# US 2014/0155394 A1 · Chemical Compounds - 759

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- Number: US 2014/0155394 A1
- Document ID: US20140155394A1
- Status: Published application
- Kind: A1
- Application number: 13/923,498
- Filed: 2013-06-21
- Published: 2014-06-05
- Earliest claimed: 2007-05-04
- Assignees: AstraZeneca AB
- Applicants: Astrazeneca AB
- Inventors: Audrey DAVIES; Stephanos IOANNIDIS; Michelle LAMB; Mei SU; Tao WANG; Hai-Jun ZHANG
- Web page: https://patentgrep.com/patent/US20140155394A1

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/06: Antiasthmatics
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 27/02: Ophthalmic agents
- A61P 27/16: Otologicals
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- 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 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 471/22: in which the condensed systems contains four or more hetero rings
- C07D 473/16: two nitrogen atoms
- C07D 473/18: one oxygen and one nitrogen atom, e.g. guanine
- C07D 473/32: Nitrogen atom
- C07D 491/22: in which the condensed system contains four or more hetero rings
- C07D 498/22: in which the condensed system contains four or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to compounds of Formula (I): and to their pharmaceutical compositions, and to their methods of use. These compounds provide a treatment for myeloproliferative disorders and cancer.

## Claims

### Claim 1

A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein
Q is selected from N and C(R3);
D is selected from N and CH;
R1 is selected from H, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, 3- to 5-membered carbocyclyl, 5-membered heterocyclyl, —OR1a, —SR1a, —N(R1a)2, —N(R1a)C(O)R1b, —N(R1a)N(R1a)2, —NO2, —C(O)H, —C(O)R1b, —C(O)2R1a, —C(O)N(R1a)2, —OC(O)N(R1a)2, —N(R1a)C(O)2R1a, —N(R1a)C(O)N(R1a)2, —OC(O)R1b, —S(O)R1b, —S(O)2R1b, —S(O)2N(R1a)2, —N(R1a)S(O)2R1b, —C(R1a)═N(R1a), and —C(R1a)═N(OR1a), wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, 3- to 5-membered carbocyclyl, and 5-membered heterocyclyl are optionally substituted with one or more R10;
R1a in each occurrence is independently selected from H and C1-6alkyl, 3- to 5-membered carbocyclyl, and 5-membered heterocyclyl, wherein said C1-6alkyl, 3- to 5-membered carbocyclyl, and 5-membered heterocyclyl in each occurrence are optionally and independently substituted with one or more R10;
R1b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, 3- to 5-membered carbocyclyl, and 5-membered heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, 3- to 5-membered carbocyclyl, and 5-membered heterocyclyl in each occurrence are optionally and independently substituted with one or more R10;
R2 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR2a, —SR2a, —N(R2a)2, —N(R2a)C(O)R2b, —N(R2a)N(R2a)2, —NO2, —C(O)H, —C(O)R2b, —C(O)2R2a, —C(O)N(R2a)2, —OC(O)N(R2a)2, —N(R2a)C(O)2R2a, —N(R2a)C(O)N(R2a)2, —OC(O)R2b, —S(O)R2b, —S(O)2R2b, —S(O)2N(R2a)2, —N(R2a)S(O)2R2b, —C(R2a)═N(R2a), and —C(R2a)═N(OR2a), wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R20;
R2a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more R20;
R2b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more R20;
R3 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, OR3a, —SR3a, —N(R3a)2, —N(R3a)C(O)R3b, —N(R3a)N(R3a)2, —NO2, —C(O)H, —C(O)R3b, —C(O)2R3a, —C(O)N(R3a)2, —OC(O)N(R3a)2, —N(R3a)C(O)2R3a, —N(R3a)C(O)N(R3a)2, —OC(O)R3b, —S(O)R3b, —S(O)2R3b, —S(O)2N(R3a)2, —N(R3a)S(O)2R3b, —C(R3a)═N(R3a), and —C(R3a)═N(OR3a), wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R30;
R3a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more R30;
R3b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more R30;
R4 is selected from H, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —N(R4a)C(O)R4b, —N(R4a)N(R4a)2, —NO2, —C(O)H, —C(O)R4b, —C(O)2R4a, —C(O)N(R4a)2, —OC(O)N(R4a)2, —N(R4a)C(O)2R4a, —N(R4a)C(O)N(R4a)2, —OC(O)R4b, —S(O)R4b, —S(O)2R4b, —S(O)2N(R4a)2, —N(R4a)S(O)2R4b, —C(R4a)═N(R4a), and —C(R4a)═N(OR4a), wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R40;
R4a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more R40;
R4b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more R40;
R5 is independently selected from halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR5a, —SR5a, —N(R5a)2, —N(R5a)C(O)R5b, —N(R5a)N(R5a)2, —NO2, —C(O)H, —C(O)R5b, —C(O)2R5a, —C(O)N(R5a)2, —OC(O)N(R5a)2, —N(R5a)C(O)2R5a, —N(R6a)C(O)N(R5a)2, —OC(O)R5b, —S(O)R5b, —S(O)2R5b, —S(O)2N(R5a)2, —N(R5a)S(O)2R5b, —C(R5a)═N(R5a), and —C(R5a)═N(OR5a);
R5a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl;
R5b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl;
R10 in each occurrence is independently selected from halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR10a, —SR10a, —N(R10a)2, —N(R10a)C(O)R10b, —N(R10a)N(R10a)2, —NO2, —C(O)H, —C(O)R10b, —C(O)2R10a, —C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)2R10a, —N(R10a)C(O)N(R10a)2, —OC(O)R10b, —S(O)R10b, —S(O)2R10b, —S(O)2N(R10a)2, —N(R10a)S(O)2R10b, —C(R10a)═N(R10a), and —C(R10a)═N(OR10a);
R10a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl;
R10b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl;
R20 in each occurrence is independently selected from halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR20a, —SR20a, —N(R20a)2, —N(R20a)C(O)R20b, —N(R20a)N(R20a)2, —NO2, —C(O)H, —C(O)R20b, —C(O)2R20a, —C(O)N(R20a)2, —OC(O)N(R20a)2, —N(R20a)C(O)2R20a, —N(R20a)C(O)N(R20a)2, —OC(O)R20b, —S(O)R20b, —S(O)2R20b, —S(O)2N(R20a)2, —N(R20a)S(O)2R20b, —C(R20a)═N(R20a), and —C(R20a)═N(OR20a);
R20a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl;
R20b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl;
R30 in each occurrence is independently selected from halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR30a, —SR30a, —N(R30a)2, —N(R30a)C(O)R30b, —N(R30a)N(R30a)2, —NO2, —C(O)H, —C(O)R30b, —C(O)2R30a, —C(O)N(R30a)2, —OC(O)N(R30a)2, —N(R30a)C(O)2R30a, —N(R30a)C(O)N(R30a)2, —OC(O)R30b, —S(O)R30b, —S(O)2R30b, —S(O)2N(R30a)2, —N(R30a)S(O)2R30b, —C(R30a)═N(R30a), and —C(R30a)═N(OR30a);
R30a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl;
R30b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl;
R40 in each occurrence is independently selected from halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR40a, —SR40a, —N(R40a)2, —N(R40a)C(O)R40b, —N(R40a)N(R40a)2, —NO2, —C(O)H, —C(O)R40b, —C(O)2R40a, —C(O)N(R40a)2, —OC(O)N(R40a)2, —N(R40a)C(O)2R40a, —N(R40a)C(O)N(R40a)2, —OC(O)R40b, —S(O)R40b, —S(O)2R40b, —S(O)2N(R40a)2, —N(R40a)S(O)2R40b, —C(R40a)═N(R40a), and —C(R40a)═N(OR40a);
R40a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl; and
R40b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl.

### Claim 2 (depends on 1)

A compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1, wherein
Q is selected from N and C(R3); and
R3 is selected from H and halo.

### Claim 3 (depends on 1)

A compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1, wherein
R1 is selected from H, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, 3- to 5-membered carbocyclyl, 5-membered heterocyclyl, —OR1a, —SR1a, —N(R1a)2, —N(R1a)C(O)R1b, —N(R1a)N(R1a)2, —NO2, —C(O)H, —C(O)R1b, —C(O)2R1a, —C(O)N(R1a)2, —OC(O)N(R1a)2, —N(R1a)C(O)2R1a, —N(R1a)C(O)N(R1a)2, —OC(O)R1b, —S(O)R1b, —S(O)2R1b, —S(O)2N(R1a)2, —N(R1a)S(O)2R1b, —C(R1a)═N(R1a), and —C(R1a)═N(OR1a);
R1a in each occurrence is independently selected from H, C1-6alkyl, 3- to 5-membered carbocyclyl, and 5-membered heterocyclyl;
R1b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, 3- to 5-membered carbocyclyl, and 5-membered heterocyclyl.

### Claim 4 (depends on 1)

A compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1, wherein
R2 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR2a, —SR2a, —N(R2a)2, —N(R2a)C(O)R2b, —N(R2a)N(R2a)2, —NO2, —C(O)H, —C(O)R2b, —C(O)2R2a, —C(O)N(R2a)2, —OC(O)N(R2a)2, —N(R2a)C(O)2R2a, —N(R2a)C(O)N(R2a)2, —OC(O)R2b, —S(O)R2b, —S(O)2R2b, —S(O)2N(R2a)2, —N(R2a)S(O)2R2b, —C(R2a)═N(R2a), and —C(R2a)═N(OR2a);
R2a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl; and
R2b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl.

### Claim 5 (depends on 1)

A compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1, wherein
R4 is selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl may be optionally substituted with one or more R40;
R40 in each occurrence is independently selected from halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR40a, —SR40a, —N(R40a)2, —N(R40a)C(O)R40b, —N(R40a)N(R40a)2, —NO2, —C(O)H, —C(O)R40b, —C(O)2R40a, —C(O)N(R40a)2, —OC(O)N(R40a)2, —N(R40a)C(O)2R40a, —N(R40a)C(O)N(R40a)2, —OC(O)R40b, —S(O)R40b, —S(O)2R40b, —S(O)2N(R40a)2, —N(R40a)S(O)2R40b, —C(R40a)═N(R40a), and —C(R40a)═N(OR40a);
R40a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl; and
R40b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl.

### Claim 6 (depends on 1)

A compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1, wherein
R5 is halo.

### Claim 7

A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein
Q is selected from N and C(R3);
D is selected from N and CH;
R1 is selected from methyl, cyclopropyl, isopropoxy, and ethoxy;
R2 is selected from H, methoxy, morpholin-4-yl, 2-morpholin-4-yl-2-oxoethyl, and tetrahydro-2H-pyran-4-ylamino;
R3 is selected from H, fluoro, and chloro;
R4 is selected from methyl, ethyl, and hydroxymethyl; and
R5 is fluoro.

### Claim 8 (depends on 1)

A method for treating cancer in a warm-blooded animal such as man, said method comprising administering to said animal an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1.

### Claim 9 (depends on 1)

A pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1, and at least one pharmaceutically acceptable carrier, diluent, or excipient.

### Claim 10 (depends on 1)

A process for preparing a compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1, wherein said process is selected from:
1) Process A—reacting a compound of Formula (A):
with a compound of Formula (B):
and
2) Process B—reacting a compound of Formula (C):
with a compound of Formula (D):
and thereafter if appropriate:
i. converting a compound of Formula (I) into another compound of Formula (I);
ii. removing any protecting groups; and/or
iii. forming a pharmaceutically acceptable salt,
wherein
L in each occurrence is the same or different, and is a leaving group.