# US 2019/0315731 A1 · 6-(buta-1,3-diyn-1-yl)benzo[d]thiazole derivatives

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2019/0315731 A1
- Document ID: US20190315731A1
- Status: Published application
- Kind: A1
- Application number: 16/303,019
- Filed: 2017-05-16
- Published: 2019-10-17
- Earliest claimed: 2016-05-17
- Assignees: Idorsia Pharmaceuticals Ltd
- Applicants: Idorsia Pharmaceuticals Ltd.
- Inventors: Stefan DIETHELM; Azely MIRRE; Philippe PANCHAUD; Christine SCHMITT; Jean-Luc SPECKLIN; Jean-Philippe SURIVET
- Web page: https://patentgrep.com/patent/US20190315731A1

## CPC

- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- A61P 31/04: Antibacterial agents
- C07D 277/64: with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
- C07D 417/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07F 9/65583: {each of the hetero rings containing nitrogen as ring hetero atom}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The invention relates to antibacterial compounds of formula I wherein the group M and R1 are as defined in the claims, and salts thereof.

## Claims

### Claim 1

A compound of formula I
wherein M is the group (4-hydroxypiperidin-1-yl)carbonyloxymethyl, (3-hydroxyazetidin-1-yl)carbonyloxymethyl or 1-(methylamino)cyclopropyl, or M represents one of the groups MA, MB, MC, MD, ME and MF represented below
wherein
XA1 represents methyl-d, methyl-d2, (C1-C4)alkyl, ω-(C2-C3)haloalkyl, ω-hydroxy(C2-C4)alkyl, 2,3-dihydroxyprop-1-yl, 3-hydroxy-2-(hydroxymethyl)prop-1-yl, oxetan-3-yl, (oxetan-3-yl)methyl, thietan-3-yl, 1,1-dioxidothietan-3-yl, (C3-C6)cycloalkyl, 3-hydroxycyclobut-1-yl, 3-(ω-hydroxy(C1-C3)alkyl)cyclobut-1-yl, tetrahydropyran-4-yl, (C3-C6)cycloalkyl(C1-C3)alkyl or ω-phosphonooxy-(C2-C4)alkyl;
XA21 and XA22 each independently represent H, (C1-C4)alkyl, (C1-C3)haloalkyl or hydroxy(C1-C3)alkyl;
XA3 represents H, (C1-C3)alkyl or halogen;
XB1 represents (C1-C4)alkyl, ω-hydroxy(C2-C3)alkyl, (C3-C6)cycloalkyl, oxetan-3-yl or tetrahydropyran-4-yl;
XB21 and XB22 each independently represent H, (C1-C4)alkyl, (C1-C3)haloalkyl or hydroxy(C1-C3)alkyl;
XB31 and XB32 each independently represent H, halogen, hydroxy, (C1-C4)alkyl, (C1-C3)haloalkyl or hydroxy(C1-C3)alkyl;
XB4 represents H, halogen, hydroxy or (C1-C3)alkyl;
XC1 represents H, (C1-C4)alkyl, (C3-C6)cycloalkyl, ω-hydroxy(C2-C3)alkyl, oxetan-3-yl or tetrahydropyran-4-yl;
XC2 represents H, (C1-C4)alkyl, (C1-C3)haloalkyl or hydroxy(C1-C3)alkyl;
XC3 represents H, halogen (especially fluorine), hydroxy, (C1-C4)alkyl, (C1-C3)haloalkyl or hydroxy(C1-C3)alkyl;
XC4 represents H, (C1-C3)alkyl, halogen or hydroxy;
XD1 represents H, (C1-C4)alkyl, ω-(C2-C3)haloalkyl or ω-hydroxy(C2-C4)alkyl;
XD2 and XD3 each independently represent H, (C1-C4)alkyl, (C1-C3)haloalkyl or hydroxy(C1-C3)alkyl;
XE1 represents H, (C1-C4)alkyl, (C1-C3)haloalkyl, 1,2-dihydroxyethyl or hydroxy(C1-C3)alkyl;
XF1 represents H, (C1-C4)alkyl, (C1-C3)haloalkyl, 1,2-dihydroxyethyl or hydroxy(C1-C3)alkyl; and
one of V or W represents —O—, —CH(OH)— or —CH2—, and the other represents —CH2—;
R1 represents H, PO3H2, SO3H, phosphonooxymethyl or the group L represented below
wherein R2 represents (C1-C4)alkylamino(C1-C4)alkyl, [di(C1-C4)alkylamino](C1-C4)alkyl, phosphonooxy(C1-C4)alkyl, phosphonooxymethoxy, 2-(phosphonooxy-(C1-C4)alkyl)-phenyl, (2-(phosphonooxy)-phenyl)-(C1-C4)alkyl (especially 2-(2-(phosphonooxy)-phenyl)-ethyl) or [2-(phosphonooxy-(C1-C4)alkyl)-phenyl]-(C1-C4)alkyl;
or a salt thereof.

### Claim 2 (depends on 1)

A compound of formula I according to claim 1, which is also a compound of formula ICE
wherein
M is the group (4-hydroxypiperidin-1-yl)carbonyloxymethyl, (3-hydroxyazetidin-1-yl)carbonyloxymethyl or 1-(methylamino)cyclopropyl, or M represents one of the groups MA, MB, MC, MD and ME represented below
wherein
XA1 represents ((C1-C4)alkyl, ω-(C2-C3)haloalkyl, ω-hydroxy(C2-C4)alkyl, oxetan-3-yl, (oxetan-3-yl)methyl, (C3-C6)cycloalkyl, 3-hydroxycyclobut-1-yl, or ω-phosphonooxy-(C2-C4)alkyl;
one of XA21 and XA22 represents H and the other represents H, (C1-C4)alkyl or hydroxy(C1-C3)alkyl;
XA3 represents H;
XB1 represents (C1-C4)alkyl;
each of XB21 and XB22 represents H;
each of XB31 and XB32 represents H;
XB4 represents halogen;
XC1 represents (C1-C4)alkyl;
XC2 represents H or hydroxy(C1-C3)alkyl;
XC3 represents H;
XC4 represents H or halogen;
XD1 represents (C1-C4)alkyl;
XD2 represents H and XD3 represents H or hydroxy(C1-C3)alkyl;
XE1 represents hydroxy(C1-C3)alkyl; and
each of V and W represents —CH2—;
R1 represents H or the group L represented below
wherein R2 represents (2-(phosphonooxy)-phenyl)-(C1-C4)alkyl;
or a salt thereof.

### Claim 3 (depends on 1)

A compound of formula I according to claim 1, wherein R1 represents H;
or a salt thereof.

### Claim 4 (depends on 1)

A compound of formula I according to claim 1, wherein R1 does not represent H;
or a salt thereof.

### Claim 5 (depends on 1)

A compound of formula I according to claim 1, wherein M is the group (4-hydroxypiperidin-1-yl)carbonyloxymethyl, (3-hydroxyazetidin-1-yl)carbonyloxymethyl or 1-(methylamino)cyclopropyl;
or a salt thereof.

### Claim 6 (depends on 1)

A compound of formula I according to claim 1, wherein M is the group MA;
or a salt thereof.

### Claim 7 (depends on 1)

A compound of formula I according to claim 1, wherein M is the group MB;
or a salt thereof.

### Claim 8 (depends on 1)

A compound of formula I according to claim 1, wherein M is the group MC;
or a salt thereof.

### Claim 9 (depends on 1)

A compound of formula I according to claim 1, wherein M is the group MD;
or a salt thereof.

### Claim 10 (depends on 1)

A compound of formula I according to claim 1, wherein M is the group ME;
or a salt thereof.

### Claim 11 (depends on 1)

A compound of formula I according to claim 1, wherein R1 represents H and
M is the group (4-hydroxypiperidin-1-yl)carbonyloxymethyl, (3-hydroxyazetidin-1-yl)carbonyloxymethyl or 1-(methylamino)cyclopropyl; or
M represents the group MA wherein XA1 represents ω-hydroxy(C2-C4)alkyl, oxetan-3-yl, (oxetan-3-yl)methyl, (C3-C6)cycloalkyl, 3-hydroxycyclobut-1-yl; one of XA21 and XA22 represents H and the other represents H or (C1-C4)alkyl; and XA3 represents H; or
M represents the group MC wherein XC1 represents (C1-C4)alkyl; XC2 represents H; XC3 represents H; and XC4 represents halogen;
M represents the group MD wherein XD1 represents (C1-C4)alkyl; XD2 represents H; and XD3 represents hydroxy(C1-C3)alkyl;
M represents the group ME wherein XE1 represents hydroxy(C1-C3)alkyl; and
each of V and W represents —CH2—;
or a salt thereof.

### Claim 12 (depends on 1)

A compound of formula I according to claim 1, which is selected from:
(2R)—N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(6-((1-(oxetan-3-yl)azetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)butanamide;
(2R)-5-(2-(4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl)benzo[d]thiazol-6-yl)penta-2,4-diyn-1-yl 4-hydroxypiperidine-1-carboxylate;
(2R)-5-(2-(4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl)benzo[d]thiazol-6-yl)penta-2,4-diyn-1-yl 3-hydroxyazetidine-1-carboxylate;
(2R)—N-hydroxy-2-methyl-4-(6-((1-methylazetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-(methylsulfonyl)butanamide;
(2R)—N-hydroxy-4-(6-((1-(2-hydroxyethyl)azetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-methyl-2-(methylsulfonyl)butanamide;
(R)-2-(3-((2-(4-(hydroxyamino)-3-methyl-3-(methylsulfonyl)-4-oxobutyl)benzo[d]thiazol-6-yl)buta-1,3-diyn-1-yl)azetidin-1-yl)ethyl dihydrogen phosphate;
(2R)—N-hydroxy-4-(6-(((1R,2R)-2-(hydroxymethyl)cyclobutyl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-methyl-2-(methylsulfonyl)butanamide;
(2R)—N-hydroxy-2-methyl-4-(6-(((2S)-1-methylazetidin-2-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-(methylsulfonyl)butanamide;
(2R)—N-hydroxy-2-methyl-2-(methylsulfonyl)-4-(6-((((1-(oxetan-3-ylmethyl)azetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)butanamide;
(2R)—N-hydroxy-4-(6-((1-(3-hydroxypropyl)azetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-methyl-2-(methylsulfonyl)butanamide;
(2R)-4-(6-((1-cyclopropylazetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;
(2R)—N-hydroxy-4-(6-((1-(3-hydroxycyclobutyl)azetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-methyl-2-(methylsulfonyl)butanamide;
(2R)-4-(6-((1-(2-fluoroethyl)azetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;
(2R)-4-(6-(((3-fluoro-1-methylpyrrolidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;
(2R)-4-(6-((4-fluoro-1-methylpiperidin-4-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;
(2R)-4-(6-(((2R,3S)-1,2-dimethylazetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;
(2R)—N-hydroxy-4-(6-(((2R,3R)-2-(hydroxymethyl)-1-methylazetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-methyl-2-methylsulfonyl)butanamide;
(2R)—N-hydroxy-2-methyl-4-(6-((1-(methylamino)cyclopropyl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-(methylsulfonyl)butanamide;
(2R)—N-hydroxy-4-(6-(((2R,3R)-2-(hydroxymethyl)-1-methylazetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-methyl-2-methylsulfonyl)butanamide;
(2R)—N-hydroxy-4-(6-(((3R,5R)-5-(hydroxymethyl)-1-methylpyrrolidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-methyl-2-(methylsulfonyl)butanamide; or
(2R)-2-(3-((4-(5-((1-(3-hydroxypropyl)azetidin-3-yl)buta-1,3-diyn-1-yl)benzo[d]thiazol-2-yl)-2-methyl-2-(methylsulfonyl)butanamido)oxy)-3-oxopropyl)phenyl dihydrogen phosphate;
or a salt thereof.

### Claim 13 (depends on 1)

A medicament comprising the compound of formula I as defined in claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 1)

A pharmaceutical composition containing, as active principle, a compound of formula I as defined in claim 1, or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

### Claim 15 (depends on 1)

A method for the prevention or treatment of a bacterial infection comprising administering the compound of formula I as defined in claim 1, or a pharmaceutically acceptable salt thereof, to a patient in need thereof.