- Thiazole ring-containing amide compounds as well as preparation method and application thereof
-
The invention discloses thiazole ring-containing amide compounds as well as a preparation method and application thereof, and belongs to the field of chemical technologies and pesticides. According to the present invention, p-phenylenediamine is adopted as a raw material to synthesize a series of the thiazole ring-containing amide compounds, and the synthesized thiazole ring-containing amide compounds have good inhibition effects on Xanthomonas oryzae pv.Oryza (Xoo), Xanthomonas oryzae pv.Oryzcola (Xoc) and Xanthomonas axonophora pv.Citri (Xac) in agricultural diseases and insect pests, and can be used for preparing the anti-plant bacterium agent.
- -
-
Paragraph 0044; 0051; 0093; 0097; 0171; 0176; 0248; 0253
(2021/06/23)
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- Based on isoxazole substitution of benzamide derivatives and anti-prostate cancer drug applications
-
The present invention discloses a class (I), formula (II) structure based on isoxazole substituted benzamide derivatives and antiprostate cancer drug applications, such isoxazole substituted benzamide derivatives, can effectively inhibit the activity of a
- -
-
Paragraph 0065; 0073-0074
(2022/01/10)
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- N-(1-CYANO-PYRROLIDIN-3-YL)-5-(3-(TRIFLUOROMETHYL)PHENYL)OXAZOLE-2-CARBOXAMIDE DERIVATIVES AND THE CORRESPONDING OXADIAZOLE DERIVATIVES AS USP30 INHIBITORS FOR THE TREATMENT OF MITOCHONDRIAL DYSFUNCTION
-
The present invention relates to a class of N-cyanopyrrolidines with activity as inhibitors of the deubiquitylating enzyme USP30, having utility in a variety of therapeutic areas, including conditions involving mitochondrial dysfunction, cancer and fibros
- -
-
Page/Page column 38
(2021/12/08)
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- Thiadiazole amide compound and application thereof
-
The invention discloses a thiadiazole amide compound and application thereof, and belongs to the field of medicines. The structural general formula of the compound is shown as a formula (I) and is a novel compound with androgen receptor antagonistic activity, wherein one of the key targets is a binding pocket between the androgen receptor ligand binding domain dimer interface. The compound provided by the invention has high activity for antagonizing the transcription of androgen receptor and is at the molecular level. The cell level and the animal level all show good biological activity, and have better safety. , The invention can be applied to the preparation of drugs for treating androgen receptor abnormal expression tumors, including but not limited to prostate cancer, metastatic prostate cancer, castration-resistant prostate cancer, breast cancer and ovarian cancer.
- -
-
Paragraph 0042; 0043; 0121; 0124; 0125; 0126
(2021/09/29)
-
- Nickel-catalyzed asymmetric arylative cyclization of N-alkynones: Efficient access to 1,2,3,6-tetrahydropyridines with a tertiary alcohol
-
Nickel/(S)-t-Bu-PHOX complex catalyzed asymmetric arylative cyclization of N-alkynones has been achieved, delivering 1,2,3,6-tetrahydropyridines containing a chiral tertiary alcohol in high yields and excellent enantioselectivities, which provides efficient access to chiral tetrahydropyridine and piperidine analogues.
- Tian, Jiangyan,Li, Wendian,Li, Ruihao,He, Lin,Lv, Hui
-
supporting information
p. 4038 - 4040
(2021/07/06)
-
- Selective Debromination of α,α,α-Tribromomethylketones with HBr–H2O Reductive Catalytic System
-
A debromination of α,α,α-tribromomethylketones is developed for chemoselective synthesis of α-mono- and α,α-dibromomethylketones with high selectivity under H2O–HBr reductive conditions. This method offers an efficient and direct way to synthesize α-mono or α,α-dibromomethylketone compounds in high to excellent yields through the process of HBr self-circulation in water.
- Cheng, Zhao,Guo, Hongmei,Huang, Guozheng,Rexit, Abulikemu Abudu,Wang, Hui,Zheng, Meng-Xia
-
p. 6455 - 6458
(2020/10/21)
-
- Usnic Acid Enaminone-Coupled 1,2,3-Triazoles as Antibacterial and Antitubercular Agents
-
(+)-Usnic acid, a product of secondary metabolism in lichens, has displayed a broad range of biological properties such as antitumor, antimicrobial, antiviral, anti-inflammatory, and insecticidal activities. Interested by these pharmacological activities and to tap into its potential, we herein present the synthesis and biological evaluation of new usnic acid enaminone-conjugated 1,2,3-triazoles 10-44 as antimycobacterial agents. (+)-Usnic acid was condensed with propargyl amine to give usnic acid enaminone 8 with a terminal ethynyl moiety. It was further reacted with various azides A1-A35 under copper catalysis to give triazoles 10-44 in good yields. Among the synthesized compounds, saccharin derivative 36 proved to be the most active analogue, inhibiting Mycobacterium tuberculosis (Mtb) at an MIC value of 2.5 μM. Analogues 16 and 27, with 3,4-difluorophenacyl and 2-acylnaphthalene units, respectively, inhibited Mtb at MIC values of 5.4 and 5.3 μM, respectively. Among the tested Gram-positive and Gram-negative bacteria, the new derivatives were active on Bacillus subtilis, with compounds 18 [3-(trifluoromethyl)phenacyl] and 29 (N-acylmorpholinyl) showing inhibitory concentrations of 41 and 90.7 μM, respectively, while they were inactive on the other tested bacterial strains. Overall, the study presented here is useful for converting natural (+)-usnic acid into antitubercular and antibacterial agents via incorporation of enaminone and 1,2,3-triazole functionalities.
- Bangalore, Pavan K.,Vagolu, Siva K.,Bollikanda, Rakesh K.,Veeragoni, Dileep K.,Choudante, Pallavi C.,Misra, Sunil,Sriram, Dharmarajan,Sridhar, Balasubramanian,Kantevari, Srinivas
-
supporting information
p. 26 - 35
(2020/01/03)
-
- Synthesis and Antibacterial Evaluation of N-phenylacetamide Derivatives Containing 4-Arylthiazole Moieties
-
A series of new N-phenylacetamide derivatives containing 4-arylthiazole moieties was designed and synthesized by introducing the thiazole moiety into the amide scaffold. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR and HRMS. Their in vitro antibacterial activities were evaluated against three kinds of bacteria-Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac) and X.oryzae pv. oryzicola (Xoc)-showing promising results. The minimum 50% effective concentration (EC50) value of N-(4-((4-(4-fluoro-phenyl)thiazol-2-yl)amino)phenyl)acetamide (A1) is 156.7 μM, which is superior to bismerthiazol (230.5 μM) and thiodiazole copper (545.2 μM). A scanning electron microscopy (SEM) investigation has confirmed that compound A1 could cause cell membrane rupture of Xoo. In addition, the nematicidal activity of the compounds against Meloidogyne incognita (M. incognita) was also tested, and compound A23 displayed excellent nematicidal activity, with mortality of 100% and 53.2% at 500 μg/mL and 100 μg/mL after 24 h of treatment, respectively. The preliminary structure-activity relationship (SAR) studies of these compounds are also briefly described. These results demonstrated that phenylacetamide derivatives may be considered as potential leads in the design of antibacterial agents.
- Jin, Linhong,Lu, Hui,Wang, Lei,Zhou, Xia
-
-
- Nonenzymatic Dynamic Kinetic Resolution of in situ Generated Hemithioacetals: Access to 1,3-Disubstituted Phthalans
-
The first nonenzymatic DKR reaction of hemithioacetals is developed. Hemithioacetals were formed in situ via thiol addition and subsequently underwent an intramolecular oxa-Michael reaction. The scope of the reaction was quite broad ranging from aliphatic to aromatic substituents and 1,3-disubstituted-1,3-dihyroisobenzofuran products were obtained in good yields with moderate diastereoselectivities and high enantioselectivities. (Figure presented.).
- Nath, Utpal,Chowdhury, Deepan,Pan, Subhas Chandra
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supporting information
p. 1628 - 1633
(2018/03/21)
-
- 1,3-Dibromo-5,5-dimethylhydantoin mediated oxidative amidation of terminal alkenes in water
-
A variety of terminal alkenes were converted to the corresponding amides in yields of 25 to 86% in water via treatment with 1,3-dibromo-5,5-dimethylhydantoin, followed by reaction with molecular iodine and aq. NH3 (or amine) in one pot. This metal- and organic solvent-free protocol is not only suitable for styrene derivatives, but also, for the first time, works well on terminal aliphatic alkenes.
- Ma, Chunhua,Fan, Guojie,Wu, Ping,Li, Zhi,Zhou, Yang,Ding, Qingjie,Zhang, Wei
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p. 9889 - 9894
(2017/12/12)
-
- Visible Light as a Sole Requirement for Intramolecular C(sp3)-H Imination
-
A novel, simple, and practical visible-light-mediated intramolecular α-C(sp3)-H imination of tertiary aliphatic amines containing β-O-aryl oximes leading to N-heterocycles has been developed. The reaction was performed well at rt with tolerance of some functional groups. Importantly, the selective C-H functionalization did not require added catalyst, oxidant, additive, acid, and base; visible light was the sole requirement.
- Li, Jingjing,Zhang, Pengxiang,Jiang, Min,Yang, Haijun,Zhao, Yufen,Fu, Hua
-
supporting information
p. 1994 - 1997
(2017/04/28)
-
- Heterocyclic acene propanoic derivative as well as preparation method and application thereof
-
The invention relates to a heterocyclic acene propanoic derivative as well as a preparation method and application thereof. A structural formula of the derivative is shown in the description. The heterocyclic acene propanoic derivative shows agonist activ
- -
-
Paragraph 0137; 0139; 0140; 0141
(2018/01/09)
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- Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents
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Series of styryl hydrazine thiazole hybrids inspired from dehydrozingerone (DZG) scaffold were designed and synthesized by molecular hybridization approach. In vitro antimycobacterial activity of synthesized compounds was evaluated against Mycobacterium tuberculosis H37Rv strain. Among the series, compound 6o exhibited significant activity (MIC = 1.5 μM; IC50 = 0.48 μM) along with bactericidal (MBC = 12 μM) and intracellular antimycobacterial activities (IC50 = 0.098 μM). Furthermore, 6o displayed prominent antimycobacterial activity under hypoxic (MIC = 46 μM) and normal oxygen (MIC = 0.28 μM) conditions along with antimycobacterial efficiency against isoniazid (MIC = 3.2 μM for INH-R1; 1.5 μM for INH-R2) and rifampicin (MIC = 2.2 μM for RIF-R1; 6.3 μM for RIF-R2) resistant strains of Mtb. Presence of electron donating groups on the phenyl ring of thiazole moiety had positive correlation for biological activity, suggesting the importance of molecular hybridization approach for the development of newer DZG clubbed hydrazine thiazole hybrids as potential antimycobacterial agents.
- Hampannavar, Girish A.,Karpoormath, Rajshekhar,Palkar, Mahesh B.,Shaikh, Mahamadhanif S.,Chandrasekaran, Balakumar
-
supporting information
p. 686 - 691
(2016/07/26)
-
- Identification of novel 2-aminothiazole conjugated nitrofuran as antitubercular and antibacterial agents
-
The emergence of antibiotic resistant pathogens is an ongoing main problem in the therapy of bacterial infections. In order to develop promising antitubercular and antibacterial lead compounds, we designed and synthesized a new series of derivatives of 2-aminothiazole conjugated nitrofuran with activities against both Mycobacterium tuberculosis and Staphylococcus aureus. Eight compounds 12e, 12k, 12l, 12m, 18a, 18d, 18e, and 18j emerged as promising antitubercular agents. Structure–activity relationships (SARs) were discussed and showed that the derivatives substituted at the position-3 of benzene of 5-nitro-N-(4-phenylthiazol-2-yl)furan-2-carboxamide exhibited superior potency. The most potent compound 18e, substituted with benzamide at this position, displayed minimum inhibitory concentrations (MICs) of 0.27 μg/mL against Mtb H37Ra and 1.36 μg/mL against S. aureus. Furthermore, compound 18e had no obvious cytotoxicity to normal Vero cells (IC50= 50.2 μM). The results suggest that the novel scaffolds of aminothiazole conjugated nitrofuran would be a promising class of potent antitubercular and antimicrobial agents.
- Ran, Kai,Gao, Chao,Deng, Hongxia,Lei, Qian,You, Xinyu,Wang, Ningyu,Shi, Yaojie,Liu, Zhihao,Wei, Wei,Peng, Cuiting,Xiong, Lu,Xiao, Kunjie,Yu, Luoting
-
supporting information
p. 3669 - 3674
(2016/07/21)
-
- Synthesis and structure-activity relationship of aminoarylthiazole derivatives as correctors of the chloride transport defect in cystic fibrosis
-
Abstract The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel present in the membrane of epithelial cells. Mutations affecting the CFTR gene cause cystic fibrosis (CF), a multi-organ severe disease. The most common CF mutation, F508del, impairs the processing and activity (gating) of CFTR protein. Other mutations, like G551D, only cause a gating defect. Processing and gating defects can be targeted by small molecules called generically correctors and potentiators, respectively. Aminoarylthiazoles (AATs) represent an interesting class of compounds that includes molecules with dual activity, as correctors and potentiators. With the aim to improve the activity profile of AATs, we have now designed and synthesized a library of novel compounds in order to establish an initial SAR that may provide indications about the chemical groups that are beneficial or detrimental for rescue activity. The new compounds were tested as correctors and potentiators in CFBE41o-expressing F508del-CFTR using a functional assay. A dual active compound, AAT-4a, characterized by improved efficacy and marked synergy when combined with the corrector VX-809 has been identified. Moreover, by computational methods, a possible binding site for AATs in nucleotide binding domain NBD1 has been detected. These results will direct the synthesis of new analogues with possibly improved activity.
- Pesce, Emanuela,Bellotti, Marta,Liessi, Nara,Guariento, Sara,Damonte, Gianluca,Cichero, Elena,Galatini, Andrea,Salis, Annalisa,Gianotti, Ambra,Pedemonte, Nicoletta,Zegarra-Moran, Olga,Fossa, Paola,Galietta, Luis J.V.,Millo, Enrico
-
supporting information
p. 14 - 35
(2015/06/08)
-
- Design, Synthesis and Biological Evaluation of Imidazo[1,2-a]pyridine Derivatives as Novel DPP-4 Inhibitors
-
A new series of DPP-4 inhibitors with imidazo[1,2-a]pyridine scaffold were designed by exploiting scaffold hopping strategy and docking study. Based on docking binding model, structural modifications of 2-benzene ring and pyridine moieties of compound 5a led to the identification of compound 5d with 2, 4-dichlorophenyl group at the 2-position as a potent (IC50 = 0.13 μm), selective (DPP-8/DPP-4 = 215 and DPP-9/DPP-4 = 192) and in vivo efficacious DPP-4 inhibitor. Further, molecular docking revealed that compound 5d could retain key binding features of DPP-4 with the pyridine moiety of imidazo[1,2-a]pyridine ring providing an additional π-π interaction with Phe357 of DPP-4. Compound 5d might be a promising lead for further development of novel DPP-4 inhibitor treating T2DM.
- Li, Qing,Zhou, Muxing,Han, Li,Cao, Qing,Wang, Xinning,Zhao, Leilei,Zhou, Jinpei,Zhang, Huibin
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p. 849 - 856
(2015/10/06)
-
- Diarylthiazole: An antimycobacterial scaffold potentially targeting PrrB-PrrA two-component system
-
Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to optimize the potency and physicochemical properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochemical properties. The potent antimycobacterial activity, in conjunction with low molecular weight, made the series an attractive lead (antibacterial ligand efficiency (ALE) >0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational analysis showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.
- Bellale, Eknath,Naik, Maruti,Vb, Varun,Ambady, Anisha,Narayan, Ashwini,Ravishankar, Sudha,Ramachandran, Vasanthi,Kaur, Parvinder,McLaughlin, Robert,Whiteaker, James,Morayya, Sapna,Guptha, Supreeth,Sharma, Sreevalli,Raichurkar, Anandkumar,Awasthy, Disha,Achar, Vijayshree,Vachaspati, Prakash,Bandodkar, Balachandra,Panda, Manoranjan,Chatterji, Monalisa
-
supporting information
p. 6572 - 6582
(2014/10/15)
-
- New insights into the bacterial RNA polymerase inhibitor CBR703 as a starting point for optimization as an anti-infective agent
-
CBR703 was reported to inhibit bacterial RNA polymerase (RNAP) and biofilm formation, considering it to be a good candidate for further optimization. While synthesized derivatives of CBR703 did not result in more-active RNAP inhibitors, we observed promising antibacterial activities. These again correlated with a significant cytotoxicity toward mammalian cells. Furthermore, we suspect the promising effects on biofilm formation to be artifacts. Consequently, this class of compounds can be considered unattractive as antibacterial agents. Copyright
- Zhu, Weixing,Haupenthal, J?rgm,Groh, Matthias,Fountain, Michelle,Hartmann, Rolf W.
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supporting information
p. 4242 - 4245
(2014/07/08)
-
- Discovery of the first potent and orally available agonist of the orphan G-protein-coupled receptor 52
-
G-protein-coupled receptor 52 (GPR52) is an orphan Gs-coupled G-protein-coupled receptor. GPR52 inhibits dopamine D2 receptor signaling and activates dopamine D1/N-methyl-d-aspartate receptors via intracellular cAMP accumulation, and therefore, GPR52 agonists may have potential as a novel class of antipsychotics. A series of GPR52 agonists with a bicyclic core was designed to fix the conformation of the phenethyl ether moiety of compounds 2a and 2b. 3-[2-(3-Chloro-5-fluorobenzyl)-1-benzothiophen-7-yl]-N- (2-methoxyethyl)benzamide 7m showed potent activity (pEC50 = 7.53 ± 0.08) and good pharmacokinetic properties. Compound 7m significantly suppressed methamphetamine-induced hyperactivity in mice after oral administration of 3 mg/kg without disturbance of motor function.
- Setoh, Masaki,Ishii, Naoki,Kono, Mitsunori,Miyanohana, Yuhei,Shiraishi, Eri,Harasawa, Toshiya,Ota, Hiroyuki,Odani, Tomoyuki,Kanzaki, Naoyuki,Aoyama, Kazunobu,Hamada, Teruki,Kori, Masakuni
-
p. 5226 - 5237
(2014/07/08)
-
- Rapid development and scale-up of a 1 H -4-substituted imidazole intermediate enabled by chemistry in continuous plug flow reactors
-
The development of reactions in a continuous fashion in plug flow tube reactors (PFR) offers unique advantages to the drug development and scale-up process and can also enable chemistry that would be difficult to perform via batch processing. Herein, we r
- May, Scott A.,Johnson, Martin D.,Braden, Timothy M.,Calvin, Joel R.,Haeberle, Brian D.,Jines, Amy R.,Miller, Richard D.,Plocharczyk, Edward F.,Rener, Gregory A.,Richey, Rachel N.,Schmid, Christopher R.,Vaid, Radhe K.,Yu, Hannah
-
experimental part
p. 982 - 1002
(2012/08/27)
-
- COMPOUNDS AND METHODS FOR INHIBITING PHOSPHATE TRANSPORT
-
Compounds having activity as phosphate transport inhibitors, more specifically, inhibitors of intestinal apical membrane Na/phosphate co-transport, are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically ac
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Page/Page column 55-56
(2012/02/01)
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- COMPOUNDS USEFUL AS RETINOID-RELATED ORPHAN RECEPTOR GAMMA MODULATORS
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Disclosed are retinoid-related orphan receptor gamma (RORγ) modulators of Formula (I) and their use in the treatment of diseases mediated by RORγ, wherein the radicals have the meanings as defined in the invention.
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Page/Page column 26
(2012/08/08)
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- Structure-activity relationships of 2,4-diphenyl-1H-imidazole analogs as CB2 receptor agonists for the treatment of chronic pain
-
A series of 2,4-diphenyl-1H-imidazole analogs have been synthesized and displayed potent human CB2 agonist activity. Many of these analogs showed high functional selectivity over human CB1 receptors. The syntheses, structure-activity relationships, and selected pharmacokinetic data of these analogs are described.
- Yang, Shu-Wei,Smotryski, Jennifer,Matasi, Julius,Ho, Ginny,Tulshian, Deen,Greenlee, William J.,Brusa, Rossella,Beltramo, Massimiliano,Cox, Kathleen
-
scheme or table
p. 182 - 185
(2011/02/27)
-
- Synthesis and discovery of 2,3-dihydro-3,8-diphenylbenzo[1,4]oxazines as a novel class of potent cholesteryl ester transfer protein inhibitors
-
2,3-Dihydro-3,8-diphenylbenzo[1,4]oxazines were identified as a new class of potent cholesteryl ester transfer protein inhibitors. The most potent compound 6a (IC50 = 26 nM) possessed a favorable pharmacokinetic profile with good oral bioavailability in rat (F = 53%) and long human liver microsome stability (t1/2 = 62 min). It increased HDL-C in human CETP transgenic mice and high-fat fed hamsters. The structure and activity relationship of this series will be described in this Letter.
- Wang, Aihua,Prouty, Catherine P.,Pelton, Patricia D.,Yong, Maria,Demarest, Keith T.,Murray, William V.,Kuo, Gee-Hong
-
scheme or table
p. 1432 - 1435
(2010/07/06)
-
- IMIDAZOPYRIDINE AND RELATED ANALOGS AS SIRTUIN MODULATORS
-
Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Page/Page column 68
(2009/12/27)
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- P70 S6 KINASE INHIBITORS
-
The present invention provides p70 S6 kinase inhibitors of the formula: pharmaceutical formulations comprising them, and methods for their use.
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-
Page/Page column 56
(2009/01/20)
-
- Halogenation of ketones with N-halosuccinimides under solvent-free reaction conditions
-
Several aryl substituted ketones, cyclic ketones, 1,3-diketones and a β-ketoamide were halogenated with N-halosuccinimides under solvent-free reaction conditions (SFRC) at various temperatures (20-80 °C), whereas less enolized ketones required the presence of an acid catalyst (p-toluenesulfonic acid, PTSA). Bromination of substituted acetophenones obeys first order kinetics v=kBr[ketone] and the following correlation with the keto-enol equilibrium constant: log kBr=0.3pKE+C1, less enolized substrates being more reactive; the moderate positive charge developed in the rate determining step was confirmed by the Hammett correlation (ρ=-0.5). On the other hand, in cyclic ketones an opposite relation was observed: log kBr=-0.6pKE+C2, indicating higher reactivity of substrates with higher enolization constant (KE). The important role of the nature of the solvent (MeCN, MeOH) in preorganization of the ketone-NBS-PTSA mixture prior to SFRC bromination was found.
- Pravst, Igor,Zupan, Marko,Stavber, Stojan
-
p. 5191 - 5199
(2008/09/21)
-
- Thiazolidinone CFTR inhibitors with improved water solubility identified by structure-activity analysis
-
The thiazolidinone 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (CFTRinh-172) inhibits cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel conductance with submicromolar affinity and blocks cholera toxin-induced intestinal fluid secretion. Fifty-eight CFTRinh-172 analogs were synthesized to identify CFTR inhibitors with improved water solubility, exploring modifications in its two phenyl rings, thiazolidinone core, and core-phenyl connectors. Greatest CFTR inhibition potency was found for 3-CF3 and polar group-substituted-phenyl rings, and a thiazolidinone core. Two compounds with ~1 μM CFTR inhibition potency and solubility >180 μM (>10-fold more than CFTRinh-172) were identified: Tetrazolo-172, containing 4-tetrazolophenyl in place of 4-carboxyphenyl, and Oxo-172, containing thiazolidinedione in place of the thiazolidinone core. These water soluble thiazolidinone analogs had low cellular toxicity. The improved water solubility of Tetrazolo- and Oxo-172 make them potential lead candidates for therapy of secretory diarrheas and polycystic kidney disease.
- Sonawane,Verkman
-
body text
p. 8187 - 8195
(2009/04/11)
-
- 3-PHENYL-CINNOLINE HOMOLOGUE AND ANTITUMOR AGENT CONTAINING THE SAME
-
The present invention relates to a 3-phenyl-cinnoline analogue or a physiologically acceptable salt thereof, and a cell proliferation inhibitor and an antitumor agent comprising the same, as an active ingredient.
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-
Page/Page column 28
(2008/06/13)
-
- NOVEL 3-PHENYLTETRAHYDROCINNOLIN-5-OL DERIVATIVE AND MEDICINAL USE THEREOF
-
A 3-phenyltetrahydrocinnolin-5-ol derivative represented by the following general formula (1) (wherein Z represents 2-carboxyethyl, 3-dimethylaminopropyl, etc.; X represents trifluoromethyl, etc.; X' represents hydrogen, etc.; and Y and Y' each represents
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-
Page/Page column 16
(2008/06/13)
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- DIAMINOTHIAZOLES
-
The present invention is directed to novel diaminothiazoles of formula These compounds inhibit cyclin-dependent kinase 4 (Cdk4) and are selective against Cdk2 and Cdk1. These compounds and their pharmaceutically acceptable salts and esters have antiproliferative activity and are useful in the treatment or control of cancer, in particular solid tumors. This invention is also directed to pharmaceutical compositions containing such compounds and to methods of treating or controlling cancer, most particularly the treatment 6r control of breast, lung and colon and prostate tumors.
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Page/Page column 92
(2010/02/05)
-
- Synthesis and anthelmintic activity of 3,6-disubstituted-7H-s-triazolo(3,4-b) (1,3,4) thiadiazines
-
A series of 3,6-disubstituted-7H-s-triazolo (3,4-b) (1,3,4)thiadiazines was synthesized by the condensation of the appropriate 3-substituted-4-amino-5-mercapto (1,2,4) triazoles with substituted phenacyl bromides in alcoholic medium. These compounds have been studied for their in vivo anthelmintic activity in albino mice. A number of compounds showed promising activity when given by the oral route.
- Nadkarni,Kamat,Khadse
-
p. 569 - 573
(2007/10/03)
-
- Three-step synthesis of an array of substituted benzofurans using polymer-supported reagents
-
An efficient combinatorial route to substituted 3-phenyl-benzofurans, is achieved by the bromination of acetophenones to α-bromoacetophenones by polymer-supported pyridinium bromide perbromide (PSPBP). The subsequent clean substitution of the obtained bromides by phenols using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD-P) and cyclodehydration of the resulting α-phenoxyacetophenones using Amberlyst 15, affords pure products without the need for any chromatographic purification step.
- Habermann, Joerg,Ley, Steven V.,Smits, Rene
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p. 2421 - 2423
(2007/10/03)
-
- Synthesis of 6-ethoxy-6H-1,2-oxazines by hetero Diels-Alder reaction of 1-bromo-2-ethoxyethene with α-nitroso alkenes
-
A variety of 6H-1,2-oxazines 10 could efficiently be prepared by hetero Diels-Alder reaction of α-nitroso alkenes 2 with 1-bromo-2-ethoxyethene (8) and consecutive elimination of HBr by DBU. Heterodienes 2 were generated in situ from α-halogen oximes 6. Primary cycloadducts 9 were isolated in singular cases, however, an attempt to substitute bromide in 9e by an azido group gave the desired compound 11 only as minor component together with elimation product 10e. 6H-1,2-oxazines 10 are valuable precursors for addition reactions which open new synthetic possibilities.
- Homann, Kai,Angermann, Joerg,Collas, Markus,Zimmer, Reinhold,Reissig, Hans-Ulrich
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experimental part
p. 649 - 655
(2011/10/09)
-
- Novel thiazole-based heterocycles as selective inhibitors of fibrinogen- mediated platelet aggregation
-
The synthesis and biological activity of novel thiazole-based heterocycles as inhibitors of thrombin-induced human platelet aggregation are described. Further evaluation of selected compounds show they inhibit platelet aggregation as stimulated by a varie
- Sanfilippo,Urbanski,Beers,Eckardt,Falotico,Ginsberg,Offord,Press,Tighe,Tomko,Andrade-Gordon
-
-
- Photochemical Generation of Radical Anions of Photolabile Aryl Ketones
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The radical anions of a series of substituted α-(aryloxy)acetophenones have been generated by trapping the solvated electron produced by 355-nm laser-induced photoionization of 4,4'-dimethoxystilbene in either acetonitrile or dimethylformamide (DMF).The radical anion of the parent ketone, α-phenoxyacetophenone, has λmax at 500 nm and decays with a rate constant 7 x 1E5 s-1.This rate constant reflects the rate of β-cleavage to generate phenoxide ion and phenylacyl radical.The rate constant for β-cleavage decreases for ketones with electron donating substituents in the α-aryloxy ring.Substituent effects on the acetophenone ring are in the opposite direction, and many of the 4-substituted (aryloxy)acetophenones have half-lives in excess of 10 μs that reflect a combination of second order processes and are not limited by β-cleavage.The generality of the photoionization/electron trapping method for the generation of radical anions of ketones with short-lived excited states that preclude direct excitation is illustrated by its application to other aryl ketones that undergo α-cleavage, β-phenyl quenching, and intramolecular hydrogen abstraction reactions.
- Mathivanan, N.,Johnston, L. J.,Wayner, D.D.M.
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p. 8190 - 8195
(2007/10/02)
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- Studies on Cerebral Protective Agents. VIII. Synthesis of 2-Aminothiazoles and 2-Thiazolecarboxamides with Anti-anoxic Activity
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Various 2-aminothiazoles (2a-s and 3a-g) and 2-thiazolecarboxamides (4a-h), possessing a nitrogeneous basic moiety at the C-2 position of the thiazole ring, were prepared and tested for anti-anoxic (AA) activity in mice.Among them, N-4-(3-trifluoromethylphenyl)-2-thiazolecarbaxamide hydrochloride (4e, FR108143) (minimum effective doses of 3,2 mg/kg i.p. and 10 mg/kg p.o., respectively) exhibited more potent AA activity than either FK360 or compound 1, each of which has a nitrogeneous basic moiety at the C-5 position.The structure-activity relationship with regard to AA activity of this series of compounds are discussed, and the three-dimensional electrostatic potentials (3D-MEP) around the basic nitrogen atom of FK360 and the thiazole derivative (4e) are compared.Key words cerebral protective agent; anti-anoxia; 2-aminothiazole; 2-thiazolecarboxamide; structure-activity relationship; FK360
- Okhubo, Mitsuru,Kuno, Atsushi,Nakanishi,Isao,Takasugi, Hisashi
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p. 1497 - 1504
(2007/10/03)
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- Oxazolidin-2-one derivatives as hypoglycemic agents
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Certain 4-[2-(5-(optionally-substituted-aryl- and heteroaryl)oxazolidin-2-on-3-yl)alkyl]benzoic acids and ester, glycinamide, oxazole and thiazolidinedione derivatives thereof are useful as hypoglycemic agents.
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- Substituent Effects upon Efficiency of Excited-State Acetophenones Produced on Thermolysis of 3,4-Diaryl-3,4-dimethyl-1,2-dioxetanes
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The effects of meta and para substituents upon the triplet (αT) and singlet (αS) efficiencies in the thermolysis of 3,4-diaryl-3,4-dimethyl-1,2-dioxetanes 3, 3-aryl-3,4,4-trimethyl-1,2-dioxetanes 4, and 3-aryl-3-(bromomethyl)-4,4-dimethyl-1,2-dioxetanes 5 are reported.Triplet efficiencies for series 3 dioxetanes, where the two proketone moieties are identical, are sensitive to aryl substituent changes.Attempted correlation of log αT with Hammett-type substituents constants failed, and the best correlation of log αT was with the lowest triplet energy of the acetophenones T) = (0.77+/-0.19)ET1(ArCOCH3)-55.05+/-14.00, r=0.834, Sy*x=+/-0.336>.This type of correlation was previously observed with 3-aryl-3-methyl- and 3-aryl-3-methyl-3,3-(2,2'-biphenyldiyl)-1,2-dioxetanes, where the slopes (S values) are 0.38+/-0.14 and 0.52+/-0.08, respectively.In these two dioxetane series, the triplet energies of the companion proketones (formaldehyde and fluorenone) to ArCOCH3 are approximately equal to and less than ET1(ArCOCH3).For the 4 and 5 series dioxetanes, there was no change in triplet efficiency with various aryl substituents, where the average αT values are 29.1+/-2.4percent for 4 and 28.1+/- 0.7percent for 5.For these two dioxetane series, the triplet energy of the companion proketone (acetone) is higher than ET1(ArCOCH3).With regard to triplet efficiencies, all of these dioxetane series fall into two categories: (i) where the companion proketones possess triplet energies approximately equal to or less than ET1(ArCOCH3) and where αT is dependent upon substituent changes in the ArCOCH3 moiety; (ii) where the companion proketone possesses a triplet energy higher than ET1(ArCOCH3) and αT is independent of substitution changes in the ArCOCH3 moiety.An exciplex or encounter complex process is proposed to explain the apparent communication between the two proketone moieties in category i dioxetanes.Activation parameters for series 3-5 were typical of most other tetrasubstituted dioxetanes.The ρ values for ?+ correlations of series 3 and 4 plus 5 dioxetanes are -0.285 +/- 0.033 and -0.20 +/- 0.05, respectively, which is consistent with a 1,4-dioxy biradical decomposition process.
- Richardson, William H.,Stiggal-Estberg, Diana L.,Chen, Zhangping,Baker, John C.,Burns, David M.,Sherman, David G.
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p. 3143 - 3150
(2007/10/02)
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- Heterocycles. 9. 2-Aryl-2H-1,4-tetrahydrooxazines (1,2)
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Reaction of 2-bromo-1-phenylethanones with diethanolamine gave 2-hydroxymorpholines.Acetylation gave mono or diacetates.Acid catalyzed dehydratations gave several types of products whose structures are discussed.
- Meyer, Donald, R.,Weintraub, Philip M.
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p. 451 - 453
(2007/10/02)
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- 2[5-(3-Trifluoromethylphenyl)-1,3,4-oxadiazol-2-yl] benzoates
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The invention relates to compounds of the formula STR1 wherein R is H, lower alkyl or agriculturally acceptable cations; and wherein A is a 1,3,4-oxadiazol, 1,3-oxazole and 1,3,4-triazole which are useful as plant growth regulators.
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- Pharmaceutical compositions and methods of producing coronary vasodilation
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Pharmaceutical compositions and methods of producing coronary vasodilation by administering substituted benzofurans, for example 2-n-butyl-3-[4' -(2-hydroxy-3-isopropylamino)propoxybenzoyl] benzofuran.
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- Substituted benzofurans and benzothiophenes
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The compounds of this invention are substituted benzofurans and benzothiophenes having pharmacological activity. In particular, these compounds have coronary vasodilator activity and are useful in the treatment angina pectoris.
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