# US 11,110,090 B2 · Aminopyrimidines as ALK inhibitors

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- Number: US 11,110,090 B2
- Document ID: US11110090B2
- Status: Granted
- Kind: B2
- Application number: 16/914,518
- Filed: 2020-06-29
- Published: 2020-10-22
- Granted: 2021-09-07
- Earliest claimed: 2016-08-29
- Assignees: The Regents of the University of Michigan
- Applicants: The Regents of the University of Michigan
- Inventors: Shaomeng Wang; Jianyong Chen
- Web page: https://patentgrep.com/patent/US11110090B2

## CPC

- A61K 31/506: not condensed and containing further heterocyclic rings
- A61P 35/00: Antineoplastic agents
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present disclosure provides compounds represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6, and R7 are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat a condition or disorder responsive to inhibition of ALK such as cancer.

## Claims

### Claim 1

A method of treating a patient comprising administering to the patient a therapeutically effective amount of a compound having Formula I, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein the patient has a cancer in which anaplastic lymphoma kinase (ALK) has a role and the compound of Formula I has a structure:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
Rla and R1b are independently selected from the group consisting of hydrogen, C1-6 alkyl, and C3-8 cycloalkyl;
R2a and R2b are independently selected from the group consisting of hydrogen, C1-6 alkyl, and C3-8 cycloalkyl;
R3 is selected from the group consisting of hydrogen, C1-6 alkyl, C3-6 cycloalkyl, and C4-8 heterocyclo,
R4 is selected from the group consisting of C1-4 alkyl, and C3-6 cycloalkyl;
R5 is halo;
R6 is selected from the group consisting of C1-4 alkyl, and C3-6 cycloalkyl; and
R7 is selected from the group consisting of hydrogen, C1-4 alkyl, and C3-6 cycloalkyl, with proviso that when R1a, R1b, R2a, and R2b are each hydrogen, then R3 is selected from the group consisting of C3-6 cycloalkyl and C4-8 heterocyclo.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cancer is selected from the group consisting of anaplastic large-cell lymphoma, non-small cell lung cancer, diffuse large B-cell lymphoma, inflammatory myofibroblastic tumors, neuroblastoma, anaplastic thyroid cancer, rhabdomyosarcoma, breast cancer, colorectal cancer, esophageal squamous cell cancer, and renal cell carcinoma.

### Claim 3 (depends on 1)

The method of claim 1 comprising administering a compound having Formula II:
or a pharmaceutically acceptable salt thereof, wherein:
R1a and R1b are independently selected from the group consisting of hydrogen, C1-4 alkyl, and C3-6 cycloalkyl;
R2a and R2b are independently selected from the group consisting of hydrogen, C1-4 alkyl, and C3-6 cycloalkyl; and
R3 is selected from the group consisting of hydrogen, C1-4 alkyl, C3-6 cycloalkyl, and C4-8 heterocyclo.

### Claim 4 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1b and R2b are each hydrogen.

### Claim 5 (depends on 4)

The method of claim 4, or a pharmaceutically acceptable salt thereof, wherein Ria and R1a and R2a are each hydrogen.

### Claim 6 (depends on 4)

The method of claim 4, or a pharmaceutically acceptable salt thereof, wherein R1a and R2a are each C1-4 alkyl or C3-6 cycloalkyl.

### Claim 7 (depends on 6)

The method of claim 6, or a pharmaceutically acceptable salt thereof, wherein R1a and R2a are each methyl or are each cyclopropyl.

### Claim 8 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein Rla, R1b, R2a, and R2b are each C1-3 alkyl.

### Claim 9 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein Rla, R1b, R2a, and R2b are each methyl.

### Claim 10 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, comprising administering a compound having Formula III:
wherein:
R1a and R2a are each independently selected from the group consisting of C1-4 alkyl, and C3-6 cycloalkyl; and
the compound has an enantiomeric excess of 90% or more.

### Claim 11 (depends on 2)

The method of claim 2, or a pharmaceutically acceptable salt thereof comprising administering a compound, having Formula IV:
wherein:
Rla and R2a are each independently selected from the group consisting of C1-4 alkyl, and C3-6 cycloalkyl; and
the compound has an enantiomeric excess of 90% or more.

### Claim 12 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof comprising administering a compound, having Formula V:
wherein:
R1a and R2a are each independently selected from the group consisting of C1-4 alkyl, and C3-6 cycloalkyl; and
the compound has an enantiomeric excess of 90% or more.

### Claim 13 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof comprising administering a compound, having Formula VI:
wherein:
Rla and R2a are each independently selected from the group consisting of C1-4 alkyl, and C3-6 cycloalkyl; and
the compound has an enantiomeric excess of 90% or more.

### Claim 14 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3 is hydrogen, C1-3 alkyl, or C3-6 heterocyclo.

### Claim 15 (depends on 14)

The method of claim 14, or a pharmaceutically acceptable salt thereof, wherein R3 is selected from the group consisting of:

### Claim 16 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
5-chloro-N2-(2-isopropoxy-5-methyl-4-(1,2,2,6,6-pentamethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-(2,2,6,6-tetramethyl-1,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine:
5-chloro-N2-(4-((cis)-2,6-diethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((cis)-2,6-diethyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-(1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-(1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((cis)-2,6-dicyclobutyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((cis)-2,6-dicyclobutyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((cis)-2,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-((cis)-1,2,6-trimethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-diethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-diethyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-((trans)-1,2,6-trimethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((cis)-2,6-dicyclopropyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((cis)-2,6-dicyclopropyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dicyclobutyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dicyclobutyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dicyclopropyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dicyclopropyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((cis)-2,6-dimethyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4-((cis)-2,6-dimethyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-diethyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S6S)-2,6-diethyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dimethyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dimethyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((cis)-2,6-dicyclopropyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4-((cis)-2,6-dicyclopropyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dicyclobutyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dicyclobutyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dicyclopropyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4-((trans)-2,6-dicyclopropyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S,6R)-2,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-(2S,6R)-1,2,6-trimethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6R)-2,6-dicyclopropyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6R)-2,6-dicyclopropyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6S)-2,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-(2R,6S)-1,2,6-trimethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S,6S)-2,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-(2S,6S)-1,2,6-trimethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6R)-2,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-(2R,6R)-1,2,6-trimethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S,6S)-2,6-dicyclopropyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S,6S)-2,6-dicyclopropyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6S)-2,6-dicyclopropyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6S)-2,6-dicyclopropyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine
5-chloro-N2-(4-(2S,6R)-2,6-dicyclopropyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S,6R)-2,6-dicyclopropyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6S)-2,6-dimethyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4(2R,6S)-2,6-dimethyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S,6S)-2,6-dimethyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S,6S)-2,6-dimethyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6R)-2,6-dimethyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6R)-2,6-dimethyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S,6S)-2,6-dicyclopropyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S,6S)-2,6-dicyclopropyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6S)-2,6-dicyclopropyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2R,6S)-2,6-dicyclopropyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenvl)pyrimidine-2,4-diamine;
5-chloro-N2-(4-(2S,6R)-2,6-dicyclopropyl-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine; and
5-chloro-N2-(4-(2S,6R)-2,6-dicyclopropyl-1-(oxetan-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-2-isopropoxy-5-methylphenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine.

### Claim 17 (depends on 16)

The method of claim 16, or a pharmaceutically acceptable salt thereof, which is 5-chloro-N2-(2-isopropoxy-5-methyl-4-(1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl) pyrimidine-2,4-diamine.

### Claim 18

A kit comprising the compound having Formula I or a pharmaceutically acceptable salt thereof, and instructions for administering the compound, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, to a patient having cancer in which anaplastic lymphoma kinase (ALK) has a role, wherein the compound of Formula I has a structure:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
R1a and R1b are independently selected from the group consisting of hydrogen, C1-6 alkyl, and C3-8 cycloalkyl;
R2a and R2b are independently selected from the group consisting of hydrogen, C1-6 alkyl, and C3-8 cycloalkyl;
R3 is selected from the group consisting of hydrogen, C1-6 alkyl, C3-6 cycloalkyl, and C4-8 heterocyclo,
R4 is selected from the group consisting of C1-4 alkyl, and C3-6 cycloalkyl;
R5 is halo;
R6 is selected from the group consisting of C1-4 alkyl, and C3-6 cycloalkyl; and
R7 is selected from the group consisting of hydrogen, C1-4 alkyl, and C3-6 cycloalkyl,
with proviso that when Rla, R1b, R2a, and R2b are each hydrogen, then R3 is selected from the group consisting of C3-6 cycloalkyl and C4-8 heterocyclo.