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US 12,544,384 B2Granted
Antibiotic conjugates
AssigneeUniversity of Notre Dame du Lac
InventorsMarvin J. Miller, Rui Liu, Patricia Miller, Sergei Vakulenko, Nichole K. Stewart, William Boggess, Jr.
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Abstract
Provided are antibiotic conjugate compounds of formula (I) and pharmaceutical compositions thereof. Also provided are methods of treating treat bacterial infection, including infections caused by Gram-negative bacteria, by administering compounds of formula (I).
Claims28
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof, wherein
- Sid is a siderophore moiety selected from the group consisting of
- L is a bond, —C(O)—, —C(O)NHCH(R1)—C(O)—, —C(O)OCH(R2)—C(O)—, or
- R1 and R2 are each hydrogen, C1-6alkyl, cyano, C3-6cycloalkyl, C3-6cycloalkenyl, 6- to 12-membered aryl, or 5- to 12-membered heteroaryl, wherein the C3-6cycloalkyl, C3-6cycloalkenyl, 6- to 12-membered aryl, or 5- to 12-membered heteroaryl is optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, C1-4alkyl, C1-4 haloalkyl, —OC1-4alkyl, —OC1-4haloalkyl, OH, oxo, and cyano;
- R3 and R4 are each independently hydrogen, C1-6alkyl, or Rand R4 together with the C atom to which they are attached form a 3- to 8-membered ring;
- Cyc1 is a 6- to 12-membered aryl or 5- to 12-membered heteroaryl, wherein the 6- to 12-membered aryl or 5- to 12-membered heteroaryl is optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, C1-4alkyl, C1-4haloalkyl, —OC1-4alkyl, —OC1-4haloalkyl, OH, oxo, and cyano;
- Y is O or NH;
- G is -G1 or —X—(CH2)pC(O)-G1;
- X is O or S;
- p is 0, 1, 2, 3, 4, or 5;
- and
- G1 is a drug moiety attached through an oxygen or nitrogen atom,
- a wherein G1 is an oxazolidinone antibiotic.
10 more elements
A compound of formula (A):
- wherein
- Siderophore is selected from the group consisting of
- Drug is an oxazolidinone antibiotic;
- n is 0 or 1;
- and
- m is 0 or 1,
- or a pharmaceutically acceptable salt thereof.
4 more elements
Dependencies are inferred from the claim text.