Polyacid glycopeptide derivatives
View Patent ↗Disclosed are derivatives of glycopeptides that are substituted at the C-terminus with a substituent that comprises two or more (e.g. 2, 3, 4, or 5) carboxy (CO 2 H) groups; and pharmaceutical compositions containing such glycopeptide derivatives. The disclosed glycopeptide derivatives are useful as antibacterial agents.
1. A compound of formula II:
wherein:
R 17 is a dicarboxy-substituted alkyl group having from 3 to 10 carbon atoms;
R 18 is selected from the group consisting of hydrogen and alkyl group;
R 20 is selected from —CH 2 CH 2 CH 2 —NH—(CH 2 ) 8 CH 3 ; —CH 2 CH 2 CH 2 CH 2 —NH—(CH 2 ) 7 CH 3 ; —CH 2 CH 2 —NHSO 2 —(CH 2 ) 9 CH 3 ; —CH 2 CH 2 —NHSO 2 —(CH 2 ) 11 CH 3 ; —CH 2 CH 2 —S—(CH 2 ) 8 CH 3 ; —CH 2 CH 2 —S—(CH 2 ) 9 CH 3 ; —CH 2 CH 2 —S—(CH 2 ) 10 CH 3 ; —CH 2 CH 2 CH 2 —S—(CH 2 ) 8 CH 3 ; —CH 2 CH 2 CH 2 —S—(CH 2 ) 9 CH 3 ; —CH 2 CH 2 CH 2 —S—(CH 2 ) 3 CH═CH—(CH 2 ) 4 CH 3 (trans); —CH 2 CH 2 CH 2 CH 2 —S—(CH 2 ) 7 CH 3 ; —CH 2 CH 2 —S(O)—(CH 2 ) 9 CH 3 ; —CH 2 CH 2 —S—(CH 2 ) 6 Ph; —CH 2 CH 2 —S—(CH 2 ) 8 Ph; —CH 2 CH 2 CH 2 —S—(CH 2 ) 8 Ph; —CH 2 CH 2 —NH—CH 2 -4-(4-Cl-Ph)-Ph; —CH 2 CH 2 —NH—CH 2 -4-[4-(CH 3 ) 2 CHCH 2 —]-Ph; —CH 2 CH 2 —NH—CH 2 -4-(4-CF 3 -Ph)-Ph; —CH 2 CH 2 —S—CH 2 -4-(4-Cl-Ph)-Ph; —CH 2 CH 2 —S(O)—CH 2 -4-(4-Cl-Ph)-Ph; —CH 2 CH 2 CH 2 —S—CH 2 -4-(4-Cl-Ph)-Ph; —CH 2 CH 2 CH 2 —S(O)—CH 2 -4-(4-Cl-Ph)-Ph; —CH 2 CH 2 CH 2 —S—CH 2 -4-[3,4-di-Cl-PhCH 2 O—)-Ph; —CH 2 CH 2 —NHSO 2 —CH 2 -4-[4-(4-Ph)-Ph]-Ph; —CH 2 CH 2 CH 2 —NHSO 2 —CH 2 -4-(4-Cl-Ph)-Ph; —CH 2 CH 2 CH 2 —NHSO 2 —CH 2 -4-(Ph-C≡C—)-Ph; —CH 2 CH 2 CH 2 —NHSO 2 -4-(4-Cl-Ph)-Ph; —CH 2 CH 2 CH 2 NHSO 2 -4-(naphth-2-yl)-Ph; 4-(4-chlorophenyl)benzyl; and 4-(4-chlorobenzyloxy)benzyl;
or a pharmaceutically acceptable salt, or stereoisomer thereof.
2. The compound of claim 1 , wherein R 20 is selected from —CH 2 CH 2 —S—(CH 2 ) 8 CH 3 ; —CH 2 CH 2 —S—(CH 2 ) 9 CH 3 ; —CH 2 CH 2 —S—(CH 2 ) 10 CH 3 ; —CH 2 CH 2 CH 2 —S—(CH 2 ) 8 CH 3 ; —CH 2 CH 2 CH 2 —S—(CH 2 ) 9 CH 3 ; —CH 2 CH 2 CH 2 —S—(CH 2 ) 3 —CH═CH—(CH 2 ) 4 CH 3 (trans); —CH 2 CH 2 CH 2 CH 2 —S—(CH 2 ) 7 CH 3 ; —CH 2 CH 2 —S(O)—(CH 2 ) 9 CH 3 ; —CH 2 CH 2 —S—(CH 2 ) 6 Ph; —CH 2 CH 2 —S—(CH 2 ) 8 Ph; —CH 2 CH 2 CH 2 —S—(CH 2 ) 8 Ph; —CH 2 CH 2 —S—CH 2 -4-(4-Cl-Ph)-Ph; —CH 2 CH 2 —S(O)—CH 2 -4-(4-Cl-Ph)-Ph; —CH 2 CH 2 CH 2 —S—CH 2 -4-(4-Cl-Ph)-Ph; —CH 2 CH 2 CH 2 —S(O)—CH 2 -4-(4-Cl-Ph)-Ph; and —CH 2 CH 2 CH 2 —S—CH 2 -4-[3,4-di-Cl-PhCH 2 O—)-Ph.
3. The compound of claim 1 , wherein R 20 is —CH 2 CH 2 —S—(CH 2 ) 9 CH 3 .
4. The compound of claim 1 , wherein R 20 is 4-(4-chlorophenyl)benzyl.
5. The compound of claim 1 , wherein R 20 is 4-(4-chlorobenzyloxy)benzyl.
6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of any one of claims 1 , and 2 – 5 .
7. A method of treating a bacterial disease in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a compound of any one of claims 1 , and 2 – 5 .