Cephalosporin antibacterial compound and preparation method therefor

1 . A compound of formula I or a pharmaceutically acceptable salt thereof,

wherein,

X is N, CH or C—Cl;

T is S, S═O, CH 2 or O;

E is

 wherein R 1 and R 2 are each independently selected from the group consisting of hydrogen, halogen, phenyl, alkylthio, and alkyl optionally substituted with carbamoyl; R 11 and R 12 are each independently selected from the group consisting of hydrogen, carboxyl, and alkyl optionally substituted with carbamoyl; m is an integer of 1-5;

F is a single bond;

A is C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene;

each R 5 is independently selected from the group consisting of halogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl and C 1 -C 6 haloalkoxy;

G 1 is

R 1 ′ and R 2 ′ are each independently selected from the group consisting of hydrogen, halogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl and C 1 -C 6 haloalkoxy;

R 3 is C 1 -C 6 alkyl substituted with

R 3 ′ is selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 alkyl and C 1 -C 6 alkoxy, wherein the alkyl and alkoxy are optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, halogen, hydroxy, sulfhydryl, —NR i R j ,

 oxo, thio, —C(O)R k , —C(O)OR k , —C(S)R k , nitro, cyano, C 1 -C 6 alkoxy and C 1 -C 6 alkylthioether group;

each R m is independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, 6- to 10-membered aryl and 5- to 8-membered heteroaryl, wherein the alkyl, alkoxy, aryl and heteroaryl are optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, halogen, hydroxy, sulfhydryl, amino, carboxyl, nitro, cyano and C 1 -C 6 alkoxy;

each R 4 is independently selected from the group consisting of halogen, hydroxy, sulfhydryl and —NR i R j ;

R i and R j are each independently selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 alkyl and C 1 -C 6 alkoxy;

each R k is independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxy, C 1 -C 6 alkoxy and —NR i R j , wherein the alkyl, haloalkyl and alkoxy are optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, halogen, hydroxy, sulfhydryl, —NR i R j , oxo, thio, carboxyl, nitro, cyano, C 1 -C 6 alkoxy, C 1 -C 6 alkylthioether group, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocyclyl, 6- to 10-membered aryl and 5- to 8-membered heteroaryl;

p is an integer of 0-5;

q is an integer of 0-5;

x is 3;

n is an integer of 0-3.

2 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein A is C 1 -C 6 alkylene.

3 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 ′ and R 2 ′ are both hydrogen atoms.

4 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3 is selected from C 3 -C 6 alkyl substituted with

5 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein

is

wherein each R n is independently selected from the group consisting of C 1 -C 6 alkyl, hydroxy and halogen, and r is independently an integer of 0-5.

6 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3 ′ is selected from the group consisting of hydrogen and C 1 -C 6 alkyl substituted with

7 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein

is

wherein each R n is independently selected from the group consisting of C 1 -C 6 alkyl, hydroxy and halogen, and r is independently an integer of 0-5.

8 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound of formula I is selected from

9 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , being selected from

or a pharmaceutically acceptable salt thereof.

10 . An isotopically substituted form of the compound or the pharmaceutically acceptable salt thereof according to claim 1 .

11 . A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.

12 . A method of treating or preventing a disease caused by gram-negative bacteria in a subject in need thereof, the method comprising administering to the subject the compound or the pharmaceutically acceptable salt thereof according to claim 1 .

13 . A method of treating or preventing a disease caused by pathogenic bacteria in a subject in need thereof, the method comprising administering to the subject the compound or the pharmaceutically acceptable salt thereof according to claim 1 .

14 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein

is

15 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein

is

16 . The isotopically substituted form of the compound or the pharmaceutically acceptable salt thereof according to claim 10 , wherein the isotopic substitution is a substitution with a deuterium atom.

17 . The method according to claim 12 , wherein the disease is selected from the group consisting of airway infectious diseases, urinary system infectious diseases, respiratory system infectious diseases, septicemia, nephritis, cholecystitis, oral infectious diseases, endocarditis, pneumonia, bone marrow membrane myelitis, otitis media, enteritis, empyema, traumatic infectious diseases and opportunistic infections.

18 . The method according to claim 12 , wherein the gram-negative bacteria is selected from the group consisting of E. coli, Klebsiella, Serratia, Enterobacter, Citrobacter, Morganella, Providencia, Proteus, Haemophilus, Moraxella, Pseudomonas aeruginosa, Pseudomonas other than P. aeruginosa, Stenotrophomonas, Burkholderia and Acinetobacter.