Conformations of drugs

Coupling constants and NOEs are the main NMR parameters used in determining the solution conformations of drug leads. NOEs provide information about through-space proxim-... 

Iwase K, Hirono S (1999) Estimation of active conformations of drugs by a new molecular superposing procedure. J Comput Aided Mol Des 13 499-512... 

Butler, K.T., Luque, F.J., and Barril, X. (2009) Toward accurate relative energy predictions of the bioactive conformation of drugs. Journal of Computational Chemistry, 30, 601-610. 

Solid State Conformations of Drugs and Biologically Active Molecules... 

Computational studies made by Kier and his coworkers, most recently on amino acids,62,63 dopamine,thyroxine, 5 oxotremorine, and phenyl choline ether,are close to views shared by medicinal chemists since the calculations deal with the conformations of drug agents. Work such as Kler s is valuable since not only can the most stable conformations accessible to a drug molecule be calculated (these can frequently be determined by X-ray or n.m.r. techniques) but also less stable, potentially undetected conformations available to a molecule could be Indicated. At least one of the... 

Table 3 Conformation of drugs containing piperidine and piperidin-4-one moieties in protein structures... 

Traditional methods of drug discovery involved a search amongst a range of diverse compounds that were derived from nature. This was a long and arduous process in which advances were due more often to serendipity rather than scientific thought and technique. The means to study the three-dimensional conformation of drugs and their receptors opened the door to a more rational approach in which compounds could be synthesized to better interact with a... 

The temperature of a simulation depends on your objectives. You might use high temperatures to search for additional conformations of a molecule (see Quenched Dynamics on page 78). Room temperature simulations generally provide dynamic properties of molecules such as proteins, peptides, and small drug molecules. Low temperatures (<250 K) often promote a molecule to a lower energy conformation than you could obtain by geometry optimization alone. 

Trioxane 210 has been used as a model system by Gu and coworkers to study the antimalarial drug artemisinin 211 (Scheme 137) [97CPL234, 99JST103]. It is the boat/twist form rather than the chair conformer of 210 that describes the subunit in 211. Moreover, geometric parameters and vibrational frequencies can only reliably be computed at the DFT level and by post-Hartree-Fock methods. B3-LYP/6-31G calculations on the conformers of 3,3,6,6-tetramethyl-1,2,4,5-tetroxane show that the chair conformer is stabilized with respect to the twisted conformer by about -2.8 kcal/mol [00JST85]. No corresponding boat conformer was found. 

Derivatized amylose is the basis for the Chiralpak AD CSP. This CSP has been utilized for the resolution of ibuprofen and flurbiprofen, as well as other members of the family of nonsteroidal inflammatory drugs (NSAIDs) [39, 61]. Ibuprofen was not resolved on the Chiralpak AD CSP in LC. Pressure-related effects on stereoselectivity were observed by Bargmann-Leyder et al. on a Chiralpak AD CSP [58]. No corresponding effect of pressure on selectivity was observed with a Chiralcel OD CSP. The authors speculated that the helical conformation of the amylose-based CSP is more flexible than that of the cellulose-based CSP. 

The strange amino-acid (4) is a fat version of phenylalanine (5) having a side chain which is rigid and inert, but which is also space filling rather than flat. Optically active (4) was needed to study peptide conformation and the biological activity of drugs. 

Perola, E., Charifson, P. S. Conformational analysis of drug-like molecules bound to proteins an extensive study of ligand reorganization upon binding. /. Med. Chem. 2004, 47, 2499-2510. 

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