- Electrochemical [4+2] Annulation-Rearrangement-Aromatization of Styrenes: Synthesis of Naphthalene Derivatives
-
We report the first electrochemical strategy to synthesize functionalized naphthalene derivatives through [4+2] annulation—rearrangement–aromatization from styrenes under mild conditions. The electrolysis does not require metals, oxidants and high valence substrates, indicating the atom and step-economy ideals. The dehydrodimer produced through [4+2] cycloaddition of 4-methoxy α-methyl styrene is isolated and proved to be the key intermediate for the following oxydehydrogenation to form carbon cation, which undergoes rearrangement–aromatization to afford the final products. This reaction represents a powerful access to construct multi-substituted naphthalene blocks in a single step.
- Ma, Yueyue,Lv, Jufeng,Liu, Chengyu,Yao, Xiantong,Yan, Guoming,Yu, Wei,Ye, Jinxing
-
supporting information
p. 6756 - 6760
(2019/04/17)
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- Nickel-Catalyzed Decarboxylative Alkenylation of Anhydrides with Vinyl Triflates or Halides
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Decarboxylative cross-coupling of aliphatic acid anhydrides with vinyl triflates or halides was accomplished via nickel catalysis. This methodology works well with a broad array of substrates and features abundant functional group tolerance. Notably, our approach addresses the issue of safe and environmental installation of methyl or ethyl group into molecular scaffolds. The method possesses high chemoselectivity toward alkyl groups when aliphatic/aromatic mixed anhydrides are involved. Furthermore, diverse ketones could be modified with our strategy.
- Chen, Hui,Sun, Shuhao,Liao, Xuebin
-
supporting information
p. 3625 - 3630
(2019/05/24)
-
- PYRAZOLO-TRIAZINE AND/OR PYRAZOLO-PYRIMIDINE DERIVATIVES AS SELECTIVE INHIBITOR OF CYCLIN DEPENDENT KINASE
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The present invention relates to pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[l,5-a]pyrimidine derivatives and/or pharmaceutically acceptable salts thereof, the use of these derivatives as pharmaceutically active agents, especially for the prophylaxis and/or treatment of cell proliferative diseases, inflammatory diseases, immunological diseases, cardiovascular diseases and infectious diseases. Furthermore, the present invention is directed towards pharmaceutical compositions containing at least one of the pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[1,5-a]pyrimidine derivatives and/or pharmaceutically acceptable salts thereof.
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Page/Page column 50; 101-102
(2019/11/04)
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- Synthesis of 1,3-Diketones and β-Keto Thioesters via Soft Enolization
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Ketones and thioesters undergo soft enolization and acylation using crude acid chlorides on treatment with MgBr2·OEt2 and i-Pr2NEt to give 1,3-diketones and β-keto thioesters, respectively. The use of crude acid chlorides adds efficiency and cost reduction by avoiding the need to purify and/or purchase them. The process is conducted in a direct fashion that does not require prior enolate formation, further enhancing its efficiency and making it very easy to carry out. The method is suitable for large scale applications. ?
- Aderibigbe, Sabrina O.,Coltart, Don M.
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p. 9770 - 9777
(2019/08/27)
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- Molecularly imprinted artificial esterases with highly specific active sites and precisely installed catalytic groups
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A difficult challenge in synthetic enzymes is the creation of substrate-selective active sites with accurately positioned catalytic groups. Covalent molecular imprinting in cross-linked micelles afforded such active sites in protein-sized, water-soluble nanoparticle catalysts. Our method allowed a systematic tuning of the distance of the catalytic group to the bound substrate. The catalysts displayed enzyme-like kinetics and easily distinguished substrates with subtle structural differences.
- Hu, Lan,Zhao, Yan
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supporting information
p. 5580 - 5584
(2018/08/17)
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- Primary, Secondary, and Tertiary γ-C(sp3)-H Vinylation of Amides via Organic Photoredox-Catalyzed Hydrogen Atom Transfer
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An efficient strategy for primary, secondary and tertiary aliphatic γ-C(sp3)-H vinylation of amides with alkenylboronic acids is reported. These reactions are catalyzed by visible-light organic photoredox agents. Regioselective γ-C(sp3)-H vinylation of amides is controlled by a 1,5-hydrogen atom transfer of an amidyl radical generated in situ.
- Chen, Hui,Guo, Liangliang,Yu, Shouyun
-
supporting information
p. 6255 - 6259
(2018/10/05)
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- Design and Synthesis of 2-Methyl-7-aminobenzoxazole as Auxiliary in the Palladium(II)-Catalyzed Arylation of a beta-Positioned C(sp3)-H Bond
-
A palladium(II)-catalyzed direct arylation of methylene C(sp3)-H bonds by 2-methyl-7-aminobenzoxazole as an effective auxiliary is reported. This process exhibited high beta-site selectivity, broad substrate scope, and compatibility with different functional groups with moderate to high yields up to 89%.
- Luo, Feihua,Yang, Jun,Li, Zhengkai,Xiang, Haifeng,Zhou, Xiangge
-
supporting information
p. 887 - 893
(2016/04/05)
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- Iron-Catalyzed, Fluoroamide-Directed C-H Fluorination
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This communication describes a mild, amide-directed fluorination of benzylic, allylic, and unactivated C-H bonds mediated by iron. Upon exposure to a catalytic amount of iron(II) triflate (Fe(OTf)2), N-fluoro-2-methylbenzamides undergo chemoselective fluorine transfer to provide the corresponding fluorides in high yield. The reaction demonstrates broad substrate scope and functional group tolerance without the use of any noble metal additives. Mechanistic and computational experiments suggest that the reaction proceeds through short-lived radical intermediates with F-transfer mediated directly by iron.
- Groendyke, Brian J.,Abusalim, Deyaa I.,Cook, Silas P.
-
supporting information
p. 12771 - 12774
(2016/10/13)
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- Ligand-enabled γ-C-H olefination and carbonylation: Construction of β-quaternary carbon centers
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Monoselective γ-C-H olefination and carbonylation of aliphatic acids has been accomplished by using a combination of a quinoline-based ligand and a weakly coordinating amide directing group. The reaction provides a new route for constructing richly functionalized all-carbon quaternary carbon centers at the β-position of aliphatic acids.
- Li, Suhua,Chen, Gang,Feng, Chen-Guo,Gong, Wei,Yu, Jin-Quan
-
supporting information
p. 5267 - 5270
(2014/05/06)
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- Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis
-
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons in cortex, brain stem, and spinal cord die progressively, resulting in muscle wasting, paralysis, and death. Currently, effective therapies for ALS are lacking; however, identification of pathological TAR DNA-binding protein 43 (TDP-43) as the hallmark lesion in sporadic ALS suggests new therapeutic targets for pharmacological intervention. Pathological TDP-43 phosphorylation appears to drive the onset and progression of ALS and may result from upregulation of the protein kinase CK-1 in affected neurons, resulting in postranslational TDP-43 modification. Consequently, brain penetrant specific CK-1 inhibitors may provide a new therapeutic strategy for treating ALS and other TDP-43 proteinopathies. Using a chemical genetic approach, we report the discovery and further optimization of a number of potent CK-1δ inhibitors. Moreover, these small heterocyclic molecules are able to prevent TDP-43 phosphorylation in cell cultures, to increase Drosophila lifespan by reduction of TDP-43 neurotoxicity, and are predicted to cross the blood-brain barrier. Thus, N-(benzothiazolyl)-2-phenyl-acetamides are valuable drug candidates for further studies and may be a new therapeutic approach for ALS and others pathologies in which TDP-43 is involved.
- Salado, Irene G.,Redondo, Miriam,Bello, Murilo L.,Perez, Concepción,Liachko, Nicole F.,Kraemer, Brian C.,Miguel, Laetitia,Lecourtois, Magalie,Gil, Carmen,Martinez, Ana,Perez, Daniel I.
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p. 2755 - 2772
(2014/04/17)
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- Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): Pharmacological characterization and assessment in a rat model of cocaine dependence
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As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu 3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.
- Dhanya, Raveendra-Panickar,Sheffler, Douglas J.,Dahl, Russell,Davis, Melinda,Lee, Pooi San,Yang, Li,Nickols, Hilary Highfield,Cho, Hyekyung P.,Smith, Layton H.,D'Souza, Manoranjan S.,Conn, P. Jeffrey,Der-Avakian, Andre,Markou, Athina,Cosford, Nicholas D.P.
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p. 4154 - 4172
(2014/06/09)
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- Copper-catalyzed site-selective intramolecular amidation of unactivated C(sp3)-H bonds
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The intramolecular dehydrogenative amidation of aliphatic amides, directed by a bidentate ligand, was developed using a copper-catalyzed sp3 C-H bond functionalization process. The reaction favors predominantly the C-H bonds of β-methyl groups over the unactivated methylene C-H bonds. Moreover, a preference for activating sp3 C-H bonds of β-methyl groups, via a five-membered ring intermediate, over the aromatic sp2 C-H bonds was also observed in the cyclometalation step. Additionally, sp3 C-H bonds of unactivated secondary sp3 C-H bonds could be functionalized by favoring the ring carbon atoms over the linear carbon atoms. Getting ahead on tams: The intramolecular dehydrogenative amidation of aliphatic amides, directed by a bidentate ligand, was developed using a copper-catalyzed sp 3 C-H bond functionalization process to deliver β-lactams. The reaction favors the C-H bonds of β-methyl groups over the unactivated methylene C-H bonds, as well as aromatic C(sp2)-H bonds and unactivated secondary C(sp3)-H bonds of rings.
- Wu, Xuesong,Zhao, Yan,Zhang, Guangwu,Ge, Haibo
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supporting information
p. 3706 - 3710
(2014/04/17)
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- Bromination of enamines from tertiary amides using the petasis reagent: A convenient one-pot regioselective route to bromomethyl ketones
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An original one-pot synthesis of bromomethyl ketones is achived using the Petasis reagent (dimethyltitanocene) as a key for enamine generation. Several amides were used to test the limits of the procedure by changing either the alkyl chain R or the amino portion of the starting materials. The enamines generated in situ were allowed to react with bromine at low temperature followed by hydrolysis to yield bromomethyl ketones in excellent yields (85 to 95%). Mechanistic details and optimum conditions for the reaction are briefly discussed. The present approach offers several advantages such as regioselectivity in enamine formation, good yields, mild reaction conditions, and ease of experimentation.
- Kobeissi, Marwan,Cherry, Khalil,Jomaa, Wissam
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supporting information
p. 2955 - 2965
(2013/09/02)
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- POSITIVE ALLOSTERIC MODULATORS OF MGLUR2
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The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds modulate the mGluR2 receptor and may be useful for the treatment of various disorders of the central nervous system. Formula (I):
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Page/Page column 40
(2014/01/09)
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- A simple method for asymmetric trifluoromethylation of N-acyl oxazolidinones via Ru-catalyzed radical addition to zirconium enolates
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A Ru-catalyzed direct thermal trifluoromethylation and perfluoroalkylation of N-acyloxazolidinones has been developed. The reaction is experimentally simple and requires inexpensive reagents while providing good yields of products with good levels of stereocontrol. Preliminary studies have shown notable compatibility with functional groups, aromatics, and certain heteroaromatic substituents. The described method provides a useful alternative for the synthesis of fluorinated materials in an experimentally convenient manner.
- Herrmann, Aaron T.,Smith, Lindsay L.,Zakarian, Armen
-
supporting information; experimental part
p. 6976 - 6979
(2012/06/15)
-
- Selective hydrogenation of 3,3-dimethylbutanoyl chloride to 3,3-dimethylbutyraldehyde with silica supported Pd nanoparticle catalyst
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A novel method for selective hydrogenation of 3,3-dimethylbutanoyl chloride (DMBC) to 3,3-dimethylbutyraldehyde (DMBA) with silica supported Pd nanoparticle catalyst (Pd/SiO2) is developed. The catalysts were characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, N2 physisorption and transmission electron microscopy. The performance of the Pd/SiO2 catalyst was compared with Pd/C and Pd/BaSO4 catalysts with or without being pretreated by quinoline-sulfur. The Pd/SiO2 catalyst activated at 80 °C by bubbling hydrogen in cyclohexane for 1 h showed the highest yield of DMBA. For 3 wt.% Pd/SiO2, the yield of DMBA reached 84.6%, which exhibited much higher value than Pd/C and Pd/BaSO4 catalysts.
- Li, Sifang,Chen, Guoqin,Sun, Lan
-
experimental part
p. 813 - 816
(2012/05/05)
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- Syntheses and evaluation of anticonvulsant profile and teratogenicity of novel amide derivatives of branched aliphatic carboxylic acids with 4-aminobenzensulfonamide
-
Despite the availability of 14 new antiepileptic drugs (AEDs), about 30% of epileptic patients are not seizure-free. Consequently there is substantial need to develop new effective AEDs. A novel class of aromatic amides composed of phenylacetic acid or branched aliphatic carboxylic acids, with five to nine carbons in their carboxylic moiety, and aminobenzenesulfonamide were synthesized and evaluated in the anticonvulsant rat-maximal electroshock (MES) and subcutaneous metrazol seizure (scMet) tests. Fourteen of the synthesized amides had an anticonvulsant ED50 of 50 values of 7.6, 9.9, and 9.4 mg/kg and remarkable protective index (PI = TD 50/ED50) values of 65.7, 50.5, and 53.2, respectively. These potent sulfanylamides caused neural tube defects only at doses markedly exceeding their effective dose. The anticonvulsant properties of these compounds make them potential candidates for further development as new, potent, and safe AEDs.
- Hen, Naama,Bialer, Meir,Wlodarczyk, Bogdan,Finnell, Richard H.,Yagen, Boris
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scheme or table
p. 4177 - 4186
(2010/09/04)
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- Highly twisted C=C double bonds in 4-methyleneisoxazolones
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As determined by X-ray crystallography, isoxazol-5(4H)-one derivatives 1219 feature dihedral angles around the exocyclic C4=C6 double bonds of 2690. In the most highly twisted bis-tert-butylamino derivatives 18 and 19, the C4C6 bonds are essentially single bonds. Density functional theory calculations at the B3LYP/6-31G(d) level with inclusion of a simulated solvent field, which helps stabilize zwitterionic structures, are in good agreement with the experimental crystallographic data. A good correlation between bond lengths and calculated π/π*orbital occupation quotients is observed. A good correlation between the twisting angle and the charge separation, measured by the calculated negative charge on the isoxazolone moiety, is also observed. Low barriers to rotation about the twisted exocyclic double bonds C4=C6 in compounds 13, 20, and 21 (G ? = 1516 kcal mol-1 (6367 kJ mol -1)) were determined by dynamic 1H NMR coalescence measurements. The rotational barrier for 17 was estimated to be less than 10 kcal mol-1. The rotational barriers for compounds 10 and 18 were calculated to be ～8 kcal mol-1. CSIRO 2009.
- Kvaskoff, David,Bernhardt, Paul V.,Koch, Rainer,Wentrup, Curt
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experimental part
p. 1068 - 1078
(2010/03/23)
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- Synthesis and evaluation of antiallodynic and anticonvulsant activity of novel amide and urea derivatives of valproic acid analogues
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Valproic acid (VPA, 1) is a major broad spectrum antiepileptic and central nervous system drug widely used to treat epilepsy, bipolar disorder, and migraine. VPA's clinical use is limited by two severe and lifethreatening side effects, teratogenicity and hepatotoxicity. A number of VPA analogues and their amide, N-methylamide and urea derivatives, were synthesized and evaluated in animal models of neuropathic pain and epilepsy. Among these, two amide and two urea derivatives of 1 showed the highest potency as antineuropathic pain compounds, with ED50 values of 49 and 51 mg/kg for the amides (19 and 20) and 49 and 74 mg/kg for the urea derivatives (29 and 33), respectively. 19, 20, and 29 were equipotent to gabapentin, a leading drug for the treatment of neuropathic pain. These data indicate strong potential for the above-mentioned novel compounds as candidates for future drug development for the treatment of neuropathic pain. 2009 American Chemical Society.
- Kaufmann, Dan,Bialer, Meir,Shimshoni, Jakob Avi,Devor, Marshall,Yagen, Boris
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scheme or table
p. 7236 - 7248
(2010/07/04)
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- FUSED IMIDAZOLE DERIVATIVES FOR THE TREATMENT OF DISORDERS MEDIATED BY ALDOSTERONE SYNTHASE AND/OR 11-BETA-HYDROXYLASE AND/OR AROMATASE
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The present invention provides a compound of formula (I); said compound is inhibitor of aldosterone synthase, and/or 11beta-hydroxylase (CYP11B1), and/or aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase, aromatase, or CYP11B1. Accordingly, the compound of formula (I) can be used in treatment of hypokalemia, hypertension, congestive heart failure, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, increased formation of collagen, fibrosis and remodeling following hypertension and endothelial dysfunction. Finally, the present invention also provides a pharmaceutical composition.
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-
Page/Page column 52-53
(2008/06/13)
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- Structure activity studies with xenobiotic substrates using carboxylesterases isolated from Arabidopsis thaliana
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Carboxylesterases (CXEs) catalyse the hydrolysis of xenobiotics and natural products radically altering their biological activities. Whereas the substrate selectivity of animal CXEs, such as porcine liver esterase (PLE) have been well studied, the respective enzymes in plants have yet to be defined and their activities determined. Using Arabidopsis thaliana (At) as a source, five representative members of the α/β hydrolase AtCXE family of proteins have been cloned, expressed and the purified recombinant proteins assayed for esterase activity with xenobiotic substrates. Two members, AtCXE5 and AtCXE18 were found to be active carboxylesterases, though AtCXE5 proved to be highly unstable as a soluble protein. AtCXE18 and the previously characterised S-formylglutathione hydrolase from Arabidopsis (AtSFGH) were assayed against a series of esters based on methylumbelliferone in which the acyl moiety was varied with respect to size and conformation. The same series was used to assay crude esterase preparation from Arabidopsis plants and the results compared with those obtained with the commonly used PLE. With straight chain esters, AtCXE18 behaved like PLE, but the Arabidopsis hydrolases proved less tolerant of branched chain acyl components than the mammalian enzyme. While none of the enzyme preparations accurately reflected all the activities determined with crude Arabidopsis protein extracts, the plant enzymes proved more useful than PLE in predicting the hydrolysis of the more sterically constrained esters.
- Cummins, Ian,Landrum, Marie,Steel, Patrick G.,Edwards, Robert
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p. 811 - 818
(2008/03/13)
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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. Thesd compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
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Page/Page column 113
(2008/06/13)
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- Dynamically stable helices of poly(N-propargylamides) with bulky aliphatic groups
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N-Propargylamides with bulky pendent groups [HC≡CCH2NHCOR, 9: R = CH2C(CH3)3, 10: R=C(CH 3)3 11: R = C(CH3)2CH 2CH2CH3,12: R = CH(CH2CH 3)2, 13: R = CH(CH2CH2CH 3)2] were polymerized with a rhodium catalyst, (nbd)Rh+B-(C8H5)4 (nbd = 2,5-norbornadiene), to obtain the polymers in 80-92% yields. Poly(11) and poly(12) possessed moderate molecular weights (Mn ≥ 10 000) and were totally soluble in a few solvents including chloroform. On the other hand, the Mn values of poly(9), poly(10), and poly(13) were no more than 5000, and these polymers were not completely soluble in any solvents. The conformational transition behavior of these polymers was examined by temperature-variable UV-vis spectroscopy in chloroform solution, which revealed that poly(10) - poly(13) could form dynamically stable helical conformation even at 60°C. By copolymerizations of monomers 9 and 10 with monomer 4, HC≡CCH2NHCO(CH2)4H, the solubility of the polymers was effectively improved and almost all the copolymers totally dissolved in chloroform, while the molecular weights of the copolymers increased up to 18 600-45 000. Moreover, the helix contents of poly(40.63-co- 90.37) and poly(40.40-co-100.60) were the highest among the two series of (co)polymers, respectively. It is concluded that the copolymerization of 9 and 10 with 4 effectively decreased the steric repulsion between the crowded side chains, which probably allowed the copolymers to take helical conformation efficiently.
- Deng, Jianping,Tabei, Junichi,Shiotsuki, Masashi,Sanda, Fumio,Masuda, Toshio
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p. 5149 - 5154
(2007/10/03)
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- Spirodiclofen and spiromesifen - Novel acaricidal and insecticidal tetronic acid derivatives with a new mode of action
-
The broad spectrum acaricides spirodiclofen (BAJ2740, trade name: Envidor) and spiromesifen (BSN2060, trade name: Oberon) with an additional excellent activity against whiteflies, both belong to the new chemical class of tetronic acid derivatives discovered at Bayer CropScience during the 1990s. The discovery process starting from herbicidal PPO (protoporphyrinogen oxidase) chemistry, the synthetic routes leading to the products, and some insight into process development of central intermediates is given. Spirodiclofen and spiromesifen have a new mode of action (interference with lipid biosynthesis), show no cross-resistance to any resistant mite or whitefly field population and are therefore valuable tools for resistance management.
- Bretschneider, Thomas,Benet-Buchholz, Jordi,Fischer, Reiner,Nauen, Ralf
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p. 697 - 701
(2007/10/03)
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- Induction of one-handed helix sense in achiral poly(N-propargylamides)
-
Achiral N-propargylamides, i.e., N-propargyl-3-methylbutanamide (1), N-propargyl-2-ethylbutanamide (2), and N-propargyl-3,3-dimethylbutanamide (3), were polymerized with (nbd)Rh+[η6-C6H5B- (C6H5)] to afford polymers with moderate molecular weights (Mn = 6000-22000) in good yields. The 1H NMR and UV-vis spectra demonstrated that the polymers, poly(1)-poly(3), have stereoregular structures (cis = 100%) and equally populated right- and left-handed helical conformation. A predominant helix sense was induced in these polymers by the addition of chiral alcohols or amine, which was confirmed by CD and UV-vis spectroscopies. 1H NMR and CD spectroscopic studies strongly suggested that the poly(N-propargylamides) interacted with the chiral alcohols by hydrogen bonding at the amide groups of the polymer side chain. Chiral terpenes could also induce single-handed helical conformation. It is likely that hydrophobic interaction led to the one-handed helical conformation in the case of the chiral terpenes because the addition of n-hexane decreased the CD signal.
- Tabei, Junichi,Nomura, Ryoji,Sanda, Fumio,Masuda, Toshio
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p. 8603 - 8608
(2007/10/03)
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- The synthesis, physical, and spectral properties, and some reactions of a new stable bis-α-lactam (aziridinone) with a terpene skeleton
-
A synthesis of a new stable bis-α-lactam, cis-1,1′(p-menth-1,8-ylene) bis(3-tert-butyl-2-azirididone) (4), derived from p-menthane, is described. Complete spontaneous thermal decomposition required lh of reflux in boiling n-decane (b.p. 174°C) and the products are 2,2-dimethylpropanal (pivalaldehyde) (6) and 1,8-diisocyano-p-menthane (7). Reaction with benzylamine yielded the unexpected bis-benzylamide (13a), while reaction with sodium methoxide gave the bisα-amino acid ester (14).
- Lengyel,Cesare,Taldone,Uliss
-
p. 3671 - 3683
(2007/10/03)
-
- Imidazopyridines as pharmaceutical agents
-
Described herein are novel imidazopyridine derivatives of the formula I STR1 wherein R is STR2 and R1, R2, R3 and R4 are as defined in Patent Claim 1, and their salts, which exhibit antagonistic properties towards angiotensin II and can be used for the treatment of hypertension, aldosteronism, cardiac insufficiency and increased intraocular pressure, and of disorders of the central nervous system.
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-
-
- Reactivity of 1,3-di-tert-butylaziridinones with phenyl substituents. A new fragmentation of α-lactams
-
Several isolable aziridinones with bulky substituents were prepared and their reactions with nucleophiles, i.e., methanol, sodium methoxide and benzylamine, were investigated. A novel fragmentation of aziridinones having a phenyl group on the C3 moiety was found.
- Shimazu, Masako,Endo, Yasuyuki,Shudo, Koichi
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p. 735 - 744
(2007/10/03)
-
- Synthesis and Coordination Behaviors of New Double-Sided Porphyrinatoiron(II) Complexes: Effect of the Pocket-Size for Imidazole on Dioxygen Binding
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The synthesis and characteristic ligation behaviors of new "double-sided porphyrinatoiron(II) complexes" having two pockets of different spacing-size on each side of a ring plane and a larger sized one on both sides of a macrocycle, are described.The equilibrium constants for the imidazole derivatives to the four-coordinated porphyrinatoiron(II)s were increased in proportion to the size of the pocket-space, which is reflected by the ΔH term.The five-coordinated complexes of the porphyrinatoirons, obtained by the addition of 1,2-dimethylimidazole (1,2-dmim) in a toluene solution, formed stable and reversible dioxygen adducts at 25 deg.The oxygen affinities for the iron(II) complexes increased as the steric bulk on the rear side of the porphyrin plane was relieved.These changes in the oxygen affinity are attributed to the strength of the ?-electron donation from the imidazole to the central iron ion.
- Tsuchida, Eishun,Hasegawa, Etsuo,Komatsu, Teruyuki,Nakata, Taisaku
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p. 888 - 894
(2007/10/02)
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- Lipophilic 5,6,7,8-tetrahydropterin substrates for phenylalanine hydroxylase (monkey brain), tryptophan hydroxylase (rat brain) and tyrosine hydroxylase (rat brain)
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A high yielding unambiguous synthesis of (+/-)-6-alkyl-5,6,7,8-tetrahydropterin 5a-f hydrochlorides starting from ethyl α-isocyanoacetate 1 and the respective alkanoic anhydrides or alkanoyl chlorides in four steps is described.All the six pterins 5a-f that have been synthesised are substrates for mammalian phenylalanine, tryptophan and tyrosine hydroxylases and their activities have been compared with those of natural 6R-tetrahydrobiopterin under similar conditions.The data allowed the choice of 6-n-propyl-5,6,7,8-tetrahydropterin 5c for further studies as a candidate for tetrahydrobiopterin drug therapy.Keywords: (+/-)-6-alkyltetrahydropterinsydroxylase / tryptophan hydroxylase / tyrosine hydroxylase
- Armarego, Wilfred L. F.,Taguchi, Hiroyasu,Cotton, Richard G. H.,Battiston, Sandra,Leong, Lillian
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p. 283 - 292
(2007/10/02)
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- NOUVELLES METHODES DE DESHALOGENATION ET DE FORMATION D'ETHERS D'ENOL TRIMETHYLSILYLIQUES PAR ACTION DE iPr2NLi SUR QUELQUES α-MONOBROMO- ET α,α'-DIBROMOCETONES
-
Attempts to prepare 2-bromo-2,4-dimethyl,3-trimethylsiloxy 3-pentene reacting lithium diisopropylamide (LDA) with 2-bromo-2,4-dimethyl-3 pentanone have revealed two new reactions.After a few minutes quantitative yields are obtained of either the dehalogenated ketone (after hydrolysis) or the trimethylsilyl enol ether (after addition of trimethylsilyl chloride).These reactions are general and have been extended to other α-monobromoketones and α,α'-dibromoketones.In the latter case, the reaction is more complex and leads generally to dehalogenation or reduction products.
- Lion, Claude,Dubois, Jacques-Emile,Lebbar, Khadija
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p. 119 - 126
(2007/10/02)
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- THE INVENTION OF NEW RADICAL CHAIN REACTIONS. PART VIII. RADICAL CHEMISTRY OF THIOHYDROXAMIC ESTERS; A NEW METHOD FOR THE GENERATION OF CARBON RADICALS FROM CARBOXYLIC ACIDS.
-
The aliphatic and alicyclic esters of N-hydroxy-pyridine-2-thione are readily reduced by tributylstannane in a radical chain reaction to furnish nor-alkanes.In the absence of the stannane a smooth decarboxylative rearrangement occurs to give 2-substituted thiopyridines.The radicals present in this reaction provoke with t-butylthiol an efficient radical reaction with formation of nor-alkane and 2-pyridyl-t-butyl disulphide.Similarly these carbon radicals can be captured by halogen atom transfer to give noralkyl chlorides, bromides and iodides.With oxygen in the presence of t-butylthiol the corresponding noralkyl hydroperoxides are formed in another radical chain reaction.
- Barton, Derek H. R.,Crich, David,Motherwell, William B.
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p. 3901 - 3924
(2007/10/02)
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- Enones with Strained Double Bonds. 7. Precursors for Substituted Bicyclononane Systems
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Compounds 11c, 12, and 13 have been synthesized as potential precursors for the 2-substituted bicyclonon-1(2)-en-3-ones 5 (R = Ph and t-Bu).The lactone 34 and its derivatives 32 have also been synthesized as potential precursors for the parent bicyclo enone 1.
- House, Herbert O.,Outcalt, Russell J.,Cliffton, Michael D.
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p. 2413 - 2419
(2007/10/02)
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- Cyclopentanone Synthesis by Intramolecular Carbon-Hydrogen Insertion of Diazo Ketones. A Diterpene-to-Steroid Skeleton Conversion
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Intramolecular carbon-hydrogen insertion on cupric sulfate assisted decomposition of diazomethyl ketones derived from four 1-methylcycloalkanecarboxylic acids and (hexahydrophenyl)acetic, homopivalic, and enanthic acids is shown to yield mostly cyclopentanones.The yields are appreciable in the conformationally favorable cases, and insertion in the solvent cyclohexane can be avoided by the use of Freon TF as the solvent.The conversion of a primaradienic diterpene into a 14-iso-16-androstanone derivative shows the power of the new method of cyclopentanone synthesis.
- Wenkert, Ernest,Davis, Linda L.,Mylari, Banavara L.,Solomon, Mary F.,Silva, Roberto R. da,et al.
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p. 3242 - 3247
(2007/10/02)
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- 2-Acyl-3-substituted cyclopentan-1-ones and process for their preparation
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1,3-Dicarbonyl compounds useful as medicines, agricultural chemicals, perfumes, and their intermediates are prepared by reacting a specific α,β-unsaturated carbonyl compound with a specific organic copper lithium compound in the presence of an aprotic inert organic solvent, and then reacting the reaction product with an organic carboxylic acid halide or anhydride. In particular, novel 2-acyl-3-substituted cyclopentan-1-ones and 2-acyl-3-substituted cyclohexan-1-ones having important physiological activities are provided.
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- Method of making 4-amino-6-t-butyl-3-mercapto-1,2,4-triazin-5-one
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Method of making 4-amino-6-t-butyl-3-mercapto-1,2,4-triazin-5-one comprising halogenating a 3,3-dimethylbutyric acid with Br2 or Cl2 to produce a 2,2-dihalo-3,3-dimethylbutyric acid then reacting the latter with thiocarbohydrazide. Alternatively, a 3,3-dimethylbutyryl chloride can be used as starting material, in which case the halogenation product is contacted with water, an aqueous base, an alcohol, a mercaptan, or an amine to convert it to an acid or salt thereof, anhydride, ester, thioester or amide, and the latter is reacted with thiocarbohydrazide.
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