US 12,226,386 B2
Compositions and methods for treating biofilms
Clarissa J. Nobile, Merced, CA (US); and Megha Gulati, Merced, CA (US)
Assigned to The Regents of the University of California, Oakland, CA (US)
Appl. No. 17/295,656
Filed by The Regents of the University of California, Oakland, CA (US)
PCT Filed Dec. 3, 2019, PCT No. PCT/US2019/064165
§ 371(c)(1), (2) Date May 20, 2021,
PCT Pub. No. WO2020/117755, PCT Pub. Date Jun. 11, 2020.
Claims priority of provisional application 62/774,737, filed on Dec. 3, 2018.
Prior Publication US 2022/0110897 A1, Apr. 14, 2022
Int. Cl. A61K 31/198 (2006.01); A61K 47/10 (2017.01); A61P 31/04 (2006.01)
CPC A61K 31/198 (2013.01) [A61K 47/10 (2013.01); A61P 31/04 (2018.01)] 18 Claims
 
1. A method of inhibiting or disrupting a biofilm on a surface, treating a bacterial infection in a subject in need thereof, or treating a fungal infection in a subject in need thereof, the method comprising contacting the surface with a composition or administering a composition to the subject; wherein the composition comprises:
(a) a first compound of formula (I) or a salt thereof, wherein
(i) R1 is —SR5,
(ii) R5 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, or 3 to 12 membered heterocycle; optionally substituted with one or more substituents selected from the group consisting of halogen, —CN, —NO2, —OH, —NH2, —COOH, and —OCH3, and
(iii) n is 0, 1, 2, 3, 4, or 5;
(b) a second compound of formula (I) or a salt thereof, wherein
(i) R1 is —CO(O)R5,
(ii) R5 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, or 3 to 12 membered heterocycle; optionally substituted with one or more substituents selected from the group consisting of halogen, —CN, —NO2, —OH, —NH2, —COOH, and —OCH3, and
(iii) n is 0, 2, 3, 4, or 5;
(c) a third compound of formula (I) or a salt thereof, wherein
(i) R1 is —CO(O)R5,
(ii) R5 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocycle, or 3 to 12 membered heterocycle; optionally substituted with one or more substituents selected from the group consisting of halogen, —CN, —NO2, —OH, —NH2, —COOH, and —OCH3, and
(iii) n is 0, 1, 3, 4, or 5;
wherein the compound of formula (I) is:

OG Complex Work Unit Chemistry
wherein:
R2 and R3 are hydrogen; or one of R2 and R3 is hydrogen, and the other of R2 and R3 with R1 is taken together with the atoms to which they are attached to form a heterocycle substituted with one or more R6; and
each R6 is independently halogen, —NO2, —CN, —OR5, —SR5, —N(R5)2, —C(O)R5, —C(O)OR5, —OC(O)R5, —OC(O)OR5, —OC(O)N(R5)2, —NR5C(O)R5, —C(O)N(R5)2, ═O, ═S, ═N(R5), C1-10 alkyl, C2-10 alkenyl, or C2-10 alkynyl; each of which is independently and optionally substituted at each occurrence with one or more substituents selected from the group consisting of halogen, —CN, —NO2, —OH, —NH2, —COOH, and —OCH3.