US 12,234,238 B2
Antimicrobial compounds and methods of making and using the same
Erin M. Duffy, Deep River, CT (US); Ashoke Bhattacharjee, Cheshire, CT (US); Zoltan F. Kanyo, North Haven, CT (US); Joseph A. Ippolito, Guilford, CT (US); and Andrea Marra, New Haven, CT (US)
Assigned to BIOVERSYS AG, Basel (CH)
Filed by BIOVERSYS AG, Basel (CH)
Filed on Feb. 17, 2021, as Appl. No. 17/177,756.
Application 17/177,756 is a continuation of application No. 16/622,969, abandoned, previously published as PCT/US2018/037908, filed on Jun. 15, 2018.
Claims priority of provisional application 62/681,498, filed on Jun. 6, 2018.
Claims priority of provisional application 62/660,747, filed on Apr. 20, 2018.
Claims priority of provisional application 62/660,782, filed on Apr. 20, 2018.
Claims priority of provisional application 62/633,454, filed on Feb. 21, 2018.
Claims priority of provisional application 62/633,554, filed on Feb. 21, 2018.
Claims priority of provisional application 62/593,445, filed on Dec. 1, 2017.
Claims priority of provisional application 62/522,574, filed on Jun. 20, 2017.
Claims priority of provisional application 62/521,835, filed on Jun. 19, 2017.
Prior Publication US 2021/0171533 A1, Jun. 10, 2021
Int. Cl. C07D 487/04 (2006.01); A61P 31/04 (2006.01)
CPC C07D 487/04 (2013.01) [A61P 31/04 (2018.01)] 17 Claims
 
1. A compound of formula (AA):

OG Complex Work Unit Chemistry
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, wherein:
J is selected from

OG Complex Work Unit Chemistry
X is selected from a 5- or 6-membered heterocyclyl ring and phenyl, wherein each of the 5- or 6-membered heterocyclyl ring and phenyl is optionally substituted with one or more Rx;
Z is selected from

OG Complex Work Unit Chemistry
each of R1, R2, and R3 is independently selected from H and C1-3 alkyl, provided that one or two of R1, R2, and R3 is H, and when two of R1, R2, and R3 are H and the other is C1-3 alkyl, or when one of R1, R2, and R3 is H and the other two are C1-3 alkyl;
or R1 is Hand R2 and R3 together with the nitrogen atoms to which they are attached and the carbon atom connecting the two nitrogen atoms form a 5- or 6-membered ring;
R4 is C1-3 alkyl;
R5 is selected from H and C1-6 alkyl;
R6 is selected from H, C1-6 alkyl, C2-6 alkenyl, and C3-6 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, ORa, SRa, —C(O)ORa, —SC(NH)NH2, C3-6 cycloalkyl, and 3-6 membered heterocyclyl;
R7 is selected from H and C1-6 alkyl;
or R6 and R7 together with the carbon and nitrogen atoms to which they are attached form a ring having one of the formulas:

OG Complex Work Unit Chemistry
wherein the ring is optionally substituted on a ring carbon atom with C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more OH;
or R5 and R7 together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form a ring having one of the formulas:

OG Complex Work Unit Chemistry
wherein the ring is optionally substituted on a ring carbon atom with OH;
Q is selected from C1-2 alkylene or —C(O)—;
R21 is selected from H, C1-6alkyl optionally substituted with 1-3 halo;
R8 is selected from H and halogen;
each RX is independently selected from halogen, C1-6 alkyl, C1-4 haloalkyl, ORC, N(Rc)2, —C(O)ORc, —C(O)Rc, C3-6 cycloalkyl, and aryl, wherein the C1-6 alkyl is optionally substituted with one or more Rb,
or two adjacent Rx come together with the atoms to which they are attached to form a 5- or 6-membered ring;
each Ra is independently selected from H and C1-6 alkyl;
each Rb is independently selected from C2-6alkenyl, ORc, N(Rc)2, —C(O)ORc, C3-6 cycloalkyl, OC(NH)NH2, and aryl;
each Rc is independently selected from H, C1-6 alkyl, aryl, —C(O) aryl, and —(CH2)aryl, wherein the C1-6 alkyl and the aryl are each optionally substituted with one or more Rd; and
each Rd is independently selected from C1-3alkyl, OH, O(C1-3 alkyl), NO2, NH2, NH(C1-3 alkyl), and N(C1-3 alkyl)2.