- Salts of 2- or 3-haloalkylamines in the synthesis of N-aminoalkyl derivatives of heterocyclic and aromatic amines
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Reactions of 2-haloethyl- or 3-halopropylamine salts with NH-substrates (indoline, 1,2,3,4-tetrahydroquinoline, aniline, and N-ethylaniline) in the presence of NaHCO3 in water furnished various N-aminoalkyl derivatives of heterocyclic and aromatic amines.
- Vasilyeva,Vorobyeva,Osipov
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- Design, synthesis and evaluation of γ-turn mimetics as LSD1-selective inhibitors
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Lysine-specific demethylase 1 (LSD1) is an attractive molecular target for cancer therapy. We have previously reported potent LSD1-selective inhibitors (i.e., NCD18, NCD38, and their analogs) consisting of trans-2-phenylcyclopropylamine (PCPA) or trans-2-arylcyclopropylamine (ACPA) and a lysine moiety that could form a γ-turn structure in the active site of LSD1. Herein we report the design, synthesis and evaluation of γ-turn mimetic compounds for further improvement of LSD1 inhibitory activity and anticancer activity. Among a series of γ-turn mimetic compounds synthesized by a Mitsunobu-reaction-based amination strategy, we identified 1n as a potent and selective LSD1 inhibitor. Compound 1n induced cell cycle arrest and apoptosis through histone methylation in human lung cancer cells. The γ-turn mimetics approach should offer new insights into drug design for LSD1-selective inhibitors.
- Ota, Yosuke,Miyamura, Shin,Araki, Misaho,Itoh, Yukihiro,Yasuda, Shusuke,Masuda, Mitsuharu,Taniguchi, Tomoyuki,Sowa, Yoshihiro,Sakai, Toshiyuki,Itami, Kenichiro,Yamaguchi, Junichiro,Suzuki, Takayoshi
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Read Online
- Design and synthesis of new potent 5-HT7 receptor ligands as a candidate for the treatment of central nervous system diseases
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Owing to their multifunctional pharmacological profiles (including dual 5-HT1A/5-HT7 action), arylpiperazine derivatives are widely used for treating central nervous system diseases including the depression or neuropathic pain. Herein we describe the design, synthesis and evaluation of biological activity of novel 5-HT7 ligands derived of 2,4,6-triamino-1,3,5-triazine. The studied compounds showed affinity and high selectively towards 5-HT7 receptor with the two most active compounds 34 (Ki = 61 nM), 22 (Ki = 109 nM) showing good metabolic stability and moderate affinity to CYP3A4 isoenzyme. Compound 22 had high hepatotoxicity at a concentration below 50 μM, while compound 34 showed low hepatotoxicity even at a concentration above 50 μM.
- Drabczyk, Anna K.,Ja?kowska, Jolanta,Ku?aga, Damian,Latacz, Gniewomir,Pla?uk, Damian,Rózga, Karolina,Sata?a, Grzegorz
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supporting information
(2021/10/29)
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- A Nanocrystal Catalyst Incorporating a Surface Bound Transition Metal to Induce Photocatalytic Sequential Electron Transfer Events
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Heterogeneous photocatalysis is less common but can provide unique avenues for inducing novel chemical transformations and can also be utilized for energy transductions, i.e., the energy in the photons can be captured in chemical bonds. Here, we developed a novel heterogeneous photocatalytic system that employs a lead-halide perovskite nanocrystal (NC) to capture photons and direct photogenerated holes to a surface bound transition metal Cu-site, resulting in a N-N heterocyclization reaction. The reaction starts from surface coordinated diamine substrates and requires two subsequent photo-oxidation events per reaction cycle. We establish a photocatalytic pathway that incorporates sequential inner sphere electron transfer events, photons absorbed by the NC generate holes that are sequentially funneled to the Cu-surface site to perform the reaction. The photocatalyst is readily prepared via a controlled cation-exchange reaction and provides new opportunities in photodriven heterogeneous catalysis.
- Beard, Matthew C.,Chen, Xihan,Han, Chuang,Lin, Yixiong,Martin, Jovan San,Miller, Collin,Wang, Xiaoming,Yamamoto, Nobuyuki,Yan, Yanfa,Yan, Yong,Yazdi, Sadegh,Zeng, Xianghua
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supporting information
p. 11361 - 11369
(2021/08/16)
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- Phosphorescent Cyclometalated Platinum(II) Imidazolinylidene Complexes
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We present the synthesis and characterization of six novel bidentate (Formula presented.) cyclometalated platinum(ii) complexes derived from saturated N-heterocyclic carbene precursors, namely 1-aryl-3-methyl-1H-4,5-dihydroimidazolium salts. The title compounds were then synthesized by a multi-step reaction, which includes an in situ generation of the silver carbene complex, followed by transmetalation to platinum and subsequent introduction of the β-diketonate ligand. Structural characterization by NMR experiments and solid-state structures prove the cyclometalation and the saturated backbone of the NHC motif. Photophysical and electrochemical properties of the platinum(ii) complexes were examined and studied in detail by DFT calculations. The title compounds are strongly emissive at room temperature in the sky-blue region of the visible spectrum and show quantum yields of up to 71 % in a PMMA matrix.
- Stipurin, Sergej,Strassner, Thomas
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p. 804 - 813
(2021/02/05)
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- Method for preparing secondary aromatic amine or tertiary aromatic amine by conducting amination on aryl halide or alkyl halide
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The invention discloses a method for preparing secondary aromatic amine or tertiary aromatic amine by conducting amination on aryl halide or alkyl halide. That is to say, the alkyl halide or the arylhalide and organic amine are mixed according to a certain ratio, and under light irradiation, C-N coupling reaction is carried out, so that a corresponding target product is generated for preparing the secondary amine or the tertiary amine. Compared with existing synthesis technologies, the method has the advantages that the aryl halide or the alkyl halide which is cheap and easy to get is selected as a reaction substrate, the method has good universality for different organic amine separately, moreover, the product selectivity is high, and separation and purification are easy; moreover, the synthesis method does not need to be conducted under severe conditions of high temperature and the like, a green and sustainable light source is adopted as driving force, the atom economy is high, andthe method has wide application prospects.
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Paragraph 0029-0035; 0160; 0132; 0133; 0162
(2019/01/14)
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- Naphthalene dianhydride based selective detection targetable fluorescent probe for monitoring exogenous Iron in living cells
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A green emissive PET operating fluorescent turn-on cell permeable novel probe R1 has been successfully developed and utilized for the detection of Fe+3 in the pure aqueous system at sub-nanomolar level. Moreover, probe R1 demonstrate highly sensitive and selective towards Fe+3 over the other divalent and trivalent metal ions and was established by using fluorescence spectroscopy. The efficiency and aid of R1 was demonstrated by the fluorescence imaging of captured Fe+3 within Pollen grains by using fluorescence microscopy. These results indicate that, this is the first fluorescent turn-on PET probe to detect sub-nanomolar Fe+3 in the pure aqueous system and in cellular level.
- Rohini, Gandhaveeti,Ramaiah, Konakanchi,Sreekanth, Anandaram
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supporting information
p. 3858 - 3862
(2018/09/25)
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- Design, synthesis and antimycobacterial activity of novel imidazo[1,2-a]pyridine-3-carboxamide derivatives
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We report herein the design and synthesis of “novel imidazo [1,2-a]pyridine-3-carboxamides (IPAs)” bearing a variety of different linkers, based on the structure of IMB-1402 discovered in our lab. Results reveal that 2,6-dimethyl-N-[2-(phenylamino)ethyl] IPAs with an electron-donating group on the benzene ring as a potent scaffold. Compounds 26g and 26h have considerable activity (MIC: 0.041–2.64 μM) against drug-sensitive/resistant MTB strains, and they have acceptable safety indices against MTB H37Rv with the SI values of 4395 and 1405, respectively. Moreover, N-[2-(piperazin-1-yl)ethyl] moiety was also identified as a potentially alternative linker (compound 31), opening a new direction for further SAR studies.
- Lv, Kai,Li, Linhu,Wang, Bo,Liu, Mingliang,Wang, Bin,Shen, Weiyi,Guo, Huiyuan,Lu, Yu
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p. 117 - 125
(2017/06/05)
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- COMPOUND HAVING γ TURN STRUCTURE AND LSD1 INHIBITOR USING THE SAME
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PROBLEM TO BE SOLVED: To provide a compound having LSD1 inhibitory activity and cancer cell growth inhibitory effect. SOLUTION: There is provided a compound represented by the formula (1) and a salt thereof. (1), where R1 is an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group or a heteroaryl group, R2 is H, an alkyl group, a cycloalkyl group, an aryl group or a heteroaryl group, R3 is H, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group or a heteroaryl group, R4 is an aryl group or a heteroaryl group, each of the above described groups may be substituted, n is an integer of 2 to 10 and *1 and *2 are asymmetric carbons. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPO&INPIT
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Paragraph 0185-0190
(2017/12/27)
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- A PI3K/Akt Raf/MEK/ERK and as the target of the double-channel inhibitors
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The invention discloses a dual-channel inhibitor using Raf/MEK/ERK and PI3K/Akt as targets. The chemical name of the composition is 1-(2-amido) ethyl-3-(3-(4-methoxyl) phenyl) allyl indole-2-ketone hydrochloride, and the structural formula (I) of the composition is as shown in the specification. The invention also discloses a preparation method of the composition and an application of the composition for preparing an anti-tumor drug. The dual-channel inhibitor disclosed by the invention has the advantages of improving titer and reducing the occurrence probability of drug resistance as well as reducing toxicity and improving the compliance of patients. Thus, the design and development of the dual-channel inhibitor provide a new chemical tool for cancer research groups, and the dual-channel inhibitor is possible to be developed as a new anti-cancer agent.
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Paragraph 0031; 0054; 0055
(2016/11/09)
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- Cu2O/nano-CuFe2O4: An efficient and magnetically recoverable catalyst for the ligand-free N-arylation of amines and nitrogen heterocycles with aryl halides
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An efficient strategy has been developed for the N-arylation of azoles and aliphatic amines with aryl halide using a Cu2O/nano-CuFe2O4 magnetic composite as the catalyst and KOH as the base. The methodology is found to be applicable to a variety of nitrogen-containing heterocycles, such as imidazole, indole, and pyrrole, as well as aliphatic amines in high yields with practical simplicity under cost-effective "ligand-free" conditions. The magnetic property of the catalyst allowed its fast separation from the reaction medium by an external magnet. Additionally, the inexpensive catalyst could be recycled for five consecutive runs with small drops in catalytic activity.
- Elhampour, Ali,Nemati, Firouzeh,Kaveh, Mahdieh
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supporting information
p. 223 - 225
(2016/03/01)
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- Isoflavone amide type derivative, preparation method and medical application thereof
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The invention relates to the field of medicinal chemistry, and relates to an isoflavone amide type derivative, a preparation method and a medical application thereof, in particular to an isoflavone amide type derivative with the general formula (I), a preparation method thereof, medicine compositions including the isoflavone amide type derivative and a medical application thereof, especially an application of the isoflavone amide type derivative as a medicine for preventing or curing hyperlipemia, obesity or type II diabetes. The general formula (I) is shown in the description.
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Paragraph 0016; 0074; 0075; 0076
(2016/10/10)
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- An efficient and recyclable chitosan supported copper(II) heterogeneous catalyst for C-N cross coupling between aryl halides and aliphatic diamines
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A useful and convenient methodology has been developed for synthesis of mono N-arylated aliphatic 1,2- and 1,3-diamines and amino alcohols. A highly efficient and renewable heterogeneous chitosan supported copper(II) catalyst has been employed for the C-N cross coupling between aryl halides and aliphatic diamines/amino alcohols. The main advantages of this reaction are the high yields of the products, reduced reaction time, convenient work up procedure, renewability of the catalyst, and less metal contamination of the products. All these factors make the present C-N cross coupling reaction economical, green, and sustainable.
- Bodhak, Chandan,Kundu, Ashis,Pramanik, Animesh
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p. 419 - 424
(2015/04/27)
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- Highly Efficient Mechanochemical N-Arylation of Amino Alcohols and Diamines with Cu0 Powder
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Cu0-catalysed arylations have rightly acquired great importance over the last decade. This paper reports the N-arylation of amino alcohols and diamines with iodobenzene derivatives in a planetary ball mill and an investigation into the procedure. This newly developed solvent-free protocol is fast, efficient and occurs under the mechanochemical activation of metallic copper powder. It does not require additional ligands and gives excellent yields. This paper aims to broaden the scope of mechanochemical Cu0-activation and so a new one-pot, two-step synthesis that combines CuAAC and N-arylation has been successfully performed and reported herein.
- Martina, Katia,Rinaldi, Laura,Baricco, Francesca,Boffa, Luisa,Cravotto, Giancarlo
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p. 2789 - 2794
(2015/12/18)
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- Copper-catalyzed C-N cross-coupling reactions for the preparation of aryl diamines applying mild conditions
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In this work, aryl diamines were prepared by C-N cross-coupling reactions between aryl halides and ethylenediamine. These reactions were successfully catalyzed by low quantities of Cu2O or CuO (1 mol %) employing low reflux temperature and low diamine excess. Products were afforded in good yields (up to 95%).
- Costa, Márcio V.,Viana, Gil M.,De Souza, Thaís M.,Malta, Luiz Fernando B.,Aguiar, Lúcia C.S.
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p. 2332 - 2335
(2013/06/27)
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- Solvent-free copper-catalyzed N-arylation of amino alcohols and diamines with aryl halides
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A simple and mild method for the coupling of aryl halides with amino alcohols and diamines is described. The reactions can be performed under ligand-free and solvent-free conditions, and generate the products in good yield.
- Yin, Huiqing,Jin, Ming,Chen, Wei,Chen, Chen,Zheng, Likang,Wei, Ping,Han, Shiqing
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supporting information; experimental part
p. 1265 - 1270
(2012/03/27)
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- Control of peroxyoxalate chemiluminescence by nitrogen-containing ligand quenching: Turning off and on by ligand-metal ion host-guest interactions
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The control of peroxyoxalate chemiluminescence (PO-CL) by the coordination of nitrogen-containing ligands and metal cations was investigated. Turning the CL off and on was done by PO-CL using 15-monoazacrown-5-tethered anthracene and alkali metal ions. CL quenching and regeneration was also observed in the separated molecular system of 15-monoazacrown-5 and the fluorophores. CL quenching by a number of ligands bearing dipicolylamino groups was evaluated by these PO-CL reactions and found to be closely related to their oxidation potentials, which is dependent on the Weller rate law for electron exchange and this provides strong support for the existence of the CIEEL PO-CL process. When Zn2+ or Cu2+ are added to the PO-CL system quenched by the ligand, N-[2-(2,2′-dipicolylamino)ethyl]aniline, CL was turned on because the electron donating ability of the ligands was modulated. This was controlled by the coordination of the studied metal ions and, therefore, this system results in CL because of host-guest interactions.
- Maruyama, Takayuki,Fujie, Yasuyuki,Oya, Noriyuki,Hosaka, Eisuke,Kanazawa, Aki,Tanaka, Daisuke,Hattori, Yoshiyuki,Motoyoshiya, Jiro
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experimental part
p. 6927 - 6933
(2011/10/02)
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- Synthesis and characterization of N-substitutional ethylenediamine derivatives
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N-Substituted and N,N-disubstituted ethylenediamine derivatives were prepared rapidly in aqueous conditions from 30 to 76 % yields, respectively, on a multi-gram scale starting from inexpensive and commercially available starting materials. The steps involved Michael addition, hydrazinolysis and Curtius rearrangements. The highlight of this method lies on its convenience and economy in accessing these intermediates.
- Yao, Ri-Sheng,Jiang, Lai-En,Wu, Sheng-Hua,Deng, Sheng-Song,Yang, Yang
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experimental part
p. 3792 - 3794
(2012/01/05)
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- Inhibitors of the glycine transporter type-2 (GlyT-2): synthesis and biological activity of benzoylpiperidine derivatives.
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A series of benzoylpiperidine analogs related to 4a was prepared, and their ability to inhibit the uptake of [(14)C]-glycine in COS7 cells transfected with human glycine transporter type-2 (GlyT-2) was evaluated. Small structural changes to the benzoylpiperidine region of the molecule led to a significant decrease in GlyT-2 inhibitory activity. In contrast, the distal aryl ring was more tolerant to functional group modifications and could accommodate a variety of substitutes at the C-2 or C-3 positions. Comparable activities to 4a were obtained by replacing the anilino nitrogen with an ether linkage 27 or by exchanging the isopropoxy ether moiety with an isopropyl amino group 15. A distinct preference for a 2-carbon tether (n=1) was observed relative to the corresponding 3-carbon homolog (n=2).
- Wolin, Ronald L,Santillan Jr., Alejandro,Tang, Liu,Huang, Charles,Jiang, Xiaoxia,Lovenberg, Timothy W
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p. 4511 - 4532
(2007/10/03)
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- Synthesis and study of 1-aryl-1H-4,5-dihydroimidazoles
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An easy synthesis of 1-aryl-1H-4,5-dihydroimidazoles 1 by cyclocondensation of N-aryl-N′-formylethylenediamines 2 is described. Such precursors were synthesized by selective formylation of N-arylethylenediamines 3 with p-nitrophenyl formate. Cyclizations were performed using trimethylsilyl polyphosphate. Chemical properties of compounds 1, typical of amidine system, were studied. Reaction of 1 with methyl iodide leads to the corresponding 1-aryl-3-methyl-1H-4,5-dihydroimidazolium salts 5. Reduction of dihydroimidazoles 1 with sodium cyanoborohydride provides a convenient access to N-aryl-N′-methylethylenediamines 4.
- Perillo, Isabel,Caterina, M. Cristina,Lopez, Julieta,Salerno, Alejandra
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p. 851 - 856
(2007/10/03)
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- Lithiation of 1-arylimidazol-2(1H)-ones and 1-aryl-4,5-dihydroimidazol- 2(1H)-ones
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1-Arylimidazol-2(1H)-ones are shown to be readily lithiated, using 2 mol equiv. of n-butyllithium, on the benzene ring, ortho to the heterocycle. 1-Aryl-4,5-dihydroimidazol-2(1H)-ones also undergo metalation on the aromatic substitutuent ortho to the heterocycle, but less efficiently. 1-Aryl-3-methylimidazol-2(1H)-ones are lithiated on the heterocyclic ring and then on the benzene ring ortho to the heterocycle. No ortho-directing effect was found for 1-aryl-4,5-dihydro-3-methylimidazol-2(1H)-ones.
- Llopart, Carme Cantos,Ferrer, Conchita,Joule, John A.
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p. 1649 - 1661
(2007/10/03)
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- Cleavage of the etheric bond in cyclopentadienyliron phenolphthalein complexes
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The reaction of aliphatic primary amines with phenolphthalein-containing dicyclopentadienyliron complexes led to etheric bond cleavage. This unique cleavage reaction is due to nucleophilic attack by the amines ipso to the etheric group of the complexed arene, which is activated by coordination to the cationic cyclopentadienyliron moiety.
- Abd-El-Aziz,Bernardin,Tran
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p. 1835 - 1838
(2007/10/03)
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- Method and apparatus for sunless tanning
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Apparatus for simulating skin tanning comprises a receptacle containing a fluid comprising dihydroxyacetone, a receptacle containing a fluid comprising a secondary polyamine, and dispensing means for simultaneously or sequentially providing desired amounts of dihydroxyacetone and polyamine.
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- Phenylimidazolidin-2-one derivatives as selective 5-HT3 receptor antagonists and refinement of the pharmacophore model for 5-HT3 receptor binding
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A possible bioisosterism between the benzamido and the phenylimidazolidin-2-one moieties has been suggested on the basis of the similarity between the molecular electrostatic potential (MEP) of metoclopramide, a D2 receptor antagonist with weak 5-HT3 receptor antagonist properties, and zetidoline, a D2 receptor antagonist. Starting from this premise, a series of phenylimidazolidin-2-one derivatives bearing a basic azabicycloalkyl or an imidazolylalkyl moiety were synthesized and evaluated for 5-HT3 receptor radioligand binding affinity ([3H]-GR 43694). In vitro 5-HT3 receptor antagonist activity was tested in the guinea pig ileum assay (GPI). A number of high-affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the Bezold-Jarisch reflex in the anesthetized rat. In general, the imidazolylalkyl derivatives were found to be more active than azabicycloalkyls. 1-(3,5-Dichlorophenyl)-3-[(5-methyl-1H-imidazol-4- yl)methyl]imidazolidin-2-one (58), in particular, displayed very high affinity for the 5-HT3 receptor (K(i) of 0.038 nM) with a K(b) of 5.62 nM in the GPI assay, being more potent than the reference compounds (ondansetron, tropisetron, granisetron, and BRL 46470) tested. 58 showed an ID50 comparable to that of ondansetron (2.2 μg/kg iv) in the Bezold-Jarisch reflex. A molecular modeling study based on this structurally novel series of compounds allowed the refinement of previously reported 5-HT3 receptor antagonist pharmacophore models.
- Heidempergher, Franco,Pillan, Antonio,Pinciroli, Vittorio,Vaghi, Fabrizio,Arrigoni, Claudio,Bolis, Giorgio,Caccia, Carla,Dho, Luciano,McArthur, Robert,Varasi, Mario
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p. 3369 - 3380
(2007/10/03)
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- The Use of 2-Oxazolidinones as Latent Aziridine Equivalents. 2. Aminoethylation of Aromatic Amines, Phenols, and Thiophenols
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The utility of 2-oxazolidinones 1 as latent, carboxylated aziridine functionalities was examined.Reaction of 2-oxazolidinone (1a), 3-methyl2-oxazolidinone (1b), 3-(phenylmethyl)-2-oxazolidinone (1c), 3-phenyl-2-oxazolidinone (1d) 4,4-dimethyl-2-oxazolidinone (1e), and 5-ethyl-2-oxazolidinone (1f) with aromatic amine salts, phenol, or thiophenols at elevated temperatures (> 130 deg C) afforded aminoethylated adducts.The aminoethylation occurred with concomitant loss of carbon dioxide to furnish variously substituted N-aryl-1,2-ethanediamines 4, 1-(2-phenoxyethyl)-2-imidazolidinone (8), or 2-(arylthio)ethanamines 9 on reactions of 1 with aromatic amine salts, phenol, and thiophenols, respectively.Imidazolidinone 8 is believed to be a secondary reaction product resulting from the condensation of the initially formed 2-phenoxyethanamine with starting oxazolidinone 1a.The aminoethylation reaction did not proceed with aliphatic amine hydrochlorides or alkyl mercaptans.Preliminary mechanistic pathways for these ring openings were also investigated employing a specific, C-5 deuterium-labeled oxazolidinone 1b-d2.Ring-opening experiments of 1b-d2 with N-methylaniline hydrochloride suggest reaction can occur through either a dioxazolinium 5 and/or 5 intermediate.In contrast, reaction of 1b-d2 with thiophenol suggests ring-opening to proceed only via the dioxazolinium pathway.
- Poindexter, Graham S.,Owens, Donald A.,Dolan, Peter L.,Woo, Edmund
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p. 6257 - 6265
(2007/10/02)
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- Aminoethylation process
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2-Oxazolidinone or N-substituted derivatives thereof are reacted with aromatic amine hydrochlorides at elevated temperatures to produce 1,2-ethanediamines.
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