US 2019/0224210 A1 · HETEROCYCLIC COMPOUNDS AND THEIR USE IN PREVENTING OR TREATING BACTERIAL INFECTIONS

Heterocyclic compounds and their use in preventing or treating bacterial infections

AssigneeMutabilis

InventorsJulien BARBION, Audrey CARAVANO, Sophie CHASSET, Francis CHEVREUIL, Fabien FAIVRE, Rémi LEBEL, Nicolas LECOINTE, Benoît LEDOUSSAL, Frédéric LE-STRAT, Christophe SIMON, Chrystelle OLIVEIRA, Géraldine LE FRALLIEC, Julie BRIAS, Laurence FARESCOUR, Sophie VOMSCHEID, Sébastien RICHARD

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Abstract

A compound of formula (I) or a racemate, an enantiomer, a diastereoisomer, a geometric isomer or a pharmaceutically acceptable salt thereof, and its use as antibacterial agent.

Claims20

Dependent claims

1-17. (canceled)

A compound of formula (I)

wherein:
R1 represents a 5-membered heterocycle, optionally substituted by one or more T1, that is saturated, partially unsaturated, or aromatic and that comprises a nitrogen atom, wherein said 5-membered heterocycle is linked to the structure by said nitrogen atom, and wherein said nitrogen atom may be quaternized;
R2 represents —SO3H, —CFHCOOH, or —CF2COOH;
T1, identical or different, independently represents a fluorine atom;
═O;
—C(O)Q1;
—(CH2)m—S(O)2—NQ1Q2;
—(CH2)m—C(═NOQ1)Q3;
—(X)—(CH2)p—S(O)2NQ1Q2;
—C(O)—(CH2)n—S(O)2NQ1Q2;
—(CH2)m—O—(CH2)p—O—(CH2)p-NQ1Q2;
—(CH2)mOQ1;
—(CH2)m—CN;
—(CH2)m—OC(O)Q1;
—(CH2)m—C(O)OQ1;
—(CH2)m—OC(O)OQ1;
—(CH2)m—OC(O)NQ1Q2;
—(CH2)m—C(O)NQ1Q2;
—(CH2)m—C(O)ONQ1Q2;
—(CH2)m—C(O)NQ1OQ2;
—(CH2)m—C(O)NQ1-NQ1Q2-(CH2)m-NQ1C(O)Q2;
—(CH2)m-NQ1S(O)2NQ1Q2;
—(CH2)m-NQ1S(O)2Q2;
—(CH2)m-NQ1C(O)OQ2;
—(CH2)m-NQ1C(O)NQ1Q2;
—(CH2)m-NQ1Q2;
—(CH2)m—NH—C(NHQ3)═NQ4;
—(CH2)m—NH—CH═NQ3;
—(CH2)m—C(NHQ3)═NQ4;
—(X)—(CH2)pOQ1;
—(X)—(CH2)n—CN;
—(X)—(CH2)p—OC(O)Q1;
—(X)—(CH2)n—C(O)OQ1;
—(X)—(CH2)p—OC(O)OQ1;
—(X)—(CH2)p—OC(O)NQ1Q2;
—(X)—(CH2)n—C(O)NQ1Q2;
—(X)—(CH2)n—C(O)ONQ1Q2;
—(X)—(CH2)n—C(O)NQ1OQ2;
—(X)—(CH2)n—C(O)NQ1-NQ1Q2;
—(X)—(CH2)p-NQ1C(O)Q2;
—(X)—(CH2)p-NQ1S(O)2NQ1Q2;
—(X)—(CH2)p-NQ1S(O)2Q2;
—(X)—(CH2)p-NQ1C(O)OQ2;
—(X)—(CH2)p-NQ1C(O)NQ1Q2;
—(X)—(CH2)p-NQ1Q2;
—(X)—(CH2)p—NH—C(NHQ3)═NQ4;
—(X)—(CH2)p—NH—CH═NQ3;
—(X)—(CH2)n—C(NHQ3)═NQ4;
—C(O)—(CH2)nOQ1;
—C(O)—(CH2)n—CN;
—C(O)—(CH2)n—OC(O)Q1;
—C(O)—(CH2)n—C(O)OQ1;
—C(O)—(CH2)n—OC(O)OQ1;
—C(O)—(CH2)n—OC(O)NQQ2;
—C(O)—(CH2)n—C(O)NQ1Q2;
—C(O)—(CH2)n—C(O)ONQ1Q2;
—C(O)—(CH2)n—C(O)NQ1OQ2;
—C(O)—(CH2)n—C(O)NQ1NQ1Q2;
—C(O)—(CH2)n-NQ1C(O)Q2;
—C(O)—(CH2)n-NQ1S(O)2NQ1Q2;
—C(O)—(CH2)n-NQ1S(O)2Q2;
—C(O)—(CH2)n-NQ1C(O)OQ2;
—C(O)—(CH2)n-NQ1C(O)NQ1Q2;
—C(O)—(CH2)n-NQ1Q2;
—C(O)—(CH2)n—NH—C(NHQ3)═NQ4;
—C(O)—(CH2)n—NH—CH═NQ3;
or —C(O)—(CH2)n—C(NHQ3)═NQ4;
or
T1, identical or different, independently represents an unsubstituted or substituted by one or more T2, —(CH2)m-(4-, 5- or 6-membered saturated, partially or totally unsaturated, or aromatic heterocycle);
—(X)—(CH2)m-(4-, 5- or 6-membered saturated, partially or totally unsaturated, or aromatic heterocycle);
(C1-C3)-alkyl;
(C1-C3)-fluoroalkyl;
—(X)—(C1-C3)-alkyl;
—(X)—(C1-C3)-fluoroalkyl;
—(CH2)m—(C3-C6)-cycloalkyl;
—(X)—(CH2)m—(C3-C6)-cycloalkyl;
—(CH2)m—(C3-C6)-cyclofluoroalkyl;
—(X)—(CH2)m—(C3-C6)-cyclofluoroalkyl;
—C(O)—(CH2)m-(4-, 5- or 6-membered saturated, partially or totally unsaturated, or aromatic heterocycle);
—C(O)—(C1-C3)-alkyl;
—C(O)—(C1-C3)-fluoroalkyl;
—C(O)O—(C1-C3)-fluoroalkyl;
—C(O)—(CH2)m—(C3-C6)-cycloalkyl;
—C(O)—(CH2)m—(C3-C6)-cycloalkyl;
—C(O)—(CH2)m—(C3-C6)-cyclofluoroalkyl;
or —C(O)—(CH2)m—(C3-C6)-cyclofluoroalkyl;
T2, identical or different, independently represents —OH;
—NH2;
or —CONH2;
Q1 and Q2, identical or different, independently represent a hydrogen atom;
—(CH2)r—NHQ3;
—(CH2)rNH—C(NHQ3)═NQ4;
—(CH2)rNH—CH═NQ3;
(CH2)n—C(NHQ3)═NQ4;
—(CH2)rOQ3;
—(CH2)n—CONHQ3;
an unsubstituted or substituted by one or more T2, (C1-C3)-alkyl;
(C1-C3)-fluoroalkyl;
or a saturated, partially or totally unsaturated, or aromatic-(CH2)m-(4-, 5- or 6-membered heterocycle comprising at least one nitrogen atom);
or
Q1, Q2, and the nitrogen atom to which they are bonded, form together an unsubstituted or substituted by one or more T2, saturated or partially unsaturated 4-, 5- or 6-membered heterocycle comprising 1, 2, or 3 heteroatoms;
Q3 and Q4, identical or different, independently represent a hydrogen atom or (C1-C3)-alkyl;
m, identical or different, independently represents 0, 1, 2 or 3;
n, identical or different, independently represents 1, 2 or 3;
p, identical or different, independently represents 2 or 3;
r is 1, 2 or 3 when the (CH2)r is directly linked to a carbon atom or 2 or 3 otherwise;
and
X, identical or different, independently represents O;
S;
S(O);
S(O)2 or N(Q3);
and
wherein:
any carbon atom present within a group selected from alkyl, cycloalkyl, fluoroalkyl, cyclofluoroalkyl and heterocycle can be oxidized to form a C═O group;
any sulphur atom present within a heterocycle can be oxidized to form a S═O group or a S(O)2 group;
and
any nitrogen atom present within a heterocycle or present within group wherein it is trisubstituted thus forming a tertiary amino group, can be further quaternized by a methyl group;
or a racemate, an enantiomer, a diastereoisomer, a geometric isomer or a pharmaceutically acceptable salt of the formula (I) compound, but excluding the following compounds:

115 more elements

A compound of formula

wherein:
R1 represents a 5-membered heterocycle, optionally substituted by one or more T1, that is saturated, partially unsaturated, or aromatic and that comprises a nitrogen atom, wherein said 5-membered heterocycle is linked to the structure by said nitrogen atom, and wherein said nitrogen atom may be quaternized;
T1, identical or different, independently represents a fluorine atom;
═O;
—C(O)Q1;
—(CH2)m—S(O)2—NQ1Q2;
—(CH2)m—C(═NOQ1)Q3;
—(X)—(CH2)p—S(O)2NQ1Q2;
—C(O)—(CH2)n—S(O)2NQ1Q2;
—(CH2)m—O—(CH2)p—O—(CH2)p-NQ1Q2;
—(CH2)mOQ1;
—(CH2)m—CN;
—(CH2)m—OC(O)Q1;
—(CH2)m—C(O)OQ1;
—(CH2)m—OC(O)OQ1;
—(CH2)m—OC(O)NQ1Q2;
—(CH2)m—C(O)NQ1Q2;
—(CH2)m—C(O)ONQ1Q2;
—(CH2)m—C(O)NQ1OQ2;
—(CH2)m—C(O)NQ1-NQ1Q2-(CH2)m-NQ1C(O)Q2;
—(CH2)m-NQ1S(O)2NQ1Q2;
—(CH2)m-NQ1S(O)2Q2;
—(CH2)m-NQ1C(O)OQ2;
—(CH2)m-NQ1C(O)NQ1Q2;
—(CH2)m-NQ1Q2;
—(CH2)m—NH—C(NHQ3)═NQ4;
—(CH2)m—NH—CH═NQ1;
—(CH2)m—C(NHQ3)═NQ4;
—(X)—(CH2)pOQ1;
—(X)—(CH2)n—CN;
—(X)—(CH2)p—OC(O)Q1;
—(X)—(CH2)n—C(O)OQ1;
—(X)—(CH2)p—OC(O)OQ1;
—(X)—(CH2)p—OC(O)NQ1Q2;
—(X)—(CH2)n—C(O)NQ1Q2;
—(X)—(CH2)n—C(O)ONQ1Q2;
—(X)—(CH2)n—C(O)NQ1OQ2;
—(X)—(CH2)n—C(O)NQ1-NQ1Q2;
—(X)—(CH2)p-NQ1C(O)Q2;
—(X)—(CH2)p-NQ1S(O)2NQ1Q2;
—(X)—(CH2)p-NQ1S(O)2Q2;
—(X)—(CH2)p-NQ1C(O)OQ2;
—(X)—(CH2)p-NQ1C(O)NQ1Q2;
—(X)—(CH2)p-NQ1Q2;
—(X)—(CH2)p—NH—C(NHQ3)═NQ4;
—(X)—(CH2)p—NH—CH═NQ1;
—(X)—(CH2)n—C(NHQ3)═NQ4;
—C(O)—(CH2)nOQ1;
—C(O)—(CH2)n—CN;
—C(O)—(CH2)n—OC(O)Q1;
—C(O)—(CH2)n—C(O)OQ1;
—C(O)—(CH2)n—OC(O)OQ1;
—C(O)—(CH2)n—OC(O)NQ1Q2;
—C(O)—(CH2)n—C(O)NQ1Q2;
—C(O)—(CH2)n—C(O)ONQ1Q2;
—C(O)—(CH2)n—C(O)NQ1OQ2;
—C(O)—(CH2)n—C(O)NQ1NQ1Q2;
—C(O)—(CH2)n-NQ1C(O)Q2;
—C(O)—(CH2)n-NQ1S(O)2NQ1Q2;
—C(O)—(CH2)n-NQ1S(O)2Q2;
—C(O)—(CH2)n-NQ1C(O)OQ2;
—C(O)—(CH2)n-NQ1C(O)NQ1Q2;
—C(O)—(CH2)n-NQ1Q2;
—C(O)—(CH2)n—NH—C(NHQ3)═NQ4;
—C(O)—(CH2)n—NH—CH═NQ3;
or —C(O)—(CH2)n—C(NHQ3)═NQ4;
or
T1, identical or different, independently represents an unsubstituted or substituted by one or more T2, —(CH2)m-(4-, 5- or 6-membered saturated, partially or totally unsaturated, or aromatic heterocycle);
—(X)—(CH2)m-(4-, 5- or 6-membered saturated, partially or totally unsaturated, or aromatic heterocycle);
(C1-C3)-alkyl;
(C1-C3)-fluoroalkyl;
—(X)—(C1-C3)-alkyl;
—(X)—(C1-C3)-fluoroalkyl;
—(CH2)m—(C3-C6)-cycloalkyl;
—(X)—(CH2)m—(C3-C6)-cycloalkyl;
—(CH2)m—(C3-C6)-cyclofluoroalkyl;
—(X)—(CH2)m—(C3-C6)-cyclofluoroalkyl;
—C(O)—(CH2)m-(4-, 5- or 6-membered saturated, partially or totally unsaturated, or aromatic heterocycle);
—C(O)—(C1-C3)-alkyl;
—C(O)—(C1-C3)-fluoroalkyl;
—C(O)O—(C1-C3)-fluoroalkyl;
—C(O)—(CH2)m—(C3-C6)-cycloalkyl;
—C(O)—(CH2)m—(C3-C6)-cycloalkyl;
—C(O)—(CH2)m—(C3-C6)-cyclofluoroalkyl;
or —C(O)—(CH2)m—(C3-C6)-cyclofluoroalkyl;
T2, identical or different, independently represents —OH;
—NH2;
or —CONH2;
Q1 and Q2, identical or different, independently represent a hydrogen atom;
—(CH2)r—NHQ3;
—(CH2)rNH—C(NHQ3)═NQ4;
—(CH2)rNH—CH═NQ3;
(CH2)n—C(NHQ3)═NQ4;
—(CH2)rOQ3;
—(CH2)n—CONHQ3;
an unsubstituted or substituted by one or more T2, (C1-C3)-alkyl;
(C1-C3)-fluoroalkyl;
or a saturated, partially or totally unsaturated, or aromatic-(CH2)m-(4-, 5- or 6-membered heterocycle comprising at least one nitrogen atom);
or
Q Q1, Q2, and the nitrogen atom to which they are bonded, form together an unsubstituted or substituted by one or more T2, saturated or partially unsaturated 4-, 5- or 6-membered heterocycle comprising 1, 2, or 3 heteroatoms;
Q3 and Q4, identical or different, independently represent a hydrogen atom or (C1-C3)-alkyl;
m, identical or different, independently represents 0, 1, 2 or 3;
n, identical or different, independently represents 1, 2 or 3;
p, identical or different, independently represents 2 or 3;
r is 1, 2 or 3 when the (CH2)r is directly linked to a carbon atom or 2 or 3 otherwise;
and
X, identical or different, independently represents O;
S;
S(O);
S(O)2 or N(Q3);
and
wherein:
any carbon atom present within a group selected from alkyl, cycloalkyl, fluoroalkyl, cyclofluoroalkyl and heterocycle can be oxidized to form a C═O group;
any sulphur atom present within a heterocycle can be oxidized to form a S═O group or a S(O)2 group;
and
any nitrogen atom present within a heterocycle or present within group wherein it is trisubstituted thus forming a tertiary amino group, can be further quaternized by a methyl group.

113 more elements

Dependencies are inferred from the claim text.