- TMSN3-Bu2Sn(OAc)2: A modified and mild reagent system for Wittenberger tetrazole-synthesis
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Treatments of various nitriles with TMSN3 and Bu2Sn(OAc)2 at 30 °C in benzene for 60 h yielded the corresponding 5-substituted 1H-tetrazoles in good to excellent yields. This method is a mild and efficient alternative reagent system for Wittenberger tetrazole-synthesis that uses TMSN3 and Bu2SnO in toluene at high temperature (93–110 °C) for 24–72 h.
- Yoneyama, Hiroki,Oka, Naoki,Usami, Yoshihide,Harusawa, Shinya
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supporting information
(2020/01/21)
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- Tetrazolylpropan-2-ones as inhibitors of fatty acid amide hydrolase: Studies on structure-activity relationships and metabolic stability
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A series of derivatives of 1-(4-octylphenoxy)-3-(2H-tetrazol-2-yl)propan-2-one (3) and 1-(4-octylphenoxy)-3-(1H-tetrazol-1-yl)propan-2-one (4) was synthesized and tested for fatty acid amide hydrolase (FAAH) inhibitory potency and phase I metabolic stability. Introduction of certain substituents like 4-chlorophenyl, 4-methoxycarbonylphenyl and carboxyl in position 5 of the tetrazole ring of 3 led to a significant increase of the metabolic stability of the scissile ketone pharmacophore, while the high activity towards FAAH was not affected markedly. In contrast, substituents in position 5 of the heterocyclic system of 4 did not have a considerable impact on the undesired ketone reduction. Furthermore, the effect of shielding the ketone group of some derivatives of 3 by a methyl substituent in position 3 of the propan-2-one scaffold and the consequences of the replacement of the lipophilic octyl residue of these compounds by more drug-like substituents were examined.
- Garzinsky, David,Zahov, Stefan,Ekodo Voundi, Merlin,Hanekamp, Walburga,Lehr, Matthias
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supporting information
p. 183 - 192
(2018/10/21)
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- Pathways in the Degradation of Geminal Diazides
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The degradation of geminal diazides is described. We show that diazido acetates are converted into tetrazoles through the treatment with bases. The reaction of dichloro ketones with azide anions provides acyl azides, through in situ formation of diazido ketones. We present experimental and theoretical evidence that both fragmentations may involve the generation of acyl cyanide intermediates. The controlled degradation of terminal alkynes into amides (by loss of one carbon) or ureas (by loss of two carbons) is also shown.
- Holzschneider, Kristina,H?ring, Andreas P.,Haack, Alexander,Corey, Daniel J.,Benter, Thorsten,Kirsch, Stefan F.
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p. 8242 - 8250
(2017/08/14)
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- Efficient transformation of inactive nitriles into 5-substituted 1 H-tetrazoles using microwave irradiation and their applications
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Efficient transformations of inactive nitriles into 5-substituted 1H-tetrazoles in DMF in a microwave reactor are described. The present method is applied to the synthesis of tetrazolato-bridged dinuclear platinum(II) complex and tetrazole C1-ribonucleoside phosphoramidite. Georg Thieme Verlag Stuttgart, New York.
- Yoneyama, Hiroki,Usami, Yoshihide,Komeda, Seiji,Harusawa, Shinya
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p. 1051 - 1059
(2013/05/09)
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- A simple, advantageous synthesis of 5-substituted 1 h -tetrazoles
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An advantageous synthesis of 5-substituted 1H-tetrazoles has been developed by treatment of organic nitriles with NaN3 in the presence of iodine or the heterogeneous catalyst, silica-supported sodium hydrogen sulfate (NaHSO4SiO2). Georg Thieme Verlag Stuttgart New York.
- Das, Biswanath,Reddy, Cheruku Ravindra,Kumar, Duddukuri Nandan,Krishnaiah, Martha,Narender, Ravirala
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scheme or table
p. 391 - 394
(2010/04/24)
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- Cu2(OTf)2-catalyzed and microwave-controlled preparation of tetrazoles from nitriles and organic azides under mild, safe conditions
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Avoiding hazards: Cu2(OTf)2·C 6H6 (OTf = O3SCF3) is the catalyst of choice for the [3+2] cycloaddition of organic azides and ethyl cyanoformate or related nitriles (see scheme; PG = protect
- Bosch, Lluis,Vilarrasa, Jaume
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p. 3926 - 3930
(2008/03/11)
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- 1,3-Dipolar cycloaddition: Click chemistry for the synthesis of 5-substituted tetrazoles from organoaluminum azides and nitriles
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Cheap and safe: Conventional methods to prepare tetrazoles employ dangerous, toxic reagents. A new route to these heterocycles (see scheme) uses inexpensive and nontoxic dialkyl aluminum azides. The cycloaddition occurs under mild conditions and tolerates a variety of functional groups. The low cost and ecocompatibility make this process attractive for large-scale preparation. (Chemical Equation Presented).
- Aureggi, Valentina,Sedelmeier, Gottfried
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p. 8440 - 8444
(2008/09/19)
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- Aromatic heterocycle compounds having HIV integrase inhibiting activities
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A compound of the formula (I): wherein X is hydroxy, protected hydroxy or optionally substituted amino; Y is —COORAwherein RAis hydrogen or ester residue, —CONRBRCwherein RBand RCeach is independently hydrogen or amide residue, optionally substituted aryl or optionally substituted heteroaryl; and A1is optionally substituted heteroaryl; provided that a compound wherein Y and/or A1is optionally substituted indol-3-yl is excluded, a tautomer, a prodrug, a pharmaceutically acceptable salt or a hydrate thereof has an inhibitory activity against an integrase.
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- INTEGRASE INHIBITORS CONTAINING AROMATIC HETEROCYCLE DERIVATIVES
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A compound of the formula (I): whereinX is hydroxy or the like;Y is -C(=R2)-R3-R4 wherein R2 and R3 is oxygen atom or the like, R4 is hydrogen, optionally substituted alkyl, optionally subs
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- Process for preparing tetrazole-5-carboxylic acid derivatives
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A process for preparing a compound of structure (I) or a hydrate or solvate thereof in which R1 is C1-6 alkyl, optionally substituted phenyl or optionally substituted phenylC1-6 alkyl, which comprises reacting an azide of the structure (II): M≈ N3? with a cyanoformate of the structure (III): NC.CO2 R1 in which M is an alkali metal atom, and R1 is as described for structure (I), to form an intermediate salt of structure (IV), in which R1 is as described for structure (I) and M is as described for structure (II) followed by conversion of the salt (IV) to the free tetrazole (I) or to a hydrate or solvate thereof.
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- Inhibitors of acyl-CoA:cholesterol O-acyltransferase. Synthesis and pharmacological activity of (±)-2-dodecyl-α-phenyl-N-(2,4,6- trimethoxyphenyl)-2H-tetrazole-5-acetamide and structurally related tetrazole amide derivatives
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A series of tetrazole amide derivatives of (±)-2-dodecyl-α-phenyl-N- (2,4,6-trimethoxyphenyl)-2H-tetrazole-5-acetamide (1) was prepared and evaluated for their ability to inhibit acyl-CoA: cholesterol O- acyltransferase (ACAT) in vitro and to lower plasma total cholesterol in vivo. For this series of compounds, our objective was to systematically replace substituents appended to the amide and tetrazole moieties of 1 with structurally diverse functionalities and assess the effect that these changes have on biological activity. The ensuing structure-activity relationship (SAR) studies identified aryl (7b) and heteroaryl (7f,g) replacements for 2,4,6-trimethoxyphenyl that potently inhibit liver microsomal and macrophage ACAT in vitro and exhibit good cholesterol lowering activity (56-66% decreases in plasma total cholesterol at 30 mg/kg), relative to 1, when compared in the acute rat model of hypercholesterolemia. Replacement of the α-phenyl moiety with electron-withdrawing substituents (13e-h), however, significantly reduced liver microsomal ACAT inhibitory activity (IC50 > 1 μM). This is in contrast to electron-donating substituents (13ij,m-q), which produce IC50 values ranging from 5 to 75 nM in the hepatic microsomal assay. For selected tetrazole amides (1, 7b, 13n,o), reversing the order of substituents appended to the 2- and 5-positions in the tetrazole ring (36a- d), in general, improved macrophage ACAT inhibitory activity and provided excellent cholesterol-lowering activity (ranging from 65% to 77% decreases in plasma total cholesterol at 30 mg/kg) in the acute rat screen. The most potent isomeric pair in this set of unsubstituted methylene derivatives (13n and 36a) caused adrenocortical cell degeneration in guinea pigs treated with these inhibitors. In contrast, adrenal glands taken from guinea pigs treated with the corresponding α-phenyl-substituted analogs (7b and 36c) were essentially unchanged compared to untreated controls. Subsequent evaluation of 7b and 36c in a rabbit bioassay showed that both compounds and/or their metabolites were present in plasma after oral dosing. Unlike 7b and 36c, compound 1 and related 2,4,6-trimethoxyanilides (13j, 30c,d) showed poor oral activity in the rabbit bioassay. Nevertheless, in cholesterol-fed rabbits, both systemically available (7b, 36c) and poorly absorbed inhibitors (1, 36d) were more effective in lowering plasma total cholesterol than the fatty acid amide CI-976.
- O'Brien,Sliskovic,Picard,Lee,Purchase II,Roth,White,Anderson,Mueller,Bocan,Bousley,Hamelehle,Homan,Lee,Krause,Reindel,Stanfield,Turluck
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p. 2354 - 2366
(2007/10/03)
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- Tetrazole-substituted urea acat inhibitors
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Novel ACAT inhibitors useful in the treatment of atherosclerosis which are tetrazole-substituted ureas,
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- 2'Hydroxy tetrazole-5-carboxanilides and anti-allergic use thereof
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New tetrazole derivatives of the general formula: STR1 [wherein R1 represents a halogen atom, a straight- or branched-chain alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl or alkylsulphamoyl group, each such group containing from 1 to 6 carbon atoms, a dialkylsulphamoyl, dialkylamino, or dialkylcarbamoyl group (wherein the two alkyl groups may be the same or different and each contains from 1 to 4 carbon atoms), a straight- or branched-chain alkanoyl, alkoxycarbonyl, alkoxycarbonylamino, alkylcarbamoyl or alkanoylamino group containing from 2 to 6 carbon atoms, a cycloalkylcarbonyl group containing from 3 to 8 carbon atoms in the cycloalkyl moiety, or a hydroxy, formyl, nitro, trifluoromethyl, trifluoroacetyl, aryl, benzyloxycarbonylamino, amino, sulphamoyl, cyano, tetrazol-5-yl, carboxy, carbamoyl, benzyloxy, aralkanoyl or aroyl group, or a group of the formula: (wherein R2 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 5 carbon atoms, an aryl, aralkyl or trifluoromethyl group, or a cycloalkyl group containing from 3 to 8 carbon atoms, and R3 represents a hydrogen atom, or a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms optionally substituted by a phenyl group, or represents an aryl group optionally substituted by one or more substituents selected from halogen atoms and straight- or branched-chain alkyl and alkoxy groups containing from 1 to 6 carbon atoms and hydroxy, trifluoromethyl and nitro groups), and m represents zero or an integer 1, 2 or 3, the substituents R1 being the same or different when m represents 2 or 3] possess pharmacological properties, in particular properties of value in the treatment of allergic conditions.
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