- Ditertiary phosphines bearing a –N–C–C(O)–N(H)– linker and their corresponding dichloroplatinum(II) complexes
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The preparation of a small library of new –N–C–C(O)–N(H)– modified ditertiary phosphines is reported along with their square-planar dichloroplatinum(II) complexes. All compounds were characterized by 31P{1H} and 1H NMR spectroscopy, FT–IR spectroscopy and elemental analysis. The single crystal X-ray structures of four PtII complexes have been determined. Intra- (N–H···N) and intermolecular (N–H···N) hydrogen bonding is principally observed.
- Elsegood, Mark R. J.,Lake, Andrew J.,Smith, Martin B.,Weaver, George W.
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Read Online
- Design, synthesis and biological evaluation of novel o-aminobenzamide derivatives as potential anti-gastric cancer agents in vitro and in vivo
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Although gastric cancer has become a major public health problem, oral agents applied in clinics for gastric cancer therapy are scarce. Therefore, to explore new oral chemical entities with high efficiency and low toxicity, 41 o-aminobenzamide derivatives based on the scaffolds of MS-275 and SAHA were designed, synthesized, and evaluated for their anti-gastric cancer abilities in vitro and in vivo. Structure-activity relationships were discussed, leading to the identification of compounds F8 (IC50 = 0.28 μM against HGC-27 cell) and T9 (IC50 = 1.84 μM against HGC-27 cell) with improved cytotoxicity, anti-gastric cancer proliferation potency, induction of cell apoptosis and cell cycle arrest ability, inhibition of cell migration and invasion. What is worth mentioning is that compound F8 was more efficient and less toxic than the positive drug capecitabine in vivo on the HGC-27-xenograft model. Meanwhile, compound F8 exhibited suitable pharmacokinetic properties and less acute toxicity (LD50 > 1000 mg/kg). Besides, western blotting analysis, IHC analysis, differentially expressed proteins analysis and ABPP experiment indicated that compound F8 could modulate molecular pathways involved in apoptosis and cell cycle progression. Consequently, compound F8 is a strong candidate for the development of human gastric cancer therapy.
- Deng, Xuemei,Feng, Hanzhong,Feng, Yiyue,He, Yongxing,Jiang, Weifan,Li, Junfang,Li, Zhao,Liu, Dan,Lu, Yingmei,Shi, Tao,Wang, Zhen,Zhang, Honghua,Zhang, Jian
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- Vorinostat skeleton-based anthranilamide compound as well as preparation and application thereof
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The invention provides a vorinostat skeleton-based anthranilamide compound as well as preparation and application of the anthranilamide compound. The structural formula of the o-aminobenzamide compound based on a vorinostat skeleton is shown in the specification, wherein n is equal to 1-6, and R is methylamino, dimethylamino, hydroxyl, NH2 or the like. The anthranilamide compound based on the vorinostat skeleton has the effect of inhibiting gastric cancer cell proliferation through MTT method determination, and can be used for preparing anti-gastric cancer drugs.
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Paragraph 0025; 0027
(2021/08/06)
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- New isoleucine derived dipeptides as antiprotozoal agent: Synthesis, in silico and in vivo studies.
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The increasing emergence of malaria drug-resistant parasites and the deficiency in effective chemotherapy for trypanosomiasis represents a huge challenge in infectious disease treatment in tropical regions. As regards to developing effective antiprotozoal agents, ten new ile-gly dipeptide sulphonamide derivatives were synthesized by condensing compound (10) with (8a-j)using peptide coupling reagents. Compounds11b, 11i and 11j were most potent in clearing Trypanosome brucei in mice with 11b showing comparable activity with diminazene aceturate. In the antimalarial study, 11b was the most active compound, even better than the standard. Molecular docking result suggests good interaction between the reported compounds and the target protein. The results of haematological analysis, liver and kidney function tests showed that the compounds had no adverse effect on the blood and organs. Compound 11b stands out amongst the derivatives haven shown better activity in both the antimalarial and antitrypanosomal assay.
- Ekoh, Ogechi C.,Okoro, Uchechukwu C.,Ali, Rafat,Ugwu, David I.,Okafor, Sunday N.,Ezugwu, James A.
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- New glycine derived peptides bearing benzenesulphonamide as an antiplasmodial agent
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In the tropics, malaria is among the most serious infectious diseases in developing countries. The discovery of the artemesinin antimalarial drug not too long ago was a major breakthrough in the effort to combat the malaria disease. However, recent reports of resistance even to combination therapy involving artemisinin are very worrisome and have led to the search for new chemical agents to sustain the fight against malaria. The carboxamide functionality has been shown to be an important pharmacophore in over 25% of commercial chemotherapeutic agents. Three benzensulphonamides (3a-c) were prepared from the reaction of the appropriate benzensulphonyl chloride (1a-c) and alanine (2) in aqueous basic medium. Eight tert-butylamino-oxo-ethylcarbamates (5a-h) were also prepared from reacting commercially available boc-glycine (4) and different amines using peptide coupling reagents such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBt), with triethyl amine and dichloromethane (DCM) as solvents. The target compounds were prepared by reacting compounds 3a-c with compounds 5a-h in the presence of coupling reagents to get twenty four (24) different compounds. The compounds were characterized and evaluated for their antiplasmodial activity. Computed molecular descriptors and assessed biochemical parameters showed that the compounds were drug-like and safe. All the compounds had favourable binding interactions with residues at the PABA binding site of homologically modeled P. falciparum dihydropteroate synthase and henceforward the in vitro and in vivo antiplasmodial activities were evaluated. Compounds 7a-7x showed activity against P. falciparum (W2 strain) at MIC values ranging from 3.52 to 0.09 μM. Moreover, seven of the compounds (7c, 7d, 7i, 7j, 7p, 7r and 7s) showed better activity than quinine (MIC = 0.72 μM). In addition, 16 of the 24 compounds were found to clear more than 50 percent of P. berghei (NK-65 strain) from the blood of infected mice at 12 days post-infection. The percentages of parasites cleared by 20 mg kg-1 of the three most effective compounds (7g, 7n and 7r) were 74.98, 74.98 and 74.07, respectively. In conclusion, 7r (MIC 0.71 μM) from this class of glycine derived sulfonamides has the ability to clear 74.07% of P. berghei from blood of infected mice at 20 mg kg-1 and an interesting pharmacokinetic profile (MW = 430.31 Da, HBA = 7, HBD = 3, log?P = 2.56, NRB = 9 and TPSA = 104.37 ?2), which is in agreement with the Lipinski rule of 5 for a compound to be qualified as a drug candidate. 7r could serve as a lead in developing new antiplasmodial agents. This journal is
- Ugwuja, Daniel Izuchukwu,Okoro, Uchechukwu,Soman, Shubhanji,Ibezim, Akachukwu,Ugwu, David,Soni, Rina,Obi, Bonaventure,Ezugwu, James,Ekoh, Ogechi
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p. 3660 - 3674
(2021/03/03)
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- Synthesis, molecular docking and antimalarial activity of phenylalanine-glycine dipeptide bearing sulphonamide moiety
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Ten novel phenylalanine-glycine dipeptide sulphonamide conjugate were synthesized and characterized using 1HNMR, 13CNMR, FTIR and HRMS spectroscopic techniques. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with standard drugs. The in vivo antimalarial study, hematological study, liver and kidney function test were evaluated on the synthesized compounds. Compounds 7h, 7i and 7j inhibited the parasite by 34.5–60.2% on day 4 of after-treatment exposure. Compound 7j inhibited the multiplication of the parasite by 60.2% on day 4 of after-treatment which was comparable with that of the standard drug with 68.8% inhibition at same day of after-treatment exposure.
- Ali, Rafat.,Aronimo, Babatunde. S.,Ezugwu, James. A.,Ibeji, Collins. U.,Okoro, Uchechukwu. C.,Ugwu, David. I.
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- Glycinamide hydrochloride as a transient directing group: Synthesis of 2-benzylbenzaldehydes by C(sp3)?H arylation
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Glycinamide hydrochloride as an inexpensive and commercially available transient directing group for the C(sp3)?H arylation of 2-methylbenzaldehydes is described. A series of practical 2-benzylbenzaldehydes bearing various functional groups are efficiently synthesized in satisfactory yield by this strategy. This method can also be extended to gram scale.
- Wen, Fei,Li, Zheng
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supporting information
p. 3462 - 3474
(2020/08/10)
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- Design, synthesis and biological evaluation of novel naturally-inspired multifunctional molecules for the management of Alzheimer's disease
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In our overall goal to overcome the limitations associated with natural products for the management of Alzheimer's disease and to develop in-vivo active multifunctional cholinergic inhibitors, we embarked on the development of ferulic acid analogs. A systematic SAR study to improve upon the cholinesterase inhibition of ferulic acid with analogs that also had lower logP was carried out. Enzyme inhibition and kinetic studies identified compound 7a as a lead molecule with preferential acetylcholinesterase inhibition (AChE IC50 = 5.74 ± 0.13 μM; BChE IC50 = 14.05 ± 0.10 μM) compared to the parent molecule ferulic acid (% inhibition of AChE and BChE at 20 μM, 15.19 ± 0.59 and 19.73 ± 0.91, respectively). Molecular docking and dynamics studies revealed that 7a fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Asp74, Trp286, and Tyr337 in AChE and with Tyr128, Trp231, Leu286, Ala328, Phe329, and Tyr341 in BChE. Compound 7a was found to be an efficacious antioxidant in a DPPH assay (IC50 = 57.35 ± 0.27 μM), and it also was able to chelate iron. Data from atomic force microscopy images demonstrated that 7a was able to modulate aggregation of amyloid β1-42. Upon oral administration, 7a exhibited promising in-vivo activity in the scopolamine-induced AD animal model and was able to improve spatial memory in cognitive deficit mice in the Y-maze model. Analog 7a could effectively reverse the increased levels of AChE and BChE in scopolamine-treated animals and exhibited potent ex-vivo antioxidant properties. These findings suggest that 7a can act as a lead molecule for the development of naturally-inspired multifunctional molecules for the management of Alzheimer's and other neurodegenerative disorders.
- Chittiboyina, Amar G.,Doerksen, Robert J.,Modi, Gyan,Nayak, Prasanta Kumar,Pandey, Amruta,Pandey, Pankaj,Priya, Khushbu,Rai, Geeta,Shankar, Gauri,Singh, Yash Pal,Tej, Gullanki Naga Venkata Charan,Vishwakarma, Swati
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- Amido pyrimidine compound
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The invention provides an amido pyrimidine compound with a novel structure as shown in a formula (I) and a preparation method and application of the amido pyrimidine compound. The amido pyrimidine compound is a compound shown as the formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof and the like. The amido pyrimidine compound provided bythe invention has a relatively good proliferation inhibition effect on various cancer cells; according to the present invention, the compound has characteristics of low tumor cell inhibition concentration, significantly-improved compound activity, good tumor cell selectivity and good solubility, and is expected to be a specific drug for treatment of malignant tumor cell abnormal proliferation diseases caused by EGFR mutation.
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Paragraph 0152-0154
(2020/06/20)
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- Design, synthesis and preliminary bioactivity evaluations of 8-hydroxyquinoline derivatives as matrix metalloproteinase (MMP) inhibitors
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Matrix metalloproteinases (MMPs) play important roles in many diseases including cancer. With moderate metal-binding affinity, 8-hydroxyquinoline has gained much interest in current drug design and development. Specially, it has been reported that 8-hydroxyquinoline derivatives serve as MMP-2 inhibitors with micromolar IC50 values. In the current study, a series of 8-hydroxyquinoline derivatives were designed and synthesized as new MMP-2 and MMP-9 inhibitors. The most active compounds 5e and 5h not only displayed good inhibitory activities against MMP-2/9 with IC50 at submicromolar level, but also possessed potent anti-proliferative, anti-invasive and anti-angiogenesis activity in A549 cell line. Western blot also revealed that 5e and 5h down-regulate the expression of MMP-2 and MMP-9 in A549 cell line. Moreover, flow cytometry analysis indicated that compound 5e could promote apoptosis of A549 cells in vitro. Molecular docking analysis also revealed favorable binding modes of 5e in the active sites of MMP-2 and MMP-9.
- Chen, Chen,Yang, Xinying,Fang, Hao,Hou
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- New peptide derived antimalaria and antimicrobial agents bearing sulphonamide moiety
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Fourteen novel dipeptide carboxamide derivatives bearing benzensulphonamoyl propanamide were synthesized and characterized using 1H NMR, 13C NMR, FTIR and MS spectroscopic techniques. In vivo antimalarial and in vitro antimicrobial studies were carried out on these synthesized compounds. Molecular docking, haematological analysis, liver and kidney function tests were also evaluated to assess the effect of the compounds on the organs. At 200 mg/kg body weight, 7i inhibited the multiplication of the parasite by 81.38% on day 12 of post-treatment exposure. This was comparable to the 82.34% reduction with artemisinin. The minimum inhibitory concentration (MIC) in μM ranged from 0.03 to 2.34 with 7h having MIC of 0.03 μM against Plasmodium falciparium. The in vitro antibacterial activity of the compounds against some clinically isolated bacteria strains showed varied activities with some of the new compounds showing better activities against the bacteria and the fungi more than the reference drug ciprofloxacin and fluconazole.
- Ugwuja,Okoro,Soman,Soni,Okafor,Ugwu
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p. 1388 - 1399
(2019/08/22)
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- A novel C3v-symmetric molecular clip with tris(diamide) recognition sites on trindane platform for H2PO4? recognition
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To avoid the deprotonation events occurred in the receptor upon recognition of basic anions, a novel C3v-symmetric anion receptor 2 with two amide groups appended in each arm was designed and synthesized by using the trindane tricarboxylic acid as tripodal molecular framework. The anion recognition ability by 2 was examined by 1H NMR titration study in DMSO-d6, which revealed that the addition of H2PO4? guests caused substantial downfield shifts of the amide-NH protons peaks due to the formation of a host-guest complex in 1:1 binding stoichiometry with the estimated binding constant (Ka) of 244 M?1. No noticeable binding of 2 was observed with other tested anions such as F?, Cl?, Br?, I?, NO3? and HSO4? under similar conditions.
- Kim, Gi-Dong,Bothra, Shilpa,Sahoo, Suban K.,Choi, Heung-Jin
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supporting information
p. 1679 - 1682
(2018/03/29)
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- Substituted carboxamide analogues as a new class of local anesthetic agents: Synthesis and bio-evaluation
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A series of N-(2-oxo-2-(phenylamino) ethyl) substituted-4-carboxamide derivatives were synthesized as local anesthetic agents. The structures of carboxamide derivatives were established on the basis of IR, and1H spectral data. All the compounds were subjected to surface local anesthetic activity assay and infiltration local anesthetic activity assay. Among the tested compounds, N-(2-oxo-2-(p-tolylamino) ethyl) piperidine-1-carboxamide (4h) and N-(2-((4-methoxyphenyl) amino)-2-oxoethyl) piperidine-1-carboxamide (4m) were most promising compounds in terms of surface local anaesthetic and infiltration local anaesthetic activity on rats having considerably lower liver toxicity.
- Al-Otaibi, Faisal
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p. 649 - 658
(2018/08/03)
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- COMPOUNDS WHICH HAVE A PROTECTIVE ACTIVITY WITH RESPECT TO THE ACTION OF TOXINS AND OF VIRUSES WITH AN INTRACELLULAR MODE OF ACTION
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The subject matter of the present invention is novel families of compounds which are aromatic amine, imine, aminoadamantane and benzodiazepine derivatives, medicaments comprising same and the use thereof as inhibitors of the toxic effects of toxins with intracellular activity, such as, for example, ricin, and of viruses that use the internalization pathway for infecting cells.
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Paragraph 0335
(2016/04/19)
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- Synthesis of 3-Amino-2-carboxamide Tetrahydropyrrolo[2,3- b ]quinolines
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This article communicates the first synthesis of 3-amino-2-carboxamide pyrrolo[2,3-b]quinolines and fused-ring pyrrolopyridines in an efficient synthesis via a Thorpe-Ziegler transformation. The reported synthetic route allows for a wide range of nitrogen analogues of thienopyridines - compounds which have potent bioactivities but poor aqueous solubility.
- Pilkington, Lisa I.,Haverkate, Natalie A.,Van Rensburg, Michelle,Reynisson, Johannes,Leung, Euphemia,Barker, David
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supporting information
p. 2811 - 2814
(2016/12/16)
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- High-throughput evaluation system based on fluorescence intensity distribution analysis-polarization to investigate carbohydratecarbohydrate interactions
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We synthesized rhodamine-labeled β-lactoside and assessed its rotatory diffusion rates in aqueous media containing various oligosaccharides through fluorescence intensity distribution analysis-polarization measurements to find that its rotatory diffusion rates decrease in the presence of the coexisting oligosaccharides. Especially, the coexisting lactose lowered the rotatory diffusion rate more effectively than the other disaccharides did. This restrained rotatory diffusion arises from intermolecular carbohydratecarbohydrate interactions between the rhodaminelabeled β-lactoside and the coexisting lactose. We also detected intermolecular bindings between the rhodamine-labeled β-lactoside and monosialyl-disaccharides (3′- and 6′-sialyllactoses). These data clearly show that the fluorescence intensity distribution analysis-polarization-based system is quite advantageous to probe carbohydratecarbohydrate interactions.
- Iwamura, Maho,Koyama, Ryoichi,Nonaka, Yuki,Dai, Fumiko,Matsuoka, Ryoji,Nakamura, Masaki,Iwabuchi, Haruo,Okada, Takahiro,Hasegawa, Teruaki
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p. 617 - 625
(2016/06/01)
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- Templated C-C and C-N Bond Formation Facilitated by a Molybdenum(VI) Metal Center
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Preparation of molybdenum dioxido complexes with novel iminophenolate ligands bearing pendant secondary amide functionalities led to unprecedented C-C and C-N coupling reactions of two α-iminoamides upon coordination. The diastereoselective cyclization to asymmetric imidazolidines occurs at the metal center in two consecutive steps via a monocoupled intermediate. A meaningful mechanism is proposed on the basis of full characterization of intermediate and final molybdenum-containing products by spectroscopic means and by single-crystal X-ray diffraction analyses. This process constitutes the first example of a diastereoselective self-cyclization of two α-iminoamides.
- Zwettler, Niklas,Dupé, Antoine,Schachner, J?rg A.,Belaj, Ferdinand,M?sch-Zanetti, Nadia C.
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p. 11969 - 11976
(2015/12/30)
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- Synthesis and anticonvulsant activity of some N-(benzoyl)glycinanilide derivatives
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Glycine is a major inhibitory neurotransmitter and recent studies have shown that certain lipophilic glycine derivatives demonstrate anticonvulsant activity in animal epilepsy models. On the other hand, anilide is another fruitful structure for designing potential anticonvulsant agents. Ameltolide, ralitoline and some phthalimide derivatives are the examples of anilide analogs with potent anticonvulsant activity. In this study, two key structural pharmacophores were combined and a series of N-benzoylglycinanilide derivatives were designed. Their anticonvulsant activities evaluated against maximal electroshock (MES) and subcutaneous metrazole seizure tests, whereas their neurotoxicity was examined by rotarod test. The preliminary screening results indicated that majority of the compounds were effective in the MES test. None of the compounds showed neurotoxicity according to the rotarod test at studied doses. The most active compound in the series is N-(2-((4-methoxyphenyl)amino)- 2-oxoethyl)benzamide (compound 8) which bearing 4-methoxy substituent on the N-phenyl ring.
- Soyer, Zeynep,Akgul, Ozlem,Tarikogullari, Ayse H.,Calis, Unsal
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p. 4708 - 4714
(2013/09/23)
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- Flavone-based analogues inspired by the natural product simocyclinone D8 as DNA gyrase inhibitors
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The increasing occurrence of drug-resistant bacterial infections in the clinic has created a need for new antibacterial agents. Natural products have historically been a rich source of both antibiotics and lead compounds for new antibacterial agents. The natural product simocyclinone D8 (SD8) has been reported to inhibit DNA gyrase, a validated antibacterial drug target, by a unique catalytic inhibition mechanism of action. In this work, we have prepared simplified flavone-based analogues inspired by the complex natural product and evaluated their inhibitory activity and mechanism of action. While two of these compounds do inhibit DNA gyrase, they do so by a different mechanism of action than SD8, namely DNA intercalation.
- Verghese, Jenson,Nguyen, Thuy,Oppegard, Lisa M.,Seivert, Lauren M.,Hiasa, Hiroshi,Ellis, Keith C.
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supporting information
p. 5874 - 5877
(2013/10/22)
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- CATALYST FOR ASYMMETRIC HYDROGENATION AND METHOD FOR MANUFACTURING OPTICALLY ACTIVE CARBONYL COMPOUND USING THE SAME
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The present invention provides a catalyst used for manufacturing an optically active carbonyl compound by selective asymmetric hydrogenation of an α,β-unsaturated carbonyl compound, which is insoluble in a reaction mixture, and a method for manufacturing the corresponding optically active carbonyl compound. Particularly, the invention provides a catalyst for obtaining an optically active citronellal useful as a flavor or fragrance, by selective asymmetric hydrogenation of citral, geranial or neral. The invention relates to a catalyst for asymmetric hydrogenation of an α,β-unsaturated carbonyl compound, which comprises: a powder of at least one metal selected from metals belonging to Group 8 to Group 10 of the Periodic Table, or a metal-supported substance in which the at least one metal is supported on a support; an optically active peptide compound; and an acid, and also relates to a method for manufacturing an optically active carbonyl compound using the same.
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Page/Page column 11-12; 23
(2012/06/16)
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- Active site mapping of trypsin, thrombin and matriptase-2 by sulfamoyl benzamidines
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The benzamidine moiety, a well-known arginine mimetic, has been introduced in a variety of ligands, including peptidomimetic inhibitors of trypsin-like serine proteases. According to their primary substrate specificity, the benzamidine residue interacts with the negatively charged aspartate at the bottom of the S1 pocket of such enzymes. Six series of benzamidine derivatives (1-73) were synthesized and evaluated as inhibitors of two prototype serine proteases, that is, bovine trypsin and human thrombin. As a further target, human matriptase-2, a recently discovered type II transmembrane serine protease, was investigated. Matriptase-2 represents an important regulatory protease in iron homeostasis by down-regulation of the hepcidin expression. Compounds 1-73 were designed to contain a fixed sulfamoyl benzamidine moiety as arginine mimetic and a linker-connected additional substructure, such as a tert-butyl ester, carboxylate or second benzamidine functionality. A systematic mapping approach was performed with these inhibitors to scan the active site of the three target proteases. In particular, bisbenzamidines, able to interact with both the S1 and S3/S4 binding sites, showed notable affinity. In branched bisbenzamidines 66-73 containing a third hydrophobic residue, opposite effects of the stereochemistry on trypsin and thrombin inhibition were observed.
- Dosa, Stefan,Stirnberg, Marit,Luelsdorff, Verena,Haeussler, Daniela,Maurer, Eva,Guetschow, Michael
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supporting information
p. 6489 - 6505,17
(2012/12/11)
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- A ratiometric and exclusively selective CuII fluorescent probe based on internal charge transfer (ICT)
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A new ratiometric and exclusively selective fluorescent probe N-butyl-4,5-di[N-(phenyl)-2-(amino)-acetamino]-1,8-naphthalimide (1) was designed and synthesized on the basis of the mechanism of internal charge transfer (ICT). The probe 1 showed exclusively selectivity for CuII in the presence of a variety of other metal ions in aqueous ethanol solutions and the binding mode of probe 1 with CuII was 1:1 metal-ligand complex. Fluorescent emission spectra of probe 1 in the presence of Cu II showed a 50 nm blue shift, which is from 521 nm to 471 nm. Furthermore, probe 1 shows the same fluorescent change with the CuII in living cells.
- Chen, Xiufu,Wang, Jingyun,Cui, Jingnan,Xu, Zhaochao,Peng, Xiaojun
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experimental part
p. 4869 - 4873
(2011/08/03)
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- COMPOUNDS FOR TREATING CANCER
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Compounds of general formula (I): wherein R1, R2, R3, R4, R5, R6, X and Y are as defined herein are inhibitors of Bcl-2 and are useful for treating diseases characterised by abnormal cell growth and/or dysregulated apoptosis.
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Page/Page column 54
(2010/07/02)
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- Oxadiazole-carbonylaminothioureas as SIRT1 and SIRT2 inhibitors
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A new inhibitor for human sirtuin type proteins 1 and 2 (SIRT1 and SIRT2) was discovered through virtual database screening in search of new scaffolds. A series of compounds was synthesized based on the hit compound (3-[[3-(4-tert-butylphenyl)1,2,4-oxadiazole-5-carbonyl]ammo]-1-[3- (trifluoromethyl)phenyl]thiourea). The most potent compound in the series was nearly as potent as the reference compound (6-chloro-2,3,4,9-tetrahydro-1H- carbazole-1-carboxamide).
- Huhtiniemi, Tero,Suuronen, Tiina,Rinne, Valtteri M.,Wittekindt, Carsten,Lahtela-Kakkonen, Maija,Jarho, Elina,Wallén, Erik A. A.,Salminen, Antero,Poso, Antti,Lepp?nen, Jukka
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supporting information; experimental part
p. 4377 - 4380
(2009/06/17)
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- Proline-based dipeptides with two amide units as organocatalyst for the asymmetric aldol reaction of cyclohexanone with aldehydes
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A series of proline-based dipeptide organocatalysts with two amide units (1-16) have been developed and evaluated in the direct catalytic asymmetric aldol reactions of aldehydes with cyclohexanone. These catalysts showed good solubility in organic solvents compared with their corresponding carboxyl terminal dipeptides. The robust amide bond formation allowed structural modifications and fine tuning of catalyst properties by varying the stereo and electronic effects of the terminal amide to affect the ability of hydrogen bonding formation between the catalysts and the substrates. The reactions proceeded smoothly in high yields (up to 99%), enantioselectivities (up to 98% ee) and anti-diastereoselectivities (up to 99:1) in the presence of bifunctional organocatalyst 4 under the optimal reaction conditions.
- Chen, Fubin,Huang, Shi,Zhang, Hui,Liu, Fengying,Peng, Yungui
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p. 9585 - 9591
(2008/12/22)
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- Formation and ring contraction of benzo[f][1,2]thiazepine-1,1-dioxides from and to benzo[e][1,2]thiazine-1,1-dioxides
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Alkoxide-promoted ring expansion of the novel ethyl 2-(6,7-dimethoxy-3-oxo- 3,4-dihydrobenzo[e][1,2]thiazine-1,1-dioxide-2-yl)acetate 3a and analogous 4,4-diethyl derivative 3b and cyclization of methyl 2-[2- (phenylaminocarbonylmethyl sulfamoyl)-4,5-dimethoxyphenyl] acetate 9 to the corresponding new 3-carboxylates and 3-carboxanilide of 7,8-dimethoxy-4-hydroxy- 2,5-dihydrobenzo[f][1,2]thiazepine-1,1-dioxide (5a,b and 10 respectively) is described. Compound 5a was deacylated upon treatment with sodium hydroxide followed by hydrochloric acid to give 7,8-dimethoxy-2,3-dihydrobenzo[f][1,2] thiazepine-1,1-dioxide-4 (5H)-one 8 and its N-ethyl derivative transferred to 6,7-dimethoxy-2-ethyl-3-oxo-3,4-dihydrobenzo[e][1,2]thiazine-1,1-dioxide 7 by the reaction with ethyl methyl ketone in the presence of pyrrolidine. Copyright Taylor & Francis Group, LLC.
- Khalaj, Ali,Adibpour, Neda
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p. 3662 - 3671
(2008/12/23)
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- Dihydropyridine derivative
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Dihydropyridine derivatives of the following formula, analogs thereof and pharmaceutically acceptable salts thereof have an activity of selectively inhibiting the action of N-type calcium channel. They are used as remedies for various diseases relating to the N-type calcium channel. STR1
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Page column 32
(2008/06/13)
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- Phthalocyanine reactive dyestuffs
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Phthalocyanine reactive dyestuffs which, in the form of the free acid, have the formula (1) STR1 in which the variable radicals have the meaning given in the description, are prepared by condensation of the corresponding amines with cyanuric fluoride or cyanuric chloride in any desired order. The reactive dyestuffs according to the invention exhibit good wet and light fastness properties and are used for the dyeing and printing of cotton.
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- Thermodynamics of enzymic synthesis of solid-phase peptides
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The Gibbs free energy changes of the individual and net synthetic equilibrium of solid-phase tert-butyloxycarbonyl-Phe-Gly p-substituted anilides are calculated from the HPLC analysis data for the equilibrium concentrations. A linear free energy relationship is observed for the net synthetic equilibrium and precipitation equilibrium, suggesting that the latter provides the driving force for the chymotryptic synthesis of these insoluble peptides. This conclusion is strongly supported by a linear correlation between the synthetic yield and the square root of the product solubility.
- Ivanov, Ivailo P.,Todorov, Nikolay P.,Petkov, Dimiter D.
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p. 2307 - 2316
(2007/10/02)
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- 7-Oxabicycloheptyl Carboxylic Acids as Thromboxane A2 Antagonists: Aza ω-Chain Analogues
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A novel bicyclic prostaglandin analogue, >-7-acetyl>amino>methyl>-7-oxabicyclohept-2-yl>-5-heptenoic acid ((-)-7) was found to be a potent and selective thromboxane A2 (TxA2) receptor antagonist.Unlike the related series of ω-chain allylic alcohols, amide 7 and its congeners were uniformly free of direct contractile activity in vitro (bovine coronary) and in vivo (anesthetized guinea pig).Amide 7 was effective in the inhibition of (a) arachidonic acid induced platelet aggregation of human platelet-richplasma (I50 = 0.18 +/- 0.006 μM), (b) 11,9-epoxymethano-PGH2 induced platelet aggregation of human platelet-rich plasma (I50 = 0.24 μM), (c) 11,9-epoxymethano-PGH2 induced contraction of guinea pig trachea (Kb = 3.0 +/- 0.3 nM) or rat aorta (Kb = 8.8 +/- 1.1 nM), and (d) arachidonic acid induced bronchoconstriction in the anesthetized guinea pig (0.1-1.0 mg/kg iv).Amide 7 inhibited the binding of ->-7-hydrazino>methyl>-7-oxabicyclohept-2-yl>-5-heptenoic acid to human platelet membranes in a specific and saturable manner with a Kd = 49.6 +/- 1.4 nM.
- Nakane, Masami,Reid, Joyce A.,Han, Wen-Ching,Das, Jagabandhu,Truc, Vu Chi,et al.
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p. 2465 - 2476
(2007/10/02)
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- Benzotriazoles, and their production and use
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A compound of the formula: STR1 wherein R is a C1 -C5 alkyl group, a C3 -C5 alkenyl group, a C3 -C5 alkynyl group or a C3 -C7 cycloalkyl group, which is useful as a herbicide.
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- Process for the preparation of optically active phenyl glycine amide
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The invention is directed to a process for the separation of L-phenyl glycine amide from D-phenyl glycine amide by resolving a mixture containing the two optically active antipodes with an optically active acid, and racemizing the undesired antipode in the presence of a ketone and the optically active acid.
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- Glycylglycine amide preparations and method of use antiarrhythmic
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A novel class of glycylglycine amides has been discovered having value as antiarrhythmic agents. The preferred compound of the present invention has the structural formula EQU1 Also included within the scope of this invention are compounds having C1 -C3 alkyl, alkoxy and halo substituents in the ortho, para or meta positions of the aromatic ring, compounds in which the phenyl group is replaced by benzyl or substituted benzyl and compounds in which the glycylglycine chain may be substituted with lower alkyl groups or may contain heterocyclic rings.
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