Tag: 200-300

Zhang, Bo-Sheng; Li, Yuke; Zhang, Zhe; An, Yang; Wen, Yu-Hua; Gou, Xue-Ya; Quan, Si-Qi; Wang, Xin-Gang; Liang, Yong-Min published an article in Journal of the American Chemical Society. The title of the article was 《Synthesis of C4-Aminated Indoles via a Catellani and Retro-Diels-Alder Strategy》.COA of Formula: C12H15N3 The author mentioned the following in the article:

Highly functionalized 4-aminoindoles were synthesized via the three-component cross-coupling of o-iodoaniline, N-benzoyloxyamines, and norbornadiene. The Catellani and retro-Diels-Alder strategy was used in this domino process. o-Iodoaniline, with electron-donating and sterically hindered protecting groups, made the reaction selective toward o-C-H amination. On the basis of d. functional theory calculations, the intramol. Buchwald coupling of this reaction underwent a dearomatization and a 1,3-palladium migration process. The reasons for the control of the chem. selectivity by the protecting groups are given. Moreover, synthetic applications toward 4-piperazinylindole and a GOT1 inhibitor were realized. After reading the article, we found that the author used 4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0COA of Formula: C12H15N3)

4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.COA of Formula: C12H15N3

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

Akama, Tsutomu; Zhang, Yong-Kang; Freund, Yvonne R.; Berry, Pamela; Lee, Joanne; Easom, Eric E.; Jacobs, Robert T.; Plattner, Jacob J.; Witty, Michael J.; Peter, Rosemary; Rowan, Tim G.; Gillingwater, Kirsten; Brun, Reto; Nare, Bakela; Mercer, Luke; Xu, Musheng; Wang, Jiangong; Liang, Hao published an article in Bioorganic & Medicinal Chemistry Letters. The title of the article was 《Identification of a 4-fluorobenzyl L-valinate amide benzoxaborole (AN11736) as a potential development candidate for the treatment of Animal African Trypanosomiasis (AAT)》.Product Details of 123987-13-3 The author mentioned the following in the article:

Novel L-valinate amide benzoxaboroles and analogs were designed and synthesized for a structure-activity-relationship (SAR) investigation to optimize the growth inhibitory activity against Trypanosoma congolense (T. congolense) and Trypanosoma vivax (T. vivax) parasites. The study identified 4-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate (5, AN11736), which showed IC50 values of 0.15 nM against T. congolense and 1.3 nM against T. vivax, and demonstrated 100% efficacy with a single dose of 10 mg/kg against both T. congolense and T. vivax in mouse models of infection (IP dosing) and in the target animal, cattle, dosed i.m. AN11736 has been advanced to early development studies.(3-(4-Methylpiperazin-1-yl)phenyl)methanol(cas: 123987-13-3Product Details of 123987-13-3) was used in this study.

(3-(4-Methylpiperazin-1-yl)phenyl)methanol(cas: 123987-13-3) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.Product Details of 123987-13-3

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

《Yawning and hypothermia in rats: effects of dopamine D3 and D2 agonists and antagonists》 was written by Collins, Gregory T.; Newman, Amy Hauck; Grundt, Peter; Rice, Kenner C.; Husbands, Stephen M.; Chauvignac, Cedric; Chen, Jianyong; Wang, Shaomeng; Woods, James H.. HPLC of Formula: 70006-24-5 And the article was included in Psychopharmacology (Berlin, Germany) on August 31 ,2007. The article conveys some information:

Identification of behaviors specifically mediated by the dopamine D2 and D3 receptors would allow for the determination of in vivo receptor selectivity and aide the development of novel therapeutics for dopamine-related diseases. These studies were aimed at evaluating the specific receptors involved in the mediation of D2/D3 agonist-induced yawning and hypothermia. The relative potencies of a series of D2-like agonists to produce yawning and hypothermia were determined The ability of D3-selective and D2-selective antagonists to inhibit the induction of yawning and hypothermia were assessed and a series of D2/D3 antagonists were characterized with respect to their ability to alter yawning induced by a low and high dose of PD-128,907 and sumanirole-induced hypothermia. D3-preferring agonists induced yawning at lower doses than those required to induce hypothermia and the D2-preferring agonist, sumanirole, induced hypothermia at lower doses than were necessary to induce yawning. The rank order of D3 selectivity was pramipexole > PD-128,907=7-OH-DPAT = quinpirole = quinelorane > apomorphine = U91356A. Sumanirole had only D2 agonist effects. PG01037, SB-277011A, and U99194 were all D3-selective antagonists, whereas haloperidol and L-741,626 were D2-selective antagonists and nafadotride’s profile of action was more similar to the D2 antagonists than to the D3 antagonists. D3 and D2 receptors have specific roles in the mediation of yawning and hypothermia, resp., and the anal. of these effects allow inferences to be made regarding the selectivity of D2/D3 agonists and antagonists with respect to their actions at D2 and D3 receptors. The results came from multiple reactions, including the reaction of Abt-724(cas: 70006-24-5HPLC of Formula: 70006-24-5)

Abt-724(cas: 70006-24-5) belongs to piperazines. 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).HPLC of Formula: 70006-24-5

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

Safety of 4-(Piperazin-1-yl)-1H-indoleOn September 1, 2018 ,《Discovery and optimization of aspartate aminotransferase 1 inhibitors to target redox balance in pancreatic ductal adenocarcinoma》 was published in Bioorganic & Medicinal Chemistry Letters. The article was written by Anglin, Justin; Zavareh, Reza Beheshti; Sander, Philipp N.; Haldar, Daniel; Mullarky, Edouard; Cantley, Lewis C.; Kimmelman, Alec C.; Lyssiotis, Costas A.; Lairson, Luke L.. The article contains the following contents:

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is extremely refractory to the therapeutic approaches that have been evaluated to date. Recently, it has been demonstrated that PDAC tumors are dependent upon a metabolic pathway involving aspartate aminotransferase 1, also known as glutamate-oxaloacetate transaminase 1 (GOT1), for the maintenance of redox homeostasis and sustained proliferation. As such, small mol. inhibitors targeting this metabolic pathway may provide a novel therapeutic approach for the treatment of this devastating disease. To this end, from a high throughput screen of ∼800,000 mols., 4-(1H-indol-4-yl)-N-phenylpiperazine-1-carboxamide was identified as an inhibitor of GOT1. Mouse pharmacokinetic studies revealed that potency, rather than inherent metabolic instability, would limit immediate cell- and rodent xenograft-based experiments aimed at validating this potential cancer metabolism-related target. Medicinal chem.-based optimization resulted in the identification of multiple derivatives with >10-fold improvements in potency, as well as the identification of a tryptamine-based series of GOT1 inhibitors.4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0Safety of 4-(Piperazin-1-yl)-1H-indole) was used in this study.

4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.Safety of 4-(Piperazin-1-yl)-1H-indole

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

Product Details of 70006-24-5On October 31, 2015 ,《Role of dopamine D4 receptors in copulatory behavior: Studies with selective D4 agonists and antagonists in male rats》 appeared in Pharmacology, Biochemistry and Behavior. The author of the article were Sanna, Fabrizio; Contini, Andrea; Melis, Maria Rosaria; Argiolas, Antonio. The article conveys some information:

Dopamine influences the anticipatory and consummatory phases of sexual behavior, by acting on receptors of the D2 family (D2, D3 and D4) and in particular of the D2 subtype, although evidence for a role of D4 receptors in erectile function and copulatory behavior is also available. In order to clarify such a role of D4 receptors, the effect of selective D4 receptor agonists and antagonists on copulatory behavior of sexually potent male rats in classic copulation tests with a receptive female, was compared with that of apomorphine and haloperidol, a classic dopamine receptor agonist and antagonist, resp. PD-168,077 (0.05-0.2 mg/kg) and ABT-724 (0.01-0.04 mg/kg), two selective D4 receptor agonists, given s.c., improved dose-dependently copulatory behavior as shown by the decrease of mount frequency and post ejaculatory interval induced by PD-168,077, and of mount frequency, ejaculation latency, post ejaculatory and inter intromission intervals induced by ABT-724, and by the increase of ejaculation frequency and copulatory efficacy induced by both drugs. Conversely, L-745,870 (1-5 mg/kg), a selective D4 receptor antagonist, given i.p., impaired dose-dependently copulatory behavior, as shown by the increase in intromission and ejaculation latencies, mount frequency, post ejaculatory interval and the decrease in ejaculation frequency and copulatory efficacy induced by this drug. L-745,870 (5 mg/kg) administered before PD-168,077 (0.2 mg/kg) or ABT-724 (0.04 mg/kg), also abolished completely the facilitatory effects of both PD-168,077 and ABT-724 on sexual behavior. These results confirm the involvement of D4 receptors in specific aspects of male rat copulatory behavior that overlap only partially with those influenced by apomorphine and haloperidol. In the experiment, the researchers used Abt-724(cas: 70006-24-5Product Details of 70006-24-5)

Abt-724(cas: 70006-24-5) belongs to piperazines. 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).Product Details of 70006-24-5

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

Zajdel, Pawel; Kos, Tomasz; Marciniec, Krzysztof; Satala, Grzegorz; Canale, Vittorio; Kaminski, Krzysztof; Holuj, Malgorzata; Lenda, Tomasz; Koralewski, Robert; Bednarski, Marek; Nowinski, Leszek; Wojcikowski, Jacek; Daniel, Wladyslawa A.; Nikiforuk, Agnieszka; Nalepa, Irena; Chmielarz, Piotr; Kusmierczyk, Justyna; Bojarski, Andrzej J.; Popik, Piotr published an article on February 10 ,2018. The article was titled 《Novel multi-target azinesulfonamides of cyclic amine derivatives as potential antipsychotics with pro-social and pro-cognitive effects》, and you may find the article in European Journal of Medicinal Chemistry.Recommanded Product: 4-(Piperazin-1-yl)-1H-indole The information in the text is summarized as follows:

Currently used antipsychotics are characterized by multireceptor mode of action. While antagonism of dopamine D2 receptors is responsible for the alleviation of “”pos.”” symptoms of schizophrenia and the effects at other, particularly serotonergic receptors are necessary for their addnl. therapeutic effects, there is no consensus regarding an “”ideal”” target engagement. Here, a detailed SAR anal. in a series of 45 novel azinesulfonamides of cyclic amine derivatives, involving the aryl-piperazine/piperidine pharmacophore, central alicyclic amine and azinesulfonamide groups has led to the selection of (S)-4-((2-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)sulfonyl)isoquinoline (62). The polypharmacol. profile of 62, characterized by partial 5-HT1AR agonism, 5-HT2A/5-HT7/D2/D3R antagonism, and blockade of SERT, reduced the “”pos.””-like, and “”neg.””-like symptoms of psychoses. Compound 62 produced no catalepsy, demonstrated a low hyperprolactinemia liability and displayed pro-cognitive effects in the novel object recognition task and attentional set-shifting test. While association of in vitro features with the promising in vivo profile of 62 is still not fully established, its clin. efficacy should be verified in further stages of development. The experimental part of the paper was very detailed, including the reaction process of 4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0Recommanded Product: 4-(Piperazin-1-yl)-1H-indole)

4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0) belongs to piperazines. 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).Recommanded Product: 4-(Piperazin-1-yl)-1H-indole

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

Miller-Moslin, Karen; Peukert, Stefan; Jain, Rishi K.; McEwan, Michael A.; Karki, Rajesh; Llamas, Luis; Yusuff, Naeem; He, Feng; Li, Yanhong; Sun, Yingchuan; Dai, Miao; Perez, Lawrence; Michael, Walter; Sheng, Tao; Lei, Huangshu; Zhang, Rui; Williams, Juliet; Bourret, Aaron; Ramamurthy, Arun; Yuan, Jing; Guo, Ribo; Matsumoto, Melissa; Vattay, Anthony; Maniara, Wieslawa; Amaral, Adam; Dorsch, Marion; Kelleher, Joseph F. III published an article in Journal of Medicinal Chemistry. The title of the article was 《1-Amino-4-benzylphthalazines as Orally Bioavailable Smoothened Antagonists with Antitumor Activity》.Application of 1057682-05-9 The author mentioned the following in the article:

Abnormal activation of the Hedgehog (Hh) signaling pathway has been linked to several types of human cancers, and the development of small-mol. inhibitors of this pathway represents a promising route toward novel anticancer therapeutics. A cell-based screen performed in our laboratories identified a new class of Hh pathway inhibitors, 1-amino-4-benzylphthalazines, e.g. I, that act via antagonism of the Smoothened receptor. A variety of analogs were synthesized and their structure-activity relationships determined This optimization resulted in the discovery of high affinity Smoothened antagonists, one of which was further profiled in vivo. This compound displayed a good pharmacokinetic profile and also afforded tumor regression in a genetic mouse model of medulloblastoma. After reading the article, we found that the author used (R)-6-(3-Methylpiperazin-1-yl)nicotinonitrile(cas: 1057682-05-9Application of 1057682-05-9)

(R)-6-(3-Methylpiperazin-1-yl)nicotinonitrile(cas: 1057682-05-9) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.Application of 1057682-05-9

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

Computed Properties of C12H15N3On May 26, 2015, Kooistra, Albert J.; Leurs, Rob; de Esch, Iwan J. P.; de Graaf, Chris published an article in Journal of Chemical Information and Modeling. The article was 《Structure-based prediction of G-protein-coupled receptor ligand function: A β-adrenoceptor case study》. The article mentions the following:

The spectacular advances in G-protein-coupled receptor (GPCR) structure determination have opened up new possibilities for structure-based GPCR ligand discovery. The structure-based prediction of whether a ligand stimulates (full/partial agonist), blocks (antagonist), or reduces (inverse agonist) GPCR signaling activity is, however, still challenging. A total of 31 β1 (β1R) and β2 (β2R) adrenoceptor crystal structures, including antagonist, inverse agonist, and partial/full agonist-bound structures, allowed the authors to explore the possibilities and limitations of structure-based prediction of GPCR ligand function. The authors used all unique protein-ligand interaction fingerprints (IFPs) derived from all ligand-bound β-adrenergic crystal structure monomers to post-process the docking poses of known β1R/β2R partial/full agonists, antagonists/inverse agonists, and physicochem. similar decoys in each of the β1R/β2R structures. The systematic anal. of these 1920 unique IFP-structure combinations offered new insights into the relative impact of protein conformation and IFP scoring on selective virtual screening (VS) for ligands with a specific functional effect. The authors’ studies show that ligands with the same function can be efficiently classified on the basis of their protein-ligand interaction profile. Small differences between the receptor conformation (used for docking) and reference IFP (used for scoring of the docking poses) determine, however, the enrichment of specific ligand types in VS hit lists. Interestingly, the selective enrichment of partial/full agonists can be achieved by using agonist IFPs to post-process docking poses in agonist-bound as well as antagonist-bound structures. The authors have identified optimal structure-IFP combinations for the identification and discrimination of antagonists/inverse agonist and partial/full agonists, and defined a predicted IFP for the small full agonist norepinephrine that gave the highest retrieval rate of agonists over antagonists for all structures (with an enrichment factor of 46 for agonists and 8 for antagonists on average at a 1% false-pos. rate). This β-adrenoceptor case study provides new insights into the opportunities for selective structure-based discovery of GPCR ligands with a desired function and emphasizes the importance of IFPs in scoring docking poses. The results came from multiple reactions, including the reaction of 4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0Computed Properties of C12H15N3)

4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.Computed Properties of C12H15N3

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

Synthetic Route of C12H15N3On May 31, 2020, Zhu, Chenghao; Sawrey-Kubicek, Lisa; Beals, Elizabeth; Rhodes, Chris H.; Houts, Hannah Eve; Sacchi, Romina; Zivkovic, Angela M. published an article in Nutrition Research (New York, NY, United States). The article was 《Human gut microbiome composition and tryptophan metabolites were changed differently by fast food and Mediterranean diet in 4 days: a pilot study》. The article mentions the following:

Diets rich in animal source foods vs plant-based diets have different macronutrient composition, and they have been shown to have differential effects on the gut microbiome. In this study, we hypothesized that diets with very different nutrient composition are able to change gut microbiome composition and metabolites in a very short period. We compared a fast food (FF) diet (ie, burgers and fries) with a Mediterranean (Med) diet, which is rich in vegetables, whole grains, olive oil, nuts, and fish. Plasma metabolites and bile acids were analyzed using liquid chromatog.-mass spectrometry. Certain bile-tolerant microbial genera and species including Collinsella, Parabacteroides, and Bilophila wadsworthia significantly increased after the FF diet. Some fiber-fermenting bacteria, including Lachnospiraceae and Butyricicoccus, increased significantly after the Med diet and decreased after the FF diet. Bacterially produced metabolites indole-3-lactic acid and indole-3-propionic acid, which have been shown to confer beneficial effects on neuronal cells, increased after the Med diet and decreased after the FF diet. Interindividual variability in response to the treatments may be related to differences in background diet, for example as shown by differences in Bilophila response in relationship to the saturated fat content of the baseline diet. In conclusion, an animal fat-rich, low-fiber FF diet v. a high-fiber Med diet altered human gut microbiome composition and its metabolites after just 4 days. The results came from multiple reactions, including the reaction of 4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0Synthetic Route of C12H15N3)

4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0) belongs to piperazines. 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).Synthetic Route of C12H15N3

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

Heusler, Peter; Bruins Slot, Liesbeth; Rauly-Lestienne, Isabelle; Palmier, Christiane; Tardif, Stephanie; Tourette, Amelie; Ailhaud, Marie-Christine; Cussac, Didier published an article on January 31 ,2009. The article was titled 《Activation of G proteins and extracellular signal-regulated kinase 1/2 phosphorylation via human dopamine D4.4 receptors: differential pathway-dependent potencies of receptor agonists》, and you may find the article in Naunyn-Schmiedeberg’s Archives of Pharmacology.Computed Properties of C17H19N5 The information in the text is summarized as follows:

Agonist activity at recombinant human dopamine D4.4 receptors was compared in stably transfected CHO cells using two functional readouts: G protein activation by [35S]GTPγS binding and phosphorylation of extracellular signal-regulated kinase 1/2 (pERK1/2). Results with a large series of agonists reveal markedly higher relative agonist efficacy in the pERK1/2 assay compared with [35S]GTPγS binding, while potencies were generally higher in the latter readout. Whereas efficacies were highly correlated when comparing both tests, potencies determined using the pERK1/2 assay were neither correlated with those for G protein activation nor with binding affinities. To examine if these differences may be attributable to distinct assay conditions (5 min incubation for pERK1/2 compared with binding equilibrium conditions for [35S]GTPγS), selected compounds were tested in a modified short-duration [35S]GTPγS binding assay. In these experiments, potencies were generally reduced; however, compounds exhibiting comparably high potency in the pERK1/2 assay were not affected by this duration-dependent potency shift. The authors conclude that assay parameters such as signal amplification and incubation time have to be considered with respect to the appropriate choice of exptl. approaches that best reflect agonist activity at dopamine D4 receptors in vivo. In the experiment, the researchers used Abt-724(cas: 70006-24-5Computed Properties of C17H19N5)

Abt-724(cas: 70006-24-5) belongs to piperazines. 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).Computed Properties of C17H19N5

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