# US 9,434,726 B2 · Substituted pyrido[3,4-b]pyrazines as Syk inhibitors

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- Number: US 9,434,726 B2
- Document ID: US9434726B2
- Status: Granted
- Kind: B2
- Application number: 14/124,325
- Filed: 2012-06-07
- Published: 2014-05-01
- Granted: 2016-09-06
- Earliest claimed: 2011-06-08
- Assignees: Hutchison Medipharma Limited
- Applicants: Wei-Guo Su; Wei Deng; Jianguo Ji
- Inventors: Wei-Guo Su; Wei Deng; Jianguo Ji
- Web page: https://patentgrep.com/patent/US9434726B2

## CPC

- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/541: Non-condensed thiazines containing further heterocyclic rings
- A61K 31/551: having two nitrogen atoms, e.g. dilazep
- A61K 31/553: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/06: Antianaemics
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- 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 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- 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 471/04: Ortho-condensed systems
- 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
- 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

Provided are pyridopyrazine compounds of formula (I), pharmaceutical compositions thereof and methods of use therefore, wherein R1, R2, R3, R4 and m are as defined in the specification.

## Claims

### Claim 1

A compound of formula (I):
and/or a pharmaceutically acceptable salt thereof, wherein
R1 is independently chosen from hydrogen and C1-C6 alkyl;
R2 is aryl, or heteroaryl, which is optionally substituted by one or more groups (i) selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, or —S(O)nNR5R6, or (ii) selected from C1-6 alkyl, cycloalkyl, heterocycyl, heteroaryl, and aryl, wherein each of (ii) is optionally substituted with one or more groups selected from halo, hydroxy, —C1-C4 alkyl, —C1-C4 haloalkyl, —O—C1-C4 alkyl, —C1-C4 alkyl-OH, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), —CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —N(C1-C4 alkyl)C(O)(C1-C4 alkyl), —C(O) C1-C4 alkyl, —C(O) C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, —SO2NH(C1-C4 alkyl), —NHSO2(C1-C4 alkyl), and heterocyclyl optionally substituted by —SO2(C1-C4 alkyl),
R3 and R4 are independently selected from hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, —S(O)nNR5R6, C1-6 alkyl, cycloalkyl, heterocyclyl, heteroaryl, aryl, alkenyl, and alkynyl, wherein the heterocyclyl is optionally substituted by one or more groups selected from —C1-C4 alkyl, —C1-C4 haloalkyl, —C1-C4 alkyl-OH, halo, hydroxy, —CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —C(O)C1-C4 alkyl, —C(O)C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, and heteroaryl,
or R3 and R4, together with the N atom to which they are attached, can form a 4-12 membered monocyclic, fused bicyclic or spirocyclic ring optionally containing an additional 1-3 heteroatoms chosen from N and O, which is optionally substituted with one or more groups selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, —S(O)nNR5R6, C1-6 alkyl, cycloalkyl, heterocyclyl, heteroaryl, aryl, alkenyl, and alkynyl, wherein the C1-6 alkyl is optionally substituted by one or more groups selected from hydroxy, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), and —NHSO2(C1-C4 alkyl),
m is 0, 1 or 2,
n is 1 or 2,
R5, R6, R7, R8, R9, R10, and R11 are independently selected from hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, heterocyclyl, amino, and amide, wherein the amino is optionally substituted by one or two —C1-C4 alkyl,
or R5 and R6, R5 and R7, R5 and R8, R5 and R9, and R5 and R10 together with the atom(s) to which they are attached can form a ring, which is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, heterocycyl, amino, and amide.

### Claim 2 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein
R1 is independently chosen from hydrogen, and C1-C6 alkyl;
R2 is C5-C10aryl or 5-10 membered heteroaryl, which is optionally substituted by one or more groups (i) selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NO2, or —S(O)nNR5R6, or (ii) selected from C1-C6 alkyl, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, 5-10 membered heteroaryl, or C5-C10 aryl, wherein each of (ii) is optionally substituted with one or more groups selected from halo, hydroxy, —C1-C4 alkyl, —C1-C4 haloalkyl, —O—C1-C4 alkyl, —C1-C4 alkyl-OH, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —N(C1-C4 alkyl)C(O)(C1-C4 alkyl), —C(O) C1-C4 alkyl, —C(O)—C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, —SO2NH(C1-C4 alkyl), —NHSO2(C1-C4 alkyl), and heterocyclyl optionally substituted by —SO2(C1-C4 alkyl),
R3 and R4 are independently selected from hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, and 3-8 membered heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, —NR5R6, —OR7, —C(O)OR7, —CN, —C(O)NR5R6, —S(O)nNR5R6, C1-C6 alkyl, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, 5-10 membered heteroaryl, and C5-C10 aryl, wherein the 3-8 membered heterocyclyl is optionally substituted by one or more groups selected from —C1-C4 alkyl, —C1-C4 haloalkyl, —C1-C4 alkyl-OH, halo, -hydroxy, —CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —C(O)C1-C4 alkyl, —C(O)C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, and heteroaryl,
or R3 and R4, together with the N atom to which they are attached, can form a 4-12 membered monocyclic, fused bicyclic or spirocyclic ring optionally containing an additional 1-3 heteroatoms chosen from N and O, which is optionally substituted with one or more groups selected from —NR5R6, —OR7, —C(O)OR7, —C(O)NR5R6, —NR5S(O)nNR10R11, —NR5C(O)NR10R11, —S(O)nNR5R6, C1-C6 alkyl, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, 5-10 membered heteroaryl, and C5-C10 aryl, wherein the C1-6 alkyl is optionally substituted by one or more groups selected from hydroxy, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), and —NHSO2(C1-C4 alkyl),
m is 0 or 1,
n is 2,
R5, R6, R7, R8, R9, R10, and R11 are independently selected from hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, heterocyclyl, amino, and amide, wherein the amino is optionally substituted by one or two —C1-C4 alkyl,
or R5 and R6, R5 and R7, R5 and R8, R5 and R9, and R5 and R10 together with the atom(s) to which they are attached can form a ring.

### Claim 3 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein
R1 is independently chosen from hydrogen and methyl;
R2 is independently selected from phenyl, pyridyl, pyrimidinyl, pyrazolyl, furyl, and indolyl, which is optionally substituted by one or more groups (i) selected from halo, —NR5R6, —OR7, —S(O)nR8, —CN, —C(O)NR5R6, —NR5S(O)nR8, or —S(O)nNR5R6; or (ii) selected from methyl, ethyl, i-propyl, t-butyl, cyclopentyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, diazepanyl, oxazepanyl, pyrazolyl, imidazolinyl, and phenyl, wherein each of (ii) is optionally substituted by one or more groups selected from halo, hydroxy, —C1-C4 alkyl, —C1-C4 haloalkyl, —O—C1-C4 alkyl, —C1-C4 alkyl-OH, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —N(C1-C4 alkyl)C(O)(C1-C4 alkyl), —C(O)—C1-C4 alkyl, —C(O)—C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, —SO2NH(C1-C4 alkyl), —NHSO2(C1-C4 alkyl), and heterocycyl optionally substituted by —SO2(C1-C4 alkyl),
R3 and R4 are independently selected from hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclohexyl, phenyl, pyrrolidinyl, and pipericnyl, each of which, except for hydrogen, is optionally substituted with one or more groups (i) selected from halo, —NR5R6, —OR7, —C(O)OR7, —CN, —C(O)NR5R6, —S(O)nNR5R6; or (ii) selected from cyclopropyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, diazepanyl, oxazepanyl, pyridyl, pyrazolyl, and imidazolinyl, each of said piperidinyl, morpholinyl, and thiomorpholinyl is optionally substituted by one or more groups selected from —C1-C4 alkyl, —C1-C4 haloalkyl, —C1-C4 alkyl-OH, halo, hydroxy, —CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —C(O)C1-C4 alkyl, —C(O)C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, and heteroaryl,
or R3 and R4, together with the N atom to which they are attached, can form a 4-12 membered monocyclic, fused bicyclic or spirocyclic ring optionally containing an additional 1-3 heteroatoms chosen from N and O, which is optionally substituted with one or more groups (i) selected from —NR5R6, —OR7, —C(O)NR5R6, —NR5S(O)nNR10R11, —NRC(O)NR10R10, and —S(O)nR5R6; or (ii) selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl, wherein each of (ii) is optionally substituted by one or more groups selected from hydroxy, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), and —NHSO2(C1-C4 alkyl),
m is 0 or 1,
n is 2,
R5, R6, R7, R8, R9, R10, and R11 are independently selected from hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, pyrrolidinyl, tetrahydrofuryl, and piperidinyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, methoxy, ethoxy, n-propoxy, i-propoxy, pyrrolidinyl, tetrahydrofuryl, piperidinyl, morpholinyl, amino, and amide, wherein amino is optionally substituted by one or two —C1-C4 alkyl,
or R5 an R6, R5 and R7, R5 and R8, R5 and R9, and R5 an R10 together with the atom(s) to which they are attached can form a ring.

### Claim 4 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein
R1 is independently selected from hydrogen, methyl, ethyl, n-propyl, and i-propyl;
R2 is independently selected from phenyl, naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, and quinolinyl, which is optionally substituted by one or more groups selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, and —S(O)nR5R6;
R3 and R4 are independently selected from hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, phenyl, naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, benzofuryl, benzothienyl, benzoimidazolinyl, indolyl, quinolinyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, homomorpholinyl, thiomorpholinyl, diazepanyl, and oxazepanyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, and —S(O)nR5R6;
or R3 and R4, together with the N atom to which they are attached, form a 4-12 membered monocyclic, fused bicyclic or spirocyclic ring optionally containing an additional 1-3 heteroatoms chosen from N and O, which is optionally substituted with one or more groups selected from (i) halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, and —S(O)nR5R6; or (ii) selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, homomorpholinyl, thiomorpholinyl, diazepanyl, oxazepanyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, benzofuryl, benzothienyl, benzoimidazolinyl, indolyl, quinolinyl, phenyl, naphthyl, and C2-C6 alkynyl;
m is 0, 1 or 2;
n is 1 or 2;
R5, R6, R7, R8, R9, R10, and R11 are independently selected from hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, phenyl, naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, benzofuryl, benzothienyl, benzoimidazolinyl, indolyl, quinolinyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, homomorpholinyl, thiomorpholinyl, diazepanyl, and oxazepanyl;
or R5 and R6, R5 and R7, R5 and R8, R5 and R9, and R5 and R10 together with the atom(s) to which they are attached form a ring, which is optionally substituted with one or more groups selected from (i) halo and hydroxy; or (ii) selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, homomorpholinyl, thiomorpholinyl, diazepanyl, oxazepanyl, amino, and amide.

### Claim 5 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R1 is independently chosen from hydrogen, methyl, ethyl, n-propyl, or i-propyl.

### Claim 6 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R1 is hydrogen.

### Claim 7 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R2 is C5-C10aryl, or 5-10 membered heteroaryl, which is optionally substituted by one or more groups (i) selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, or —S(O)nNR5R6, or (ii) selected from C1-C6 alkyl, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, 5-10 membered heteroaryl, and C5-C10 aryl, wherein each of (ii) is optionally substituted with one or more groups selected from halo, hydroxy, —C1-C4 alkyl, —C1-C4 haloalkyl, —O—C1-C4 alkyl, —C1-C4 alkyl-OH, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), —CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —N(C1-C4 alkyl)C(O)(C1-C4 alkyl), —C(O) C1-C4 alkyl, —C(O)C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, SO2NH(C1-C4 alkyl), —NHSO2(C1-C4 alkyl), and heterocyclyl optionally substituted by —SO2(C1-C4 alkyl),
R5, R6, R7, R8, R9, R10, and R11 are independently selected from hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide, wherein the amino is optionally substituted by one or two —C1-C4 alkyl,
or R5 and R6, R5 and R7, R5 and R8, R5 and R9, and R5 and R10 together with the atom(s) to which they are attached can form a ring, which is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide.

### Claim 8 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R2 is independently selected from phenyl-naphtyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, benzofuryl, benzothienyl, benzoimidazolinyl, indolyl, or quinolinyl, which is optionally substituted by one or more groups (i) selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, or —S(O)nNR5R6; or (ii) selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, homomorpholinyl, thiomorpholinyl, diazepanyl, oxazepanyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, benzofuryl, benzothienyl, benzoimidazolinyl, indolyl, quinolinyl, phenyl, or naphthyl, wherein each of (ii) is optionally substituted with one or more groups selected from halo, hydroxy, —C1-C4 alkyl, —C1-C4 haloalkyl, —O—C1-C4 alkyl, —C1-C4 alkyl-OH, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —N(C1-C4 alkyl)C(O)(C1-C4 alkyl), —C(O)—C1-C4 alkyl, —C(O)—C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, —SO2NH(C1-C4 alkyl), —NHSO2(C1-C4 alkyl), and heterocyclyl optionally substituted by —SO2(C1-C4 alkyl),
R5, R6, R7, R8, R9, R10, and R11 are independently selected from hydrogen alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide, wherein the amino is optionally substituted by one or two —C1-C4 alkyl,
or R5 and R6, R5 and R7, R5 and R8, R5 and R9, and R5 and R10 together with the atom(s) to which they are attached can form a ring, which is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, or and amide.

### Claim 9 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R2 is independently selected from
each of which is optionally substituted by one or more groups (i) selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, or —S(O)nNR5R6, or (ii) selected from C1-6 alkyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl, wherein each of (ii) is optionally substituted with one or more groups selected from halo, hydroxy, —C1-C4 alkyl, —C1-C4 haloalkyl, —O—C1-C4 alkyl, —C1-C4 alkyl-OH, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), —CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —N(C1-C4 alkyl)C(O)(C1-C4 alkyl), —C(O)—C1-C4 alkyl, —C(O)—C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, —SO2NH(C1-C4 alkyl), —NHSO2(C1-C4 alkyl), and heterocyclyl optionally substituted by —SO2(C1-C4 alkyl),
R5, R6, R7, R8, R9, R10, and R11 are independently selected from hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide, wherein the amino is optionally substituted by one or two —C1-C4 alkyl,
or R5 and R6, R5 and R7, R5 and R8, R5 and R9, and R5 and R10 together with the atom(s) to which they are attached can form a ring, which is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide.

### Claim 10 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R2 is
which is optionally substituted by one or more groups (i) selected from halo, —NR5R6, —OR7, —S(O)nR8, —CN, —C(O)NR5R6, —NR5S(O)nR8, or —S(O)nNR5R6, or (ii) selected from C1-6 alkyl, cycloalkyl, heterocyclyl, heteroaryl, aryl, wherein each of (ii) is optionally substituted with one or more groups selected from halo, hydroxy, —C1-C4 alkyl, —C1-C4 haloalkyl, —O—C1-C4 alkyl, —NH2, —C(O)—C1-C4 alkyl, —C(O)—C1-C4 haloalkyl, —SO2(C1-C4 alkyl), and —SO2(C1-C4 haloalkyl),
R5, R6, R7, and R8 are independently selected from hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide, or R5 and R6, R5 and R7, and R5 and R8 together with the atom(s) to which they are attached can form a ring.

### Claim 11 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R2 is
which is optionally substituted by one or more groups (i) selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NO2, or —S(O)nNR5R6, or (ii) selected from C1-6 alkyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl, wherein each of (ii) is optionally substituted with one or more groups selected from halo, hydroxy, —C1-C4 alkyl, —C1-C4 haloalkyl, —O—C1-C4 alkyl, —C1-C4 alkyl-OH, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —N(C1-C4 alkyl)C(O)(C1-C4 alkyl), —C(O)C1-C4 alkyl, —C(O)C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, —SO2NH(C1-C4 alkyl), —NHSO2(C1-C4 alkyl), and heterocyclyl optionally substituted by —SO2(C1-C4 alkyl),
R5, R6, R7, R8, and R9, are independently selected from hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide, wherein the amino is optionally substituted by one or two —C1-C4 alkyl, or R5 and R6, R5 and R7, R5 and R8, and R5 and R9 together with the atom(s) to which they are attached can form a ring, which is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide.

### Claim 12 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R2 is independently selected from phenyl, naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, benzofuryl, benzothienyl, benzoimidazolinyl, indolyl, and quinolinyl, which is optionally substituted by one or more groups selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, and —S(O)nR5R6.

### Claim 13 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R2 is independently selected from
which is optionally substituted by one or more groups selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)R8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, and —S(O)nR5R6.

### Claim 14 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R2 is
which is optionally substituted by one or more groups selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NRC(O)OR7, —NR5C(O)NR10R11, —NO2, and —S(O)nR5R6.

### Claim 15 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R2 is
which is optionally substituted by one or more groups selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, and —S(O)nR5R6.

### Claim 16 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R3 and R4 are independently selected from hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C5-C10aryl, 5-10 membered heteroaryl, and 3-8 membered heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, —NR5R6, —OR7, —C(O)OR7, —CN, —C(O)NR5R6, or —S(O)nNR5R6, C1-C6 alkyl, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, 5-10 membered heteroaryl, and C5-C10aryl, wherein the 3-8 membered heterocyclyl is optionally substituted by one or more groups selected from —C1-C4 alkyl, —C1-C4 haloalkyl, —C1-C4 alkyl-OH, halo, hydroxy, oxo, —CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —C(O)C1-C4 alkyl, —C(O)C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, and heteroaryl,
or R3 and R4, together with the N atom to which they are attached, can form a 4-12 membered monocyclic, fused bicyclic or spirocyclic ring optionally containing an additional 1-3 heteroatoms chosen from N and O, which is optionally substituted with one or more groups selected from —NR5R6, —OR7, —C(O)OR7, —CN, —C(O)NR5R6, —NR5S(O)nNR10R11, —NR5C(O)NR10R11, —S(O)nNR5R6, C1-C6 alkyl, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, 5-10 membered heteroaryl, and C5-C10 aryl, wherein the C1-C6 alkyl is optionally substituted by one or more groups selected from hydroxy, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), and —NHSO2(C1-C4 alkyl),
R5, R6, R7, R10, and R11 are independently selected from hydrogen, alkyl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide,
or R5 and R6, R5 and R7, and R5 and R10 together with the atom(s) to which they are attached can form a ring.

### Claim 17 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R3 and R4 are independently selected from hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, phenyl, naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, benzofuryl, benzothienyl, benzoimidazolinyl, indolyl, quinolinyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, homomorpholinyl, thiomorpholinyl, diazepanyl, and oxazepanyl, each of which, except for hydrogen, is optionally substituted with one or more groups (i) selected from halo, —NR5R6, —OR7, —C(O)OR7, —CN, —C(O)NR5R6, and —S(O)nNR5R6; or (ii) selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, homomorpholinyl, thiomorpholinyl, diazepanyl, oxazepanyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, benzofuryl, benzothienyl, benzoimidazolinyl, indolyl, quinolinyl, phenyl, and naphthyl,
or R3 and R4, together with the N atom to which they are attached, can form a 4-12 membered monocyclic, fused bicyclic or spirocyclic ring optionally containing an additional 1-3 heteroatoms chosen from N and O, which is optionally substituted with one or more groups (i) selected from halo, —NR5R6, —OR7, —C(O)OR7, —C(O)NR5R6, —NR5S(O)nNR10R11, —NR5C(O)NR10R11, or —S(O)nNR5R6; or (ii) selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, homomorpholinyl, thiomorpholinyl, diazepanyl, oxazepanyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, benzofuryl, benzothienyl, benzoimidazolinyl, indolyl, quinolinyl, phenyl, and naphthyl,
R5, R6, R7, R10, and R11 are independently selected from hydrogen, alkyl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide,
or R5 and R6, R5 and R7, and R5 and R10 together with the atom(s) to which they are attached can form a ring.

### Claim 18 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R3 and R4 are independently selected from hydrogen, alkyl, cycloalkyl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, —NR5R6, —OR7, —C(O)OR7, —CN, —C(O)NR5R6, —S(O)nNR5R6, C1-6 alkyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl, wherein the 3-8 membered heterocyclyl is optionally substituted by one or more groups selected from C1-C4 alkyl, C1-C4 haloalkyl, —C1-C4 alkyl-OH, halo, hydroxy, oxo, —CON(C1-C4 alkyl)(C1-C4 alkyl), CONH(C1-C4 alkyl), —CONH2, —C(O)C1-C4 alkyl, —C(O)C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, and heteroaryl,
R5, R6, and R7 are independently selected from hydrogen, alkyl, and heterocyclyl, each of which except for hydrogen, is optionally substituted with one or more group selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide,
or R5 and R6, R5 and R7, and R5 and R10 together with the atom(s) to which they are attached can form a ring.

### Claim 19 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R3 and R4, together with the N atom to which they are attached form a 4-7 membered monocyclic ring optionally containing an additional 1-3 heteroatoms chosen from N and O, which is optionally substituted with one or more groups selected from —NR5R6, —OR7, —C(O)OR7, —C(O)NR5R6, —NR5S(O)nNR10R11, —NR5C(O)NR10R11, —S(O)nNR5R6, C1-6 alkyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl, wherein the C1-6 alkyl is optionally substituted by one or more groups selected from hydroxy, —NH2, —N(C1-C4 alkyl)(C1-C4 alkyl), —NH(C1-C4 alkyl), and —NHSO2(C1-C4 alkyl),
R5, R6, R7, R10, and R11 are independently selected from hydrogen, alkyl, and heterocyclyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, hydroxy, C1-6 alkyl, cycloalkyl, amino, and amide,
or R5 and R6, R5 and R7, R5 and R8, R5 and R9, and R5 and R10 together with the atom(s) to which they are attached can form a ring.

### Claim 20 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R3 and R4 are independently selected from hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, phenyl, naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolinyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, benzofuryl, benzothienyl, benzoimidazolinyl, indolyl, quinolinyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, piperazinyl, morpholinyl, homomorpholinyl, thiomorpholinyl, diazepanyl, and oxazepanyl, each of which, except for hydrogen, is optionally substituted with one or more groups selected from halo, —NR5R6, —OR7, —S(O)nR8, —C(O)R9, —C(O)OR7, —CN, —C(O)NR5R6, —NR5C(O)R9, —NR5S(O)nR8, —NR5S(O)nNR10R11, —NR5C(O)OR7, —NR5C(O)NR10R11, —NO2, and —S(O)nR5R6.

### Claim 21 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R4 is hydrogen and R3 is C1-6alkyl, which is optionally substituted with one or more groups selected from alkyl, cycloalkyl, heterocyclyl and heteroaryl, wherein heterocyclyl is optionally substituted by one or more groups chosen from C1-C4 alkyl, C1-C4 haloalkyl, —C1-C4 alkyl-OH, halo, hydroxy, oxo, —CON(C1-C4 alkyl)(C1-C4 alkyl), —CONH(C1-C4 alkyl), —CONH2, —C(O)C1-C4 alkyl, —C(O)C1-C4 haloalkyl, —SO2(C1-C4 alkyl), —SO2(C1-C4 haloalkyl), —SO2NH2, and heteroaryl.

### Claim 22 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R3 and R4, together with the N atom to which they are attached can form a 7-12 membered fused bicyclic ring optionally containing an additional 1-3 heteroatoms chosen from N and O.

### Claim 23 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein R3 and R4, together with the N atom to which they are attached can form a 7-12 membered spirocyclic ring optionally containing an additional 1-3 heteroatoms chosen from N and O.

### Claim 24 (depends on 1)

The compound of claim 1, and/or a pharmaceutically acceptable salt thereof, wherein m is 1.

### Claim 25 (depends on 1)

A pharmaceutical composition comprising at least one compound of claim 1, and/or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier.

### Claim 26 (depends on 1)

A method for inhibiting a spleen tyrosine kinase in a system or a subject, comprising administering to a system or a subject in need thereof a therapeutically effective amount of a compound of claim 1.

### Claim 27 (depends on 26)

The method of claim 26, wherein the subject suffers from a disease chosen from the group consisting of allergic asthma, allergic rhinitis, rheumatoid arthritis, multiple sclerosis, lupus, systemic lupus erythematosus, lymphoma, B cell lymphoma, T cell lymphoma, leukemia, leucopenia, neutropenia, thrombocytopenia, granuloctopenia, pancytoia and idiopathic thrombocytopenic purpura.

### Claim 28

A compound chosen from the group consisting of: 1 to 233, 236-238, 241, 246-250, 253, 256-275, 279-280, 283-288, 290, 293, 303-306, 308-310, 312-367, 372-373, 380-381, 384-391, 394-482, and 484-516
Compound
Structure
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232, 233
236
237
238
241
246
247
248
249
250
253
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
279
280
283
284
285
286
287
288
290
293
303
304
305
306
308
309
310
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
372, 373
380, 381
384, 385
386, 387
388, 389
390, 391
394, 395
396, 397
398, 399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476, 477
478
479
480
481
482
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507, 508
509
510
511
512
513
514
515
and 516
and/or a pharmaceutically acceptable salt thereof.