Tag: 300-400

Amyotrophic Lateral Sclerosis as an Adverse Drug Reaction: A Disproportionality Analysis of the Food and Drug Administration Adverse Event Reporting System was written by Gaimari, Anna;Fusaroli, Michele;Raschi, Emanuel;Baldin, Elisa;Vignatelli, Luca;Nonino, Francesco;De Ponti, Fabrizio;Mandrioli, Jessica;Poluzzi, Elisabetta. And the article was included in Drug Safety in 2022.Synthetic Route of C16H21Cl2N3O2 The following contents are mentioned in the article:

Amyotrophic lateral sclerosis is a fatal progressive disease with a still unclear multi-factorial etiol. This study focused on the potential relationship between drug exposure and the development of amyotrophic lateral sclerosis by performing a detailed anal. of events reported in the FDA Adverse Event Reporting System database. The FDA Adverse Event Reporting System quarterly data (Jan. 2004-June 2020) were downloaded and deduplicated. The reporting odds ratios and their 95% confidence intervals were calculated as a disproportionality measure. The robustness of the disproportion was assessed accounting for major confounders (i.e., using a broader query, restricting to suspect drugs, and excluding reports with amyotrophic lateral sclerosis as an indication). Disproportionality signals were prioritized based on their consistency across analyses (reporting odds ratio stability). We retained 1188 amyotrophic lateral sclerosis cases. Sixty-two drugs showed significant disproportionality for amyotrophic lateral sclerosis onset in at least one anal., and 31 had consistent reporting odds ratio stability, including tumor necrosis factor-alpha inhibitors and statins. Disproportionality signals from ustekinumab, an immunomodulator against interleukins 12-23 used in autoimmune diseases, and the anti-IgE omalizumab were consistent among analyses and unexpected. For each drug emerging as possibly associated with amyotrophic lateral sclerosis onset, biol. plausibility, underlying disease, and reverse causality could be argued. Our findings strengthened the plausibility of a precipitating role of drugs primarily through immunomodulation (e.g., tumor necrosis factor-alpha, ustekinumab, and omalizumab), but also by impacting metabolism and the musculoskeletal integrity (e.g., statins and bisphosphonates). Complement and NF-kB dysregulation could represent interesting topics for planning translational mechanistic studies on amyotrophic lateral sclerosis as an adverse drug effect. This study involved multiple reactions and reactants, such as 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7Synthetic Route of C16H21Cl2N3O2).

4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7) belongs to imidazole derivatives. Imidazole is a heterocyclic compound with a five-membered planar ring. It is amphoteric and highly polar. Imidazole based anticancer drug find applications in cancer chemotherapy. It is used as buffer component for purification of the histidine tagged recombinant proteins in immobilized metal-affinity chromatography (IMAC).Synthetic Route of C16H21Cl2N3O2

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Simultaneous quantitative analysis of six proton- pump inhibitors with a single marker and evaluation of stability of investigated drugs in polypropylene syringes for continuous infusion use was written by Chen, Fuchao;He, Xudong;Fang, Baoxia;Wang, Sicen. And the article was included in Drug Design, Development and Therapy in 2020.Application of 117976-90-6 The following contents are mentioned in the article:

Objective: We developed and validated a simple, convenient and reproducible method for simultaneous estimation of six proton-pump inhibitors (PPIs), omeprazole (OPZ), esomeprazole (EOPZ), lansoprazole (LPZ), pantoprazole (PPZ), rabeprazole (RPZ) and ilaprazole (IPZ) in pharmaceutical dosage forms by a single marker. Meanwhile, the stability of the cited PPIs in 0.9% sodium chloride injection stored in polypropylene syringes up to 48 h for continuous infusion use was investigated. Materials and Methods: The chromatog. separation was achieved on an InterSustain C18 column (150 x 4.6 mm, 5 μm). The isocratic mobile phase made up of 0.05 M potassium dihydrogen phosphate buffer (pH 4.0): acetonitrile (65:35, volume/volume) was pumped through the column at a temperature maintained at 30°C and a flow rate of 1.0 mL/min. The relative retention time, UV spectral similarity and relative correction factors between OPZ and the other five PPIs were calculated and investigated using the quant. anal. of multi-components with a single marker (QAMS) method. The stability study examined phys. parameters, pH values and drug concentrations of the PPIs mixtures Results: Under these conditions, all cited PPIs were separated simultaneously at a retention time of 6.0, 7.3, 7.3, 9.9, 12.5 and 13.9 min for RPZ, OPZ, EOPZ, IPZ, PPZ and LPZ, resp., with a total run time less than 20.0 min. Comparative anal. results indicated that there were no significant differences observed between the QAMS method and the external standard method. The percentage of initial concentration of each PPI gradually decreased during the storage time. Conclusion: The proposed method, which is selective, economical and accurate, was applied successfully for determination of the cited PPIs in their resp. pharmaceutical dosage forms. Admixtures of OPZ, EOPZ, PPZ, IPZ in 0.9% sodium chloride injection were stable for 24 h and LPZ, RPZ in 0.9% sodium chloride injection were stable for 8 h in polypropylene syringes. This study involved multiple reactions and reactants, such as Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6Application of 117976-90-6).

Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6) belongs to imidazole derivatives. Imidazole derivatives generally have good solubility in protic solvents. Simple imidazole derivatives, such as 1H-imidazole, 2-methyl-1H-imidazole, and 1,2-dimethylimidazole, have very high solubility in water. Imidazole also acts as a microtubule destabilizing agents and inhibits topoisomerase and Cytochrome P450 Family 26 Subfamily A Member 1 (CYP26A1) enzymes.Application of 117976-90-6

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

High-Throughput Screening Assays for Cancer Immunotherapy Targets: Ectonucleotidases CD39 and CD73 was written by Kumar, Meera;Lowery, Robert;Kumar, Vaishnav. And the article was included in SLAS Discovery in 2020.Category: imidazoles-derivatives The following contents are mentioned in the article:

Production of adenosine in the extracellular tumor microenvironment elicits strong immunosuppression and is associated with tumor progression. Thus, targeting adenosine-generating ectonucleotidases is a potential strategy to stimulate and prolong antitumor immunity. Because the reaction products of ectonucleotidases differ by a single phosphate group, selective detection in an assay format that is compatible with high-throughput screening (HTS) has been elusive. We report the development of biochem. assays capable of measuring the activity of ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1; also known as CD39) and ecto-5′-nucleotidase (CD73). Both assays leverage the Transcreener HTS Assay platform, which facilitates selective immunodetection of nucleotides with homogenous fluorescent readouts, fluorescence polarization or time-resolved fluorescence energy transfer. The Transcreener AMP2 Assay was used to measure CD39 activity, allowing detection of adenosine monophosphate (AMP) production (Z> 0.6) with subnanomolar amounts of CD39, allowing IC50 determination for tool compounds, consistent with previously reported values. To detect the production of adenosine by CD73, the Transcreener ADP2 Assay was coupled with adenosine kinase (AK); conversion of adenosine to AMP and ADP (ADP) by AK allows detection with ADP2 antibody. The Transcreener AMP2 Assay was used to screen a 1280 Library of Pharmacol. Active Compounds (LOPAC) library and a 1600-compound subset of a ChemBridge diversity library for CD39 inhibitors, allowing the identification of nine and eight candidate compounds from each library, resp. The Transcreener ADP2 Assay was used to screen 1600 compounds from the ChemBridge diversity library for CD73 inhibitors and identified 14 potential candidates. HTS-compatible assays for ectonucleotidase activity may allow identification of purinergic signaling pathway inhibitors important for tumor-specific immune responses during tumor pathogenesis. This study involved multiple reactions and reactants, such as Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6Category: imidazoles-derivatives).

Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6) belongs to imidazole derivatives. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. Imidazole based anticancer drug find applications in cancer chemotherapy. It is used as buffer component for purification of the histidine tagged recombinant proteins in immobilized metal-affinity chromatography (IMAC).Category: imidazoles-derivatives

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Durvalumab as monotherapy and in combination therapy in patients with lymphoma or chronic lymphocytic leukemia: The FUSION NHL 001 trial was written by Casulo, Carla;Santoro, Armando;Cartron, Guillaume;Ando, Kiyoshi;Munoz, Javier;Le Gouill, Steven;Izutsu, Koji;Rule, Simon;Lugtenburg, Pieternella;Ruan, Jia;Arcaini, Luca;Casadebaig, Marie-Laure;Fox, Brian;Kilavuz, Nurgul;Rettby, Nils;Dell′Aringa, Justine;Taningco, Lilia;Delarue, Richard;Czuczman, Myron;Witzig, Thomas. And the article was included in Cancer Reports (New York, NY, United States).Electric Literature of C16H21Cl2N3O2 The following contents are mentioned in the article:

Studies suggest that immune checkpoint inhibitors may represent a promising strategy for boosting immune responses and improving the antitumor activity of standard therapies in patients with relapsed/refractory hematol. malignancies. Phase 1/2 FUSION NHL 001 was designed to determine the safety and efficacy of durvalumab, an anti-programmed death ligand 1 (PD-L1) antibody, combined with standard-of-care therapies for lymphoma or chronic lymphocytic leukemia (CLL). The primary endpoints were to determine the recommended phase 2 dose of the drugs used in combination with durvalumab (durvalumab was administered at the previously recommended dose of 1500 mg every 4 wk) and to assess safety and tolerability. Patients were enrolled into one of four arms: durvalumab monotherapy (Arm D) or durvalumab in combination with lenalidomide ± rituximab (Arm A), ibrutinib (Arm B), or rituximab ± bendamustine (Arm C). A total of 106 patients with relapsed/refractory lymphoma were enrolled. All but two patients experienced at least one treatment-emergent adverse event (TEAE); those not experiencing a TEAE were in Arm C (diffuse large B-cell lymphoma [DLBCL]) and Arm D (DLBCL during the durvalumab monotherapy treatment period). No new safety signals were identified, and TEAEs were consistent with the resp. safety profiles for each study treatment. Across the study, patients with follicular lymphoma (FL; n = 23) had an overall response rate (ORR) of 59%; ORR among DLBCL patients (n = 37) was 18%. Exploratory biomarker anal. showed that response to durvalumab monotherapy or combination therapy was associated with higher interferon-γ signature scores in patients with FL (p = .02). Durvalumab as monotherapy or in combination is tolerable but requires close monitoring. The high rate of TEAEs during this study may reflect on the difficulty in combining durvalumab with full doses of other agents. Durvalumab alone or in combination appeared to add limited benefit to therapy. This study involved multiple reactions and reactants, such as 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7Electric Literature of C16H21Cl2N3O2).

4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. The pharmacophore of imidazole exists in bioactive compounds including amino acids, plant growth regulators and therapeutic agents.n increase of the alkyl chain length of the alcohols. Electric Literature of C16H21Cl2N3O2

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Epidemiology, treatment patterns and survival of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) in Taiwan, 2006-2015 was written by Ko, Bor-Sheng;Chen, Li-Ju;Huang, Huai-Hsuan;Chen, Ho-Min;Hsiao, Fei-Yuan. And the article was included in International Journal of Clinical Practice in 2021.Application In Synthesis of 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid The following contents are mentioned in the article:

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is one of the most frequent types of leukemia/lymphoma in adults in Western countries. However, there are few studies regarding its epidemiol. and treatment patterns in Asian countries. To investigate CLL/SLL in Asian populations, we identified CLL/SLL patients diagnosed during 2006 to 2015 from the Taiwan Cancer Registry Database and estimated the incidence. Further, patients diagnosed during 2008 to 2015 were included for the anal. of treatment patterns and survivals. Treatments for CLL/SLL were retrieved from the Taiwan’s National Health Insurance Research Database and survival data from the National Death Registry. In total, 1497 patients who were older than 20 years and had newly diagnosed CLL/SLL during 2006-2015 were identified. The age-standardized incidence rates of CLL/SLL (0.36 per 100 000 persons in 2006, and 0.54 in 2015) increased during the 10-yr period. The sex ratio was ranged from 1.21 to 2.63 with male predominant during 2006 and 2015. For the anal. of treatment patterns (n = 1236), 72.8% patients received chemotherapies. The median duration between the diagnosis and start of treatments was 27 days, and monotherapy of chlorambucil, bendamustine or cyclophosphamide was the most common regimen in initial treatments. The median follow-up duration for the patients receiving therapies was 29.6 mo, and 45.0% patients experienced relapse or refractory. In patients with relapse/refractory CLL/SLL, 34.1% received rituximab-containing chemotherapies. Three hundred and ninety-nine (32.3%) patients received intensive treatments, and 175 (43.9%) of them received rituximab-containing chemotherapies. The 5-yr overall survival (OS) rate was 61%, and age was an important prognostic factor for CLL/SLL patients. This study is the first population-based study in Asia and provides comprehensive evidence of epidemiol., treatment patterns and survivals of CLL/SLL in an Asian population. This study involved multiple reactions and reactants, such as 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7Application In Synthesis of 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid).

4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7) belongs to imidazole derivatives. The solubility of imidazoles in ethers is lower than that in alcohols and decreases with increasing chain length of the ethers . In contrast, the solubility of benzimidazoles in alcohols (C3–C6) is higher than in water and generally decreases with a Imidazole derivatives have antibacterial, antifungal and anticancer functionality. It interacts with DNA and also binds to protein and stops cell division.Application In Synthesis of 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Rabeprazole plus amoxicillin dual therapy is equally effective to bismuth-containing quadruple therapy for Helicobacter pylori eradication in central China: A single-center, prospective, open-label, randomized-controlled trial was written by Shao, Qiao-Qiao;Yu, Xue-Chun;Yu, Miao;Ma, Jing;Zhao, Jun-Bo;Yuan, Lin;Qi, Ya-Bin;Hu, Ruo-Bing;Wei, Pei-Ru;Xiao, Wei;Lan, Ling;Jia, Bai-Ling;Zhang, Lian-Zhong;Ding, Song-Ze. And the article was included in Helicobacter in 2022.Formula: C18H20N3NaO3S The following contents are mentioned in the article:

Background : Antibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High-dose dual therapy has recently shown encouraging results in H. pylori eradication, but it has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first-line therapy for H. pylori eradication, and factors that affect the curing rate. Methods : This is a single-center, prospective, open-label, randomized-controlled trial. Naive patients (n=292) were randomly treated with bismuth-containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by ¹³C-urea breath test. Results : In per-protocol (PP) anal., H. pylori eradication rate was 91.2in BQT group, 89.6in RADT, and 51.0in RFDT group. In intention-to-treat (ITT) anal., infection was eradicated in 86.7of patients in BQT group, 85.8in RADT, and 48.1in RFDT groups, resp. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group. Conclusions : Rabeprazole-amoxicillin dual therapy is equally effective to the bismuth-containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non-smoking condition, which deserves future stratified anal. for refinement and optimization. This study involved multiple reactions and reactants, such as Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6Formula: C18H20N3NaO3S).

Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6) belongs to imidazole derivatives. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. Imidazole also acts as a microtubule destabilizing agents and inhibits topoisomerase and Cytochrome P450 Family 26 Subfamily A Member 1 (CYP26A1) enzymes.Formula: C18H20N3NaO3S

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Protocol of a randomized, double-blind, placebo-controlled study of the effect of probiotics on the gut microbiome of patients with gastro-oesophageal reflux disease treated with rabeprazole was written by Liu, Wenjun;Xie, Yong;Li, Yingmeng;Zheng, Longjin;Xiao, Qiuping;Zhou, Xu;Li, Qiong;Yang, Ni;Zuo, Kexuan;Xu, Tielong;Lu, Nong-Hua;Zhang, Heping. And the article was included in BMC Gastroenterology in 2022.Computed Properties of C18H20N3NaO3S The following contents are mentioned in the article:

For patients with gastro-oesophageal reflux symptoms, the preferred treatment is proton pump inhibitor (PPI) administration for approx. 8 wk. However, long-term use of PPIs can cause gut microbiome (GM) disturbances. This study is designed to evaluate the effect of probiotics combined with a PPI on the GM and gastrointestinal symptoms of patients with gastro-oesophageal reflux disease (GERD). This is a randomized, double-blind, placebo-controlled trial. A total of 120 eligible patients with GERD will be randomized into the exptl. group or the control group. The treatment includes two phases: the initial treatment period lasts 8 wk (weeks 1-8), and the maintenance treatment period lasts 4 wk (weeks 9-12). During the initial treatment period, the exptl. group will take rabeprazole and LiHuo probiotics, and the control group will take rabeprazole and a probiotic placebo; during the maintenance treatment period, the exptl. group will take LiHuo probiotics, and the control group will take a probiotic placebo. The primary measure is the change in the GM. The secondary measures are the Reflux Disease Questionnaire (RDQ) score, Gastrointestinal Symptom Rating Scale (GSRS) score, faecal metabolome (FM), body mass index, Los Angeles grade of oesophagitis, adverse event (AE) rate and treatment compliance. Each outcome indicator will be assessed at day 0 (before administration), day 28 and/or 56 (during administration), and day 84 (end of administration) to reveal intragroup differences. AEs will be monitored to assess the safety of LiHuo probiotics. This will be the first trial to use the intestinal flora metagene method to analyze the effects of probiotics on patients with GERD receiving long-term PPI treatment. The goal is to provide evidence for the use of probiotics to reduce intestinal flora disorders and other symptoms of gastrointestinal discomfort in patients with GERD who have used PPIs for a long period. This study involved multiple reactions and reactants, such as Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6Computed Properties of C18H20N3NaO3S).

Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6) belongs to imidazole derivatives. 1H-imidazole is an imidazole tautomer which has the migrating hydrogen at position 1. It is a conjugate base of an imidazolium cation. It is a conjugate acid of an imidazolide. It is a tautomer of a 4H-imidazole. Imidazole has been usedin the lysis, wash and elution buffer for the purification of histidine tagged Sonic Hedgehog(shh-N) protein, in elution buffer in stepwise gradient for the purification of histidine tagged aldo keto reductases using nickel affinity chromatography, as a component of homogenization buffer for the purification of phagosomal compartments from dendritic cells.Computed Properties of C18H20N3NaO3S

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Graft-versus-Host Disease Prophylaxis with Post-Transplantation Bendamustine in Patients with Refractory Acute Leukemia: A Dose-Ranging Study was written by Moiseev, Ivan;Bondarenko, Sergey;Morozova, Elena;Vlasova, Yulia;Dotsenko, Anna;Epifanovskaya, Olga;Babenko, Elena;Botina, Anna;Baykov, Vadim;Surkova, Elena;Lapin, Sergey;Beynarovich, Anastasiya;Borzenkova, Evgeniya;Golosgchapov, Oleg;Kanunnikov, Mikhail;Kudyasheva, Olga;Ovechkina, Varvara;Pirogova, Olga;Porunova, Valentina;Rudakova, Tatyana;Smikova, Olesya;Smirnova, Anna;Afansyev, Boris. And the article was included in Transplantation and Cellular Therapy in 2021.HPLC of Formula: 16506-27-7 The following contents are mentioned in the article:

The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy is dismal. Salvage allogeneic hematopoietic stem cell transplantation (HSCT) is widely used option for these patients, but only 10% to 15% of patients are cured by the procedure. Preclin. studies indicate that substitution of post-transplantation cyclophosphamide with bendamustine (PTB) in a prophylaxis regimen may be associated with an augmented graft-vs.-leukemia (GVL) reaction. The aim of this study was to establish the optimal dose of PTB and evaluate the antileukemic effect of HSCT with this type of graft-vs.-host disease (GVHD) prophylaxis. In the prospective trial (NCT02799147), PTB was administered in doses of 140, 100, and 70 mg/m2 on days +3 and +4. Myeloablative conditioning with fludarabine and oral busulfan was provided to all patients. The first 12 patients received single-agent PTB, and subsequent patients received combination therapy with tacrolimus and mycophenolate mofetil (MMF). Inclusion criteria were acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) refractory to at least one induction course of chemotherapy or target therapy and ≥5% clonal blasts in the bone marrow. The study cohort comprised 22 patients with AML and 5 with ALL. Seven patients were enrolled in the 140 mg/m2 group (due to a stopping rule), and 10 each were enrolled in the 100 mg/m2 and 70 mg/m2 groups. Primary refractory disease was documented in 41% of the patients, and secondary refractory was documented in 59%. The median blast count in the bone marrow at the start of the conditioning was 18% (range, 6% to 97%). Transplantation was performed with a matched sibling donor in 5 patients, a matched or mismatched unrelated donor in 15, and a haploidentical donor in 7. Engraftment was documented in 93% of the patients, including 89% with complete remission and 63% without measurable residual disease. After PTB prophylaxis, we observed an unusual complication, a cytokine release syndrome (CRS), in 70% of the patients, including grade 3 to 5 CRS in 44%. The most frequent clin. symptoms included high fever in 67% of patients, abnormal liver function tests in 67%, pancreatitis in 63%, skin vasculitis in 56%, enterocolitis in 48%, inflammation of oral mucosa in 37%, disseminated intravascular coagulation in 37%, and central nervous system toxicity in 26%. The development of CRS was associated with use of an HLA-mismatched donor (75% vs. 20%; P = .0043). Classic acute GVHD was documented in 44% of the patients. Grade II-IV acute GVHD was associated with grade 3 to 5 CRS (67% vs. 25%; P = .031). Moderate and severe chronic GVHD in the 100-day survivors were more often observed after single-agent PTB than after the combination immunosuppression (100% vs. 18%; P = .002). A relatively low relapse rate was observed for this patient population. Three-year overall survival was 28% (95% confidence interval [CI], 13% to 46%), and event-free survival was 29% (95% CI, 13% to 46%). Nonrelapse mortality was 46% (95% CI, 25% to 64%), and the cumulative incidence of relapse was 26% (95% CI, 11% to 44%). No relapses were documented after day +100. There were no statistically significant differences among the dose groups (P = .3481); however, survival was higher in the 100 mg/kg group. Survival was higher in patients with AML compared with those with ALL (35% vs. 0%; P = .0157). PTB represents a promising option to augment the GVL effect in refractory AML; however, the high CRS-associated mortality necessitates addnl. studies to reduce the risk of this complication. Thus, routine clin. application of PTB cannot be currently recommended. Combination immunosuppression with tacrolimus and MMF partially ameliorates these complications, at least in the setting of HLA-matched allografts. Biol. mechanisms of CRS and GVL after PTB require further elucidation. This study involved multiple reactions and reactants, such as 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7HPLC of Formula: 16506-27-7).

4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7) belongs to imidazole derivatives. Imidazole is a heterocyclic compound with a five-membered planar ring. It is amphoteric and highly polar. Imidazole also acts as a microtubule destabilizing agents and inhibits topoisomerase and Cytochrome P450 Family 26 Subfamily A Member 1 (CYP26A1) enzymes.HPLC of Formula: 16506-27-7

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Bioequivalence of a Newly Developed Dabigatran Etexilate Tablet Versus the Commercial Capsule and Impact of Rabeprazole-Induced Elevated Gastric pH on Exposure in Healthy Subjects was written by Harada, Akiko;Ikushima, Ippei;Haranaka, Miwa;Yanagihara, Aki;Nakayama, Daisuke. And the article was included in American Journal of Cardiovascular Drugs in 2020.Formula: C18H20N3NaO3S The following contents are mentioned in the article:

Background and Objective: Dabigatran etexilate (DE) is an anticoagulant with proven efficacy and tolerability for stroke prevention in patients with non-valvular atrial fibrillation. For the com. capsule, a complex formulation is used to maintain the acidic microenvironment required for maximal absorption. Consequently, its efficacy and safety are similar with or without concomitant intake of proton-pump inhibitors (PPIs). A simplified DE tablet formulation was developed and tested in two studies. One investigated bioequivalence (BE) of the novel DE tablet vs. the com. DE capsule. The other investigated DE bioavailability (BA) under pretreatment with the PPI rabeprazole and assessed the effect of elevated pH on exposure to dabigatran. Methods: BE of the novel DE tablet vs. the DE capsule was assessed in a randomized two-treatment, four-period, two-sequence crossover study (NCT03070171). The effect of rabeprazole on the BA of the DE tablet was assessed in an open-label, single-arm study (NCT03143166). Both studies were conducted at sites in Japan. Participants were healthy male volunteers, aged ≥ 20-40 years. In the BE study, participants received the DE tablet or capsule (single oral dose, 110 mg); primary endpoints were area under the concentration-time curve from baseline to the last quantifiable data point (AUC_0-tz) and maximum plasma concentration (C_max) of unconjugated dabigatran. In the relative BA study, participants received the DE tablet (single oral dose, 110 mg) with or without rabeprazole pretreatment (once daily for 5 days, 20 mg); primary endpoints were AUC_0-tz and C_max of total dabigatran. Results: In total, 160 participants were randomized in the BE study; 36 participants were enrolled in the BA study. The 90% confidence intervals of geometric mean (gMean) ratios for AUC_0-tz (101.4-116.0%) and C_max (101.8-116.6%) of unconjugated dabigatran were within pre-defined acceptance criteria for BE. In the relative BA study, the gMeans of AUC_0-tz (667 to 192 ng h/mL) and C_max (83.1 to 21.8 ng/mL) were decreased by approx. 70% when the tablet was administered under rabeprazole pretreatment. The reduction in BA was observed at a mean gastric pH of 5.3. Treatment was well tolerated; no deaths, serious adverse events (AEs) or significant AEs were reported in either study. Conclusion: The DE tablet demonstrated BE to the capsule; however, at high gastric pH, BA of the tablet was reduced by approx. 70%, which may lead to reduced efficacy. Data indicate the importance of examining not only BE under standard conditions, but relative BA at elevated gastric pH. Such investigations may avoid the reduced BA at elevated pH that is quite common in the target population (the elderly and/or patients treated with gastric-acid modifying co-medications), and therefore reduce treatment failure with DE. This study involved multiple reactions and reactants, such as Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6Formula: C18H20N3NaO3S).

Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.Formula: C18H20N3NaO3S

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Cationic Ir(III) Complexes Featuring Phenylimidazole-type Cyclometalated Ligands: Fluorine-Free Blue Phosphorescent Emitters for Light-Emitting Devices was written by Song, Yongjun;Yu, Renyou;Chen, Mengzhen;He, Lei. And the article was included in Inorganic Chemistry in 2021.HPLC of Formula: 914306-50-6 The following contents are mentioned in the article:

The development of blue emissive cationic Ir(III) complexes with no F substitutions but with sufficient blue-color purity and high phosphorescence efficiency has remained challenging. Here, F-free cyan to deep-blue emissive cationic Ir(III) complexes with phenylimidazole type cyclometalated ligands (CN̂) are reported, which are [Ir(dphim)₂(dmapzpy)]PF₆ (1), [Ir(ipr-dphim)₂(dmapzpy)]PF₆ (2), [Ir(ipr-dphim)₂(bipz)]PF₆ (3), and [Ir(ipr-dphim)₂(bicb)]PF₆ (4). 1,2-diphenyl-1H-imidazole (dphim) and 1-(2,6-diisopropylphenyl)-2-phenyl-1H-imidazole (ipr-dphim) are the phenylimidazole type CN̂ ligands, and 4-dimethylamino-2-(1H-pyrazol-1-yl)pyridine (dmapzpy), di(1H-pyrazol-1-yl)methane (bipz), and 3,3′-methylenebis(1-Me-1H-imidazol-3-ium-2-ide) (bicb) are the neutral ancillary ligands (AÂ). In both solution and diluted films, 1 shows cyan emission with the emission maximum at ∼472 and 495 nm, and 2–4 provide deep-blue emission with the emission maximum at ∼460 and 480 nm. While the complexes exhibit low to moderate phosphorescent efficiencies (0.05-0.35) in degassed MeCN solution, they exhibit high phosphorescent efficiencies (≤0.82) in diluted films. Theor. calculations revealed that the mixed ³π-π^* (CN̂-centered)/³MLCT (Ir → CN̂) states are responsible for the emission afforded by 1–4, which undergo nonradiative deactivations induced by different types of metal-centered states. Organic light-emitting diodes (OLEDs) with 1–4 as phosphorescent dopants are fabricated by solution-process, which afford blue-green to blue emission with the emission maximum at ∼460 and 490 nm for the blue devices and a high current-efficiency at 28.1 cd A^-1 for the blue-green device. Solid-state light-emitting electrochem. cells (LECs) are fabricated with 1–2 as phosphorescent dopants, which provide green-blue to blue emission with high luminance (up to 840 cd m^-2) and current-efficiency (≤16.8 cd A^-1) under a constant-current driving. By using phenylimidazole type CN̂ ligands and optimized AÂ ligands, blue emissive cationic Ir(III) complexes with no F substitutions but with sufficient blue-color purity and high phosphorescence efficiency can be developed. This study involved multiple reactions and reactants, such as 1-(2,6-Diisopropylphenyl)-2-phenyl-1H-imidazole (cas: 914306-50-6HPLC of Formula: 914306-50-6).

1-(2,6-Diisopropylphenyl)-2-phenyl-1H-imidazole (cas: 914306-50-6) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Imidazole has been usedin the lysis, wash and elution buffer for the purification of histidine tagged Sonic Hedgehog(shh-N) protein, in elution buffer in stepwise gradient for the purification of histidine tagged aldo keto reductases using nickel affinity chromatography, as a component of homogenization buffer for the purification of phagosomal compartments from dendritic cells.HPLC of Formula: 914306-50-6

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem