Compositions useful as inhibitors of voltage-gated sodium channels

• US 8,309,543 B2
• Filed: 05/23/2012
• Issued: 11/13/2012
• Est. Priority Date: 08/08/2003
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Gonzalez, Jesus E. III, Termin, Andreas P., Martinborough, Esther, Hilgraf, Nicole
• Primary Examiner(s): Loewe, Sun Jae
• Application Number:
  US13/478,538
• Publication Number:
  US 20120238578A1
• Time in Patent Office: 174 Days
• Field of Search: None
• US Class Current: 514/225.8
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/10 for petit-mal
• CPC Class Codes: A61P 25/12 for grand-mal
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: 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
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: C04B 35/632 : Organic additives
• CPC Class Codes: C07C 2601/02 : with a three-membered ring
• CPC Class Codes: C07C 2601/08 : the ring being saturated
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 311/46 : Y being a hydrogen or a carbon atom
• CPC Class Codes: C07C 311/51 : Y being a hydrogen or a carbon atom
• CPC Class Codes: C07D 209/80 : [b, c]- or [b, d]-condensed
• CPC Class Codes: C07D 209/92 : Naphthostyrils
• CPC Class Codes: C07D 213/76 : to which a second hetero atom is attached nitro radicals C07D213/61
• CPC Class Codes: C07D 231/38 : Nitrogen atoms nitro radicals C07D231/16
• CPC Class Codes: C07D 231/42 : Benzene-sulfonamido pyrazoles
• CPC Class Codes: C07D 237/20 : Nitrogen atoms nitro radicals C07D237/12
• CPC Class Codes: C07D 237/22 : Nitrogen and oxygen atoms
• CPC Class Codes: C07D 239/42 : One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 239/47 : One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
• CPC Class Codes: C07D 239/52 : Two oxygen atoms
• CPC Class Codes: C07D 239/545 : with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
• CPC Class Codes: C07D 239/69 : Benzenesulfonamido-pyrimidines
• CPC Class Codes: C07D 241/22 : Benzenesulfonamido pyrazines
• CPC Class Codes: C07D 261/16 : Benzene-sulfonamido isoxazoles
• CPC Class Codes: C07D 263/50 : Benzene-sulfonamido oxazoles
• CPC Class Codes: C07D 277/52 : to sulfur atoms, e.g. sulfonamides
• CPC Class Codes: C07D 277/82 : Nitrogen atoms
• CPC Class Codes: C07D 285/125 : with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 285/135 : Nitrogen atoms
• CPC Class Codes: C07D 295/26 : Sulfur atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 407/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 513/04 : Ortho-condensed systems

Abstract

The present invention relates to compounds useful as inhibitors of voltage-gated sodium channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

Claims

1. A method of inhibiting one or more of NaV1.1, NaV1.2, NaV1.3, NaV1.4, NaV1.5, NaV1.6, NaV1.7, NaV1.8, NaV1.9, or CaV2.2 activity in:

(a) a patient;

or

(b) a biological sample;

which method comprising administering to said patient, or contacting said biological sample with a compound selected from the following;

2. A method of treating or lessening the severity of a disease, disorder, or condition selected from acute, chronic, neuropathic, or inflammatory pain, migraine, cluster headaches, trigeminal neuralgia, epilepsy arrhythmia, visceral pain, osteoarthritis pain, postherpetic neuralgia, radicular pain, sciatica, back pain, head or neck pain, severe or intractable pain, nociceptive pain, breakthrough pain, postsurgical pain, or cancer pain, comprising the step of administering to said patient an effective amount of a compound selected from the following:

3. The method according to claim 2, wherein the disease, condition, or disorder is implicated in the activation or hyperactivity of voltage-gated sodium channels.

4. The method according to claim 2, wherein the disease, condition, or disorder is radicular pain, sciatica, back pain, head pain, neck pain.

5. The method according to claim 2, wherein the disease, condition, or disorder is severe or intractable pain, acute pain, postsurgical pain, back pain, or cancer pain.

6. The method according to claim 2, wherein the disease, condition, or disorder is implicated in the activation or hyperactivity of voltage-gated calcium channels.

7. The method according to claim 6, wherein the disease, condition, or disorder is acute, chronic, neuropathic, or inflammatory pain.