Claims
- 1. A compound of the formula: ##STR14## wherein X is selected from the group consisting of --CN, --(CH.sub.2).sub.n CO.sub.2 H, --(CH.sub.2).sub.n CONHOH, --O(CH.sub.2).sub.m CO.sub.2 H, --O(CH.sub.2).sub.m CONHOH, --(CH.sub.2).sub.n CONHNH.sub.2, --(CH.sub.2).sub.n COZ, --(CH.sub.2).sub.n Z, --CH(CO.sub.2 H)(CH.sub.2).sub.m CO.sub.2 H, --(CH.sub.2).sub.n O(CH.sub.2).sub.m CO.sub.2 H, --CONH(CH.sub.2).sub.m CO.sub.2 H, --CH(OZ)(CO.sub.2 H), --CH(Z)(CO.sub.2 H), --(CH.sub.2).sub.n SO.sub.3 H, --(CH.sub.2).sub.n PO.sub.3 D.sub.1 D.sub.2, --NH(CH.sub.2).sub.m CO.sub.2 H, --CONH(CHR.sub.3)CO.sub.2 H, (1-H-tetrazolyl-5-alkyl-), and --OH;
- For divalent structures, Y is --(CH.sub.2).sub.f --, --CO(CH.sub.2).sub.f CO--, --(CH.sub.2).sub.f O(CH.sub.2).sub.f --, --CO(CH.sub.2).sub.f O(CH.sub.2).sub.f CO--, --(CH.sub.2).sub.g S(O).sub.b (CH.sub.2).sub.f S(O).sub.b (CH.sub.2).sub.g --, --CO(CH.sub.2).sub.g S(O).sub.b (CH.sub.2).sub.f S(O).sub.b (CH.sub.2).sub.g CO--, --(CH.sub.2).sub.f V(CH.sub.2).sub.f --, --(CH.sub.2).sub.f COVCO(CH.sub.2).sub.f --, --CO(CH.sub.2).sub.f COVCO(CH.sub.2).sub.f O--, --CO(CH.sub.2).sub.f V(CH.sub.2).sub.f CO--, --CONH(CH.sub.2).sub.f NHCO--, --CO(CH.sub.2).sub.f W(CH.sub.2).sub.f CO--, --(CH.sub.2).sub.f WSW(CH.sub.2).sub.f --, --(CH.sub.2).sub.f CONH(CH.sub.2).sub.f NHCO(CH.sub.2).sub.f --, --(CH.sub.2).sub.f COW(CH.sub.2).sub.f WCO(CH.sub.2).sub.f, or --CH.sub.2 (CH.sub.2).sub.f W(CH.sub.2).sub.f CH.sub.2 -- where V is --N�(CH.sub.2).sub.q !.sub.2 N-- and q is independently 2 to 4, and W is aryl or heteroaryl;
- For trivalent structures, Y is: ##STR15## and T is selected from the group consisting of --(CH.sub.2).sub.f --, --CO(CH.sub.2).sub.f --, --(CH.sub.2).sub.g S(O).sub.b (CH.sub.2).sub.f --, and --CO(CH.sub.2).sub.g S(O).sub.b (CH.sub.2).sub.f, where the carbonyl group is positioned contiguous to the biphenyl unit;
- R.sub.1 and R.sub.2 are independently selected from the group consisting of hydrogen, alkyl, halogen, --OZ, --NO.sub.2, --(CH.sub.2).sub.n CO.sub.2 H, --NH.sub.2 and --NHZ;
- R.sub.3 is selected from the group consisting of hydrogen, alkyl, aralkyl, hydroxyalkyl, aminoalkyl, alkyl carboxylic acid and alkyl carboxamide;
- f is 1 to 16, g is 0 to 6, n is 0 to 6, m is 1 to 6, p is 0 to 6, b is 0 to 2, Z is alkyl, aryl or aralkyl, and D.sub.1 and D.sub.2 are independently hydrogen or alkyl, and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof.
- 2. A compound of the formula: ##STR16## where X is --COOH, --(CH.sub.2).sub.n COOH or --O(CH.sub.2).sub.n COOH and Y is --(CH.sub.2).sub.n --, --(CH.sub.2).sub.n W(CH.sub.2).sub.n --, --(CH.sub.2).sub.n WOW(CH.sub.2).sub.n --, --(CH.sub.2).sub.n S(CH.sub.2).sub.n S(CH.sub.2).sub.n --, --CO(CH.sub.2).sub.n CO--, or --(CH.sub.2).sub.n COW(CH.sub.2).sub.n WCO(CH.sub.2).sub.n -- where W is aryl or heteroaryl, and n is 0 to 6, and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof.
- 3. A compound of claim 2 where Y is --(CH.sub.2).sub.f -- or --CH.sub.2 (CH.sub.2).sub.f W(CH.sub.2).sub.f H.sub.2 --.
- 4. A compound of claim 2 where X is 3--CH.sub.2 CO.sub.2 H and Y is --(CH.sub.2).sub.f -- or --CH.sub.2 (CH.sub.2).sub.f W(CH.sub.2).sub.f CH.sub.2.
- 5. A compound selected from:
- 1,7-bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)phenyl!heptane,
- 1,6-bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)phenyl!hexane,
- 1,5-bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)phenyl!pentane,
- 1,4-bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)phenyl!butane,
- N,N'-bis-�4-(3-(3-carboxymethylphenyl)-4-(.alpha.-D-mannopyranosyloxy)phenyl).sub.butan- 1-oyl!-4,4'-trimethylenedipiperidine,
- S,S'-bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)-3-phenylprop-1-yl!-1,3-dithiopropane,
- 1. 7-bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)phenyl!-1,7-bis-oxoheptane,
- 1,6-bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)phenyl!-1,6-bis-oxohexane,
- 1,5-bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)phenyl!-1,5-bis-oxopentane,
- 1,4-bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)phenyl!-1,4-bis-oxobutane,
- 1,3,5-tris-�3-(3-carboxymethylphenyl)4-(2-.alpha.-D-mannopyranosyloxy)phenylmethyl!benzene, and
- 1,3,5-tris-�4-�3-(3-carboxymethylphenyl)-4-(.alpha.-D-mannopyranosyloxy)phenyl!-4-oxo-2-thiobutyl!benzene.
- 6. 1,6-Bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)phenyl!hexane.
- 7. A pharmaceutical composition comprising a compound as in claim 1 and a pharmaceutically acceptable carrier.
- 8. A method of inhibiting the binding of E-selectin, P-selectin or L-selectin to sLe.sup.x or sLe.sup.a comprising administering to a patient an effective amount of a compound of claim 1.
- 9. A method of inhibiting the binding of E-selectin, P-selectin or L-selectin to sLe.sup.x or sLe.sup.a comprising administering to a patient an effective amount of 1,6-bis-�3-(3-carboxymethylphenyl)-4-(2-.alpha.-D-mannopyranosyloxy)phenyl!hexane.
Parent Case Info
This application is a 371 of PCT/US 96/11032 filed Jun. 26, 1996.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US96/11032 |
6/26/1996 |
|
|
2/11/1998 |
2/11/1998 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/01335 |
1/16/1997 |
|
|
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
5444050 |
Kogan et al. |
Aug 1995 |
|
5498775 |
Novak et al. |
Mar 1996 |
|