scholarly journals The synthesis and preliminary pharmacological evaluation of racemic cis and trans 3-alkylfentanyl analogues

2004 ◽  
Vol 69 (7) ◽  
pp. 511-526 ◽  
Author(s):  
Milovan Ivanovic ◽  
I.V. Micovic ◽  
Sonja Vuckovic ◽  
Milica Prostran ◽  
Zoran Todorovic ◽  
...  
Keyword(s):  
Alkyl Halides ◽  
The Novel ◽  
Subsequent Reduction ◽  
Mild Acid Hydrolysis ◽  
Step Method ◽  
Structure Activity ◽  
Quantitative Separation ◽  
Propionyl Chloride ◽  
Cis And Trans ◽  
Mild Acid

A general, five step method for the synthesis of 3-alkylfentanyl analogues (i.e., cis and trans 3-alkyl-4-anilidopiperidines 6.1?6.6) has been developed. The starting N-phenethyl- 4-piperidone 1 was first converted into the cyclohexylimine derivative 2, ?-deprotonated with butyllithium and the resulting imine anion efficiently monoalkylated with primary and secondary alkyl halides. After mild acid hydrolysis, the obtained 3-alkyl-4-piperidones 3.1?3.6 were isolated in good yields (79?85 %), then condensed with aniline to form imines 4.1?4.6. Subsequent reduction of the imines (LiAlH4/THF) yielded cis/trans mixtures of 3-alkyl-4-anilinopiperidines 5.1?5.6. Quantitative separation of the diastereoisomers by column chromatography of Al2O3 gave pure cis 5.1?5.6 (29?51 % yield) and trans 5.1?5.6 (19?27%yield) with the cis/trans ratio in the range 7/3?6/4. The synthesiswas concluded by N-acylation of the purified 5.1?5.6, with propionyl chloride, to afford cis and trans 3-alkyl- 4-anilidopiperidines 6.1?6.6 (? 95 % yield, as monooxalate salts). No enatioseparation was attempted at any stage. The relative cis/trans stereochemistry was provisionally assigned from the 1H-NMR spectra. Of the twelve synthesized 3-alkylfentanyls, ten compounds (two known and eight novel derivatives, all as the monooxalate salts) were preliminarily tested as analgesics in rats, comparing the potency to fentanyl. Except for the known (?)-cis-3-Me fentanyl 6.1cis, (8 x fentanyl), and the novel (?)-cis-3-Et fentanyl 6.2 cis, (1.5 x fentanyl), all of the others were less active than fentanyl or inactive. Some tentative conclusions on the structure- activity relationship (SAR) in this series of derivatives have been made.

Cis- and trans-2,4-dimethoxytetrahydropyran. Models for the study of the anomeric effect

1968 ◽  
Vol 46 (9) ◽  
pp. 1543-1548 ◽  
Author(s):  
F. Sweet ◽  
R. K. Brown
Keyword(s):  
Good Yield ◽  
Methoxy Group ◽  
Equilibrium Mixture ◽  
Anomeric Effect ◽  
Kcal Mole ◽  
Mild Acid Hydrolysis ◽  
Acid Catalyzed ◽  
Cis And Trans ◽  
Hydrolysis Of ◽  
Mild Acid

Acid-catalyzed methanolysis of 2-methoxy-5,6-dihydro-2H-pyran gave, in good yield, a 4.0:1.0 mixture of trans- and cis-2,4-dimethoxytetrahydropyran. Mild acid hydrolysis of 2-methoxy-5,6-dihydro-2H-pyran followed by acid-catalyzed reaction with methanol gave a cis-trans mixture of 4-hydroxy-2-methoxytetrahydropyran in very poor yield.From the equilibrium mixture of trans- and cis-2,4-dimethoxytetrahydropyran (4.0:1.0), the magnitude of the anomeric effect of the 2-methoxy group was calculated to be 1.4 kcal/mole.

Trypanocidal Structure-Activity Relationshipfor Cis- and Trans-methylpluviatolide

Planta Medica ◽  
2008 ◽  
Vol 74 (03) ◽  
Author(s):  
R Silva ◽  
J Saraiva ◽  
S Albuquerque ◽  
C Curti ◽  
PM Donate ◽  
...  
Keyword(s):  
Structure Activity ◽  
Cis And Trans

Amino acid sequence of cyanogen bromide fragment CB5 of human hemopexin

1989 ◽  
Vol 54 (3) ◽  
pp. 803-810 ◽  
Author(s):  
Ivan Kluh ◽  
Ladislav Morávek ◽  
Manfred Pavlík
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Acid Hydrolysis ◽  
Cyanogen Bromide ◽  
Polypeptide Chain ◽  
Amino Acid Residues ◽  
Mild Acid Hydrolysis ◽  
Methionine Residue ◽  
Cyanogen Bromide Fragment ◽  
Mild Acid

Cyanogen bromide fragment CB5 represents the region of the polypeptide chain of hemopexin between the fourth and fifth methionine residue (residues 232-352). It contains 120 amino acid residues in the following sequence: Arg-Cys-Ser-Pro-His-Leu-Val-Leu-Ser-Ala-Leu-Thr-Ser-Asp-Asn-His-Gly-Ala-Thr-Tyr-Ala-Phe-Ser-Gly-Thr-His-Tyr-Trp-Arg-Leu-Asp-Thr-Ser-Arg-Asp-Gly-Trp-His-Ser-Trp-Pro-Ile-Ala-His-Gln-Trp-Pro-Gln-Gly-Pro-Ser-Ala-Val-Asp-Ala-Ala-Phe-Ser-Trp-Glu-Glu-Lys-Leu-Tyr-Leu-Val-Gln-Gly-Thr-Gln-Val-Tyr-Val-Phe-Leu-Thr-Lys-Gly-Gly-Tyr-Thr-Leu-Val-Ser-Gly-Tyr-Pro-Lys-Arg-Leu-Glu-Lys-Glu-Val-Gly-Thr-Pro-His-Gly-Ile-Ile-Leu-Asp-Ser-Val-Asp-Ala-Ala-Phe-Ile-Cys-Pro-Gly-Ser-Ser-Arg-Leu-His-Ile-Met. The sequence was derived from the data on peptides prepared by cleavage of fragment CB5 by mild acid hydrolysis, by trypsin and chymotrypsin.

scholarly journals The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 509 ◽  
Author(s):  
Steffen Glöckner ◽  
Khang Ngo ◽  
Björn Wagner ◽  
Andreas Heine ◽  
Gerhard Klebe
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
The Novel ◽  
Binding Modes ◽  
X Ray ◽  
Structure Activity ◽  
Small Set ◽  
Novel Method ◽  
Human Carbonic Anhydrase ◽  
Kinetics Of

The fluorination of lead-like compounds is a common tool in medicinal chemistry to alter molecular properties in various ways and with different goals. We herein present a detailed study of the binding of fluorinated benzenesulfonamides to human Carbonic Anhydrase II by complementing macromolecular X-ray crystallographic observations with thermodynamic and kinetic data collected with the novel method of kinITC. Our findings comprise so far unknown alternative binding modes in the crystalline state for some of the investigated compounds as well as complex thermodynamic and kinetic structure-activity relationships. They suggest that fluorination of the benzenesulfonamide core is especially advantageous in one position with respect to the kinetic signatures of binding and that a higher degree of fluorination does not necessarily provide for a higher affinity or more favorable kinetic binding profiles. Lastly, we propose a relationship between the kinetics of binding and ligand acidity based on a small set of compounds with similar substitution patterns.

scholarly journals Synthesis and structure-activity relationships of the novel isothiobarbamine analogues with lowered basicity

2020 ◽  
Author(s):  
I. A. Novakov ◽  
L. L. Brunilina ◽  
V. V. Chapurkin ◽  
M. B. Nawrozkij ◽  
D. S. Sheikin ◽  
...  
Keyword(s):  
The Novel ◽  
Structure Activity Relationships ◽  
Structure Activity

scholarly journals A New Look at the Enterobacterial Common Antigen Forms Obtained during Rough Lipopolysaccharides Purification

2021 ◽  
Vol 22 (2) ◽  
pp. 701
Author(s):  
Tomasz K Gozdziewicz ◽  
Anna Maciejewska ◽  
Alona Tsybulska ◽  
Czeslaw Lugowski ◽  
Jolanta Lukasiewicz
Keyword(s):  
Current Knowledge ◽  
Membrane Integrity ◽  
Gel Filtration ◽  
Common Antigen ◽  
Mild Acid Hydrolysis ◽  
Enterobacterial Common Antigen ◽  
Lipopolysaccharide Endotoxin ◽  
Lipid Moiety ◽  
Detailed Composition ◽  
Mild Acid

Enterobacterial common antigen (ECA) is a conserved antigen expressed by enterobacteria. It is built by trisaccharide repeating units: →3)-α-D-Fucp4NAc-(1→4)-β-D-ManpNAcA-(1→4)-α-D-GlcpNAc-(1→ and occurs in three forms: as surface-bound linear polysaccharides linked to a phosphoglyceride (ECAPG) or lipopolysaccharide − endotoxin (ECALPS), and cyclic form (ECACYC). ECA maintains, outer membrane integrity, immunogenicity, and viability of enterobacteria. A supernatant obtained after LPS ultracentrifugation was reported as a source for ECA isolation, but it has never been assessed for detailed composition besides ECACYC. We used mild acid hydrolysis and gel filtration, or zwitterionic-hydrophilic interaction liquid (ZIC®HILIC) chromatography combined with mass spectrometry for purification, fractionation, and structural analysis of rough Shigella sonnei and Escherichia coli R1 and K12 crude LPS preparations. Presented work is the first report concerning complex characteristic of all ECA forms present in LPS-derived supernatants. We demonstrated high heterogeneity of the supernatant-derived ECA that contaminate LPS purified by ultracentrifugation. Not only previously reported O-acetylated tetrameric, pentameric, and hexameric ECACYC have been identified, but also devoid of lipid moiety linear ECA built from 7 to 11 repeating units. Described results were common for all selected strains. The origin of linear ECA is discussed against the current knowledge about ECAPG and ECALPS.

Pigments of marine animals. XI. Angular naphthopyrones from the crinoid Comanthus parvicirrus timorensis

1971 ◽  
Vol 24 (7) ◽  
pp. 1487 ◽  
Author(s):  
IR Smith ◽  
MD Sutherland
Keyword(s):  
Methyl Ether ◽  
Dry Weight ◽  
Water Soluble ◽  
Spectral Studies ◽  
Mild Acid Hydrolysis ◽  
Marine Animals ◽  
Yellow Colour ◽  
Methoxy Derivative ◽  
Colour Variant ◽  
Mild Acid

Green specimens of the comatulid crinoid, Comanthus parvicirrus timorensis J. Muller, yield to acetone three yellow water-soluble colouring matters, comaparvin sulphate, 6-methoxycomaparvin sulphate, and 6-methoxycomaparvin 5-methyl ether sulphate in approximately 0.1 %, 0.7 %, and 0.7 % yield respectively of the dry weight of the animal, Mild acid hydrolysis yields the corresponding phenols, the structures of which have been deduced largely by spectral studies as very probably 5,8-dihydroxy-10-methoxy-2-n-propyl-4H-naphtho[1,2-b]pyran-4-one (1), the 6-methoxy derivative of (1), and the 6-methoxy methyl ether of (1) respectively. A yellow colour variant of the same species yielded the same colouring matters in slightly different proportions. The calcareous skeleton contains what are probably polyhydroxynaphthoquinones in combined form.

The synthesis of a carbohydrate-like dihydrooxazine and tetrahydrooxazine as putative inhibitors of glycoside hydrolases: A direct synthesis of isofagomine

2002 ◽  
Vol 80 (8) ◽  
pp. 857-865 ◽  
Author(s):  
Wayne M Best ◽  
James M Macdonald ◽  
Brian W Skelton ◽  
Robert V Stick ◽  
D Matthew G Tilbrook ◽  
...  
Keyword(s):  
Direct Synthesis ◽  
Glycoside Hydrolases ◽  
Crystalline Solid ◽  
Glycosidase Inhibitors ◽  
Protecting Group ◽  
Mild Acid Hydrolysis ◽  
Catalytic Hydrogenolysis ◽  
Palladium On Carbon ◽  
Mild Acid

The treatment of benzyl 2,3-O-isopropylidene-β-L-xylopyranoside with N-hydroxyphthalimide under Mitsunobu conditions, followed by protecting-group interchange, gave benzyl 4-O-[(tert-butoxycarbonyl)amino]-2,3- O-isopropylidene-α-D-arabinoside. Mild acid hydrolysis and catalytic hydrogenolysis afforded 4-O-[(tert-butoxycarbonyl)amino]-D-arabinose that, upon heating in water, gave the dihydrooxazine [(4R,5S,6R)-5,6-dihydro-4,5-dihydroxy-6-hydroxymethyl-4H-1,2-oxazine] as a crystalline solid. A single-crystal structure determination of this solid showed it to exist in the 5H6 conformation. Reduction of the dihydrooxazine gave the tetrahydrooxazine [(4R,5S,6R)-4,5-dihydroxy-6-hydroxymethyl-3,4,5,6-tetrahydro-2H-1,2-oxazine]. The dihydrooxazine was an effective inhibitor of two β-glucosidases (Ki = 27 and 35 µM). Benzyl 2,3-O-isopropylidene-β-L-xylopyranoside, via the derived imidazylate, was converted into a nitrile that, upon reduction and protecting-group manipulations, gave benzyl 4-C-aminomethyl-4-deoxy-α-D-arabinoside. Treatment of this amine with hydrogen and palladium-on-carbon gave isofagomine.Key words: dihydrooxazine, tetrahydrooxazine, isofagomine, iminosugars, glycosidase inhibitors.

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