TY - JOUR
T1 - Synthesis, structural characterization and thromboxane A receptor antagonistic activity of 3-substituted 2-[(arylsulfonyl)imino]-2,3- dihydrothiazolyl derivatives
AU - Lacan, F.
AU - Varache-Lembège, M.
AU - Vercauteren, J.
AU - Léger, J.-M.
AU - Masereel, B.
AU - Dogné, J.-M.
AU - Nuhrich, A.
PY - 1999/4/1
Y1 - 1999/4/1
N2 - A series of new 2-[(arylsulfonyl)imino]-2,3-dihydrothiazolyl derivatives substituted on the heterocyclic N by a phenoxyacetic moiety was prepared according to a Hantzsch's synthesis between N, N'-disubstituted thioureas and chloroacetaldehyde. The regiochemistry of the cyclocondensation reaction was established by high resolution NMR methods. Potential thromboxane A/prostaglandin H (TxA/PGH) receptor antagonism was evaluated using human platelet aggregation assays and radioligand binding studies. The results showed that the affinity for the TxA/PGH receptor was strongly dependent on the position of the oxyacetic acid side chain. On the basis of the X-ray crystal analysis of compound 9f, a molecular modelling was undertaken on compounds 3d, 3e, and 3f. Comparison with the 3D structure of sulotroban was discussed.
AB - A series of new 2-[(arylsulfonyl)imino]-2,3-dihydrothiazolyl derivatives substituted on the heterocyclic N by a phenoxyacetic moiety was prepared according to a Hantzsch's synthesis between N, N'-disubstituted thioureas and chloroacetaldehyde. The regiochemistry of the cyclocondensation reaction was established by high resolution NMR methods. Potential thromboxane A/prostaglandin H (TxA/PGH) receptor antagonism was evaluated using human platelet aggregation assays and radioligand binding studies. The results showed that the affinity for the TxA/PGH receptor was strongly dependent on the position of the oxyacetic acid side chain. On the basis of the X-ray crystal analysis of compound 9f, a molecular modelling was undertaken on compounds 3d, 3e, and 3f. Comparison with the 3D structure of sulotroban was discussed.
UR - http://www.scopus.com/inward/record.url?scp=0032727674&partnerID=8YFLogxK
U2 - 10.1016/S0223-5234(99)80082-8
DO - 10.1016/S0223-5234(99)80082-8
M3 - Article
AN - SCOPUS:0032727674
SN - 0223-5234
VL - 34
SP - 311
EP - 328
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 4
ER -