Conformationally constrained analogues of diacylglycerol. 12.1 Ultrapotent protein kinase C ligands based on a chiral 4,4-disubstituted heptono-1,4-lactone template

Journal of Medicinal Chemistry

Volumn 39, Issue 1, 1996, Pages 36-45

  Lee, Jeewoo ^a   Sharma, Rajiv ^a   Wang, Shaomeng ^a   Milne, George W A ^a   Lewin, Nancy E ^a   Szallasi, Zoltan ^a   Blumberg, Peter M ^a   George, Clifford ^b   Marquez, Victor E ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b NAVAL RESEARCH LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 (HYDROXYMETHYL) 5 [2 (METHOXYCARBONYL)ETHENYL] 3 (9 OCTADECENYLIDENE)TETRAHYDRO 2 FURANONE; 5 (HYDROXYMETHYL) 5 [2 (TETRADECANOYL)ETHENYL]TETRAHYDRO 2 FURANONE; 5 (HYDROXYMETHYL) 5 [2 (TETRADECANOYL)ETHYL]TETRAHYDRO 2 FURANONE; DIACYLGLYCEROL; PHORBOL 13 ACETATE 12 MYRISTATE; PROTEIN KINASE C; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CHIRALITY; DOWN REGULATION; DRUG CONFORMATION; EDEMA; ENANTIOMER; ENTROPY; HYPERPLASIA; RACEMIC MIXTURE; STEREOSPECIFICITY;

4-BUTYROLACTONE; ANIMALS; BINDING, COMPETITIVE; DIGLYCERIDES; EPIDERMAL GROWTH FACTOR; KERATINOCYTES; LIGANDS; MAGNETIC RESONANCE SPECTROSCOPY; MICE; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; PEPTIDES; PHORBOL ESTERS; PHOSPHORYLATION; PROTEIN KINASE C; STEREOISOMERISM;

EID: 0030023919     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950278f     Document Type: Article

References (15)

1. Lee, J.; Wang, S.; Lewin, N. E.; Blumberg, P. M.; Marquez, V. E. J. Med. Chem. 1996, 39, 29-35.
2. Sharma, R.; Lee, J.; Lewin, N. E.; Blumberg, P. M.; Marquez, V. E. J. Med. Chem. 1996, 39, 19-28.
3. Lee, J.; Sharma, R.; Teng, K.; Lewin, N. E.; Blumberg, P. M.; Marquez, V. E. Conformationally Constrained Analogues of DAG. 8. Changes in PK-C Binding Affinity Produced by Isosteric Groups of the 3-O-Acyl Function in 2-Deoxy-L-Ribonolactones. BioMed. Chem. Lett. 1994, 4, 1369-1374.
4. Morimoto, Y.; Mikami, A.; Shirahama, H. Unprecented Stability of δ-Lactones with Axial Substituents rather than Equatorial Ones; Comparison with Prelog-Djerassi Lactone Derivative. J. Chem. Soc., Chem. Commun. 1991, 1376-1378.
5. Wang, S.; Milne, G. W. A.; Nicklaus, M. C.; Marquez, V. E.; Lee, J.; Blumberg, P. M. Protein Kinase C. Modeling of the Binding Site and Prediction of Binding Constants. J. Med. Chem. 1994, 4, 1326-1338.
6. Marquez, V. E.; Lee, J.; Sharma, R.; Teng, K.; Wang, S.; Lewin, N. E.; Bahador, A.; Kazanietz, M. G.; Blumberg, P. M. Conformationally Constrained Analogues of Diacylglycerol. 6. Changes in PK-C Binding Affinity for 3-O-Acyl-2-Deoxy-L-Ribonolactones Bearing Different Acyl Chains. BioMed. Chem. Lett. 1994, 4, 355-360.
7. The relative stereochemistry at C-5 is the same in both templates; however, the presence of the double bond in 5 (as well as in 7 and 8) causes the chiral center to change from "R" to "S".
8. Floch, Y. L.; Yuergnaux, F.; Toupet, L.; Gree, R. Syntheses et Reactivite d'ω-Aldehydophosphoranes; Application a Ia Preparation de Lactones α,β-Insaturees. (Synthesis and Reactivity of ω-Aldehydophosphoranes. Application for the Preparation α,β-Unsaturated Lactones.) Bull. Soc. Chim. Fr. 1991, 128, 742-758.
9. Dahlman, O.; Garegg, P. J.; Mayer, H.; Schramek, S. Synthesis of Three 3-C-Hydroxymethylpentoses with the D-Ribo-, D-Xylo-and L-Lyxo-Configurations. Identification of the Latter with a Monosaccharide Isolated from Phase I Coxiella Burnetii Li-popolysaccharide. Acta Chem. Scand. B 1986, 40, 15-20.
10. Howie, G. A.; Manni, P. E.; Cassady, J. M. Synthesis of Alkyl-Substituted α,β-Unsaturated γ-Lactones as Potential Antitumor Agents. J. Med. Chem. 1974, 17, 840-843.
11. Szallasi, Z.; Denning, M. F.; Smith, C. B.; Dlugosz, A. A.; Yuspa, S. H.; Pettit, G. R.; Blumberg, P. M. Mol. Pharmacol. 1994, 46, 840.
12. Blumberg, P. M.; Acs, G.; Areces, L. B.; Kazanietz, M. G.; Lewin, N. E.; Szallasi, A. In Receptor-Mediated Biological Processes: Implications for Evaluating Carcinogenesis; Spirer, H. L., Slaga, T. J., Eds.; Wiley-Liss: New York, 1994; pp 3-19.
13. Szallasi, Z.; Kosa, K.; Smith, C. B.; Dlugosz, A. A.; Williams, E. K.; Yuspa, S. H.; Blumberg, P. M. Differential Regulation by Anti-Tumor-Promoting 12-Deoxyphorbol-13-phenylacetate Reveals Distinct Roles of the Classical and Novel Protein Kinase C Isozymes in Biological Response of Primary Responses of Primary Mouse Keratinocytes. Mol. Pharmacol. 1995, 47, 258-265.
14. Teng, K.; Marquez, V. E.; Milne, G. W. A.; Barchi, Jr. J. J.; Kazanietz, M. G.; Lewin, N. E.; Blumberg, P. M.; Abushanab, E. Conformationally Constrained Analogues of Diacylglycerol. Interaction of γ-Lactones with the Phorbol Ester Receptor of Protein Kinase C. J. Am. Chem. Soc. 1992, 114, 1059-1070.
15. Kazanietz, M. G.; Areres, L. B.; Bahador, A.; Mischak, H.; Goodnight, J.; Mushinski, J. F.; Blumberg, P. M. Characterization of Ligand and Substrate Specificity for the Calcium-Dependent and Calcium-Independent Protein Kinase C Isozymes. Mol. Pharmacol. 1993, 44, 298-307.