2,3-substituted 2-azanorbornanes as polar β-turn mimetics

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 1, 1997, Pages 31-36

  Horwell, David C ^a   Naylor, Dorica ^a   Willems, Henriëtte M G ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 AZANORBORNANE DERIVATIVE; 3 BENZYL 1 [2 (3 INDOLYL)ACETYL]PYRROLIDINE; MEN 10627; NEUROKININ 2 RECEPTOR; NEUROKININ 2 RECEPTOR ANTAGONIST; NORBORNANE DERIVATIVE; RECEPTOR SUBTYPE; TACHYKININ RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; COMPUTER SIMULATION; CONTROLLED STUDY; DIPOLE; DRUG CONFORMATION; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; HUMAN TISSUE; IN VITRO STUDY; NONHUMAN; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

EID: 0031022686     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(96)00570-7     Document Type: Article

References (12)

1. G. D. Rose, L. M. Gierasch, J. A. Smith, Adv. Protein Chem., 1985, 37, 1-109.
2. a) D. F. Veber, Proc. 12th Am. Pept. Symp., ed. J. A. Smith, J. E. Rivier, Escom, Leiden, 1992, 1-14.
3. b) Y.-B. He, Z. Huang, K. Raynor, T. Reisine, M Goodman, J. Am. Chem. Soc., 1993, 115, 8066-8072.
4. V. Pavone, A. Lombardi, F. Nastri, M. Saviano, O. Maglio, G. D'Auria, L. Quartara, C. A. Maggi, C. Pedone, J. Chem. Soc., Perkin Trans. 2, 1995, 987-993.
5. D. C. Horwell, W. Howson, D. Naylor, H. M. G. Willems, BioMed Chem. Lett., 1995, 5, 1445-1450.
6. Dipole moment calculations (in Debyes) were based on the point charge distribution in the molecule. The point charge distribution for each molecule was calculated using the Gasteiger-Hückel method. The dipoles were displayed using SYBYL-Basic.
7. -1. The lowest energy conformer found was overlayed by the method of least squares with MEN10627. The molecules were aligned by superimposing the Cαs and Cβs of the Trp and Phe residues of MEN10627 on the corresponding atoms of 3. The side chains appended to the azanorbornane template were subsequently rotated to overlay with the Tip and Phe side chains of the peptide. The energy of the resulting conformation of 3 was calculated and compared with the lowest energy value. The rms distance over 6 points (i.e. between the Cαs, Cβs and Cγs of MEN10627's Trp and Phe residues and the corresponding atoms on 3) of the template in this conformation to the peptide was 0.36 Å.
8. P. A. Grieco, S. D. Larsen, W. F. Fobare, Tetrahedron Lett, 1986, 27, 1975-1978.
9. +, 16%).
10. a) S. Boyle, S. Guard, M. Higginbottom, D. C. Horwell, W. Howson, A.T. McKnight, K. Martin, M. C. Pritchard, J. O'Toole, J. Raphy, D. C. Rees, E. Roberts, K. J. Watling, G. N. Woodruff, J. Hughes, BioMed Chem., 1994, 2, 357-370.
11. b) S. Boyle, S. Guard, J. Hodgson, D. C. Horwell, W. Howson, J. Hughes, A. McKnight, K. Martin, M. C. Pritchard, K. J. Watling, G. N. Woodruff, BioMed Chem., 1994, 2, 101-113.
12. c) P. Boden, J. M. Eden, J. Hodgson, D. C. Horwell, W. Howson, J. Hughes, A. T. McKnight, K. Meecham, M. C. Pritchard, J. Raphy, G. S. Ratcliffe, N. Suman-Chauhan, G. N. Woodruff, BioMed. Chem.Lett., 1994, 4, 1679-1684.