# US 2010/0168102 A9 · Amide Derivatives as Kinase Inhibitors

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- Number: US 2010/0168102 A9
- Document ID: US20100168102A9
- Status: Published application
- Kind: A9
- Application number: 11/988,699
- Filed: 2006-07-11
- Published: 2010-07-01
- Earliest claimed: 2005-07-11
- Assignees: Devgen NV
- Inventors: Olivier Raynald Defert; Gert De Wilde; Petra Blom; Dirk Casimir Maria Leysen; Thomas Brown; Nadzeya Kaval
- Web page: https://patentgrep.com/patent/US20100168102A9

## CPC

- C07D 213/75: Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/08: Vasodilators for multiple indications
- 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 9/12: Antihypertensives
- A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/10: of the bladder
- A61P 13/12: of the kidneys
- A61P 15/06: Antiabortive agents; Labour repressants
- A61P 15/10: for impotence
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/10: for osteoporosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/22: Anxiolytics
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 25/30: for treating abuse or dependence
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- 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 31/04: Antibacterial agents
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 39/02: Antidotes
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 213/81: Amides; Imides
- C07D 213/82: in position 3
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D 409/14: containing three or more hetero rings
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 473/00: Heterocyclic compounds containing purine ring systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to new AGC kinase inhibitors, in particular to compounds of Formula (I) or (II) or a stereoisomer tautomer, racemic, metabolite, pro- or predrug, salt, hydrate, or solvate thereof, wherein Ar1, Ar2, R1, R3, p and n have the meaning defined in the claims In particular, the present invention relates to more specifically AGC kinases inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease.

## Claims

### Claim 1

A compound of Formula I or II or a stereoisomer, tautomer, racemic, salt, hydrate, or solvate thereof,
wherein:
Ar1 is an aromatic 6-membered first ring containing carbon atoms and at least one nitrogen atom, said first ring being optionally fused to a saturated, unsaturated or aromatic 4-, 5-, 6-, or 7-membered second ring containing carbon atoms and optionally at least one nitrogen atom, said first or said second rings being independently substituted with one or more substituents independently selected from the group comprising hydrogen, halogen, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, heteroarylalkyl, cycloalkylalkyl, acyl, aryl or heteroaryl wherein said substituents are optionally substituted by one or more further substituents selected from the group comprising halo, hydroxyl, oxo, nitro, amido, carboxy, amino, cyano, haloalkoxy, and haloalkyl;
Ar2 is an aromatic 5- or 6-membered third ring containing carbon atoms and optionally one or two heteroatoms, said third ring optionally fused to an aromatic 6-membered fourth ring containing carbon atoms and optionally at least one heteroatom atom, wherein said third ring is optionally substituted with one or more substituents selected from the group comprising halogen, alkenyl, alkyl, alkynyl, acylamino, alkoxy, arylamino, nitro, haloalkoxy, aryl or heteroaryl, wherein said substituents are optionally substituted by one or more further substituents selected from the group comprising halo, hydroxyl, oxo, nitro, amido, carboxy, amino, cyano, haloalkoxy, and haloalkyl;
n is an integer selected from 1, 2 or 3; and
p is an integer selected from 2, 3, 4 or 5; and
R1 is selected from the Formula:
wherein
R3 is selected from the Formula:
A is an oxygen or sulfur atom;
R5, R6 and R7 are each independently selected from the group comprising
hydrogen, a group selected from alkoxy, alkyl, alkylamino, alkylaminoalkyl, alkylcarbonyl, alkylcarbonylamino, amino, aralkyl, aryl, carbonylamino, cycloalkyl, formylamino, heteroaryl, heteroarylalkyl, heterocyclyl, or fused to the cycloalkyl, aryl, heterocyclyl or heteroaryl group may be one or more cycloalkyl, aryl, heterocyclyl or heteroaryl,
each group being optionally substituted by one or more substituent selected from halo, alkenylaminooxy, alkoxy, alkyl, alkylamino, alkylaminosulfonyl, alkylcarbonyl, alkylcarbonylamino, alkyloxyaminoalkenyl, alkyloxycarbonyl, alkylsulfonyl, alkylsulfonylamino, alkylthio, amino, aralkyl, aryl, arylalkenylaminooxy, arylamino, arylaminosulfonyl, arylcarbonyl, arylcarbonylamino, aryloxy, cyano, cycloalkyl, haloalkoxy, haloalkyl, haloaryl, heteroaryl, heteroarylalkenylaminooxy, heteroarylalkyl, heteroarylcarbonylamino, heterocyclyl, hydroxyalkyl, nitro, oxo, sulfonyl, or fused to the cycloalkyl, aryl, heterocyclyl substituent or heteroaryl may be one or more cycloalkyl, aryl, heterocyclyl or heteroaryl,
each of said substituent being optionally substituted by one or more further substituent selected from halo, alkoxy, alkyl, alkylamino, alkylcarbonyl, alkylheteroaryl, alkylsuphonyl, aralkyl, aryl, arylamino, aryloxy, cyano, haloalkoxy, haloalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocyclyl, hydroxy, nitro, oxo, or sulfonyl.

### Claim 2 (depends on 1)

The compound according to claim 1 wherein n is 1.

### Claim 3 (depends on 1)

The compound according to claim 1 wherein n is 2.

### Claim 4 (depends on 1)

The compound according to claim 1 wherein R1 is selected from the Formula:
wherein A, R5, R6 and R7 have the same meaning as in any of the previous claims.

### Claim 5 (depends on 1)

The compound according to claim 1 having one of the structural Formula
wherein Ar1, Ar2, A, R5, R6 and R7 have the same meaning as in any of the previous claims.

### Claim 6 (depends on 5)

The compound of claim 5 wherein R5 is hydrogen, alkyl or cycloalkyl and A is an oxygen or a sulfur atom.

### Claim 7 (depends on 1)

The compound according to claim 1 wherein Ar1— is of any of the Formula:
wherein
m is an integer selected from 0, 1, 2 or 3, preferably 0;
W is C(R2) or N, preferably C(R2), more preferably CH;
Y and Z are independently selected from the group comprising N and CR2
R2 is selected from hydrogen, halogen, or a group selected from alkyl, cycloalkyl, alkenyl, alkynyl, aryl or heteroaryl wherein each of said group is optionally substituted by one or more substituents selected from the group comprising halo, hydroxyl, amido, carboxy, amino, cyano, haloalkoxy, and haloalkyl.

### Claim 8 (depends on 7)

The compound according to claim 7 wherein W is N or C(R2), wherein R2 has the same meaning as in claim 7.

### Claim 9 (depends on 8)

The compound according to claim 8 wherein W is N or CH.

### Claim 10 (depends on 7)

The compound according to claim 7 wherein m is 0.

### Claim 11 (depends on 1)

The compound according to claim 1 wherein p is 3 or 4.

### Claim 12 (depends on 1)

The compound according to claim 1
wherein —Ar2— is of any of the Formula:
wherein
R8 is selected from hydrogen or halogen, or a group selected from alkenyl, alkyl, alkynyl, acylamino, alkoxy, arylamino, nitro, cyano, haloalkoxy, aryl or heteroaryl, each group being optionally substituted by one or more substituents selected from the group comprising halogen, alkyl, haloalkyl, nitro, haloalkoxy, aryl and heteroaryl; and
R9 is selected from the group comprising hydrogen, halogen and alkyl.

### Claim 13 (depends on 12)

The compound according to claim 12, wherein R8 is hydrogen.

### Claim 14 (depends on 1)

The compound according to claim 1, wherein R6 and R7 are each independently selected from
wherein
Y1 is selected from —CH2—, —CH(R14)—, —NH—, —O—, —S— or —C(═O)—,
Y3 is selected from —CH2—, —CH2—CH2—, —O—, —S— or —NH—,
X6 is selected from N or CH,
X7 is selected from N, C(═O) or CH,
X8 is selected from N, NH or CH,
X9 is selected from N or CH,
X10 is selected from S, O or NH,
X11 is selected from O, CH2, C(═O), S or NH,
X12 is selected from N, NH, O, S or CH,
X13 is selected from NH, O, S or CH,
X14 is selected from S, N, NH or CH,
Z1 is selected from O or NH,
q is an integer selected from 1, 2, 3 or 4,
n is an integer selected from 1, 2, 3, 4, 5, 6 or 7,
wherein R10 and R11 are each independently a selected from hydrogen, alkyl, cycloalkyl, aryl, or aralkyl,
wherein R12 is selected from aryl, cycloalkyl, heteroaryl or heterocyclyl, each being optionally substituted by one or more substituent selected from halo, alkoxy, alkyl, alkylamino, alkylcarbonyl, alkylheteroaryl, alkylsuphonyl, aralkyl, aryl, arylamino, aryloxy, cyano, haloalkoxy, haloalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocyclyl, hydroxy, nitro, oxo, or sulfonyl,
r is an integer selected from 0, 1, 2 or 3,
wherein R13 and R14 are each independently selected from hydrogen or alkyl,
or R13 and R14 form together with the carbon atoms to which they are attached form an aryl, an heteroaryl, a cycloalkyl or a heterocyclyl,
or r is 2 and two R13 form together with the carbon atoms to which they are attached form an aryl, an heteroaryl, a cycloalkyl or a heterocyclyl,
wherein R15 and R16 together with the carbon atom to which they are attached form an aryl, a cycloalkyl, a heteroaryl a heterocyclyl, each being optionally substituted with one or more substituent selected from halo, alkoxy, alkyl, alkylamino, alkylcarbonyl, alkylheteroaryl, alkylsuphonyl, aralkyl, aryl, arylamino, aryloxy, cyano, haloalkoxy, haloalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocyclyl, hydroxy, nitro, oxo, or sulfonyl,
s is an integer selected from 0, 1, 2, 3 or 4,
wherein R17 is selected from halo, or a group selected from alkenylaminooxy, alkoxy, alkyl, alkylamino, alkylaminosulfonyl, alkylcarbonyl, alkylcarbonylamino, alkyloxyaminoalkenyl, alkyloxycarbonyl, alkylsulfonyl, alkylsulfonylamino, alkylthio, amino, aralkyl, aryl, arylalkenylaminooxy, arylamino, arylaminosulfonyl, arylcarbonyl, arylcarbonylamino, aryloxy, cyano, cycloalkyl, haloalkoxy, haloalkyl, haloaryl, heteroaryl, heteroarylalkenylaminooxy, heteroarylalkyl, heteroarylcarbonylamino, heterocyclyl, hydroxyalkyl, nitro, oxo, sulfonyl, or two R17 together with the atoms to which they are attached form an aryl, heteroaryl, cycloalkyl, or heterocyclyl, each group being optionally substituted with one or more substituents selected from halo, alkoxy, alkyl, alkylamino, alkylcarbonyl, alkylheteroaryl, alkylsuphonyl, aralkyl, aryl, arylamino, aryloxy, cyano, haloalkoxy, haloalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocyclyl, hydroxy, nitro, oxo, or sulfonyl,
wherein R18 and R19 are each independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl or heteroarylalkyl,
wherein R20 is selected from hydrogen, or a group selected from alkyl, cycloalkyl, alkylaminoalkyl, alkylamino, alkylcarbonylamino, alkylcarbonylaminoalkyl, alkylsulfonyl, alkylsulfonylamino, alkylsulfonylaminoalkyl, amino, aminoalkyl, heterocyclyl, heterocyclylalkyl, cyano, cyanoalkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, carboxy, alkoxycarbonylalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, each group being optionally substituted by one or more substituent selected from halo, alkoxy, alkyl, alkylamino, alkylcarbonyl, alkylheteroaryl, alkylsuphonyl, aralkyl, aryl, arylamino, aryloxy, cyano, haloalkoxy, haloalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocyclyl, hydroxy, nitro, oxo, or sulfonyl,
wherein R21 is selected from alkyl, aryl, alkylcarbonyl, heteroaryl or heteroarylcarbonyl.

### Claim 15 (depends on 1)

The compound according to claim 1 having one of the structural Formula
wherein Ar1, Ar2, A, s, p, q, r, n, Y1, R5, R10, R11, R12, R13, R15, R16, and R17 same meaning as in any of the previous claims.

### Claim 16 (depends on 1)

The compound according to claim 1 having one of the structural Formula
wherein Ar1, Ar2, A, s, p, q, r, n, W, Y, Y1, Z, R2, R5, R6, R7, R10, R11, R12, R13, R15, R16, and R17 have the same meaning as in any of the previous claims.

### Claim 17 (depends on 1)

The compound according to claim 1 having one of the structural Formula
wherein Ar1, A, s, p, q, r, n, Y1, R5, R10, R11, R12, R13, R15, R16, R17, R18, R19 and R20 have the same meaning as in any of the previous claims.

### Claim 18 (depends on 1)

The compound according to claim 1 having one of the structural Formula
wherein Ar2, A, s, p, q, r, m, n, W, Y, Y1, Z, R2, R5, R10, R11, R12, R13, R15, R16, R17, R18, R19 and R20 have the same meaning as in any of the previous claims.

### Claim 19 (depends on 1)

The compound according to claim 1 having one of the structural Formula
wherein A, s, p, q, r, n, m, W, Y, Y1, Z, R2, R5, R10, R11, R12, R13, R15, R16, R17, R18, R19 and R20 have the same meaning as in any of the previous claims.

### Claim 20 (depends on 1)

The compound according to claim 1 wherein:
Y1 is selected from —CH2—, —CH(R14)—, —NH—, —O—, —S— or —C(═O)—,
Y3 is selected from —CH2—, —CH2—CH2—, —O—, —S— or —NH—,
A is O or S, W is N or CR2, Y is N or CR2, Z is N or CR2, wherein R2 is hydrogen or alkyl,
R5 is hydrogen, alkyl or cycloalkyl,
p is 3 or 4,
q is an integer selected from 1, 2, 3 or 4,
n is an integer selected from 1, 2, 3, 4, 5, 6 or 7,
wherein R10 and R11 are each independently a selected from hydrogen, alkyl, cycloalkyl, aryl, or aralkyl,
wherein R12 is selected from aryl, cycloalkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more substituent selected from halo, alkoxy, alkyl, alkylamino, alkylcarbonyl, alkylheteroaryl, alkylsuphonyl, aralkyl, aryl, arylamino, aryloxy, cyano, haloalkoxy, haloalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocyclyl, hydroxy, nitro, oxo, or sulfonyl,
r is an integer selected from 0, 1, 2 or 3,
wherein R13 and R14 are each independently selected from hydrogen or alkyl,
or R13 and R14 form together with the carbon atoms to which they are attached form an aryl, an heteroaryl, a cycloalkyl or a heterocyclyl,
or r is 2 and two R13 form together with the carbon atoms to which they are attached form an aryl, an heteroaryl, a cycloalkyl or a heterocyclyl,
wherein R15 and R16 together with the carbon atom to which they are attached form an aryl, a cycloalkyl, a heteroaryl a heterocyclyl, each optionally substituted with one or more substituent selected from halo, alkoxy, alkyl, alkylamino, alkylcarbonyl, alkylheteroaryl, alkylsuphonyl, aralkyl, aryl, arylamino, aryloxy, cyano, haloalkoxy, haloalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocyclyl, hydroxy, nitro, oxo, or sulfonyl,
s is an integer selected from 0, 1, 2, 3 or 4,
wherein R17 is selected from halo, or a group selected from alkenylaminooxy, alkoxy, alkyl, alkylamino, alkylaminosulfonyl, alkylcarbonyl, alkylcarbonylamino, alkyloxyaminoalkenyl, alkyloxycarbonyl, alkylsulfonyl, alkylsulfonylamino, alkylthio, amino, aralkyl, aryl, arylalkenylaminooxy, arylamino, arylaminosulfonyl, arylcarbonyl, arylcarbonylamino, aryloxy, cyano, cycloalkyl, haloalkoxy, haloalkyl, haloaryl, heteroaryl, heteroarylalkenylaminooxy, heteroarylalkyl, heteroarylcarbonylamino, heterocyclyl, hydroxyalkyl, nitro, oxo, sulfonyl, or two R17 together with the atoms to which they are attached form an aryl, heteroaryl, cycloalkyl, or heterocyclyl, each group being optionally substituted with one or more substituents selected from halo, alkoxy, alkyl, alkylamino, alkylcarbonyl, alkylheteroaryl, alkylsuphonyl, aralkyl, aryl, arylamino, aryloxy, cyano, haloalkoxy, haloalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocyclyl, hydroxy, nitro, oxo, or sulfonyl,
wherein R18 and R19 are each independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl or heteroarylalkyl,
wherein R20 is selected from hydrogen, or a group selected from alkyl, cycloalkyl, alkylaminoalkyl, alkylamino, alkylcarbonylamino, alkylcarbonylaminoalkyl, alkylsulfonyl, alkylsulfonylamino, alkylsulfonylaminoalkyl, amino, aminoalkyl, heterocyclyl, heterocyclylalkyl, cyano, cyanoalkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, carboxy, alkoxycarbonylalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, each group being optionally substituted by one or more substituent selected from halo, alkoxy, alkyl, alkylamino, alkylcarbonyl, alkylheteroaryl, alkylsuphonyl, aralkyl, aryl, arylamino, aryloxy, cyano, haloalkoxy, haloalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocyclyl, hydroxy, nitro, oxo, or sulfonyl,
wherein R21 is selected from alkyl, aryl, alkylcarbonyl, heteroaryl or heteroarylcarbonyl.

### Claim 21 (depends on 1)

The compound according to claim 1 wherein:
A is O or S,
W is N or CR2, Y is N or CR2, Z is CH or N, wherein R2 is hydrogen or methyl,
p is 3 or 4, m is 0, s is selected from 0, 1, 2 or 3, r is 1 or 2, n is selected from 0, 1, 2, 3, 4, 5, 6, 7 or 8,
wherein R5 is selected from hydrogen, alkyl or cycloalkyl,
q is selected from 1, 2, 3 or 4,
R10 and R11 are each independently a selected from hydrogen, alkyl, cycloalkyl, aryl, or aralkyl,
R17 is selected from halo, alkoxy, alkyl, alkylamino, alkylcarbonyl, alkylheteroaryl, alkylsuphonyl, aralkyl, aryl, arylamino, aryloxy, cyano, haloalkoxy, haloalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocyclyl, hydroxy, nitro, oxo, or sulfonyl,
Y2 is selected from —CH(R14)—, —S—, —NH—, —O—, —C(═O)—,
R13 and R14 are each independently selected from hydrogen or alkyl or together with the carbon atoms to which they are attached form an aryl ring,
Y3 is selected from —CH2—, —S—, —CH2—CH2—, —NH—, —O—, —C(═O)—,
wherein when X1, X2 or X3 are each independently selected from CH or N,
X4 is selected from N, S or CH,
X5 is selected from CH or S.

### Claim 22 (depends on 1)

The compound according to claim 1, selected from a compound as listed in any of Tables 1 to 8.

### Claim 23

A method for synthesizing a compound of Formula XXIII comprising the steps of reacting a compound of Formula XX:
with Noyori's catalyst thereby obtaining a compound of Formula XXI,
reacting compound of Formula XXI with diphenylphosphoryl azide (DPPA) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) thereby obtaining azide of Formula XXII, and
reacting compound of Formula XXII with Pd/C thereby obtaining the compound of Formula XXIII,
wherein Ar2 is phenylene and Ar1, R5 and R7 have the same meaning as defined in any of the preceding claims.

### Claim 24 (depends on 23)

A compound obtainable by the method of claim 23.

### Claim 25 (depends on 1)

A pharmaceutical and/or veterinary composition comprising a compound as defined in claim 1.

### Claim 26 (depends on 25)

A pharmaceutical and/or veterinary composition according to claim 25 comprising at least one carrier, excipient or diluent acceptable for pharmaceutical and/or veterinary purposes.

### Claim 27

(canceled)

### Claim 28 (depends on 1)

A method for the prevention and/or treatment of at least one disease and/or disorder selected from the group consisting of metabolic diseases; diabetes; anxiety; addiction; withdrawal symptoms; muscle spasms; convulsive seizures; epilepsy; pain; cardiovascular disease; vascular diseases; inflammatory diseases and/or for regulating the immune system and/or an immune response and/or inflammatory response in a mammal comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 29 (depends on 28)

A method according to claim 28 wherein said metabolic disease or disorder is at least one of the following:
hyperglycemic conditions and/or other conditions and/or diseases that are associated with insulin, selected from the group consisting of Type I and Type II diabetes, severe insulin resistance, hyperinsulinemia, hyperlipidemia, and insulin-resistant diabetes comprising Mendenhall's Syndrome, Werner Syndrome, leprechaunism and lipoatrophic diabetes, and other lipoatrophies;
obesity;
conditions caused or usually associated with hyperglycemic conditions and/or obesity, including hypertension, osteoporosis and/or lipodystrophy; or
metabolic syndrome;
and inherited metabolic diseases; and/or for preventing, treating and/or alleviating complications and/or symptoms associated with these metabolic diseases.

### Claim 30 (depends on 1)

A method for the prevention and/or treatment of type II diabetes, and/or for preventing, treating and/or alleviating complications and/or symptoms associated therewith comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 31 (depends on 1)

A method for the prevention and/or treatment of obesity, and/or for preventing, treating and/or alleviating complications and/or symptoms associated therewith comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 32 (depends on 1)

A method for the prevention, treatment and/or management of pain, and/or for preventing, treating and/or alleviating complications and/or symptoms associated therewith comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 33 (depends on 1)

A method for the prevention and/or treatment of inflammatory diseases selected from the group consisting of contact dermatitis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, and/or for preventing, treating and/or alleviating complications and/or symptoms and/or inflammatory responses associated therewith comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 34 (depends on 1)

A method for the prevention and/or treatment of cardiovascular and vascular diseases selected from the group consisting of acute stroke, congestive heart failure, cardiovascular ischemia, heart disease, cardiac remodeling, angina, coronary vasospasm, cerebral vasospasm, pulmonary vasoconstriction, restenosis, hypertension, pulmonary hypertension, arteriosclerosis, thrombosis and platelet related diseases, and/or for preventing, treating and/or alleviating complications and/or symptoms associated therewith comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 35 (depends on 1)

A method for the prevention and/or treatment of at least one disease and/or disorder selected from the group consisting of eye diseases; erectile dysfunction; cardiovascular diseases; vascular diseases; proliferative diseases; inflammatory diseases; neurological diseases and disease of the central nervous system (CNS); bronchial asthma; osteoporosis; renal diseases and AIDS comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 36 (depends on 1)

A method for the prevention and/or treatment of at least one disease and/or disorder selected from the group consisting of erectile dysfunction, bronchial asthma, osteoporosis, inflammatory diseases, renal diseases or AIDS, and/or for preventing, treating and/or alleviating complications and/or symptoms associated therewith comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 37 (depends on 1)

A method for the prevention and/or treatment of eyes diseases selected from the group consisting of retinopathy, macular degeneration and glaucoma, and/or for preventing, treating and/or alleviating complications and/or symptoms associated therewith comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 38 (depends on 1)

A method for the prevention, treatment and/or management of neurological and CNS disorders selected from the group consisting of stroke, multiple sclerosis, brain or spinal cord injury, inflammatory diseases and demyelinating diseases comprising Alzheimer's disease, MS and neuropathic pain, and/or for preventing, treating and/or alleviating complications and/or symptoms associated therewith comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 39 (depends on 1)

A method for the prevention and/or treatment of cancer selected from the group consisting of cancer of the brain (gliomas), breast, colon, intestine, skin, head and neck, kidney, lung, liver, ovarian, pancreatic, prostate, or thyroid; leukemia; lymphoma; sarcoma; melanoma; and/or for preventing, treating and/or alleviating complications and/or symptoms and/or inflammatory responses associated therewith comprising administering to an individual in need of such treatment an effective amount of a compound according to claim 1.

### Claim 40 (depends on 1)

A method for inhibiting the activity of at least one kinase, in vitro or in vivo using a compound according to claim 1, or a composition comprising such a compound.

### Claim 41 (depends on 40)

The method of claim 40 wherein said use is in vitro.

### Claim 42 (depends on 40)

The method of claim 40 wherein the at least one kinase is PKC epsilon.

### Claim 43 (depends on 40)

The method of claim 40 for inhibiting the activity of PKC epsilon and PKC theta.

### Claim 44 (depends on 40)

The method of claim 40 wherein the at least one kinase is ROCK.

### Claim 45 (depends on 44)

The method according to claim 44 in which the at least one kinase is chosen from the alpha and/or beta isoforms of ROCK.

### Claim 46 (depends on 44)

The method according to claim 44 in which the at least one kinase is chosen from the alpha isoform of ROCK.