Granted Patent B2

US 12,533,356 · App. 18/463,865 · Granted Jan 27, 2026

Inventors: Andrew Simon Bell (Dundee, GB); Adrian Michael Schreyer (Dundee, GB); Stephanie Versluys (Toulouse, FR)

Assignees: EVOTECH INTERNATIONAL GMBH; RECURSION PHARMACEUTICALS, INC.

A61K31/519A61P35/00C07D487/04G01N33/566

Abstract

Claims (63)

1 . A compound of formula (I), or pharmaceutically acceptable ester, amide, carbamate, solvate or salt thereof, including a salt of such an ester, amide or carbamate,

wherein R 1 is an optionally substituted phenyl, or an optionally substituted 5- or 6-membered aromatic heterocycle comprising 1, 2 or 3 heteroatoms independently selected from the group consisting of N, S and O, wherein said phenyl is optionally substituted with 1, 2 or 3 substituents, each substituent being independently selected from the group consisting of fluorine, meta-chlorine, para-chorine, OH, C 1-8 alkyl, C 1-8 alkyl substituted with 1, 2 or 3 halogens or OH groups, OC 1-8 alkyl, and OC 1-8 alkyl substituted with 1, 2 or 3 halogens or OH groups, and wherein said 5- or 6-membered aromatic heterocycle is optionally substituted with 1, 2 or 3 substituents, each substituent being independently selected from the group consisting of halogen, OH, C 1-8 alkyl, C 1-8 alkyl substituted with 1, 2 or 3 halogens or OH groups, OC 1-8 alkyl, and OC 1-8 alkyl substituted with 1, 2 or 3 halogens or OH groups; and

R 2 is an optionally substituted 5- or 6-membered aromatic heterocycle comprising 2 or 3 heteroatoms independently selected from the group consisting of N, S and O, wherein said 5- or 6-membered aromatic heterocycle is optionally substituted with 1, 2 or 3 substituents, each substituent being independently selected from the group consisting of C 1-3 alkyl and C 1 -3alkyl substituted with 1, 2 or 3 halogens.

2 . A compound as claimed in claim 1 , wherein R 1 is an optionally substituted phenyl, or an optionally substituted 5- or 6-membered aromatic heterocycle comprising 1 or 2 heteroatoms independently selected from the group consisting of N and S.

3 . A compound as claimed in claim 1 , wherein when R 1 is a substituted phenyl, said phenyl is substituted with 1, 2 or 3 substituents, each substituent being independently selected from the group consisting of halogen (preferably F or Cl, and more preferably F or meta or para Cl), C 1-8 alkyl, C 1-8 alkyl substituted with 1, 2 or 3 halogens (preferably F) or OH groups, OC 1-8 alkyl, and OC 1-8 alkyl substituted with 1, 2 or 3 halogens (preferably F).

4 . A compound as claimed in claim 1 , wherein when R 1 is a substituted phenyl, said phenyl is substituted with 1 or 2 substituents, each substituent being independently selected from the group consisting of C 1-4 alkyl, C 1-4 alkyl substituted with 1, 2 or 3 halogens (preferably F) or OH groups, OC 1-4 alkyl, and OC 1-4 alkyl substituted with 1, 2 or 3 halogens (preferably F) or OH groups.

5 . A compound as claimed in claim 1 , wherein when R 1 is a substituted phenyl, said phenyl is substituted with 1 or 2 substituents, each substituent being independently selected from the group consisting of F, meta-chlorine, para-chorine, C 1-4 alkyl, C 1-4 alkyl substituted with 1, 2 or 3 halogens (preferably F) or OH groups, and OC 1-4 alkyl; and more preferably each substituent being independently selected from the group consisting of halogen (e.g. F or Cl), C 1-4 alkyl, C 1-4 alkyl substituted with 1 OH group and OC 1-4 alkyl.

6 . A compound as claimed in claim 1 , wherein R 1 is a substituted phenyl.

7 . A compound as claimed in claim 1 , wherein R 2 is an optionally substituted 5- or 6-membered aromatic heterocycle comprising 2 or 3 heteroatoms independently selected from the group consisting of N, S and O, wherein at least one of the heteroatoms is N.

8 . A compound as claimed in claim 1 , wherein R 2 is an optionally substituted 5- or 6-membered aromatic heterocycle selected from the group consisting of imidazolyl (1,3-diazolyl), pyrazolyl (1,2-diazolyl), 1,3-oxazolyl, isoxazolyl (1,2-oxazolyl), thiazolyl (1,3-thiazolyl), isothiazolyl (1,2-thiazolyl), 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl, 4H-1,2,4-triazolyl, furazanyl (1,2,5-oxadiazolyl), 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, pyridazinyl (1,2-diazinyl), pyrimidinyl (1,3-diazinyl), pyrazinyl (1,4-di azirtyl), 1,2,3-triazinyl, 1,2,4-triazinyl, and 1,3,5-triazinyl; or

wherein R 2 is an optionally substituted 5- or 6-membered aromatic heterocycle selected from the group consisting of 1,3-oxazolyl, isoxazolyl (1,2-oxazolyl), thiazolyl (1,3-thiazolyl), isothiazolyl (1,2-thiazolyl), 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, pyridazinyl (1,2-diazinyl), pyrimidinyl (1,3-diazinyl), and pyrazinyl (1,4-diazinyl).

9 . A compound as claimed in claim 1 , wherein R 2 is an optionally substituted 5- or 6-membered aromatic heterocycle selected from the group consisting of imidazolyl (1,3-diazolyl), pyrazolyl (1,2-diazolyl), 1,3-oxazolyl, isoxazolyl (1,2-oxazolyl), thiazol-2-yl (1,3-thiazol-2-yl), isothiazolyl (1,2-thiazolyl), 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl, 4H-1,2,4-triazolyl, furazanyl (1,2,5-oxadiazolyl), 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, pyridazinyl (1,2-diazinyl), pyrimidinyl (1,3-diazinyl), pyrazinyl (1,4-diazinyl), 1,2,3-triazinyl, 1,2,4-triazinyl, and 1,3,5-triazinyl; or

wherein R 2 is an optionally substituted 5- or 6-membered aromatic heterocycle selected from the group consisting of 1,3-oxazolyl, isoxazolyl (1,2-oxazolyl), thiazol-2-yl (1,3-thiazol-2-yl), isothiazolyl (1,2-thiazolyl), 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, pyridazinyl (1,2-diazinyl), pyrimidinyl (1,3-diazinyl), and pyrazinyl (1,4-diazinyl).

10 . A compound as claimed in claim 1 , wherein, R 2 is an optionally substituted 5- or 6-membered aromatic heterocycle, and wherein said 5- or 6-membered aromatic heterocycle is optionally substituted with 1 or 2 substituents (preferably 1 substituent), each substituent being independently selected from the group consisting of C 1-3 alkyl and C 1-3 alkyl substituted with 1, 2 or 3 fluorines; and preferably each substituent is methyl; or

wherein R 2 is an unsubstituted 5- or 6-membered aromatic heterocycle.

11 . A compound as claimed in claim 1 , wherein the compound is selected from the group consisting of

2-[(3-methylphenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methoxyphenyl)methyl]-6-(pyrazin-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-{[4-amino-6-(pyrazin-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl]methyl}phenol;

2-[(3-methoxyphenyl)methyl]-6-(1,3-oxazol-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methoxyphenyl)methyl]-6-(4-methyl-1,3-thiazol-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methoxyphenyl)methyl]-6-(3-methyl-1,2-oxazol-5-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methoxyphenyl)methyl]-6-(4-methyl-1,2,3-thiadiazol-5-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methoxyphenyl)methyl]-6-(1,3-thiazol-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methoxyphenyl)methyl]-6-(1,3-thiazol-4-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methoxyphenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methoxyphenyl)methyl]-6-(1,3-oxazol-5-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(4-methylphenyl)methyl]-6-(pyrazin-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(4-methylphenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(4-methylphenyl)methyl]-6-(1,3-thiazol-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(4-methoxyphenyl)methyl]-6-(pyrazin-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

6-(1,2-thiazol-3-yl)-2-{[3-(trifluoromethoxy)phenyl]methyl}-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

6-(1,2-thiazol-3-yl)-2-{[4-(trifluoromethyl)phenyl]methyl}-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methoxy-4-methylphenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-fluoro-4-methylphenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3,4-dimethylphenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(pyridin-2-yl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(6-methylpyridin-3-yl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-{[4-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(2-methoxy-4-methylphenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methylphenyl)methyl]-6-(1,3-oxazol-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-methylphenyl)methyl]-6-(pyrazin-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

6-(pyrazin-2-yl)-2-{[3-(trifluoromethyl)phenyl]methyl}-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-fluorophenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-fluorophenyl)methyl]-6-(pyrazin-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(2-methylphenyl)methyl]-6-(pyrazin-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(2-methylphenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

6-(1,3-thiazol-2-yl)-2-[(1,3-thiazol-2-yl)methyl]-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(1,3-thiazol-2-yl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-chlorophenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3-chlorophenyl)methyl]-6-(pyrazin-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(2-methoxyphenyl)methyl]-6-(pyrazin-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(2-methoxyphenyl)methyl]-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(2-methoxyphenyl)methyl]-6-(1,3-oxazol-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(2-methoxyphenyl)methyl]-6-(1,3-oxazol-5-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

2-[(3,4-dimethoxyphenyl)methyl]-6-(pyrazin-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine;

3-{[4-amino-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl]methyl}phenol;

2-{[4-amino-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl]methyl}-5-methylphenol;

2-{[4-amino-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl]methyl}phenol;

5-{[4-amino-6-(1,2-thiazol-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl]methyl}-2-methylphenol; and

[3-[(4-amino-6-(1,2-thiazol-3-yl)-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]methanol;

or pharmaceutically acceptable ester, amide, carbamate, solvate or salt thereof, including a salt of such an ester, amide or carbamate.

12 . A pharmaceutical composition which comprises a compound as claimed in claim 1 , together with a pharmaceutically suitable carrier, and optionally also comprises a further therapeutic agent.

Assignments (3)

Priority Claims (1)

Continuity (2)

References Cited (83)