Enriching chemical space with diversity-oriented synthesis

Current Opinion in Drug Discovery and Development

Volumn 9, Issue 6, 2006, Pages 700-712

  Thomas, Gemma L ^a   Wyatt, Emma E ^a   Spring, David R ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Chemical genetics; Chemical genomics; Combinatorial chemistry; DOS; Molecular descriptors; Structural diversity and complexity

Indexed keywords

2 (3 PYRIDYL)ETHYLAMINE; ACETIC ACID DERIVATIVE; ALKALOID DERIVATIVE; BENZODIAZEPINE DERIVATIVE; BENZOPYRAN DERIVATIVE; CARBAZOLE DERIVATIVE; CHROMONE DERIVATIVE; ETHYLAMINE; GAMMA LACTAM DERIVATIVE; HYDANTOIN DERIVATIVE; INDOLE DERIVATIVE; OLIGOMER; OXAZOLE DERIVATIVE; PALLADIUM COMPLEX; PIPERAZINEDIONE; PROTEIN KINASE INHIBITOR; RUTHENIUM COMPLEX; SCAFFOLD PROTEIN; STEROID; THROMBIN INHIBITOR; UNCLASSIFIED DRUG;

ALGORITHM; CATALYSIS; CHEMICAL GENETICS; CHEMICAL MODIFICATION; CHEMICAL REACTION; CYCLOADDITION; DIPOLE; DRUG QUALITY; DRUG RESEARCH; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; HUMAN; LIPOPHILICITY; MOLECULAR WEIGHT; PROTEIN MODIFICATION; REVIEW; RING CLOSING METATHESIS;

COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DESIGN; MODELS, CHEMICAL; MOLECULAR STRUCTURE;

EID: 33751060195     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (30)

1. Clardy J, Walsh C: Lessons from natural molecules. Nature (2004) 432(7019):829-837.
2. Messer R, Fuhrer CA, Häner R: Natural product-like libraries based on non-aromatic, polycyclic motifs. Curr Opin Chem Biol (2005) 9(3):259-265.
3. Seitz M, Reiser O: Synthetic approaches towards structurally diverse γ-butyrolactone natural-product-like compounds. Curr Opin Chem Biol (2005) 9(3):285-292.
4. Bohacek RS, McMartin C, Guida WC: The art and practice of structure-based drug design: A molecular modeling perspective. Med Res Rev(1996) 16(1):3-50.
5. Lipinski C, Hopkins A: Navigating chemical space for biology and medicine. Nature (2004) 432(7019):855-861.
6. Koch MA, Schuffenhauer A, Scheck M, Wetzel S, Casaulta M, Odermatt A, Ertl P, Waldmann H: Charting biologically relevant chemical space: A structural classification of natural products (SCONP). Proc Natl Acad Sci (2005) 102(48):17272-17277.
7. Haggarty SJ: The principle of complementarity: Chemical versus biological space. Curr Opin Chem Biol (2005) 9(3):296-303.
8. Dobson CM: Chemical space and biology. Nature (2004) 432(7019):824-828.
9. Fergus S, Bender A, Spring DR: Assessment of structural diversity in combinatorial synthesis. Curr Opin Chem Biol (2005) 9(3):304-309.
10. Spring DR: Chemical genetics to chemical genomics: Small molecules offer big insights. Chem Soc Rev (2005) 34(6):472-482.
11. Lloyd DQ, Golfis G, Knox AJ, Fayne D, Meegan MJ, Oprea TI: Oncology exploration: Charting cancer medicinal chemistry space. Drug Disc Today (2006) 11(3-4):149-159. Studies the charting of areas of chemical space and offers an idea of where to search for new anticancer agents.
12. Reayi A, Arya P: Natural product-like chemical space: Search for chemical dissectors of macromolecular interactions. Curr Opin Chem Biol (2005) 9(3):240-247.
13. Tan DS: Diversity-oriented synthesis: Exploring the intersections between chemistry and biology. Nat Chem Rev (2005) 1(2):74-84.
14. Arya P, Joseph R, Gan Z, Rakic B: Exploring new chemical space by stereocontrolled diversity-oriented synthesis. Chem Biol (2005) 12(2):163-180.
15. Massee CE, Ng PY, Fukase Y, Sánchez-Roselló M, Shaw JT: Divergent structural complexity from a linear reaction sequence: Synthesis of fused and spirobicyclic ylactams from common synthetic precursors. J Comb Chem (2006) 8(3):293-296.
16. Oguri H, Schreiber SL: Skeletal diversity via a folding pathway: Synthesis of indole alkaloid-like skeletons. Org Lett (2005) 7(1): 47-50.
17. Beeler AB, Schaus SE, Porco JA Jr Chemical library synthesis using convergent approaches. Curr Opin Chem Biol (2005) 9(3):277-284.
18. Wyatt EE, Fergus S, Galloway WRJD, Bender A, Fox DJ, Plowright AT, Jessiman AS, Welch M, Spring DR: Skeletal diversity construction via a branching synthetic strategy. Chem Commun (2006) (31):3296-3298.
19. Mitchell JM, Shaw JT: A structurally diverse library of polycyclic lactams resulting from systematic placement of proximal functional groups. Angew Chem-Int Ed (2006) 45(11):1722-1726.
20. Zhang W, Lu Y, Chen CHT, Curran OP, Geib S: Fluorous synthesis of hydantoin-, piperazinedione-, and benzodiazeplnedione-fused tricyclic and tetracyclic ring systems. Eur J Org Chem (2006) 26(9):2055-2059.
21. Fayol A, Zhu J: Multicomponent synthesis of epoxytetrahydronaphthyridine and structural diversification by subsequent fragmentation. Tetrahedron (2005) 61(48): 11511-11519.
22. Goess BC, Hannoush RN, Chan LK, Kirchhausen T, Shair MD: Synthesis of a 10,000-membered library of molecules resembling carpanone and discovery of vesicular traffic inhibitors. J Am Chem Soc(2006) 128(16)15391-5403.
23. Zhou C, Dubrovsky AV, Larock RC: Diversity-oriented synthesis of 3-iodochromones and heteroatom analogues via ICI-induced cyclization. J Org Chem(2006) 71(4): 1626-1632.
24. Ko SK, Jang HJ, Kim E, Park SB: Concise and diversity-oriented synthesis of novel scaffolds embedded with privileged benzopyran motif. Chem Commun (2006) (28):2962-2964.
25. Bregman H, Carroll PJ, Meggers E: Rapid access to unexplored chemical space by ligand scanning around a ruthenium center: Discovery of potent and selective protein kinase inhibitors. J Am Chem Soc (2006) 128(3):877-884. A library of compounds is prepared which contains a metal core, enabling access of a new area of chemical space.
26. Kumar N, Kiuchi M, Tallarico JA, Schreiber SL: Small-molecule diversity using a skeletal transformation strategy. Org Lett (2005) 7(13):2535-2538.
27. Kim YK, Arai MA, Arai T, Lamenzo JO, Dean EF 3rd, Patterson N, Clemons PA, Schreiber SL: Relationship of stereochemical and skeletal diversity of small molecules to cellular measurement space. J Am Chem Soc (2004) 126(45):14740-14745. The total sequence of a library synthesis and subsequent screening is described.
28. Hotha S, Tripathi A: Diversity-oriented synthesis of tricyclic compounds from glycals using the Ferrier and Pauson-Khand reactions. J Comb Chem (2005) 7(6):968-979
29. Kumagai N, Muncipinto G, Schreiber SL: Short synthesis of sketetally and stereochemically diverse small molecules by coupling petasis condensation reactions to cyclization reactions. Angew Chem-Int Ed (2006) 45(22):3635-3638. An example of a large number of different skeletons formed from a single starting material during a short divergent DOS pathway.
30. Chen C, Li X, Neumann CS, Lo MM, Schreiber SL: Convergent diversity-oriented synthesis of small-molecule hybrids. Angew Chem-Int Ed (2005) 44(15):2249-2252. A convergent DOS library is prepared using both solution- and-solid-phase methodologies.