# US 2023/0057568 A1 · Compounds for treating familial dysautonomia

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- Number: US 2023/0057568 A1
- Document ID: US20230057568A1
- Status: Published application
- Kind: A1
- Application number: 17/783,941
- Filed: 2020-12-07
- Published: 2023-02-23
- Earliest claimed: 2019-12-12
- Assignees: PTC Therapeutics, Inc.
- Applicants: Ptc Therapeutics, Inc.
- Inventors: Nanjing ZHANG; Michael A. ARNOLD; Amal DAKKA; Gary Mitchell KARP; Tom Tuan LUONG; Christie MORRILL; Jana NARASIMHAN; Nikolai A. NARYSHKIN; Anthony TURPOFF; Jiashi WANG; Xiaoyan ZHANG
- Web page: https://patentgrep.com/patent/US20230057568A1

## CPC

- C07D 495/04: Ortho-condensed systems
- A61P 25/00: Drugs for disorders of the nervous system
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present description relates to compounds useful for improving pre-mRNA splicing in a cell. In particular, another aspect of the present description relates to substituted thieno [3,2-d]pyrimidine compounds, forms, and pharmaceutical compositions thereof and methods of use for treating or ameliorating familial dysautonomia.

## Claims

### Claim 1

A compound of Formula (I):
or a form thereof, wherein
R1 is selected from the group consisting of aryl and heteroaryl, optionally substituted with one, two, three, or four independently selected R1a substituents;
R1a selected from the group consisting of cyano, halo, hydroxy, C1-6alkyl, halo-C1-6alkyl, deutero-C1-6alkyl, and C1-6alkoxy;
R2 selected from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, aryl, heterocyclyl, and heteroaryl,
wherein each instance of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, aryl, heterocyclyl, and heteroaryl is optionally substituted with one, two, three, or four independently selected R2a substituents, and
wherein each instance of C1-6alkyl, C2-6alkenyl, C2-6alkynyl and heterocyclyl optionally contains a chiral carbon having an (R) or (S) configuration;
R2a selected from the group consisting of cyano, halo, hydroxy, oxo, C1-6alkyl, halo-C1-6alkyl, deutero-C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, halo-C1-6alkoxy, carboxyl, amino, C1-6alkyl-amino, halo-C1-6alkyl-amino, deutero-C1-6alkyl-amino, (C1-6alkyl)2-amino, C3-10cycloalkyl-amino, aryl-amino, heterocyclyl-amino, heteroaryl-amino, C1-6alkyl-thio, C1-6alkyl-sulfonyl, C3-10cycloalkyl, aryl, heterocyclyl, and heteroaryl,
wherein each instance of C3-10cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted with one, two, three or four independently selected R2a′ substituents;
R2a′ selected from the group consisting of cyano, halo, hydroxy, oxo, C1-6alkyl, halo-C1-6alkyl, deutero-C1-6alkyl, and C1-6alkoxy;
R3 selected from the group consisting of hydrogen, cyano, halo, hydroxy, C1-6alkyl, halo-C1-6alkyl, C1-6alkoxy, amino, C1-6alkyl-amino, (C1-6alkyl)2-amino, C3-10ocycloalkyl, aryl, heterocyclyl, and heteroaryl,
wherein each instance of C1-6alkyl, C3-10cycloalkyl, aryl, heterocyclyl, or heteroaryl are optionally substituted with one, two, three, or four independently selected R3a substituents;
R3a selected from the group consisting of cyano, halo, hydroxy, C1-6alkyl, halo-C1-6alkyl, and C1-6alkoxy; and
R4 selected from the group consisting of hydrogen, cyano, halo, hydroxy, C1-6alkyl, halo-C1-6alkyl, C1-6alkoxy, carbamoyl, C3-10cycloalkyl, aryl, and heterocyclyl;
wherein the form of the compound is selected from the group consisting of a salt, hydrate, solvate, racemate, enantiomer, diastereomer, stereoisomer, and tautomer form thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R1 is phenyl optionally substituted with one, two, three, or four independently selected R1a substituents.

### Claim 3 (depends on 1)

The compound of claim 1, wherein R1 is heteroaryl selected from the group consisting of furanyl, thiophenyl, 1H-pyrazolyl, 1H-imidazolyl, isoxazolyl, 1,2-thiazolyl, 1,3-thiazolyl, 1,2-oxazolyl, 1,3-oxazolyl, tetrazolyl, 1,2,3-triazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzofuranyl, and quinolinyl, wherein heteoraryl is optionally substituted with one, two, three, or four independently selected R1a substituents.

### Claim 4 (depends on 1)

The compound of claim 1, wherein R1 is heteroaryl selected from the group consisting of furanyl, thiophenyl, 1H-pyrazolyl, 1H-imidazolyl, 1,2-thiazolyl, 1,3-thiazolyl, 1,2-oxazolyl, 1,3-oxazolyl, pyridinyl, pyrimidinyl, and pyrazinyl, wherein heteroaryl is optionally substituted with one, two, three, or four independently selected R1a substituents.

### Claim 5 (depends on 1)

The compound of claim 1, wherein R1a is selected from the group consisting of halo and C1-6alkyl.

### Claim 6 (depends on 1)

The compound of claim 1, wherein R2 is selected from the group consisting of hydrogen, C1-6alkyl, and heterocyclyl, wherein each instance of C1-6alkyl and heterocyclyl is optionally substituted with one, two, three, or four independently selected Rea substituents, and wherein each instance of C1-6alkyl and heterocyclyl optionally contains a chiral carbon having an (R) or (S) configuration.

### Claim 7 (depends on 1)

The compound of claim 1, wherein R2 is C1-6alkyl selected from the group consisting of methyl, ethyl, propyl, butyl, and pentyl.

### Claim 8 (depends on 1)

The compound of claim 1, wherein R2 is C1-6alkyl, wherein C1-6alkyl contains a chiral carbon having the (R) configuration.

### Claim 9 (depends on 1)

The compound of claim 1, wherein R2 is C1-6alkyl, wherein C1-6alkyl contains a chiral carbon having the (S) configuration.

### Claim 10

A compound, or a form thereof, selected from the group consisting of:
2-chloro-N-[(pyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminobutyl]-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2R)-2-amino-3-methylbutyl]-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2R,3S)-2-amino-3-methylpentyl]-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2R)-2-amino-3,3-dimethylbutyl]-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-N-[furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(pyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminobutyl]-2-chloro-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-N-[pyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminobutyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-N-[(furan-2-yl)methyl]-2,7-dimethylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-ethyl-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-cyclopropyl-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
(2R)-2-amino-3-(2-chloro-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidin-6-yl)propan-1-ol;
6-[(2S)-2-aminopropyl]-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidine-2-carboxamide;
6-[(2S)-2-aminopropyl]-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidine-2-carbonitrile;
(2R)-2-amino-3-(2-chloro-4-{[(furan-2-yl)methyl]amino}thieno[3,2-d]pyrimidin-6-yl)propan-1-ol;
2-chloro-7-methyl-N-[(pyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(5-methylfuran-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
N-[(furan-2-yl)methyl]-7-methyl-2-(trifluoromethyl)thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-N-[(furan-2-yl)methyl]-7-methyl-2-(trifluoromethyl)thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(4-methyl-1,3-thiazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,3-thiazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(3-methylfuran-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(5-methyl-1,3-thiazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(pyrazin-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(5-fluorothiophen-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-N-benzyl-2-chloro-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(3-fluoropyridin-4-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-cyclopropyl-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminobutyl]-2-chloro-7-methyl-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-bromo-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,2-oxazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-7-bromo-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-(azetidin-3-yl)-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
7-bromo-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
7-bromo-2-chloro-N-[(pyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(2-fluorophenyl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(pyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(1 S)-1-aminoethyl]-7-bromo-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(1S)-1-aminoethyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(1S)-1-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(1R)-1-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(pyrimidin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-amino-4-fluorobutyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
(4S)-4-[(2-chloro-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidin-6-yl)methyl]-1,3-oxazinan-2-one;
6-[(2S)-2-aminobutyl]-2-chloro-N-[(3-fluoropyridin-4-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminobutyl]-2-chloro-7-methyl-N-[(1,3-thiazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(pyrimidin-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
(2R)-2-amino-3-(2-chloro-7-methyl-4-{[(thiophen-2-yl)methyl]amino}thieno[3,2-d]pyrimidin-6-yl)propan-1-ol;
2-chloro-N-[(furan-2-yl)methyl]-7-methyl-6-(pyrrolidin-3-yl)thieno[3,2-d]pyrimidin-4-amine;
6-[(1S)-1-aminoethyl]-2-chloro-N-[(furan-2-yl)methyl]-7-phenylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(3-fluoropyridin-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(2-fluoropyridin-3-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(1S)-1-aminoethyl]-N-[(furan-2-yl)methyl]-2,7-diphenylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminobutyl]-2-chloro-7-methyl-N-[(1,2-thiazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
3-(2-chloro-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidin-6-yl)propan-1-ol;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(3,5-difluoropyridin-4-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-(4-methoxyphenyl)thieno[3,2-d]pyrimidin-4-amine;
(2S)-3-(2-chloro-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidin-6-yl)-2-methylpropan-1-ol;
6-(3-aminopropyl)-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-7-bromo-2-chloro-N-[(3-fluoropyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminobutyl]-2-chloro-7-methyl-N-[(1,3-oxazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-3-amino-2-methylpropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
(2R)-3-(2-chloro-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidin-6-yl)-2-methylpropan-1-ol;
6-[(2R)-3-amino-2-methylpropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(1H-imidazol-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,3-thiazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,3-oxazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2R)-2-amino-3-methoxypropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-ethyl-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
2-chloro-6-[(2S)-2-(cyclobutylamino)propyl]-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
2-chloro-N-[(furan-2-yl)methyl]-7-methyl-6-[(2S)-2-(methylamino)propyl]thieno[3,2-d]pyrimidin-4-amine;
7-bromo-2-chloro-N-[(thiophen-2-yl)methyl]thieno[3 ,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1-methyl-1H-pyrazol-5-yl)methyl]thieno[3 ,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-7-bromo-2-chloro-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-7-bromo-4-{[(thiophen-2-yl)methyl]amino}thieno[3,2-d]p yrimidine-2-c arbonitrile;
2-chloro-4-{[(thiophen-2-yl)methyl]amino}thieno[3 ,2-d]pyrimidine-7-carbonitrile;
6-[(2S)-2-aminopropyl]-4-{[(thiophen-2-yl)methyl]amino}thieno[3 ,2-d]pyrimidine-2,7-dicarbonitrile;
6-[(2S)-2-aminopropyl]-2-chloro-7-cyclopropyl-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-phenyl-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-7-(4-chlorophenyl)-N-[(thiophen-2-yl)methyl]thieno[3 ,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminobutyl]-2-chloro-7-methyl-N-[(pyrimidin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(3-fluorothiophen-2-yl)methyl]-7-methylthieno[3 ,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminobutyl]-2-chloro-N-[(3-fluorothiophen-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(4-fluoro-1,3-thiazol-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(5-fluoro-1,3-thiazol-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
6-[(1R)-1-aminoethyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine;
2-chloro-N-[(pyrimidin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
2-chloro-N-[(1,3-thiazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
(3S)-3-amino-4-(2-chloro-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidin-6-yl)butan-1-ol;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(5-fluoropyrimidin-4-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine, and
(2R)-2-amino-3-(2-chloro-7-methoxy-4-{[(thiophen-2-yl)methyl]amino}thieno[3,2-d]pyrimidin-6-yl)propan-1-ol;
wherein the form of the compound is selected from the group consisting of a salt, hydrate, solvate, racemate, enantiomer, diastereomer, stereoisomer, and tautomer form thereof.

### Claim 11 (depends on 1)

The compound of claim 1, or a form thereof, wherein the compound is selected from the group consisting of:
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(thiophen-3-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1H-pyrazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1-methyl-1H-imidazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-3-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1H-pyrrol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,2-oxazol-3-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1-methyl-1H-pyrazol-3-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,2-oxazol-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,2-thiazol-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1H-pyrazol-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1-methyl-1H-pyrazol-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,3-oxazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,3-oxazol-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,3-thiazol-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-N-[(1H-imidazol-5-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1-methyl-1H-imidazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1-methyl-1H-imidazol-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(2H-1,2,3-triazol-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1H-tetrazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1-methyl-1H-pyrrol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1H-pyrrol-3-yl)methyl]thieno[3,2-d]pyrimidin-4-amine
6-[(S)-(1-(1-aminoethyl)cyclopropyl)]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine
6-[(S)-(1-(amino(cyclopropyl)methyl)cyclopropyl)]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine
6-[(2R)-2-amino-2-cyclopropylethyl]-7-bromo-2-chloro-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine, and
6-[(2R)-2-amino-2-cyclopropylethyl]-2-chloro-7-methyl-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine;
wherein the form of the compound is selected from the group consisting of a salt, hydrate, solvate, racemate, enantiomer, diastereomer, stereoisomer, and tautomer form thereof.

### Claim 12

A compound, or a form thereof, selected from the group consisting of:
6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminobutyl]-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2R)-2-amino-3-methylbutyl]-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2R,3S)-2-amino-3-methylpentyl]-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2R)-2-amino-3,3-dimethylbutyl]-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-N-[furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(pyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminobutyl]-2-chloro-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-N-[pyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminobutyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-N-[furan-2-yl)methyl]-2,7-dimethylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-ethyl-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-cyclopropyl-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine hydrochloride;
(2R)-2-amino-3-(2-chloro-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidin-6-yl)propan-1-ol dihydrochloride;
6-[(2S)-2-aminopropyl]-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidine-2-carboxamide trifluoroacetate;
6-[(2S)-2-aminopropyl]-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidine-2-carbonitrile trifluoroacetate;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(5-methylfuran-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-N-[furan-2-yl)methyl]-7-methyl-2-(trifluoromethyl)thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(4-methyl-1,3-thiazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,3-thiazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine trifluoroacetate;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(3-methylfuran-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(5-methyl-1,3-thiazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(pyrazin-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(5-fluorothiophen-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-N-benzyl-2-chloro-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(3-fluoropyridin-4-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-cyclopropyl-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine trifluoroacetate;
6-[(2S)-2-aminobutyl]-2-chloro-7-methyl-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-bromo-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine trifluoroacetate;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,2-oxazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(2S)-2-aminopropyl]-7-bromo-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-(azetidin-3-yl)-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine trifluoroacetate;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(2-fluorophenyl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(pyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(1S)-1-aminoethyl]-7-bromo-2-chloro-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(1S)-1-aminoethyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(1S)-1-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(1R)-1-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(pyrimidin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-amino-4-fluorobutyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminobutyl]-2-chloro-N-[(3-fluoropyridin-4-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminobutyl]-2-chloro-7-methyl-N-[(1,3-thiazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(pyrimidin-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
(2R)-2-amino-3-(2-chloro-7-methyl-4-{[(thiophen-2-yl)methyl]amino}thieno[3,2-d]pyrimidin-6-yl)propan-1-ol dihydrochloride;
2-chloro-N-[(furan-2-yl)methyl]-7-methyl-6-(pyrrolidin-3-yl)thieno[3,2-d]pyrimidin-4-amine formate;
6-[(1S)-1-aminoethyl]-2-chloro-N-[(furan-2-yl)methyl]-7-phenylthieno[3,2-d]pyrimidin-4-amine formate;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(3-fluoropyridin-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(2-fluoropyridin-3-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(1S)-1-aminoethyl]-N-[(furan-2-yl)methyl]-2,7-diphenylthieno[3,2-d]pyrimidin-4-amine formate;
6-[(2S)-2-aminobutyl]-2-chloro-7-methyl-N-[(1,2-thiazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine formate;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(3,5-difluoropyridin-4-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-(4-methoxyphenyl)thieno[3,2-d]pyrimidin-4-amine formate;
6-(3-aminopropyl)-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(2S)-2-aminopropyl]-7-bromo-2-chloro-N-[(3-fluoropyridin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminobutyl]-2-chloro-7-methyl-N-[(1,3-oxazol-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-3-amino-2-methylpropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(2R)-3-amino-2-methylpropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(1H-imidazol-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,3-thiazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1,3-oxazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2R)-2-amino-3-methoxypropyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-ethyl-N-[(furan-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine hydrochloride;
2-chloro-6-[(2S)-2-(cyclobutylamino)propyl]-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine formate;
2-chloro-N-[(furan-2-yl)methyl]-7-methyl-6-[(2S)-2-(methylamino)propyl]thieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(1-methyl-1H-pyrazol-5-yl)methyl]thieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(2S)-2-aminopropyl]-7-bromo-2-chloro-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(2S)-2-aminopropyl]-7-bromo-4-{[(thiophen-2-yl)methyl]amino}thieno[3,2-d]pyrimidine-2-carbonitrile formate;
6-[(2S)-2-aminopropyl]-4-{[(thiophen-2-yl)methyl]amino}thieno[3,2-d]pyrimidine-2,7-dicarbonitrile hydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-cyclopropyl-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine formate;
6-[(2S)-2-aminopropyl]-2-chloro-7-phenyl-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-7-(4-chlorophenyl)-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine hydrochloride;
6-[(2S)-2-aminobutyl]-2-chloro-7-methyl-N-[(pyrimidin-4-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(3-fluorothiophen-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminobutyl]-2-chloro-N-[(3-fluorothiophen-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(4-fluoro-1,3-thiazol-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(5-fluoro-1,3-thiazol-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine dihydrochloride;
6-[(1R)-1-aminoethyl]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine hydrochloride;
(3S)-3-amino-4-(2-chloro-4-{[(furan-2-yl)methyl]amino}-7-methylthieno[3,2-d]pyrimidin-6-yl)butan-1-ol dihydrochloride;
6-[(2S)-2-aminopropyl]-2-chloro-N-[(5-fluoropyrimidin-4-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine formate, and
(2R)-2-amino-3-(2-chloro-7-methoxy-4-{[(thiophen-2-yl)methyl]amino}thieno[3,2-d]pyrimidin-6-yl)propan-1-ol dihydrochloride;
or form thereof, wherein the form of the compound salt is selected from the group consisting of a hydrate, solvate, racemate, enantiomer, diastereomer, stereoisomer, and tautomer form thereof.

### Claim 13 (depends on 1)

The compound of claim 1, or a form thereof, wherein the compound salt is selected from the group consisting of:
6-[(S)-(1-(1-aminoethyl)cyclopropyl)]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine formate
6-[(S)-(1-(amino(cyclopropyl)methyl)cyclopropyl)]-2-chloro-N-[(furan-2-yl)methyl]-7-methylthieno[3,2-d]pyrimidin-4-amine formate
6-[(2R)-2-amino-2-cyclopropylethyl]-7-bromo-2-chloro-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride, and
6-[(2R)-2-amino-2-cyclopropylethyl]-2-chloro-7-methyl-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine dihydrochloride;
wherein the form of the compound salt is selected from the group consisting of a hydrate, solvate, racemate, enantiomer, diastereomer, stereoisomer, and tautomer form thereof.

### Claim 14 (depends on 1)

A method of treating familial dysautonomia comprising administering to a subject in need thereof an effective amount of the compound of claim 1.

### Claim 15 (depends on 10)

A method of treating familial dysautonomia comprising administering to a subject in need thereof an effective amount of the compound of claim 10.

### Claim 16 (depends on 12)

A method of treating familial dysautonomia comprising administering to a subject in need thereof an effective amount of the compound of claim 12.

### Claim 17 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1 in an admixture with a pharmaceutically acceptable excipient.

### Claim 18 (depends on 10)

A pharmaceutical composition comprising the compound of claim 10 in an admixture with a pharmaceutically acceptable excipient.

### Claim 19 (depends on 12)

A pharmaceutical composition comprising the compound of claim 12 in an admixture with a pharmaceutically acceptable excipient.

### Claim at position 20

-25. (canceled)