# US 10,501,478 B2 · Tricyclic heterocyclic compounds as phosphoinositide 3-kinase inhibitors

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- Number: US 10,501,478 B2
- Document ID: US10501478B2
- Status: Granted
- Kind: B2
- Application number: 15/909,011
- Filed: 2018-03-01
- Published: 2019-02-07
- Granted: 2019-12-10
- Earliest claimed: 2009-08-20
- Assignees: Karus Therapeutics Limited
- Applicants: Karus Therapeutics Limited
- Inventors: Stephen Joseph Shuttleworth; Alexander Richard Liam Cecil; Thomas James Hill; Franck Alexandre Silva
- Web page: https://patentgrep.com/patent/US10501478B2

## CPC

- C07D 495/14: Ortho-condensed systems
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 491/147: the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein: W is O, N—H, N—(C1-C10 alkyl) or S; each X is independently CH or N; R1 is a 5 to 7-membered saturated or unsaturated, optionally substituted heterocycle containing at least 1 heteroatom selected from N or O; R2 is (LQ)mY; and each R3 is independently H, C1-C10alkyl, aryl or heteroaryl, are surprisingly found to be inhibitors of PI3K-p110δ, and therefore have utility in therapy.

## Claims

### Claim 1

A pharmaceutical composition comprising a compound represented by formula I:
or a pharmaceutically acceptable salt thereof, wherein:
W is O;
X is CH;
R2 is (LQ)mY;
m is 0, 1, or 2;
L is C1alkylene;
Q is selected from the group consisting of: heteroarylene, —NR3—, —C(O)—, —NR4R5—, and —C(O)NR4R5, where R4 and R5 together with the nitrogen to which they are attached form a 5 to 7-membered heterocycle linker;
Y is selected from the group consisting of: H, C1-C10 alkyl, C3-C10 cycloalkyl, —OR3, —N(R3)2, —SO2—R3, —SO2—N(R3)2, halogen, —CN, and —C(halogen)bR3(3-b),
b is from 1 to 3; and
R3 is independently selected for each occurrence from H or C1-C10 alkyl; and
a pharmaceutically acceptable excipient.

### Claim 2 (depends on 1)

The composition of claim 1, wherein both of the R3 groups that are attached to the 6,5-ring system in formula I are H.

### Claim 3 (depends on 1)

The composition of claim 1, wherein Y is H.

### Claim 4 (depends on 1)

The composition of claim 1, wherein Q is selected from —NR3— and —NR4R5—.

### Claim 5 (depends on 1)

The composition of claim 1, wherein Q is —NR4R5 wherein R4 and R5 together with the nitrogen to which they are attached form a 5 to 7-membered heterocycle linker having an additional heteroatom 0; and Y is H.

### Claim 6

A method of treating lymphoma in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound represented by:
or a pharmaceutically acceptable salt thereof, wherein:
W is O;
X is CH;
R2 is (LQ)mY;
m is 0, 1, or 2;
L is C1alkylene:
Q is a heterocyclic linker;
Y is selected from the group consisting of: H, C1-10alkyl, —OR3, and —C(O)N(R3)2; and
R3 is H.

### Claim 7 (depends on 6)

The method of claim 6, wherein Y is H.