6293-56-7Relevant academic research and scientific papers
Synthesis and biological evaluation at nicotinic acetylcholine receptors of N-arylalkyl- and N-aryl-7-azabicyclo[2.2.1]heptanes
Cheng, Jie,Zhang, Chunming,Stevens, Edwin D.,Izenwasser, Sari,Wade, Dean,Chen, Shaoyi,Paul, Dennis,Trudell, Mark L.
, p. 3041 - 3047 (2002)
A new series of N-arylalkyl-substituted 7-azabicyclo[2.2.1]heptanes and N-aryl-substituted 7-azabicyclo[2.2.1]heptanes were synthesized and evaluated as potential ligands for neuronal nicotinic acetylcholine receptors. The in vitro binding affinities (Ki) of the 7-azabicyclo[2.2.1]heptane derivatives were measured by inhibition of [3H]cytisine binding to rat brain tissue, The most potent ligand of the series was found to be N-(3-pyridylmethyl)-7-azabicyclo[2.2.1]heptane (5b, Ki = 98 nM). The chloro analogue (5a, Ki = 245 nM) 5a and epibatidine (1) produced dose-dependent analgesia in both hotplate and tail-flick tests when administered subcutaneously. However, when compounds 1 and 5a,b were administered intrathecally, all produced analgesia in the tail-flick test but only 5a produced analgesia in the hotplate test.
Functional Group Interconversion of Alkylidenemalononitriles to Primary Alcohols by a Cooperative Redox Operation
Emmetiere, Fabien,Grenning, Alexander J.
supporting information, p. 3077 - 3085 (2020/08/10)
Functional group interconversions are essential chemical processes enabling synthesis. In this report, we describe a strategy to convert alkylidenemalononitriles into primary alcohols in one step. The reaction relies on a choreographed redox process invol
COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF
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Page/Page column 152; 153, (2019/01/21)
Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.
Synthesis and antitumor activity of novel pyridinium fullerene derivatives
Yasuno, Takumi,Ohe, Tomoyuki,Ikeda, Hitomi,Takahashi, Kyoko,Nakamura, Shigeo,Mashino, Tadahiko
, p. 6325 - 6337 (2019/08/28)
Purpose: We have previously reported that some cationic fullerene derivatives exhibited anticancer activity, and they are expected to be a potential lead compound for an anti-drug resistant cancer agent. However, they are bis-adducts and a mixture of multiple regioisomers, which cannot be readily separated due to the variability of substituent positions on the fullerene cage. To overcome this issue, we evaluated the antiproliferative activities of a set of mono-adduct derivatives and examined their structure-activity relationship. In addition, the in vivo antitumor activity of selected derivatives was also examined. Methods: Nineteen pyridinium fullerene derivatives were newly designed and synthesized in this study. Their antiproliferative activities were evaluated using several cancer cell lines including drug-resistant cells. Furthermore, in vivo antitumor activity of several derivatives was investigated in mouse xenograft model of human lung cancer. Results: The derivatives inhibited the proliferation of cancer cell lines, including cisplatin-resistant cells and doxorubicin-resistant cells. It was also shown that compound 10 (10 μM), 13 (10 μM) and cis-14 (10 μM) induced the intracellular oxidative stress. In addition, compound 13 (20 mg/kg) and cis-14 (15 mg/kg) significantly exhibited antitumor activity in mouse xenograft model of human lung cancer. Conclusion: We synthesized a novel set of mono-adduct fullerene derivatives functionalized with pyridinium groups and found that most of them show potent antiproliferative activities against cancer cell lines and some of them show significant antitumor activities in vivo. We propose that these fullerene derivatives serve as the lead compounds for a novel type of antitumor agents.
COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH APJ RECEPTOR ACTIVITY
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Page/Page column 146-147, (2019/09/18)
This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize) the apelin receptor (also referred to herein as the APJ receptor; gene symbol "APLNR"). This disclosure also features compositions containing the same as well as other methods of using and making the same. The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which a decrease in APJ receptor activity (e.g., repressed or impaired APJ receptor signaling; e.g., repressed or impaired apelin-APJ receptor signaling) or downregulation of endogenous apelin contributes to the pathology and/or symptoms and/or progression of the disease, disorder, or condition. Non-limiting examples of such diseases, disorders, or conditions include: (i) cardiovascular disease; (ii) metabolic disorders; (iii) diseases, disorders, and conditions associated with vascular pathology; and (iv) organ failure; (v) diseases, disorders, and conditions associated with infections (e.g., microbial infections); and (vi) diseases, disorders, or conditions that are sequela or comorbid with any of the foregoing or any disclosed herein. More particular non-limiting examples of such diseases, disorders, or conditions include pulmonary hypertension (e.g., PAH); heart failure; type II diabetes; renal failure; sepsis; and systemic hypertension.
One-Carbon Homologation of Primary Alcohols and the Reductive Homologation of Aldehydes Involving a Jocic-Type Reaction
Li, Zhexi,Gupta, Manoj K.,Snowden, Timothy S.
, p. 7009 - 7019 (2015/11/16)
(Trichloromethyl)carbinols, which are formed in one operation from either alcohols or aldehydes, can be converted into primary alcohols in a Jocic-type reaction involving LiBH4. The net result is a convenient two-step, one-carbon homologation of primary alcohols or a reductive one-carbon homologation of aldehydes featuring a broad substrate scope. The method is step-economical, and it nicely complements established one-carbon homologation strategies. (Trichloromethyl)carbinols, which are formed in one operation from either alcohols or aldehydes, can be converted into primary alcohols in a Jocic-type reaction involving LiBH4. The net result is a convenient two-step, one-carbon homologation of primary alcohols or a reductive one-carbon homologation of aldehydes featuring a broad substrate scope.
α-Alkylidene-γ-butyrolactone synthesis via one-pot C-H insertion/olefination: substrate scope and the total synthesis of (±)-cedarmycins A and B
Lloyd, Matthew G.,D'Acunto, Mariantonietta,Taylor, Richard J.K.,Unsworth, William P.
, p. 7107 - 7123 (2015/02/19)
Abstract A system for the synthesis of α-alkylidene-γ-butyrolactones via a one-pot C-H insertion/olefination sequence is described. The process is based on the rhodium catalysed C-H insertion reaction of α-diazo-α-(diethoxyphosphoryl)acetates. The mild reaction conditions, operational simplicity and ready availability of starting materials are all key features. A wide range of successful reaction systems are reported (41 examples) highlighting the generality of the method. The application of this method in the total synthesis of the natural products (±)-cedarmycins A and B is also described.
PROCESS FOR PREPARING BISPHENOL
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, (2011/12/12)
Provided is a process for producing a bisphenol compound stably at a high conversion and with high selectivity over a long period. A process for producing a bisphenol compound by feeding a phenol compound and a carbonyl compound continuously to a reactor packed with an acid catalyst, characterized in that the acid catalyst is a sulfonic-acid-form cation-exchange resin in which part of the sulfo groups have been modified with at least any one of 2-pyridylalkanethiol compounds and 3-pyridylalkanethiol compounds.
Zinc-catalyzed chemoselective reduction of esters to alcohols
Das, Shoubhik,Moeller, Konstanze,Junge, Kathrin,Beller, Matthias
experimental part, p. 7414 - 7417 (2011/08/05)
Economical alcohols! A general and chemoselective catalytic reduction of esters to alcohols using inexpensive zinc acetate and silanes has been developed. The operational simplicity and the high functional group tolerance, without the need for protecting and deprotecting steps, make this procedure particularly attractive for organic synthesis. Copyright
Catalysis of the β-elimination of HF from isomeric 2-fluoroethylpyridines and 1-methyl-2-fluoroethylpyridinium salts. Proton-activating factors and methyl-activating factors as a mechanistic test to distinguish between concerted E2 and E1cb irreversible mechanisms
Alunni, Sergio,Laureti, Valeria,Ottavi, Laura,Ruzziconi, Renzo
, p. 718 - 725 (2007/10/03)
Second-order rate constants, kOHN, M-1 s-1, for the β-elimination reactions of HF with 2-(2-fluoroethyl)pyridine (2), 3-(2-fluoroethyl)pyridine (3), and 4-(2-fluoroethyl)pyridine (4) in OH-/H2O, at 50°C and μ = 1 M KCl, are kOHN = 0.646 × 10-4 M-1 s-1, kOHN = 2.97 × 10-6 M-1 s-1, and kOHN = 5.28 × 10-4 M-1 s-1, respectively. When compared with the second-order rate constants for the same processes with the nitrogen-methylated substrates 1-methyl-2-(2-fluoroethyl)pyridinium iodide (5), 1-methyl-3-(2-fluoroethyl)pyridinium iodide (6), and 1-methyl-4-(2-fluoroethyl)pyridinium iodide (7), the methyl-activating factor (MethylAF) can be calculated from the ratio kOHNCH3/kOHN, and a value of 8.7 × 105 is obtained with substrates 5/2, a value of 1.6 × 103 with 6/3, and a value of 2.1 × 104 with 7/4. The high values of MethylAF are in agreement with an irreversible E1cb mechanism (ANDE* + DN) for substrates 5 and 7 and with the high stability of the intermediate carbanion related to its enamine-type structure. In acetohydroxamate/acetohydroxamic acid buffers (pH 8.45-9.42) and acetate/acetic acid buffers (pH 4.13-5.13), the β-elimination reactions of HF, with substrates 2 and 4, occur at NH+, the substrates protonated at the nitrogen atom of the pyridine ring, even when the [NH+] is much lower than the [N], the unprotonated substrate, due to the high proton-activating factor (PAF) value observed: 3.6 × 105 for 2 and 6.5 × 104 for 4 with acetohydroxamate base. These high PAF values are indicative of an irreversible E1cb mechanism rather than a concerted E2 (ANDEDN) mechanism. Finally, the rate constant for carbanion formation from NH+ with 2 is kBNH+ = 0.35 M-1 s-1, which is lower than when chlorine is the leaving group (kBNH+ = 1.05 M-1 s-1; Alunni, S.; Busti, A. J. Chem. Soc., Perkin Trans. 2 2001, 778). This is direct experimental evidence that some lengthening of the carbon-leaving group bond can occur in the intermediate carbanion. This is a point of interest for interpreting a heavy-atom isotope effect.
