Combinatorial chemistry in drug research from a new vantage point

Bioorganic and Medicinal Chemistry

Volumn 5, Issue 3, 1997, Pages 473-491

  Maehr, Hubert ^a  

^a HOFFMANN LA ROCHE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG DESIGN; DRUG MIXTURE; DRUG RESEARCH; DRUG SCREENING; DRUG SYNTHESIS; MATHEMATICS; PROBABILITY; REVIEW; STRUCTURE ACTIVITY RELATION; TECHNIQUE;

EID: 0031104682     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0968-0896(96)00277-5     Document Type: Review

References (63)

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44. 44. Reality may deviate from the underlying assumptions so that the members identified by the combinatorial product and their computed order may not be congruent with the actual ones. Practice has shown, however, that identification of the lead compounds by the methods described herein is remarkably successful.
45. k occupies the intersection point at the jth row and the kth column displays each pair only once.
46. 40AB).
47. 6B).
48. k) as a reduced set.
49. 2).
50. 50. Maehr, H.; Yang, R. Bioorg. Med. Chem., following article. The paper provides an example of library construction in liquid phase and illustrates lead identification and arrangement of the elements in the order of their bioactivities as suggested by the combinatorial product of a set obtained by bioassays of the last partition and two sets based on data of partitions of two reduced sets.
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53. 53. Freier et al. (ref 60) refer to the identification process via reduced sets as synthetic unrandomization of randomized fragments ('SURF').
54. 54. Bioassay results of the second reduced set are assumed to be the same as those of the A-partition specified in Figure 7(A).
55. 55. In contrast, simultaneous evaluation of all partitions (section 4.1) considered the three-dimensional sample space as the product of three coordinates.
56. xA) requires nx additional steps. To include the B-type partition, a total of 2(n + n√n) synthetic operations are needed.
57. nN N) followed by additional p operations, so that a total of 5n + p steps are required.
58. k) requires the same number of operations, so that the total number of synthetic steps is 2p + q + 4√n.
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