ability to screen billions of compounds at once has spurred increasing interest in DEL development and utilization. Although DEL provides access to libraries of unprecedented size and diversity, the idiosyncratic and hydrophilic nature of the DNA tag severely limits the scope of applicable chemistries. It is known that biomacromols. can be reversibly, noncovalently adsorbed and eluted from solid supports, and this phenomenon has been utilized to perform synthetic modification of biomols. in a strategy we have described as reversible adsorption to solid support (RASS). Herein, we present the adaptation of RASS for a DEL setting, which allows reactions to be performed in organic solvents at near anhydrous conditions opening previously inaccessible chem. reactivities to DEL. The RASS approach enabled the rapid development of C(sp²)-C(sp³) decarboxylative cross-couplings with broad substrate scope, an electrochem. amination (the first electrochem. synthetic transformation performed in a DEL context), and improved reductive amination conditions. The utility of these reactions was demonstrated through a DEL-rehearsal in which all newly developed chemistries were orchestrated to afford a compound rich in diverse skeletal linkages. We believe that RASS will offer expedient access to new DEL reactivities, expanded chem. space, and ultimately more drug-like libraries. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Electric Literature of C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. 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. Electric Literature of C16H22N2O4

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

Hitting a Moving Target: Simulation and Crystallography Study of ATAD2 Bromodomain Blockers was written by Dolbois, Aymeric;Batiste, Laurent;Wiedmer, Lars;Dong, Jing;Brutsch, Manuela;Huang, Danzhi;Deerain, Nicholas M.;Spiliotopoulos, Dimitrios;Cheng-Sanchez, Ivan;Laul, Eleen;Nevado, Cristina;Sledz, Pawel;Caflisch, Amedeo. And the article was included in ACS Medicinal Chemistry Letters in 2020.Name: 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid This article mentions the following:

Small mol. ligand binding to the ATAD2 bromodomain is investigated here through the synergistic combination of mol. dynamics and protein crystallog. A previously unexplored conformation of the binding pocket upon rearrangement of the gatekeeper residue Ile1074 has been found. Further, our investigations reveal how minor structural differences in the ligands result in binding with different plasticity of the ZA loop for this difficult-to-drug bromodomain. In the experiment, the researchers used many compounds, for example, 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2Name: 4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid).

4-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (cas: 149057-19-2) 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. 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-((Benzyloxy)carbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid

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

Synthesis and SAR of piperazinyl-N-phenylbenzamides as inhibitors of hepatitis C virus RNA replication in cell culture was written by Conte, Immacolata;Giuliano, Claudio;Ercolani, Caterina;Narjes, Frank;Koch, Uwe;Rowley, Michael;Altamura, Sergio;De Francesco, Raffaele;Neddermann, Petra;Migliaccio, Giovanni;Stansfield, Ian. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2009.Computed Properties of C16H22N2O4 This article mentions the following:

The RNA replication machinery of HCV is a multi-subunit membrane-associated complex. NS5A has emerged as an active component of HCV replicase, possibly involved in regulation of viral replication and resistance to the antiviral effect of interferon. Substituted piperazinyl-N-(aryl)benzamides were prepared as potent inhibitors of HCV replication exerted via modulation of the dimerization of NS5A. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Computed Properties of C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Computed Properties of C16H22N2O4

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

gem-Difluoromethylene Alkyne-Enabled Diverse C-H Functionalization and Application to the on-DNA Synthesis of Difluorinated Isocoumarins was written by Gao, Hui;Lin, Shuang;Zhang, Shuning;Chen, Weijie;Liu, Xiawen;Yang, Guang;Lerner, Richard A.;Xu, Hongtao;Zhou, Zhi;Yi, Wei. And the article was included in Angewandte Chemie, International Edition in 2021.Computed Properties of C16H22N2O4 This article mentions the following:

Using gem-difluoromethylene alkynes as effectors, unprecedented diverse C-H activation/[4+2] annulations of simple benzoic acids are reported. The chemodivergent reaction outcomes are well-tuned by Rh/Ir-catalyzed system; in the Rh^III catalysis, 3-alkenyl-1H-isochromen-1-one and 3,4-dialkylideneisochroman-1-one skeletons are afforded in a solvent-dependent manner (e.g., benzoic acid + I → II (in MeOH)/III (in TFE)) under whereas difluoromethylene-substituted 1H-isochromen-1-ones (IV) are generated under the Ir^III-catalyzed system. Mechanistic studies revealed that unusually double β-F eliminations and fluorine effect-induced regioselective reductive elimination are independently involved to enable distinct reaction modes for divergent product formations. Besides, synthetic application in both the derivatization of obtained diene products and the on-DNA synthesis of DNA-tagged difluorinated isocoumarin have been demonstrated, which manifested great potential for synthetic utility of the developed protocols. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Computed Properties of C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) 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. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Computed Properties of C16H22N2O4

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

Fragment-Based Design of Symmetrical Bis-benzimidazoles as Selective Inhibitors of the Trimethoprim-Resistant, Type II R67 Dihydrofolate Reductase was written by Bastien, Dominic;Ebert, Maximilian C. C. J. C.;Forge, Delphine;Toulouse, Jacynthe;Kadnikova, Natalia;Perron, Florent;Mayence, Annie;Huang, Tien L.;Vanden Eynde, Jean Jacques;Pelletier, Joelle N.. And the article was included in Journal of Medicinal Chemistry in 2012.Synthetic Route of C16H22N2O4 This article mentions the following:

The continuously increasing use of trimethoprim as a common antibiotic for medical use and for prophylactic application in terrestrial and aquatic animal farming has increased its prevalence in the environment. This has been accompanied by increased drug resistance, generally in the form of alterations in the drug target, dihydrofolate reductase (DHFR). The most highly resistant variants of DHFR are known as type II DHFR, among which R67 DHFR is the most broadly studied variant. We report the first attempt at designing specific inhibitors to this emerging drug target by fragment-based design. The detection of inhibition in R67 DHFR was accompanied by parallel monitoring of the human DHFR, as an assessment of compound selectivity. By those means, small aromatic mols. of 150-250 g/mol (fragments) inhibiting R67 DHFR selectively in the low millimolar range were identified. More complex, sym. bis-benzimidazoles and a bis-carboxyphenyl were then assayed as fragment-based leads, which procured selective inhibition of the target in the low micromolar range (K_i = 2-4 μM). The putative mode of inhibition is discussed according to mol. modeling supported by in vitro tests. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Synthetic Route of C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) 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. 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.Synthetic Route of C16H22N2O4

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

Synthesis, biological evaluation and molecular docking studies of 2-piperazin-1-yl-quinazolines as platelet aggregation inhibitors and ligands of integrin α_IIbβ₃ was written by Krysko, Andrei A.;Kornylov, Alexander Yu.;Polishchuk, Pavel G.;Samoylenko, Georgiy V.;Krysko, Olga L.;Kabanova, Tatyana A.;Kravtsov, Victor Ch.;Kabanov, Vladimir M.;Wicher, Barbara;Andronati, Sergei A.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2016.Reference of 162046-66-4 This article mentions the following:

A series of 2-piperazin-1-yl-quinazolines were synthesized and evaluated for their antiaggregative activity. The synthesized small mol. compounds have potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to α_IIbβ₃ integrin in a suspension of washed human platelets. The key α_IIbβ₃ protein-ligand interactions were determined in docking experiments and some correlations have been observed between values of the affinity and docking scores. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Reference of 162046-66-4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. 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.Reference of 162046-66-4

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

Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer was written by Han, Xin;Zhao, Lijie;Xiang, Weiguo;Qin, Chong;Miao, Bukeyan;McEachern, Donna;Wang, Yu;Metwally, Hoda;Wang, Lu;Matvekas, Aleksas;Wen, Bo;Sun, Duxin;Wang, Shaomeng. And the article was included in Journal of Medicinal Chemistry in 2021.Synthetic Route of C16H22N2O4 This article mentions the following:

Proteolysis targeting chimera (PROTAC) small-mol. degraders have emerged as a promising new type of therapeutic agents, but the design of PROTAC degraders with excellent oral pharmacokinetics is a major challenge. In this study, we present our strategies toward the discovery of highly potent PROTAC degraders of androgen receptor (AR) with excellent oral pharmacokinetics. Employing thalidomide to recruit cereblon/cullin 4A E3 ligase and through the rigidification of the linker, we discovered highly potent AR degraders with good oral pharmacokinetic properties in mice with ARD-2128 (I) being the best compound ARD-2128 achieves 67% oral bioavailability in mice, effectively reduces AR protein and suppresses AR-regulated genes in tumor tissues with oral administration, leading to the effective inhibition of tumor growth in mice without signs of toxicity. This study supports the development of an orally active PROTAC AR degrader for the treatment of prostate cancer and provides insights and guidance into the design of orally active PROTAC degraders. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Synthetic Route of C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) 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 125â€?30 °C. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Synthetic Route of C16H22N2O4

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