Chromane amidine monobactam compounds for the treatment of bacterial infections

A compound of Formula I

• or a pharmaceutically acceptable salt thereof, wherein:
• T is CH, or N, provided that no more than two of T, U and V are N;
• U is CH, or N;
• V is CH or N;
• X is selected from the group consisting of:
• 1) O, and
• 2) CH2;
• Y is selected from the group consisting of:
• 1) O,
• 2) NR8,
• 3) S, and
• 4) CH2,
• provided that when Y is O, NR8 or S then X is not O;
• Z is
• 1) O,
• 2) S,
• 3) CH2, or
• 4) NH,
• provided that when Z is O, S or NH, then X is not O;
• W is selected from the group consisting of:
• 1) bond, and
• 2) O;
• Q is selected from the group consisting of:
• 1) N, and
• 2) CR8;
• L is selected from the group consisting of:
• 1) —C1-6alkyl-,
• 2) —C1-6alkyl-O—,
• 3) —C1-6alkyl-O—C1-6alkyl-,
• 4) —C1-6alkyl-S—,
• 5) —C1-6alkyl-S—C1-6alkyl-,
• 6) —C1-6alkyl-N(Rm)—, and
• 7) —C1-6alkyl-N(Rm)—C1-6alkyl-,
• wherein alkyl is unsubstituted or substituted with one to three substituents selected from:
• halogen, C1-3alkyl, —OC1-3alkyl, —NHC(O)C1-3alkyl, —C(O)NHC1-3alkyl, NHC1-3alkyl, and SC1-3alkyl;
• R1 is selected from the group consisting of:
• 1) —C3-12cycloalkyl,
• 2) —C3-12cycloalkenyl,
• 3) C2-11cycloheteroalkyl,
• 4) C2-11cycloheteroalkenyl,
• 5) aryl, and
• 6) heteroaryl,
• wherein cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl are unsubstituted or substituted with one to five substituents selected from Ra;
• R2 is selected from the group consisting of:
• 1) hydrogen,
• 2) C1-6alkyl,
• 3) C1-6alkyl-OR4, and
• 4) C1-6alkyl-NHR4,
• wherein alkyl is unsubstituted or substituted with one to three halogens;
• R3 is selected from the group consisting of:
• 1) hydrogen, and
• 2) OH;
• R4 is selected from the group consisting of:
• 1) hydrogen,
• 2) C1-3alkyl, and
• 3) C3cycloalkyl,
• wherein alkyl and cycloalkyl are unsubstituted or substituted with one to three halogens or OC1-3alkyl;
• R5 is selected from the group consisting of:
• 1) —CO2H, and
• 2) tetrazole;
• R6 and R7 are selected from the group consisting of:
• 1) hydrogen, and
• 2) C1-6alkyl,
• wherein alkyl is unsubstituted or substituted with one to three halogens, provided that at least one of R6 and R7 is hydrogen;
• R8 is independently selected from the group consisting of:
• 1) hydrogen,
• 2) C1-4alkyl,
• 3) halogen, and
• 4) C3-7cycloalkyl,
• wherein alkyl and cycloalkyl are unsubstituted or substituted with one to three substituents selected from:
• —OH, halogen, NH2, and —OC1-3alkyl;
• R9 and R10 are selected from the group consisting of:
• 1) hydrogen, and
• 2) C1-6alkyl,
• wherein alkyl is unsubstituted or substituted with one to three substituents selected from:
• halogen, OH, —OC1-3alkyl, —NHC(O)C1-3alkyl, —C(O)NHC1-3alkyl, NHC1-3alkyl, and SC1-3alkyl, provided that one or both of R9 and R10 are C1-6alkyl,
• or alternatively R9 and R10 together with the carbon to which they are attached form a monocyclic C3-5cycloalkyl or a monocyclic C2-5cycloheteroalkyl, wherein cycloalkyl and cycloheteroalkyl are unsubstituted or substituted with one to three substituents independently selected from halogen, —OH and —OC1-3alkyl;
• each Ra is independently selected from the group consisting of:
• 1) halogen,
• 2) —C1-6alkyl,
• 3) —C0-6alkyl-O—C1-6alkyl,
• 4) —C0-6alkyl-OH,
• 5) —C0-6alkyl S(O)rRj,
• 6) —C0-6alkyl S(O)rNRkRl,
• 7) —C0-6alkyl C(O)Ri,
• 8) —C0-6alkyl OC(O)Ri,
• 9) —C0-6alkyl C(O)OR1,
• 10) —C0-6alkyl CN,
• 11) —C0-6alkyl C(O)NkRl,
• 12) —C0-6alkyl C(NH)NRkRl,
• 13) —C0-6alkylNRkRl,
• 14) —C0-6alkyl N(Rk)(C(O)Ri),
• 15) —C0-6alkyl N(Rk)(C(O)ORh),
• 16) —C0-6alkyl N(Rk)(C(O)NRfRg), and
• 17) —C0-6alkyl N(Rk)(S(O)vRj),
• wherein alkyl is unsubstituted or substituted with one to three substituents selected from:
• halogen, OH, —OC1-3alkyl, —C1-3alkyl, —CO2C1-3alkyl, —C(O)NH2, —C0-6alkylNH2, and —C0-6alkylNH(C1-3alkyl);
• each Rb is independently selected from the group consisting of:
• 1) hydrogen,
• 2) C1-6alkyl,
• 3) C0-6alkyl-O—C1-6alkyl,
• 4) C0-6alkyl-OH,
• 5) C0-6alkyl-S(O)uRd,
• 6) C1-6alkyl-C(O—N(Rc)2,
• 7) C1-6alkylN(Re)C(O)Re,
• 8) C0-6alkyl-N(Re)2, and
• 9) halogen,
• wherein alkyl is unsubstituted or substituted with one to three halogens, or wherein two Rb substituents together with the atoms they are attached to can cyclize to form a 3 to 6 membered ring;
• each Rc is independently selected from the group consisting of:
• 1) hydrogen,
• 2) C1-6alkyl,
• 3) C0-6alkyl-O—C1-6alkyl,
• 4) C0-6alkyl-OH,
• 5) C0-6alkyl-S(O)vRf,
• 6) C0-6alkyl-S(O)vN(Rg)2,
• 7) C1-6alkyl C(O)—N(Rg)2,
• 8) C1-6alkylN(Rg)C(O)Rg,
• 9) C0-6alkyl-N(Rg)2, and
• 10) halogen,
• wherein alkyl is unsubstituted or substituted with one to three halogens;
• each Rd is independently selected from the group consisting of:
• 1) hydrogen, and
• 2) —C1-6 alkyl,
• wherein each alkyl is unsubstituted or substituted with one to three halogens;
• each Re is independently selected from the group consisting of:
• 1) hydrogen, and
• 2) —C1-6 alkyl,
• wherein each alkyl is unsubstituted or substituted with one to three halogens;
• each Rf is independently selected from the group consisting of:
• 1) hydrogen, and
• 2) —C1-6alkyl,
• wherein each alkyl is unsubstituted or substituted with one to three halogens;
• each Rg is independently selected from the group consisting of:
• 1) hydrogen, and
• 2) —C1-6 alkyl,
• wherein each alkyl is unsubstituted or substituted with one to three halogens;
• each Rh is independently selected from the group consisting of:
• 1) hydrogen, and
• 2) —C1-6 alkyl,
• wherein each alkyl is unsubstituted or substituted with one to three halogens;
• each Ri is —C1-6 alkyl, wherein each alkyl is unsubstituted or substituted with one to three halogens;
• each Rj is independently selected from the group consisting of:
• 1) hydrogen,
• 2) OH, and
• 3) —C1-6 alkyl,
• wherein each alkyl is unsubstituted or substituted with one to three halogens;
• each Rk is independently selected from the group consisting of:
• 1) hydrogen, and
• 2) —C1-6alkyl,
• wherein each alkyl is unsubstituted or substituted with one to three halogens;
• each Rl is independently selected from the group consisting of:
• 1) hydrogen, and
• 2) —C1-6alkyl,
• wherein each alkyl is unsubstituted or substituted with one to three halogens;
• each Rm is independently selected from the group consisting of:
• 1) hydrogen, and
• 2) —C1-6alkyl,
• wherein each alkyl is unsubstituted or substituted with one to three halogens;
• each r is independently 0, 1 or 2;
• each s is independently 0, 1, 2, 3, 4 or 5;
• each t is independently 0, 1, 2 or 3;
• each u is independently selected from 0, 1 or 2;
• and
• each v is independently selected from 0, 1 or 2.