- Antitubercular agents. Part 1: Synthesis of phthalimido- and naphthalimido-linked phenazines as new prototype antitubercular agents
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The preparation and antitubercular properties of a series of phthalimido- and naphthalimido-linked phenazines are described. Some of these new compounds inhibited the growth of Mycobacterium tuberculosis ATCC 27294, Mycobacterium avium ATCC 49601, Mycobacterium intracellulare ATCC 13950 and some clinical isolates.
- Kamal, Ahmed,Babu, A. Hari,Ramana, A. Venkata,Sinha, Rakesh,Yadav,Arora, Sudarshan K.
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Read Online
- An efficient and fast procedure for the preparation of 2-nitrophenylamines under microwave conditions
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2-Nitrophenylamines were prepared in good yields from 2-chloronitrobenzen (or 2-fluoronitrobenzene) and amines in the presence of anhydrous potassium fluoride under microwave irradiation and solvent free conditions.
- Xu, Zhi-Bin,Lu, Ying,Guo, Zong-Ru
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Read Online
- Design, synthesis, and biological evaluation of benzo[d]imidazole-2-carboxamides as new anti-TB agents
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Tuberculosis is the leading cause of death globally among infectious diseases. Due to the development of resistance of Mycobacterium tuberculosis to currently used anti-TB medicines and the TB-HIV synergism the urgent need to develop novel anti-mycobacterial agents has been realized. The drug-to-target path has been the successful strategy for new anti-TB drug development. All the six drug candidates that have shown promise during the clinical trials and some of these being approved for treatment against MDR TB are the results of phenotype screening of small molecule compound libraries. In search of compounds belonging to novel pharmacophoric class that could be subjected to whole cell assay to generate new anti-TB leads the benzo[d]imidazole-2-carboxamide moiety has been designed as a novel anti-TB scaffold. The design was based on the identification of the benzimidazole ring as a prominent substructure of the FDA approved drugs, the structural analysis of reported anti-TB benzimidazoles, and the presence of the C-2 carboxamido functionality in novel bioisoteric anti-TB benzothiazoles. Twenty seven final compounds have been prepared via NH4Cl-catalyzed amidation of ethyl benzo[d]imidazole-2-carboxylates, as the required intermediates, obtained through a green “all water” one-pot synthetic route following a tandem N-arylation-reduction-cyclocondensation procedure. All of the synthesised target compounds were assessed for anti-TB potential using H37Rv ATCC27294 strain. Thirteen compounds were found with better MIC (0.78–6.25 μg/mL) than the standard drugs and being non-cytotoxic nature ( 60) and a few others e.g., 8a, 8f, 8k and 8o are the next best anti-TB hits (MIC: 1.56 μg/mL). The determination and analysis of various physiochemical parameters revealed favorable druglike properties of the active compounds. The compounds 8a-l and 8o, with MIC values of ≤ 6.25 μg/mL, have high LipE values (10.66–11.77) that are higher than that of the suggested value of > 6 derived from empirical evidence for quality drug candidates and highlight their therapeutic potential. The highest LipE value of 11.77 of the best active compound 8e with the MIC of 0.78 μg/mL indicates its better absorption and clearance as a probable clinical candidate for anti-TB drug discovery. These findings highlight the discovery of benzimidazole-2-carboxamides for further development as new anti-TB agents.
- Dhameliya, Tejas M.,Patel, Kshitij I.,Tiwari, Rishu,Vagolu, Siva Krishna,Panda, Dulal,Sriram, Dharmarajan,Chakraborti, Asit K.
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- A green and practical reduction of N-(4-chlorophenyl)-2-nitroaniline and its derivatives to corresponding N-substituted-benzene-1,2-diamines using thiourea dioxide
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A new effective approach for synthesizing diverse N-substituted-benzene-1,2-diamines is reported. The treatment of N-substituted-2-nitroanilines with thiourea dioxide in the presence of sodium hydroxide efficiently formed the corresponding N-substituted-benzene-1,2-diamines, including N-(4-chlorophenyl)benzene-1,2-diamine with a good yield of 94%. The by-product is environmentally-friendly urea and is easy to separate from the product by filtration procedure that enhances the convenience of the approach.
- Cui, Jian-Lan,Wang, Ning,Wang, Xiao,Yu, Si-Yuan,Zhong, Cong-Shan
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supporting information
(2020/01/22)
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- Design, synthesis and biological evaluation of novel 4-phenoxypyridine based 3-oxo-3,4-dihydroquinoxaline-2-carboxamide derivatives as potential c-Met kinase inhibitors
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Blocking c-Met kinase activity by small-molecule inhibitors has been identified as a promising approach for the treatment of cancers. Herein, we described the design, synthesis, and biological evaluation of a series of 4-phenoxypyridine-based 3-oxo-3,4-dihydroquinoxaline derivatives as c-Met kinase inhibitors. Inhibitory activitives against c-Met kinase evaluation indicated that most of compounds showed excellent c-Met kinase activity in vitro, and IC50 values of ten compounds (23a, 23e, 23f, 23l, 23r, 23s, 23v, 23w, 23x and 23y) were less than 10.00 nM. Notably, three of them (23v, 23w and 23y) showed remarkable potency with IC50 values of 2.31 nM, 1.91 nM and 2.44 nM, respectively, and thus they were more potent than positive control drug foretinib (c-Met, IC50 = 2.53 nM). Cytotoxic evaluation indicated the most promising compound 23w showed remarkable cytotoxicity against A549, H460 and HT-29 cell lines with IC50 values of 1.57 μM, 0.94 μM and 0.65 μM, respectively. Furthermore, the acridine orange/ethidium bromide (AO/EB) staining, cell apoptosis assays by flow cytometry, wound-healing assays and transwell migration assays on HT-29 and/or A549 cells of 23w were performed. Especially compound 23w, which displayed potent antitumor, apoptosis induction and antimetastatic activity, could be used as a promising lead for further development. Meanwhile, their preliminary structure-activity relationships (SARs) were also discussed.
- Wang, Zhen,Shi, Jiantao,Zhu, Xianglong,Zhao, Wenwen,Gong, Yilin,Hao, Xuechen,Hou, Yunlei,Liu, Yajing,Ding, Shi,Liu, Ju,Chen, Ye
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- Preparation and characterization of isatin complexed with Cu supported on 4-(aminomethyl) benzoic acid-functionalized Fe3O4 nanoparticles as a novel magnetic catalyst for the Ullmann coupling reaction
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Isatin complexed with Cu supported on 4-(aminomethyl) benzoic acid-functionalized Fe3O4 nanoparticles (Cu-IS-AMBA-MNPs) as a new catalyst was designed, prepared and characterized by appropriate analyses. The heterogeneous reusable catalyst was successfully used for the efficient and widespread syntheses of diaryl ethers and diarylamines via the Ullmann coupling reaction. This green catalyst was easily removed, reused several times with no significant loss of its activity, and provided a clean synthesis with excellent yield and reduced time.
- Khodaei, Mohammad Mehdi,Alizadeh, Abdolhamid,Haghipour, Maryam
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p. 2727 - 2747
(2019/02/13)
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- Decarboxylative ipso Amination of Activated Benzoic Acids
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In the presence of a bimetallic Pd/Cu system with 1,10-phenanthroline as the ligand and either air or N-methylmorpholine N-oxide as the oxidant, electron-deficient benzoic acids undergo oxidative decarboxylative coupling with unprotected amines. This operationally simple aniline synthesis is widely applicable with respect to the amine and gives good yields, even on multigram scale. The orthogonality of this reaction to other Pd-catalyzed cross-couplings allows the concise synthesis of multisubstituted arenes by sequential C?C, C?Cl, and C?N functionalizations. Mechanistic investigations suggest the intermediacy of a hypervalent Pd species.
- Pichette Drapeau, Martin,Bahri, Janet,Lichte, Dominik,Goo?en, Lukas J.
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supporting information
p. 892 - 896
(2019/01/04)
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- Selenium-Catalyzed Carbonylative Synthesis of 2-Benzimidazolones from 2-Nitroanilines with TFBen as the CO Source
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A selenium-catalyzed carbonylative reaction for the synthesis of 2-benzimidazolones from 2-nitroanilines has been developed. In this strategy, to avoid the usage of toxic CO gas, TFBen (benzene-1,3,5-triyl triformate) was used as a solid and stable CO precursor, and a variety of desired 2-benzimidazolones were produced in moderate to excellent yields.
- Qi, Xinxin,Zhou, Rong,Peng, Jin-Bao,Ying, Jun,Wu, Xiao-Feng
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supporting information
p. 5161 - 5164
(2019/01/25)
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- Preparation method for clofazimine intermediate
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The invention relates to a preparation method for a clofazimine intermediate N-(4-chlorophenyl)-2-nitrobenzene as shown in a formula III which is described in the specification. The preparation method is simple and safe to operate, good in yield, small in environmental pollution, excellent in economic effect and suitable for industrial production.
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Paragraph 0016; 0017; 0018; 0019; 0020; 0021; 0022-0024
(2017/08/30)
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- Design, synthesis and biological evaluation of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety as c-Met kinase inhibitors
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A series of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety were synthesized and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against five cancer cell lines (HT-29, H460, A549, MKN-45 and U87MG) in vitro. Most of the compounds exhibited moderate-to-significant cytotoxicity as compared with foretinib. The most promising compound 41 (with c-Met IC50 value of 0.90?nM) showed remarkable cytotoxicity against HT-29, H460, A549, MKN-45 and U87MG cell lines with IC50 values of 0.06?μM, 0.05?μM, 0.18?μM, 0.023?μM and 0.66?μM, respectively, and thus it was 1.22- to 3.50-fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity.
- Liu, Ju,Yang, Di,Yang, Xiuxiu,Nie, Minhua,Wu, Guodong,Wang, Zhunchao,Li, Wei,Liu, Yajing,Gong, Ping
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p. 4475 - 4486
(2017/07/22)
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- Method for synthesizing N-(4-chlorphenyl)-1,2-phenylenediamine as key clofazimine intermediate
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The invention provides a method for synthesizing N-(4-chlorphenyl)-1,2-phenylenediamine as a key clofazimine intermediate. The method specifically comprises the following steps: 1) by taking o-fluoronitrobenzene and p-chloroaniline as raw materials and utilizing organic base as a catalyst for condensation reaction, reacting in an organic solvent and performing conventional treatment after ending the reaction, thereby acquiring a condensation intermediate N-(4-chlorphenyl)-2-nitryl-1-aniline; 2) by utilizing metallic nickel as the catalyst, performing catalytic hydrogenation reaction on the acquired condensation intermediate in the organic solvent and performing conventional treatment after reducing, thereby acquiring a rough product of N-(4-chlorphenyl)-1,2-phenylenediamine; and 3) re-crystallizing the acquired rough product with the organic solvent, thereby acquiring the end product.
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Paragraph 0033; 0034; 0035; 0036; 0037; 0038; 0039-0045
(2017/12/30)
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- Design, synthesis and antifungal activity of novel fenfuram-diarylamine hybrids
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Ten novel fenfuram-diarylamine hybrids were designed and synthesized. And their antifungal activities against four phytopathogenic fungi have been evaluated in vitro and most of the compounds demonstrated a significant antifungal activities against Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 5e exhibited the most potent antifungal activity against R. solani with an EC50value of 0.037 mg/L, far superior to the commercially available fungicide boscalid (EC50= 1.71 mg/L) and lead fungicide fenfuram (EC50= 6.18 mg/L). Furthermore, scanning electron microscopy images showed that the mycelia on treated media grew abnormally with tenuous, wizened and overlapping colonies compared to the negative control. Molecular docking studies revealed that compound 5e featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 3-chlorophenyl group in compound 5e formed a CH-π interaction with B/Trp-206 and a Cl-π interaction with D/Tyr-128, rendering compound 5e more active than fenfuram against SDH.
- Wang, Hongyu,Gao, Xuheng,Zhang, Xiaoxiao,Jin, Hong,Tao, Ke,Hou, Taiping
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supporting information
p. 90 - 93
(2016/12/09)
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- Synthesis and biological evaluation of novel pyrazole carboxamide with diarylamine-modi?ed scaffold as potent antifungal agents
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Twenty-seven novel pyrazole carboxamides with diarylamine-modi?ed scaffold were designed, synthesized and characterized in detail via 1H NMR, 13C NMR, IR and ESI-HRMS. Preliminary bioassays showed that some of the target compounds exhibited good antifungal activity against Rhizoctonia solani, Rhizoctonia cerealis and Sclerotinia sclerotiorum. Among them, compound 9c-7 exhibited the highest antifungal activities against R. solani, R. cerealis and S. sclerotiorum in vitro with IC50 values of 0.013, 1.608 and 1.874?μg/mL, respectively. Notably, compound 9c-7 still presented the highest fungicidal activities against R. solani in vivo with an IC50 value of 22.21?μg/mL. Molecular docking simulation results reveal that compound 9c-7 binds well to the hydrophobic pockets of the receptor protein succinate dehydrogenase. This study suggests that compound 9c-7 could act as a potential fungicide to be used for further optimization.
- Zhang, Xiao-Xiao,Jin, Hong,Deng, Yuan-Jie,Gao, Xu-Heng,Li, Yong,Zhao, Yong-Tian,Tao, Ke,Hou, Tai-Ping
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p. 1731 - 1736
(2017/07/27)
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- Selective Hydrogenation of Halogenated Nitroaromatics to Haloanilines in Batch and Flow
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The selective hydrogenation of functionalized nitroaromatics poses a major challenge from both academic as well as industrial viewpoints. As part of the CHEM21 initiative (www.chem21.eu), we are interested in highly selective, catalytic hydrogenations of halogenated nitroaromatics. Initially, the catalytic reduction of 1-iodo-4-nitrobenzene to 4-iodoaniline served as a model system to investigate commercial heterogeneous catalysts. After determining optimal hydrogenation conditions and profiling performances of the best catalysts, hydrogenations were transferred from batch to continuous flow. Finally, the optimized flow conditions were applied to transformations which represent important steps in the syntheses of the active pharmaceutical ingredients clofazimine and vismodegib.
- Loos, Patrick,Alex, Hannes,Hassfeld, Jorma,Lovis, Kai,Platzek, Johannes,Steinfeldt, Norbert,Hübner, Sandra
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p. 452 - 464
(2016/03/04)
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- Discovery of Benzotriazolo[4,3-d][1,4]diazepines as Orally Active Inhibitors of BET Bromodomains
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Inhibition of the bromodomains of the BET family, of which BRD4 is a member, has been shown to decrease myc and interleukin (IL) 6 in vivo, markers that are of therapeutic relevance to cancer and inflammatory disease, respectively. Herein we report substituted benzo[b]isoxazolo[4,5-d]azepines and benzotriazolo[4,3-d][1,4]diazepines as fragment-derived novel inhibitors of the bromodomain of BRD4. Compounds from these series were potent and selective in cells, and subsequent optimization of microsomal stability yielded representatives that demonstrated dose- and time-dependent reduction of plasma IL-6 in mice.
- Taylor, Alexander M.,Vaswani, Rishi G.,Gehling, Victor S.,Hewitt, Michael C.,Leblanc, Yves,Audia, James E.,Bellon, Steve,Cummings, Richard T.,Co?té, Alexandre,Harmange, Jean-Christophe,Jayaram, Hari,Joshi, Shivangi,Lora, Jose M.,Mertz, Jennifer A.,Neiss, Adrianne,Pardo, Eneida,Nasveschuk, Christopher G.,Poy, Florence,Sandy, Peter,Setser, Jeremy W.,Sims, Robert J.,Tang, Yong,Albrecht, Brian K.
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supporting information
p. 145 - 150
(2016/03/01)
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- Square planar nickel(II) complexes with halogenated o- diiminobenzosemiquinonato ligation: Synthesis, characterization, and redox property
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Seven square planar bis(o-diiminobenzosemiquinonato)nickel(II) complexes, [Ni(o-C6H4(NH)(NAr))2] (Ar=Mes, 1; p-F-C 6H4, 2; p-Cl-C6H4, 3), [Ni(o-4,5-F2-C6H2(NH)(NPh))2] (4), and [Ni(o-4,5-Cl2-C6H2(NH)(NAr))2] (Ar=Ph, 5; 2,6-F2-C6H3, 6; 2,6-Cl 2-C6H3, 7), have been synthesized and characterized by 1H NMR, 13C NMR, 19F NMR, IR, UV-Vis-NIR, elemental analyses, HRMS, as well as single-crystal X-ray diffraction studies (1 and 7). The cyclic voltammograms of these complexes exhibit two reversible redox processes of [NiL2]0/1- and [NiL2]1-/2-, and one irreversible process of [NiL 2]0/2+. Substituent effects on the redox properties of these complexes, in addition with those of the known complexes [Ni(o-C 6H4(NH)(NPh))2] (8) and [Ni(o-3,5-Bu t2-C6H2(NH)2) 2] (9), are identified by comparing the half-wave potentials of the reduction waves, as 1≈92] parallels the electron-donating and -withdrawing ability of the substituent group. Reduction of 1 with one or two equivalents of sodium metal in THF has led to the isolation of [Na(THF) 3][1] and [Na(THF)3]2[1]. The structure data of these two complexes revealed by low-temperature X-ray crystallography suggest their corresponding electronic structures of [NiII(1L ·1-)(1L2-)]1- and [Ni II(1L2-)2]2-, which are in line with those of [9]n (n=1-, 2-) suggested by spectroelectrochemical study. Copyright
- Zuo, Wansheng,Zhang, Long,Xie, Meihua,Deng, Liang
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supporting information
p. 1473 - 1482
(2014/01/06)
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- Systematic evaluation of structure-activity relationships of the riminophenazine class and discovery of a C2 pyridylamino series for the treatment of multidrug-resistant tuberculosis
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Clofazimine, a member of the riminophenazine class of drugs, is the cornerstone agent for the treatment of leprosy. This agent is currently being studied in clinical trials for the treatment of multidrug-resistant tuberculosis to address the urgent need for new drugs that can overcome existing and emerging drug resistance. However, the use of clofazimine in tuberculosis treatment is hampered by its high lipophilicity and skin pigmentation side effects. To identify a new generation of riminophenazines that is less lipophilic and skin staining, while maintaining efficacy, we have performed a systematic structure-activity relationship (SAR) investigation by synthesizing a variety of analogs of clofazimine and evaluating their anti-tuberculosis activity. The study reveals that the central tricyclic phenazine system and the pendant aromatic rings are important for anti-tuberculosis activity. However, the phenyl groups attached to the C2 and N5 position of clofazimine can be replaced by a pyridyl group to provide analogs with improved physicochemical properties and pharmacokinetic characteristics. Replacement of the phenyl group attached to the C2 position by a pyridyl group has led to a promising new series of compounds with improved physicochemical properties, improved anti-tuberculosis potency, and reduced pigmentation potential.
- Liu, Binna,Liu, Kai,Lu, Yu,Zhang, Dongfeng,Yang, Tianming,Li, Xuan,Ma, Chen,Zheng, Meiqin,Wang, Bin,Zhang, Gang,Wang, Fei,Ma, Zhenkun,Li, Chun,Huang, Haihong,Yin, Dali
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experimental part
p. 4545 - 4559
(2012/07/01)
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- BROMODOMAIN INHIBITORS AND USES THEREOF
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The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.
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Page/Page column 103
(2012/11/14)
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- RIMINOPHENAZINES WITH 2-(HETEROARYL)AMINO SUBSTITUENTS AND THEIR ANTI-MICROBIAL ACTIVITY
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The present invention relates to riminophenazines having heteroaromatic substitutions, including those with 2-heteroaryl-amino substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.
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Page/Page column 44-45
(2012/01/15)
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- Synthesis, biological evaluation and SAR studies of benzimidazole derivatives as H1-antihistamine agents
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A series of benzimidazole derivatives have been designed, synthesized and evaluated for H1 antihistamine activity. Six compounds have showed potent antihistamine H1 activity. The primary SAR analysis indicated that benzyl or benzylidinyl substituted on the exo-nitrogen atom and C2 of the benzimidazole were significant. Further experiments indicated that compound 17d displayed excellent activity to reduce mast cell degranulation, moderate anti-PAF activity and decreased potency on hERG compared to astermizole. Hence compound 17d could serve as anti-allergic agent for further development.
- Wang, Xiao Jian,Xi, Mei Yang,Fu, Ji Hua,Zhang, Fu Rong,Cheng, Gui Fang,Yin, Da Li,You, Qi Dong
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scheme or table
p. 707 - 710
(2012/07/03)
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- Identification of less lipophilic riminophenazine derivatives for the treatment of drug-resistant tuberculosis
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Clofazimine (CFZ), a member of the riminophenazine class, has been studied in clinical trials for the treatment of multidrug-resistant tuberculosis (MDR-TB). CFZ has several side effects which can be attributed to its extremely high lipophilicity. A series of novel riminophenazine analogues bearing a C-2 pyridyl substituent was designed and synthesized with the goal of maintaining potent activity against Mycobacterium tuberculosis (M. tuberculosis) while improving upon its safety profile by lowering the lipophilicity. All compounds were evaluated for their in vitro activity and cytotoxicity. The results demonstrated that many new compounds had potent activity against M. tuberculosis with MICs of less than 0.03 μg/mL and low cytotoxicity with IC50 values greater than 64 μg/mL. Some compounds were tested for in vivo efficacy against MDR-TB in an experimental mouse infection model. Two compounds demonstrated equivalent or better efficacy than CFZ in this model with significantly reduced skin discoloration potential.
- Zhang, Dongfeng,Liu, Kai,Liu, Binna,Wang, Jingbin,Zhang, Gang,Zhang, Hao,Liu, Yang,Hou, Yanyan,Gong, Ningbo,Lv, Yang,Li, Chun,Yin, Dali,Huang, Haihong,Lu, Yu,Wang, Bin,Zheng, Meiqin,Fu, Lei,Cooper, Christopher B.,Upton, Anna M.,Ma, Zhenkun
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p. 8409 - 8417,9
(2020/09/15)
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- Simple synthesis of N-aryl-2-nitrosoanilines in the reaction of nitroarenes with aniline anion derivatives
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Anions generated from primary arylamines react with substituted nitrobenzenes to form H-adducts, which, under basic reaction conditions, undergo transformation to N-aryl-2-nitroso?amines. Competitive substitution of reactive halogens in the nit
- Wrobel, Zbigniew,Kwast, Andrzej
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experimental part
p. 3865 - 3872
(2010/12/25)
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- Benzimidazole and imidazole inhibitors of histone deacetylases: Synthesis and biological activity
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A series of N-hydroxy-3-[3-(1-substituted-1H-benzoimidazol-2-yl)-phenyl]-acrylamides (5a-5ab) and N-hydroxy-3-[3-(1,4,5-trisubstituted-1H-imidazol-2-yl)-phenyl]-acrylamides (12a-s) were designed, synthesized, and found to be nanomolar inhibitors of human histone deacetylases. Multiple compounds bearing an N1-piperidine demonstrate EC50s of 20-100 nM in human A549, HL60, and PC3 cells, in vitro and in vivo hyperacetylation of histones H3 and H4, and induction of p21waf. Compound 5x displays efficacy in human tumor xenograft models.
- Bressi, Jerome C.,Jong, Ron de,Wu, Yiqin,Jennings, Andy J.,Brown, Jason W.,O'Connell, Shawn,Tari, Leslie W.,Skene, Robert J.,Vu, Phong,Navre, Marc,Cao, Xiaodong,Gangloff, Anthony R.
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scheme or table
p. 3138 - 3141
(2010/09/03)
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- Discovery of novel, orally available benzimidazoles as melanin concentrating hormone receptor 1 (MCHR1) antagonists
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Melanin concentrating hormone (MCH) is an important mediator of energy homeostasis and plays role in several disorders such as obesity, stress, depression and anxiety. The synthesis and biological evaluation of novel benzimidazole derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified.
- Sasmal, Pradip K.,Sasmal, Sanjita,Rao, P. Tirumala,Venkatesham,Roshaiah,Abbineni, Chandrasekhar,Khanna, Ish,Jadhav, Vikram P.,Suresh,Talwar, Rashmi,Muzeeb, Syed,Receveur, Jean-Marie,Frimurer, Thomas M.,Rist, ?ystein,Elster, Lisbeth,H?gberg, Thomas
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scheme or table
p. 5443 - 5448
(2011/01/03)
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- An improved synthesis of N-substituted-2-nitroanilines
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The reaction of 2-chloronitrobenzene with substituted amines/ anilines in the presence of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) gives N-substituted-2-nitroanilines in good to excellent yields (>75-90%).
- Chauhan,Singh, Ram,Geetanjali
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p. 2899 - 2906
(2007/10/03)
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- Sulfonamide derivatives and drugs containing the same as the active ingredient
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The present invention discloses a sulfonamide derivative represented by the following formula (1): [wherein A represents a nitrogen atom, —CH═, etc.; Z represents an oxygen atom, etc.; Ar1represents an aryl group, etc.; Ar2represents an alkyl group, etc.; Rarepresents a hydrogen atom, etc.; Rbrepresents a hydrogen atom, etc.; and Rcrepresents an alkyl group, etc.], or a salt thereof; and drugs containing the derivative or a salt thereof as an active ingredient. This compound exhibits radical scavenging action, gastric mucous secretion augmenting action, and anti-HP action, and thus is effective as a peptic ulcer therapeutic agent.
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- Synthesis and Characterization of Water-Soluble and Photolabile 10-Arylisoalloxazines: Tools for Studying the Mechanism of Action of Flavin-Type Antimalarials
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Isoalloxazine derivatives such as 1a-d are promising antimalarial agents which act as inhibitors of the antioxidant enzyme glutathione reductase and possibly of other proteins.The molecular mechanism of the pharmacological effects has not been studied in detail because compounds 1a-d are poorly soluble in aqueous solutions of physiological pH.In the present study we introduce two new types of isoalloxazine derivatives with improved solubility properties.The 10-aryl-3-carboxymethylisoalloxazines 2a-d, and the isomeric 3-methyl-10-(N-methylpyridiniumyl)isoalloxazine salts 3 and 4.In addition, for the purpose of photoaffinity labeling experiments, the 10-aryl-8-azido-3-methylisoalloxazine 5 was designed.The syntheses and characterizations of these new flavins as well as an alternative synthetic approach to the known antimalarials 1a-d are described. - Keywords: Flavins/Isoalloxazines/Arylisoalloxazines/Malaria/Antimalarials/Glutathione reductase inhibitors/Photoaffinity labels
- Kirsch, Peer,Schoenleben-Janas, Annette,Schirmer, R. Heiner
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p. 1275 - 1282
(2007/10/02)
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