Dissimilar Structures Selection

Holliday JD, Ranade SS, Willett P, A fast algorithm for selecting sets of dissimilar structures from large chemical databases, Quant. Struct-Act. Relat., 15 285-289, 1996. 

Holliday, J.D., Ranade S.S. and Willett, P. A Fast Algorithm for Selecting Sets of Dissimilar Structures from Large Chemical Databases. QSAR, 1996,15,285-289. 

Maximum Dissimilarity-Based Selection The original algorithm for dissimilarity ranking in the chemical structure context seems to have been proposed by Bawden, although the basic algorithm may be due to Kennard and Stone. The basic operation of a dissimilarity selection algorithm is to start with a compound selected at random and make this the first selected compound. Subsequent compounds are selected so that they are maximally dissimilar to all those in the currendy selected set. Dissimilarity may be measured by... 

The key learning of the AA(H)/AIm work was that the introduction of unsaturation with softening molecules of dissimilar structure to the fatty amidoamine increases the efficacy and the concentratability of the softener emulsion. This learning became the basis for the selection of the next combination system based on environmentally safe fatty amidoamine, AA, and triethanolamine diester quaternary methyl sulfate (DEQ and DEQ-H) [11,12,28,29]. It was possible to develop concentrates with as high as 36% actives (Eig. 8). The emulsions of fatty amidoamine and DEQ were of low viscosity (<600 cP) and exhibited acceptable viscosity stability with time (Tables 4,5). 

Holiday J D, S R Ranade and P Willett 1995. A Fast Algorithm For Selecting Sets Of Dissimilar Molecule From Large Chemical Databases. Quantitative Structure-Activity Relationships 14 501-506. 

Each step in dendrimer synthesis occurs independent of the other steps therefore, a dendrimer can take on the characteristics defined by the chemical properties of the monomers used to construct it. Dendrimers thus can have almost limitless properties depending on the methods and materials used for their synthesis. Characteristics can include hydrophilic or hydrophobic regions, the presence of functional groups or reactive groups, metal chelating properties, core/shell dissimilarity, electrical conductivity, hemispherical divergence, biospecific affinity, photoactivity, or the dendrimers can be selectively cleavable at particular points within their structure. 

Willett, P. Dissimilarity-based algorithms for selecting structurally diverse sets of compounds./. Comput. Biol. 1999, 6, 447-457. 

The first application of a computational method to select structurally diverse compounds for purchase started in 1992 at the Upjohn Company, which predated the formation of Pharmacia Upjohn by about three years. The basic approach selected compounds using a method based upon maximum dissimilarity and was implemented using SAS software [11]. This later evolved into the program Dfragall, which was written in C and is described in Section 13.6.3. Basically, a set of compounds that is maximally dissimilar from the corporate compound collection is chosen from the set of available vendor compounds. Early versions of the process relied solely on diversity-based metrics but it was found that many nondrug like compounds were identified. As a result, structural exclusion criteria were developed to eliminate compounds that were considered unsuitable for... 

Reboxetine is the only selective and reasonably potent noradrenaline reuptake inhibitor available clinically at the present time. Reboxetine has a chemical structure not dissimilar from viloxazine, an antidepressant which was of only limited clinical interest in the 1970s because of its weak efficacy and unacceptable side effects (nausea, vomiting and occasionally seizures). Unlike the secondary amine TCA antidepressants, such as maprotiline, desipramine, nortriptyline and protriptyline, reboxetine does not affect any other transporter or receptor system and therefore is largely devoid of TCA and SSRI-like side effects. In clinical trials, reboxetine has been shown to be as effective as the SSRIs in the... 

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