- Rapid and high-yield synthesis of aryloxyacetates under microwave irradiation and phase-transfer catalysis conditions
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A series of methyl aryloxyacetates (3a-3f) have been synthesized by the reaction of substituted phenol with methyl chloroacetate under the conditions of microwave irradiation and phase-transfer catalysis. By the optimization of the reaction conditions, we developed a good method for the preparation of methyl aryloxyacetates, which have the advantages of high yields, short reaction times, ease of workup, and simple operation. Copyright Taylor & Francis, Inc.
- Wei, Tai-Bao,Liu, Hong,Li, Man-Lin,Zhang, You-Ming
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Read Online
- Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors
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A series of aryloxyacetic acid derivatives were designed and synthesized as 4-hydoxyphenylpyruvate dioxygenase (HPPD) inhibitors. Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD (AtHPPD) inhibitors, in particular compounds I12 (Ki = 0.011 μM) and I23 (Ki = 0.012 μM), which exhibit similar activities to that of mesotrione, a commercial HPPD herbicide (Ki = 0.013 μM). Furthermore, the newly synthesized compounds show significant greenhouse herbicidal activities against tested weeds at dosages of 150 g ai/ha. In particular, II4 exhibited high herbicidal activity for pre-emergence treatment that was slightly better than that of mesotrione. In addition, compound II4 was safe for weed control in maize fields at a rate of 150 g ai/ha, and was identified as the most potent candidate for a novel HPPD inhibitor herbicide. The compounds described herein may provide useful guidance for the design of new HPPD inhibiting herbicides and their modification.
- Huang, Hao,Liu, Jian-Min,Shu, Lei,Wang, Man-Man,Yan, Yi-Le,Zhang, Da-Yong,Zhang, Jian-Qiu
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supporting information
p. 233 - 247
(2020/03/27)
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- Selective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core
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Janus kinases (JAKs) are non-receptor tyrosine kinases that are essential components of the JAK-STAT signaling pathway. Associated aberrant signaling is responsible for many forms of cancer and disorders of the immune system. The present focus is on the d
- Liosi, Maria-Elena,Krimmer, Stefan G.,Newton, Ana S.,Dawson, Thomas K.,Puleo, David E.,Cutrona, Kara J.,Suzuki, Yoshihisa,Schlessinger, Joseph,Jorgensen, William L.
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p. 5324 - 5340
(2020/06/10)
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- Design, synthesis and biological evaluation of novel FFA1/GPR40 agonists: New breakthrough in an old scaffold
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Based on an old phenoxyacetic acid scaffold, CPU014 (compound 14) has been identified as a superior agonist by comprehensive exploration of structure-activity relationship. In vitro toxicity study suggested that CPU014 has lower risk of hepatotoxicity than TAK-875. During acute toxicity study (5–500 mg/kg), a favorable therapeutic window of CPU014 was observed by evaluation of plasma profiles and liver slices. Moreover, CPU014 promotes insulin secretion in a glucose-dependent manner, while no GLP-1 secretion has been enhanced. Other than good pharmacokinetic properties, CPU014 significantly improved glucose tolerance both in normal and diabetic models without the risk of hypoglycemia. These subversive findings provided a safer candidate CPU014, which is currently in preclinical study to assess its potential for the treatment of diabetes.
- Li,Liu, Chunxia,Yang, Jianyong,Zhou,Ye, Zhiwen,Feng,Yue, Na,Tong,Huang, Wenlong,Qian, Hai
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p. 608 - 622
(2019/07/05)
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- New: N -phenyl-4,5-dibromopyrrolamides as DNA gyrase B inhibitors
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Due to the rapid development of antimicrobial resistance, the discovery of new antibacterials is essential in the fight against potentially lethal infections. The DNA gyrase B (GyrB) subunit of bacterial DNA gyrase is an excellent target for the design of
- Zidar, Nace,Macut, Helena,Toma?i?, Tihomir,Peterlin Ma?i?, Lucija,Ila?, Janez,Zega, Anamarija,Tammela, P?ivi,Kikelj, Danijel
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supporting information
p. 1007 - 1017
(2019/06/27)
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- Histone deacetylase inhibitors and its preparation method and use thereof
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The invention discloses a histone deacetylase inhibitor and its preparation method and use, the invention discloses a compound of the formula I as shown, or its crystalline form, or its pharmaceutically acceptable salt, or solvate thereof, or prodrug thereof, or its metabolic product. The invention of the formula I illustrated new compound, has shown good deacetylase inhibition activity, with the histone deacetylase for clinical treatment of diseases associated with abnormal activity of a new pharmaceutical may be.
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Paragraph 0198-0203
(2019/05/15)
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- Synthesis and molecular structures of 1-hydroxyethyl-2-(p-substituted) phenoxymethyl benzimidazoles
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Five novel 1-hydroxyethyl-2-(p-substituted) phenoxymethyl benzimidazoles were synthesized by a three-step route. Under microwave irradiation, the p-substituted phenols were firstly O-carboxymethylated to prepare the corresponding p-substituted phenoxymethyl acids, which then reacted with o-phenylendiamine to get the key intermediates 2-(p-substituted) phenoxymethyl benzimidazole. Finally, the solid-liquid phase transfer catalysis method, where tetrabutyl ammonium bromide (TBAB) was used as the catalyst, was applied to synthesize the target compounds c1-c5 by the N-hydroxyethylation reaction with 2-chloroethyl alcohol. The structures of the obtained compounds were well characterized and confirmed by elemental analysis, MS, IR, 1H NMR, 13C NMR and single-crystal X-ray diffraction analysis.
- Wu, Jiacheng,Zhao, Li,Zhao, Changqing,Wang, Zhiyuan,Gu, Haibin,Chen, Wuyong
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p. 974 - 980
(2016/11/22)
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- Novel Quinazoline Derivatives Bearing Various 4-Aniline Moieties as Potent EGFR Inhibitors with Enhanced Activity Against NSCLC Cell Lines
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A class of novel quinazoline derivatives bearing various C-4 aniline moieties was synthesized and biologically evaluated as potent epidermal growth factor receptor (EGFR) inhibitors for intervention of non-small-cell lung cancer (NSCLC). Most of these inhibitors are comparable to gefitinib in inhibiting these cancer cell lines, and several of them even displayed superior inhibitory activity. In particular, analogue 5b with an IC50 of 0.10 μm against the EGFR wild-type A431 cells and 5c with an IC50 of 0.001 μm against the gefitinib-sensitive HCC827 cells (EGFR del E746-A750) was identified as highly active EGFR inhibitors. It was also significant that the discovered analogue 2f, not only has high potency against the gefitinib-sensitive cells (IC50 = 0.031 μm), but also possesses remarkably improved activity against the gefitinib-resistant cells. In addition, the enzymatic assays and the Western blot analysis for evaluating the effects of the typical inhibitors indicated that these molecules strongly interfere with the EGFR target.
- Wang, Changyan,Sun, Yajun,Zhu, Xingqi,Wu, Bin,Wang, Qiao,Zhen, Yuhong,Shu, Xiaohong,Liu, Kexin,Zhou, Youwen,Ma, Xiaodong
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p. 635 - 643
(2016/03/19)
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- N-Phenyl-4,5-dibromopyrrolamides and N-Phenylindolamides as ATP Competitive DNA Gyrase B Inhibitors: Design, Synthesis, and Evaluation
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Bacterial DNA gyrase is a well-known and validated target in the design of antibacterial drugs. However, inhibitors of its ATP binding subunit, DNA gyrase B (GyrB), have so far not reached clinical use. In the present study, three different series of N-ph
- Zidar, Nace,Macut, Helena,Toma?i?, Tihomir,Brvar, Matja?,Montalv?o, Sofia,Tammela, P?ivi,Solmajer, Tom,Peterlin Ma?i?, Lucija,Ila?, Janez,Kikelj, Danijel
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supporting information
p. 6179 - 6194
(2015/08/24)
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- Pyrrolidinyl phenylurea derivatives as novel CCR3 antagonists
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Optimization starting with our lead compound 1 (IC50 = 4.9 nM) led to the identification of pyrrolidinyl phenylurea derivatives. Further modification toward improvement of the bioavailability provided (R)-1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2- hydroxyethoxy)phenyl)urea 32 (IC50 = 1.7 nM), a potent and orally active CCR3 antagonist.
- Nitta, Aiko,Iura, Yosuke,Inoue, Hideki,Imaoka, Takayuki,Takahashi, Toshiya,Sato, Ippei,Morihira, Koichiro,Kubota, Hirokazu,Morokata, Tatsuaki,Takeuchi, Makoto,Ohta, Mitsuaki,Tsukamoto, Shin-Ichi
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p. 6876 - 6881,6
(2020/09/02)
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- Aza-Michael addition of acrylonitrile with 2-aryloxymethylbenzimidazole derivatives under microwave irradiation
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A simple, rapid, and highly efficient method has been developed for the aza-Michael addition of acrylonitrile to 2-aryl-oxymethylbenzimidazole derivatives in the presence of anhydrous potassium carbonate under microwave irradiation. A series novel of 1-cyanoethyl-2-aryloxymethylbenzimidazole derivatives have been prepared and characterised by 1H NMR, 13C NMR, IR spectra and elemental analysis.
- Wei, Tai-Bao,Hua, Mao-Tang,Shi, Hai-Xiong,Liu, Yong,Zhang, You-Ming
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scheme or table
p. 452 - 454
(2010/12/24)
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- Synthesis, structural activity-relationships, and biological evaluation of novel amide-based allosteric binding site antagonists in NR1A/NR2B N-methyl-d-aspartate receptors
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The synthesis and structure-activity relationship analysis of a novel class of amide-based biaryl NR2B-selective NMDA receptor antagonists are presented. Some of the studied compounds are potent, selective, non-competitive, and voltage-independent antagonists of NR2B-containing NMDA receptors. Like the founding member of this class of antagonists (ifenprodil), several interesting compounds of the series bind to the amino terminal domain of the NR2B subunit to inhibit function. Analogue potency is modulated by linker length, flexibility, and hydrogen bonding opportunities. However, unlike previously described classes of NR2B-selective NMDA antagonists that exhibit off-target activity at a variety of monoamine receptors, the compounds described herein show much diminished effects against the hERG channel and α1-adrenergic receptors. Selections of the compounds discussed have acceptable half-lives in vivo and are predicted to permeate the blood-brain barrier. These data together suggest that masking charged atoms on the linker region of NR2B-selective antagonists can decrease undesirable side effects while still maintaining on-target potency.
- Mosley, Cara A.,Myers, Scott J.,Murray, Ernest E.,Santangelo, Rose,Tahirovic, Yesim A.,Kurtkaya, Natalie,Mullasseril, Praseeda,Yuan, Hongjie,Lyuboslavsky, Polina,Le, Phuong,Wilson, Lawrence J.,Yepes, Manuel,Dingledine, Ray,Traynelis, Stephen F.,Liotta, Dennis C.
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experimental part
p. 6463 - 6480
(2011/03/17)
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- FUNCTIONALIZED PHENOLIC COMPOUNDS AND POLYMERS THEREFROM
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The present invention relates to compounds of formula I, which are functionalized phenolic compounds, and polymers formed from the same. Ar—[O—(X)p—R′]q??I Polymers formed from the functionalized phenolics are expected to have controllable degradation profiles, enabling them to release an active component over a desired time range. The polymers are also expected to be useful in a variety of medical applications.
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Page/Page column 34
(2009/07/17)
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- Functionalized drugs and polymers derived therefrom
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Compounds selected from: where DRUG-OH, DRUG-COOH and DRUG-NH2 are biologically active compounds; each X is independently selected from —CH2COO— (glycolic acid moiety), —CH(CH3)COO— (lactic acid moiety), —CH2CH2OCH2COO— (dioxanone moiety), —CH2CH2CH2CH2CH2COO— (caprolactone moiety), —(CH2)yCOO—, where y is 2-4 or 6-24 and —(CH2CH2O)zCH2COO—, where z is 2-24; each Y is independently selected from —COCH2O— (glycolic ester moiety), —COCH(CH3)O— (lactic ester moiety), —COCH2OCH2CH2O— (dioxanone ester moiety), —COCH2CH2CH2CH2CH2O— (caprolactone ester moiety), —CO(CH2)mO—, where m is 2-4 or 6-24 and —COCH2O(CH2CH2O)n— where n is between 2-24; R′ is hydrogen, benzyl or an alkyl group, the alkyl group being either straight-chained or branched; and p is 1-6. Multi-functional compounds and drug dimers, oligomers and polymers are also disclosed.
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Page/Page column 18
(2008/06/13)
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- A rapid and high-yield synthesis of aryloxyacetic acid in one pot under microwave irradiation and phase transfer catalysis conditions
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A series of aryloxyacetic acid 3a-h has been synthesized in one pot under microwave irradiation and phase transfer catalysis conditions. By the optimization of the reaction condition, a rapid, high-yield and efficient method for the preparation of aryloxyacetic acid is reported.
- Wei, Tai-Bao,Liu, Hong,Li, Man-Lin,Zhang, You-Ming
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p. 1312 - 1314
(2007/10/03)
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- A rapid and high-yield synthesis of aryloxyacetyl hydrazides under microwave irradiation and with phase transfer catalysis
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A series of aryloxyacetyl hydrazides 4a-l were synthesised under microwave irradiation and phase transfer catalysis conditions. By the optimisation of the reaction conditions, a rapid, high-yield and efficient method for the preparation of aryloxyacety hydrazide was given.
- Wei, Tai-Bao,Liu, Hong,Li, Man-Lin,Zhang, You-Ming
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p. 432 - 433
(2007/10/03)
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- Chemokine receptor binding compounds
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The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR5. These compounds
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Page/Page column 20
(2008/06/13)
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- Synthesis of Aryloxyacetic Acids, Esters, and Hydrazides Assisted by Microwave Irradiation
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Under microwave irradiation on clay a series of transformations of a number of phenols into their aryloxyacetic acids 3 and then their methyl esters 4 and hydrazides 5 has been achieved efficiently in good yields.
- Hamid, Hamida M. Abdel,Ramadan, El Sayed,Hagar, Mohamed,El Ashry, El Sayed H.
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p. 377 - 382
(2007/10/03)
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- Microsomal triglyceride transfer protein inhibitor
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The present invention provides inhibitors of microsomal triglyceride transfer protein (MTP) and/or apolipoprotein B (Apo B) secretion having Formula (I) which are useful for the treatment of obesity and related diseases, as well as prevention and treatment of atherosclerosis and its clinical sequelae, for lowering serum lipids, and in the prevention and treatment of related diseases. The invention further relates to pharmaceutical compositions comprising the compounds of the present invention and to methods of treating obesity, atherosclerosis, and related diseases and/or conditions with the compounds of the present invention, either alone or in combination with other medicaments, including lipid-lowering agents.
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Page/Page column 23
(2010/02/07)
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- HETEROCYCLIC BETA-3 ADRENERGIC RECEPTOR AGONISTS
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This invention provides compounds of Formula I having the structure U, V, W, X, and Y are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.
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- Molecular design, synthesis, and hypoglycemic activity of a series of thiazolidine-2,4-diones
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A series of imidazopyridine thiazolidine-2,4-diones were designed and synthesized from their corresponding pyridines. These compounds represent conformationally restricted analogues of the novel hypoglycemic compound rosiglitazone (5). The series was evaluated for its effect on insulin-induced 3T3-L1 adipocyte differentiation in vitro and its hypoglycemic activity in the genetically diabetic KK mouse in vivo. The structure-activity relationships are discussed. On the basis of the in vivo potency, 5-[4-(5-methoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-ylmethoxy)ben zyl]thiazolidine-2,4-dione (19a) was selected as the candidate for further studies in a clinical setting.
- Oguchi,Wada,Honma,Tanaka,Kaneko,Sakakibara,Ohsumi,Serizawa,Fujiwara,Horikoshi,Fujita
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p. 3052 - 3066
(2007/10/03)
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- Benzimidazole derivatives, their preparation and their therapeutic use
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Compounds of formula (I): STR1 [wherein: X represents an optionally substituted benzimidazole group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethlyl group; R represents hydrogen, alkyl, alkoxy, halogen, hydroxy, nitro, amino or aralkyl; and m is an integer from 1 to 5]; have valuable activity for the treatment and/or prophylaxis of a variety of disorders, including one or more of: hyperlipemia, hyperglycemia, obesity, impaired glucose tolerance (IGT), insulin resistance and diabetic complications.
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- Treatment of arteriosclerosis and xanthoma
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A combination of one or more HMG-CoA reductase inhibitors (for example pravastatin, lovastatin, simvastatin, fluvastatin, rivastatin or atorvastatin) with one or more insulin sensitizers (for example troglitazone, pioglitazone, englitazone, BRL-49653, 5-(4-{2-?1-(4-2'-pyridylphenyl)ethylideneaminooxy!-ethoxy}benzyl)thiazolidine-2,4-dione, 5-{4-(5-methoxy-3-methylimidazo?5,4-b!pyridin-2-yl-methoxy)benzyl}thiazolidine-2,4-dione or its hydrochloride, 5-?4-(6-methoxy-l-methylbenzimidazol-2-ylmethoxy)benzyl!thiazolidine-2,4-dione, 5-?4-(l-methylbenzimidazol-2-ylmethoxy)benzyl!-thiazolidine-2,4-dione and 5-?4-(5-hydroxy-1,4,6,7-tetramethylbenzimidazol-2-ylmethoxy) benzyllthiazolidine-2,4-dione) exhibits a synergistic effect and is significantly better at preventing and/or treating arteriosclerosis and/or xanthoma than is either of the components of the combination alone.
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- Benzimidazole derivatives
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Disclosed are compounds represented by the following chemical formula (I) and pharmacologically acceptable salts thereof which are novel compounds useful as anticancer agents, antiviral agents or antimicrobial agents. STR1
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- Heterocyclic compounds having anti-diabetic activity and their use
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Compounds of formula (I): STR1 [wherein: X represents an unsubstituted or substituted indolyl, indolinyl, azaindolyl, azaindolinyl, imidazopyridyl or imidazopyrimidinyl group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethyl group; R represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, a hydroxy group, a nitro group, an aralkyl group or a unsubstituted or substituted amino group; and m is an integer of from 1 to 5] have hypoglycemic and anti-diabetic activities.
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- Benzimidazole derivatives, their preparation and their therapeutic use
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Compounds of formula (I): [in which: X represents an optionally substituted benzimidazole group; Y represents an oxygen or sulphur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxo-oxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethyl group; R represents hydrogen, alkyl, alkoxy, halogen, hydroxy, nitro, amino or aralkyl; and mis an integer from 1 to 5]; have valuable activity for the treatment and/or prophylaxis of a variety of disorders, including one or more of: hyperlipemia, hyperglycemia, obesity, impaired glucose tolerance (IGT), insulin resistance and diabetic complications.
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- Applicability of Hammett Equation to the Kinetics of Acid-catalysed Esterification of meta- and para-Substituted Phenoxyacetic Acids by Methanol
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Rate constants have been determined for the acid-catalysed esterification of meta- and para-substituted phenoxyacetic acids by methanol, with hydrogen chloride as catalyst.The applicability of the Hammett equation to the rate data has been examined.The para-substituted benzoic acids react slower than the corresponding para-substituted phenoxyacetic acids.The probable cause of this behaviour is discussed.
- Baliah, V.,Gurumurthy, R.
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p. 629 - 631
(2007/10/02)
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- Influence of meta- and para-Substituents on the Kinetics of Esterification of Phenoxyacetic Acids by Methanol
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The influence of meta- and para- substituents on the kinetics of acid-catalysed esterification of phenoxyacetic acids is discussed.In the case of para Cl, Br and I substituents, d-orbital resonance is suggested to explain the observed behaviour.The possibility of protonation of the methoxy oxygen in the acid medium employed is indicated to explain the slower rate of reaction of m- and p-methoxyphenoxyacetic acids.
- Baliah, V.,Gurumurthy, R.
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p. 1082 - 1083
(2007/10/02)
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