Pharmacophore fingerprint and construction of primary library for quantitative structure-activity relationship

摘要

Specialized apparatus and methods may be used for identifying, representing, and productively using high activity regions of chemical structure space. At least two representations of chemical structure space provide valuable information. A first representation has many dimensions representing members of a pharmacophore basis set and one or more additional dimensions representing defined chemical activity (e.g., pharmacological activity). A second representation has many fewer dimensions, each of which represents a principle component obtained by transforming the first representation via principal component analysis used on pharmacophore fingerprint/activity data for a collection of compounds. When the collection of compounds has the defined chemical activity, that activity will be reflected as a "high activity" region of chemical space in the second representation. A "transformation" procedure may convert between the first and second representations. If pharmacophore fingerprints for an "investigation" set of compounds is transformed to the second representation of chemical space, those compounds can be "screened" for high activity. Those compounds residing in the region of high activity may likely have the desired activity. Those compounds residing outside the region probably do not have the desired activity. The compounds falling within high activity region may be selected for a primary library or a more constrained library, depending upon the specificity of the high activity region.