- Iron-catalyzed directed alkylation of aromatic and olefinic carboxamides with primary and secondary alkyl tosylates, mesylates, and halides
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Alkenes, arenes, and heteroarenes possessing an 8-quinolylamide group as the directing group are alkylated with primary and secondary alkyl tosylates, mesylate, and halides in the presence of Fe(acac) 3/ diphosphine as a catalyst and ArZnBr as a base. The reaction proceeds stereospeci fically for alkene substrates and takes place without loss of regiochemical integrity of the starting secondary tosylate, but with loss of the stereochemistry of the chiral center.
- Ilies, Laurean,Matsubara, Tatsuaki,Ichikawa, Saki,Asako, Sobi,Nakamura, Eiichi
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Read Online
- Preparation method of mirabilone related substance and intermediate thereof
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The invention relates to the technical field of drug synthesis. The invention provides a preparation method of mirabilone related substance and an intermediate thereof. To the invention, the phenylethanol alcohol and the sulfonyl chloride compound are fir
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Paragraph 0078-0080
(2021/10/11)
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- Synthesis of N-alkylated pyrazolo[3,4-d]pyrimidine analogs and evaluation of acetylcholinesterase and carbonic anhydrase inhibition properties
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Fused pyrimidines, especially pyrazolo[3,4-d]pyrimidines, are among the most preferred building blocks for pharmacology studies, as they exhibit a broad spectrum of biological activity. In this study, new derivatives of pyrazolo[3,4-d]pyrimidine were synthesized by alkylation of the N1 nitrogen atom. We synthesized 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine 2 from commercially available aminopyrazolopyrimidine 1 using N-iodosuccinimide as an iodinating agent. The synthesis of compound 2 started with nucleophilic substitution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine with R–X (X: –OMs, –Br, –Cl), affording?N-alkylated pyrazolo[3,4-d]pyrimidine. We performed this synthesis using a weak inorganic base?and the mild temperature was also used for a two-step procedure to generate N-alkylated pyrazolo[3,4-d]pyrimidine derivatives. Also, all compounds were tested for their ability to inhibit acetylcholinesterase (AChE) and the human carbonic anhydrase (hCA) isoforms I and II, with Ki values in the range of 15.41 ± 1.39–63.03 ± 10.68 nM for AChE, 17.68 ± 1.92–66.27 ± 5.43 nM for hCA I, and 8.41 ± 2.03–28.60 ± 7.32 nM for hCA II. Notably, compound 10 was the most selective and potent CA I inhibitor with a significant selectivity ratio of 26.90.
- Aydin, Busra O.,Anil, Derya,Demir, Yeliz
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- Convenient Continuous Flow Synthesis of N-Methyl Secondary Amines from Alkyl Mesylates and Epoxides
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The first continuous flow process was developed to synthesize N-methyl secondary amines from alkyl mesylates and epoxides via a nucleophilic substitution using aqueous methylamine. A variety of N-methyl secondary amines were produced in good to excellent yields, including a number of bioactive compounds or their precursors. Up to 10.6 g (88% yield) of an N-methyl secondary amine was produced in 140 min process time. The amination procedure included an in-line workup, and the starting mesylate material was also produced in continuous flow from the corresponding alcohol. Finally, an in-line process combining the mesylate synthesis and nucleophilic substitution was developed.
- Lebel, Hélène,Mathieu, Gary,Patel, Heena
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supporting information
p. 2157 - 2168
(2020/11/23)
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- Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry
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The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089 ± 0.007 μM, which was two orders of magnitude lower than that of bestatin (IC50 = 9.4 ± 0.5 μM). Compound 13v also showed dose-dependent anti-angiogenesis activities. Even at the lower concentration (10 μM), compound 13v presented similar anti-angiogenesis activity compared with bestatin at 100 μM in both the human umbilical vein endothelial cells (HUVECs) capillary tube formation assay and the rat thoracic aorta rings test. Moreover, compared with bestatin, 13v exhibited comparable, if not better in vivo anti-metastasis activity in a mouse H22 pulmonary metastasis model.
- Cao, Jiangying,Ma, Chunhua,Zang, Jie,Gao, Shuai,Gao, Qianwen,Kong, Xiujie,Yan, Yugang,Liang, Xuewu,Ding, Qin'ge,Zhao, Chunlong,Wang, Binghe,Xu, Wenfang,Zhang, Yingjie
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p. 3145 - 3157
(2018/06/01)
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- Visible-light-driven Efficient Photocatalytic Reduction of Organic Azides to Amines over CdS Sheet–rGO Nanocomposite
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CdS sheet–rGO nanocomposite as a heterogeneous photocatalyst enables visible-light-induced photocatalytic reduction of aromatic, heteroaromatic, aliphatic and sulfonyl azides to the corresponding amines using hydrazine hydrate as a reductant. The reaction shows excellent conversion and chemoselectivity towards the formation of the amine without self-photoactivated azo compounds. In the adopted strategy, CdS not only accelerates the formation of nitrene through photoactivation of azide but also enhances the decomposition of azide to a certain extent, which entirely suppressed formation of the azo compound. The developed CdS sheet-rGO nanocomposite catalyst is very active, providing excellent results under irradiation with a 40 W simple household CFL lamp.
- Singha, Krishnadipti,Mondal, Aniruddha,Ghosh, Subhash Chandra,Panda, Asit Baran
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supporting information
p. 255 - 260
(2018/01/15)
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- Coupling of arylboronic acids with benzyl halides or mesylates without adding transition metal catalysts
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We report herein a transition-metal-free coupling reaction of arylboronic acids with benzyl halides and mesylates for the construction of C(sp2)[sbnd]C(sp3) bonds. A unique feature of this coupling reaction is the formation regioisomers in some cases. Mechanistic studies suggest that this reaction may proceed via an unprecedented Friedel–Crafts-type reaction pathway under base conditions with the assistance of boronic acid moiety.
- Wu, Guojiao,Xu, Shuai,Deng, Yifan,Wu, Chaoqiang,Zhao, Xia,Ji, Wenzhi,Zhang, Yan,Wang, Jianbo
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p. 8022 - 8030
(2016/11/19)
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- 6,11-dihydro-5H-benzo[d]imidazo[1,2-a]azepines derivatives as histamine H4 receptor ligands
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The present patent application concerns new ligands of the H4-receptor, their process of preparation and their therapeutic use.
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Page/Page column 54
(2016/03/06)
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- Discovery of LASSBio-772, a 1,3-benzodioxole N-phenylpiperazine derivative with potent alpha 1A/D-Adrenergic receptor blocking properties
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We described herein the discovery of 1-(2-(benzo[d] [1,3]dioxol-6-yl)ethyl) -4-(2-methoxyphenyl) piperazine (LASSBio-772), as a novel potent and selective alpha 1A/1D adrenoceptor (AR) antagonist selected after screening of functionalized N-phenylpiperazine derivatives in phenylephrine-induced vasoconstriction of rabbit aorta rings. The affinity of LASSBio-772 for alpha 1A and alpha 1B AR subtypes was determined through displacement of [ 3H]prazosin binding. We obtained Ki values of 0.14 nM for the alpha 1A-AR, similar to that displayed by tamsulosin (Ki = 0.13 nM) and 5.55 nM for the alpha 1B-AR, representing a 40-fold higher affinity for alpha 1A-AR. LASSBio-772 also presented high affinity (KB = 0.025 nM) for the alpha 1D-AR subtype in the functional rat aorta assay, showing to be equipotent to tamsulosin (KB = 0.017 nM).
- Romeiro, Luiz A.S.,Da Silva Ferreira, Marcos,Da Silva, Leandro L.,Castro, Helena C.,Miranda, Ana L.P.,Silva, Cláudia L.M.,No?l, Franois,Nascimento, Jéssica B.,Araújo, Claudia V.,Tibiri?á, Eduardo,Barreiro, Eliezer J.,Fraga, Carlos A.M.
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supporting information; experimental part
p. 3000 - 3012
(2011/07/08)
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- Novel and efficient synthesis of tert-butyl-2-(4-(2-aminoethyl)phenylthio)- 2-methylpropanoate, a key intermediate in the synthesis of ureido thioisobutyric acid
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A convenient and cost-effective synthesis of pharmacologically important tert-butyl-2-(4-2-aminoethyl)phenylthio)-2-methylpropanoate from commercially available 2-2-phenyl-1-ethanol is described.
- Desai, Jigar,Argade, Anil,Gite, Sanjay,Shah, Kiran,Pavase, Laxmikant,Thombare, Pravin,Patel, Pankaj
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experimental part
p. 748 - 753
(2011/03/21)
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- Benzophenone Dicarboxylic Acid Antagonists of Leukotriene B4. 2. Structure-Activity Relationships of the Lipophilic Side Chain
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A series of lipophilic benzophenone dicarboxylic acid derivatives were found to inhibit the binding of the potent chemotoxin leukotriene B4 (LTB4) to its receptor on intact human neutrophils.Activity at the LTB4 receptor was determined by using a 3H>LTB4-binding assay.The structure-activity relationship for the lipophilic side chain was systematically investigated.Compounds with n-alkyl side chains of varying lengths were prepared and tested.Best inhibition of 3H>LTB4 binding was observed with the n-decyl derivative.Analogues with alkyl chains terminated with an aromatic ring showed improved activity.The 6-phenylhexyl side chain was optimal.Substitution on the terminal aromatic ring was also evaluated.Methoxyl, methylsulfinyl, and methyl substituents greatly enhanced the activity of the compound.For a given substituent, the para isomer had the best activity.Thus the nature of the lipophilic side chain can greatly influence the ability of the compounds to inhibit the binding of LTB4 to its receptor on intact human neutrophils.The most active compound from this series, 84 (LY223982), bound to the LTB4 receptor with the affinity approaching that of the agonist.
- Gapinski, D. Mark,Mallett, Barbara E.,Froelich, Larry L.,Jackson, William T.
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p. 2807 - 2813
(2007/10/02)
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- Synthesis and Pharmacological Studies of 4,4-Disubstituted Piperidines: A New Class of Compounds with Potent Analgesic Properties
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A series of 4,4-disubstituted piperidines has been synthesized and evaluated for analgesic activity.Several of these analogues show analgesic potency comparable to morphine in the mouse writhing and tail-flick tests.A number of compounds exhibit high affi
- Huegi, Bruno S.,Ebnoether, Anton M.,Rissi, Erwin,Gadient, Fulvio,Hauser, Daniel,et al.
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