The Most Professional Analysis Report On Homopiperazine(505-66-8)

1. www.aasraw.com The Most Professional Analysis Report On Homopiperazine(505-66-8) 1. Homopiperazine--CAS: 505-66-8...............................................................................................1 2. Homopiperazine Compounds......................................................................................................2 3. Homopiperazine Mechanism of Action--CAS no. 505-66-8................................................... 3 4. Reaction of Homopiperazine with Different Compounds.......................................................4 5. Safety and Handling When You Take Homopiperazine..........................................................8 Take Homopiperazine powder now!!!...........................................................................................9 1. Homopiperazine--CAS: 505-66-8 Homopiperazine is used prepare to 1,4-bis-(2-thiazolyl)-1,4-diazacyc loheptane by 2-bromo-thiazole. It acts as an intermediate for repaglinide and fasudil hydrochloride. It is also used in the preparation of potent H3 receptor antagonists, which is used for the neurodegenerative Further, it is used in vesicant, cosmetic, emulsifier energetic material. It acts as a corrosion inhibitor for iron. In reacting with treatment conditions. of and pharmaceuticals, it is employed as antipyretic and reducing blood sugar, adiposity, calm, antipsychotic and anti-nervous. 1 aas11@aasraw.com

2. www.aasraw.com 2. Homopiperazine Compounds Homopiperazine compounds is a chronic allergic lung disease and seizures are caused by the interaction of the environmental factors and a poor physical state. In the long run, severe irreversible structural airway alterations with a lack of responsiveness to treatment are frequently observed. Smooth hypertrophy and hyperplasia are features of airway remodeling, which significantly contribute to the decline of lung function and frequent episodes of asthma attacks. Increasing levels of cytoskeletal proteins, inflammatory cytokines, enzymes, receptors and adhesion molecules have been reported to be associated with complex pathophysiology of Homopiperazine compounds, including the myosin light chain kinase (MLCK). Almost all eukaryotes produce MLCK, which is a Ca2+/calmodulin-dependent protein kinase (CaMK) with a catalytic core and autoregulatory segments in the C-terminus. MLCK has a variety of different isoforms, the two major types of which are smooth-muscle MLCK (130–150 kDa) and nonmuscle MLCK (210–220 kDa), which are emanated from the same gene. The phosphorylation of MLC has an important role in airway smooth muscle contraction and relaxation. It also promotes airway inflammation and airway remodeling by activating airway smooth muscle, fibroblasts and myoblasts, which subsequently secrete cytokines, chemokines and extracellular matrix. Previous studies have demonstrated that MLCK regulates numerous biological functions through up-regulation of NADPH oxidase, tumor necrosis factor receptor 2 signaling and notch signaling. The signaling effect of MLCK in chronic asthma has been reported by several studies, including the regulation of the inflammatory permeability. The mechanism of MLCK in smooth muscle cells and the immune regulation of T cells is complex, inducing a variety of cytokines in the occurrence and development of disease. (5-Iodonaphthalene-1-sulfonyl) homopiperazine compounds (ML-7), customarily used as an MLCK inhibitor. This inhibitor combines with the catalytic perssad of the MLCK and then decreases the activity of the enzyme and is frequently applied in animal and cytological experiments. muscle response and vascular a membrane-permeable agent, is In Homopiperazine compounds, the imbalance of the proportion of T-helper type 1 (Th1) to Th2 cells activates the CD4+ Th2 cell immune response and the release of interleukin (IL)-13, −25, −5, −4 and −33, prompting the 2 aas11@aasraw.com

3. www.aasraw.com transformation of B cells into immunoglobulin (Ig)E-secreting cells (23,24). Among these ILs, IL-25 and −33 are known as vital pro-inflammatory mediators that induce the release of Th2-associated cytokines, including IL-5, IL-4 and IL-13, which elevate hyperresponsiveness, remodeling and mucus hypersecretion (25–28). However, in asthma, little is known regarding the correlation of MLCK with Th2 cytokines. serum IgE, as well as airway Based on the above, the present study hypothesized that MLCK accelerates airway remodeling through the induction of Th2 cytokines, which may be one of the mechanisms underlying the pathogenesis of asthma. 3. Homopiperazine Mechanism of Action--CAS no. 505-66-8 Benzodiazepines act by binding at the interface of the α and γ subunits of the GABAA receptor. This binding site is distinct from that of endogenous agonist GABA (which binds between the α and β subunits), and also from other GABAergic drugs, such as barbiturates (Figure 11-6). Benzodiazepines allosterically modulate the receptor such that it has greater affinity for GABA. This increases the opening time of the associated chloride channel, which leads to hyperpolarization or stabilization of the resting membrane potential near the chloride equilibrium potential. Because binding requires a specific histidine residue in the α subunit, benzodiazepines act only at receptors containing α1, α2, α3, or α5 subunits, and have no action on receptors containing α4 or α6 subunits. Benzodiazepines are heterogeneous in their affinities for various GABAA receptor subtypes, which pharmacologic effects. For example, anxiolysis is associated with greater relative affinity for the α2 subunit. underlies the differences in their Most benzodiazepines are highly protein bound and undergo microsomal oxidation in the liver via CYP enzymes, especially CYP 3A4. Their metabolism is therefore altered by the presence of drugs that either inhibit or induce CYP activity, as well as by age and disease. Several benzodiazepines have active metabolites, including a number with half-lives considerably longer than the parent compound; the half-life of the partial agonist N-desmethyldiazepam, the 3 aas11@aasraw.com

4. www.aasraw.com hours. principal benzodiazepines—oxazepam, lorazepam, and temazepam—are metabolized by glucuronidation and have no significantly active metabolites; these are therefore preferred in older adults and in patients with hepatic disease. metabolite of diazepam, can exceed 100 Three 4. Reaction of Homopiperazine with Different Compounds (1) Psychiatry related information on Homopiperazine To test whether chronic treatment of an oral Rho kinase inhibitor (fasudil, 5-Isoquinolinesulfonyl homopiperazine) could prevent the development of both vasculogenic erectile dysfunction and pelvic atherosclerosis in a rat model. (2) High impact information on Homopiperazine ♦ However, the binding data showed that compound 32 displayed a 10-fold decrease in affinity at the DAT and a 100-fold decrease in selectivity at the DAT 4 aas11@aasraw.com

5. www.aasraw.com relative to the SERT compared to its corresponding homopiperazine compound 4. ♦ Synthesis and action on the central nervous system of mescaline analogues containing piperazine or homopiperazine rings. ♦ Small molecule inhibitors of the CCR2b receptor. Part 1: Discovery and optimization of homopiperazine derivatives. ♦ Herein we report a novel series of fXa inhibitors in which the 1,4-diazepane moiety was designed to interact with the S4 aryl-binding domain of the fXa active site. ♦ New mu-opioid receptor (MOR) agonists containing piperazine and homopiperazine moieties in the structures were synthesized and their affinities to and agonist potencies on MOR were evaluated. (3) Biological context of Homopiperazine Structure-activity nitriles employing various D-amino acid moieties and their N-furanoyl analogues were undertaken. relationships of homopiperazine-containing alkoxybiaryl (4) Associations of Homopiperazine with other chemical compounds The bisbenzamidine with a homopiperazine ring as the central linker was found to be the most potent NMDA receptor antagonist among all the pentamidine analogues tested so far. (5) Reaction of Homopiperazine with Endogenous Formaldehyde 5 aas11@aasraw.com

6. www.aasraw.com Understanding the metabolic fate of putative drug candidates both in vitro and in vivo is a key component of Rapid production information describing the rate of clearance and site of metabolism is essential for directing iterative synthetic chemistry cycles toward promising structural templates with properties for an effective drug. drug discovery. of early make-test the requisite Reactive drug metabolites are of great concern in the pharmaceutical industry (Evans et al., 2004; Baillie 2006, 2009). Although their identification is relatively straightforward with appropriate in vitro trapping experiments, sometimes additional reactive compounds are found unexpectedly. In general, early metabolism studies involve incubation in hepatocytes or microsomes to mimic the most prevalent metabolic processes occurring in the liver. Incubate samples at t = 0 min and at a terminal time point (usually 30–60 min) are then compared by LC-UV-MS/MS. These studies can be both challenging and time-consuming even when only a small number of metabolites are identified. Simply mining the raw data to find the metabolites in the terminal sample often requires the use of a variety of techniques, ranging from simple UV comparison to complex common fragment searching (commonly referred to as broad band or MSe) or the use of sophisticated MS subtraction routines such as mass defect filtering. Experiments are therefore normally performed using state-of-the-art instruments offering a variety of options to aid detection and structure identification. The information is then used to direct and modify the chemistry toward compounds with favorable metabolic properties. Improved understanding of bioactivation mechanisms, reactive intermediate formation (so-called reactive metabolites), and adverse toxicity has led to the front loading of biotransformation studies. In response, most pharmaceutical companies now employ reactive metabolite trapping screens using liver microsomes (usually human) fortified with nucleophiles such as GSH, cysteine, KCN, and methoxylamine (Prakash et al., 2008). The nucleophiles trap reactive 6 aas11@aasraw.com

7. www.aasraw.com electrophilic species at sufficient concentration to favor the formation of a stable product identified by their unique MS/MS spectral characteristics. Both early site of metabolism and reactive metabolite trapping studies rely on in vitro systems to generate the metabolites. However, metabolites can also be formed in complete biological systems, which could be missed if the metabolic pathways are unknown and/or the endogenous reagents are not represented in these in vitro systems. Hence, in our laboratories potential drug candidates undergo nonradiolabeled in vivo metabolite identification studies. These generally involve either a bile duct-cannulated study in rats, with collection of urine and bile over a 24-h period or collection of blood and urine from a high-dose rat pharmacokinetic study. The studies aid the identification of the excreted metabolites and ensure identification of any unexpected reactive metabolites not generated or detected in the preliminary in vitro systems. During recent rat in vivo metabolite identification studies with a series of lead compounds, cyclized GSH adducts were detected, similar to those reported by Doss et al. (2005), highlighting a potential reactive metabolite alert. This alert was not raised in the conventional GSH trapping screen, because of the type of the GSH rearrangement (data not shown). The reactophore in these lead compounds consisted of a terminal piperazine, which was responsible for this bioactivation. To preserve the potency of the compounds and remove the reactive metabolite risk, the chemistry was changed to a homopiperazine series. Hence, several promising homopiperazine compounds from this series were dosed to rats to assess whether these GSH adducts were also formed. Instead, the analyses led to the observation of unusual, novel products with a molecular weight gain of 13 Da (while showing an apparent increase of +12 Da by mass spectrometry) as the major parent-related material in the urine and blood samples, which were not detected in the preliminary in vitro studies. The formation of these products, N-(3-(3-fluorophenyl)-1,2,4-thiadiazol-5-yl)-4-(4-isopropyl-1,4-diaze-pane-2-c arbonyl)piperazine-1-carboxamide (AZX) + 13 throughout, is subject to further investigation in this article, with compound AZX (Fig. 1) as a representative structure for the “homopiperazine series.” referred to as 7 aas11@aasraw.com

8. www.aasraw.com 5. Safety and Handling When You Take Homopiperazine GHS H Statement: ♣ Harmful in contact with skin. ♣ Causes serious eye damage. ♣ Causes severe skin burns and eye damage. GHS P Statement: ♣ Wear protective gloves/protective clothing/eye protection/face protection. ♣ IF SWALLOWED: rinse mouth. Do NOT induce vomiting. ♣ Wear eye protection/face protection. ♣ IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. ♣ Immediately call a POISON CENTER or doctor/physician. ♣ IF ON SKIN: Wash with plenty of soap and water. WARNING: The information provided on this web site was developed in compliance with European Union (EU) regulations and is correct to the best of our knowledge, information and belief at the date of its publication. The 8 aas11@aasraw.com

9. www.aasraw.com information given is designed only as a guide for safe handling and use. It is not to be considered as either a warranty or quality specification. Take Homopiperazine powder now!!! 9 aas11@aasraw.com