# US 9,040,508 B2 · Compositions of protein receptor tyrosine kinase inhibitors

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- Number: US 9,040,508 B2
- Document ID: US9040508B2
- Status: Granted
- Kind: B2
- Application number: 13/133,565
- Filed: 2009-12-08
- Published: 2011-12-08
- Granted: 2015-05-26
- Earliest claimed: 2008-12-08
- Assignees: VM Pharma LLC
- Applicants: Jay Jie-Qiang Wu; Ling Wang
- Inventors: Jay Jie-Qiang Wu; Ling Wang
- Web page: https://patentgrep.com/patent/US9040508B2

## CPC

- C07D 498/06: Peri-condensed systems
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/497: containing further heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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 11/00: Drugs for disorders of the respiratory system
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 13/10: of the bladder
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 23/00: Anaesthetics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 25/30: for treating abuse or dependence
- A61P 25/32: Alcohol-abuse
- A61P 25/34: Tobacco-abuse
- 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 31/12: Antivirals
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 39/02: Antidotes
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 215/20: Oxygen atoms
- C07D 221/06: Ring systems of three rings
- C07D 223/32: containing carbocyclic rings other than six-membered
- C07D 241/44: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D 261/20: condensed with carbocyclic rings or ring systems
- C07D 265/36: condensed with one six-membered ring
- C07D 279/16: condensed with one six-membered ring
- C07D 295/13: to an acyclic saturated chain
- C07D 307/77: ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D 403/14: containing three or more hetero rings
- C07D 407/12: linked by a chain containing hetero atoms as chain links
- C07D 413/10: linked by a carbon chain containing aromatic rings
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 471/04: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D 491/04: Ortho-condensed systems
- C07D 493/06: Peri-condensed systems
- C07D 495/04: Ortho-condensed systems
- C07D 498/04: Ortho-condensed systems
- C07D 513/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

## Abstract

The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and/or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF receptor TrkA.

## Claims

### Claim 1

An oral unit dosage form, comprising: a therapeutically effective amount of a compound of
or a salt, solvate, ester or prodrug thereof; and at least one pharmaceutically acceptable vehicle;
wherein the oral unit dosage form is suitable for administration of about 0.001 mg/kg to about 200 mg/kg of the compound.

### Claim 2 (depends on 1)

The oral unit dosage form of claim 1, which is in a form selected from: tablets, pills, pellets, capsules, powders, lozenges, granules, solutions, suspensions, emulsion, syrups, elixirs, sustained-release formulations, aerosols, and sprays.

### Claim 3 (depends on 1)

The oral unit dosage form of claim 1, which is in a form of a tablet or capsule.

### Claim 4 (depends on 1)

The oral unit dosage form of claim 1, which is an oral liquid preparation.

### Claim 5 (depends on 1)

The oral unit dosage form of claim 1, which further comprises one or more optional agents selected from: sweetening agents, flavoring agents, coloring agents, preserving agents, time delay or delay disintegration materials, standard oral vehicles, suitable carriers, excipients and diluents.

### Claim 6

An intravenous unit dosage form, comprising: a therapeutically effective amount of a compound of
or a salt, solvate, ester or prodrug thereof; and at least one pharmaceutically acceptable vehicle;
wherein the intravenous unit dosage form is suitable for administration of about 0.01 mg/kg to about 100 mg/kg of the compound.

### Claim 7 (depends on 6)

The intravenous unit dosage form of claim 6, which is suitable for administration of about 0.01 mg/kg to about 1 mg/kg of the compound.

### Claim 8 (depends on 6)

The intravenous unit dosage form of claim 6, which is in the form of an aqueous solution.

### Claim 9

An intranasal unit dosage form, comprising: a therapeutically effective amount of a compound of
or a salt, solvate, ester or prodrug thereof; and at least one pharmaceutically acceptable vehicle;
wherein the intranasal unit dosage form is suitable for administration of about 0.01 mg to about 1 mg of the compound per kilogram of body weight.

### Claim 10 (depends on 9)

The intranasal unit dosage form of claim 9, which is in the form of an aqueous solution.

### Claim 11

A suppository unit dosage form, comprising: a therapeutically effective amount of a compound of
or a salt, solvate, ester or prodrug thereof; and at least one pharmaceutically acceptable vehicle;
wherein the suppository unit dosage form is suitable for administration of about 0.01 mg to about 50 mg of the compound per kilogram of body weight and comprises active ingredient in the rage of about 0.5% to about 10% by weight.

### Claim 12

An intradermal, intramuscular, intraperitoneal, subcutaneous, epidural, sublingual or intracerebral unit dosage form, comprising: a therapeutically effective amount of a compound of
or a salt, solvate, ester or prodrug thereof; and at least one pharmaceutically acceptable vehicle;
wherein the intradermal, intramuscular, intraperitoneal, subcutaneous, epidural, sublingual or intracerebral unit dosage form is suitable for administration of about 0.001 mg to about 200 mg of the compound per kilogram of body weight.