Tag: 200-300

Category: piperazinesOn May 1, 2010 ,《Discovery of novel leukotriene A4 hydrolase inhibitors based on piperidine and piperazine scaffolds》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Sandanayaka, Vincent; Mamat, Bjorn; Bhagat, Nikhil; Bedell, Louis; Halldorsdottir, Gudrun; Sigthorsdottir, Heida; Andresson, Torkell; Kiselyov, Alex; Gurney, Mark; Singh, Jasbir. The article conveys some information:

Novel piperidine and piperazine derivatives have been designed and tested as inhibitors of LTA4 hydrolase (LTA4H). Most potent compounds showed good potency in both enzymic and functional human whole blood assay. Crystallog. studies further confirmed observed structure-activity relationship and LTA4H binding mode for analogs from the piperidine series. In addition to this study using (4-Benzylpiperazin-2-yl)methanol, there are many other studies that have used (4-Benzylpiperazin-2-yl)methanol(cas: 85817-34-1Category: piperazines) was used in this study.

(4-Benzylpiperazin-2-yl)methanol(cas: 85817-34-1) 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).Category: piperazines

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

Computed Properties of C17H19N5On September 23, 2013 ,《Computational Profiling of Bioactive Compounds Using a Target-Dependent Composite Workflow》 was published in Journal of Chemical Information and Modeling. The article was written by Meslamani, Jamel; Bhajun, Ricky; Martz, Francois; Rognan, Didier. The article contains the following contents:

Computational target fishing is a chemoinformatic method aimed at determining main and secondary targets of bioactive compounds in order to explain their mechanism of action, anticipate potential side effects, or repurpose existing drugs for novel therapeutic indications. Many existing successes in this area have been based on a use of a single computational method to estimate potentially new target-ligand associations We herewith present an automated workflow using several methods to optimally browse target-ligand space according to existing knowledge on either ligand and target space under investigation. The protocol uses four ligand-based (SVM classification, SVR affinity prediction, nearest neighbors interpolation, shape similarity) and two structure-based approaches (docking, protein-ligand pharmacophore match) in series, according to well-defined ligand and target property checks. The workflow was remarkably accurate (72%) in identifying the main target of 189 clin. candidates and proposed two novel off-targets which could be exptl. validated. Rolofylline, an adenosine A1 receptor antagonist, was confirmed to inhibit phosphodiesterase 5 with a moderate affinity (IC50 = 13.8 μM). More interestingly, we describe a strong binding (IC50 = 142 nM) of a claimed selective phosphodiesterase 10 A inhibitor (PF-2545920) with the cysteinyl leukotriene type 1 G protein-coupled receptor. The results came from multiple reactions, including the reaction of 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

Synthetic Route of C8H20Cl2N2O2SOn November 18, 2011 ,《Application of PAT tools for the safe and reliable production of a dihydro-1H-imidazole》 appeared in Organic Process Research & Development. The author of the article were Barrios Sosa, Ana C.; Conway, Ryan; Williamson, R. Thomas; Suchy, James P.; Edwards, William; Cleary, Thomas. The article conveys some information:

The application of two Process Anal. Technol. (PAT) tools was studied and implemented for the safe and reliable synthesis of an advanced intermediate (4S,5R-7) (I) of a member of the dihydro-1H-imidazole class of compounds Real time data were generated using ReactIR to track the complete breakdown of phosgene precursors to phosgene and confirm the absence of these hazardous materials prior to batch transfer operations. In addition, the chiral resolution by crystallization of rac7 was monitored by a Lasentec FBRM probe-based system. Implementation of the latter helped to track the crystallization process to minimize the risk of cocrystn. of undesired isomer 4R,5S-7. In addition to this study using 1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride, there are many other studies that have used 1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride(cas: 939983-66-1Synthetic Route of C8H20Cl2N2O2S) was used in this study.

1-(3-(Methylsulfonyl)propyl)piperazine dihydrochloride(cas: 939983-66-1) is a member of sulfones.The sulfones, like the sulfonamides, are structural analogs of para-aminobenzoic acid that interfere with folic acid metabolism by acting as competitive inhibitors of dihydropteroate synthetase. All sulfones of clinical value are derivatives of dapsone, the most widely used member of this class.Synthetic Route of C8H20Cl2N2O2S

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

Rudolph, Dale A.; Alcazar, Jesus; Ameriks, Michael K.; Anton, Ana Belen; Ao, Hong; Bonaventure, Pascal; Carruthers, Nicholas I.; Chrovian, Christa C.; De Angelis, Meri; Lord, Brian; Rech, Jason C.; Wang, Qi; Bhattacharya, Anindya; Andres, Jose Ignacio; Letavic, Michael A. published their research in Bioorganic & Medicinal Chemistry Letters on August 15 ,2015. The article was titled 《Novel methyl substituted 1-(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanones are P2X7 antagonists》.Computed Properties of C10H18N2O3 The article contains the following contents:

The optimization efforts that led to a novel series of Me substituted 1-(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanones that are potent rat and human P2X7 antagonists are described. These efforts resulted in the discovery of compounds with good drug-like properties that are capable of high P2X7 receptor occupancy in rat following oral administration, including compounds I (P2X7 IC50 = 7.7 nM) and II (P2X7 IC50 = 7.7 nM). These compounds are expected to be useful tools for characterizing the effects of P2X7 antagonism in models of depression and epilepsy, and several of the compounds prepared are candidates for effective P2X7 PET tracers. The results came from multiple reactions, including the reaction of (S)-tert-Butyl 2-methyl-3-oxopiperazine-1-carboxylate(cas: 1799971-34-8Computed Properties of C10H18N2O3)

(S)-tert-Butyl 2-methyl-3-oxopiperazine-1-carboxylate(cas: 1799971-34-8) 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 C10H18N2O3

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

Evrard, Deborah A.; Zhou, Ping; Yi, Soo Y.; Zhou, Dahui; Smith, Deborah L.; Sullivan, Kelly M.; Hornby, Geoffrey A.; Schechter, Lee E.; Andree, Terrance H.; Mewshaw, Richard E. published an article on February 15 ,2005. The article was titled 《Studies towards the next generation of antidepressants. Part 4: Derivatives of 4-(5-fluoro-1H-indol-3-yl)cyclohexylamine with affinity for the serotonin transporter and the 5-HT1A receptor》, and you may find the article in Bioorganic & Medicinal Chemistry Letters.Category: piperazines The information in the text is summarized as follows:

Derivatives of the serotonin reuptake inhibitor 4-(5-fluoro-1H-indol-3-yl)cyclohexylamine, in which serotonin 1A (5-HT1A) receptor pharmacophoric elements are incorporated, are reported. Analogs exhibiting affinity for both the serotonin transporter and the 5-HT1A receptor are described. Compounds containing 1-(4-indolyl)piperazine and 2-(1H-indol-4-yloxy)ethylamine are promising leads for further SAR studies. In the experimental materials used by the author, we found 4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0Category: piperazines)

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.Category: piperazines

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

《Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI》 was written by Marona-Lewicka, Danuta; Chemel, Benjamin R.; Nichols, David E.. COA of Formula: C17H19N5 And the article was included in Psychopharmacology (Berlin, Germany) on April 30 ,2009. The article conveys some information:

Rationale: Lysergic acid diethylamide (LSD) differs from other types of hallucinogens in that it possesses direct dopaminergic effects. The exact nature of this component has not been elucidated. Objective: The present study sought to characterize the effects of several dopamine D4 agonists and antagonists on the discriminative stimulus effect of LSD at two pretreatment times and 2,5-dimethoxy-4-iodoamphetamine (DOI), a selective 5-HT2A/2C agonist. Materials and methods: Male Sprague-Dawley rats were trained in a two-lever, fixed ratio (FR) 50, food-reinforced task with LSD-30 (0.08 mg/kg, i.p., 30-min pretreatment time), LSD-90 (0.16 mg/kg, i.p., 90-min pretreatment time), and DOI (0.4 mg/kg, i.p., 30-min pretreatment time) as discriminative stimuli. Substitution and combination tests with the dopamine D4 agonists, ABT-724 and WAY 100635, were performed in all groups. Combination tests were run using the dopamine D4 antagonists A-381393 and L-745,870 and two antipsychotic drugs, clozapine and olanzapine. Results: WAY 100635 produced full substitution in LSD-90 rats, partial substitution in LSD-30 rats, and saline appropriate responding in DOI-trained rats. ABT-724 partially mimicked the LSD-90 and LSD-30 cues, but produced no substitution in DOI-trained rats. In combination tests, both agonists shifted the dose-response curve of LSD leftward, most potently for the LSD-90 cue. The D4 antagonists significantly attenuated both the LSD-90 and LSD-30 cue, but had no effect on the DOI cue. Conclusion: Dopamine D4 receptor activation plays a significant modulatory role in the discriminative stimulus effects in LSD-90-trained rats, most markedly for the later temporal phase of LSD, but has no effect on the cue produced by DOI.Abt-724(cas: 70006-24-5COA of Formula: C17H19N5) was used in this study.

Abt-724(cas: 70006-24-5) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.COA of Formula: C17H19N5

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

Pullagurla, Manik; Siripurapu, Uma; Kolanos, Renata; Bondarev, Mikhail L.; Dukat, Malgorzata; Setola, V.; Roth, B. L.; Glennon, Richard A. published their research in Bioorganic & Medicinal Chemistry Letters on December 1 ,2005. The article was titled 《Binding of amine-substituted N 1-benzenesulfonylindoles at human 5-HT6 serotonin receptors》.Reference of 4-(Piperazin-1-yl)-1H-indole The article contains the following contents:

An examination of several amine-substituted analogs of N1-benzenesulfonylindoles reveals that although they bind at human 5-HT6 serotonin receptors with high affinity, they are likely to bind in a dissimilar manner. The experimental part of the paper was very detailed, including the reaction process of 4-(Piperazin-1-yl)-1H-indole(cas: 84807-09-0Reference of 4-(Piperazin-1-yl)-1H-indole)

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.Reference of 4-(Piperazin-1-yl)-1H-indole

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

《Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats》 was written by Brioni, Jorge D.; Moreland, Robert B.; Cowart, Marlon; Hsieh, Gin C.; Stewart, Andrew O.; Hedlund, Petter; Donnelly-Roberts, Diana L.; Nakane, Masaki; Lynch, James J. III; Kolasa, Teodozyi; Polakowski, James S.; Osinski, Mark A.; Marsh, Kennan; Andersson, Karl-Erik; Sullivan, James P.. Related Products of 70006-24-5 And the article was included in Proceedings of the National Academy of Sciences of the United States of America on April 27 ,2004. The article conveys some information:

Apomorphine, a nonselective dopamine receptor agonist, facilitates penile erection and is effective in patients suffering from erectile dysfunction. The specific dopamine receptor subtype(s) responsible for its erectogenic effect is not known. Here we report that the dopamine D4 receptor plays a role in the regulation of penile function. ABT-724 is a selective dopamine D4 receptor agonist that activates human dopamine D4 receptors with an EC50 of 12.4 nM and 61% efficacy, with no effect on dopamine D1, D2, D3, or D5 receptors. ABT-724 dose-dependently facilitates penile erection when given s.c. to conscious rats, an effect that is blocked by haloperidol and clozapine but not by domperidone. A proerectile effect is observed after intracerebroventricular but not intrathecal administration, suggesting a supraspinal site of action. S.c. injections of ABT-724 increase intracavernosal pressure in awake freely moving rats. In the presence of sildenafil, a potentiation of the proerectile effect of ABT-724 is observed in conscious rats. The ability of ABT-724 to facilitate penile erection together with the favorable side-effect profile indicates that ABT-724 could be useful for the treatment of erectile dysfunction. In the experiment, the researchers used Abt-724(cas: 70006-24-5Related Products of 70006-24-5)

Abt-724(cas: 70006-24-5) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.Related Products of 70006-24-5

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

《Ring substituents on substituted benzamide ligands indirectly mediate interactions with position 7.39 of transmembrane helix 7 of the D4 dopamine receptor》 was written by Ericksen, Spencer S.; Cummings, David F.; Teer, Michael E.; Amdani, Shahnawaz; Schetz, John A.. Synthetic Route of C17H19N5 And the article was included in Journal of Pharmacology and Experimental Therapeutics on August 31 ,2012. The article conveys some information:

In an effort to delineate how specific mol. interactions of dopamine receptor ligand classes vary between D2-like dopamine receptor subtypes, a conserved threonine in transmembrane (TM) helix 7 (Thr7.39), implicated as a key ligand interaction site with biogenic amine G protein-coupled receptors, was substituted with alanine in D2 and D4 receptors. Interrogation of different ligand chemotypes for sensitivity to this substitution revealed enhanced affinity in the D4, but not the D2 receptor, specifically for substituted benzamides (SBAs) having polar 4- (para) and/or 5- (meta) benzamide ring substituents. D4-T7.39A was fully functional, and the mutation did not alter the sodium-mediated pos. and neg. allostery observed with SBAs and agonists, resp. With the exception of the non-SBA ligand (+)-butaclamol, which, in contrast to certain SBAs, had decreased affinity for the D4-T7.39A mutant, the interactions of numerous other ligands were unaffected by this mutation. SBAs were docked into D4 models in the same mode as observed for eticlopride in the D3 crystal structure. In this mode, interactions with TM5 and TM6 residues constrain the SBA ring position that produces distal steric crowding between pyrrolidinyl/diethylamine moieties and D4-Thr7.39. Ligand-residue interaction energy profiles suggest this crowding is mitigated by substitution with a smaller alanine. The profiles indicate sites that contribute to the SBA binding interaction and site-specific energy changes imparted by the D4-T7.39A mutation. Substantial interaction energy changes are observed at only a few positions, some of which are not conserved among the dopamine receptor subtypes and thus seem to account for this D4 subtype-specific structure-activity relationship. In the experiment, the researchers used many compounds, for example, Abt-724(cas: 70006-24-5Synthetic Route 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).Synthetic Route of C17H19N5

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

Safety of Abt-724On May 31, 2008, Newman-Tancredi, Adrian; Heusler, Peter; Martel, Jean-Claude; Ormiere, Anne-Marie; Leduc, Nathalie; Cussac, Didier published an article in International Journal of Neuropsychopharmacology. The article was 《Agonist and antagonist properties of antipsychotics at human dopamine D4.4 receptors: G-protein activation and K+ channel modulation in transfected cells》. The article mentions the following:

Interaction at dopamine D4 receptors may improve cognitive function, which is highly impaired in individuals with schizophrenia, but comparative studies of recent antipsychotics in cellular models of D4 receptor activation are lacking. Here, we report the in-vitro profile of over 30 ligands at recombinant hD4.4 receptors. In [35S]GTPγS binding experiments using membranes of CHO-hD4.4 cells, apomorphine, preclamol and the selective D4 agonists, ABT724, CP226269, Ro-10-5824 and PD168077, behaved as partial agonists (Emax 20-60% vs. dopamine), whereas L745870 and RBI257, displayed antagonist properties. The conventional’ antipsychotic, haloperidol and the atypicals’, clozapine and risperidone, exhibited antagonist properties, while third generation’ compounds bifeprunox, SLV313 and F15063, acted as partial agonists (10-30%). Aripiprazole and SSR181507 slightly stimulated [35S]GTPγS binding at micromolar concentrations In Xenopus laevis oocytes co-expressing hD4.4 receptors with G-protein-coupled inwardly rectifying potassium (GIRK) channels, apomorphine, preclamol, ABT724, CP226269, and PD168077 stimulated GIRK currents (Emax 70-80%). The 5-HT1A receptor ligands, WAY100635 and flibanserin, also exhibited partial agonist activity (30% and 15%, resp.). Haloperidol, clozapine, olanzapine and nemonapride did not stimulate GIRK currents, whereas aripiprazole, bifeprunox, SLV313 and F15063, but not SSR181507, exhibited partial agonism (Emax 20-35%). In-vitro responses depended on exptl. conditions: increasing NaCl concentration (30 mm to 100 mm) reduced agonist efficacy in [35S]GTPγS binding, whereas decreasing the amount of hD4.4 cRNA injected into oocytes (from 2.0 to 0.5 ng/oocyte) reduced agonist efficacy of several compounds These data indicate that, unlike conventional or atypical’ antipsychotics, several third generation’ agents display D4 receptor partial agonism that may be sufficient to influence physiol. D4 receptor activity in vivo. In the experiment, the researchers used many compounds, for example, Abt-724(cas: 70006-24-5Safety of Abt-724)

Abt-724(cas: 70006-24-5) belongs to piperazines. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines.Safety of Abt-724

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