29568-78-3Relevant academic research and scientific papers
Phosphine Sequentially Catalyzed Domino 1,6-Addition/Annulation: Access to Functionalized Chromans and Tetrahydroquinolines with an Ethynyl-Substituted All-Carbon Quaternary Center
Zhu, Yannan,Wang, Dan,Huang, You
, p. 908 - 912 (2019)
A novel phosphine sequentially catalyzed domino 1, 6-addition/annulation process has been developed using p-quinone methides (p-QMs) and α-substituted allenoates which generates a series of chroman and tetrahydroquinoline derivatives containing an ethynyl-substituted all-carbon quaternary center with up to 97% yield and 20:1 dr. value. In this reaction, allenoates act as C2 synthons.
Anthranilamide-based 2-phenylcyclopropane-1-carboxamides, 1,1'-biphenyl-4-carboxamides and 1,1'-biphenyl-2-carboxamides: Synthesis biological evaluation and mechanism of action
Raffa, Demetrio,Plescia, Fabiana,Maggio, Benedetta,Raimondi, Maria Valeria,D'Anneo, Antonella,Lauricella, Marianna,Daidone, Giuseppe
, p. 262 - 273 (2017/04/03)
Several anthranilamide-based 2-phenylcyclopropane-1-carboxamides 13a-f, 1,1’-biphenyl-4-carboxamides 14a-f and 1,1’-biphenyl-2-carboxamides 17a-f were obtained by a multistep procedure starting from the (1S,2S)-2-phenylcyclopropane-1-carbonyl chloride 11, the 1,1'-biphenyl-4-carbonyl chloride 12 or the 1,1'-biphenyl-2-carbonyl chloride 16 with the appropriate anthranilamide derivative 10a-f. Derivatives 13a-f, 14a-f and 17a-f showed antiproliferative activity against human leukemia K562?cells. Among these derivatives 13b, 14b and 17b exerted a particular cytotoxic effect on tumor cells. Derivative 17b showed a better antitumoral effect on K562?cells than 13b and 14b. Analyses performed to explore 17b mode of action revealed that it induced an arrest in G2/M phase of cell cycle which was consequent to DNA lesions as demonstrated by the increase in phospho-ATM and γH2AX, two known markers of DNA repair response system. The effect of 17b was also related to ROS generation, activation of JNK and induction of caspase-3 dependent apoptosis.
Copper-Catalyzed One-pot Synthesis of Pyrimidines from Amides, N,N′-dimethylformamide dimethylacetal, and Enamines
Jalani, Hitesh B.,Cai, Wangshui,Lu, Hongjian
supporting information, p. 2509 - 2513 (2017/07/22)
A versatile copper catalyzed one-pot synthesis of diversely substituted pyrimidines directly from amides, N,N′-dimethylformamide dimethylacetal (DMF?DMA) and enamines has been established. The reaction involved the two C?N bonds and one C?C bond formation by formal [2+1+3] annulation approach to pyrimidines. This protocol is based on the use of readily available primary amides, DMF?DMA and enamines to install di- and tri-substituted pyrimidine structure with diverse functionality in one-pot manner, which makes this strategy to be appealing for the medicinal chemistry. (Figure presented.).
6,7-dimethoxyquinazolines as potential cytotoxic agents: Synthesis and in vitro activity
Yadav, Mange Ram,Chauhan, Bishram Singh,Naik, Prashant,Gandhi, Hardik,Giridhar, Rajani
, p. 190 - 205 (2015/04/14)
It has been reported that 6,7-dimethoxyquinazoline derivatives have cytotoxic potential independent of their a1-adrenoceptor blocking potential. Bioisosteres of 2-arylquinazolines are considered to have anti-tumor properties. In the present study, we have synthesized the 2-aryl and 2-arylmethyl derivatives of quinazolin-4(3H)-one while retaining the 6,7-dimethoxy substituents. Derivatives with n-butyl group attached to position-3 of quinazolinone nucleus were synthesized with the aim of increasing their lipophilicity. The potential of these synthesized compounds was evaluated against NCI (National Cancer Institute) 60 cell panel using the NCI disease oriented antitumor screen protocol. Based on the results of this screening we generalized that compounds having aryl groups directly attached to the quinazoline ring are less active than those which have one atom linker in between the two ring systems. Substitution of a lipophilic group like nbutyl decreases cytotoxic activity among the compounds and 4-aminoquinazolines showed better activity than 4-quinazolinones. Lipophilic groups in the aromatic ring yielded more active compounds as cytotoxic agents. Among the selected compounds, 4h and 13b were found to be potential lead compounds which could be further optimized as potential anti-neoplastic agents.
Reversal of P-gp and BCRP-mediated MDR by tariquidar derivatives
Li, Xu-Qin,Wang, Lin,Lei, Yan,Hu, Tao,Zhang, Fei-Long,Cho, Chi-Hin,To, Kenneth K.W.
, p. 560 - 572 (2015/07/28)
Abstract With an aim to generate non-toxic, specific and highly potent multidrug resistance (MDR) modulators, a novel series of anthranilic acid amide-substituted tariquidar derivatives were synthesized. The new compounds were evaluated for their cytotoxicity toward normal human colon fibroblasts (CCD18-Co), human gastric epithelial cell line (HFE) and primary rat liver cells, and for their ability to inhibit P-gp/BCRP-mediated drug efflux and reversal of P-gp and BCRP-mediated MDR in parental and drug-resistant cancer cell lines (LCC6 MDR1, MCF-7 FLV1000, R-HepG2, SW620-Ad300). While tariquidar is highly toxic to normal cells, the new derivatives exhibited much lower or negligible cytotoxicity. Some of the new tariquidar derivatives inhibited both P-gp and BCRP-mediated drug efflux whereas a few of them bearing a sulfonamide functional group (1, 5, and 16) are specific to P-gp. The new compounds were also found to potentiate the anticancer activity of the transporter substrate anticancer drugs in the corresponding transporter-overexpressing cell lines. The extent of resistance reversal was found to be consistent with the transporter inhibitory effect of the new derivatives. To further understand the mechanism of P-gp and BCRP inhibition, the tariquidar derivatives were found to interact with the transporters using an antibody-based UIC2 or 5D3 shift assay. Moreover, the transporters-inhibiting derivatives were found to modulate the ATPase activities of the two MDR transporters. Our data thus advocate further development of the new compounds for the circumvention of MDR.
Synthesis, antiproliferative activity and possible mechanism of action of novel 2-acetamidobenzamides bearing the 2-phenoxy functionality
Raffa, Demetrio,Maggio, Benedetta,Plescia, Fabiana,Cascioferro, Stella,Raimondi, Maria Valeria,Cancemi, Gabriella,D'Anneo, Antonella,Lauricella, Marianna,Cusimano, Maria Grazia,Bai, Ruoli,Hamel, Ernest,Daidone, Giuseppe
, p. 6305 - 6316 (2015/10/05)
Several new 2-(2-phenoxyacetamido)benzamides 17a-v, 21 and 22 were synthesized by stirring in pyridine the acid chlorides 16a-e and the appropriate5-R-4-R1-2-aminobenzamide 15a-e and initially evaluated in vitro for antiproliferative activity against the K562 (human chronic myelogenous leukemia) cell line. Some of synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). The most active compounds caused an arrest of K562 cells in the G0-G1 phase of cell cycle and induction of apoptosis, which was mediated by caspase activation.
PYRROLOBENZODIAZEPINE COMPOUNDS
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Page/Page column 65-70; 73, (2015/11/24)
The invention relates to pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) of formula (I) and in particular to PBD dimers linked through the C1 position, and PBD monomers linked through the C1 position to aromatic groups, and pharmaceutically acceptable salts the
Synthesis of novel piperazine-linked anthranilic acids as potential small molecule kinase inhibitors
Chakravorty, Santanu,Klein, Hanna F.,Hodson, Luke E.,Rabillier, Matthias,Fang, Zhizhou,Richters, Andre,Pelly, Stephen C.,Rauh, Daniel,Van Otterlo, Willem A.L.
, p. 71 - 79 (2014/06/09)
Substituted anthranilic acid and piperazines were used as building blocks to prepare two libraries of compounds, with the aim being that they would exhibit biochemical activity as small molecule kinase inhibitors. The synthesized anthranilamidepiperazine
Synthesis and Quantitative Structure-Activity Relationships of Selective BCRP Inhibitors
Marighetti, Federico,Steggemann, Kerstin,Hanl, Markus,Wiese, Michael
, p. 125 - 135 (2013/02/26)
The breast cancer resistance protein (BCRP/ABCG2) is a member of the ABC transporter superfamily. This protein has a number of physiological functions, including protection of the human body from xenobiotics. The overexpression of BCRP in certain tumor cell lines causes cross-resistance against various drugs used in chemotherapeutic treatment. In a previous work we showed that a new class of compounds derived from XR9576 (tariquidar) selectively inhibits BCRP. In this work we synthesized more members of this class, with modification on the second and third aromatic rings. The inhibitory activities against BCRP and P-gp were assayed using a Hoechst 33342 assay for BCRP and a calcein AM assay for P-gp. Finally, quantitative structure-activity relationships for both aromatic rings were established. The results obtained show the importance of the electron density on the third aromatic ring, influenced by substituents, pointing to interactions with aromatic residues of the protein binding site. In the second aromatic ring the activity of compounds is influenced by the steric volume of the substituents.
2-Cinnamamido, 2-(3-phenylpropiolamido), and 2-(3-phenylpropanamido) benzamides: Synthesis, antiproliferativeactivity, and mechanism of action
Raffa, Demetrio,Maggio, Benedetta,Raimondi, Maria Valeria,Cusimano, Maria Grazia,Amico, Giandomenico,Carollo, Anna,Conaldi, Pier Giulio,Bai, Ruoli,Hamel, Ernest,Daidone, Giuseppe
, p. 427 - 435 (2013/10/01)
Several new benzamides 4a-q were synthesized by stirring in pyridine the acid chlorides 3a-q with the appropriate anthranilamide derivatives 2a-g. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against a panel of 5 human cell lines (K562 human chronic myelogenous leukemia cells, MCF-7 breast cancer cells, HTC-116 and HT26 colon cancer cells and NCI H460 non-small cell lung cancer cells).
