- Access to α,α-dihaloacetophenones through anodic C[dbnd]C bond cleavage in enaminones
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We have developed a method to synthesize α,α-dihaloketones under electrochemical conditions. In this reaction, the Cl- or Br- is oxidized to Cl2 or Br2 at the anode, which undergoes two-step addition reactions with the N,N-dimethyl enaminone, and finally breaks C[dbnd]C of the N,N-dimethyl enaminone to generate α,α-dihaloketones. The electrosynthesis reaction can be conveniently carried out in an undivided electrolytic cell at room temperature. In addition, various functional groups are compatible with this green protocol which can be applied simultaneously to the gram scale without significantly lower yield.
- Zhang, Zhenlei,Yang, Jiusi,Wu, Kairui,Yu, Renjie,Bu, Jiping,Huang, Zijun,Li, Shaoke,Ma, Xiantao
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supporting information
(2021/12/20)
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- Metal-free synthesis of gem-difluorinated heterocycles from enaminones and difluorocarbene precursors
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A cascade strategy to synthesise gem-difluorinated 2H-furans from reactions of BrCF2CO2Et with enaminones has been described. The reactions tolerate a wide variety of functional groups under metal-free conditions. An active aminocyclopropane is proposed to be a key intermediate through the cyclopropanation of difluorocarbene with enaminones, which further triggers a regioselective C-C bond cleavage in situ to afford the corresponding gem-difluorinated 2H-furans.
- Chen, Jie,Fu, Rui,Jiang, Yaojia,Rong, Jiaxin,Wang, Enfu,Wang, Fei,Zhang, Jian,Zhang, Zhengyu
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supporting information
p. 3477 - 3480
(2022/03/31)
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- An expedient synthesis of highly functionalized 1,3-dienes by employing cyclopropenes asC4units
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An efficient method has been described to synthesize dicarbonyl functionalized 1,3-dienes by cleaving the CC bond of enaminones with cyclopropenes in the presence of a rhodium catalyst. The acetate-substituted cyclopropenes are judiciously chosen as standardC4units of 1,3-diene precursors. The reactions are believed to undergo a unique cutting and insertion process, involving a CC bond cleavage of the enaminone and insertion of a newC(sp2) source with the formation of two C-C single bonds. A broad range of substrates can be used to synthesize the corresponding 1,3-dienes under very mild reaction conditions, including low catalyst-loading, ambient temperature, and a neutral reaction solvent.
- Jiang, Chengzhou,Wu, Jiamin,Han, Jiabin,Chen, Kai,Qian, Yang,Zhang, Zhengyu,Jiang, Yaojia
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supporting information
p. 5710 - 5713
(2021/06/16)
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- Structure-Based Discovery of Pyrimidine Aminobenzene Derivatives as Potent Oral Reversal Agents against P-gp- And BCRP-Mediated Multidrug Resistance
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Overexpression of ATP binding cassette (ABC) transporters, including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), is an important factor leading to multidrug resistance (MDR) in cancer treatments. Three subclasses of dual inhibitors of P-gp and BCRP were designed based on the active moieties of BCRP inhibitors, tyrosine kinase inhibitors, and P-gp inhibitors, of which compound 21 possessed low cytotoxicity, high reversal potency, and good lipid distribution coefficient. 21 also increased the accumulation of Adriamycin (ADM) and Mitoxantrone (MX), blocked Rh123 efflux, and made no change in the protein expression of P-gp and BCRP. Importantly, coadministration of 21 can significantly improve the oral bioavailability of paclitaxel (PTX). It was also demonstrated that 21 significantly inhibited the growth of K562/A02 xenograft tumors by increasing the sensitivity of ADM in vivo. In summary, 21 has the potential to overcome MDR caused by P-gp and BCRP and to improve the oral bioavailability of PTX.
- Qiu, Qianqian,Zou, Feng,Li, Huilan,Shi, Wei,Zhou, Daoguang,Zhang, Ping,Li, Teng,Yin, Ziyu,Cai, Zilong,Jiang, Yuxuan,Huang, Wenlong,Qian, Hai
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p. 6179 - 6197
(2021/06/01)
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- An Atom-Economic Synthesis of Functionalized Pyridazines via Multicomponent Reactions Under Pressure and Ultrasonication
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Abstract: A three-component reaction of 1 mol of arylhydrazonals with 2 mol of an active methylene compound is realized under pressure to obtained novel functionalized pyridazines with a 96% atom economy. The reaction of arylhydrazonals with active methyl
- Al-Zaydi,Al-Solami,Basudan,Elnagdi,Elnagdi
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p. 1309 - 1320
(2021/09/30)
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- One-Pot Synthesis of Symmetrical and Asymmetrical 3-Amino Diynes via Cu(I)-Catalyzed Reaction of Enaminones with Terminal Alkynes
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An economical and efficient protocol for the direct construction of amino skipped diynes through the Cu(I)-catalyzed reaction of enaminones and terminal alkynes has been described. Different kinds of symmetrical and asymmetrical 3-amino diynes could be ob
- Zhang, Changyuan,Guo, Huosheng,Chen, Lulu,Zhang, Jiantao,Guo, Mengping,Zhu, Xuncheng,Shen, Chan,Li, Zeng
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supporting information
p. 8169 - 8173
(2021/11/01)
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- Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors
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Herein we report a microscale parallel synthetic approach allowing for rapid access to libraries of N-acylated aminotriazoles and screening of their inhibitory activity against factor XIIa (FXIIa) and thrombin, which are targets for antithrombotic drugs. This approach, in combination with post-screening structure optimization, yielded a potent 7 nM inhibitor of FXIIa and a 25 nM thrombin inhibitor; both compounds showed no inhibition of the other tested serine proteases. Selected N-acylated aminotriazoles exhibited anticoagulant properties in vitro influencing the intrinsic blood coagulation pathway, but not extrinsic coagulation. Mechanistic studies of FXIIa inhibition suggested that synthesized N-acylated aminotriazoles are covalent inhibitors of FXIIa. These synthesized compounds may serve as a promising starting point for the development of novel antithrombotic drugs.
- Platte, Simon,Korff, Marvin,Imberg, Lukas,Balicioglu, Ilker,Erbacher, Catharina,Will, Jonas M.,Daniliuc, Constantin G.,Karst, Uwe,Kalinin, Dmitrii V.
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supporting information
p. 3672 - 3690
(2021/08/07)
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- Discovery of highly potent tubulin polymerization inhibitors: Design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines
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By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.
- Huo, Xian-Sen,Jian, Xie-Er,Ou-Yang, Jie,Chen, Lin,Yang, Fang,Lv, Dong-Xin,You, Wen-Wei,Rao, Jin-Jun,Zhao, Pei-Liang
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- Synthesis, in vitro, and in vivo (Zebra fish) antitubercular activity of 7,8-dihydroquinolin-5(6H)-ylidenehydrazinecarbothioamides
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We, herein, describe the synthesis of a series of novel aryl tethered 7,8-dihydroquinolin-5(6H)-ylidenehydrazinecarbothioamides 4a–v, which showed in vitro and in vivo antimycobacterial activity against Mycobacterium tuberculosis (Mtb) H37Rv. The intermed
- Kantevari, Srinivas,Krishna, Vagolu Siva,Marvadi, Sandeep kumar,Sridhar, Balasubramanian,Srilakshmi Reshma, Rudraraju,Sriram, Dharmarajan,Surineni, Goverdhan
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- Sulfonamide-based ring-fused analogues for CAN508 as novel carbonic anhydrase inhibitors endowed with antitumor activity: Design, synthesis, and in vitro biological evaluation
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In the present study, we report the design and synthesis of novel CAN508 sulfonamide-based analogues (4, 8a-e, 9a-h and 10a-e) as novel carbonic anhydrase (CA) inhibitors with potential CDK inhibitory activity. A bioisosteric replacement approach was adop
- Said, Mohamed A.,Eldehna, Wagdy M.,Nocentini, Alessio,Fahim, Samar H.,Bonardi, Alessandro,Elgazar, Abdullah A.,Kry?tof, Vladimír,Soliman, Dalia H.,Abdel-Aziz, Hatem A.,Gratteri, Paola,Abou-Seri, Sahar M.,Supuran, Claudiu T.
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- Synthesis of some novel substituted nicotines and evaluation of their antimicrobial activity
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A VARIETY of some novel substituted nicotines were synthesized and characterized by spectroscopic means where nicotinic acid hydrazide (6a) and/or (6b) are used as a key intermediate in the synthesis of hydrazones (8a-l) and (10a-f) by the reaction with different aromatic aldehydes (7a-f) and isatines (9a-e), respectively. Moreover, nicotinic acid hydrazide reacted with pentane-2,4-dione (11), 2-ethoxymethylene-malononitrile (13) and thiosemicarbazone (15) generating pyrazoles (12), (14) and 1,2,4-triazole (16), respectively. The newly synthesized compounds were tested against nine microbial strains. Some of these compounds showed a significant activity against several of the microorganisms. Compounds (8d), (10b) and (10c) were determined to be the most active compounds. Compound (8d) showed activity against S. aureus, B. subtilis and A. flavus with IZ = 2.4, 3.2 and 2.6 mm, respectively when compared with reference drugs (Amoxicillin, IZ = 2.3, 3.5 and Griseofulvin, IZ = 2.4 mm). Additionally, compound (10b) showed potent activity against P. aeruginosa and P. expansum with IZ = 2.6 and 2.8, respectively when compared with reference drugs (Amoxicillin, IZ = 2.2 mm and Griseofulvin, IZ = 2.8 mm), respectively, while (10c) showed the same activity as Griseofulvin against P. expansum with IZ = 2.8 mm. The biological activity (SAR) of the evaluated compounds and the relationship between the functional group variations are discussed.
- Masoud, Doaa M.,Azzam, Rasha A.,Hussein, Hussein S.,Mekawey, Aml A.I.,Abdel-Aziz, Hatem A.
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p. 791 - 803
(2020/04/17)
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- I2-Promoted [4 + 2] cycloaddition of: In situ generated azoalkenes with enaminones: Facile and efficient synthesis of 1,4-dihydropyridazines and pyridazines
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A facile and efficient strategy for the synthesis of 1,4-dihydropyridazines and pyridazines through I2-promoted [4 + 2] cycloaddition of in situ generated azoalkenes with enaminones has been developed. The switch in selectivity is attributed to the judici
- Baell, Jonathan B.,Feng, Jiajun,He, Tiantong,Huang, Fei,Xie, Yuxing,Yu, Yang
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supporting information
p. 9483 - 9493
(2020/12/15)
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- Stereoselective synthesis of trifluoromethyl-substituted 2: H -furan-amines from enaminones
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A straightforward strategy for synthesis of highly functionalized trifluoromethyl 2H-furans is described. The copper catalyzed method relies on a cascade cyclic reaction between enaminones and N-tosylhydrazones. This method allows the synthesis of 2-amino
- Liang, Xiaoyu,Guo, Pan,Yang, Wenjie,Li, Meng,Jiang, Chengzhou,Sun, Wangbin,Loh, Teck-Peng,Jiang, Yaojia
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supporting information
p. 2043 - 2046
(2020/02/22)
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- Synthesis of novel morpholine, thiomorpholine and N-substituted piperazine coupled 2-(thiophen-2-yl)dihydroquinolines as potent inhibitors of Mycobacterium tuberculosis
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A series of novel morpholine, thiomorpholine and N-substituted piperazine coupled 2-(thiophen-2-yl)dihydroquinolines 7a–p was designed and synthesized from 2-acetyl thiophene in six step reaction sequence involving modified Bohlmann-Rahtz and Vilsmeier-Haack-Arnold reactions as key transformations. 2-(Thiophen-2-yl)dihydroquinoline was formylated and subsequently chlorinated using DMF-POCl3. The resulting aldehyde was reduced to give an alcohol and then converted to bromide using PBr3. Further coupling of bromide with morpholine, thiomorpholine and N-substituted piperazines resulted in the desired quinolines 7a-p in very good yields. All the new derivatives 7a–p were characterized by their NMR and mass spectral analysis. In vitro screening of new compounds for antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), resulted in two derivatives 7f and 7p as most potent antitubercular agents (MIC:1.56 μg/mL) with lower cytotoxicity profiles.
- Marvadi, Sandeep Kumar,Krishna, Vagolu Siva,Sriram, Dharmarajan,Kantevari, Srinivas
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p. 171 - 178
(2019/01/03)
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- Synthesis and evaluation of novel substituted 1,2,3-triazolyldihydroquinolines as promising antitubercular agents
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A series of novel substituted 1,2,3-triazolyldihydroquinolines 6a–o was designed and synthesized from 2-acetylthiophene in five-step reaction sequence involving modified Boltzmann-Rahtz reaction of β-Enaminone; Vilsmeier-Haack chloroformylation using DMF/
- Marvadi, Sandeep Kumar,Krishna, Vagolu Siva,Sriram, Dharmarajan,Kantevari, Srinivas
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p. 529 - 533
(2019/01/11)
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- SLC-0111 enaminone analogs, 3/4-(3-aryl-3-oxopropenyl) aminobenzenesulfonamides, as novel selective subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform IX
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SLC-0111, an ureido substituted benzenesulfonamide, is a selective carbonic anhydrase (CA, EC 4.2.1.1) IX inhibitor that is currently in Phase I/II clinical trials for the treatment of advanced hypoxic tumors complicated with metastases. Herein we report
- Eldehna, Wagdy M.,Abo-Ashour, Mahmoud F.,Berrino, Emanuela,Vullo, Daniela,Ghabbour, Hazem A.,Al-Rashood, Sara T.,Hassan, Ghada S.,Alkahtani, Hamad M.,Almehizia, Abdulrahman A.,Alharbi, Amal,Abdel-Aziz, Hatem A.,Supuran, Claudiu T.
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p. 549 - 558
(2018/11/26)
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- Harnessing Stereospecific Z-Enamides through Silver-Free Cp?Rh(III) Catalysis by Using Isoxazoles as Masked Electrophiles
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The stereospecific synthesis of Z-enamides is described in this paper. For the first time, isoxazoles have been employed as electrophiles in C-H functionalization to afford thermodynamically less stable Z-enamides utilizing salicylaldehydes in an atom- and step-economic fashion. The stereochemistry of enamides might originate from the relative disposition of atoms present in isoxazole and the intramolecular hydrogen bonding. The reaction showed excellent scope as several structurally and electronically diverse salicylaldehydes and isoxazoles reacted efficiently.
- Debbarma, Suvankar,Bera, Sourav Sekhar,Maji, Modhu Sudan
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supporting information
p. 835 - 839
(2019/01/26)
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- Design, synthesis and SAR study of novel sulfonylurea derivatives containing arylpyrimidine moieties as potential anti-phytopathogenic fungal agents
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Acetohydroxyacid synthase (AHAS) was considered as a promising target for antifungal agents. Herein, three series of novel sulfonylureas (SUs) 9?11 containing aromatic-substituted pyrimidines were designed and synthesized according to pharmacophore-combin
- Chen, Wei,Li, Yuxin,Zhou, Yunyun,Ma, Yi,Li, Zhengming
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supporting information
p. 2160 - 2162
(2019/05/17)
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- The use of enaminones and enamines as effective synthons for MSA-catalyzed regioselective synthesis of 1,3,4-tri- And 1,3,4,5-tetrasubstituted pyrazoles
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In the present work, an efficient regioselective synthesis of 1,3,4-tri- and 1,3,4,5-tetrasubstituted pyrazoles via a methanesulfonic acid (MSA)-catalyzed reaction of hydrazones with enaminones or enamines is reported. Mechanistically, the formation of the title compounds involves the [2+3] cycloaddition of hydrazones with enaminones or enamines followed by aromatization with acid and oxygen. This convenient method under mild conditions with various hydrazones, enaminones, and enamines was well-tolerated to afford products in good to excellent yields. Compared with the literature methods, this strategy has advantages such as materials that are available economically, metal-free catalysis, excellent regioselectivity, and high efficiency.
- Duan, Liancheng,Zhou, Hui,Gu, Yucheng,Gong, Ping,Qin, Mingze
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supporting information
p. 16131 - 16137
(2019/11/03)
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- Design, synthesis, and biological evaluation of triazolyl- and triazinyl-quinazolinediones as potential antitumor agents
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Novel 6(3-1H-1,2,4-triazol-1-yl)-3-phenylquinazoline-2,4(1H,3H)-diones (7a-e) were synthesized from different enaminones (6a-e) with 6-hydrazinyl-3-phenylquinazoline-2,4(1H,3H)-dione. 2,6(4-2-Substituted-1,3,5-triazin-1(2H)-yl)-3-phenylquinazoline-2,4(1H,3H)-diones (8a-k) were synthesized from the reaction of 1-(2,4-dioxo-3-phenyl-1,2,3,4-tetrahydroquinazolin-6-yl)thiourea, urea, or guanidine (3a-c) with enaminones (6a-e), and a series from 3-substituted-2-imino-1,3,5-triazin-1(2H)-yl-sulfonyl-phenyl-1-methylquinazoline-2,4(1H,3H)-dione (12a-j) were obtained from the reaction of N-(diaminomethylene)-4-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)benzenesulfonamide (11) with the enaminone (6a-j). The antitumor activity of the synthesized compounds was evaluated against two human cell lines: human colon carcinoma HCT116 and human hepatocellular carcinoma HEP-G2. Some of the tested compounds showed significant potency compared to the reference drug staurosporin.
- Al-Romaizan, Abeer N.,Ahmed, Nesreen S.,Elfeky, Sherin M.
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- Synthesis method of key intermediate for preparing duloxetine hydrochloride from 2-acetylthiophene
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The invention provides a synthesis method of a key intermediate for preparing duloxetine hydrochloride from 2-acetylthiophene and belongs to the technical field of chemical synthesis. The synthesis method comprises the following steps: reacting cyanuric chloride and N,N-dimethylformamide with 2-acetylthiophene to obtain 3-(dimethylamino)-1-(2-thienyl)-2-propenyl-1-one; reducing 3-(dimethylamino)-1-(2-thienyl)-2-propenyl-1-one through lithium aluminum hydride to obtain a duloxetine hydrochloride intermediate which is (R,S)-N,N-dimethyl-3-hydroxy-3-(2-thienyl)propylamine. The synthesis method iscapable of synthesizing a target product which is a key intermediate of duloxetine hydrochloride through two-step reaction, is cheap in raw materials, simple in process, simple and convenient to operate, mild in reaction condition, short in reaction period and free of expensive catalysts, is environmentally friendly, and is suitable for industrial production; the prepared products are high in yield and purity.
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Paragraph 0017; 0018; 0019; 0020; 0021; 0022; 0023; 0024
(2018/11/03)
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- COMPOUND OF 5-HYDROXYL-1,7-NAPHTHYRIDINE SUBSTITUTED BY ARYL OR HETEROARYL, PREPARATION METHOD THEREOF AND PHARMACEUTICAL USE THEREOF
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Disclosed are a compound of the following formula (I) or a pharmaceutically acceptable salt thereof, a preparation method thereof, pharmaceutical compositions and uses thereof in the preparation of a medicine for inhibiting HIF prolyl hydroxylase or a medicine for promoting the generation of endogenous EPO, wherein in the formula (I), R1 and R2 are each independently hydrogen; R3 is hydrogen or C1-3 alkyl; and Ar is an aromatic ring or an heteroaromatic ring selected from a naphthalene ring, a pyridine ring, a thiophene ring, a furan ring and a substituted benzene ring.
- -
-
Paragraph 0133
(2018/03/25)
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- Design and synthesis of novel benzenesulfonamide containing 1,2,3-triazoles as potent human carbonic anhydrase isoforms I, II, IV and IX inhibitors
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In a quest to discover new biologically active compounds, a series of twenty novel heterocyclic derivatives substituted at position 5 with -H (7a-7j) or -CF3 (8a-8j), bearing benzenesulfonamide at N-1 position and various aroyl groups at position 4 of the 1,2,3-triazole ring was synthesized and screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibition potential against four human (h) isoforms hCA I, II, IV and IX. All the compounds (7a-7j and 8a-8j) were synthesized via [3+2] cycloaddition reaction from 4-azidobenzenesulfonamide. Interestingly, compounds 7a-7j were prepared in one pot manner via enaminone intermediate using novel methodology. All the newly synthesized compounds (7a-7j & 8a-8j) were found to be excellent inhibitors of edema related isoform hCA I with their inhibition constant (Ki) ranging from 30.1 to 86.8 nM as compared to standard drug acetazolamide (AAZ) with Ki = 250 nM. Further it was found that most of tested compounds were weaker inhibitors of isoform, hCA II although compounds 7b, 7d-7e, 8a, 8d-8f, 8i (mostly with electron withdrawing substituents) have shown better inhibition potential (Ki i = 52.4 nM) than AAZ (Ki = 74 nM) while against tumor associated hCA IX, all the compounds have shown moderate inhibition potential. Present study have added one more step in exploring the 1,2,3-triazlole moiety in the medicinal field.
- Kumar, Rajiv,Vats, Lalit,Bua, Silvia,Supuran, Claudiu T.,Sharma, Pawan K.
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p. 545 - 551
(2018/06/18)
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- Discovery and structure-activity relationships study of thieno[2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors
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Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC50 = 33.8 μM) characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC50 = 16.8 μM) and 9d (IC50 = 12.3 μM) with potent inhibition of hepatic glucose production and good drug-like properties. Furthermore, the mechanism of 8e for the inhibition of hepatic glucose production was also identified, which could be effective through the reductive expression of the mRNA transcription level of gluconeogenic genes, including glucose-6-phosphatase (G6Pase) and hepatic phosphoenolpyruvate carboxykinase (PEPCK). Additionally, 8e could also reduce the fasting blood glucose and improve the oral glucose tolerance and pyruvate tolerance in db/db mice. The optimization of this class of derivatives had provided us a start point to develop new anti-hepatic gluconeogenesis agents.
- Ma, Fei,Liu, Jian,Zhou, Tingting,Lei, Min,Chen, Jing,Wang, Xiachang,Zhang, Yinan,Shen, Xu,Hu, Lihong
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p. 307 - 317
(2018/05/22)
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- A copper-catalyzed three component reaction of aryl acetylene, sulfonyl azide and enaminone to form iminolactone via 6π electrocyclization
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We developed a copper-catalyzed three component reaction of aryl acetylene, enaminone and sulfonyl azide to construct iminolactone via a cascade process involving copper-catalyzed alkyne-azide cycloaddition (CuAAC), Michael addition of metalated ketenimin
- Sun, Jiarui,Cheng, Xiangsheng,Mansaray, John Kamanda,Fei, Weihong,Wan, Jieping,Yao, Weijun
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supporting information
p. 13953 - 13956
(2019/01/03)
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- 3-Formylpyrazolo[1,5- a]pyrimidines as Key Intermediates for the Preparation of Functional Fluorophores
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A one-pot route for the regioselective synthesis of 3-formylpyrazolo[1,5-a]pyrimidines 4a-k in good yields through a microwave-assisted process is provided. The synthesis proceeds via a cyclocondensation reaction between β-enaminones 1 with NH-3-aminopyrazoles 2, followed by formylation with an iminium salt moiety (Vilsmeyer-Haack reagent). These N-heteroaryl aldehydes 4 were successfully used as strategic intermediates for the preparation of novel functional fluorophores with yields up to 98%. The structures of the products obtained and regioselectivity of the reactions were determined on the basis of NMR measurements and X-ray diffraction analysis. Since pyrazolo[1,5-a]pyrimidines (PPs) 3 have shown an important fluorescence, photophysical properties of four 2-methylderivatives substituted at position 7 with different acceptor (A) or donor (D) groups were investigated. The compounds evaluated exhibited large Stokes shift in different solvents, but only the substituted p-methoxyphenyl (4-An) showed a strong fluorescence intensity with quantum yields up to 44% due to its greater ICT. Therefore, hybrid systems based on pyrazolo[1,5-a]pyrimidines could be used as fluorescent probes to detect biologically or environmentally relevant species.
- Castillo, Juan-Carlos,Tigreros, Alexis,Portilla, Jaime
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p. 10887 - 10897
(2018/08/11)
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- Highly Site-Selective Metal-Free C-H Acyloxylation of Stable Enamines
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A highly site-selective acyloxylation of stable enamines with PhI(OAc)2 under metal-free conditions to afford (E)-vinyl acetate derivatives in good to excellent yields is described. Depending on the judicious choice of the solvent system, either the α- or β-site-selective product could be obtained with high selectivity. For the α-site-selective product, the rearranged amide compound is obtained as the major product. This reaction proceeds under mild reaction conditions (room temperature, metal-free, and open-flask) and features a broad substrate scope.
- Wang, Fei,Sun, Wangbing,Wang, Yixin,Jiang, Yaojia,Loh, Teck-Peng
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supporting information
p. 1256 - 1260
(2018/02/23)
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- Metal-free TBAI-catalyzed oxidative Csp3–S bond formation through Csp2–Csp2 bond and S–N bond cleavage: A new route to β-keto-Sulfones
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A novel TBAI-catalyzed radical sulfonylation of readily available N,N-dimethylenaminones with sulfonylhydrazides to afford functionalized β-keto-sulfones has been developed. Various functional groups were tolerated well under the present oxidative conditions and the corresponding β-keto-sulfone compounds were obtained in moderate to good yields. Importantly, this transformation offered the first protocol for Csp3–S bond formation by oxidative Csp2–Csp2 bond cleavage in one step.
- Tang, Yucai,Chen, Ying,Liu, Hui,Guo, Min
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supporting information
p. 3703 - 3705
(2018/09/14)
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- Syntheses, crystal structures and photophysical properties of d10 transition-metal (Ag+, Cu+, Cd2+ and Zn2+) coordination complexes based on a thiophene-containing heterocyclic thioamide
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Four d10 transition-metal coordination complexes 1–4 (1: [Ag2(TPT)2(TPTH)2]; 2: [Cu6(TPT)6]·2DMF; 3: [Cd(TPT)2(TPTH)]·CH3CH2OH, 4: [Zn(TPT)2]n) have been constructed from a newly designed heterocyclic thioamide ligand, TPTH (TPTH?=?4-(thiophen-2-yl)-pyrimidine-2-thiol). All complexes have been structurally elucidated by single crystal X-ray diffraction analyses. Except for 4, which shows a one-dimensional (1-D) chain structure, 1–3 are all discrete coordination complexes featuring dinuclear, hexanuclear and mononuclear entities, respectively. Their photophysical properties have been evaluated in the solid state at room temperature by UV–vis diffuse reflectance and luminescence spectra. Among them, 2 exhibits a strong red luminescence (λem?=?699?nm) with a remarkable red-shift of the maximum emission compared to that of the TPTH ligand (λem?=?536?nm). The red emission observed with 2 is ascribed to a LMCT (ligand-to-metal charge transfer) transition which agrees with the DFT calculations.
- Wei, Yu-Zhen,Cheng, Zheng,Li, Wei,Zhu, Hai-Bin
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p. 2900 - 2915
(2017/09/06)
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- Preparation method of (S)-3-N,N-disubstituted amino-1-(2-thienyl)-1-propanol
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The invention discloses a preparation method of (S)-3-N,N-disubstituted amino-1-(2-thienyl)-1-propanol shown as the formula (I). The method comprises: taking 2-acetyl thiophene shown in the formula (II) as a raw material, and allowing 2-acetyl thiophene to completely react with di(trichloromethyl)carbonic ester (III) and N,N-disubstituted methanamide (IV) in an organic solvent under the catalysis of an organic base to obtain N,N-disubstituted amino-1-(2-thienyl)-1-acrylketone shown as the formula (V); and performing hydrogenation reduction with lithium aluminium hydride to obtain N,N-disubstituted amino-1-(2-thienyl)-1-propanol shown as the formula (VI); and performing splitting with S-mandelic acid and recrystallization with ethyl acetate to obtain the target product shown as the formula (I). The preparation method is low in cost, mild in reaction condition, less in waste water, waste gas and industrial residue, small in energy consumption, and high in yield. The preparation method is safe and is suitable for industrial production.
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Paragraph 0022-0031
(2018/03/24)
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- Synthesis of C5-tethered indolyl-3-glyoxylamide derivatives as tubulin polymerization inhibitors
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A series of C5-tethered Indolyl-3-glyoxylamide derivatives were synthesized and evaluated for their in?vitro cytotoxic activity against DU145 (prostate), PC-3 (prostate), A549 (lung) and HCT-15 (colon) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compound 7f displayed cytotoxicity of IC50?=?140?nM towards DU145 cancer cell line. The treatment of DU145?cells with 7f led to inhibition of cell migration ability. Futher, the detailed studies such as acridine orange/ethidium Bromide (AO/EB), DAPI, annexin V-FITC/propidium iodide staining assay suggested that the compound 7f induced apoptosis in DU145?cells. The influence of the cytotoxic compound 7f on the cell cycle distribution was assessed on the DU145?cell line, exhibiting a cell cycle arrest at the G2/M phase (hallmark of tubulin polymerization) and next inhibited tubulin polymerization with IC500.40?μM. Furthermore, the treatment with compound 7f caused collapse of mitochondrial membrane potential and elevated intracellular superoxide ROS levels in DU145?cells. Western blotting was performed to examine the levels of apoptotic proteins (Bcl-2 and Bax); the study confirmed that compound 7f induced apoptosis through apoptosis-related protein expression. Thus, these studies provided a new molecular scaffold for the further development of anticancer agents that target tubulin.
- Guggilapu, Sravanthi Devi,Lalita, Guntuku,Reddy, T. Srinivasa,Prajapti, Santosh Kumar,Nagarsenkar, Atulya,Ramu, Shymala,Brahma, Uma Rani,Lakshmi, Uppa Jaya,Vegi, Ganga Modi Naidu,Bhargava, Suresh K.,Babu, Bathini Nagendra
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- Directed C-C bond cleavage of a cyclopropane intermediate generated from: N -tosylhydrazones and stable enaminones: Expedient synthesis of functionalized 1,4-ketoaldehydes
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An efficient method to construct functionalized 1,4-ketoaldehydes bearing all-carbon α-quaternary centers via regioselective C-C bond activation has been described. The cyclopropanation of bench-stable enaminones with in situ generated diazo reagents from
- Ni, Meiyan,Zhang, Jianguo,Liang, Xiaoyu,Jiang, Yaojia,Loh, Teck-Peng
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supporting information
p. 12286 - 12289
(2017/11/20)
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- Metal-Free Route for the Synthesis of 4-Acyl-1,2,3-Triazoles from Readily Available Building Blocks
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Functionalized 1,2,3-triazole heterocycles have been known for a long time and hold an extraordinary potential in diverse research areas ranging from medicinal chemistry to material science. However, the scope of therapeutically important 1-substituted 4-acyl-1H-1,2,3-triazoles is much less explored, probably due to the lack of synthetic methodologies of good scope and practicality. Here, we describe a practical and efficient one-pot multicomponent reaction for the synthesis of α-ketotriazoles from readily available building blocks such as methyl ketones, N,N-dimethylformamide dimethyl acetal, and organic azides with 100 % regioselectivity. This reaction is enabled by the in situ formation of an enaminone intermediate followed by its 1,3-dipolar cycloaddition reaction with an organic azide. We effectively utilized the developed strategy for the derivatization of various heterocycles and natural products, a protocol which is difficult or impossible to realize by other means.
- Thomas, Joice,Goyvaerts, Vince,Liekens, Sandra,Dehaen, Wim
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supporting information
p. 9966 - 9970
(2016/07/19)
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- 2-thiophene pyridine compound, and applications thereof
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The invention discloses a 2-thiophene pyridine compound, or a salt thereof. The structure of the 2-thiophene pyridine compound is represented by a general formula I, and the substituent groups are defined in the specification. The compound represented by
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Paragraph 0319; 0320; 0321
(2016/10/09)
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- Synthesis and biological evaluation of oxindole linked indolyl-pyrimidine derivatives as potential cytotoxic agents
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In our endeavor towards the development of effective cytotoxic agents, a series of oxindole linked indolyl-pyrimidine derivatives were synthesized and characterized by IR, 1H NMR, 13C NMR and Mass spectral analysis. All the newly synthesized target compounds were assessed against PA-1 (ovarian), U-87MG (glioblastoma), LnCaP (prostate), and MCF-7 (Breast) cancer cell lines for their cytotoxic potential, with majority of them showing inhibitory activity at low micro-molar concentrations. Significantly, compound 8e was found to be most potent amongst all the tested compounds with an IC50 value of (2.43 ± 0.29 μM) on PA-1 cells. The influence of the most active cytotoxic compound 8e on the cell cycle distribution was assessed on the PA-1 cell line, exhibiting a cell cycle arrest at the G2/M phase. Moreover, acridine orange/ethidium bromide staining and annexin V binding assay confirmed that compound 8e can induce cell apoptosis in PA-1 cells. These preliminary results persuade further investigation on the synthesized compounds aiming to the development of potential cytotoxic agents.
- Prajapti, Santosh Kumar,Nagarsenkar, Atulya,Guggilapu, Sravanthi Devi,Gupta, Keshav Kumar,Allakonda, Lingesh,Jeengar, Manish Kumar,Naidu,Babu, Bathini Nagendra
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supporting information
p. 3024 - 3028
(2016/06/13)
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- Palladium-Catalyzed C–S Bond Formation of Stable Enamines with Arene/Alkanethiols: Highly Regioselective Synthesis of β-Amino Sulfides
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A direct and regiocontrolled thiolation method to access β-amino sulfides through the palladium-catalyzed C(sp2)–H functionalization of stable enamines was described. The reaction was realized under mild conditions by adding an external phosphi
- Jiang, Yaojia,Liang, Gaohui,Zhang, Cong,Loh, Teck-Peng
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supporting information
p. 3326 - 3330
(2016/07/23)
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- Design, synthesis and antitubercular activity of certain nicotinic acid hydrazides
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Three series of 6-Aryl-2-methylnicotinohydrazides 4a-i, N'-Arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a-f, and N'-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a-c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M.Tuberculosis. The results showed that isatin hydrazides 8a-c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 μg/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives.
- Eldehna, Wagdy M.,Fares, Mohamed,Abdel-Aziz, Marwa M,Abdel-Aziz, Hatem A
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p. 8800 - 8815
(2016/09/04)
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- First examples of 2,6-diarylnicotinaldehydes prepared under conventional and microwave conditions
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Enaminoketones undergo unexpected self condensation in acetic acid to produce a wide range of 2,3,6-trisubstituted pyridine derivatives in excellent yields in the presence of NH4OAc. This is the first Letter on the synthesis of 2,6-diarylnicoti
- Shankaraiah,Chandrasekhar,Siva Nagi Reddy,Sabitha, Gowravaram
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p. 842 - 846
(2015/03/04)
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- Discovery and structure-activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors
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Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. And then, structure activity relationship study of the hit compound led to the discovery of several potent compounds without obvious cytotoxicity in vitro (12c, EC50 = 3.3 μM, SI >30.3, 12b, EC50 = 3.5 μM, SI >28.6, 10l, EC50 = 3.9 μM, SI >25.6, 12o, EC 50 = 4.5 μM, SI >22.2, respectively). Although the mechanism of them had not been clearly elucidated, our preliminary optimization of this class of compounds had provided us a start point to develop new anti-HCV agents.
- Wang, Ning-Yu,Zuo, Wei-Qiong,Xu, Ying,Gao, Chao,Zeng, Xiu-Xiu,Zhang, Li-Dan,You, Xin-Yu,Peng, Cui-Ting,Shen, Yang,Yang, Sheng-Yong,Wei, Yu-Quan,Yu, Luo-Ting
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supporting information
p. 1581 - 1588
(2014/03/21)
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- Novel synthesis of 6-substituted 2-picolines from aryl/heteroaryl β-enaminones and meldrum's acid using cecl3.7H2o/nai
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One-pot condensation of aryl/heteroaryl β-enaminones, Meldrum's acid, and ammonium acetate in the presence of CeCl3.7H2O/NaI via tandem Michael addition-cyclodehydration-elimination sequence led to the formation of novel regioselecti
- Addla, Dinesh,Kantevari, Srinivas
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p. E384-E388
(2014/11/08)
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- Design and synthesis of novel thiophenes bearing biologically active aniline, aminopyridine, benzylamine, nicotinamide, pyrimidine and triazolopyrimidine moieties searching for cytotoxic agents
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To discover new bioactive lead compounds for medicinal purposes, herein, (E)-3-(substituted amino)-1-thiophen-2-yl-prop-2-en-1-ones 3-8, aminopyridines 9-11, benzylamine 12, nicotinamide 13, pyrimidines 14, 15, hexanoic acid 16 and triazolopyrimidine 19 w
- Ghorab, Mostafa M.,El-Gazzar, Marwa G.,Alsaid, Mansour S.
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p. 401 - 407
(2014/06/09)
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- Pd-catalyzed site selective C-H acetoxylation of aryl/heteroaryl/thiophenyl tethered dihydroquinolinones
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Described herein is an efficient protocol for the site selective oxidative C-H activation/acetoxylation of a series of 2-aryl/heteroaryl/thiophenyl tethered dihydroquinolinones using palladium acetate as the catalyst and iodobenzene diacetate as an oxidan
- Patpi, Santhosh Reddy,Sridhar, Balasubramanian,Tadikamalla, Prabhakar Rao,Kantevari, Srinivas
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p. 10251 - 10261
(2013/09/02)
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- Simple approach to the synthesis of 3-fluoro pyrazolo[1,5-a]pyrimidine analogues
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A simple method for the synthesis of novel 3-fluoro pyrazolo[1,5-a] pyrimidine analogues has been developed starting from fluoro acetonitrile and benzoyl chloride. The desired compounds are synthesized from a 3-amino-4-fluoro pyrazole intermediate. The versatility of the approach was demonstrated by the synthesis of a small library of pyrazolo[1,5-a]pyrimidine.
- Bel Abed, Hassen,Mammoliti, Oscar,Van Lommen, Guy,Herdewijn, Piet
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p. 2612 - 2614
(2013/06/05)
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- Synthesis and docking studies of some 3-amino-6-(thiophen-2-yl)thieno[2,3- b]pyridine derivatives
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Some 3-amino-6-(thiophen-2-yl)thieno[2,3-b]pyridine derivatives (4a-j) were synthesized and characterized by 1H NMR, 13C NMR and elemental microanalyses based on the hit compound DZ9202, a nicotinate mononucleotide adenylyltransferase inhibitor against Bacillus anthracis. In the next step, molecular modeling and relative potency of these structures were studied. Copyright
- Salarian,Asadi-Eskandar,Sakhteman,Abdi
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p. 1275 - 1278
(2013/05/09)
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- Synthesis and dual 5-ht1a/ssri activities of some novel arylpiperazine derivatives of duloxetine
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A series of novel arylpiperazine derivatives of duloxetine were designed and synthesized from the key intermediate 5 by acylation, alkylation and reduction based on 5-HT1A/SSRI drugs design strategies. Compound 5 was obtained through the reaction sequence including condensation, reduction, O-etherification, Von Braun reaction, hydrolysis reaction. Structures of the synthesized compounds were confirmed by MS, 1H NMR and HRMS. Furthermore, these compounds were evaluated for their dual 5-HT1A/5-HTT activities. The results indicated that all the compounds exhibited certain affinity to 5-HTT and 5-HT1A receptor.
- Chen, Shao-Rui,Li, Ai-Jun,Chen, Ming-Ming
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experimental part
p. 1680 - 1684
(2012/08/28)
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- Synthesis and antimicrobial activity of novel 7-(Heteroaryl)-1,2,4- triazolo[1,5-a]-pyrimidine derivatives
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The synthesis, characterization and antimicrobial activity of novel 1,2,4-triazolo[1,5-a]pyrimidines have been reported. The compounds were prepared by acid catalyzed condensation of 3-amino-1,2,4-triazole with 3-(dialkylamino)acryloalkanone.
- Rama Rao, R. Janaki,Rao, A.K.S. Bhujanga,Swapna,Rani, B. Baby,Murthy
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experimental part
p. 1837 - 1843
(2012/08/07)
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- A "catch-react-release" method for the flow synthesis of 2-aminopyrimidines and preparation of the imatinib base
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The development of a monolith-supported synthetic procedure is reported, taking advantage of flow processing and the superior flow characteristics of monolithic reagents over gel-phase beads, to allow facile access to an important family of 2-aminopyrimidine derivatives. The process has been successfully applied to a key precursor on route to Imatinib (Ar = 3-pyridyl, R1 = 2-methyl-5-nitrobenzyl, R2 = H).
- Ingham, Richard J.,Riva, Elena,Nikbin, Nikzad,Baxendale, Ian R.,Ley, Steven V.
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supporting information; experimental part
p. 3920 - 3923
(2012/09/22)
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- L-proline-catalyzed activation of methyl ketones or active methylene compounds and DMF-DMA for syntheses of (2E)-3-dimethylamino-2- propen-1-ones
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A cascade organocatalysis is reported for the nucleophilic and electrophilic dual activation taking place in the reaction of methyl ketones or active methylene compounds with DMF-DMA (N,N-dimethylformamide dimethyl acetal). L-Proline serves as an efficient organocatalyst in the covalent and noncovalent synchronous mode for the ambiphilic activation of various aryl, heteroaryl, and styryl methyl ketones, cyclic ketones, and 1,3-diketones with DMF-DMA to achieve the convenient syntheses of the versatile synthons (2E)-1-aryl/ heteroaryl/styryl-3-(dimethylamino)-2-propen-1-ones, (E)-α- [(dimethylamino)formylidene]cycloalkanones, and (E)-2-(dimethylamino) formylidene-1,3-diketones in high yields under solvent-free conditions.
- Kumar, Dinesh,Kommi, Damodara N.,Chopra, Pradeep,Ansari, Md Imam,Chakraborti, Asit K.
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p. 6407 - 6413,7
(2020/09/16)
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- Synthesis and antitubercular evaluation of novel substituted aryl and thiophenyl tethered dihydro-6H-quinolin-5-ones
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A series of novel aryl and thiophenyl tethered dihydro-6H-quinolin-5-ones have been synthesized in very good yields through CeCl3· 7H2O-NaI catalyzed one-pot condensation of β-enaminones derived from the respective methyl ketones; 1,
- Kantevari, Srinivas,Patpi, Santhosh Reddy,Sridhar, Balasubramanian,Yogeeswari, Perumal,Sriram, Dharmarajan
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scheme or table
p. 1214 - 1217
(2011/04/16)
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- Synthesis and antibacterial activity of novel 5-(heteroaryl)isoxazole derivatives
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The synthesis, characterization and antibacterial activity of novel isoxazole derivatives were reported. 3-Di (alkylamino)acryloalkanones were prepared and used as synthons to get the target isoxazole derivatives via reaction with hydroxylamine hydrochloride or hydroxylamine-O-sulphonic acid.
- RamaRao, R. Janaki,Rao, A.K.S. Bhujanga,Sreenivas,Kumar, B. Suneel,Murthy
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experimental part
p. 243 - 250
(2011/06/26)
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