摘要:

AbstractThere is a growing number of biologically active peptides which have potential for the development of new therapeutics. However, native peptides are only rarely directly usable as drugs, due to inherent limitations which include rapid proteolysis and metabolism, poor transport properties, rapid excretion by the liver and kidneys, and low oral activity. Furthermore, peptides are often aselective in their actions owing to their flexible structure. In efforts to address these limitations, peptides are modified into mimetics with specific physical, chemical and biological characteristics. These so‐called peptidomimetics are derived from peptides by partly or completely removing the amide bonds while retaining essential amino acid side chains in a defined, spatial relationship. They can be developed in a rational design cycle which starts either from a lead compound obtained in a screening programme or from the parent peptide. In the latter approach, which is the focus of this overview, first the smallest, active sequence is found, and the significance of each amino acid for the biological activity is determined. In the following steps the bioactive conformation is defined by the introduction of local and global constraints. In the final step the essential amino acid side chains are positioned onto a scaffold, preferably a small, polyfunctional ring of defined stereochemistry, using structural information obtained in earlier steps. Five examples of the application of the peptidomimetic design cycle in medicinal chemistry are described here, illustrating the progression from native peptides to therapeutically useful drug

ISSN:0165-0513    

DOI:10.1002/recl.19941130202

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractSeveral long‐chain alkyl‐D‐glucofuranosidurono‐6,3‐lactones were synthesized by the acid‐catalysed glycosidation of glucurono‐6,3‐lactone. The alkyl β‐D‐glucofuranosidurono‐6,3‐lactones were reacted with sodium borohydride to give the corresponding alkyl β‐D‐glucofuranosides, and with 2‐aminoethanol andN,N‐dimethylethanediamine to give the corresponding alkyl‐N‐(2‐hydroxyethyl)‐β‐D‐glucofuranosiduronamides and alkyl‐N‐[2‐(dimethylamino)ethyl]‐β‐D‐glucofuranosiduronamides, respectively. The dodecyl‐N‐[2‐(dimethylamino)ethyl]‐β‐D‐glucofuranosiduronamides were quaternized with iodomethane to give the ammonium iodides. These new compounds, and some representative derivatives, were characterised by1H‐ and13C‐NMR spectroscopy. The physical properties (liquid‐crystal be

ISSN:0165-0513    

DOI:10.1002/recl.19941130203

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractThe synthesis and characterization of the rigid bidentate nitrogen ligands bis‐(phenylimino)camphane (Ph‐BIC) and a series of bis(arylimino)acenaphthenes (Ar‐BIAN) is described. These ligands were synthesized by the reaction of camphorquinone or acenaphthenequinone with the corresponding (substituted) aniline in the presence of ZnCl2or NiBr2, followed by removal of the metal salt in a subsequent step. NDDO calculations onpTol‐BIAN showed that the electronic properties of this ligand are comparable to the open‐chain analogue Ph‐DAB (DAB = 1,4‐diaza‐1,3‐butadiene). The aromatic group on the imine N atom of Ar‐BIAN ligands is orientated out of the bis(imino)acenaphthene plane, leading to the formation ofsynandantiisomers for theortho‐substituted derivativeso‐MeC6H4‐BIAN ando‐iPrC6H4‐BIAN. In solution one isomer is observed for these ligands, but upon coordination to a Pd(Me)Cl fragment bothsynandantiforms are present, as two isomers are formed. Furthermore, the attempted synthesis of bis(isopropylimino)cyclohexane is described, but it was found that a tautomeric imine‐enamine compound is formed which coordinates to palladium(II) in a monodentate fashion, which could not be converted to a chelating ligand. The structures ofpTol‐BIAN and Pd(Me)Cl(o,o′‐iPr2C6H3‐BIAN) in the solid state were determined by X‐ray diffraction.pTol‐BIAN is monoclinic, space groupC2,a= 20.021(2),b= 8.7703(10),c= 5.5664(10) Å, β = 103.37(1)°,Z= 2, finalR= 0.040 for 963 reflections withI>2.5σ(I). Pd(Me)Cl(o,o′‐iPr2C6H3‐BIAN) is orthorhombic, space groupPbca,a= 11.440(2),b= 21.250(3),c= 27.087(2) Å,Z

ISSN:0165-0513    

DOI:10.1002/recl.19941130204

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractThe conformations of all‐E‐retinal (1), (1S)‐all‐E‐8,16‐methano‐18‐norretinal [(1S)‐2], all‐E‐8,16‐methanoretinal (3) and all‐E‐17,18‐dinor‐8,16‐methanoretinal (4) in solution were studied by1H‐NMR spectroscopy and molecular‐mechanics and molecular‐dynamics simulations. The1H‐NMR spectrum of1is characterized by fast inversion of two half‐chair rings and by a skewed 6‐s‐cisgeometry of the polyene chain. Molecular‐dynamics simulations at 1000K on1show the existence of two, dynamically stable, skewed 6‐s‐cisconformers (torsion angle C5‐C6‐C7‐C8: 84° and —83°), separated by a 6‐s‐transtransition state. The conformationally locked structures of2, 3and4have similar conformations and are, in a geometrical sense, ideal model compounds to study rho

ISSN:0165-0513    

DOI:10.1002/recl.19941130205

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractThe synthesis of magnesium porphyrazines substituted with sulfur‐containing 15‐crown‐5 and 18‐crown‐6 macrocycles is reported as well as the single crystal structure of the 18‐crown‐6 substituted porphyrazine; the larger crown ether compound is shown to form dimers with Ag+ions, unlike the porphyrazine with the smaller crow

ISSN:0165-0513    

DOI:10.1002/recl.19941130206

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

ISSN:0165-0513    

DOI:10.1002/recl.19941130207

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

ISSN:0165-0513    

DOI:10.1002/recl.19941130210

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

ISSN:0165-0513    

DOI:10.1002/recl.19941130212

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

ISSN:0165-0513    

DOI:10.1002/recl.19941130214

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY

ISSN:0165-0513    

DOI:10.1002/recl.19941130201

出版商:WILEY‐VCH Verlag    

年代:1994

数据来源: WILEY