- Solid state properties of 1,2-epoxy-3-(2-methoxyphenyloxy)-propane - Valuable intermediate in non-racemic drug synthesis
-
Racemic 1,2-epoxy-3-(2-methoxyphenyloxy)-propane 1 undergoes spontaneous resolution upon crystallization. This fact is confirmed by coincidence of the IR spectra of racemic and scalemic crystalline samples of 1, by thermal analysis (single eutectic V-shape binary melting phase diagram), and X-ray analysis (space group P212121, Z = 4). Racemic 1 could be resolved into (S)-(+)- and (R)-(-)-1 by a preferential crystallization procedure.
- Bredikhin, Alexander A.,Strunskaya, Elena I.,Zakharychev, Dmitry V.,Krivolapov, Dmitry B.,Litvinov, Igor A.,Bredikhina, Zemfira A.
-
-
Read Online
- Efficient synthesis of 8-methoxy-3,4-dihydro-2H-1-benzopyran-3-ol
-
The article reports a practical, simple, and inexpensive procedure for the synthesis of 8-methoxy-3,4-dihydro-2H-1-benzopyran-3-ol (1). 2-Methoxy phenol on treatment offers the oxirane compound, which undergoes ring cleavage under acidic conditions to give a chlorohydrin, which on acylation and cyclization in the presence of stannic chloride followed by hydrolysis of the acetyl group, yields the desired compound (1).
- Shindikar,Viswanathan
-
-
Read Online
- Alternating and regioregular copolymers with high refractive index from COS and biomass-derived epoxides
-
This study describes the catalytic formation of alternating and regioregular copolymers from carbonyl sulfide (COS) and epoxides along with eugenol-based glycidyl ether (EGE) and guaiacol-based glycidyl ether (GGE), derived from eugenol and guaiacol, respectively. The (salen)CrCl [salen = N,N′-bis(salicylidene) cyclohexanediimine] complex, accompanied with various organic bases, was highly active towards the EGE/COS, GGE/COS copolymerization and EGE/GGE/COS terpolymerization. The turnover of frequency (TOF) of the (salen)CrCl complex for the EGE/COS copolymerization was up to 12000 h-1. The number-average molecular weight (Mn) of the resultant EGE/COS copolymer was up to 62.2 kg mol-1. In the presence of 0.5-1.5 mol% chlorohydrin, which was a by-product of the synthetic process of EGE, α-Cl, ω-OH EGE/COS copolymers were obtained. This result suggests that chlorohydrin could act as a very efficient chain transfer agent for the copolymerization. The EGE/COS, GGE/COS, and EGE/GGE/COS copolymers were soluble in most of the common solvents and exhibited a high refractive index of more than 1.58 with high Abbe numbers of up to 40.4. This study provides an unprecedented and sustainable synthetic route for making soluble sulfur-rich polymers with high optical properties.
- Hu, Lan-Fang,Li, Yang,Liu, Bin,Zhang, Ying-Ying,Zhang, Xing-Hong
-
-
Read Online
- Lariat Ethers. Synthesis and Cation Binding of Macrocyclic Polyethers Possessing Axially Disposed Secondary Donor Groups
-
The synthesis and cation binding properties of a series of macrocyclic polyethers which possess ligating arms that enhance cation binding is presented.
- Gokel, George W.,Dishong, Dennis M.,Diamond, Craig J.
-
-
Read Online
- Substituted diaryl compound and preparation method and application thereof
-
The invention relates to the field of medicinal chemistry, in particular to a substituted diaryl compound (I). The preparation method comprises the following steps: medicine preparation and medical application thereof. Test results show that the substituted diaryl compound has a good inhibition effect on human lung cancer (A549), human ovarian cancer (SKOV3), human melanoma (A375) and human colon cancer (LOVO) cells. Formula (I):
- -
-
Paragraph 0073-0075; 0076
(2021/09/15)
-
- A low toxic CRM1 degrader: Synthesis and anti-proliferation on MGC803 and HGC27
-
Chromosome region maintenance 1 (CRM1) is the sole nuclear exporter of several tumor suppressor, a growth regulatory protein as an attractive cancer drug target. In the present work, a novel CRM1 degrader was discovered from newly synthesized α, β-unsaturated-δ-lactone based on a natural product Goniothalamin. It induces apoptosis of both MGC803 and HGC27 cell lines via degrading CRM1. Selective inhibition was observed for the proliferation of gastric cancer cell lines MGC803, HGC27 comparing to Human Gastric Mucosal Epithelial Cell Line (GES1). For the first time, CRM1 inhibitor or degrader inducing apoptosis in gastric carcinoma was investigated.
- Jia, Shilong,Jin, Cheng-Yun,Li, Xiaobo,Liu, Mengbo,Meng, Xia,Wang, Menglin,Wu, Xinxin,Xu, Hai-Wei,Yu, Lu
-
-
- Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H1 antagonize activities
-
To improve the anti-inflammatory activity of desloratadine, we designed and synthesized a series of novel desloratadine derivatives. All compounds were evaluated for their anti-inflammatory and H1 antagonistic activities. Among them, compound 2c showed the strongest H1 antagonistic and anti-inflammatory activity. It also exhibited promising pharmacokinetic profiles and low toxicity. All these results suggest that compound 2c as a novel anti-allergic agent is worthy of further investigation.
- Li, Feng,Xu, Qinlong,Zhu, Qihua,Chu, Zhaoxing,Lin, Gaofeng,Mo, Jiajia,Zhao, Yan,Li, Jiaming,He, Guangwei,Xu, Yungen
-
-
- Design, Synthesis, and Biological Evaluation of a New Series of Carvedilol Derivatives That Protect Sensory Hair Cells from Aminoglycoside-Induced Damage by Blocking the Mechanoelectrical Transducer Channel
-
Aminoglycosides (AGs) are broad-spectrum antibiotics used for the treatment of serious bacterial infections but have use-limiting side effects including irreversible hearing loss. Here, we assessed the otoprotective profile of carvedilol in mouse cochlear cultures and in vivo zebrafish assays and investigated its mechanism of protection which, we found, may be mediated by a block of the hair cell's mechanoelectrical transducer (MET) channel, the major entry route for the AGs. To understand the full otoprotective potential of carvedilol, a series of 18 analogues were prepared and evaluated for their effect against AG-induced damage as well as their affinity for the MET channel. One derivative was found to confer greater protection than carvedilol itself in cochlear cultures and also to bind more tightly to the MET channel. At higher concentrations, both carvedilol and this derivative were toxic in cochlear cultures but not in zebrafish, suggesting a good therapeutic window under in vivo conditions.
- O'Reilly, Molly,Kirkwood, Nerissa K.,Kenyon, Emma J.,Huckvale, Rosemary,Cantillon, Daire M.,Waddell, Simon J.,Ward, Simon E.,Richardson, Guy P.,Kros, Corné J.,Derudas, Marco
-
p. 5312 - 5329
(2019/06/07)
-
- Improving the activity and enantioselectivity of PvEH1, a Phaseolus vulgaris epoxide hydrolase, for o-methylphenyl glycidyl ether by multiple site-directed mutagenesis on the basis of rational design
-
Substrate spectrum assay exhibited that PvEH1, which is an epoxide hydrolase from P. vulgaris, had the highest specific activity and enantiomeric ratio (E) for racemic o-methylphenyl glycidyl ether (rac-1) among tested aryl glycidyl ethers (1–5). To produce (R)-1 via kinetic resolution of rac-1 efficiently, the catalytic properties of PvEH1 were further improved on the basis of rational design. Firstly, the seven single-site variants of PvEH1-encoding gene (pveh1) were PCR-amplified as designed, and expressed in E. coli BL21(DE3). Among all expressed single-site mutants, PvEH1L105I and PvEH1V106I had the highest specific activities of 17.6 and 16.4 U/mg protein, respectively, while PvEH1L196D had an enhanced E value of 9.2. Secondly, to combine their respective merits, one triple-site variant, pveh1L105I/V106I/L196D, was also amplified, and expressed. The specific activity, E value, and catalytic efficiency of PvEH1L105I/V106I/L196D were 23.1 U/mg, 10.9, and 6.65 mM?1 s?1, respectively, which were 2.0-, 1.8- and 2.4-fold higher than those of wild-type PvEH1. The source of PvEH1L105I/V106I/L196D with enhanced E value for rac-1 was preliminarily analyzed by molecular docking simulation. Finally, the scale-up kinetic resolution of 100 mM rac-1 was conducted using 5 mg wet cells/mL E. coli/pveh1L105I/V106I/L196D at 25 °C for 1.5 h, producing (R)-1 with 95.0% ees, 32.1% yield and 3.52 g/L/h space-time yield.
- Li, Chuang,Kan, Ting-Ting,Hu, Die,Wang, Ting-Ting,Su, Yong-Jun,Zhang, Chen,Cheng, Jian-Qing,Wu, Min-Chen
-
-
- Chiral Bifunctional Metalloporphyrin Catalysts for Kinetic Resolution of Epoxides with Carbon Dioxide
-
Chiral binaphthyl-strapped Zn(II) porphyrins with triazolium halide units were synthesized as bifunctional catalysts for kinetic resolution of epoxides with CO2. Several catalysts were screened by changing the linker length and nucleophilic counteranions, and the optimized catalyst accelerated the enantioselective reaction at ambient temperature to produce optically active cyclic carbonates and epoxides.
- Maeda, Chihiro,Mitsuzane, Mayato,Ema, Tadashi
-
supporting information
p. 1853 - 1856
(2019/03/11)
-
- Compounds for treating anginapectoris, preparation method and application
-
The invention relates to the field of medicinal chemistry, and particularly relates to compounds I, II and III corporation ranolazine derivatives or pharmaceutically acceptable salt thereof, a preparation method of the compounds, a medicinal composition containing the compounds and medical application of the compounds. Pharmacodynamic experiments prove that the compounds disclosed by the invention have an effect of treating anginapectoris. (the compounds are shown in the specification).
- -
-
Sheet 0053; 0054; 0055; 0056
(2017/09/01)
-
- Chiral Macrocyclic Organocatalysts for Kinetic Resolution of Disubstituted Epoxides with Carbon Dioxide
-
Among chiral macrocycles 1 synthesized, 1m with the 3,5-bis(trifluoromethyl)phenylethynyl group was the best organocatalyst for the enantioselective synthesis of cyclic carbonates from disubstituted or monosubstituted epoxides and CO2. The X-ray crystal structure of 1m revealed a well-defined chiral cavity with multiple hydrogen-bonding sites that is suitable for the enantioselective activation of epoxides. A catalytic cycle proposed was supported by DFT calculations.
- Ema, Tadashi,Yokoyama, Maki,Watanabe, Sagiri,Sasaki, Sota,Ota, Hiromi,Takaishi, Kazuto
-
supporting information
p. 4070 - 4073
(2017/08/15)
-
- NOVEL PROCESS FOR THE PREPARATION OF RANOLAZINE
-
The present invention relates to novel processes for the preparation of Ranolazine (I) and its acid addition salts and the novel process for the preparation of compound of formula (7).
- -
-
Page/Page column 17
(2016/09/26)
-
- Chemical modifications of lignin for the preparation of macromers containing cyclic carbonates
-
An epoxidized lignin derivative was prepared directly inserting epichlorohydrin on the phenolic functionalities. The epoxidized lignin was then converted to cyclic carbonates through the coupling reaction of CO2 with the oxirane rings. Imidazolium based ionic liquids, acting as both solvents and catalysts, were successfully employed in the carbonation reaction. Moreover, the ionic liquid was reused up to three times without significant loss in activity. Finally, an exhaustive spectroscopic characterization was carried out on the epoxidized and carbonated lignins by quantitative 31P and 13C NMR analyses.
- Salanti, Anika,Zoia, Luca,Orlandi, Marco
-
p. 4063 - 4072
(2016/07/21)
-
- Discovery of (phenoxy-2-hydroxypropyl)piperidines as a novel class of voltage-gated sodium channel 1.7 inhibitors
-
A novel class of NaV1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse NaV1.7 inhibitory activities with fair subtype selectivity over NaV1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin.
- Suzuki, Sayaka,Kuroda, Takeshi,Kimoto, Hiroko,Domon, Yuki,Kubota, Kazufumi,Kitano, Yutaka,Yokoyama, Tomihisa,Shimizugawa, Akiko,Sugita, Ryusuke,Koishi, Ryuta,Asano, Daigo,Tamaki, Kazuhiko,Shinozuka, Tsuyoshi,Kobayashi, Hiroyuki
-
p. 5419 - 5423
(2015/11/09)
-
- A smart library of epoxide hydrolase variants and the top hits for synthesis of (S)-β-blocker precursors
-
Microtuning of the enzyme active pocket has led to a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots. This study represents a breakthrough in protein engineering of epoxide hydrolases and resulted in enhanced activity toward bulky substrates. Hot pockets: Microtuning of the enzyme active pocket gives a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots, and enhanced activity toward bulky substrates was found.
- Kong, Xu-Dong,Ma, Qian,Zhou, Jiahai,Zeng, Bu-Bing,Xu, Jian-He
-
supporting information
p. 6641 - 6644
(2014/07/08)
-
- Synthesis of ranolazine derivatives containing the (1S,4S)-2,5- diazabicyclo[2.2.1]heptane moiety and their evaluation as vasodilating agents
-
Two diazabicyclic analogues of ranolazine, (S,S,S)-5 and (S,S,R)-5, and their epimeric mixture were synthesized. Furthermore, their vasomotor effects on rat aorta rings precontracted with phenylephrine were analyzed. These compounds showed vasodilating effects significantly greater than ranolazine. The vasodilating activities of these analogues have two components, one that depends on the endothelium, due to the release of NO, and another one due to a direct effect on the vascular smooth muscle. The compounds [(S,S,S)(S,S,R)]-5 and (S,S,R)-5 induce, in a manner similar to ranolazine, the release of a prostanoid from the cyclooxygenase pathway, whose vasoconstrictor effect is masked by the predominant vasodilation induced by these compounds. Two diazabicyclic analogues of ranolazine, (S,S,S)-5 and (S,S,R)-5, and their epimeric mixture showed a vasodilating effect significantly greater than ranolazine. This vasodilating activity has two components, one of them endothelium dependent, due to the release of NO, and the other one due to a direct effect on the vascular smooth muscle. In a manner similar to ranolazine, [(S,S,S)(S,S,R)]-5 and (S,S,R)-5 induce the release of a prostanoid, whose vasoconstrictor effect is masked by the predominant vasodilation induced by these compounds.
- López-Ortiz, Manuel,Monsalvo, Ivan,Demare, Patricia,Paredes, Cristina,Mascher, Dieter,Hernández, Carlos,Hernández, Marcos,Regla, Ignacio
-
p. 710 - 720
(2014/06/09)
-
- Guaifenesin derivatives promote neurite outgrowth and protect diabetic mice from neuropathy
-
In diabetic patients, an early index of peripheral neuropathy is the slowing of conduction velocity in large myelinated neurons and a lack of understanding of the basic pathogenic mechanisms hindered therapeutics development. Racemic (R/S)-guaifenesin (1) was identified as a potent enhancer of neurite outgrowth using an in vitro screen. Its R-enantiomer (R)-1 carried the most biological activity, whereas the S-enantiomer (S)-1 was inactive. Focused structural variations to (R/S)-1 was conducted to identify potentially essential groups for the neurite outgrowth activity. In vivo therapeutic studies indicated that both (R/S)-1 and (R)-1 partially prevented motor nerve conduction velocity slowing in a mouse model of type 1 diabetes. In vitro microsomal assays suggested that compounds (R)-1 and (S)-1 are not metabolized rapidly, and PAMPA assay indicated moderate permeability through the membrane. Findings revealed here could lead to the development of novel drugs for diabetic neuropathy.
- Hadimani, Mallinath B.,Purohit, Meena K.,Vanampally, Chandrashaker,Van Der Ploeg, Randy,Arballo, Victor,Morrow, Dwane,Frizzi, Katie E.,Calcutt, Nigel A.,Fernyhough, Paul,Kotra, Lakshmi P.
-
p. 5071 - 5078
(2013/07/26)
-
- An efficient synthesis of 1-(2-Methoxyphenoxy)-2,3-epoxypropane: Key intermediate of β-adrenoblockers
-
An efficient process for the preparation of 1-(2-methoxyphenoxy)-2,3- epoxypropane, a key intermediate for the synthesis of ranolazine is described.
- Madivada, Lokeswara Rao,Anumala, Raghupathi Reddy,Gilla, Goverdhan,Kagga, Mukkanti,Bandichhor, Rakeshwar
-
p. 1660 - 1664
(2013/02/25)
-
- Improved process for ranolazine: An antianginal agent
-
An improved process has been developed for the active pharmaceutical ingredient, ranolazine with 99.9% purity and 47% overall yield (including three chemical reactions and one recrystallization). Formation and control of all the possible impurities is described. All the solvents used in the process were recovered and reused. The unreacted piperazine is recovered as piperazine monophosphate monohydrate salt.
- Aalla, Sampath,Gilla, Goverdhan,Anumula, Raghupathi Reddy,Kurella, Srinivas,Padi, Pratap Reddy,Vummenthala, Prabhakar Reddy
-
scheme or table
p. 748 - 754
(2012/08/27)
-
- Enantioselective α-hydroxylation of β-keto esters catalyzed by chiral S-timolol derivatives
-
A screen of aryloxy aminopropanol organocatalysts derived from the β-blocker inhibitor S-timolol determined the most active catalyst of asymmetric α-hydroxylation of β-keto esters. (R)-1-(tert-butylamino)- 3-(3,4,5-trimethoxyphenoxy) propan-2-ol (3k) was the most effective derivative, enantioselectively catalyzing α-hydroxylation of β-keto esters using tert-butyl hydroperoxide as the oxidant in hexane to afford the corresponding products in excellent yield and with good enantioselectivity (up to 96% yield, 88% ee).
- Cai, Yuanchun,Lian, Mingming,Li, Zhi,Meng, Qingwei
-
experimental part
p. 7973 - 7977
(2012/09/21)
-
- PREPARATION OF RANOLAZINE, ITS SALTS AND INTERMEDIATES THEREOF
-
The present patent application relates to an improved process for the preparation of Ranolazine, pharmaceutically acceptable salts and intermediates thereof. Specifically it relates to processes for preparation of 1-(2-methoxy phenoxy)-2,3-epoxy propane in substantially aqueous solvent medium and 2-chloro-N-(2,6-dimethylphenyl) acetamide without using any additional base, which are intermediates, useful in the preparation of Ranolazine and pharmaceutically acceptable salts thereof.
- -
-
Page/Page column 14; 15
(2010/04/06)
-
- PREPARATION OF RANOLAZINE
-
Preparation of ranolazine and intermediates thereof, for use in pharmaceutical compositions comprising ranolazine.
- -
-
Page/Page column 49
(2010/04/06)
-
- Thienopyrimidines as β3-adrenoceptor agonists: Hit-to-lead optimization
-
Resulting from a vHTS based on a pharmacophore alignment on known β3-adrenoceptor ligands, an aryloxypropanolamine scaffold comprising a thienopyrimidine moiety was further optimized as a human β3-AR agonist, yielding a lead compound with an excellent cellular activity of EC50 = 20 pM, selectivity over hβ1- and hβ2-adrenoceptors and a promising safety profile.
- Tasler, Stefan,Baumgartner, Roland,Ammendola, Astrid,Schachtner, Josef,Wieber, Tanja,Blisse, Marcus,Rath, Sandra,Zaja, Mirko,Klahn, Philipp,Quotschalla, Udo,Ney, Peter
-
scheme or table
p. 6108 - 6115
(2010/11/19)
-
- Bacillus alcalophilus MTCC10234 catalyzed enantioselective kinetic resolution of aryl glycidyl ethers
-
The phenyl glycidyl ether derivatives have been kinetically resolved with the growing cells of Bacillus alcalophilus MTCC10234 yielding (S)-epoxides with up to >99% ee and (R)-diols with up to 89% ee. The enantiomeric ratio (E) of up to 67 has been obtained for biohydrolysis process. The effect of different substituents of phenyl glycidyl ether on the biocatalytic efficiency of B. alcalophilus MTCC10234 showed preference for methyl- and chloro-substituted aryl glycidyl ether derivatives whereas nitro-derivatives were transformed at a slower rate. 2,6-Dimethylphenyl glycidyl ether which contains a bulky aryl group having methyl group on both the ortho positions was resolved with an E=39.
- Bala, Neeraj,Chimni, Swapandeep Singh,Saini, Harvinder Singh,Chadha, Bhupinder Singh
-
experimental part
p. 128 - 134
(2010/10/04)
-
- Regioselective cleavage of 2-aryloxymethyloxiranes to 3-aryloxy-l- halogenopropan-2-ols
-
A series of new 2-ary loxymethy loxiranes prepared from epichlorohydrin and substituted phenols was subjected to nucleophilic opening of the oxirane ring. A comparison of regioselectivity and product yield for oxirane cleavage by means of aqueous hydrohalogenic acids or lithium tetrahalogenocuprates under anhydrous conditions was performed. The latter method provided very high regioselectivity for 3-aryloxy-l-halo-genopropan-2-ols as well as excellent yields.
- Maciejewski,Poltorak,Kaminska
-
experimental part
p. 595 - 604
(2009/12/26)
-
- Synthesis of ranolazine metabolites and their anti-myocardial ischemia activities
-
The anti-anginal drug Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, is thought to modulate the metabolism during myocardial ischemia by activating pyruvate dehydrogenase activity to promote glucose oxidation. Ranolazine and its five principal metabolites: CVT-2512, CVT-2513, CVT-2514, CVT-2738 and CVT-4786, were synthesized. The effect of Ranolazine and its metabolites on the ECG (electrocardiogram) of mice with myocardial ischemia induced by isoprenaline and their effect on alleviating the symptom of myocardial ischemia were tested and compared. The results showed that CVT-2738 and CVT-2513 could be protective against mice myocardial ischemia induced by isoprenaline. Within all the metabolites tested in this study, CVT-2738 exhibited the best potency, however, it was still less potent than Ranolazine.
- Yao, Zhangyu,Gong, Shubo,Guan, Teng,Li, Yunman,Wu, Xiaoming,Sun, Hongbin
-
experimental part
p. 1218 - 1222
(2010/06/16)
-
- SUBSTITUTED PIPERAZINES
-
Disclosed herein are substituted piperazine late Na+ channel modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Page/Page column 31
(2009/01/24)
-
- IMPROVED PROCESS FOR THE PREPARATION OF RANOLAZINE
-
The present invention provides an improved process for the preparation of ranolazine of formula I and pharmaceutically acceptable salts thereof, by reacting 2,6-dimethylaniline derivative with chloroacetyl chloride in the presence of base in water and resulting amide intermediate is reacted with piperazine and the resulting piperazinc derivative is further condensed with an appropriate oxirane derivative ( prepared by the reaction of 2-methoxyphenol with epichlorohydrin in the presence of base using phase transfer catalyst) in an inert solvent, and highly pure ranolazine is isolated and converted to its acid salts using excess of mineral acid.
- -
-
Page/Page column 12; 14
(2008/12/05)
-
- Improvement and simplification of synthesis of 3-aryloxy-1,2-epoxypropanes using solvent-free conditions and microwave irradiations. Relation with medium effects and reaction mechanism
-
Some 3-aryloxy-1,2-epoxypropanes, interesting as potential synthons in β-adrenergic receptor antagonists preparation, were obtained in excellent yields (65-96% within 2-17 min) by microwave activation (monomode system) using solid-liquid solvent-free phase transfer catalysis (PTC). The best results for the O-alkylation of some phenols with epichlorohydrin were obtained using TBAB and NaOH/K2CO3 (1:4 mol/mol) as phase transfer catalyst and more acceptable basic system, respectively. These new procedure is compared with classical methods. Significant specific microwave effect (non-purely thermal) was evidenced in all cases. They were discussed in terms of reaction medium and mechanism, taking into account the variations in polarity of the systems.
- Pchelka, Beata K.,Loupy, Andre,Petit, Alain
-
p. 10968 - 10979
(2007/10/03)
-
- Synthesis, anorexigenic activity and QSAR of substituted aryloxypropanolamines
-
Substituted aryloxypropanolamines (6-20) were synthesized and evaluated for their anorexigenic activity. Among them 4-cyanoaryloxy (7), 2-methylaryloxy (9), 2-methoxyl aryloxy (10), 4-acetamidoaryloxy (15), 4-bromoaryloxy (16) and 4-ethylaminoaryloxy (20) exhibited potent anorexigenic activity. According to QSAR studies, the electronic parameter 'σ' plays an important role in describing the variance in activity. Birkhaeuser Boston 2004.
- Srivastava, Shipra,Bhandari, Kalpana,Shankar, Girija,Singh,Saxena, Anil K.
-
p. 631 - 642
(2007/10/03)
-
- New series of morpholine and 1,4-oxazepane derivatives as dopamine D 4 receptor ligands: Synthesis and 3D-QSAR model
-
Since the identification of the dopamine D43 receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D4 ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthesis of a new series of 2,4-disubstituted morpholines and 2,4-disubstituted 1,4-oxazepanes with selectivity for the dopamine D4 receptor. A 3D-QSAR analysis using the GRID/GOLPE methodology was performed with the purpose to get a better understanding of the relationship between chemical structure and biological activity. Inspection of the coefficient plots allowed us to identify that regions which are important for affinity are situated around the two benzene ring systems, a p-chlorobenzyl group, and the aliphatic amine belonging to the morpholine or 1,4-oxazepane system. In addition, the size of the morpholine or 1,4-oxazepane ring seems to be important for affinity.
- Audouze, Karine,Nielsen, Elsebet ?stergaard.,Peters, Dan
-
p. 3089 - 3104
(2007/10/03)
-
- Jacobsen-type enantioselective hydrolysis of aryl glycidyl ethers. 31P NMR analysis of the enantiomeric composition of oxiranes
-
The enantioselective partial hydrolysis of a number of racemic aryl glycidyl ethers in the presence of chiral Co(salen)-catalyst was studied. The enantiomeric composition of the isolated (R)-aryl glycidyl ethers was analyzed by 31P NMR using optically active substituted 2-chloro-1,3,2- dioxaphospholanes. A synthesis of β-adrenoblocking agents (S)-toliprolol and (S)-moprolol based on the simultaneously obtained (S)-3-aryloxypropane-1,2- diols was proposed.
- Bredikhin,Strunskaya,Novikova,Azancheev,Sharafutdinova,Bredikhina
-
p. 213 - 218
(2007/10/03)
-
- Design of new beta1-selective adrenoceptor ligands as potential radioligands for in vivo imaging.
-
In general, the failing human heart is characterized by a selective reduction in beta(1)-adrenoceptors (beta(1)-ARs) without change in beta(2)-AR density. Medical imaging techniques, either single photon emission computed tomography (SPECT) or positron emission tomography (PET) with appropriate radioligands, offer the possibility of assessing beta-adrenoceptor density non-invasively in humans. To date, neither a SPECT nor a PET radioligand is available for the selective imaging of cardiac beta(1)-ARs. The aim of this study was to develop potential high affinity beta(1)-selective AR radioligands for the non-invasive in vivo imaging of the beta(1)-AR density in the human heart using SPECT or PET. A variety of racemic N-aryl-N'-[2-[3-aryloxy-2-hydroxy-propylamino]-ethyl]-urea derivatives and chain-elongated analogues, related to the established beta(1)-AR antagonist, ICI 89,406 8i, were synthesized. Competition studies using the non-selective AR ligand, [(125)I]iodocyanopindolol ([(125)I]ICYP), and ventricular membrane preparations of wild-type mice revealed nine ligands with higher beta(1)-AR affinities (up to 76-fold) and beta(1)-AR selectivities (up to 139-fold) than 8i. Mostly, these ligands possess a 2-substituted phenoxy group and a 4-substituted phenyl residue in contrast to the lead compound 8i. The non-radioactive counterparts of the desired SPECT- and PET-radiotracers were synthesized as reference compounds [e.g., 8f, 8g, 8h and 8l as the non-radioactive analogues of the radioiodinated SPECT radioligands, 8e and 8h as the non-radioactive compounds of C-11 labelled PET-tracers (C-11 in the methoxy group)]. The established library of high affinity beta(1)-selective AR antagonists was screened for chemical precursors for the radiosynthesis of the mentioned radioligands. Furthermore, the library consists of some comparison compounds that are unsubstituted, allyl- and alkyl-substituted or chain-elongated (e.g., 8a, 8j, 8o and 8r-t). Future steps will include radiolabelling and pharmacokinetic evaluation of the beta(1)-selective target compounds, which could be applied as sympathetic innervation agents for in vivo investigations and diagnostics in patients suffering from cardiac diseases like heart failure and ventricular arrhythmias.
- Kopka, Klaus,Wagner, Stefan,Riemann, Burkhard,Law, Marilyn P,Puke, Carsten,Luthra, Sajinder K,Pike, Victor W,Wichter, Thomas,Schmitz, Wilhelm,Schober, Otmar,Schaefers, Michael
-
p. 3513 - 3527
(2007/10/03)
-
- Resolution of racemic 3-aryloxy-1-nitrooxypropan-2-ols by lipase-catalyzed enantioselective acetylation
-
Both (R)- and (S)-enantiomers of 3-aryloxy-1-nitrooxypropan-2-ols (R)-(-)-1, (S)-(+)-2 were prepared in high enantiomeric excess by lipase from Pseudomonas cepacia (Amano PS) or Pseudomonas fluorescens (Amano AK)-catalyzed acetylation of racemic alcohols 1a-g with vinyl acetate in n-hexane at 4 or 22°C. The enantioselectivity of this transformation was dependent on the substitution pattern of the aryl ring with E-values ranging from 31 to 111.
- Pchelka, Beata Krystyna,Loupy, Andre,Plenkiewicz, Jan,Petit, Alain,Blanco, Luis
-
p. 2109 - 2119
(2007/10/03)
-
- Enantioselective ring opening of epoxides with trimethylsilyl azide (TMSN3) in the presence of β-cyclodextrin: An efficient route to 1,2-azido alcohols
-
The ring opening of epoxides with nucleophiles such as TMSN3 and isopropylamine takes place enantioselectively in the presence of β- cyclodextrin under extremely mild conditions and the azido alcohols and amino alcohols are formed as (S)-isomers. (C) 1999 Published by Elsevier Science Ltd.
- Kamal, Ahmed,Arifuddin,Rao, Maddamsetty V.
-
p. 4261 - 4264
(2007/10/03)
-
- Efficient asymmetric hydrogenation of α-amino ketone derivatives. A highly enantioselective synthesis of phenylephrine, levamisole, carnitine and propranolol
-
The complexes of pyrrolidine bisphosphine ligands (CPMs) with rhodium (I) were found to be efficient catalysts for asymmetric hydrogenation of α-amino ketone hydrochloride derivatives. Utilizing this methodology, we have developed efficient asymmetric syntheses of the optically active β-amino alcohols, phenylephrine, levamisole, carnitine and propranolol.
- Sukuraba,Takahashi,Takeda,Achiwa
-
p. 738 - 747
(2007/10/02)
-
- A novel method for synthesis of aryl glycidyl ethers
-
A solid-liquid phase-transfer catalytic method for the synthesis of aryl glycidyl ethers has been described, and the factors affecting the reaction yield have been examined.
- Liu,Chen,Cao,Li
-
p. 833 - 838
(2007/10/02)
-
- Design and synthesis of a series of combined vasodilator/β-adrenoceptor antagonists based on 6-arylpyridazinones
-
A series of new 6-[4-[[(aryloxy)acyl]amino]phenyl]-4,5-dihydropyridazinones have been synthesized and evaluated as combined vasodilator/β-adrenoceptor antagonists and potential antihypertensive agents. Many of the early compounds displayed an unacceptably high level of intrinsic sympathomimetic activity (ISA) and a relatively short duration of action. Disubstitution in the 2,3-positions or in the 4-position of the aryloxy ring gave compounds with low ISA levels and, in some instances, improved duration of action. All of the compounds were vasodilators, but the 5-methylpyridazinone derivatives showed consistently greater antihypertensive activity than their 5-H lower homologues. Further detailed pharmacological investigations led to the selection of 6-[4-[3-[[2-hydroxy-3-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]propyl]amino ]propionamido]phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone (4t) (SK&F 95018) as a development candidate.
- Slater,Howson,Swayne,Taylor,Reavill
-
p. 345 - 351
(2007/10/02)
-
- Crown Cation Complex Effects. 20. Syntheses and Cation Binding Properties of Carbon-Pivot Lariat Ethers
-
In an effort devise synthetic cation binders that will mimic the behavior of naturally occuring ionophores such as valinomycin, we have prepared approximately 30 macrocyclic (crown) polyethers bearing flexible side chains attached to the macro ring at carbon.In many of these "carbon-pivot" compounds, the side chain contains one or more neutral donor groups that, if in a suitable geometrical arrangement, may provide additional solvation to the macro-ring-bound cation.Although such donors often enhanced the cation binding ability, overall, the increases in stability constants were modest.The physical resemblance and concept of "roping and tying" the cation suggest the name "lariat ethers".Syntheses of these molecules and binding by them of Na+ and K+ cations are reported and conclusions drawn about the structural requirements and cation binding efficacy of these materials.
- Dishong, Dennis M.,Diamond, Craig J.,Cinoman, Michael I.,Gokel, Geoge W.
-
p. 586 - 593
(2007/10/02)
-
- Preparation of aliphatic/aromatic ethers
-
Aliphatic/aromatic ethers are prepared by reacting an aliphatic halide with either an alkali or alkaline earth metal, or ammonium phenolate or naphtholate, in an inert organic solvent, and in the presence of at least one tertiary amine sequestering agent having the formula:
- -
-
-
