Figure 8.

TP receptor antagonists. Conversion of PGH₂ to TXA₂ by thromboxane synthase (TXS) is shown in the box; α and ω represent natural 2-series side-chains. The pinane-thromboxane residue (related to 1(S)-α-pinene) is shown in blue; the 6-oxabicyclo(2.2.1)heptane system is in red. AH-23848 has the same α- and ω-chains as GR-32191. Benzenesulphonamide residues present in both prostanoid and non-prostanoid antagonists are shown in cerise. TP antagonists with two types of additional activity are presented. (A) IP agonism is conferred by the diphenylmethyl-heteroatomic unit in the bicyclo[2.2.2]octene analogue EP-157. (B) TXS inhibitory activity is conferred by the pyridin-3-yl residue (green) in isbogrel and ZD-1542 and by a similar replacement for ring A in relatives of GR-32191 (e.g. GR-83783; see text). Additionally, the broken arrows (lower right) typically indicate attachment of part of a TP antagonist to isbogrel (or ridogrel) to generate novel combined TP antagonist/TXS inhibitors; the tether (0–11 carbon units) has also been attached to the left-hand phenyl ring of ICI-192605 (2–8 carbon units) (Ackerley et al., 1995).