2,5-Diaryl tetrahydrofurans and analogs thereof as PAF-antagonists
AssigneeMerck & Co., Inc.
InventorsTesfaye Biftu, San-Bao Hwang, Thomas W. Doebber, Thomas R. Beattie, Tsung-Ying Shen
Life of this patent
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Abstract
Analogs of 2,5-Diaryl tetrahydrofurans which were substituted or unsubstituted at 3,4-positions were prepared. These compounds are found to have potent and specific PAF (Platelet Activating Factor) antagonistic activities and thereby useful in the treatment of various diseases or disorders mediated by the PAF, for example, inflammation, cardiovascular disorder, asthma, lung edema, adult respiratory distress syndrome, pain, and aggregation of platelets.
Claims9
A compound of formula:
- ##STR14## wherein R and R' independently are (a) hydrogen:
- (b) haloloweralkyl;
- (c) halo;
- (d) CONR.sup.2 R.sup.3 wherein R.sup.2 and R.sup.3 independently represent C.sub.1-6 alkyl and hydrogen;
- (e) loweralkenyl;
- (f) --COR.sup.2 ;
- (g) --CH.sub.2 OR.sup.2 ;
- (h) loweralkynyl;
- (i) --CH.sub.2 NR.sup.2 R.sup.3 ;
- (j) --CH.sub.2 SR.sup.2 ;
- (k) .dbd.O;
- or
- (l) --OR.sup.2 ;
- Ar and Ar.sup.1 are the same or different from each other and are substituted phenyl of formula ##STR15## where R.sup.4 -R.sup.8 independently represent R.sup.2 O--, R.sup.2 S--, R.sup.2 SO, R.sup.2 SO.sub.2 --, CF.sub.3 O--, CF.sub.3 S--, R.sup.2 R.sup.3 N--, --OCH.sub.2 CO.sub.2 R.sup.2, --SO.sub.2 NR.sup.2 R.sup.3, --CO.sub.2 R.sup.2, --NR.sup.2 SO.sub.2 R.sup.3, COR.sup.2, NO.sub.2, or CN or R.sup.4 -R.sup.5, R.sup.5 -R.sup.6, R.sup.6 -R.sup.7 and R.sup.7 -R.sup.8 are joined together forming a bridge.
A pharmaceutical composition for treating a disease or a disorder mediated by PAF comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of formula:
- ##STR17## wherein R and R' independently are (a) hydrogen;
- (b) haloloweralkyl;
- (c) halo;
- (d) CONR.sup.2 R.sup.3 wherein R.sup.2 and R.sup.3 independently represent C.sub.1-6 alkyl and hydrogen;
- (e) loweralkenyl;
- (f) --COR.sup.2 ;
- (g) --CH.sub.2 OR.sup.2 ;
- (h) loweralkynyl;
- (i) --CH.sub.2 NR.sup.2 R.sup.3 ;
- (j) --CH.sub.2 SR.sup.2 ;
- (k) .dbd.O;
- or
- (l) --OR.sup.2 ;
- Ar and Ar.sup.1 are the same or different from each other and are substituted phenyl of formula ##STR18## where R.sup.4 -R.sup.8 independently represent R.sup.2 O--, R.sup.2 S--, R.sup.2 SO, R.sup.2 SO.sub.2 --, CF.sub.3 O--, CF.sub.3 S--, R.sup.2 R.sup.3 N--, --OCH.sub.2 CO.sub.2 R.sup.2, --SO.sub.2 NR.sup.2 R.sup.3, --CO.sub.2 R.sup.2, --NR.sup.2 SO.sub.2 R.sup.3, COR.sup.2, NO.sub.2, or CN or R.sup.4, -R.sup.5, R.sup.5 -R.sup.6, R.sup.6 -R.sup.7 and R.sup.7 -R.sup.8 are joined together forming a bridge.
A method for the treatment of a disease or a disorder mediated by PAF comprising administering to a mammalian species in need of the treatment a therapeutically effective amount of a compound of formula:
- ##STR20## wherein R and R' independently are (a) hydrogen:
- (b) haloloweralkyl;
- (c) halo;
- (d) CONR.sup.2 R.sup.3 wherein R.sup.2 and R.sup.3 independently represent C.sub.1-6 alkyl and hydrogen;
- (e) loweralkenyl;
- (f) --COR.sup.2 ;
- (g) --CH.sub.2 OR.sup.2 ;
- (h) loweralkynyl;
- (i) --CH.sub.2 NR.sup.2 R.sup.3 ;
- (j) --CH.sub.2 SR.sup.2 ;
- (k) .dbd.O;
- or
- (l) --OR.sup.2 ;
- Ar and Ar.sup.1 are the same or different from each other and are phenyl or substituted phenyl of formula ##STR21## where R.sup.4 -R.sup.8 independently represent H, R.sup.2 O--, R.sup.2 S--, R.sup.2 SO, R.sup.2 SO.sub.2 --, CF.sub.3 O--, CF.sub.3 S--, R.sup.2 R.sup.3 N--, --OCH.sub.2 CO.sub.2 R.sup.2, --SO.sub.2 NR.sup.2 R.sup.3, --CO.sub.2 R.sup.2, --NR.sup.2 SO.sub.2 R.sup.3, COR.sup.2, NO.sub.2, or CN or R.sup.4 -R.sup.5, R.sup.5 -R.sup.6, R.sup.6 -R.sup.7 and R.sup.7 -R.sup.8 are joined together forming a bridge.
Dependencies are inferred from the claim text.