- Reactions of 2,4-Dinitrophenyl 5-substituted-2-thiophenecarboxylates with R2NH/R2NH2 + in 20 Mol % DMSO(aq). Effects of 5-Thienyl Substituent and Leaving Group on the Reaction Mechanism
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Reactions of 2,4-dinitrophenyl 2-thiophenecarboxylate (2a–d) with R2NH/R2NH2 + in 20 mol % DMSO(aq) have been studied. The reactions are overall second order, first order to the substrates, and first order to th
- Pyun, Sang Yong,Paik, Kyu Cheol,Han, Man So,Cho, Bong Rae
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- Design, synthesis and biochemical evaluation of novel carbonic anhydrase inhibitors triggered by structural knowledge on hCA VII
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To tackle the challenge of isoform selectivity, we explored the entrance of the cavity for selected druggable human Carbonic Anhydrases (hCAs). Based on X-ray crystallographic studies on the 4-(4-(2-chlorobenzoyl)piperazine-1-carbonyl)benzenesulfonamide in complex with the brain expressed hCA VII (PDB code: 7NC4), a series of 4-(4(hetero)aroylpiperazine-1-carbonyl)benzene-1-sulfonamides has been developed. To evaluate their capability to fit the hCA VII catalytic cavity, the newer benzenesulfonamides were preliminary investigated by means of docking simulations. Then, this series of thirteen benzenesulfonamides was synthesized and tested against selected druggable hCAs. Among them, the 4-(4-(furan-2-carbonyl)piperazine-1-carbonyl)benzenesulfonamide showed remarkable affinity towards hCA VII (Ki: 4.3 nM) and good selectivity over the physiologically widespread hCA I when compared to Topiramate (TPM).
- Mancuso, Francesca,Di Fiore, Anna,De Luca, Laura,Angeli, Andrea,De Simone, Giuseppina,Supuran, Claudiu T.,Gitto, Rosaria
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- Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer
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Poly (ADP-ribose) polymerase-1 (PARP-1) is a potential target for the discovery of chemosensitizers and anticancer drugs. Amentoflavone (AMF) is reported to be a selective PARP-1 inhibitor. Here, structural modifications and trimming of AMF have led to a series of AMF derivatives (9a-h) and apigenin-piperazine/piperidine hybrids (14a-p, 15a-p, 17a-h, and 19a-f), respectively. Among these compounds, 15l exhibited a potent PARP-1 inhibitory effect (IC50 = 14.7 nM) and possessed high selectivity to PARP-1 over PARP-2 (61.2-fold). Molecular dynamics simulation and the cellular thermal shift assay revealed that 15l directly bound to the PARP-1 structure. In in vitro and in vivo studies, 15l showed a potent chemotherapy sensitizing effect against A549 cells and a selective cytotoxic effect toward SK-OV-3 cells through PARP-1 inhibition. 15l·2HCl also displayed good ADME characteristics, pharmacokinetic parameters, and a desirable safety margin. These findings demonstrated that 15l·2HCl may serve as a lead compound for chemosensitizers and the (BRCA-1)-deficient cancer therapy.
- Long, Huan,Hu, Xiaolong,Wang, Baolin,Wang, Quan,Wang, Rong,Liu, Shumeng,Xiong, Fei,Jiang, Zhenzhou,Zhang, Xiao-Qi,Ye, Wen-Cai,Wang, Hao
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p. 12089 - 12108
(2021/09/06)
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- Design, synthesis, and biological evaluation of matrine derivatives possessing piperazine moiety as antitumor agents
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Using matrine (1) as the lead compound, a series of new piperazinyl matrine derivatives were designed, synthesized and evaluated for their antitumor activities in vitro and in vivo. Structure activity relationship (SAR) analysis indicated that introductio
- Xu, Yiming,Liang, Pengyun,Rashid, Haroon ur,Wu, Lichuan,Xie, Peng,Wang, Haodong,Zhang, Shuyan,Wang, Lisheng,Jiang, Jun
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p. 1618 - 1627
(2019/07/29)
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- Synthesis, characterization, and anti-inflammatory activities of methyl salicylate derivatives bearing piperazine moiety
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In this study, a new series of 16 methyl salicylate derivatives bearing a piperazine moiety were synthesized and characterized. The in vivo anti-inflammatory activities of target compounds were investigated against xylol-induced ear edema and carrageenan-induced paw edema in mice. The results showed that all synthesized compounds exhibited potent anti-inflammatory activities. Especially, the anti-inflammatory activities of compounds M15 and M16 were higher than that of aspirin and even equal to that of indomethacin at the same dose. In addition, the in vitro cytotoxicity activities and anti-inflammatory activities of four target compounds were performed in RAW264.7 macrophages, and compound M16 was found to significantly inhibit the release of lipopolysaccharide (LPS)-induced interleukin (IL)-6 and tumor necrosis factor (TNF)-α in a dose-dependent manner. In addition, compound M16 was found to attenuate LPS induced cyclooxygenase (COX)-2 up-regulation. The current preliminary study may provide information for the development of new and safe anti-inflammatory agents.
- Li, Jingfen,Yin, Yong,Wang, Lisheng,Liang, Pengyun,Li, Menghua,Liu, Xu,Wu, Lichuan,Yang, Hua
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- Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)- 2H-phthalazin-1-ones as potent PARP-1 inhibitors
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We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H- phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, which displayed an 8-fold improvement in enzymatic activity compared to AZD-2281. These efforts lay the foundation for our further investigation.
- Wang, Ling-Xiao,Zhou, Xin-Bo,Xiao, Meng-Liang,Jiang, Ning,Liu, Feng,Zhou, Wen-Xia,Wang, Xiao-Kui,Zheng, Zhi-Bing,Li, Song
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p. 3739 - 3743
(2014/09/17)
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- Reactions of 4-nitrophenyl 2-thiophenecarboxylates with R 2NH/R2NH2+ in 20 mol % DMSO (aq). Effects of 5-thienyl substituent and base strength
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Reactions of 4-nitrophenyl 2-thiophenecarboxylate (1a-e) with R 2NH/R2NH2+ in 20 mol % DMSO (aq) have been studied kinetically. The 2nd order kinetics, βnuc = 0.88-0.98, and linear Hammett and Yukawa-
- Pyun, Sang Yong,Cho, Bong Rae
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supporting information
p. 2036 - 2040
(2013/09/02)
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- Substituted phenoxypropyl-(R)-2-methylpyrrolidine aminomethyl ketones as histamine-3 receptor inverse agonists
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Optimization of a series of aminomethyl ketone diamine H3R antagonists to reduce the brain exposure by lowering the pKa, led to molecules with improved pharmacokinetic properties. Compounds 9, 19, and 25 had high affinity for human H3R and demonstrated in vivo H3R functional activity in the rat dipsogenia model. Compound 9 displayed modest wake-promoting activity in the rat EEG/EMG model.
- Zulli, Allison L.,Aimone, Lisa D.,Mathiasen, Joanne R.,Gruner, John A.,Raddatz, Rita,Bacon, Edward R.,Hudkins, Robert L.
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p. 2807 - 2810
(2012/05/20)
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- Efficient and continuous monoacylation with superior selectivity of symmetrical diamines in microreactors
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Efficient and continuous monoacylation of symmetrical diamines performed in microreactors yielded superior selectivity to that predicted by statistical considerations. It is highly valuable that the kinetically controlled product in high yields was achieved without any special catalyst at ambient temperature.
- Maurya, Ram Awatar,Hoang, Phan Huy,Kim, Dong-Pyo
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scheme or table
p. 65 - 68
(2012/03/26)
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- NOVEL 9-SUBSTITUTED-5-CARBOXY-OXADIAZINO-QUINOLONE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION AS ANTI-BACTERIALS
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A subject of the invention is the compounds of formula (I): wherein R1, R2, R3, R′3, R4, R′4, R5, R6 and R7 are as described in the application, in the form of enantiomers or mixtures, as well as their salts with acids and bases, their preparation and their application as anti-bacterials, in both human and veterinary medicine.
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Page/Page column 9
(2010/02/17)
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- Molecular features of the prazosin molecule required for activation of Transport-P
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Closely related structural analogues of prazosin have been synthesised and tested for inhibition and activation of Transport-P in order to identify the structural features of the prazosin molecule that appear to be necessary for activation of Transport-P. So far, all the compounds tested are less active than prazosin. It is shown that the structure of prazosin appears to be very specific for the activation. Only quinazolines have been found to activate, and the presence of the 6,7-dimethoxy and 4-amino groups appears to be critically important.
- da Silva, Joaquim Fernando Mendes,Walters, Marcus,Al-Damluji, Saad,Ganellin, C. Robin
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p. 7254 - 7263
(2008/12/23)
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- ISOTHIAZOLE DIOXIDES AS CXC- AND CC- CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of the formula (IA): and the pharmaceutically acceptable salts and solvates thereof. D and E are different groups wherein one is N and the other is CR50. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and cardiac reperfusion injury, pain (e.g., acute pain, acute and chronic inflammatory pain, and neuropathic pain) using a compound of formula IA.
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Page/Page column 249-250
(2010/02/13)
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- INHIBITORS OF MACROPHAGE MIGRATION INHIBITORY FACTOR AND METHODS FOR IDENTIFYING THE SAME
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Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures (Ia), (Ib) including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R1, R2, R3, R4, X, and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.
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- THIADIAZOLEDIOXIDES AND THIADIAZOLEOXIDES AS CXC- AND CC-CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of the formula (IA) and the pharmaceutically acceptable salts and solvates thereof. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and cardiac reperfusion injury, acute pain, acute and chronic inflammatory pain, and neuropathic pain using a compound of formula (IA).
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Page 286-287
(2008/06/13)
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- 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
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There are disclosed compounds of the formula or a pharmaceutically acceptable salt or solvate thereof which are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.
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Page 156; 157
(2008/06/13)
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- 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
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There are disclosed compounds of the formula or a pharmaceutically acceptable salt or solvate thereof which are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.
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- Direct synthesis of N-acylalkylenediamines from carboxylic acids under mild conditions
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Monoacylated piperazine derivatives were prepared directly from carboxylic acids and piperazine using triphenylphosphine (TPP) and N-bromosuccinimide (NBS) in dichloromethane. Inexpensive and readily available reagents, excellent yields, short reaction times and mild reaction conditions are important features of this method.
- Bandgar,Bettigeri
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p. 2917 - 2924
(2007/10/03)
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- Inhibitors of macrophage migration inhibitory factor and methods for identifying the same
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Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R1, R2, R3, R4, X, Y and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.
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- Solvent-free synthesis of amides from non-enolizable esters and amines using microwave irradiation
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An efficient solid state synthesis of amides is described from non- enolizable esters and amines using potassium tert-butoxide under microwave irradiation conditions.
- Varma, Rajender S.,Naicker, Kannan P.
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p. 6177 - 6180
(2007/10/03)
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- HMDS-promoted in situ amidation reactions of carboxylic acids and amines
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A number of N-acylalkylenediamines were synthesized in high yields by in situ monoamidation of carboxylic acids with diamines. The amidation reactions were carried out simply by heating the substrates at 110 °C for 5-24 h in the presence of HMDS.
- Chou, Wen-Chih,Chou, Ming-Chen,Lu, Yann-Yu,Chen, Shyh-Fong
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p. 3419 - 3422
(2007/10/03)
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