| Autor: |
Reiter LA; Pfizer Inc, Central Research Division, Groton, CT 06340, USA., Koch K, Piscopio AD, Showell HJ, Alpert R, Biggers MS, Chambers RJ, Conklyn MJ, Cooper K, Cortina SR, Dibrino JN, Dominy BW, Farrell CA, Hingorani GP, Martinelli GJ, Ramchandani M, Wright KF |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 1998 Jul 21; Vol. 8 (14), pp. 1781-6. |
| DOI: |
10.1016/s0960-894x(98)00275-3 |
| Abstrakt: |
The SAR of a series of 2-(7-chromanyl)benzoic acids has been investigated with the aim of identifying potent and selective LTB4 receptor antagonists that maintain potency in complex biological fluids. We found optimal activity in derivatives with electron-withdrawing groups in the benzoic acid ring and with an unsubstituted C-3 benzyl group on the chromanol nucleus. While compounds containing a 3-(4-phenyl)benzyl chromanol substituent were potent LTB4 receptor antagonists, the increased lipophilicity imparted by the additional phenyl substituent led to decreased potency in the presence of plasma proteins. From among the potent compounds identified, CP-195543, the 5'-trifluoromethyl 3-benzyl chromanol, was selected for development. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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