Therapeutic compounds

Abstract

Compounds of Formula I TIFF2024524213000116.tif88165 and salts thereof are disclosed herein. Compositions comprising the compounds of formula I and methods of using the compounds of formula I are also disclosed.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 213,519, filed June 22, 20021. The contents of the above-referenced application are hereby incorporated by reference in their entireties. [Background technology]

[0002] Bacterial resistance has been observed against all antibiotics introduced into the clinic, including drugs of last resort such as vancomycin, daptomycin, and colistin. The increasing rate of resistance, coupled with a declining trend in the discovery and development of new antibiotics, portends a dangerous situation. There are now pathogens that are resistant to all or nearly all available antibiotics, resulting in an increasing number of deaths from bacterial infections. According to the CDC, at least 2.8 million people in the United States become infected with antibiotic-resistant bacteria or fungi each year, resulting in more than 35,000 deaths. Without improvements in antimicrobial drug discovery and development, this problem is only expected to worsen. By 2050, it is predicted that 10 million people will die each year worldwide from drug-resistant bacterial infections.

[0003] ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae / Escherichia coli (Enterobacteriacaea), Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species cause the most nosocomial infections and frequently "escape" the action of conventional treatments. The prevalence of multidrug-resistant (MDR) Gram-negative infections continues to increase. The most recent example is the rapid spread of multidrug-resistant Gram-negative bacteria observed among patients in a dedicated coronavirus disease care unit in a hospital in Maryland, USA, in May-June 2020. The World Health Organization (WHO) published a list of antibiotic-resistant "priority pathogens" for 2017, for which new antibiotics are urgently needed. The most important groups overall include multidrug-resistant bacteria that pose a particular threat in hospitals, nursing facilities, and patients requiring devices such as ventilators and blood catheters. They include Acinetobacter, Pseudomonas, and various Enterobacteriaceae (e.g., Klebsiella, E. coli, Serratia, Proteus). They can cause severe and often fatal infections, such as bloodstream infections and pneumonia. The second and third most important groups include high and medium priority bacteria that are increasingly drug resistant, such as Neisseria gonorrhoeae.

[0004] Sexually transmitted infections (STIs) caused by the bacterium N. gonorrhoeae (gonococcal infection) have increased by 63% since 2014 and are responsible for sequelae including pelvic inflammatory disease, ectopic pregnancy, and infertility, and may facilitate transmission of the human immunodeficiency virus (HIV). The ability of N. gonorrhoeae to acquire antimicrobial resistance impacts treatment recommendations and complicates control. In 2010, CDC recommended a combination of ceftriaxone and azithromycin for the treatment of uncomplicated gonorrhea infections. However, the continued occurrence of low ceftriaxone resistance and increased azithromycin resistance has led to a reevaluation of this recommendation. Azithromycin resistance in N. gonorrhoeae is an increasing concern. Genomic epidemiology data have confirmed that azithromycin resistance can arise from multiple mechanisms. Nationwide, the proportion of N. gonorrhoeae isolates with reduced susceptibility (MIC ≥ 2.0 μg / mL) has increased more than sevenfold over a 5-year period (from 0.6% in 2013 to 4.6% in 2018). In 2018, the proportion of Gonococcal Isolate Surveillance Project (GISP) isolates with azithromycin warning values ​​was 8.6% among men who have sex with men compared with 2.9% among men who have sex only with women. Studies have associated azithromycin exposure with the occurrence of reduced azithromycin susceptibility among patients with N. gonorrhoeae infection.

[0005] Since the introduction of fluoroquinolones in 1968 and clinicians have had to rely on later generation broad-spectrum antibiotics (i.e., antibiotics effective against both gram-positive and gram-negative pathogens), especially the carbapenems, no new classes of antibiotics effective against gram-negative bacteria have been introduced into the clinic. Unfortunately, carbapenem resistance is also on the rise, and infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are estimated to have a mortality rate as much as 50% higher than carbapenem-susceptible infections. With the rise in carbapenem-resistant infections, colistin, a drug previously excluded from the clinic due to its high toxicity, has been reintroduced into the clinic. However, colistin resistance easily emerges and becomes widespread via horizontal transfer of plasmids. Pathogens that are resistant to both colistin and carbapenems are difficult to treat, with mortality rates ranging from 20 to 70%. With the rise in carbapenem-resistant and colistin-resistant infections, new broad-spectrum antibiotics need to be developed to combat the rise in gram-positive and gram-negative antibiotic resistance.

[0006] Thus, there is a need for therapeutic agents and methods for treating and / or preventing bacterial infections. Summary of the Invention [Means for solving the problem]

[0007] The compounds disclosed herein have been demonstrated to have antibacterial activity against a variety of bacteria.

[0008] Thus, in one embodiment, there is provided a compound of formula I: [ka] During the ceremony, R 1 is hydrogen, (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, -C(=O)R a , -C(=O)N(R a )2, -S(=O)2N(R a )2, -C(=NR a)N(R a )2, (C3-C7)carbocyclyl, aryl, heterocyclyl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl-, which are (C1-C6)alkyl, (C2-C6)alkynyl, (C2-C6)alkenyl, (C3-C7)carbocyclyl, aryl aryl, heterocyclyl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl- are optionally selected from the group consisting of halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R a )2, -NR a C(=NR a )N(R a )2, -C(=NR a )N(R a )2, phenyl, and -OP(=O)(OH)2, wherein the phenyl is optionally substituted with one or more halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, or (C1-C4)haloalkoxy; R 2 is hydrogen, (C1-C6) alkyl, (C2-C6) alkenyl, -C(=O)R b , -C(=O)N(R b )2, -S(=O)2N(R b )2, -C(=NR b )N(R b)2, (C3-C7)carbocyclyl, aryl, heterocyclyl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl-, and are not limited to (C1-C6)alkyl, (C2-C6)alkenyl, (C3-C7)carbocyclyl, aryl, heterocyclyl aryl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl- are optionally selected from the group consisting of halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R b )2, -NR b C(=NR b )N(R b ) 2、 -C(=NR b )N(R b or substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of -OP(=O)(OH)2 and -OP(=O)(OH); R 1 and R 2 and together with the nitrogen to which they are attached form a heterocyclyl, the heterocyclyl optionally being selected from halo, -OH, -NO2, -CN, (C1-C4) alkyl, (C1-C4) haloalkyl, (C1-C4) alkoxy, (C1-C4) haloalkoxy, -N(R ab )2, -NR ab C(=NR ab )N(R ab ) 2、 -C(=NR ab )N(R ab -O-P(=O)(OH)2; Z is -OR c 、 -N(R c )2, -SR c , -NR c C(=NR c )N(Rc )2, -C(=NR c )N(R c )2, hydrogen, (C1-C6) alkyl, (C1-C6) alkenyl, -C(=O)R c , -C(=O)N(R c )2, -S(=O)2N(R c )2, (C3-C7)carbocyclyl, aryl, heterocyclyl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl-, which are (C1-C6)alkyl, (C1-C6)alkenyl, (C3-C7)carbocyclyl, aryl, hetero Cyclyl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl are optionally selected from the group consisting of halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R c )2, -NR c C(=NR c )N(R c )2, -C(=NR c )N(R c -O-P(=O)(OH)2; X 1 CR 3 or N, X 2 CR 4 or N, R 3 is hydrogen, halo, -OH, -NO2, -CN, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkenyl, (C2-C6)alkynyl-C(=O)R d , -C(=O)N(R d )2, -S(=O)2N(R d )2, -NR d C(=NR d )N(R d)2, -C(=NR d )N(R d )2 or -N(R d )2, wherein (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl or (C2-C6)alkynyl is optionally selected from halo, -OH, -NO2, -CN, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R d )2, -NR d C(=NR d )N(R d )2, -C(=NR d )N(R d -O-P(=O)(OH)2; R 4 is hydrogen, halo, -OH, -NO2, -CN, (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, -C(=O)R e , -C(=O)N(R e )2, -S(=O)2N(R e )2, -NR e C(=NR e )N(R e )2, -C(=NR e )N(R e ) 2、 or -N(R e )2, wherein (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl or (C2-C6)alkynyl is optionally selected from halo, -OH, -NO2, -CN, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R e )2, -NR e C(=NR e )N(R e )2, -C(=NR e )N(R e -O-P(=O)(OH)2; Y 1 is NR 5a and Y 2 is N or CR 6band Y 3 is N or CR 7b and Y 1 and Y 2 The dashed bond between is a single bond, and Y 2 and Y 3 The dashed bond between is a double bond, or Y 3 is NR 7a and Y 1 is N or CR 5b and Y 2 is N or CR 6b and Y 1 and Y 2 The dashed bond between Y is a double bond. 2 and Y 3 The dashed line between is a single bond, R 5a and R 7a are each independently (C1 to C 10 ) Alkyl, (C1-C 10 )alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl, W-heterocyclyl, or -W-heteroaryl; (C1-C 10 ) Alkyl, (C1-C 10 ) alkenyl, -W-(C3-C7) carbocyclyl, -W-aryl, W-heterocyclyl, -W-heteroaryl are optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from Q; R 5b , R 6b and R 7b are each independently hydrogen, halo, -OH, -NO2, -CN, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkenyl, -C(=O)R f , -C(=O)N(R f )2, -S(=O)2N(R f )2, -NR f C(=NR f )N(R f )2, -C(=NR f )N(R f )2, or -N(R f)2, where (C1-C6)alkoxy, (C1-C6)alkyl or (C1-C6)alkenyl is optionally selected from halo, -OH, -NO2, -CN, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R f )2, -NR f C(=NR f )N(R f ) 2、 -C(=NR f )N(R f -O-P(=O)(OH)2; W does not exist or (C1~C 10 ) alkyl or (C2-C6) alkynyl, 10 )alkyl or (C2-C6)alkynyl is optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) oxo (=O)s, (C1-C 10 ) One or more carbons of the alkyl may optionally be substituted with one or more (e.g., 1, 2, 3, 4, or 5) —O— or —NR w - is replaced by Each Q is independently halo, -OH, -NO2, -CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, C(=O)R q , -C(=O)N(R q )2, -N(R q )2, -S(=O)2N(R q ) 2、 Aryl, -O-aryl, heteroaryl or -O-heteroaryl, where (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, aryl, -Oaryl, heteroaryl or -Oheteroaryl are optionally selected from halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, C(=O)R q , -C(=O)O(R q), -C(=O)N(R q )2, -S(=O)2N(R q ) 2, aryl, and heteroaryl, each of which is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of Q 1 is replaced by Each Q 1 are independently halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy or (C1-C4)haloalkoxy; Each R a , R b , R ab , R c , R d , R e and R f are independently hydrogen, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) haloalkyl, (C3-C7) carbocyclyl or aryl; Each R w are independently hydrogen or (C1-C6) alkyl; R q is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)haloalkyl, (C3-C7)carbocyclyl or aryl, where aryl is optionally halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, C(=O)R q1 , -C(=O)O(R q1 ), -C(=O)N(R q1 )2 and -S(=O)2N(R q1 ) 2; and Each R q1 are independently hydrogen, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) haloalkyl, (C3-C7) carbocyclyl or aryl; or a salt thereof.

[0009] In one embodiment, a compound of formula I is provided, [ka] During the ceremony, R 1 is hydrogen, (C1-C6) alkyl, (C1-C6) alkenyl, -C(=O)R a , -C(=O)N(R a )2, -S(=O)2N(R a )2, -C(=NR a )N(R a )2, (C3-C7)carbocyclyl, aryl, heterocyclyl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl-, and (C1-C6)alkyl, (C1-C6)alkenyl, (C3-C7)carbocyclyl, aryl, heterocyclyl aryl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl- are optionally selected from the group consisting of halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R a )2, -NR a C(=NR a )N(R a ) 2、 -C(=NR a )N(R a -O-P(=O)(OH)2; R 2 is hydrogen, (C1-C6) alkyl, (C1-C6) alkenyl, -C(=O)R b , -C(=O)N(R b )2, -S(=O)2N(R b )2, -C(=NR b )N(R b)2, (C3-C7)carbocyclyl, aryl, heterocyclyl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl-, and (C1-C6)alkyl, (C1-C6)alkenyl, (C3-C7)carbocyclyl, aryl, heterocyclyl aryl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl- are optionally selected from the group consisting of halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R b )2, -NR b C(=NR b )N(R b ) 2、 -C(=NR b )N(R b -O-P(=O)(OH)2; or R 1 and R 2 and together with the nitrogen to which they are attached form a heterocyclyl, the heterocyclyl optionally being selected from halo, -OH, -NO2, -CN, (C1-C4) alkyl, (C1-C4) haloalkyl, (C1-C4) alkoxy, (C1-C4) haloalkoxy, -N(R ab )2, -NR ab C(=NR ab )N(R ab ) 2、 -C(=NR ab )N(R ab -O-P(=O)(OH)2; Z is -OR c 、 -N(R c )2, -SR c , -NR c C(=NR c )N(Rc )2, -C(=NR c )N(R c )2, hydrogen, (C1-C6) alkyl, (C1-C6) alkenyl, -C(=O)R c , -C(=O)N(R c )2, -S(=O)2N(R c )2, (C3-C7)carbocyclyl, aryl, heterocyclyl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl-, and (C1-C6)alkyl, (C1-C6)alkenyl, (C3-C7)carbocyclyl, aryl, heterocyclyl aryl, heteroaryl, (C3-C7)carbocyclyl(C1-C6)alkyl-, aryl(C1-C6)alkyl-, heterocyclyl(C1-C6)alkyl- or heteroaryl(C1-C6)alkyl- are optionally selected from the group consisting of halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R c )2, -NR c C(=NR c )N(R c )2, -C(=NR c )N(R c -O-P(=O)(OH)2; X 1 CR 3 or N, X 2 CR 4 or N, R 3 is hydrogen, halo, -OH, -NO2, -CN, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkenyl, -C(=O)R d , -C(=O)N(R d )2, -S(=O)2N(R d )2, -NR d C(=NR d )N(R d )2, -C(=NRd )N(R d )2 or -N(R d )2, where (C1-C6)alkoxy, (C1-C6)alkyl or (C1-C6)alkenyl is optionally selected from halo, -OH, -NO2, -CN, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R d )2, -NR d C(=NR d )N(R d ) 2、 -C(=NR d )N(R d -O-P(=O)(OH)2; R 4 is hydrogen, halo, -OH, -NO2, -CN, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkenyl, -C(=O)R e , -C(=O)N(R e )2, -S(=O)2N(R e )2, -NR e C(=NR e )N(R e )2, -C(=NR e )N(R e )2 or -N(R e )2, where (C1-C6)alkoxy, (C1-C6)alkyl or (C1-C6)alkenyl is optionally selected from halo, -OH, -NO2, -CN, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R e )2, -NR e C(=NR e )N(R e )2, -C(=NR e )N(R e )2 and -OP(=O)(OH)2; Y 1 is NR 5a and Y 2 is N or CR 6b and Y 3 is N or CR 7b and Y1 and Y 2 The dashed bond between is a single bond, and Y 2 and Y 3 The dashed bond between is a double bond, or Y 3 is NR 7a and Y 1 is N or CR 5b and Y 2 is N or CR 6b and Y 1 and Y 2 The dashed bond between Y is a double bond. 2 and Y 3 The dashed line between is a single bond, R 5a and R 7a are each independently (C1 to C 10 ) Alkyl, (C1-C 10 )alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl, W-heterocyclyl, or -W-heteroaryl; (C1-C 10 ) Alkyl, (C1-C 10 ) alkenyl, -W-(C3-C7) carbocyclyl, -W-aryl, W-heterocyclyl, -W-heteroaryl are optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from Q; R 5b , R 6b and R 7b are each independently hydrogen, halo, -OH, -NO2, -CN, (C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkenyl, -C(=O)R f , -C(=O)N(R f )2, -S(=O)2N(R f )2, -NR f C(=NR f )N(R f )2, -C(=NR f )N(R f )2 or -N(R f)2, where (C1-C6)alkoxy, (C1-C6)alkyl or (C1-C6)alkenyl is optionally selected from halo, -OH, -NO2, -CN, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R f )2, -NR f C(=NR f )N(R f )2, -C(=NR f )N(R f -O-P(=O)(OH)2; W does not exist or (C1~C 10 ) alkyl, (C1-C 10 ) alkyl is optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) oxo (=O), (C1-C 10 ) One or more carbons of the alkyl may optionally be substituted with one or more (e.g., 1, 2, 3, 4, or 5) —O— or —NR w - is replaced by Each Q is independently halo, -OH, -NO2, -CN, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, C(=O)R q , -C(=O)N(R q )2, -N(R q )2, -S(=O)2N(R a ) 2、 Aryl, -O-aryl, heteroaryl or -O-heteroaryl, where (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, aryl, -Oaryl, heteroaryl or -Oheteroaryl are optionally selected from halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, C(=O)R q , -C(=O)O(R q ), -C(=O)N(R q )2, -S(=O)2N(R q) 2, aryl, and heteroaryl, each of which is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of Q 1 is replaced by Each Q 1 are independently halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy or (C1-C4)haloalkoxy; Each R a , R b , R ab , R c , R d , R e and R f are independently hydrogen, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) haloalkyl, (C3-C7) carbocyclyl or aryl; Each R w are independently hydrogen or (C1-C6) alkyl; R q is hydrogen, (C1-C6)alkyl, (C1-C6)alkenyl, (C1-C6)haloalkyl, (C3-C7)carbocyclyl or aryl, where aryl is optionally halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, C(=O)R q1 , -C(=O)O(R q1 ), -C(=O)N(R q1 )2 and -S(=O)2N(R q1 ) 2; and Each R q1 are independently hydrogen, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) haloalkyl, (C3-C7) carbocyclyl or aryl; or a salt thereof.

[0010] In one embodiment, there is provided a pharmaceutical composition comprising a compound of formula I as described herein, or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable vehicle.

[0011] In one embodiment, a pharmaceutical composition is provided that includes a compound of formula I as described herein, or a pharma- ceutically acceptable salt thereof, one or more (e.g., one or two) antibacterial agents, and a pharma- ceutically acceptable vehicle.

[0012] In one embodiment, there is provided a method of treating or preventing a bacterial infection in an animal (e.g., a mammal such as a human), the method comprising administering to the animal a compound of formula I as described herein, or a pharma- ceutically acceptable salt thereof.

[0013] In one embodiment, a method of treating or preventing a bacterial infection in an animal (e.g., a mammal such as a human) is provided, the method comprising administering to the animal a compound of formula I as described herein, or a pharma- ceutically acceptable salt thereof, and one or more (e.g., one or two) antibacterial agents.

[0014] In one embodiment, there is provided a method of treating or preventing a bacterial infection in an animal (e.g., a mammal such as a human) in need of such treatment or prevention, the method comprising administering to the animal a compound of formula I as described herein, or a pharma- ceutically acceptable salt thereof.

[0015] In one embodiment, there is provided a method of treating or preventing a bacterial infection in an animal (e.g., a mammal such as a human) infected with a bacteria, the method comprising administering to the animal a compound of formula I as described herein, or a pharma- ceutically acceptable salt thereof.

[0016] In one embodiment, there is provided a compound of formula I, or a pharma- ceutically acceptable salt thereof, as described herein, for use in medical treatment.

[0017] In one embodiment there is provided a compound of formula I as described herein, or a pharma- ceutically acceptable salt thereof, for the prophylactic or therapeutic treatment of a bacterial infection.

[0018] In one embodiment, there is provided the use of a compound of formula I, or a pharma- ceutically acceptable salt thereof, as described herein, for the preparation of a medicament for the prophylactic or therapeutic treatment of a bacterial infection in an animal.

[0019] In one embodiment, there is provided the use of a compound of formula I as described herein, or a pharma- ceutically acceptable salt thereof, for the preparation of a medicament for the treatment of a bacterial infection in an animal (e.g., a mammal, such as a human).

[0020] One embodiment provides processes and intermediates disclosed herein that are useful for preparing a compound of formula I, or a salt thereof.

[0021] In one embodiment, a prodrug of a compound of formula I is provided. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] The following definitions are used unless otherwise stated: halo or halogen is fluoro, chloro, bromo or iodo. Alkyl, alkenyl, alkoxy, etc. refer to both straight and branched chain groups, although when referring to individual radicals such as propyl, only straight chain radicals are included (branched chain isomers such as isopropyl are specifically referred to).

[0023] As used herein, the term “(C a ~C b "(H)alkyl" refers to a straight or branched chain hydrocarbon alkyl radical having from a to b carbon atoms, where a and b are integers. Thus, for example, if a is 1 and b is 6, the term includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, and n-hexyl.

[0024] The term "alkenyl," as used herein, refers to an alkyl that contains one or more double bonds.

[0025] The term "aryl" as used herein refers to a single aromatic ring or a multiple condensed ring system in which the ring atoms are carbon. For example, an aryl group can have 6-10 carbon atoms, or 6-12 carbon atoms. Aryl includes phenyl radicals. Aryl also includes multiple condensed ring systems (e.g., ring systems containing two rings) having about 9-12 carbon atoms, or 9-10 carbon atoms, in which at least one ring is aromatic. Such multiple condensed ring systems may be optionally substituted with one or more (e.g., one or two) oxo groups at any cycloalkyl portion of the multiple condensed ring system. It should be understood that the attachment point of the multiple condensed ring system may be at any position of the ring system, including the aryl or cycloalkyl portion of the ring, as defined above. Typical examples of aryl groups include, but are not limited to, phenyl, indenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, anthracenyl, and the like. In one embodiment, the aryl is phenyl or naphthyl.

[0026] The term "heteroaryl" as used herein refers to a single aromatic ring or multiple condensed ring systems that are all carbon. The term includes aromatic single rings of about 1-6 carbon atoms and about 1-4 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur. The sulfur and nitrogen atoms can also be present in oxidized form, provided that the ring is aromatic. Such systems include, but are not limited to, pyridyl, pyrimidinyl, oxazolyl or furyl. The term also includes multiple condensed ring systems (e.g., ring systems containing two rings), where a heteroaryl group as defined above may be fused to one or more heteroaryls (e.g., naphthyridinyl), heterocycles (e.g., 1,2,3,4-tetrahydronaphthyridinyl), cycloalkyls (e.g., 5,6,7,8-tetrahydroquinolyl) or aryls (e.g., indazolyl) to form multiple condensed ring systems. Such multiple fused ring systems may be optionally substituted with one or more (e.g., one or two) oxo groups at the cycloalkyl or heterocyclic portion of the fused ring. In one embodiment, the monocyclic or bicyclic heteroaryl has 5-10 ring atoms, including 1-9 carbon atoms and 1-4 heteroatoms. In one embodiment, the monocyclic or bicyclic heteroaryl has 5-10 ring atoms, including 1-9 carbon atoms and 1-4 heteroatoms, and at least one ring containing at least one heteroatom is aromatic. It should be understood that the point of attachment of the multiple fused ring system (as defined above for heteroaryl) may be at any position of the multiple fused ring system, including the heteroaryl, heterocyclic, aryl, or cycloalkyl portion of the multiple fused ring system, as well as at any suitable atom of the multiple fused ring system, including carbon atoms and heteroatoms (e.g., nitrogen). Exemplary heteroaryls include, but are not limited to, pyridyl, pyrrolyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, thienyl, indolyl, imidazolyl, oxazolyl, thiazolyl, furyl, oxadiazolyl, thiadiazolyl, quinolyl, isoquinolyl, benzothiazolyl, benzoxazolyl, indazolyl, quinoxalyl, quinazolyl, 5,6,7,8-tetrahydroisoquinolinyl, benzofuranyl, benzimidazolyl, and thianaphthenyl.

[0027] The term "heterocyclyl" or "heterocycle" as used herein refers to a single saturated or partially unsaturated ring containing at least one heteroatom or a polycyclic ring system, where at least one ring is saturated or partially unsaturated and contains at least one heteroatom. The term includes a saturated or partially unsaturated monocyclic ring (e.g., a 3-, 4-, 5-, 6-, or 7-membered ring) having about 1-6 carbon atoms and about 1-3 (e.g., 1, 2, or 3) heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur in the ring. In one embodiment, a monocyclic or bicyclic heterocyclyl has 5-10 ring atoms, where the ring atoms include 1-9 carbon atoms and 1-4 heteroatoms (e.g., 1, 2, 3, or 4) selected from the group consisting of oxygen, nitrogen, and sulfur in the ring, where at least one ring is saturated or partially unsaturated and contains at least one heteroatom. The ring may be substituted with one or more (e.g., 1, 2, or 3) oxo groups, and sulfur and nitrogen atoms may also be present in their oxidized forms. Such rings include, but are not limited to, azetidinyl, tetrahydrofuranyl, or piperidinyl. It should be understood that the attachment point of the heterocycle may be at any suitable heterocycle atom. Exemplary heterocycles include, but are not limited to, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, homopiperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, tetrahydrofuranyl, dihydrooxazolyl, tetrahydropyranyl, and tetrahydrothiopyranyl.

[0028] The term "haloalkyl" includes an alkyl group, as defined herein, that is substituted with one or more (e.g., 1, 2, 3, or 4) halo groups. One particular haloalkyl is a "(C1-C6)haloalkyl."

[0029] The term "alkoxy" refers to an --O-alkyl group.

[0030] The terms cycloalkyl, carbocycle, or carbocyclyl include saturated and partially unsaturated carbocyclic ring systems. In one embodiment, a carbocyclyl is a monocyclic carbocycle. Such carbocyclyls include "(C3-C7)carbocyclyl" and "(C3-C8)cycloalkyl." Examples of carbocyclyls include, but are not limited to, cyclopropane, cyclobutane, cyclobutene, cyclopentane, cyclopentene, cyclohexane, cyclohexene, cycloheptane, and cycloheptene.

[0031] The specific values ​​listed below for radicals, substituents, and ranges are for illustration only; they do not exclude other defined values ​​or other values ​​within the defined ranges for the radicals and substituents.

[0032] Specifically, the (C1-C6) alkyl can be methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl, pentyl, 3-pentyl or hexyl, the (C1-C6) alkoxy can be methoxy, ethoxy, propoxy, isopropoxy, butoxy, iso-butoxy, sec-butoxy, pentoxy, 3-pentoxy or hexyloxy, the (C3-C8) cycloalkyl can be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, the (C1-C6) haloalkyl can be iodomethyl, bromomethyl, chloromethyl, fluoromethyl, trifluoromethyl, aryl can be phenyl, indenyl or naphthyl; heteroaryl can be furyl, imidazolyl, triazolyl, triazinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridyl, (or its N-oxide), thienyl, pyrimidinyl (or its N-oxide), indolyl, isoquinolyl (or its N-oxide) or quinolyl (or its N-oxide).

[0033] It is understood that the embodiments provided below are for compounds of formula I and all subformulas thereof (e.g., formulas Ia, Ib, Ic, Id, Ie, If, Ig, Ih). It is understood that two or more embodiments can be combined.

[0034] In one embodiment, X 1 CR 3 It is.

[0035] In one embodiment, X 2 CR 4 It is.

[0036] In one embodiment, X 2 is N.

[0037] In one embodiment, the compound of formula I is a compound of formula Ia: [ka] or a salt thereof.

[0038] In one embodiment, the compound of formula I is a compound of formula Ib: [ka] or a salt thereof.

[0039] In one embodiment, the compound of formula I is a compound of formula Ic: [ka] or a salt thereof.

[0040] In one embodiment, Y 3 CR 7b It is.

[0041] In one embodiment, Y 2 CR 6b It is.

[0042] In one embodiment, the compound of formula I is a compound of formula Id: [ka] or a salt thereof.

[0043] In one embodiment, the compound of formula I is a compound of formula Ie: [ka] or a salt thereof.

[0044] In one embodiment, the compound of formula I is a compound of formula If: [ka] or a salt thereof.

[0045] In one embodiment, the compound of formula I is a compound of formula Ig: [ka] or a salt thereof.

[0046] In one embodiment, the compound of formula I is a compound of formula Ih: [ka] or a salt thereof.

[0047] In one embodiment, the compound of formula I is a compound of formula Ii: [ka] or a salt thereof.

[0048] In one embodiment, R 3 is hydrogen.

[0049] In one embodiment, R 3 is hydrogen or halo.

[0050] In one embodiment, R 4 is hydrogen.

[0051] In one embodiment, R 4 is hydrogen or halo.

[0052] In one embodiment, R 1 is hydrogen, (C1-C6)alkyl or aryl(C1-C6)alkyl-, where (C1-C6)alkyl or aryl(C1-C6)alkyl is optionally halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, -N(R a )2, -NR a C(=NR a )N(R a )2, -C(=NR a )N(R a )2, phenyl, and -OP(=O)(OH)2, wherein the phenyl is optionally substituted with one or more halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, or (C1-C4)haloalkoxy.

[0053] In one embodiment, R 1 R 1 is hydrogen, (C1-C6)alkyl, or aryl(C1-C6)alkyl-, where (C1-C6)alkyl or aryl(C1-C6)alkyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of halo and phenyl, and phenyl is optionally substituted with one or more halo, -OH, -NO2, -CN, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, or (C1-C4)haloalkoxy.

[0054] In one embodiment, R 1 is hydrogen.

[0055] In one embodiment, R 2 is hydrogen.

[0056] In one embodiment, Z is -N(R c )2.

[0057] In one embodiment, Z is -NH2.

[0058] In one embodiment, R 7b is hydrogen.

[0059] In one embodiment, R 6b is hydrogen.

[0060] In one embodiment, R 7b is hydrogen or (C1-C6) alkyl.

[0061] In one embodiment, R 6b is hydrogen or (C1-C6) alkyl.

[0062] In one embodiment, R 5a is (C1~C 10 )alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl or -W-heteroaryl; (C1-C 10 )Alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl, -W-heteroaryl are optionally substituted with one or more groups independently selected from Q.

[0063] In one embodiment, R 5a is (C1~C 10 ) Alkyl, (C2-C 10 ) alkenyl, -W-(C3-C7) carbocyclyl, -W-aryl or -W-heteroaryl, C1-C 10 ) Alkyl, (C2-C 10 )Alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl or -W-heteroaryl are optionally substituted with one or more groups independently selected from Q.

[0064] In one embodiment, R 5a (C2~C 10)alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl or -W-heteroaryl; (C2-C 10 )Alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl or -W-heteroaryl are optionally substituted with one or more groups independently selected from Q.

[0065] In one embodiment, W is absent or (C1-C 10 ) alkyl or (C2-C6) alkynyl, 10 )alkyl or (C2-C6)alkynyl is optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) oxo (=O)s, (C1-C 10 ) One or more carbons of the alkyl may optionally be substituted with one or more (e.g., 1, 2, 3, 4, or 5) —O— or —NR w Replaced with -.

[0066] In one embodiment, R 5a is (C2-C6)alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl, or -W-heteroaryl, where (C2-C6)alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl, -W-heteroaryl are optionally substituted with one or more groups independently selected from Q.

[0067] In one embodiment, R 5a is (C1-C6)alkyl, (C2-C6)alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl or -W-heteroaryl, where C1-C6)alkyl, (C2-C6)alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl or -W-heteroaryl is optionally substituted with one or more groups independently selected from Q.

[0068] In one embodiment, R 5ais (C2-C6)alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl, or -W-heteroaryl, where (C2-C6)alkenyl, -W-(C3-C7)carbocyclyl, -W-aryl, or -W-heteroaryl is optionally substituted with one or more groups independently selected from Q.

[0069] In one embodiment, W is absent, (C1-C6) alkyl, or (C2-C6) alkynyl, where the (C1-C6) alkyl or (C2-C6) alkynyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) oxo (=O), and (C1-C 10 ) One or more carbons of the alkyl may optionally be substituted with one or more (e.g., 1, 2, 3, 4, or 5) —O— or —NR w Replaced with -.

[0070] In one embodiment, W is absent or is (C1-C4)alkyl, wherein the (C1-C4)alkyl is optionally substituted with one or more oxo (=O).

[0071] In one embodiment, W is absent or (C1-C 10 ) alkyl or (C2-C6) alkynyl, 10 )alkyl or (C2-C6)alkynyl is optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) oxo (=O).

[0072] In one embodiment, W is absent, -CH2-, -C(=O)-, or propyne.

[0073] In one embodiment, W is absent, -CH2- or -C(=O)-.

[0074] In one embodiment, R 5a is as follows: [ka]

[0075] In one embodiment, R 5a is as follows: [ka] [ka]

[0076] In one embodiment, the compound: [ka] [ka] or a salt thereof.

[0077] In one embodiment, the compound: [ka] [ka] [ka] [ka] [ka] or a salt thereof.

[0078] In general, compounds of formula I, as well as synthetic intermediates that can be used to prepare compounds of formula I, can be prepared as shown in the following general scheme. 3 , R 4 , R 5a , R 6b , R 7b) may represent the final corresponding groups present in the compound of formula I, or they may represent groups that can be converted to the final corresponding groups present in the compound of formula I at a convenient point in the synthetic sequence. For example, the variable groups may contain one or more protecting groups that can be removed at a convenient point in the synthetic sequence to provide the final corresponding groups in the compound of formula I. Schemes 1-3 show general methods for the preparation of compounds of formula I.

[0079] Scheme 1 [ka]

[0080] Scheme 2 [ka]

[0081] Scheme 3 [ka]

[0082] Scheme 4 [ka]

[0083] A slightly less expensive cotton candy can be used A specific antifungal agent is Acinetobacter baumannii、Acinetobacter calcoaceticus、Acinetobacter haemolyticus、Acinetobacter lwoffi、Actinobacillus actinomycetemcomitans、Aeromonas hydrophilia、Aggrebacter actinomycetemcomitans、Agrobacterium tumefaciens、Bacteroides distasonis、Bacteroides eggerthii、Bacteroides forsythus、Bacteroides fragilis、Bacteroides ovalus、Bacteroides splanchnicus、Bacteroides thetaiotaomicron、Bacteroides uniformis、Bacteroides vulgatus、Bordetella bronchiseptica、Bordetella parapertussis diversus、Citrobacter freundii、Enterobacter aerogenes、Enterobacter asburiae、Enterobacter cloacae、Enterobacter sakazakii、Escherchia coli、Francisella tularensis、Fusobacterium nucleatum、Gardnerella vaginalis、Haemophilus ducreyi、Haemophilus haemolyticus、Haemophilusinfluenzae、Haemophilus parahaemolyticus、Haemophilus parainfluenzae、Helicobacter pylori、Kingella denitrificans、Kingella indologenes、Kingella kingae、Kingella oralis、Klebsiella oxytoca、Klebsiella pneumoniae、Klebsiella rhinoscleromatis、Legionella pneumophila、Listeria monocytogenes、Moraxella bovis、Moraxella catarrhalis、Moraxella lacunata、Morganella morganii、Neisseria gonorrhoeae、Neisseria meningitidis、Pantoea agglomerans、Pasteurella canis、Pasteurella haemolytica、Pasteurella multocida、Pasteurella tularensis、Porphyromonas gingivalis、Proteus mirabilis、Proteus vulgaris、Providencia alcalifaciens、Providencia rettgeri、Providencia stuartii、Pseudomonas acidovorans、Pseudomonas aeruginosa、Pseudomonas alcaligenes、Pseudomonas fluorescens、Pseudomonas putida、Salmonella enteriditis、Salmonella paratyphi、Salmonella typhi、Salmonella typhimurium、Serratia marcescens、Shigella dysenteriae、Shigella jlexneri、Shigella sonnei、Stenotrophomonas maltophilla、Veillonella parvula、Vibrio cholerae、Vibrioparahaemolyticus, Yersinia enterocolitica, Yersinia intermedia, Yersinia pestis and Yersinia pseudotuberculosis.

[0084] In one embodiment, the bacterial infection being treated is a gram-positive bacterial strain infection. In one embodiment, the Gram-positive bacterial strain is Actinomyces naeslundii, Actinomyces viscosus, Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Clostridium difficile, Corynebacterium diphtheriae, Corynebacterium ulcerans, Enterococcus faecalis, Enterococcus faecium, Micrococcus luteus, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Mycobacterium uberculosis, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus hyicus, Staphylococcus intermedius, Staphylococcus Streptococcus saccharolyticus, Staphylococcus saprophyticus, Streptococcus agalactiae, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus salivarius and Streptococcus sanguis.

[0085] The composition may optionally contain a hypnotic, a nonsteroidal anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anesthetic, a neuromuscular blocking agent, an anti-cancer drug, an antibacterial drug (e.g., an aminoglycoside, an antifungal drug, an antiparasitic drug, an antiviral drug, a carbapenem, a cephalosporin (e.g., cefepime), a fluoroquinolone, a macrolide, a penicillin, a sulfonamide, a tetracycline, another antibacterial drug), an antipsoriatic drug, a corticosteroid, an anabolism steroid, a diabetes related drug, a mineral, a nutritional drug, a thyroid drug, a vitamin, a calcium related hormone, an antidiarrheal drug, an antitussive, an antiemetic, an ulcer drug, a laxative, an anticoagulant, an erythropoietin (e.g., epoetin alpha), a filgrastim (G-CSF, Neupogen), a sarcolytic drug, a steroid ... Other active therapeutic agents may also be included, such as rugramostim (GM-CSF, Leukine), immunostimulants, immunoglobulins, immunosuppressants (e.g., basiliximab, cyclosporine, daclizumab), growth hormones, hormone replacement drugs, estrogen receptor modulators, mydriatics, cycloplegics, alkylating agents, antimetabolites, cytostatic drugs, radiopharmaceuticals, antidepressants, antimanics, antipsychotics, anxiolytics, hypnotics, sympathomimetics, stimulants, donepezil, tacrine, asthma drugs, beta agonists, inhaled steroids, leukotriene inhibitors, methylxanthines, cromolyn, epinephrine or analogs thereof, dornase alfa (Pulmozyme), cytokines, or any combination thereof.

[0086] In one embodiment, the antibacterial agent is selected from a quinolone, a tetracycline, a glycopeptide, an aminoglycoside, a β-lactam, a rifanmycin, a macrolide, a ketolide, an oxazolidone, a coumermycin, and a chloramphenicol.

[0087] It will be understood that the compounds of the present invention having chiral centers can exist and be isolated in optically active and racemic forms. Some compounds may exhibit crystalline polymorphism. It should be understood that the present invention includes any racemic, optically active, crystalline polymorphic or stereoisomer of the compounds of the present invention, or mixtures thereof, that have the useful properties described herein, and methods for preparing optically active forms (e.g., by recrystallization techniques, by resolution of racemic forms, by synthesis from optically active starting materials, by chiral synthesis, or by chromatographic separation using chiral stationary phases) are well known in the art.

[0088] In the formulas of compounds herein, when a bond is drawn in a non-stereochemical form (e.g., flat), the atom to which the bond is attached includes all stereochemical possibilities. In the formulas of compounds herein, when a bond is drawn in a defined stereochemical form (e.g., bold line, bold wedge, dashed line, or dashed wedge), the atom to which the stereochemical bond is attached is understood to be enriched in the absolute stereoisomer shown, unless otherwise indicated. In one embodiment, the compound (or composition thereof) can be at least 51% of the absolute stereoisomer shown. In another embodiment, the compound (or composition thereof) can be at least 60% of the absolute stereoisomer shown. In another embodiment, the compound (or composition thereof) can be at least 80% of the absolute stereoisomer shown. In another embodiment, the compound (or composition thereof) can be at least 90% of the absolute stereoisomer shown. In another embodiment, the compound (or composition thereof) can be at least 95% of the absolute stereoisomer shown. In another embodiment, the compound (or composition thereof) may be at least 99% of the absolute stereoisomer shown.

[0089] It will also be understood by those skilled in the art that certain compounds of the present invention can exist in two or more tautomeric forms.For example, the substituent of formula -NH-C(=O)H in formula (I) can exist in tautomeric form as -N=C(OH)H.The present invention encompasses all tautomeric forms of compounds of formula I, as well as all tautomeric forms of mixtures of compounds of formula I, that can exist in equilibrium with uncharged and charged forms depending on pH, having the useful properties described herein.

[0090] If the compound is sufficiently basic or acidic, the salt of the compound of formula I may be useful as an intermediate for isolating or purifying the compound of formula I. In addition, it may be suitable to administer the compound of formula I as a pharmaceutically acceptable acid or base salt. Examples of pharmaceutically acceptable salts are organic acid addition salts formed with acids that form physiologically acceptable anions, such as tosylate, methanesulfonate, acetate, citrate, malonate, tartrate, succinate, fumarate, benzoate, ascorbate, α-ketoglutarate, and α-glycerophosphate. Suitable inorganic salts may also be formed, including hydrochloride, sulfate, nitrate, bicarbonate, and carbonate. Salts may be obtained by reacting a compound that is sufficiently basic to give the corresponding anion, such as an amine, with a suitable acid using standard procedures well known in the art. Alkali metal (e.g., sodium, potassium, or lithium) or alkaline earth metal (e.g., calcium) salts of carboxylic acids may also be prepared.

[0091] Pharmaceutically suitable counterions include pharma- ceutically suitable cations and pharma-ceutically suitable anions known in the art. Examples of pharma-ceutically suitable anions include Cl. - , Br - , I - , CH3SO3 - , H2PO4 - , CF3SO3 - , p-CH3C6H4SO3 -Examples of anions that can be used include, but are not limited to, those mentioned above (e.g., physiologically acceptable anions), including, for example, citrate, tartrate, phosphate, malate, fumarate, formate, or acetate.

[0092] It will be understood by those skilled in the art that compounds of the invention that contain a counterion can be converted to compounds of the invention that contain a different counterion. Such conversion can be accomplished using a variety of well-known techniques and materials, including, but not limited to, ion exchange resins, ion exchange chromatography, and selective crystallization.

[0093] The compounds of formula I can be formulated as pharmaceutical compositions and administered to a mammalian host, such as a human patient, in a variety of forms adapted to the chosen route of administration, i.e., orally or parenterally, intravenously, intramuscularly, topically, or subcutaneously. For oral administration, the compounds can be formulated as solid dosage forms with or without enteric coating.

[0094] That is, the compounds of the present invention may be administered systemically, e.g., orally, in combination with a pharma- ceutically acceptable vehicle, such as an inert diluent, excipient, or assimilable edible carrier. They may be enclosed in hard or soft shell gelatin capsules, compressed into tablets, or incorporated directly into the food of the patient's diet. For therapeutic oral administration, the active compound may be combined with one or more excipients and used in the form of ingestible tablets, buccal tablets, lozenges, capsules, elixirs, suspensions, syrups, wafers, and the like. Such compositions and preparations should contain at least 0.1% of the active compound. The percentage of the compositions and preparations may, of course, vary and may conveniently be from about 2 to about 90% of the weight of a given unit dosage form. The amount of active compound in such therapeutically useful compositions is such that an effective dosage level will be obtained.

[0095] Tablets, troches, pills, capsules, etc. may also contain binders such as gum tragacanth, acacia, corn starch, or gelatin, excipients such as dicalcium phosphate, disintegrating agents such as corn starch, potato starch, alginic acid, etc., lubricants such as magnesium stearate, and sweeteners such as sucrose, fructose, lactose, or aspartame, or flavorings such as peppermint, wintergreen oil, or cherry flavoring. When the unit dosage form is a capsule, in addition to the above types of materials, it may contain a liquid carrier such as vegetable oil or polyethylene glycol. Various other materials may be present as coatings or otherwise to modify the physical form of the solid unit dosage form. For example, tablets, pills, or capsules may be coated with gelatin, wax, shellac, sugar, etc. Syrup or elixir may contain active compound, sucrose or fructose as sweetener, methylparaben and propylparaben as preservatives, dye, and flavoring such as cherry flavor or orange flavor.Of course, any material used to prepare any unit dosage form must be pharmaceutically acceptable and substantially non-toxic in the amount used.In addition, active compound can be incorporated into sustained release preparations, particles, and devices.

[0096] The active compound can be administered intravenously or intramuscularly by infusion or injection.The solution of the active compound or its salt can be prepared in water, optionally mixed with a non-toxic surfactant.Dispersions can also be prepared in glycerol, liquid polyethylene glycol, triacetin and mixtures thereof, and in oil.These preparations contain a preservative to prevent the growth of microorganisms under normal storage and use conditions.

[0097] Pharmaceutical dosage forms suitable for injection or infusion may include sterile aqueous solutions or dispersions containing the active ingredient, or sterile powders containing the active ingredient, adapted for extemporaneous preparation of sterile solutions or dispersions for injection or infusion, which are optionally encapsulated in liposomes. In any case, the final dosage form must be sterile, fluid, and stable under the conditions of manufacture and storage. The liquid carrier or liquid vehicle may be, for example, a solvent or liquid dispersion medium, including water, ethanol, polyol (for example, glycerol, propylene glycol, liquid polyethylene glycol, etc.), vegetable oils, non-toxic glyceryl esters, and suitable mixtures thereof. The proper fluidity can be maintained, for example, by forming liposomes, by maintaining the required particle size in the case of dispersions, or by using surfactants. The action of microorganisms can be suppressed by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, buffers, or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin.

[0098] Sterile injection solutions are prepared by incorporating the active compound in the required amount in a suitable solvent with various other ingredients as listed above, as required, and then sterilizing by filtration. In the case of sterile powders for preparing sterile injection solutions, the preferred preparation method is vacuum drying and freeze-drying techniques, which provide a powder of the active ingredient and any additional desired ingredients present in the previously sterile-filtered solution.

[0099] For topical administration, the compounds of the invention may be applied in pure form, i.e., in a form in which the compound is a liquid, however, it will generally be desirable to administer them to the skin as a composition or formulation in combination with a dermatologically acceptable carrier, which may be a solid or liquid.

[0100] Useful solid carriers include finely divided solids (talc, clay, microcrystalline cellulose, silica, alumina, nanoparticles, etc.). Useful liquid carriers include water, alcohol or glycol, or water-alcohol / glycol blends in which the compounds of the present invention can be dissolved or dispersed at effective levels, optionally with the aid of non-toxic surfactants. Adjuvants such as fragrances and additional antimicrobial agents can be added to optimize the properties for a given application. The resulting liquid composition can be applied from absorbent pads, used to impregnate bandages and other dressings, or sprayed onto the affected area using pump-type or aerosol sprays.

[0101] Also, thickening agents such as synthetic polymers, fatty acids, fatty acid salts and esters, fatty acid alcohols, modified cellulose, or modified mineral materials can be used with liquid carriers to form spreadable pastes, gels, ointments, soaps, and the like for application directly to the skin of the user.

[0102] Useful dosages of the compounds of Formula I can be determined by comparing their in vitro activity, and in vivo activity in animal models. Methods for the extrapolation of effective dosages in mice, and other animals, to humans are known to the art; see, for example, U.S. Patent No. 4,938,949.

[0103] The amount of the compound of the invention, or an active salt or derivative thereof, required for therapeutic use will vary depending not only on the particular salt chosen, but also on the route of administration, the nature of the condition being treated, and the age and condition of the patient, and will ultimately be at the discretion of the attending physician or clinician.

[0104] In general, however, suitable dosages will range from about 1 to about 500 mg / kg per day, for example, from about 5 to about 400 mg / kg per day, for example, from 1 to about 250 mg per kilogram of recipient body weight per day.

[0105] The compounds are conveniently formulated in unit dosage form, for example containing 5-500 mg, 10-400 mg, or 5-100 mg of active ingredient per unit dosage form. In one embodiment, the invention provides a composition comprising a compound of the invention formulated in such a unit dosage form. The desired dose may conveniently be supplied in a single dose or as multiple doses administered at appropriate intervals, for example as two, three, four or more sub-doses daily. The sub-doses themselves may be further divided, for example into loosely spaced discrete administrations.

[0106] Co-administration of a compound disclosed herein with one or more other active therapeutic agents (e.g., an antibacterial agent) generally refers to the simultaneous or sequential administration of a compound disclosed herein with one or more other active therapeutic agents such that therapeutically effective amounts of both the compound disclosed herein and the one or more other active therapeutic agents are present in the patient's body.

[0107] The ability of compounds disclosed herein to inhibit N. gonorrhoeae growth is shown in Table 1 and can be determined using the methods described in Example 34. [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8] [Table 1-9]

[0108] The ability of compounds disclosed herein to inhibit bacterial growth is shown in Table 2 and can be determined using the methods described in Example 54. Table 2 [Table 2]

[0109] The invention will now be illustrated by the following non-limiting examples.

[0110] Preparation of Amine Intermediates A, B, C, D, and E Section 1: Synthetic procedures for the preparation of intermediates A, B, C, D and E [Table 3]

[0111] Preparation of intermediate A: 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7H-Pyrrolo[2,3-h]quinazoline-2,4-diamine [ka] To a solution of 2-cyano-1-(1H-indol-4-yl)guanidine (5.2 g, 26 mmol) in dimethoxyethane (200 mL) was added BF3.Et2O (16 mL, 130 mmol) slowly at room temperature. It was stirred at 80 °C under N2 overnight, then the solvent was removed in vacuo and the residue was suspended in methanol (50 mL). NH3 / H2O (35 mL) was added to the solution. It was stirred at room temperature for 2 h, then concentrated and loaded onto silica gel. It was purified by column chromatography on silica gel using MeOH in DCM as eluent to give a brown powder (3.3 g, 64% yield). 1 H NMR (300MHz, DMSO-d6) δ11.72(s br,1H),8.02(s br,1H),7.73(d,J=9.0Hz,1H),7.42(s,1H),7.29(d,J=9.0Hz,1H),6.90(br s,1H),6.85(s,1H). MS(ESI):C 10 H 10 N5 + 200.09[M+H] + Calculated value for, measured value 199.80 [M+H] + .

[0112] The requisite intermediates were prepared as follows: [ka] 2-Cyano-1-(1H-indol-4-yl)guanidine To a solution of 4-aminoindole (5.29 g, 40 mmol) in methanol (150 mL) was added HCl solution (4 M in dioxane, 12.5 mL, 50 mmol) slowly at room temperature. The reaction mixture was stirred at room temperature for 10 min and then the solvent was removed in vacuum. The residue was dissolved in DMF (60 mL) and sodium dicyanamide (8.90 g, 100 mmol) was added at room temperature. The reaction mixture was heated at 45° C. overnight. Then the DMF was removed in vacuum. The residue was treated with water and the precipitate was filtered off, washed with water and dried in vacuum. The crude product was recovered as a grey powder (5.3 g, 67% yield) which was used in the next step reaction without purification. 1H NMR(300MHz,DMSO-d6)δ11.20(s,1H),8.88(s,1H),7.32(m,1H),7.19(t,J=8.1,Hz,2H),7.02(t,J=7.8Hz,1H),6.94(s,2H),6.44(s,1H). MS(ESI):C 10 H 10 N5 + 200.09[M+H] + Calculated value for, measured value 199.85 [M+H] + .

[0113] Preparation of intermediate B: 8-methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 8-Methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine [ka] To a solution of 2-cyano-1-(2-methyl-1H-indol-4-yl)guanidine (0.82 g, 3.8 mmol) in dimethoxyethane (30 mL) was added BF3.Et2O (2.4 mL, 20 mmol) slowly at room temperature. It was stirred at 80° C. under N2 overnight, then the solvent was removed in vacuo and the residue was suspended in a small amount of methanol (10 mL). NH3.H2O (5 mL) was added to the solution. It was stirred at room temperature for 2 h, then concentrated and loaded onto silica gel. It was purified by column chromatography on silica gel with MeOH in DCM to give a brown powder (0.68 g, 83% yield). 1 H NMR(300MHz,DMSO-d6)δ11.82(s br,1H),8.67(s br,1H),8.45(s br,1H),7.75(d,J=9.0Hz,1H),7.31(d,J=9.0Hz,1H),7.23(s br,1H),7.06(s br,1H),6.89(s br,1H),6.59(s,1H),2.44(s,3H). MS(ESI):C 11 H 12 N5 + 214.10[M+H]+ Calculated value for, measured value 213.85 [M+H] + .

[0114] The requisite intermediates were prepared as follows: [ka] 2-Cyano-1-(2-methyl-1H-indol-4-yl)guanidine To a solution of 4-aminoindole (0.83 g, 5.7 mmol) in methanol (30 mL) was added HCl solution (4 M in dioxane, 1.7 mL, 6.8 mmol) slowly at room temperature. The reaction mixture was stirred at room temperature for 5 min and then the solvent was removed in vacuum. The residue was dissolved in DMF (12 mL) and sodium dicyanamide (1.26 g, 14.2 mmol) was added at room temperature. The reaction mixture was heated at 45° C. overnight. Then the DMF was removed in vacuum. The residue was treated with water and the precipitate was filtered off, washed with water and dried in vacuum. The crude product was recovered as a grey powder (0.83 g, 69% yield) which was used in the next step reaction without purification. 1 H NMR (300MHz, DMSO-d6) δ11.02(s,1H),8.79(s,1H),7.09(t,J=7.5Hz,1H),7.04(s,1H),6.91(t,J=7.8Hz,1H),6.88(s,1H),6.11(s,1H),2.36(s,3H). MS(ESI):C 11 H 12 N5 + 214.10[M+H] + Calculated value for, measured value 213.90 [M+H] + .

[0115] Preparation of intermediate C: 5-bromo-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 5-Bromo-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine To a solution of 6-bromo-1H-indol-4-amine (0.25 g, 1.2 mmol) in methanol (10 mL) was added HCl solution (4 M in dioxane, 0.4 ML, 1.6 mmol) at room temperature. The reaction mixture was stirred at room temperature and then the solvent was removed in vacuum. The residue was dissolved in DMF (2 mL) and sodium dicyanamide (0.27 g, 3 mmol) was added at room temperature. The reaction mixture was heated at 45° C. overnight. Then the DMF was removed in vacuum. The residue was treated with water and the precipitate was filtered off, washed with water and dried in vacuum. The crude product was recovered as a grey powder. It was dissolved in dimethoxyethane (10 mL) and then BF3.Et2O (0.8 mL, 6 mmol) was added slowly at room temperature. This was stirred at 65° C. under N2 for 2 hours and then the solvent was removed in vacuum and the residue was suspended in a small amount of methanol. To the solution was added NH3.H2O (0.5 mL). It was stirred at room temperature, then concentrated and loaded onto silica gel. It was purified by column chromatography on silica gel with 0-25% MeOH (containing 2% NH3.H2O) in DCM to give a brown powder (0.10 g, 30% yield). 1 H NMR (300MHz, MeOH-d4) δ7.78(d,J=0.8Hz,1H),7.47(d,J=3.3Hz,1H),6.93(dd,J=3.3,0.8Hz,1H). MS(ESI):C 10 H 10 BrN6 + 278.00[M+H] + Calculated value for, measured value 277.85 [M+H] + .

[0116] Preparation of intermediate D: 7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4-diamine. [ka] 7H-Pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4-diamine To a mixture of 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (177 mg, 1 mmol), guanidine carbonate (721 mg, 4 mmol) and anhydrous potassium carbonate (276 mg, 2 mmol) was added NMP (15 mL). The resulting mixture was sealed under nitrogen and heated in a microwave at 150 °C for 3.5 h. After cooling to room temperature, the solvent was removed under vacuum and the residue was loaded onto silica gel and purified by column chromatography on silica gel with 0-50% MeOH (with 2% NH3H2O) in DCM to recover the product as a light brown powder (136 mg, 68% yield). 1 H NMR (300MHz, DMSO-d6) δ12.11(sbr,1H),8.94(sbr,1H),7.43(dd,J=6.2,1.78Hz,1H),6.96(sbr,2H),6.79(dd,J=6.2,1.78Hz,1H),6.41(sbr,2H). MS(ESI):C9H9N6 + 200.95[M+H] + Calculated value, measured value 201.05 [M+H] + .

[0117] Preparation of intermediate E: 7H-pyrazolo[3,4-h]quinazoline-2,4-diamine. [ka] 7H-Pyrazolo[3,4-h]quinazoline-2,4-diamine To a mixture of 4-chloro-1H-indazole-5-carbonitrile (100 mg, 0.56 mmol), guanidine carbonate (406 mg, 2.24 mmol) and anhydrous potassium carbonate (155 mg, 1.12 mmol) was added NMP (8 mL). The resulting mixture was sealed under nitrogen and heated in a microwave at 150 °C for 2 h. After cooling to room temperature, the solvent was removed under vacuum and the residue was loaded onto silica gel and purified on a silica gel column with 0-30% MeOH (with 2% NH3H2O) in DCM to recover the product as a light brown powder (38 mg, 34% yield). 1H NMR(300MHz,MeOH-d4)δ8.43(s,1H),7.85(d,J=8.4Hz,1H),7.34(d,J=8.4Hz,1H).MS(ESI):C9H9N6 + 201.09[M+H] + Calculated value, measured value 200.90 [M+H] + .

[0118] General synthetic procedures for the preparation of example compounds. To a solution of intermediates A-E or 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (1 eq.) in anhydrous DMF (1 mL / 1 mmol), NaH (60% in mineral oil, 1.5 eq.) was added under nitrogen. After stirring at room temperature for 10 min, the bromide or anhydride (1 eq.) was added. The reaction mixture was stirred at room temperature overnight, then treated with water, and the precipitate was filtered, washed with water, and dried. It was then loaded onto silica gel and purified by column chromatography on silica gel using MeOH in DCM as eluent.

[0119] Example 1 describes a representative synthesis using the general procedures described in the paragraph above.

[0120] Example 1. Preparation of 7-benzyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-Benzyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine To a solution of 7H-pyrrolo[2,3-h]-quinazoline-2,4-diamine (40 mg, 0.2 mmol) in anhydrous DMF (0.2 mL) was added NaH (60% in mineral oil, 12 mg, 0.3 mmol) under nitrogen. After stirring at room temperature for 10 min, benzyl bromide (24 μL, 0.2 mmol) was added. The reaction mixture was stirred at room temperature overnight, then treated with water, and the precipitate was filtered, washed with water, and dried. It was then suspended in DCM, loaded onto silica gel, and purified by column chromatography on silica gel using 0-10% MeOH in DCM as eluent to give the product as a white powder (12 mg, 21% yield). 1 H NMR(300MHz,CD3COCD3)δ7.60(d,J=8.7Hz,1H),7.31(m,3H),7.26(m,2H),7.16(m,2H),7.06(d,J=3.0Hz,1H),6.50(s br,2H),5.52(s br,2H),5.46(s,2H). MS(ESI):C 17 H 16 N5 + 290.13[M+H] + Calculated value for, measured value 289.80 [M+H] + .

[0121] Examples 2-53 were prepared following the procedures outlined in Example 1, General Synthetic Schemes and General Synthetic Procedures.

[0122] Example 2. Preparation of 7-(4-bromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(4-Bromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A light brown powder (182 mg, 20% yield) was obtained from 7H-pyrrolo[2,3-h]-quinazoline-2,4-diamine (500 mg, 2.5 mmol). 1H NMR(300MHz,DMSO-d6)δ7.63(d,J=9.3Hz,1H),7.49(d,J=8.4Hz,2H),7.41(m,1H),7 .19(m,1H),7.11(d,J=8.4Hz,2H),6.80(d,J=3.0Hz,1H),6.08(br,2H),5.43(s,2H). MS(ESI):C 17 H 15 BrN5 + 368.04[M+H] + Calculated value for, measured value 367.85 [M+H] + .

[0123] Example 3. Preparation of 7-(3-bromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(3-Bromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (19 mg, 26% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.2 mmol). MS (ESI): 17 H 15 BrN5 + 368.04[M+H] + Calculated value for, measured value 367.85 [M+H] + .

[0124] Example 4. Preparation of 7-(2-bromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(2-Bromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (33 mg, 18% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1H NMR(300MHz,CDCl3)δ7.61(m,1H),7.19(m,1H),7.15(m,2H),7.13(m,2H),7.06(d,J=8.7Hz,1H),6.45(m,1H),5.44(s,2H),5.29(s br,2H),4.91(s br,2H). MS(ESI):C 17 H 15 BrN5 + 368.04[M+H] + Calculated value for, measured value 367.90 [M+H] + .

[0125] Example 5. Preparation of 4-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)benzonitrile. [ka] 4-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)benzonitrile A white powder (38 mg, 24% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR(300MHz,CDCl3)δ7.59(d,J=8.4Hz,2H),7.28(d,J=9.0Hz,1H),7.19(d,J=9.0Hz,1H) ,7.14(d,J=9.0Hz,1H),7.12(d,J=8.7Hz,2H),6.99(d,J=8.7Hz,1H),5.46(s,2H),5.28(s br,2H),4.90(s br,2H). MS(ESI):C 18 H 15 N6 + 315.13[M+H] + Calculated value, measured value 314.90 [M+H] + .

[0126] Example 6. Preparation of 3-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)benzonitrile. [ka] 3-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)benzonitrile A white powder (31 mg, 20% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). MS (ESI): 18 H 15 N6 + 315.13[M+H] + Calculated value, measured value 314.90 [M+H] + .

[0127] Example 7. Preparation of 7-(4-(trifluoromethyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(4-(trifluoromethyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (34 mg, 19% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR (300MHz, CDCl3) δ7.54(d,J=7.2Hz,2H),7.28(m,1H),7.17(m,4H),7.03(d,J=9.0Hz,1H),5.45(s,2H),5.28(s br,2H),4.89(s br,2H). MS(ESI):C 18 H 15 F3N5 + 358.12[M+H] + Calculated value for, measured value 357.90 [M+H] + .

[0128] Example 8. Preparation of 7-(3-(trifluoromethyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(3-(trifluoromethyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (78 mg, 44% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR(300MHz,CDCl3)δ7.53(d,J=7.8Hz,1H),7.42(s,1H),7.38(d,J=7.5Hz,1H) ,7.29(d,J=9.0Hz,1H),7.17(m,3H),7.05(d,J=8.7Hz,1H),5.44(s,2H),5.29(s br,2H),4.91(s br,2H). MS(ESI):C 18 H 15 F3N5 + 358.12[M+H] + Calculated value for, measured value 357.90 [M+H] + .

[0129] Example 9. Preparation of 7-(4-(trifluoromethoxy)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(4-(trifluoromethoxy)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (36 mg, 19% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR(300MHz,CDCl3)δ7.56(d,J=7.2Hz,1H),7.38(m,2H),7.29(d,J=9.0Hz,1H),7. 23(m,1H),7.15(dd,J=13.8,3.0Hz,2H),7.02(d,J=8.7Hz,1H),5.42(s,2H),5.30(s br,2H),4.92(s br,2H). MS(ESI):C 18 H 15 F3N5O + 374.12[M+H] + Calculated value for, measured value 373.90 [M+H] + .

[0130] Example 10. Preparation of 7-(4-isopropylbenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(4-isopropylbenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (92 mg, 55% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR(300MHz,CDCl3)δ7.27(d,J=9.0Hz,1H),7.19(m,5H),7.14(m,2H),7.01(d,J=8.1Hz,2H),5.35(s,2H),5.28(s br,2H),4.89(s br,2H),2.86(m,1H),1.21(d,J=6.9Hz,6H). MS(ESI):C 20 H 22 N5 + 332.18[M+H] + Calculated value for, measured value 332.00 [M+H] + .

[0131] Example 11. Preparation of 7-(3-fluoro-4-(trifluoromethyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(3-fluoro-4-(trifluoromethyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (59 mg, 31% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1H NMR(300MHz,CDCl3)δ7.53(t,J=7.8Hz,1H),7.30(d,J=8.7Hz,2H),7.16(d,J=3.0Hz,1H), 7.02(d,J=8.7Hz,1H),6.90(d,J=9.0Hz,1H),6.84(d,J=11.1Hz,1H),5.44(s,2H),5.35(s br,2H). MS(ESI):C 18 H 14 F4N5 + 376.11[M+H] + Calculated value for, measured value 375.95 [M+H] + .

[0132] Example 12. Preparation of 7-(5-chloro-2-fluorobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(5-chloro-2-fluorobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (62 mg, 36% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR(300MHz,CDCl3)δ7.32(d,J=9.0Hz,1H),7.17(m,3H),7.12(d,J=9.0Hz,1H),7.05(t,J=9.0Hz,1H),6.73(dd,J=6.9,3.0Hz,1H),5.39(s,2H),5.29(s br,2H),4.89(s br,2H). MS(ESI):C 17 H 14 ClFN5 + 342.08[M+H] + Calculated value for, measured value 341.85 [M+H] + .

[0133] Example 13. Preparation of 7-(2,5-dichlorobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(2,5-Dichlorobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine An off-white powder (8 mg, 13% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.2 mmol). MS (ESI): 17 H 14 Cl2N5 + 358.05[M+H] + Calculated value for, measured value 357.90 [M+H] + .

[0134] Example 14. Preparation of 7-(3,5-dimethoxybenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(3,5-Dimethoxybenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (108 mg, 62% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR(300MHz,CDCl3)δ7.27(d,J=9.0Hz,1H),7.15(m,2H),7.11(d,J=8.7Hz,1H),6.34(t,J=2.1Hz,1H),6.21(d,J=2.4Hz,2H),5.31(s,2H),5.28(s br,2H),4.89(s br,2H),3.68(s,6H). MS(ESI):C 19 H 20 N5O2 + 350.15[M+H] + Calculated value for, measured value 349.95 [M+H] + .

[0135] Example 15. Preparation of 7-(4-phenoxybenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(4-Phenoxybenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (35 mg, 33% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (56 mg, 0.28 mmol). 1 H NMR(300MHz,CD3COCD3)δ8.19(br,2H),7.92(d,J=9.0Hz,1H),7.66(m,2H),7. 36(m,2H),7.30(d,J=8.7Hz,2H),7.11(m,2H),6.92-6.99(m,4H),5.59(s,2H). MS(ESI):C 23 H 20 N5O + 382.16[M+H] + Calculated value for, measured value 381.95 [M+H] + .

[0136] Example 16. Preparation of (4-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)phenyl)(phenyl)methanone. [ka] (4-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)phenyl)(phenyl)methanone A white powder (35 mg, 18% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR(300MHz,CDCl3)δ7.71-7.80(m,5H),7.57(m,2H),7.45(m,3H),7.17(m,2H),7.08(d,J =9.0 Hz,1H),5.48(s,2H),5.28(s br,2H),4.90(s br,2H). MS(ESI):C 24 H 20 N5O + 394.16[M+H] + Calculated value for, measured value 393.95 [M+H] + .

[0137] Example 17. Preparation of 7-([1,1'-biphenyl]-4-ylmethyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] Preparation of 7-([1,1'-biphenyl]-4-ylmethyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. A white powder (28 mg, 26% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (60 mg, 0.3 mmol). 1 H NMR(300MHz,CD3COCD3)δ7.50-7.58(m,4H),7.36-7.43(m,3H),7.26(m,2H),7.20(d,J=8.4Hz,2H),7.15(d,J=9.0Hz,1H),7.06(d,J=3.0Hz,1H),6.35(s br,2H),5.48(s,2H),5.35(s br,2H). MS(ESI):C 23 H 20 N5 + 366.16[M+H] + Calculated value, measured value 366.00 [M+H] + .

[0138] Example 18. Preparation of 7-([1,1'-biphenyl]-3-ylmethyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-([1,1'-biphenyl]-3-ylmethyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine An off-white powder (25 mg, 23% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (60 mg, 0.3 mmol). MS (ESI): 23 H 20 N5 + 366.16[M+H] + Calculated value for, measured value 365.95 [M+H] + .

[0139] Example 19. Preparation of 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile. [ka] 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile An off-white powder (27 mg, 23% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (60 mg, 0.3 mmol). 1 H NMR(300MHz,CD3OD)δ7.79(d,J=7.8Hz,1H),7.68(m,1H),7.60(d,J=9.0Hz,1H),7.41 -7.56(m,5H),7.36(d,J=3.0Hz,1H),7.25(m,2H),7.07(d,J=3.3Hz,1H),5.53(s,2H). MS(ESI):C 24 H 19 N6 + 391.16[M+H] + Calculated value for, measured value 390.95 [M+H] + .

[0140] Example 20. Preparation of methyl 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-[1,1'-biphenyl]-4-carboxylate. [ka] Methyl 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-[1,1'-biphenyl]-4-carboxylate A white powder (29 mg, 14% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1H NMR(300MHz,CDCl3)δ8.08(d,J=8.4Hz,2H),7.60(d,J=8.4Hz,2H),7.55(d,J=8.1Hz ,2H),7.29(d,J=8.7Hz,1H),7.18(m,4H),7.12(d,J=8.7Hz,1H),5.45(s,2H),5.27(s br,2H),4.90(s br,2H),3.93(s,3H). MS(ESI):C 25 H 22 N5O2 + 424.18[M+H] + Calculated value for, measured value 423.95 [M+H] + .

[0141] Example 21. Preparation of 7-(naphthalen-2-ylmethyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(Naphthalen-2-ylmethyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (20 mg, 18% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (64 mg, 0.32 mmol). 1 H NMR (300MHz, CDCl3) δ8.17(s,1H),7.92(m,3H),7.80(m,1H),7.73(m,1H),7.59(m,2H),7.44(m,3H),5.33(s,2H). MS(ESI):C 21 H 18 N5 + 340.15[M+H] + Calculated value, measured value 339.90 [M+H] + .

[0142] Example 22. Preparation of 7-((5-bromopyridin-2-yl)methyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-((5-bromopyridin-2-yl)methyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A light brown powder (27 mg, 15% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR(300MHz,CDCl3)δ8.65(d,J=2.4Hz,1H),7.64(dd,J=8.4,2.4Hz,1H),7.28(d,J=8.7 Hz,1H),7.19(s,2H),7.06(d,J=9.0Hz,1H),6.51(d,J=8.1Hz,1H),5.47(s,2H),5.27(s br,2H),4.88(s br,2H). MS(ESI):C 16 H 14 BrN6 + 369.05[M+H] + Calculated value for, measured value 368.85 [M+H] + .

[0143] Example 23. Preparation of 7-((1-methyl-1H-benzo[d]imidazol-2-yl)methyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-((1-methyl-1H-benzo[d]imidazol-2-yl)methyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A light brown powder (45 mg, 26% yield) was obtained from 7H-pyrrolo[2,3-h]-quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR(300MHz,DMSO-d6)δ7.63(d,J=9.0Hz,1H),7.56(d,J=7.5Hz,1H),7.50(d,J=8.1Hz,1H),7.39(d,J=3.0Hz ,1H),7.28(m,1H),7.20(m,1H),7.18(m,1H),6.81(d,J=3.0Hz,1H),6.00(br,2H),5.79(s,2H),3.73(s,3H). MS(ESI):C 19 H 18 N7 +343.90[M+H] + Calculated value for, measured value 344.10 [M+H] + .

[0144] Example 24. Preparation of 7-((4-phenylthiazol-2-yl)methyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-((4-phenylthiazol-2-yl)methyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (52 mg, 30% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR (300MHz, DMSO-d6) δ7.88(d,J=7.5Hz,2H),7.42(m,2H),7.36(m,4H),7.20(m,2H),5.72(s,2H),5.31(sbr,2H),4.90(sbr,2H). MS(ESI):C 20 H 17 N6S + 373.12[M+H] + Calculated value for, measured value 372.90 [M+H] + .

[0145] Example 25. Preparation of 7-(3-methylbut-2-en-1-yl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(3-Methylbut-2-en-1-yl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (15 mg, 28% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.2 mmol). 1H NMR(300MHz,CD3OD)δ7.61(d,J=9.0Hz,1H),7.24(d,J=9.0Hz,1H),7.20(d,J=3.0Hz,1H ),6.96(d,J=3.3Hz,1H),5.38(m,1H),4.80(d,J=6.9Hz,2H),1.86(s,3H),1.77(s,3H). MS(ESI):C 15 H 18 N5 + 268.15[M+H] + Calculated value for, measured value 267.85 [M+H] + .

[0146] Example 26. Preparation of 7-(cyclohex-2-en-1-yl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(Cyclohex-2-en-1-yl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (8 mg, 12% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (48 mg, 0.24 mmol). 1 H NMR(300MHz,CD3COCD3)δ7.93(d,J=8.7Hz,1H),7.71(d,J=9.0Hz,1H),7.51(d,J=3.0Hz,1H ),7.04(d,J=3.0Hz,1H),6.20(m,1H),5.83(m,1H),5.34(m,1H),2.17(m,4H),1.76(m,2H).

[0147] Example 27. Preparation of 7-(cyclohexylmethyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(Cyclohexylmethyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (56 mg, 38% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol).1 H NMR(300MHz,CDCl3)δ7.29(d,J=9.0Hz,1H),7.17(d,J=9.0Hz,1H),7.07(s,2H),5.28(s br,2H),4.88(s br,2H),3.98(d,J=8.4Hz,2H),1.84(m,1H),1.53-1.72(m,10H). MS(ESI):C 17 H 22 N5 + 296.18[M+H] + Calculated value for, measured value 295.95 [M+H] + .

[0148] Example 28. Preparation of 7-(cyclopropylmethyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(Cyclopropylmethyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (47 mg, 37% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR(300MHz,CDCl3)δ7.31(d,J=9.0Hz,1H),7.23(d,J=3.0Hz,1H),7.21(d,J=9.0,Hz,1H),7.09(d,J=3.0Hz,1H),5.27(s br,2H),4.86(s br,2H),4.04(d,J=6.3Hz,2H),1.29(m,1H),0.65(m,2H),0.38(m,2H). MS(ESI):C 14 H 16 N5 + 254.14[M+H] + Calculated value for, measured value 253.90 [M+H] + .

[0149] Example 29. Preparation of (2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)(phenyl)methanone. [ka] (2,4-Diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)(phenyl)methanone A white powder (58 mg, 38% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol) and benzoic anhydride (113 mg, 0.5 mmol). 1 H NMR(300MHz,CD3COCD3)δ7.81(d,J=8.7Hz,1H),7.64(m,2H),7.53(m,1H),7. 49(m,1H),7.42(m,2H),7.16(d,J=3.9Hz,1H),7.07(d,J=3.6Hz,1H),5.91(s br,2H),5.02(s br,2H). MS(ESI):C 17 H 14 N5O + 304.11[M+H] + Calculated value, measured value 303.90 [M+H] + .

[0150] Example 30. Preparation of 7-(3-bromobenzyl)-8-methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(3-Bromobenzyl)-8-methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (40 mg, 21% yield) was obtained from 8-methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR (300MHz, DMSO-d6) δ7.44(m,2H),7.37(m,1H),7.25(t,J=7.5Hz,1H),7.01(s,1H),6.91(d,J=8.1Hz,1H),6.74(s,1H),5.52(s,2H),2.36(s,3H). MS(ESI):C 23 H 20 N5O + 382.16[M+H] + Calculated value for, measured value 381.85 [M+H] + .

[0151] Example 31. Preparation of 4'-((2,4-diamino-8-methyl-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile. [ka] 4'-((2,4-diamino-8-methyl-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile A white powder (46 mg, 23% yield) was obtained from 8-methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). 1 H NMR (300MHz, DMSO-d6) δ7.92(m,1H),7.82(m,1H),7.74(m,2H),7.50-7.59(m,5H),7.12(d,J=8.4Hz,1H),6.80(s,1H),5.64(s,2H),2.34(s,3H). MS(ESI):C 25 H 21 N6 + 405.17[M+H] + Calculated value for, measured value 405.05 [M+H] + .

[0152] Example 32. Preparation of 7-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-8-methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-8-methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine To a solution of 8-methyl-7H-pyrrolo[2,3-h]-quinazoline-2,4-diamine (100 mg, 0.5 mmol) in anhydrous DMF (0.5 mL) was added NaH (60% in mineral oil, 30 mg, 0.75 mmol) under nitrogen. After stirring at room temperature for 10 min, 5-(4'-(bromomethyl)-[1,1'-biphenyl]-2-yl)-1-trityl-1H-tetrazole (279 mg, 0.5 mmol) was added. The reaction mixture was stirred at room temperature overnight, then treated with water, and the precipitate was filtered, washed with water, and dried. It was then suspended in DCM, loaded onto silica gel, and purified by column chromatography on silica gel using 0-10% MeOH in DCM as eluent to give the intermediate, which was purified by column chromatography on silica gel. It was then dissolved in MeOH (5 mL) and treated with HCl solution (4 M in dioxane, 0.5 mL, 2 mmol). The mixture was stirred at room temperature for 4 h and concentrated in vacuo. The residue was dissolved in MeOH and neutralized with DIPEA. After removal of the solvent, it was purified by column chromatography on silica gel using MeOH in DCM as eluent to give a white powder (43 mg, 19% yield). 1 H NMR(300MHz,DMSO-d6)δ7.82(m,1H),7.57(m,2H),7.52(m,1H),7.49(m,1H),7.43( m,1H),7.19(m,2H),7.04(d,J=8.4Hz,2H),6.90(s,1H),5.52(s,2H),2.37(s,3H). MS(ESI):C 25 H 22 N9 + 448.19[M+H] + Calculated value for, measured value 448.05 [M+H] + .

[0153] Example 33. Preparation of 7-(benzo[d]thiazol-2-ylmethyl)-8-methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(benzo[d]thiazol-2-ylmethyl)-8-methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A light brown powder (45 mg, 25% yield) was obtained from 8-methyl-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (100 mg, 0.5 mmol). MS (ESI): C 19 H 17 N6S + 361.12[M+H] + Calculated value for, measured value 360.90 [M+H] + .

[0154] Example 34. 7-(5-Bromo-2-fluorobenzyl)-7H-pyrrolo[2,3- h] Preparation of quinazoline-2,4-diamine. [ka] 7-(5-Bromo-2-fluorobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine An off-white powder (10 mg, 13% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1 H NMR (300MHz, CD3OD) δ7.66(d,J=9.3Hz,1H)7.44(m,1H),7.36(d,J=3.3Hz,1H),7.29(d,J=8.7Hz,1H),7.12-7.03(m,3H),5.50(s,2H). MS(ESI):C 17 H 14 BrFN5 + 386.04[M+H] + Calculated value for, measured value 385.95 [M+H] + .

[0155] Example 35. Preparation of 7-(2,4-dibromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(2,4-Dibromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A beige powder (29 mg, 32% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1 H NMR (300MHz, CD3OD) δ7.83(s,1H),7.59(d,J=10.2Hz,1H),7.34(d,J=8.4Hz,1H),7.26(m,1H),7.08-7.05(m,2H),6.43(d,J=7.8Hz,1H),5.45(s,2H). MS(ESI):C 17 H 14 Br2N5 + 447.96[M+H] + Calculated value for, measured value 447.90 [M+H] + .

[0156] Example 36. Preparation of 7-((2'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-((2'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A beige powder (12 mg, 14% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1 H NMR(300MHz,CD3OD)δ7.74(d,J=7.5Hz,1H),7.67-7.57(m,2H),7.50(m,1H), 7.38(d,J=3.0Hz,1H),7.31-7.17(m,6H),7.05(d,J=3.0Hz,1H),5.53(s,2H). MS(ESI):C 24 H 19 F3N5 + 434.16[M+H] + Calculated value for, measured value 434.05 [M+H] + .

[0157] Example 37. Preparation of 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-4-fluoro-[1,1'-biphenyl]-2-carbonitrile. [ka] 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl) -4-Fluoro-[1,1'-biphenyl]-2-carbonitrile A white powder (24 mg, 29% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1 H NMR(300MHz,DMSO-d6)δ7.94(m,1H),7.62(m,3H),7.47(m,3H),7.31-7.22(m,3H),7.04(s br,2H),6.81(d,J=2.4Hz,1H),6.00(s br,2H),5.54(s,2H). MS(ESI):C 24 H 18 FN6 + 409.16[M+H] + Calculated value for, measured value 409.05 [M+H] + .

[0158] Example 38. Preparation of 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-2'-fluoro-[1,1'-biphenyl]-2-carbonitrile. [ka] 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-2'-fluoro-[1,1'-biphenyl]-2-carbonitrile An off-white powder (35 mg, 43% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1H NMR(300MHz,DMSO-d6)δ7.94(d,J=7.5Hz,1H),7.77(m,1H),7.66-7.53(m,3H),7.46-7.40(m,2H),7.26-7.17(m,2H),7.09(d,J=7.8Hz,1H),7.00(s br,2H),6.82(d,J=2.7Hz,1H),5.95(sbr,2H),5.56(s,2H). MS(ESI):C 24 H 18 FN6 + 409.16[M+H] + Calculated value, measured value 409.00 [M+H] + .

[0159] Example 39. Preparation of 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-3'-fluoro-[1,1'-biphenyl]-2-carbonitrile. [ka] 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-3'-fluoro-[1,1'-biphenyl]-2-carbonitrile A white powder (32 mg, 39% yield) was obtained from 7H-pyrrolo[2,3-h]-quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1 H NMR(300MHz,DMSO-d6)δ7.60(s,2H),7.56(d,J=7.8Hz,1H),7.46(d,J=9.0Hz,1H),7.40(m,1H),7.27- 7.10(m,4H),7.46(d,J=9.0Hz,1H),6.99(d,J=8.1Hz,2H),6.76(m,1H),6.62(d,J=3.0Hz,1H),5.89(s br,2H),5.29(s,2H). MS(ESI):C 24 H 18 FN6 + 409.15[M+H] + Calculated value, measured value 409.00 [M+H] + .

[0160] Example 40. Preparation of 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-2',3'-difluoro-[1,1'-biphenyl]-2-carbonitrile. [ka] 4'-((2,4-diamino-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-2',3'-difluoro-[1,1'-biphenyl]-2-carbonitrile A yellow powder (20 mg, 23% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1 H NMR (300MHz, DMSO-d6) δ7.60(m,3H),7.45(m,1H),7.33-7.19(m,4H),6.92(m,1H),6.59(m,1H),5.43(s,2H). MS(ESI):C 24 H 17 F2N6 + 427.15[M+H] + Calculated value for, measured value 427.05 [M+H] + .

[0161] Example 41. Preparation of 7-(3-phenylprop-2-yn-1-yl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(3-phenylprop-2-yn-1-yl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine An off-white powder (12 mg, 19% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1 H NMR (300MHz, DMSO) 7.75 (d, J = 8.7 Hz, 1H), 7.50-7.28 (m, 9H), 6.83 (d, J = 3.6 Hz, 1H), 6.28 (s br, 2H), 5.39 (s, 2H). MS(ESI):C 19 H 16 N5 + 314.14[M+H]+ Calculated value, measured value 314.00 [M+H] + .

[0162] Example 42. Preparation of 7-(4-ethynylbenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(4-ethynylbenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A beige powder (16 mg, 25% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1 H NMR(300MHz,DMSO-d6)δ7.62(d,J=9.3Hz,1H),7.39(d,J=7.2Hz,2H),7.14(d,J=7.8Hz,2H),7.08(s br,2H),6.80(s,1H),6.02(s br,2H),5.46(s,2H),4.14(s,1H). MS(ESI):C 19 H 16 N5 + 314.14[M+H] + Calculated value, measured value 314.00 [M+H] + .

[0163] Example 43. Preparation of 7-(4-(phenylethynyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(4-(phenylethynyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (25 mg, 32% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1H NMR (300MHz, DMSO-d6) δ7.77(d,J=7.5Hz,1H),7.58(s,1H),7.54-7.35(m,9H),7.20(m,1H),6.98(s,1H),5.54(s,2H). MS(ESI):C 25 H 20 N5 + 390.16[M+H] + Calculated value, measured value 390.00 [M+H] + .

[0164] Example 44. Preparation of 7-(3-(phenylethynyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(3-(phenylethynyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A white powder (20 mg, 26% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1 H NMR (300MHz, DMSO-d6) δ7.83(d,J=9.3Hz,1H),7.69(s,1H),7.61-7.30(m,9H),7.25(m,1H),7.02(s,1H),5.55(s,2H). MS(ESI):C 25 H 20 N5 + 390.16[M+H] + Calculated value for, measured value 390.05 [M+H] + .

[0165] Example 45. Preparation of 7-(3-((2-(trifluoromethyl)phenyl)ethynyl)benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 7-(3-((2-(trifluoromethyl)phenyl)ethynyl) Benzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine benzyl A white powder (26 mg, 28% yield) was obtained from 7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (40 mg, 0.20 mmol). 1 H NMR (300MHz, DMSO) δ7.82-7-75(m,2H),7.71-7.64(m,2H),7.59(m,1H),7.46-7.34(m,4H),7.24(m,2H),6.84(s,1H),5.51(s,2H). MS(ESI):C 26 H 19 F3N5 + 458.15[M+H] + Calculated value for, measured value 458.05 [M+H] + .

[0166] Example 46. Preparation of 4'-((2,4-diamino-5-bromo-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-2'-fluoro-[1,1'-biphenyl]-2-carbonitrile. [ka] 4'-((2,4-diamino-5-bromo-7H-pyrrolo[2,3-h]quinazolin-7-yl)methyl)-2'-fluoro-[1,1'-biphenyl]-2-carbonitrile A white powder (26 mg, 53% yield) was obtained from 5-bromo-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (28 mg, 0.1 mmol). 1 H NMR(300MHz,CDCl3)δ7.76(d,J=8.1Hz,1H),7.65(dd,J=8.1,1.5Hz,1H),7.84(t,J=7.8Hz,2H),7.37(t,J =7.8Hz,1H),7.35(s,1H),7.13(m,2H),6.93(d,J=7.8Hz,1H),6.86(d,J=14.4Hz,1H),5.38(s,2H),4.87(s br,2H). MS(ESI):C 24 H 17 BrFN6 + 487.07[M+H] + Calculated value, measured value 487.00 [M+H] + .

[0167] Example 47. Preparation of 5-bromo-7-(3-bromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 5-Bromo-7-(3-bromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine An off-white powder (18 mg, 40% yield) was obtained from 5-bromo-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (28 mg, 0.1 mmol). 1 H NMR(300MHz,MeOH-d4)δ7.55(d,J=0.9Hz,1H),7.43(m,1H),7.33(d,J=3.2Hz,1H),7.3 2(m,1H),7.23(t,J=8.0Hz,1H),7.09(m,1H),7.02(dd,J=3.0,0.8Hz,1H),5.42(s,2H). MS(ESI):C 17 H 14 Br2N5 + 447.96[M+H] + Calculated value for, measured value 447.85 [M+H] + .

[0168] Example 48. 5-Bromo-N 2 Preparation of ,7-bis(3-bromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine. [ka] 5-Bromo-N 2 ,7-Bis(3-bromobenzyl)-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine A brown powder (9 mg, 15% yield) was obtained from 5-bromo-7H-pyrrolo[2,3-h]quinazoline-2,4-diamine (28 mg, 0.1 mmol) as a by-product. 1H NMR(300MHz,CDCl3)δ7.57(s,1H),7.42(m,1H),7.39(m,1H),7.35(m,1H),7.27(s,1H),7.20(m ,2H),7.18(m,1H),7.13(m,1H),7.10(d,J=3.2Hz,1H),7.93(m,1H),5.28(s,2H),4.71(s,2H). MS(ESI):C 24 H 19 Br3N5 + 615.92[M+H] + Calculated value for, measured value 615.85 [M+H] +

[0169] Example 49. Preparation of 4'-((2,4-diamino-7H-pyrrolo[3,2':5,6]pyrido[4,3-d]pyrimidin-7-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile. [ka] 4'-((2,4-diamino-7H-pyrrolo[3,2':5,6]pyrido[4,3-d]pyrimidin-7-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile Following the general synthesis described for Intermediate D, 4-chloro-1-((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (100 mg, 0.27 mmol) was obtained as a white powder (42 mg, 40% yield). 1 H NMR(300MHz,DMSO-d6)δ8.87(s,1H),7.90(d,J=8.0Hz,1H),7.75(t,J=8.0H z,2H),7.55(d,J=7.8Hz,2H),7.49(m,2H),7.13(m,2H),6.70(s,1H),6.57(s br,2H),5.57(s,2H). MS(ESI):C 23 H 18 N7 + 392.16[M+H] + Calculated value for, measured value 392.05 [M+H] + .

[0170] The requisite intermediates were prepared as follows: [ka] 4-Chloro-1-((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile To a solution of 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (53 mg, 0.3 mmol) in anhydrous DMF (0.5 mL) was added NaH (60% in mineral oil, 18 mg, 0.45 mmol) under nitrogen. After stirring at room temperature for 10 min, 4'-(bromomethyl)-[1,1'-biphenyl]-2-carbonitrile (82 mg, 0.3 mmol) was added. The reaction mixture was stirred at room temperature for 3 h, then treated with water, extracted with DCM, washed with water, brine and dried. After concentration, it was purified by column chromatography on silica gel using EtOAc in hexane as eluent to give the product as a white powder (100 mg, 90% yield). 1 H NMR(300MHz,CDCl3)δ8.55(s,1H),7.76(d,J=7.8Hz,1H),7.64(t,J=8.0Hz,1H),7.52(d,J=8.0Hz,2H), 7.46(d,J=7.8Hz,2H),7.41(d,J=3.6Hz,1H),7.32(d,J=8.1Hz,2H),6.73(d,J=3.6Hz,1H),5.57(s,2H).

[0171] Example 50. Preparation of 7-(3-bromobenzyl)-7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4-diamine. [ka] 7-(3-Bromobenzyl)-7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4-diamine An off-white powder (18 mg, 24% yield) was obtained from 7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4-diamine (40 mg, 0.2 mmol). 1H NMR(300MHz,MeOH-d4)δ8.87(s,1H),7.41(m,1H),7.37(m,2H),7.22(m,1H),7.17(m,1H),6.94(d,J=3.5Hz,1H),5.54(s,2H). MS(ESI):C 16 H 14 BrN6 + 369.05[M+H] + Calculated value for, measured value 368.90 [M+H] + .

[0172] Example 51. Preparation of 4'-((2,4-diamino-7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-7-yl)methyl)-2'-fluoro-[1,1'-biphenyl]-2-carbonitrile. [ka] 4'-((2,4-diamino-7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-7-yl)methyl)-2'-fluoro-[1,1'-biphenyl]-2-carbonitrile A white powder (21 mg, 35% yield) was obtained from 7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4-diamine (30 mg, 0.15 mmol). 1 H NMR(300MHz,MeOH-d4)δ8.87(s,1H),7.82(dd,J=7.8,0.9Hz,1H),7.71(td,J=8.,1.4Hz,1H),7.56(td,J=7.8,1.3Hz,1H ),7.50(d,J=8.1Hz,1H),7.42(d,J=3.6Hz,1H),7.36(d,J=7.8Hz,1H),7.10(m,2H),6.98(d,J=3.4Hz,1H),5.64(s,2H). MS(ESI):C 23 H 17 FN7 + 410.15[M+H] + Calculated value for, measured value 410.05 [M+H] + .

[0173] Example 52. Preparation of 4'-((4-amino-2-(((2'-cyano-2-fluoro-[1,1'-biphenyl]-4-yl)methyl)amino)-7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-7-yl)methyl)-2'-fluoro-[1,1'-biphenyl]-2-carbonitrile. [ka] 4'-((4-amino-2-(((2'-cyano-2-fluoro-[1,1'-biphenyl]-4-yl)methyl)amino)-7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-7-yl)methyl)-2'-fluoro-[1,1'-biphenyl]-2-carbonitrile A brown powder (10 mg, 11% yield) was obtained from 7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4-diamine (30 mg, 0.15 mmol) as a by-product. 1 H NMR(300MHz,CDCl3)δ8.75(s,1H),7.75(m,3H),7.61(m,3H),7.45(m,5H),7. 32(m,1H),7.17(m,1H),7.05(m,2H),6.95(m,1H),5.55(s,2H),4.84(s,2H). MS(ESI):C 37 H 25 F2N8 + 619.22[M+H] + Calculated value for, measured value 619.20 [M+H] + .

[0174] Example 53. Preparation of 7-(4-ethynylbenzyl)-7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4-diamine. [ka] 7-(4-ethynylbenzyl)-7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4-diamine A white powder (21 mg, 45% yield) was obtained from 7H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4-diamine (30 mg, 0.15 mmol). 1 H NMR(300MHz,MeOH-d4)δ8.84(s,1H),7.38(d,J=8.4Hz,2H),7.32(d,J=3.6Hz ,1H),7.15(d,J=8.4Hz,2H),6.93(d,J=3.6Hz,1H),5.55(s,2H),3.10(s,1H). MS(ESI):C 18 H 15 N6 + 315.14[M+H] + Calculated value, measured value 315.00 [M+H] + .

[0175] Example 54: MIC Assay MIC assays for N. gonorrhoeae were performed using the ATCC 49226 strain. The procedural guidelines recommended by the Clinical and Laboratory Standards Institute (CLSI) for broth microdilution MIC assays were modified by substituting Todd Hewitt (TH) broth for cation-adjusted Mueller-Hinton (CAMH) broth. Also, the recommended bacterial inoculum was changed to meet the high inoculum requirements necessary for N. gonorrhoeae growth. 2.5 × 10 ... 7 CFU / mL of log phase bacteria were inoculated. The final volume in each well was 200 μL. Each compound was tested in duplicate. The microtiter plates were incubated in an anaerobic environment for 24 hours at 37°C using the candle jar technique. Bacterial growth was then tested by reading the plates at 600 nm using a SpectraMax iD5 plate reader (Molecular Devices, Inc.). The MIC was defined as the lowest compound concentration that inhibited bacterial growth.

[0176] MIC assays for various Gram-negative and Gram-positive strains were performed according to the CLSI guidelines for broth microdilution. 5 × 10 5 CFU / mL of log phase bacteria were inoculated. The final volume in each well was 100 μL. Each compound was tested in duplicate. The microtiter plates were incubated at 37° C. for 18 hours in an aerobic environment. Bacterial growth was then tested by reading the plates at 600 nm using a SpectraMax iD5 plate reader (Molecular Devices, Inc.). The MIC was defined as the lowest compound concentration that inhibited bacterial growth.

[0177] The following Gram-negative and Gram-positive strains were used in the aerobic MIC procedure: P. aeruginosa ATCC27853 A. baumannii ATCC19606 E. coli ATCC25922 E. coli W4573 E. coli N43 K. pneumoniae ATCC10031 K. pneumoniae ATCC13883 S. sonnei ATCC29930 P. mirabilis ATCC29906 Methicillin-susceptible S. aureus (MSSA) ATCC19636 Methicillin-resistant S. aureus (MRSA) ATCC33951

[0178] Example 55. The following may illustrate representative pharmaceutical dosage forms containing a compound of formula I ("Compound X") or a pharma- ceutically acceptable salt thereof for therapeutic or prophylactic use in humans. Tablets may optionally include an enteric coating. (i) Tablets 1 mg / tablet Compound X= 100.0 Lactose 77.5 Povidone 15.0 Croscarmellose sodium 12.0 Crystalline cellulose 92.5 Magnesium stearate 3.0 300.0 (ii) Tablets 2 mg / tablet Compound X= 20.0 Crystalline cellulose 410.0 Starch 50.0 Sodium starch glycolate 15.0 Magnesium stearate 5.0 500.0 (iii) Capsules mg / capsule Compound X= 10.0 Colloidal silicon dioxide 1.5 Lactose 465.5 Pregelatinized starch 120.0 Magnesium stearate 3.0 600.0 (iv) Injection 1 (1 mg / mL) mg / mL Compound X=(free acid form) 1.0 Sodium phosphate dibasic 12.0 Sodium phosphate monobasic 0.7 Sodium chloride 4.5 1.0N sodium hydroxide solution (Adjust pH to 7.0-7.5) qs Water for injection qsad 1mL (v) Injection 2 (10mg / mL) mg / mL Compound X=(free acid form) 10.0 Sodium phosphate monobasic 0.3 Sodium phosphate dibasic 1.1 Polyethylene glycol 400 200.0 1.0N sodium hydroxide solution (Adjust pH to 7.0-7.5) qs Water for injection qsad 1mL (vi) Aerosol mg / can Compound X= 20.0 Oleic acid 10.0 Trichloromonofluoromethane 5,000.0.0 Dichlorodifluoromethane 10,000.0 Dichlorotetrafluoroethane 5,000.0

[0179] The above formulations may be obtained using conventional procedures well known in the pharmaceutical art.

[0180] All publications, patents, and patent applications are incorporated herein by reference as if individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.

Claims

1. A compound of formula I, 【Chemical 83】 wherein, R １ is hydrogen, (C １ ~C ６ )-alkyl, (C ２ ~C ６ )-alkenyl, (C ２ ~C ６ )-alkynyl, -C(=O)R ａ , -C(=O)N(R ａ ) ２ , -S(=O) ２ N(R ａ ) ２ , -C(=NR ａ )N(R ａ ) ２ , (C ３ ~C ７ )-carbocyclyl, aryl, heterocyclyl, heteroaryl, (C ３ ~C ７ )-carbocyclyl(C １ ~C ６ )-alkyl-, aryl(C １ ~C ６ )-alkyl-, heterocyclyl(C １ ~C ６ )-alkyl- or heteroaryl(C １ ~C ６ )-alkyl-, and the (C １ ~C ６ )-alkyl, (C ２ ~C ６ )-alkenyl, (C ２ ~C ６ )-alkynyl, (C ３ ~C ７ )-carbocyclyl, aryl, heterocyclyl, heteroaryl, (C ３ ~C ７ )-carbocyclyl(C １ ~C ６ )-alkyl-, aryl(C １ ~C ６ )-alkyl-, heterocyclyl(C １ ~C ６ )-alkyl- or heteroaryl(C １ ~C ６ )-alkyl- is optionally halo, -OH, -NO ２ , -CN, (C １ ~C ４ ), alkyl, (C １ ~C ４ ), haloalkyl, (C １ ~C ４ ), alkoxy, (C １ ~C ４ ), haloalkoxy, -N(R ａ ), ２ , -NR ａ C(=NR ａ )(NR ａ ), ２ , -C(=NR ａ )(NR ａ ), ２ , phenyl and -OP(=O)(OH) ２ selected independently from the group consisting of one or more (e.g., 1, 2, 3, 4 or 5) groups, said phenyl being optionally substituted with one or more halo, -OH, -NO ２ , -CN, (C １ ~C ４ ), alkyl, (C １ ~C ４ ), haloalkyl, (C １ ~C ４ ), alkoxy or (C １ ~C ４ ), haloalkoxy, R ２ is hydrogen, (C １ ~C ６ )-alkyl, (C ２ ~C ６ )-alkenyl, -C(=O)R ｂ , -C(=O)N(R ｂ ) ２ , -S(=O) ２ N(R ｂ ) ２ , -C(=NR ｂ )N(R ｂ ) ２ , (C ３ ~C ７ )-carbocyclic, aryl, heterocyclic, heteroaryl, (C ３ ~C ７ )-carbocyclic(C １ ~C ６ )-alkyl-, aryl(C １ ~C ６ )-alkyl-, heterocyclic(C １ ~C ６ )-alkyl- or heteroaryl(C １ ~C ６ )-alkyl-, and the (C １ ~C ６ )-alkyl, (C ２ ~C ６ )-alkenyl, (C ３ ~C ７ )-carbocyclic, aryl, heterocyclic, heteroaryl, (C ３ ~C ７ )-carbocyclic(C １ ~C ６ )-alkyl-, aryl(C １ ~C ６ )-alkyl-, heterocyclic(C １ ~C ６ )-alkyl- or heteroaryl(C １ ~C ６ )-alkyl- are optionally halo, -OH, -NO ２ , -CN, (C １ ~C ４ )-alkyl, (C １ ~C ４ )-haloalkyl, (C １ ~C ４ ), alkoxy, (C １ ~C ４ ), haloalkoxy, -N(R ｂ ), ２ , -NR ｂ C(=NR ｂ ), N(R ｂ ), ２、 -C(=NR ｂ ), N(R ｂ ), ２ and -OP(=O)(OH) ２ independently selected from the group consisting of one or more (e.g., 1, 2, 3, 4, or 5) groups, or R １ and R ２ together with the nitrogen to which they are attached form a heterocyclyl, said heterocyclyl being optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of halo, -OH, -NO ２ , -CN, (C １ ~C ４ ), alkyl, (C １ ~C ４ ), haloalkyl, (C １ ~C ４ ), alkoxy, (C １ ~C ４ ), haloalkoxy, -N(R ａｂ ), -NR ２ C(=NR ａｂ ), N(R ａｂ ), ａｂ -C(=NR ２、 ), N(R ａｂ ), ａｂ and -OP(=O)(OH) ２ and is substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of ２ ​ Z is -OR ｃ 、 -N(R ｃ ) ２ , -SR ｃ , -NR ｃ C(=NR ｃ )N(R ｃ ) ２ , -C(=NR ｃ )N(R ｃ ) ２ , hydrogen, (C １ ~C ６ )alkyl, (C ２ ~C ６ )alkenyl, -C(=O)R ｃ , -C(=O)N(R ｃ ) ２ , -S(=O) ２ N(R ｃ ) ２ , (C ３ ~C ７ )carbocyclic, aryl, heterocyclic, heteroaryl, (C ３ ~C ７ )carbocyclic(C １ ~C ６ )alkyl-, aryl(C １ ~C ６ )alkyl-, heterocyclic(C １ ~C ６ )alkyl- or heteroaryl(C １ ~C ６ )alkyl-, and the (C １ ~C ６ )alkyl, (C ２ ~C ６ )alkenyl, (C ３ ~C ７ )carbocyclic, aryl, heterocyclic, heteroaryl, (C ３ ~C ７ )carbocyclic(C １ ~C ６ )alkyl-, aryl(C １ ~C ６ )alkyl-, heterocyclic(C １ ~C ６ )alkyl- or heteroaryl(C １ ~C ６ ), the alkyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of halo, -OH, -NO ２ , -CN, (C １ ~C ４ ), alkyl, (C １ ~C ４ ), haloalkyl, (C １ ~C ４ ), alkoxy, (C １ ~C ４ ), haloalkoxy, -N(R ｃ ), -NR ２ , -NRC(=NR ｃ )(NR ｃ ), -C(=NR ｃ )(NR ２、 ), and -OP(=O)(OH) ｃ )(NR ｃ ), and is substituted with ２ and -OP(=O)(OH) ２ independently selected from the group consisting of one or more (e.g., 1, 2, 3, 4, or 5) groups X １ is either CR ３ or N, and X ２ is either CR ４ or N, and R ３ is hydrogen, halo, -OH, -NO ２ , -CN, (C １ ~C ６ ) alkoxy, (C ２ ~C ６ ) alkyl, (C ２ ~C ６ ) alkenyl, (C ２ ~C ６ ) alkynyl - C(=O)R ｄ , -C(=O)N(R ｄ ) ２ , -S(=O) ２ N(R ｄ ) ２ , -NR ｄ C(=NR ｄ )N(R ｄ ) ２ , -C(=NR ｄ )N(R ｄ ) ２ or -N(R ｄ ) ２ and wherein said (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl, (C ２ ~C ６ ) alkenyl or (C ２ ~C ６ ) alkynyl is optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of halo, -OH, -NO ２ , -CN, (C １ ~C ４ ) alkoxy, (C １ ~C ４ ) haloalkoxy, -N(R ｄ ) ２ , -NR ｄ C(=NR ｄ )N(R ｄ ) ２、 -C(=NR ｄ )N(R ｄ ) ２ and -OP(=O)(OH) ２ and is substituted with R ４ is hydrogen, halo, —OH, —NO ２ , —CN, (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl, (C ２ ~C ６ ) alkenyl, (C ２ ~C ６ ) alkynyl, —C(═O)R ｅ , —C(═O)N(R ｅ ) ２ , —S(═O) ２ N(R ｅ ) ２ , —NR ｅ C(═NR ｅ )N(R ｅ ) ２ , —C(═NR ｅ )N(R ｅ ) ２、 or —N(R ｅ ) ２ and wherein the (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl, (C ２ ~C ６ ) alkenyl or (C ２ ~C ６ ) alkynyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of halo, —OH, —NO ２ , —CN, (C １ ~C ４ ) alkoxy, (C １ ~C ４ ) haloalkoxy, —N(R ｅ ) ２ , —NR ｅ C(═NR ｅ )N(R ｅ ) ２、 —C(═NR ｅ )N(R ｅ ) ２ and —OP(═O)(OH) ２ and is substituted with Y １ is NR ５ａ and Y ２ is N or CR ６ｂ and Y ３ is N or CR ７ｂ and Y １ and Y ２ the dashed-line bond between is a single bond, and Y ２ and Y ３ the dashed-line bond between is a double bond, or Y ３ is NR ７ａ and Y １ is N or CR ５ｂ and Y ２ is N or CR ６ｂ and Y １ and Y ２ the dashed bond between is a double bond, and Y ２ and Y ３ the dashed line between is a single bond R ５ａ and R ７ａ are each independently (C １ -C １０ )alkyl, (C ２ -C １０ )alkenyl, -W-(C ３ -C ７ )carbocyclyl, -W-aryl, W-heterocyclyl, or -W-heteroaryl, and the (C １ -C １０ )alkyl, (C ２ -C １０ )alkenyl, -W-(C ３ -C ７ )carbocyclyl, -W-aryl, W-heterocyclyl, -W-heteroaryl are optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from Q, R ５ｂ 、 R ６ｂ and R ７ｂ are each independently hydrogen, halo, -OH, -NO ２ , -CN, (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl, (C ２ ~C ６ ) alkenyl, -C(=O)R ｆ , -C(=O)N(R ｆ ) ２ , -S(=O) ２ N(R ｆ ) ２ , -NR ｆ C(=NR ｆ )N(R ｆ ) ２ , -C(=NR ｆ )N(R ｆ ) ２ or -N(R ｆ ) ２ and the (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl or (C ２ ~C ６ ) alkenyl are optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of halo, -OH, -NO ２ , -CN, (C １ ~C ４ ) alkoxy, (C １ ~C ４ ) haloalkoxy, -N(R ｆ ) ２ , -NR ｆ C(=NR ｆ )N(R ｆ ) ２、 -C(=NR ｆ )N(R ｆ ) ２ and -OP(=O)(OH) ２ and are substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of: W is absent or is (C １ ~C １０ )alkyl or (C ２ ~C ６ )alkynyl, and the (C １ ~C １０ )alkyl or (C ２ ~C ６ )alkynyl is optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) oxo(=O), and one or more carbons of the (C １ ~C １０ )alkyl are optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) -O- or -NR ｗ -, Each Q is independently a halo, -OH, -NO ２ , -CN, (C １ ~C ６ ), alkyl, (C ２ ~C ６ ), alkenyl, (C ２ ~C ６ ), alkynyl, (C １ ~C ６ ), haloalkyl, (C １ ~C ６ ), alkoxy, (C １ ~C ６ ), haloalkoxy, C(=O)R ｑ , -C(=O)N(R ｑ ), ２ , -N(R ｑ ), ２ , -S(=O) ２ N(R ｑ ), ２、 aryl, -O-aryl, heteroaryl or -O-heteroaryl, and the (C １ ~C ６ ), alkyl, (C ２ ~C ６ ), alkenyl, (C ２ ~C ６ ), alkynyl, (C １ ~C ６ ), haloalkyl, (C １ ~C ６ ), alkoxy, (C １ ~C ６ ), haloalkoxy, aryl, -O aryl, heteroaryl or -O heteroaryl may optionally be halo, -OH, -NO ２ , -CN, (C １ ~C ４ ), alkyl, (C １ ~C ４ ), haloalkyl, (C １ ~C ４ ), alkoxy, (C １ ~C ４ ), haloalkoxy, C(=O)R ｑ , -C(=O)O(R ｑ ), -C(=O)N(R ｑ ), ２ , -S(=O) ２ N(R ｑ ), ２ 、 independently selected from the group consisting of aryl and heteroaryl, substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups, and said aryl or heteroaryl is optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) Q １ and substituted with Each Q １ is, independently, halo, -OH, -NO ２ , -CN, (C １ ~C ４ )alkyl, (C １ ~C ４ )haloalkyl, (C １ ~C ４ )alkoxy or (C １ ~C ４ )haloalkoxy, Each R ａ 、R ｂ 、R ａｂ 、R ｃ 、R ｄ 、R ｅ and R ｆ is independently hydrogen, (C １ ~C ６ ), alkyl, (C ２ ~C ６ ), alkenyl, (C １ ~C ６ ), haloalkyl, (C ３ ~C ７ ), carbocyclic or aryl, Each R ｗ is independently hydrogen or (C １ -C ６ ) alkyl, R ｑ is hydrogen, (C １ ~C ６ )-alkyl, (C ２ ~C ６ )-alkenyl, (C １ ~C ６ )-haloalkyl (C ３ ~C ７ )-carbocyclic or aryl, and the aryl is optionally halo, -OH, -NO ２ , -CN, (C １ ~C ４ )-alkyl, (C １ ~C ４ )-haloalkyl, (C １ ~C ４ )-alkoxy, (C １ ~C ４ )-haloalkoxy, C(=O)R ｑ１ , -C(=O)O(R ｑ１ ), -C(=O)N(R ｑ１ ) ２ and -S(=O) ２ N(R ｑ１ ) ２ is independently selected from the group consisting of one or more (e.g., 1, 2, 3, 4, or 5) groups selected from the group consisting of, and is substituted with Each R ｑ１ is, independently, hydrogen, (C １ ~C ６ )alkyl, (C ２ ~C ６ )alkenyl, (C １ ~C ６ )haloalkyl, (C ３ ~C ７ )carbocyclic or aryl, said compound, or a salt thereof.

2. R １ is hydrogen, (C １ ~C ６ )-alkyl, (C １ ~C ６ )-alkenyl, -C(=O)R ａ , -C(=O)N(R ａ ) ２ , -S(=O) ２ N(R ａ ) ２ , -C(=NR ａ )N(R ａ ) ２ , (C ３ ~C ７ )-carbocyclic, aryl, heterocyclic, heteroaryl, (C ３ ~C ７ )-carbocyclic (C １ ~C ６ )-alkyl-, aryl(C １ ~C ６ )-alkyl-, heterocyclic(C １ ~C ６ )-alkyl- or heteroaryl(C １ ~C ６ )-alkyl-, wherein the (C １ ~C ６ )-alkyl, (C １ ~C ６ )-alkenyl, (C ３ ~C ７ )-carbocyclic, aryl, heterocyclic, heteroaryl, (C ３ ~C ７ )-carbocyclic (C １ ~C ６ )-alkyl-, aryl(C １ ~C ６ )-alkyl-, heterocyclic(C １ ~C ６ )-alkyl- or heteroaryl(C １ ~C ６ )-alkyl- is optionally halo, -OH, -NO ２ , -CN, (C １ ~C ４ )-alkyl, (C １ ~C ４ )-haloalkyl, (C １ ~C ４ ), alkoxy, (C １ ~C ４ ), haloalkoxy, -N(R ａ ), ２ , -NR ａ C(=NR ａ ),N(R ａ ), ２、 -C(=NR ａ ),N(R ａ ), ２ and -OP(=O)(OH) ２ selected independently from the group consisting of one or more (e.g., 1, 2, 3, 4 or 5) groups, R ２ is hydrogen, (C １ ~C ６ )-alkyl, (C １ ~C ６ )-alkenyl, -C(=O)R ｂ , -C(=O)N(R ｂ ) ２ , -S(=O) ２ N(R ｂ ) ２ , -C(=NR ｂ )N(R ｂ ) ２ , (C ３ ~C ７ )carbocyclic, aryl, heterocyclic, heteroaryl, (C ３ ~C ７ )carbocyclic(C １ ~C ６ )alkyl-, aryl(C １ ~C ６ )alkyl-, heterocyclic(C １ ~C ６ )alkyl- or heteroaryl(C １ ~C ６ )alkyl-, wherein the (C １ ~C ６ )alkyl, (C １ ~C ６ )alkenyl, (C ３ ~C ７ )carbocyclic, aryl, heterocyclic, heteroaryl, (C ３ ~C ７ )carbocyclic(C １ ~C ６ )alkyl-, aryl(C １ ~C ６ )alkyl-, heterocyclic(C １ ~C ６ )alkyl- or heteroaryl(C １ ~C ６ )alkyl- is optionally halo, -OH, -NO ２ , -CN, (C １ ~C ４ )alkyl, (C １ ~C ４ )haloalkyl, (C １ ~C ４ ), alkoxy, (C １ ~C ４ ), haloalkoxy, -N(R ａ ), ２ , -NR ｂ C(=NR ｂ ), N(R ｂ ), ２、 -C(=NR ｂ ), N(R ｂ ), ２ and -OP(=O)(OH) ２ selected independently from the group consisting of one or more (e.g., 1, 2, 3, 4 or 5) groups, or R １ and R ２ together with the nitrogen to which they are attached form a heterocyclyl, and the heterocyclyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of halo, -OH, -NO ２ , -CN, (C １ ~C ４ ), alkyl, (C １ ~C ４ ), haloalkyl, (C １ ~C ４ ), alkoxy, (C １ ~C ４ ), haloalkoxy, -N(R ａｂ ), -NR ２ C(=NR ａｂ )(NR ａｂ ), -C(=NR ａｂ )(NR ２、 ), -C(=NR ａｂ )(NR ａｂ ), and -OP(=O)(OH) ２ and is substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of ２ ​ Z is -OR ｃ 、 -N(R ｃ ) ２ , -SR ｃ , -NR ｃ C(=NR ｃ )N(R ｃ ) ２ , -C(=NR ｃ )N(R ｃ ) ２ , hydrogen, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) alkenyl, -C(=O)R ｃ , -C(=O)N(R ｃ ) ２ , -S(=O) ２ N(R ｃ ) ２ , (C ３ ~C ７ ) carbocyclic, aryl, heterocyclic, heteroaryl, (C ３ ~C ７ ) carbocyclic (C １ ~C ６ ) alkyl-, aryl(C １ ~C ６ ) alkyl-, heterocyclic(C １ ~C ６ ) alkyl- or heteroaryl(C １ ~C ６ ) alkyl-, wherein the (C １ ~C ６ ) alkyl, (C １ ~C ６ ) alkenyl, (C ３ ~C ７ ) carbocyclic, aryl, heterocyclic, heteroaryl, (C ３ ~C ７ ) carbocyclic (C １ ~C ６ ) alkyl-, aryl(C １ ~C ６ ) alkyl-, heterocyclic(C １ ~C ６ ) alkyl- or heteroaryl(C １ ~C ６ ), alkyl- is optionally halo, -OH, -NO ２ , -CN, (C １ ~C ４ ), alkyl, (C １ ~C ４ ), haloalkyl, (C １ ~C ４ ), alkoxy, (C １ ~C ４ ), haloalkoxy, -N(R ｃ ), ２ , -NR ｃ C(=NR ｃ ),N(R ｃ ), ２、 -C(=NR ｃ ),N(R ｃ ), ２ and -OP(=O)(OH) ２ selected independently from the group consisting of one or more (e.g., 1, 2, 3, 4 or 5) groups, substituted with X １ is CR ３ or N, and X ２ is either CR ４ or N, and R ３ is hydrogen, halo, OH, -NO ２ , -CN, (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) alkenyl, -C(=O)R ｄ , -C(=O)N(R ｄ ) ２ , -S(=O) ２ N(R ｄ ) ２ , -NR ｄ C(=NR ｄ )N(R ｄ ) ２ , -C(=NR ｄ )N(R ｄ ) ２ or -N(R ｄ ) ２ and is independently selected from the group consisting of (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl, or (C １ ~C ６ ) alkenyl, optionally, halo, -OH, -NO ２ , -CN, (C １ ~C ４ ) alkoxy, (C １ ~C ４ ) haloalkoxy, -N(R ｄ ) ２ , -NR ｄ C(=NR ｄ )N(R ｄ ) ２、 -C(=NR ｄ )N(R ｄ ) ２ and -OP(=O)(OH) ２ and is substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of R ４ is hydrogen, halo, -OH, -NO ２ , -CN, (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) alkenyl, -C(=O)R ｅ , -C(=O)N(R ｅ ) ２ , -S(=O) ２ N(R ｅ ) ２ , -NR ｅ C(=NR ｅ )N(R ｅ ) ２ , -C(=NR ｅ )N(R ｅ ) ２ or -N(R ｅ ) ２ and the (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl or (C １ ~C ６ ) alkenyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of halo, -OH, -NO ２ , -CN, (C １ ~C ４ ) alkoxy, (C １ ~C ４ ) haloalkoxy, -N(R ｅ ) ２ , -NR ｅ C(=NR ｅ )N(R ｅ ) ２、 -C(=NR ｅ )N(R ｅ ) ２ and -OP(=O)(OH) ２ and is substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of Y １ is NR ５ａ and Y ２ is N or CR ６ｂ and Y ３ is N or CR ７ｂ and Y １ and Y ２ the dashed-line bond between them is a single bond, and Y ２ and Y ３ the dashed-line bond between them is a double bond, or Y ３ is NR ７ａ and Y １ is N or CR ５ｂ and Y ２ is N or CR ６ｂ and Y １ and Y ２ the dashed bond between them is a double bond, and Y ２ and Y ３ the dashed line between them is a single bond R ５ａ and R ７ａ are each independently (C １ -C １０ ), alkyl, (C １ -C １０ ), alkenyl, -W-(C ３ -C ７ ), carbocyclic, -W-aryl, W-heterocyclic, or -W-heteroaryl, wherein the (C １ -C １０ ), alkyl, (C １ -C １０ ), alkenyl, -W-(C ３ -C ７ ), carbocyclic, -W-aryl, W-heterocyclic, -W-heteroaryl are optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from Q, R ５ｂ 、R ６ｂ and R ７ｂ are each independently hydrogen, halo, -OH, -NO ２ , -CN, (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) alkenyl, -C(=O)R ｆ , -C(=O)N(R ｆ ) ２ , -S(=O) ２ N(R ｆ ) ２ , -NR ｆ C(=NR ｆ )N(R ｆ ) ２ , -C(=NR ｆ )N(R ｆ ) ２ , or -N(R ｆ ) ２ wherein the (C １ ~C ６ ) alkoxy, (C １ ~C ６ ) alkyl or (C １ ~C ６ ) alkenyl is optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of halo, -OH, -NO ２ , -CN, (C １ ~C ４ ) alkoxy, (C １ ~C ４ ) haloalkoxy, -N(R ｆ ) ２ , -NR ｆ C(=NR ｆ )N(R ｆ ) ２、 -C(=NR ｆ )N(R ｆ ) ２ and -OP(=O)(OH) ２ and is substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of halo, -OH, -NO W is absent or is (C １ ~C １０ ) alkyl, and the (C １ ~C １０ ) alkyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) oxo (=O), and one or more carbons of the (C １ ~C １０ ) alkyl are optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) -O- or -NR ｗ -, Each Q is independently halo, -OH, -NO ２ , -CN, (C １ ~C ６ )alkyl, (C １ ~C ６ )haloalkyl, (C １ ~C ６ )alkoxy, (C １ ~C ６ )haloalkoxy, C(=O)R ｑ , -C(=O)N(R ｑ ) ２ , -N(R ｑ ) ２ , -S(=O) ２ N(R ａ ) ２、 aryl, -O-aryl, heteroaryl or -O-heteroaryl, wherein the (C １ ~C ６ )alkyl, (C １ ~C ６ )haloalkyl, (C １ ~C ６ )alkoxy, (C １ ~C ６ )haloalkoxy, aryl, -Oaryl, heteroaryl or -Oheteroaryl is optionally halo, -OH, -NO ２ , -CN, (C １ ~C ４ )alkyl, (C １ ~C ４ )haloalkyl, (C １ ~C ４ )alkoxy, (C １ ~C ４ )haloalkoxy, C(=O)R ｑ , -C(=O)O(R ｑ ), -C(=O)N(R ｑ ) ２ , -S(=O) ２ N(R ｑ ) ２ , aryl and heteroaryl, and is substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of, and the aryl or heteroaryl is optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) Q １ . Each Q １ is, independently, halo, -OH, -NO ２ , -CN, (C １ ~C ４ )alkyl, (C １ ~C ４ )haloalkyl, (C １ ~C ４ )alkoxy or (C １ ~C ４ )haloalkoxy, and Each R ａ 、R ｂ 、R ａｂ 、R ｃ 、R ｄ 、R ｅ and R ｆ is independently hydrogen, (C １ ~C ６ ), alkyl, (C １ ~C ６ ), alkenyl, (C １ ~C ６ ), haloalkyl, (C ３ ~C ７ ), carbocyclic or aryl, Each R ｗ is independently hydrogen or (C １ ~C ６ ) alkyl, R ｑ is hydrogen, (C １ ~C ６ )-alkyl, (C １ ~C ６ )-alkenyl, (C １ ~C ６ )-haloalkyl (C ３ ~C ７ )-carbocyclic or aryl, and said aryl is optionally substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of halo, -OH, -NO ２ , -CN, (C １ ~C ４ )-alkyl, (C １ ~C ４ )-haloalkyl, (C １ ~C ４ )-alkoxy, (C １ ~C ４ )-haloalkoxy, C(=O)R ｑ１ , -C(=O)O(R ｑ１ ), -C(=O)N(R ｑ１ ) ２ and -S(=O) ２ N(R ｑ１ ) ２ and is substituted with one or more (e.g., 1, 2, 3, 4 or 5) groups independently selected from the group consisting of Each R ｑ１ is, independently, hydrogen, (C １ -C ６ )alkyl, (C １ -C ６ )alkenyl, (C １ -C ６ )haloalkyl, (C ３ -C ７ )carbocyclic or aryl, or or a salt thereof, the compound according to claim 1.

3. X １ is CR ３ The compound or salt according to claim 1, wherein

4. X ２ is CR ４ The compound or salt according to any one of claims 1 to 3, wherein

5. X ２ The compound or salt according to any one of claims 1 to 3, wherein X is N.

6. The compound of formula I is a compound of formula Ie: 【Chemical 84】 or a salt thereof, the compound or salt according to claim 1.

7. The compound of formula I is a compound of formula If: 【Chemical Formula 85】 or a salt thereof, the compound or salt according to claim 1.

8. The compound of formula I is a compound of formula Ig: 【Chemical 86】 or a salt thereof, the compound or salt according to claim 1.

9. The compound of formula I is a compound of formula Ia: 【Chemical 87】 or a salt thereof, the compound or salt according to claim 1.

10. The compound of formula I is a compound of formula Ib: 【Chemical 88】 or a salt thereof, the compound or salt according to claim 1.

11. Y ３ is CR ７ｂ The compound or salt according to any one of claims 1 to 3 or 6 to 10, wherein

12. Y ２ is CR ６ｂ The compound or salt according to any one of claims 1 to 3 or 6 to 10, wherein

13. The compound of formula I is a compound of formula Id: 【Chemical 89】 or a salt thereof, the compound or salt according to claim 1.

14. The compound of formula I is a compound of formula Ih: 【Chemical Formula 90】 or a salt thereof, the compound or salt according to claim 1.

15. R ３ The compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14, wherein R is hydrogen or a halogen.

16. R ３ The compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14, wherein R is hydrogen.

17. R ４ The compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14, wherein R is hydrogen.

18. R １ is hydrogen, (C １ ~C ６ ) alkyl or aryl (C １ ~C ６ ) alkyl-, and (C １ ~C ６ ) alkyl or aryl (C １ ~C ６ ) Alkyl is optionally selected from halo, —OH, —NO ２ , -CN, (C １ ~C ４ ) alkyl, (C １ ~C ４ ) haloalkyl, (C １ ~C ４ ) alkoxy, (C １ ~C ４ ) haloalkoxy, -N(R ａ ) ２ , -NR ａ C (=NR ａ ) N (R ａ ) ２ , -C(=NR ａ ) N (R ａ ) ２ , phenyl, and -OP(=O)(OH) ２ and wherein the phenyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of halo, -OH, -NO ２ , -CN, (C １ ~C ４ ) alkyl, (C １ ~C ４ ) haloalkyl, (C １ ~C ４ ) alkoxy or (C １ ~C ４ 15. The compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14, which is substituted with haloalkoxy.

19. R １ is hydrogen, (C １ ~C ６ )-alkyl or aryl(C １ ~C ６ )-alkyl, and the (C １ ~C ６ )-alkyl or aryl(C １ ~C ６ )-alkyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) groups independently selected from the group consisting of halo and phenyl, and the phenyl is optionally substituted with one or more halo, -OH, -NO ２ , -CN, (C １ ~C ４ )-alkyl, (C １ ~C ４ )-haloalkyl, (C １ ~C ４ )-alkoxy or (C １ ~C ４ )-haloalkoxy, the compound or salt according to any one of claims 1 to 3, 6 to 10, or 13 to 14.

20. R １ The compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14, wherein R is hydrogen.

21. R ２ The compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14, wherein R is hydrogen.

22. Z is -N(R ｃ ), ２ The compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14, wherein

23. Z is -NH ２ The compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14, wherein

24. R ７ｂ The compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14, wherein R is hydrogen.

25. R ６ｂ is hydrogen or (C １ ~C ６ alkyl), the compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14.

26. R ５ａ is (C １ to C １０ ) alkyl, (C ２ to C １０ ) alkenyl, -W-(C ３ to C ７ ) carbocyclic, -W-aryl or -W-heteroaryl, and the (C １ to C １０ ) alkyl, (C ２ to C １０ ) alkenyl, -W-(C ３ to C ７ ) carbocyclic, -W-aryl or -W-heteroaryl is optionally substituted with one or more groups independently selected from Q, a compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14.

27. R ５ａ is (C ２ ~C １０ ) alkenyl, -W-(C ３ ~C ７ ) carbocyclic, -W-aryl or -W-heteroaryl, and the (C ２ ~C １０ ) alkenyl, -W-(C ３ ~C ７ ) carbocyclic, -W-aryl or -W-heteroaryl is optionally substituted with one or more groups independently selected from Q, the compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14.

28. W is absent or is (C １ ~C １０ ) alkyl or (C ２ ~C ６ ) alkynyl, and the (C １ ~C １０ ) alkyl or (C ２ ~C ６ ) alkynyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) oxo (=O), and one or more carbons of the (C １ ~C １０ ) alkyl are optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) -O- or -NR ｗ -, the compound or salt according to any one of claims 1 to 3, 6 to 10, or 13 to 14.

29. W is absent or is (C １ -C １０ ) alkyl or (C ２ -C ６ ) alkynyl, and the (C １ -C １０ ) alkyl or (C ２ -C ６ ) alkynyl is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) oxo (=O). The compound or salt according to any one of claims 1 to 3, 6 to 10, or 13 to 14

30. W is absent or is -CH ２ -, -C(=O)-, or propyne, the compound or salt according to any one of claims 1 to 3, 6 to 10, or 13 to 14.

31. W is absent or is -CH ２ -, or -C(=O)-, the compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14.

32. R ５ａ is 【Chemical Formula 91-1】 【Chemical Formula 91-2】 is the compound or salt according to any one of claims 1 to 3, 6 to 10 or 13 to 14.

33. 【Fig. 92-1】 【Chemical Formula 92-2】 【Chemical Formula 92-3】 【Chemical Formula 92-4】 ​ or a salt thereof, the compound according to claim 1.

34. A pharmaceutical composition comprising the compound according to any one of claims 1 to 3, 6 to 10, 13 to 14 or 33 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

35. A composition for treating or preventing bacterial infection in an animal, comprising the compound according to any one of claims 1 to 3, 6 to 10, 13 to 14 or 33 or a pharmaceutically acceptable salt thereof.

36. The composition according to claim 35, wherein the animal is infected with bacteria.

37. The composition according to claim 35, wherein the bacterial infection is an N. gonorrhoeae, P. aeruginosa, A. baumannii, E. coli, K. pneumoniae, S. sonnei, P. mirabilis, MSSA or MRSA infection.

38. The composition according to claim 35, wherein the bacterial infection is a Gram-negative bacterial strain infection.

39. The composition according to claim 35, wherein the bacterial infection is a Gram-positive bacterial strain infection.

40. A composition for use in a medical treatment, comprising the compound according to any one of claims 1 to 3, 6 to 10, 13 to 14 or 33 or a pharmaceutically acceptable salt thereof.

41. A composition for prophylactic or therapeutic treatment of a bacterial infection, comprising the compound according to any one of claims 1 to 3, 6 to 10, 13 to 14 or 33 or a pharmaceutically acceptable salt thereof.

42. Use of the compound according to any one of claims 1 to 3, 6 to 10, 13 to 14 or 33 or a pharmaceutically acceptable salt thereof for the preparation of a medicament for prophylactic or therapeutic treatment of a bacterial infection in an animal.

43. A composition for prophylactic or therapeutic treatment of a bacterial infection in an animal, comprising the compound according to any one of claims 1 to 3, 6 to 10, 13 to 14 or 33 or a pharmaceutically acceptable salt thereof.

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