Anti-inflammatory medicaments

• US 7,342,037 B2
• Filed: 06/09/2006
• Issued: 03/11/2008
• Est. Priority Date: 12/31/2002
• Status: Expired due to Fees

• Current Assignee: Deciphera Pharmaceuticals, LLC (Deciphera Pharmaceuticals, Inc.)
• Original Assignee: Deciphera Pharmaceuticals, LLC (Deciphera Pharmaceuticals, Inc.)
• Inventors: Flynn, Daniel L., Petillo, Peter A.
• Primary Examiner(s): Anderson; Rebecca
• Assistant Examiner(s): NOLAN, JASON MICHAEL
• Application Number:
  US11/450,840
• Publication Number:
  US 20070037808A1
• Time in Patent Office: 641 Days
• Field of Search: 514/406, 514/384, 514/361, 514/237.5, 514/376, 548/263.6, 548/376.1, 548/127, 548/230, 548/371.7, 548/140
• US Class Current: 514/406
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 2601/10 : the ring being unsaturated
• CPC Class Codes: C07C 271/56 : with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07D 231/38 : Nitrogen atoms nitro radicals C07D231/16
• CPC Class Codes: C07D 231/40 : Acylated on said nitrogen atom
• CPC Class Codes: C07D 285/10 : 1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 403/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/10 : linked by a carbon chain containing aromatic rings
• 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

Abstract

Novel compounds and methods of using those compounds for the treatment of inflammatory conditions are provided. In a preferred embodiment, modulation of the activation state of p38 kinase protein comprises the step of contacting the kinase protein with the novel compounds.

Claims

1. A compound having the formula

2. The compound of claim 1, wherein A is phenyl substituted by one or more R₇′

substituents, said R₇′

substituents being halogens.

3. The compound of claim 1, wherein A is an R₇′

-substituted naphthyl.

4. The compound of claim 1, where R₇″

is selected from the group consisting of aryls and heterocyclyls.

13. A method of treating an individual suffering from a condition selected from the group consisting of human inflammation, rheumatoid arthritis, rheumatoid spondylitis, osteo-arthritis, asthma, gouty arthritis, sepsis, septic shock, endotoxic shock, Gram-negative sepsis, toxic shock syndrome, adult respiratory distress syndrome, stroke, reperfusion injury, neural trauma, neural ischemia, psoriasis, restenosis, chronic pulmonary inflammatory disease, bone resorptive diseases, graft-versus-host reaction, Crohn'"'"'s disease, ulcerative colitis, inflammatory bowel disease, pyresis, and combinations thereof, said method comprising the step of administering to said individual a compound of the formula of claim 1.

5. A method of modulating the activation state of a p38-alpha kinase comprising the step of contacting said kinase with a molecule having the formula

6. The method of claim 5, wherein A is phenyl substituted by one or more R₇′

substituents, said R₇′

substituents being halogens.

7. The method of claim 5, wherein A is an R₇′

-substituted naphthyl.

8. The method of claim 5, where R₇″

is selected from the group consisting of aryls and heterocyclyls.

9. An adduct comprising a molecule bound with a kinase, said molecule having the formula

10. The adduct of claim 9, wherein A is phenyl substituted by one or more R₇′

substituents, said R₇′

substituents being halogens.

11. The adduct of claim 9, wherein A is an R₇′

-substituted naphthyl.

12. The adduct of claim 9, where R₇″

is selected from the group consisting of aryls and heterocyclyls.