Generation of combinatorial synthetic libraries and screening for proadhesins and nonadhesins
View Patent ↗One aspect of the present invention relates to compounds, comprising at least two moieties selected from the group consisting of aryl sulfonates and aryl sulfates. A second aspect of the present invention relates to combinatorial libraries of the aforementioned compounds. The present invention also relates to compositions comprising a compound of the present invention. A fourth aspect of the present invention relates to the use of a compound or composition of the present invention in a method for inhibiting bioadhesion to a surface. Another aspect of the present invention relates to the use of a compound or composition of the present invention in a method for enhancing bioadhesion to a surface.
1. A compound represented by 1:
wherein
X represents independently for each occurrence a bond, O, S, or NR′;
Z represents independently for each occurrence alkylsulfonyl, fluoroalkylsulfonyl, arylsulfonyl, or S(O) 2 OH;
Ar and Ar′ are independently selected from the group consisting of optionally substituted aryl and heteroaryl;
T represents a covalent tether connecting Ar and Ar′, wherein said covalent tether comprises an amide, ether, substituted amine or ester moiety;
R′ represents independently for each occurrence H, alkyl, alkenyl, aryl, aralkyl, formyl, acyl, sulfonyl, or —(CH 2 ) m —R 80 ;
R 80 represents independently for each occurrence aryl, cycloalkyl, cycloalkenyl, or heterocyclyl; and
m is an integer in the range 0 to 8 inclusive.
2. The compound of claim 1 , wherein X represents independently for each occurrence a bond or O.
3. The compound of claim 1 , wherein X represents O.
4. The compound of claim 1 , wherein Z represents independently for each occurrence methylsulfonyl, trifluoromethylsulfonyl, or S(O) 2 OH.
5. The compound of claim 1 , wherein Ar and Ar′ represent independently for each occurrence optionally substituted aryl.
6. The compound of claim 1 , wherein Ar and Ar′ represent independently for each occurrence optionally substituted phenyl or naphthyl.
7. The compound of claim 1 , wherein X represents O; and Z represents independently for each occurrence alkylsulfonyl, fluoroalkylsulfonyl, arylsulfonyl, or S(O) 2 OH.
8. The compound of claim 1 , wherein X represents O; and Z represents independently for each occurrence methylsulfonyl, trifluoromethylsulfonyl, or S(O) 2 OH.
9. The compound of claim 1 , wherein X represents O; Z represents independently for each occurrence alkylsulfonyl, fluoroalkylsulfonyl, arylsulfonyl, or S(O) 2 OH; and Ar and Ar′ represent independently for each occurrence optionally substituted aryl.
10. The compound of claim 1 , wherein X represents O; Z represents independently for each occurrence methylsulfonyl, trifluoromethylsulfonyl, or S(O) 2 OH; and Ar and Ar′ represent independently for each occurrence optionally substituted aryl.
11. The compound of claim 1 , wherein X represents O; Z represents independently for each occurrence alkylsulfonyl, fluoroalkylsulfonyl, arylsulfonyl, or S(O) 2 OH; and Ar and Ar′ represent independently for each occurrence optionally substituted phenyl or naphthyl.
12. The compound of claim 1 , wherein X represents O; Z represents independently for each occurrence methylsulfonyl, trifluoromethylsulfonyl, or S(O) 2 OH; and Ar and Ar′ represent independently for each occurrence optionally substituted phenyl or naphthyl.
13. The compound of claim 1 , wherein T represents —C(O)NR-Q-NRC(O)—; Q is —(CH 2 ) n — or heterocyclyl; and n is an integer selected from the range 2 to 10 inclusive, wherein R represents independently for each occurrence H, alkyl, aryl, or aralky.
14. The compound of claim 1 , wherein T represents —(CR 2 )—NR-Q-O—; and Q represents alkyl, cycloalkyl, or heterocyclyl, wherein R represents independently for each occurrence H, alkyl, aryl, or aralkyl.
15. The compound of claim 1 , wherein T represents —(CH 2 )—NR-Q-O—C(O)— or —(CH 2 )—NR-Q-O—C(O)—(CH═CH)—; and Q represents alkyl, cycloalkyl, or heterocyclyl, wherein R represents independently for each occurrence H, alkyl, aryl, or aralkyl.
16. The compound of claim 1 , wherein T represents —(CH 2 )—NR-Q-; and Q is a bond, alkyl, or heterocyclyl, wherein R represents independently for each occurrence H, alkyl, aryl, or aralkyl.
17. The compound of claim 1 , wherein T represents —CH 2 CH(C(O)NHMe)-NRC(Q)-Q-C(O)NR-G-; Q is alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, alkenyl, aryl, heteroaryl, aralkyl, alkyl-O-alkyl, or alkyl-S-alkyl; and G is a bond, alkyl, or heterocyclyl, wherein R represents independently for each occurrence H, alkyl, aryl, or aralkyl.
18. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.