US 12,227,524 B2
Anti-infective compounds
Jaeseung Kim, Seoul (KR); Sunhee Kang, Yongin-si (KR); Juhee Kang, Gyeonggi-do (KR); Sumi Lee, Busan (KR); Jeong Jea Seo, Seoul (KR); and Mooyoung Seo, Gyeonggi-do (KR)
Assigned to INSTITUT PASTEUR KOREA, Gyeonggi-Do (KR)
Filed by INSTITUT PASTEUR KOREA, Gyeonggi-do (KR)
Filed on Jan. 31, 2022, as Appl. No. 17/588,947.
Application 17/588,947 is a division of application No. 15/319,983, granted, now 11,279,714, previously published as PCT/EP2015/063982, filed on Jun. 22, 2015.
Claims priority of provisional application 62/015,056, filed on Jun. 20, 2014.
Prior Publication US 2022/0153756 A1, May 19, 2022
Int. Cl. C07D 519/00 (2006.01); C07D 215/48 (2006.01); C07D 277/82 (2006.01); C07D 401/04 (2006.01); C07D 417/04 (2006.01); C07D 495/04 (2006.01); C07D 513/04 (2006.01)
CPC C07D 519/00 (2013.01) [C07D 215/48 (2013.01); C07D 277/82 (2013.01); C07D 401/04 (2013.01); C07D 417/04 (2013.01); C07D 495/04 (2013.01); C07D 513/04 (2013.01)] 5 Claims
 
1. A method of treatment of a bacterial infection comprising the application, to a person in need of such treatment, of a suitable amount of a compound having the general formula I:

OG Complex Work Unit Chemistry
wherein
n1 and n2 are independently 0, 1, 2, or 3;
m is 0 or 1;
A is a moiety selected from the group consisting of

OG Complex Work Unit Chemistry
R1 is selected from the group consisting of hydrogen, halogen, C1-C10 alkyl, C3-C10cycloalkyl, C1-C3haloalkyl, hydroxyl, —OR3, —CN, —NO2, —NH2, —NRbRc, aryl, heteroaryl and heterocyclyl wherein each of said alkyl, cycloalkyl, aryl heteroaryl and heterocyclyl is optionally substituted with one to four Ra groups;
R2 is selected from the group consisting of hydrogen, halogen, C1-C10 alkyl, C3-C10cycloalkyl, C1-C3haloalkyl, hydroxyl, —OR3, —CN, —NO2, —NH2, —NRbRc, —NR6C(O)Rc, —(NRd)(V)pRe, aryl, heteroaryl, heterocyclyl and groups of formula Ia shown below,
wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted with one to four Ra groups;

OG Complex Work Unit Chemistry
wherein,
is independently, at each occurrence, 0, 1, 2 or 3;
p is 0 or 1,
q is 0 or 1;
X1 is C═O, O, S, —S(O)2—, —S(O)2NR6—, —C(O)O—, —C(O)NR6—, —NHC(O)— or —(NR6)—;
X2 is CRbRc, O, S, or NR6;
Y is C1-C6 alkylene, O, S or NR6;
V and W are independently, at each occurrence, C1-C6 alkylene;
R3 is selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10cycloalkyl, C1-C10 haloalkyl C1-C6alkyl-O-alkyl, C2-C10 alkenyl, C3-C10 cycloalkenyl, C2-C10 alkynyl, aryl, heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted with one to four Ra groups;
R4 is selected from the group consisting of hydrogen, halogen, C1-C10 alkyl, C3-C10cycloalkyl, C1-C3haloalkyl, hydroxyl, —OR6, —CN, —NO2, —NH2, —NRbRc, —N(R6)C(O)R6, —C(O)R6, —C(O)OR6, —C(O)NRbRc, —S(O)R6, —S(O)2R6, —S(O)2NRbRe, aryl, heteroaryl and heterocyclyl wherein each of said alkyl, cycloalkyl, —OR6 aryl, heteroaryl and heterocyclyl is optionally substituted with one to four Ra groups;
R5 is selected from the group consisting of hydrogen, halogen, C1-C10 alkyl, C3-C10cycloalkyl, C1-C3haloalkyl, hydroxyl, —OR6, —CN, —NO2, —NH2, —NRbRc, —N(R6)C(O)R6, —N(R6)C(O)OR6, —C(O)R6, —C(O)OR6, —C(O)NRbRc, —CHOHR6, —S(O) R6, —S(O)2R6, —S(O)2NRbRc, aryl, heteroaryl and heterocyclyl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substituted with one to four Ra groups;
R6 is independently, at each occurrence, selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10cycloalkyl, C1-C3haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted with one to four Ra groups;
Z is selected from the group consisting of C1-C10 alkyl, C3-C10cycloalkyl, C1-C3haloalkyl, OR7, aryloxy, aryl, heteroaryl, heterocyclyl, and groups of formula Ib shown below, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl and groups of formula Ib is optionally substituted with one to four Ra groups;

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
wherein,
p is 0 or 1;
1 is 1, 2 or 3;
X3 is, independently at each occurrence, CH or N;
X4 is C═O, CRbRc, O, S, or NR7;
Re, if denoted in formula Ib, may also occur twice as substituent at the same carbon atom wherein Re is independently selected at each occurrence;
Ra is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C1-C3 alkyl, C1-C4 alkoxy, C1-C4 alkoxy substituted with aryl, C1-C3 haloalkyl, hydroxyl, C1-C3 alkylhydroxyl, —CN, NO2, —NRbRc, —C(O)NRbRc, —ORc, —C(O)Rc, —C(O) ORc, sulfonyl, sulfoxide, C3-C10 cycloalkyl, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, aryl, halogen, C1-C3 haloalkyl, hydroxyl, —NH2, wherein such substitution, if present, may occur in such a manner that there is more than one substituent, per carbon atom, and wherein these substituents may be the same or different;
Rb and Rc are independently, at each occurrence selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10 alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C10 cycloalkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, aryl, alkylaryl, heteroaryl, and heterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, aryloxy, C1-C3 haloalkyl, hydroxyl, C1-C3 alkylhydroxyl, —CN, —NO2, —NH2, sulfonyl, sulfoxide, C3-C10 cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein such substitution, if present, may occur in such a manner that there is more than one substituent per carbon atom, wherein such substituents may be the same or different; or
Rb and Rc are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring, or they are connected to make a fused cyclic or heterocyclic ring structure;
Rd is independently, at each occurrence, selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C3 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted with one to four Ra groups;
Rd is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C3 haloalkyl, hydroxyl, —OR7, —CN, —(CH2)1R7, with 1 being 0, 1, 2 or 3, —NO2, —NH2, —NRbRc, —N(R7)C(O)R7, —C(O)R7, —C(O)OR7, —C(O)NRbRc, —S(O) R7, —S(O)2R7, —S(O)2NRbRc, aryl, heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted with one to four Ra groups;
R7 is independently, at each occurrence, selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C3 haloalkyl, aryl, heteroaryl, and heterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted with one to four Ra groups;
and pharmaceutically acceptable salts thereof.