# US 2008/0188514 A1 · Compounds and methods for kinase modulation, and indications therefor

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- Number: US 2008/0188514 A1
- Document ID: US20080188514A1
- Status: Published application
- Kind: A1
- Application number: 11/961,901
- Filed: 2007-12-20
- Published: 2008-08-07
- Earliest claimed: 2006-12-21
- Assignees: Plexxikon Inc.
- Inventors: Guoxian Wu; Wayne Spevak; Songyuan Shi; Hanna Cho; Prabha N. Ibrahim; Chao Zhang; Shenghua Shi; Yong Zhou; Dean Artis; Jiazhong Zhang
- Web page: https://patentgrep.com/patent/US20080188514A1

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- 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 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- 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 active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

## Claims

### Claim 1

A compound having the chemical structure of Formula I,
all salts, prodrugs, tautomers and isomers thereof,
wherein:
L1 is —O—, —S—, —S(O)—, or —S(O)2—;
R1 is selected from the group consisting of hydrogen, halogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, and -L-R3,
R3 is selected from the group consisting of hydrogen, provided, however, that hydrogen is not bound to any of S(O), S(O)2, C(O) or C(S) of L, optionally substituted lower alkyl, optionally substituted lower alkenyl, provided, however, that when R3 is optionally substituted lower alkenyl, no alkene carbon thereof is bound to N, S, O, S(O), S(O)2, C(O) or C(S) of L, optionally substituted lower alkynyl, provided, however, that when R3 is optionally substituted lower alkynyl, no alkyne carbon thereof is bound to N, S, O, S(O), S(O)2, C(O) or C(S) of L, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
R2 is selected from the group consisting of -Cy, -alk-Cy, -alk-X-(alk)b-Cy, -alk-NR4-(alk)b-Cy, -alk-C(X)-(alk)b-Cy, -alk-S(O)-(alk)h-Cy, -alk-S(O)2-(alk)b-Cy, -alk-OC(X)-(alk)b-Cy, -alk-C(X)O-(alk)b-Cy, -alk-C(X)NR4-(alk)b-Cy, -alk-S(O)2NR4-(alk)b-Cy, -alk-NR4C(X)-(alk)b-Cy, -alk-NR4S(O)2-(alk)b-Cy, -alk-NR4C(X)O-(alk)b-Cy, -alk-OC(X)NR4-(alk)b-Cy, -alk-NR4C(X)NR4-(alk)b-Cy, -alk-NR4S(O)2NR4-(alk)b-Cy, and C2-4 alkyl, wherein C2-4 alkyl is optionally substituted with one or more substituents selected from the group consisting of fluoro, —OH, —NH2, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, and di-alkylamino;
L at each occurrence is independently selected from the group consisting of -(alk), —X-(alk)b-, -(alk), —NR4-(alk)b-, -(alk)a-C(X)-(alk)b-, -(alk), —S(O)-(alk)b-, -(alk)-S(O)2-(alk)b-, -(alk), —OC(X)-(alk)b-, -(alk), —C(X)O-(alk)b-, -(alk), —C(X)NR4-(alk)b-, -(alk), —S(O)2NR4-(alk)b-, -(alk)-NR4C(X)-(alk)h-, -(alk)a-NR4S(O)2-(alk)b-, -(alk)a-NR4C(X)O-(alk)b-, -(alk)a-OC(X)NR4-(alk)b-, -(alk)a-NR4C(X)NR4-(alk)b-, and -(alk)a-NR4S(O)NR4-(alk)b-;
a and b are independently 0 or 1;
alk is C1-3 alkylene or C1-3 alkylene substituted with one or more substituents selected from the group consisting of fluoro, —OH, —NH2, lower alkyl, lower alkoxy, lower alkylthio, monoalkylamino, di-alkylamino, and —NR5R6, wherein lower alkyl or the alkyl chain(s) of lower alkoxy, lower alkylthio, mono-alkylamino or di-alkylamino are optionally substituted with one or more substituents selected from the group consisting of fluoro, —OH, —NH2, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino and cycloalkylamino, provided, however, that any substitution of the alkyl chain carbon bound to O of alkoxy, S of thioalkyl or N of mono- or di-alkylamino is fluoro;
X is O or S;
Cy is optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
R4 at each occurrence is independently selected from the group consisting of hydrogen, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl; and
R5 and R6 combine with the nitrogen to which they are attached to form a 5-7 membered heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of fluoro, —OH, —NH2, lower alkyl fluoro substituted lower alkyl, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, and fluoro substituted lower alkylthio; provided, however, that the compound is not

### Claim 2 (depends on 1)

The compound of claim 1 having the chemical structure of Formula Ie,
all salts, prodrugs, tautomers and isomers thereof,
wherein:
L2 is independently selected from the group consisting of optionally substituted methylene, -(alk)a-X-(alk)b-, -(alk)a-NR4-(alk)b-, -(alk)a-C(X)-(alk)b-, -(alk)a-S(O)-(alk)b-, -(alk)a-S(O)2-(alk)b-, -(alk)3-OC(X)-(alk)b-, -(alk)a-C(X)O-(alk)b-, -(alk), —C(X)NR4-(alk)b-, -(alk)a-S(O)2NR4-(alk)b-, -(alk), —NR4C(X)-(alk)b-, -(alk)a-NR4S(O)2-(alk)b-, -(alk)a-NR4C(X)O-(alk)b-, -(alk)a-OC(X)NR4-(alk)b-, -(alk)a-NR4C(X)NR4-(alk)b-, and -(alk)a-NR4S(O)2NR4-(alk)b-.

### Claim 3 (depends on 1)

The compound of claim 1 having the chemical structure of Formula Ij,
all salts, prodrugs, tautomers and isomers thereof,
wherein:
L3 is selected from the group consisting of —O—, —S—, —CRaRb—, —NR4—, —C(O)—, —C(S)—, —S(O)—, and —S(O)2—; and
Ra and Rb at each occurrence are independently selected from the group consisting of hydrogen, fluoro, —OH, —NH2, lower alkyl, lower alkoxy, lower alkylthio, mono-alkylamino, di-alkylamino, and —NR5R6, wherein the alkyl chain(s) of lower alkyl, lower alkoxy, lower alkylthio, mono-alkylamino, or di-alkylamino are optionally substituted with one or more substituents selected from the group consisting of fluoro, —OH, —NH2, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino, and cycloalkylamino, provided, however, that any substitution of the alkyl chain carbon bound to O of alkoxy, S of thioalkyl or N of mono- or di-alkylamino is fluoro; or
Ra and Rb combine to form a 3-7 membered monocyclic cycloalkyl or 5-7 membered monocyclic heterocycloalkyl, wherein the monocyclic cycloalkyl or monocyclic heterocycloalkyl are optionally substituted with one or more substituents selected from the group consisting of halogen, —OH, —NH2, lower alkyl, fluoro substituted lower alkyl, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino, and cycloalkylamino.

### Claim 4 (depends on 1)

The compound of claim 1 having the chemical structure of Formula Ip,
all salts, prodrugs, tautomers and isomers thereof,
wherein:
R7 is selected from the group consisting of -Cy1, -alk-Cy1, -alk-X-(alk)b-Cy1, -alk-NR12-(alk)b-Cy1, -alk-C(X)-(alk)b-Cy1, -alk-S(O)-(alk)b-Cy1, -alk-S(O)2-(alk)b-Cy1, -alk-OC(X)-(alk)b-Cy1, -alk-C(X)O-(alk)b-Cy1, -alk-C(X)NR12-(alk)b-Cy1, -alk-S(O)2NR12-(alk)b-Cy1, -alk-NR12C(X)-(alk)b-Cy1, -alk-NR12S(O)2-(alk)b-Cy1, -alk-NR12C(X)O-(alk)b-Cy1, -alk-OC(X)NR12-(alk)b-Cy1, -alk-NR12C(X)NR12-(alk)b-Cy1, -alk-NR12S(O)2NR12-(alk)b-Cy1, and C2-4 alkyl, wherein C2-4 alkyl is optionally substituted with one or more substituents selected from the group consisting of fluoro, —OH, —N2, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, and di-alkylamino;
R8 is selected from the group consisting of hydrogen, halogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —OR9, —SR9, —CR10R11R9, —NR12R9, —C(O)R9, —C(S)R9, —S(O)R9, and —S(O)2R9, wherein lower alkyl, lower alkenyl, or lower alkynyl are optionally substituted with one or more substituents selected from the group consisting of fluoro, —OH, —NH2, —C(O)OH, —C(O)NH2, —OR13, —SR13, —NR12R13, —C(O)OR13, —C(O)NR12R13, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, and wherein cycloalkyl, heterocycloalkyl, aryl, or heteroaryl as R8, or a substituent of lower alkyl, lower alkenyl, or lower alkynyl are optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2, —CN, —NO2, —C(O)OH, —S(O)2NH2, —C(O)NH2, —C(S)NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —OR13, —SR13, —NR12R13, —C(O)R13, —C(S)R13, —C(O)OR13, —C(O)NR12R13, —C(S)NR12R13, —S(O)2NR12R13, —NR12C(O)R13, —NR12C(S)R13, —NR12S(O)2R13, —NR12C(O)NR12R13, —NR12C(S)NR12R13, —NR12S(O)2NR12R13, —S(O)R13, —S(O)2R13, halogen, lower alkyl, fluoro substituted lower alkyl, and cycloalkylamino.
R9 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, wherein lower alkyl, lower alkenyl, and lower alkynyl are optionally substituted with one or more substituents selected from the group consisting of fluoro, —OH, —NH2, —C(O)OH, —C(O)NH2, —OR13, —SR13, —NR12R13, —C(O)OR13, —C(O)NR12R13 cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, and wherein cycloalkyl, heterocycloalkyl, aryl, and heteroaryl as R9, or a substituent of lower alkyl, lower alkenyl, or lower alkynyl are optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2, —CN, —NO, —C(O)OH, —S(O)2NH2, —C(O)NH2, —C(S)NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —OR13, —SR13, —NR12R13, —C(O)R13, —C(S)R13, —C(O)OR13, —C(O)NR12R13, —C(S)NR12R13, —S(O)2NR12R13, —NR12C(O)R13, —NR12C(S)R13, —NR12S(O)2R13, —NR12C(O)NR12R13, —NR12C(S)NR12R13, —NR12S(O)2NR12R13, —S(O)R13, —S(O)2R13, halogen, lower alkyl, fluoro substituted lower alkyl, and cycloalkylamino;
Cy1 is cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2, —CN, —NO2, —C(O)OH, —S(O)2NH2, —C(O)NH2, —C(S)NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —OR13, —SR13, —NR12R13, —C(O)R13, —C(S)R13, —C(O)R13—C(O)NR12R13, —C(S)NR12R13, —S(O)2NR12R13, —NR12C(O)R13, —NR12C(S)R13, —NR12S(O)2R13, —NR12C(O)NR12R13, —NR12C(S)NR12R13, —NR12S(O)2NR12R13, S(O)R13, —S(O)2R13, halogen, lower alkyl, fluoro substituted lower alkyl, and cycloalkylamino;
R10 and R11 are independently selected from the group consisting of hydrogen, fluoro, lower alkyl, fluoro substituted lower alkyl, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino, and cycloalkylamino; or
R10 and R11 combine to form a 3-7 membered monocyclic cycloalkyl or 5-7 membered monocyclic heterocycloalkyl, wherein the monocyclic cycloalkyl or monocyclic heterocycloalkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, —OH, —NH2, lower alkyl, fluoro substituted lower alkyl, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino, and cycloalkylamino;
R12 at each occurrence is independently hydrogen, lower alkyl or fluoro substituted lower alkyl;
R13 at each occurrence is independently selected from the group consisting of lower alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein lower alkyl is optionally substituted with one or more substituents selected from the group consisting of fluoro, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, provided, however, that any substitution of the alkyl carbon bound to O, S, or N of —OR13, —SR13, —NR12R13, —C(O)OR13, —C(O)NR12R13, or —S(O)2NR12R13 is fluoro, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, and wherein cycloalkyl, heterocycloalkyl, aryl, and heteroaryl as R13 or as substituents of lower alkyl are optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2, —CN, —NO2, —C(O)OH, —S(O)2NH2, —C(O)NH2, —OR14, —SR14, —NR12R14, —NR12—C(O)R14, —NR12S(O)2R4, —S(O)2R14, —C(O)R14, —C(O)OR14, —C(O)NR12R14, —S(O)2NR12R14, halogen, lower alkyl, fluoro substituted lower alkyl, and cycloalkylamino; and
R14 at each occurrence is independently selected from the group consisting of lower alkyl, heterocycloalkyl and heteroaryl, wherein lower alkyl is optionally substituted with one or more substituents selected from the group consisting of fluoro, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino, and cycloalkylamino, provided, however, that any substitution of the alkyl carbon bound to O, S, or N of —OR4, —SR4, —NR12R14, —C(O)OR14, —C(O)NR12R14, or —S(O)2NR12R14 is fluoro, and wherein heterocycloalkyl and heteroaryl are optionally substituted with one or more substituents selected from the group consisting of halogen, —CN, lower alkyl, fluoro substituted lower alkyl, lower alkoxy and fluoro substituted lower alkoxy.

### Claim 5 (depends on 4)

The compound of claim 4
wherein:
R7 is selected from the group consisting of -Cy1, -alk-Cy1, -alk-X-(alk)b-Cy1, -alk-NR12-(alk)b-Cy1, -alk-C(X)-(alk)b-Cy1, -alk-S(O)-(alk)b-Cy1, -alk-S(O)2-(alk)b-Cy1, -alk-OC(X)-(alk)b-Cy1, -alk-C(X)O-(alk)h-Cy1, -alk-C(X)NR12-(alk)b-Cy1, -alk-S(O)2NR12-(alk)b-Cy1, -alk-NR12C(X)-(alk)b-Cy1, -alk-NR12S(O)2-(alk)b-Cy1, -alk-NR12C(X)O-(alk)b-Cy1, -alk-OC(X)NR12-(alk)b-Cy1, -alk-NR12C(X)NR12-(alk)b-Cy1, and -alk-NR12S(O)2NR12-(alk)b-Cy1;
R8 is selected from the group consisting of hydrogen, —OR9, —SR9, —CR10R11R9, —NR12R9, —C(O)R9, —C(S)R9, —S(O)R9, and —S(O)2R9; and
R9 is aryl or heteroaryl, wherein aryl or heteroaryl are optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2, —CN, —NO2, —C(O)OH, —S(O)2NH2, —C(O)NH2, —C(S)NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —OR13, —SR13, —NR12R13, —C(O)R13, —C(S)R13, —C(O)OR13, —C(O)NR12R13, —C(S)NR12R13, —S(O)2NR12R13, —NR12C(O)R13, —NR12C(S)R13, —NR12S(O)2R13, —NR12C(O)NR12R13, —NR12C(S)NR12R13, —NR12S(O)2NR12R13, —S(O)R13, —S(O)2R13, halogen, lower alkyl, fluoro substituted lower alkyl, and cycloalkylamino.

### Claim 6 (depends on 5)

The compound of claim 5 wherein R7 is -Cy1 or -alk-Cy1.

### Claim 7 (depends on 6)

The compound of claim 6
wherein:
Cy1 is cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein cycloalkyl, heterocycloalkyl, aryl or heteroaryl are optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2, —CN, —NO2, —S(O)2NH2, —C(O)NH2, —OR13, —NR12R13, —C(O)R13, —C(O)NR12R13, —S(O)2NR12R13, —NR12C(O)R13, —NR12S(O)2R13, —S(O)2R13, halogen, lower alkyl, fluoro substituted lower alkyl, and cycloalkylamino; and
R9 is aryl or heteroaryl, wherein aryl and heteroaryl are optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2, —CN, —NO2, —S(O)2NH2, —C(O)N2, —NHC(O)NH2, —NHS(O)2NH2, —OR13, —SR13, —NR12R13, —C(O)R13, —C(O)NR12R13, —S(O)2NR12R13, —NR12C(O)R13, —NR12S(O)2R13, —NR12C(O)NR12R13, —NR12S(O)2NR12R13, —S(O)2R13, halogen, lower alkyl, fluoro substituted lower alkyl, and cycloalkylamino.

### Claim 8 (depends on 1)

A composition comprising:
a pharmaceutically acceptable carrier; and
a compound according to claim 1.

### Claim 9 (depends on 1)

A method for treating a subject suffering from or at risk of a kinase mediated disease or condition, comprising administering to the subject an effective amount of a compound of claim 1.

### Claim 10 (depends on 9)

The method of claim 9, wherein the disease or condition is selected from the group consisting of ischemic stroke, cerebrovascular ischemia, multi-infarct dementia, head injury, spinal cord injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, dementia, senile chorea, Huntington's disease, chemotherapy-induced hypoxia, gastrointestinal stromal tumors, prostate tumors, mast cell tumors, acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, multiple myeloma, melanoma, mastocytosis, gliomas, glioblastoma, astrocytoma, neuroblastoma, sarcomas, carcinomas of the lung, breast, pancreas, colon, liver, kidney, female genital tract, squamous cells, or carcinoma in situ, histiocytic lymphoma, non-Hodgkin's lymphoma. MEN2 syndromes, neurofibromatosis, myelodysplastic syndrome, leukemia, tumor angiogenesis, cancers of the thyroid, liver, bone, skin, brain, central nervous system, pancreas, lung, breast, colon, bladder, prostate, gastrointestinal tract, endometrium, fallopian tube, testes or ovary, metastasis of tumors to other tissues, neuropathic pain, acute pain, chronic pain, bone pain, cancer related pain, migraine, heart failure, cardiac hypertrophy, thrombosis, atherosclerosis, reperfusion injury, ischemia, age-related macular degeneration, rheumatoid arthritis, allergic rhinitis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis, Sjogren's Syndrome, Wegener's granulomatosis, psoriasis, scleroderma, chronic thyroiditis, Grave's disease, myasthenia gravis, multiple sclerosis, osteoarthritis, endometriosis, scarring, vascular restenosis, fibrotic disorders, hypereosinophilia, CNS inflammation, pancreatitis, nephritis, atopic dermatitis, hepatitis, severe combined immunodeficiency, organ transplant rejection, graft versus host disease, diabetic nephropathy, polycystic kidney disease, nephrosclerosis, glomerulonephritis, interstitial nephritis, Lupus nephritis, prostate hyperplasia, chronic renal failure, tubular necrosis, diabetes-associated renal complications, hypertrophy, type 1 diabetes, type 2 diabetes, metabolic syndrome, obesity, hepatic steatosis, insulin resistance, hyperglycemia, lipolysis, obesity, Helicobacter pylori infection, Influenza virus infection, Hepatitis virus infection, fever, sepsis, chronic obstructive pulmonary disease, acute respiratory distress syndrome, asthma, allergy, bronchitis, emphysema, pulmonary fibrosis, Noonan's syndrome, Crouzon syndrome, acrocephalo-syndactyly type I, Pfeiffer's syndrome, Jackson-Weiss syndrome, Costello syndrome, LEOPARD syndrome, cardio-faciocutaneous syndrome, neural crest syndrome abnormalities causing cardiovascular, skeletal, intestinal, skin, hair or endocrine diseases, osteoporosis, increased risk of fracture, Paget's disease, hypercalcemia, metastatis of cancer to bone, Grave's disease, Hirschsprung's disease, lymphoedema, selective T-cell defect, X-linked agammaglobulinemia, diabetic retinopathy, alopecia, erectile dysfunction, tuberous sclerosis, Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Emery-Dreifuss Muscular Dystrophy, Limb-Girdle Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy, Myotonic Muscular Dystrophy, Oculopharyngeal Muscular Dystrophy, Distal Muscular Dystrophy, Congenital Muscular Dystrophy, amyotrophic lateral sclerosis, infantile progressive spinal muscular atrophy, intermediate spinal muscular atrophy, juvenile spinal muscular atrophy, spinal bulbar muscular atrophy, adult spinal muscular atrophy, dermatomyositis, polymyositis, inclusion body myositis, Lambert-Eaton syndrome, congenital myasthenic syndrome), hyperthyroid myopathy, hypothyroid myopathy, Charcot-Marie-Tooth disease, Dejerine-Sottas disease, Friedreich's ataxia, myotonia congenital paramyotonia congenita, central core disease, nemaline myopathy, myotubular myopathy, periodic paralysis, phosphorylase deficiency, acid maltase deficiency, phosphofructokinase deficiency, debrancher enzyme deficiency, mitochondrial myopathy, carnitine deficiency, carnitine palmatyl transferase deficiency, phosphoglycerate kinase deficiency, phosphoglycerate mutase deficiency, lactate dehydrogenase deficiency, and myoadenylate deaminase deficiency.

### Claim 11 (depends on 1)

A kit comprising a compound according to claim 1.

### Claim 12 (depends on 11)

The kit of claim 11, wherein the compound or composition is approved for a medical indication selected from the group consisting of ischemic stroke, cerebrovascular ischemia, multi-infarct dementia, head injury, spinal cord injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, dementia, senile chorea, Huntington's disease, chemotherapy-induced hypoxia, gastrointestinal stromal tumors, prostate tumors, mast cell tumors, acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, multiple myeloma, melanoma, mastocytosis, gliomas, glioblastoma, astrocytoma, neuroblastoma, sarcomas, carcinomas of the lung, breast, pancreas, colon, liver, kidney, female genital tract, squamous cells, or carcinoma in situ, histiocytic lymphoma, non-Hodgkin's lymphoma, MEN2 syndromes, neurofibromatosis, myelodysplastic syndrome, leukemia, tumor angiogenesis, cancers of the thyroid, liver, bone, skin, brain, central nervous system, pancreas, lung, breast, colon, bladder, prostate, gastrointestinal tract, endometrium, fallopian tube, testes or ovary, metastasis of tumors to other tissues, neuropathic pain, acute pain, chronic pain, bone pain, cancer related pain, migraine, heart failure, cardiac hypertrophy, thrombosis, atherosclerosis, reperfusion injury, ischemia, age-related macular degeneration, rheumatoid arthritis, allergic rhinitis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis, Sjogren's Syndrome, Wegener's granulomatosis, psoriasis, scleroderma, chronic thyroiditis, Grave's disease, myasthenia gravis, multiple sclerosis, osteoarthritis, endometriosis, scarring, vascular restenosis, fibrotic disorders, hypereosinophilia, CNS inflammation, pancreatitis, nephritis, atopic dermatitis, hepatitis, severe combined immunodeficiency, organ transplant rejection, graft versus host disease, diabetic nephropathy, polycystic kidney disease, nephrosclerosis, glomerulonephritis, interstitial nephritis, Lupus nephritis, prostate hyperplasia, chronic renal failure, tubular necrosis, diabetes-associated renal complications, hypertrophy, type 1 diabetes, type 2 diabetes, metabolic syndrome, obesity, hepatic steatosis, insulin resistance, hyperglycemia, lipolysis, obesity, Helicobacter pylori infection, Influenza virus infection, Hepatitis virus infection, fever, sepsis, chronic obstructive pulmonary disease, acute respiratory distress syndrome, asthma, allergy, bronchitis, emphysema, pulmonary fibrosis, Noonan's syndrome, Crouzon syndrome, acrocephalo-syndactyly type I, Pfeiffer's syndrome, Jackson-Weiss syndrome, Costello syndrome, LEOPARD syndrome, cardio-faciocutaneous syndrome, neural crest syndrome abnormalities causing cardiovascular, skeletal, intestinal, skin, hair or endocrine diseases, osteoporosis, increased risk of fracture, Paget's disease, hypercalcemia, metastatis of cancer to bone, Grave's disease, Hirschsprung's disease, lymphoedema, selective T-cell defect, X-linked agammaglobulinemia, diabetic retinopathy, alopecia, erectile dysfunction, tuberous sclerosis, Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Emery-Dreifuss Muscular Dystrophy, Limb-Girdle Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy, Myotonic Muscular Dystrophy, Oculopharyngeal Muscular Dystrophy, Distal Muscular Dystrophy, Congenital Muscular Dystrophy, amyotrophic lateral sclerosis, infantile progressive spinal muscular atrophy, intermediate spinal muscular atrophy, juvenile spinal muscular atrophy, spinal bulbar muscular atrophy, adult spinal muscular atrophy, dermatomyositis, polymyositis, inclusion body myositis, Lambert-Eaton syndrome, congenital myasthenic syndrome), hyperthyroid myopathy, hypothyroid myopathy, Charcot-Marie-Tooth disease, Dejerine-Sottas disease, Friedreich's ataxia, myotonia congenita, paramyotonia congenita, central core disease, nemaline myopathy, myotubular myopathy, periodic paralysis, phosphorylase deficiency, acid maltase deficiency, phosphofructokinase deficiency, debrancher enzyme deficiency, mitochondrial myopathy, carnitine deficiency, carnitine palmatyl transferase deficiency, phosphoglycerate kinase deficiency, phosphoglycerate mutase deficiency, lactate dehydrogenase deficiency, and myoadenylate deaminase deficiency.