Klaus Gundertofte

Lundbeck · CP&T

The Confederacy of European Patent Information User Groups (CEPIUG) was founded in 2008 to promote the sharing of experiences and expertise in patent searching across Europe. CEPIUG currently comprises patent information user groups from eight different European countries and is open to new members. Besides the exchange of information, CEPIUG also...

IntroductionStructure of TransportersMonoamine TransportersTransporters for Amino AcidsNonneurotransmitter TransportersConcluding RemarksReferences

The serotonin transporter (SERT) is one of the neurotransmitter transporters that plays a critical role in the regulation of endogenous amine concentrations and therefore is an important target for therapeutic agents affecting the central nervous system. The recently published, high resolution X-ray structure of the closely related amino acid trans...

Exhaustive conformational analyses on four selective serotonin reuptake inhibitors resulted in a pharmacophoric model explaining observed differences in enantioselectivities. A number of test compounds from a diverse set of chemical structures was included in the evaluation of the model. Furthermore, selectivity towards noradrenaline reuptake is ex...

Ginkgolides are antagonists of the inhibitory ligand-gated ion channels for the neurotransmitters glycine and gamma-aminobutyric acid (GABA). In this study the ginkgolide structure was modified in order to investigate the minimum structural requirements for glycine receptor antagonism. The five native ginkgolides and a series of 29 ginkgolide deriv...

A new similarity measure and structural clustering method has been developed in which each structure is fragmented into ring systems, linkers, and side chains, and where the similarity between structures forms a weighted sum of the similarities between each set of fragments. We have applied the MACCS keys as molecular descriptors and identified a n...

For Abstract see ChemInform Abstract in Full Text.

Three neurokinin (NK) antagonist pharmacophore models (Models 1-3) accounting for hydrogen bonding groups in the 'head' and 'tail' of NK receptor ligands have been developed by use of a new procedure for treatment of hydrogen bonds during superimposition. Instead of modelling the hydrogen bond acceptor vector in the strict direction of the lone pai...

The molecular alignments obtained from a previously reported pharmacophore model have been employed in a three-dimensional quantitative structure-activity relationship (3D QSAR) study, to obtain a more detailed insight into the structure-activity relationships for D(2) and D(4) receptor antagonists. The frequently applied CoMFA method and the relat...

A neurokinin 2 (NK2) antagonist pharmacophore model has been developed on the basis of five non-peptide antagonists from several structurally diverse classes. To evaluate the pharmacophore model, another 20 antagonists were fitted to the model. By use of exhaustive conformational analysis (MMFFs force field and the GB/SA hydration model) and least-...

A pharmacophore model for dopamine D4 antagonists has been developed on the basis of a previously reported dopamine D2 model. By using exhaustive conformational analyses (MM3* force field and the GB/SA hydration model) and least-squares molecular superimposition studies, a set of eighteen structurally diverse high affinity D4 antagonists have succe...

Much of chemistry, molecular biology, and drug design, are centered around the relationships between chemical structure and measured properties of compounds and polymers, such as viscosity, acidity, solubility, toxicity, enzyme binding, and membrane penetration. For any set of compounds, these relationships are by necessity complicated, particularl...

Several commonly used molecular mechanics force fields have been tested for accuracy in conformational energy calculations. Differences in performance between the force fields are discussed for different classes of structures. MMFF93 and force fields based on the MM2 or MM3 functional form are found to perform significantly better than other force...

Several commonly used molecular mechanics force fields have been tested for accuracy in conformational energy calculations. Differences in performance between the force fields are discussed for different classes of structures. MMFF93 and force fields based on the MM2 or MM3 functional form are found to perform significantly better than other force...

A receptor-interaction model for serotonin 5-HT2 receptor antagonists has been developed by conformational analysis with molecular mechanics (MM2(91)) and superimposition studies of serotonin 5-HT2 receptor antagonists. Substituted 3-(4-piperidinyl)-, 1-(4-piperidinyl)-, 3-(1,2,3,6-tetrahydropyridin-4-yl)-, and 1-(1,2,3,6-tetrahydropyridin-4-yl)-1H...

The molecular electrostatic potentials for a selective dopamine D-1 receptor antagonist, 7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-methylbenzazepine (SCH 23390 (1], and a selective dopamine D-1 receptor agonist, 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SK&F 38393 (2], have been calculated in order to obtain an understan...

The calculated result obtained with MM2(87) for the rotation of the isopropyl group in 3-methyl-1-butene is not in agreement with experimental data. In order to reparametrize the Csp2-Csp3-Csp-Csp3 torsional angle, 3-methyl-1-butene and 1-butene have been studied by molecular mechanics (MM2(87)) and ab initio (MP2/6-31G* and MP3/6-31G*) calculation...

Conformational energies of different conformers have been calculated for a series of molecules using various molecular mechanics and semiempirical methods. The quality of the force fields has also been tested by calculating barriers to rotation about carbon-carbon bonds. The molecular mechanics force fields used are MM2(85), Sybyl 5.1, Sybyl 5.21,...

A series of trans-1-piperazino-3-phenylindans were synthesized with the goal of replacing their established neuroleptic profile with that of peripheral 5-hydroxytryptamine (5-HT2) antagonism. Compounds with an unsubstituted or fluoro-substituted 6-position in the indan ring, and which had a five- or six-membered heterocyclic ring attached by an eth...