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US 5,296,489 AGranted
Immunosuppressive macrocyclic compounds
AssigneeFisons Limited
InventorsDavid K. Donald, Mark Furber, Martin E. Cooper
Life of this patent
Estimating the term…
Abstract
There are provided compounds of formula (I), wherein R.sup.1 represents H, OH or alkoxy; R.sup.2 represents H; in addition R.sup.1 and R.sup.2 may together represent a second bond between the carbon atoms to which they are attached; R.sup.3 represents methyl, ethyl, propyl or allyl; R.sup.4 represents H, OH, alkyl, alkoxy, halogen, amino, S-alkyl, NHCHO or NHCO-alkyl; n represents 1 or 2; X represents O, (H, OH), (H, H) or .dbd.NH; and Y represents an optionally substituted cyclohexyl or substituted cyclopentyl group; with various provisos. The compounds are useful, inter alia, as immunosuppressive agents.
Claims9
A compound of formula I, ##STR6## wherein R.sup.1 represents H, OH or C.sub.1-10 alkoxy;
- R.sup.2 represents H;
- in addition, R.sup.1 and R.sup.2 may together represent a second bond between the carbon atoms to which they are attached;
- R.sup.3 represents methyl, ethyl, propyl or allyl;
- R.sup.4 represents H, OH, C.sub.1-10 alkyl, C.sub.1-10 alkoxy, halogen, amino, S-C.sub.1-10 alkyl, NHCHO or NHCO-C.sub.1-10 alkyl;
- n represents 1 or 2;
- X represents O, (H,OH), (H,H) or .dbd.NH;
- and
- Y represents a cyclic group of formula II, ##STR7## in which R.sup.5 represents (H,H), (H,OH), (H, methoxy) or O;
- R.sup.6 represents H, (R)--OH, (S)--OH, C.sub.1-10 alkoxy, amino, C.sub.1-10 alkylamino, C.sub.1-10 alkanoylamino, formyloxy or halogen;
- R.sup.7 represents H;
- and in addition R.sup.5 and R.sup.6 may together represent a second bond between the carbon atoms to which they are attached;
- or R.sup.6 and R.sup.7 may together represent a second bond between the carbon atoms to which they are attached;
- or a cyclic group of formula III, ##STR8## in which R.sup.8 represents C.sub.1-10 alkyl substituted by one or more groups selected from OH, C.sub.1-10 alkoxy, .dbd.O, and CO.sub.2 H;
- or C.sub.2-10 alkenyl optionally substituted by one or more groups selected from OH, .dbd.O, or CO.sub.2 H;
- provided that
- (a) when n represents 1;
- R.sup.1 represents OH;
- R.sup.3 represents allyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H, methoxy);
- and R.sup.6 represents (R)--OH;
- then X does not represent O;
- (b) when n represents 2;
- (i) R.sup.1 represents OH;
- R.sup.3 represents methyl, ethyl, allyl or propyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H,methoxy);
- and R.sup.6 represents (R)--OH;
- then X does not represent O;
- (ii) when R.sup.1 and R.sup.2 together represent a second bond between the carbon atoms to which they ar attached or each represents H;
- R.sup.3 represents allyl or propyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H,methoxy);
- and R.sup.6 represents (R)--OH;
- then X does not represent O;
- (iii) when R.sup.1 represents OH, methoxy or together with R.sup.2 a second bond between the carbon atoms to which they are attached;
- R.sup.3 represents allyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H,methoxy);
- and R.sup.6 represents methoxy;
- then X does not represent O;
- (iv) when R.sup.1 represents H or OH;
- R.sup.3 represents allyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H,methoxy);
- and R.sup.6 represents (R)--OH;
- then X does not represent (H,OH);
- (v) when R.sup.1 represents H;
- R.sup.3 represents propyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H,OH);
- and R.sup.6 represents (R)--OH;
- then X does not represent O;
- (vi) when R.sup.1 represents OH;
- R.sup.3 represents ethyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H,methoxy);
- and R.sup.6 represents (R)--OH;
- then X does not represent (H,OH);
- (vii) when R.sup.1 and R.sup.2 together represent a second bond between the carbon atoms to which they are attached or each represents H;
- R.sup.3 represents ethyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H,methoxy);
- and R.sup.6 represents (R)--OH;
- then X does not represent O;
- (viii) when R.sup.1 represents OH;
- R.sup.3 represents allyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H,OH);
- or (H,methoxy);
- and R.sup.6 represents (R)--OH;
- then X does not represent (H,H);
- (ix) when R.sup.1 represents OH;
- R.sup.3 represents ethyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H,methoxy);
- and R.sup.6 represents (R)--OH;
- then X does not represent (H,H);
- (x) when R.sup.1 represents OH;
- R.sup.3 represents methyl, ethyl or allyl;
- R.sup.4 represents OH;
- R.sup.5 represents (H,OH);
- and R.sup.6 represents (R)--OH;
- then X does not represent O;
- and
- (xi) when R.sup.1 represents OH;
- R.sup.3 represents allyl;
- R.sup.4 represents OH;
- R.sup.5 represents O;
- and R.sup.6 represents (R)--OH;
- then X does not represent O;
- and pharmaceutically acceptable esters comprising a C.sub.1-6 alcohol moiety, amides comprising a C.sub.0-6 amine moiety, and salts thereof.
89 more elements
Dependencies are inferred from the claim text.