	US 12,247,013 B2
	Indane derivatives for use in the treatment of bacterial infection
Simon Leiris, Labege (FR); David Thomas Davies, Labege (FR); Martin Everett, Labege (FR); Nicolas Sprynski, Labege (FR); Lilha Beyria, Labege (FR); Thomas David Pallin, Margate (GB); Andrew Peter Cridland, Margate (GB); Toby Jonathan Blench, Margate (GB); Richard Leonard Elliott, Margate (GB); and David Edward Clark, Margate (GB)
Assigned to Antabio SAS, Labege (FR)
Appl. No. 17/277,535
Filed by Antabio SAS, Labege (FR)
PCT Filed Jul. 25, 2019, PCT No. PCT/EP2019/070116 § 371(c)(1), (2) Date Mar. 18, 2021, PCT Pub. No. WO2020/064174, PCT Pub. Date Apr. 2, 2020.
Claims priority of application No. 18290106 (EP), filed on Sep. 25, 2018; application No. 18290104 (EP), filed on Sep. 26, 2018; and application No. 18197365 (EP), filed on Sep. 27, 2018.
Prior Publication US 2022/0112169 A1, Apr. 14, 2022
Int. Cl. C07D 277/64 (2006.01); A61K 45/06 (2006.01); A61P 31/04 (2006.01); C07D 417/06 (2006.01); C07D 417/12 (2006.01)

CPC C07D 277/64 (2013.01) [A61K 45/06 (2013.01); A61P 31/04 (2018.01); C07D 417/06 (2013.01); C07D 417/12 (2013.01)]

25 Claims

1. A compound which is an indane according to Formula (I), or a pharmaceutically acceptable salt thereof,

wherein

R¹is selected from:

NHOH, OH, OR^1aand —OCH₂OC(O)R^1a, wherein R^1ais selected from an unsubstituted C₁to C₄alkyl group and phenyl; and

where the compound of Formula (I) contains a positively charged nitrogen atom, R¹may be O⁻, such that the compound forms a zwitterion;

R²is selected from H and unsubstituted C₁to C₂alkyl;

each R³group is independently selected from halogen, —OH, —NH₂, methyl and —CF₃;

n is an integer from 0 to 4;

R⁴is selected from H and unsubstituted C₁to C₂alkyl;

L is selected from a bond and a C₁to C₃alkylene group which is unsubstituted or is substituted by one group selected from halogen, —OH, —OMe, —NR²⁰R²¹;

N⁺R²⁰R²¹R²², and —CF₃;

p is 0 or 1;

R⁵is selected from —OMe, —OH, halogen, —NR²⁰R²¹; —N⁺R²⁰R²¹R²², —CF₃, and R⁶;

each R⁶is independently selected from:

—R^6aR^A, —O—R^6aR^A, —NR²⁰—R^6aR^A,—R^6bR^B, —O—R^6bR^B, and —NR²⁰—R^6bR^B;

—R^XR^R, —O—R^XR^R, —O—R^X—C(O)—R^R, —R^X—C(O)—R^R, —NR²⁰—R^XR^R, and —NR²⁰—R^X—C(O)—R^R; and

—CN; —C(O)NR²⁰R²¹; —C(O)NR²¹—R^XR^B; —C(O)NR⁴⁰R⁴¹; —SO₂R²⁰; —SO₂—R^XR^B;

—SO₂NR²⁰R²¹; —SO₂—NR²⁰—R^XR^B; and —SO₂NR⁴⁰R⁴¹;

wherein:

each R^Xis independently selected from R^6aand R^6b;

each R^6ais independently selected from C₁to C₄alkylene, C₂to C₄alkenylene and C₂to C₄alkynylene; and each R^6ais independently unsubstituted or is substituted by one group selected from —OH, halogen; —NR²⁰R²¹; —N⁺R²⁰R²¹R²²; —NR²⁰C(NR²¹)NR²²R²³;

—NR²⁰C(N⁺R²¹R²²)NR²³R²⁴; —NR²⁰C(NR²¹)R²²; —NR²⁰C(N⁺R²¹R²²)R²³;

—C(NR²⁰)NR²¹R²²; —C(N⁺R²⁰R²¹)NR²²R²³; —C(NR²⁰)R²¹; and —C(N⁺R²⁰R²¹)R²²;

—C(O)NR²⁰R²¹; —C(O)N⁺R²⁰R²¹R²²; —C(O)—R²⁰,and methoxy which is unsubstituted or is substituted by one, two or three halogen substituents;

each R^6bis independently selected from [C₁to C₃alkylene]—C(R^Z)₂R^b, [C₂to C₃alkenylene]—C(R^Z)₂R^band [C₂to C₃alkynylene]—C(R^z)₂R^b; wherein the two R^Zgroups are attached together to form, together with the atom to which they are attached, a 5- or 6-membered carbocyclic or heterocyclic group;

R^Ais selected from —NR²⁰R³⁰; —N⁺R²⁰R²¹R³⁰; —NR²⁰NR²¹R²²; —NR²⁰N⁺R²¹R²²R²³;

—N⁺R²⁰R²¹NR²²R²³; —NR²⁰C(NR²¹)NR²²R³⁰; —NR²⁰C(N⁺R²¹R²²)NR²³R³⁰;

—C(NR²⁰)NR²¹R²²; and —C(N⁺R²⁰R²¹)NR²²R²³;

R^Bis selected from —NR²⁰R²¹; —N⁺R²⁰R²¹R²²; —NR²⁰NR²¹R²²; —NR²⁰N⁺R²¹R²²R²³;

—N⁺R²⁰R²¹NR²²R²³; —NR²⁰C(NR²¹)NR²²R²³; —NR²⁰C(N⁺R²¹R²²)NR²³R²⁴,

—C(NR²⁰)NR²¹R²²; and —C(N⁺R²⁰R²¹)NR²²R²³;

R⁴⁰and R⁴¹, together with the nitrogen atom to which they are attached, form a 4- to 6-membered heterocyclic group, wherein any nitrogen atom in the ring is independently selected from secondary, tertiary and quaternary nitrogen atoms;

each R^Ris independently a 4- to 10-membered heteroaryl or heterocyclic group comprising at least one nitrogen atom, and said nitrogen atom(s) are independently selected from secondary, tertiary and quaternary nitrogen atom(s);

wherein each R^R, and each ring formed by —NR⁴⁰R⁴¹, is independently unsubstituted or is substituted with one, two or three groups independently selected from

i) halogen, —CN;

ii) oxo, providing that said R^Rgroup is a heterocyclic group;

iii) —R²⁰, —R⁷—OR²⁰; —R⁷—NR²⁰R²¹; —R⁷—N⁺R²⁰R²¹R²²; —R⁷—NR²⁰C(NR²¹)NR²²R²³;

—R⁷—NR²⁰C(N⁺R²¹R²²)NR²³R²⁴; —R⁷—NR²⁰C(NR²¹)R²²; —R⁷NR²⁰C(N⁺R²¹R²²)R²³;

—R⁷—C(NR²⁰)NR²¹R²²; —R⁷—C(N⁺R²⁰R²¹)NR²²R²³; —R⁷—C(NR²⁰)R²¹; and

—R⁷—C(N⁺R²⁰R²¹)R²²;

each R⁷is independently selected from a bond and unsubstituted C₁to C₃alkylene;

R²⁰, R²¹, R²², R²³and R²⁴are each independently selected from H and C₁to C₃alkyl which is unsubstituted or is substituted with one —OH or —OMe group or with one, two or three halogen groups;

each R³⁰is independently selected from C₂to C₃alkyl which is unsubstituted or is substituted with one —OH or —OMe group or with one, two or three halogen groups.