US 12,319,672 B2
Alpha-D-galactopyranoside derivatives
Martin Bolli, Allschwil (CH); John Gatfield, Allschwil (CH); Corinna Grisostomi, Allschwil (CH); Lubos Remen, Allschwil (CH); Christoph Sager, Allschwil (CH); and Cornelia Zumbrunn, Allschwil (CH)
Assigned to IDORSIA PHARMACEUTICALS LTD, Allschwil (CH)
Appl. No. 17/638,799
Filed by Idorsia Pharmaceuticals Ltd, Allschwil (CH)
PCT Filed Aug. 28, 2020, PCT No. PCT/EP2020/074121
§ 371(c)(1), (2) Date Feb. 25, 2022,
PCT Pub. No. WO2021/038068, PCT Pub. Date Mar. 4, 2021.
Claims priority of application No. PCT/EP2019/073063 (WO), filed on Aug. 29, 2019.
Prior Publication US 2022/0281855 A1, Sep. 8, 2022
Int. Cl. C07H 19/12 (2006.01); C07D 405/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01)
CPC C07D 405/14 (2013.01) [C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07H 19/12 (2013.01)] 23 Claims
 
1. A compound of formula (I)

OG Complex Work Unit Chemistry
wherein
Ar1 represents
aryl which is unsubstituted, or mono-, di-, tri-, tetra-, or penta-substituted, wherein the substituents are independently selected from halogen, methyl, cyano, methoxy, trifluoromethyl, trifluoromethoxy, and ethynyl;
5- or 6-membered heteroaryl, wherein said 5- or 6-membered heteroaryl independently is unsubstituted, mono- or di-substituted, wherein the substituents are independently selected from halogen, methyl, cyano, and methoxy; or
9- or 10-membered heteroaryl, wherein said 9- or 10-membered heteroaryl independently is unsubstituted, or mono-substituted with methyl;
R1 represents
hydroxy; or
methoxy;
A represents 5-membered heterocycloalkylene or 5-membered heteroarylene; wherein said 5-membered heterocycloalkylene is selected from 4,5-dihydroisoxazole-3,5-diyl, imidazolidin-4-one-1,3-diyl, oxazol-2-one-3,5-diyl and oxazolidine-2-one-3,5-diyl; and said 5-membered heteroarylene is selected from 1,2,3-triazole-1,4-diyl, isoxazole-3,5-diyl, imidazole-1,4-diyl, and isothiazole-3,5-diyl; and
R2 represents
C1-6-alkyl;
C1-6-alkyl wherein said C1-6-alkyl is mono-substituted with C1-3-alkoxy, —CO—C1-4-alkoxy, —NH2 or —NH—CO—C1-4-alkoxy;
C1-4-fluoroalkyl;
C3-6-cycloalkyl wherein said C3-6-cycloalkyl independently is unsubstituted, mono- or di-substituted wherein the substituents independently are selected from oxo, fluoro, —NH—CO—C1-4-alkoxy, C1-3-alkyl, C1-3-alkoxy, C1-fluoroalkyl, cyano, —CH2—CN, and —NH—CO—C1-4-alkyl wherein said C1-4-alkyl is mono-substituted with —NH2 or —NH—CO—C1-4-alkoxy; or said C3-6-cycloalkyl together with 1,3-dioxolan-2,2-diyl forms a spiro-bicyclic moiety;
4- to 6-membered heterocycloalkyl wherein said heterocycloalkyl contains one ring oxygen atom and wherein said 4- to 6-membered heterocycloalkyl independently is unsubstituted or mono-substituted with C1-4-alkyl;
4- to 6-membered heterocycloalkyl wherein said heterocycloalkyl contains one ring sulfur atom wherein said sulfur atom is unsubstituted or mono-substituted with oxo (=O); or said sulfur atom is disubstituted wherein one substituent is oxo (=O) and the other substituent is selected from oxo (=O), imido (=NH), C1-3-alkylimido (=N—C1-3-alkyl), 4,4-difluorocyclohexylimido and benzylimido (=N-benzyl);
4- to 7-membered heterocycloalkyl wherein said heterocycloalkyl contains one ring nitrogen atom, wherein said nitrogen atom is unsubstituted or mono-substituted with
C1-6-alkyl;
—CO—C1-6-alkyl; —CO—C4-6-cycloalkyl; —CO—C1-3-fluoroalkyl; —CO—C1-4-alkoxy; —CO—NH—C1-4-alkyl;
—SO2—C1-4-alkyl; —SO2—NH—C1-4-alkyl;
—CH2—C3-6-cycloalkyl;
—CO—C1-6-alkyl wherein the C1-6-alkyl is mono-substituted with amino;
—CH2-oxetanyl;
thiazol-2-yl; oxazol-2-yl; benzo[d]thiazol-2-yl;
—CO-benzyloxy;
—CO—NH2; —CO—NH—C3-6-cycloalkyl;
—CO—NRN31RN32 wherein RN31 and RN32 both independently represent C1-3-alkyl;
—CO—NRN41RN42 wherein RN41 and RN42 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl wherein said 5- or 6-membered heterocycloalkyl independently is unsubstituted or mono-substituted with C1-3-alkyl;
—SO—C1-6-alkyl;
—SO2—C1-3-fluoroalkyl; —SO2—NH2;
—SO2—NRN51RN52 wherein RN51 and RN52 both independently represent C1-3-alkyl;
—SO2—NRN61RN62 wherein RN61 and RN62 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl, wherein said 5- or 6-membered heterocycloalkyl independently is unsubstituted or di-substituted with fluoro;
—SO2-phenyl wherein said phenyl is unsubstituted or mono-substituted with methyl;
>—SO(NH)—C1-6-alkyl; or —SO(N—C1-3-alkyl)-C1-6-alkyl;
and wherein said 4- to 7-membered heterocycloalkyl carries no further substituent in addition to said substituent on the ring nitrogen atom, or carries one further substituent which is C1-4-alkyl (wherein it is understood that such C1-4-alkyl is attached to a ring carbon atom);

OG Complex Work Unit Chemistry
 wherein RN71 represents hydrogen or —CO—C1-4-alkoxy;
cyclopentenyl;
L-OH, wherein L represents
C1-6-alkylene;
chloro-C2-6-alkylene;
1-phenyl-ethan-1,1-diyl or 1-(2-fluorophenyl)-ethan-1,1-diyl;
(cyclopropyl)-(pyridin-2-yl)-methylene;
C4-6-cycloalkylene wherein said C4-6-cycloalkylene independently is unsubstituted, mono- or di-substituted wherein the substituents independently are methyl, fluoro, or —CO—RO2 wherein RO2 represents hydroxy or C1-4-alkoxy;
cyclopropylene-(CH2)n—* wherein n represents the integer 0 or 1, and wherein the asterisk indicates the bond which is connected to the —OH group;
4- to 7-membered heterocycloalkylene wherein said heterocycloalkylene contains one ring oxygen atom; or
4- to 7-membered heterocycloalkylene wherein said heterocycloalkylene contains one ring nitrogen atom, wherein said nitrogen atom is unsubstituted or mono-substituted with —CO—C1-4-alkyl, or —CO—C1-4-alkoxy;
5- or 6-membered heteroaryl, wherein said 5- or 6-membered heteroaryl independently is unsubstituted or mono-substituted, wherein the substituents independently are C1-4-alkyl, C1-3-fluoroalkyl, halogen, C1-4-alkoxy, or C1-4-fluoroalkoxy;
2-oxo-1,2-dihydropyridin-4-yl, 6-oxo-1,6-dihydropyridin-3-yl, or 1-methyl-2-oxo-1,2-dihydropyridin-4-yl;

OG Complex Work Unit Chemistry
 wherein m and p independently represent the integer 1 or 2; and RN81 represents hydrogen or C1-4-alkyl;
C0-3-alkylene-phenyl; wherein the phenyl independently is unsubstituted, mono-, di-, or tri-substituted, wherein the substituents independently are C1-4-alkyl, C1-3-fluoroalkyl, halogen, hydroxy, C1-4-alkoxy, or C1-4-fluoroalkoxy;
9-membered heteroaryl;

OG Complex Work Unit Chemistry
 wherein RN91 represents hydrogen or —CO—C1-4-alkoxy;
or R2 represents a group of the structure (R2-B):

OG Complex Work Unit Chemistry
wherein ring (B) represents a non-aromatic 5-membered ring fused to the phenyl group, wherein ring (B) comprises two heteroatoms independently selected from nitrogen and oxygen; wherein said ring (B) independently is mono- or di-substituted, wherein one of said substituents is oxo, and the other substituent, if present, is C1-3-alkyl;
or a pharmaceutically acceptable salt thereof.