Patent
Treating an inflammatory disorder or inhibiting respiratory burst in adherent neutrophils with chemical inhibitors of neutrophil activation
| العنوان: | Treating an inflammatory disorder or inhibiting respiratory burst in adherent neutrophils with chemical inhibitors of neutrophil activation |
|---|---|
| Patent Number: | 7,977,366 |
| تاريخ النشر: | July 12, 2011 |
| Appl. No: | 10/575683 |
| Application Filed: | October 14, 2004 |
| مستخلص: | The present invention relates to a method of treating an inflammatory disorder in a subject with an effective amount of compound having the general formula (I) as described in the present application, under conditions effective to treat the inflammatory disorder. The present invention also relates to a method of inhibiting respiratory burst in neutrophils without inhibiting degranulation in or bacterial killing by the neutrophils by contacting neutrophils with the compounds described above. [chemical expression included] |
| Inventors: | Han, Hyunsil (New York, NY, US); Lin, Gang (New York, NY, US); Nathan, Carl (Larchmont, NY, US) |
| Assignees: | Cornell Research Foundation, Inc. (Ithaca, NY, US) |
| Claim: | 1. A method of inhibiting respiratory burst in adherent neutrophils without inhibiting degranulation in neutrophils or bacterial killing by neutrophils, said method comprising: contacting adherent neutrophils with an effective amount of a chemical compound, wherein the compound has the formula: [chemical expression included] wherein: R 1 is substituted or unsubstituted phenyl; R 2 is C 1 -C 4 alkyl; and R 3 is substituted or unsubstituted quinoline with or without a linking group. |
| Claim: | 2. The method according to claim 1 , wherein the compound has the formula: [chemical expression included] |
| Claim: | 3. A method of inhibiting respiratory burst in adherent neutrophils without inhibiting degranulation in neutrophils or bacterial killing by neutrophils, said method comprising: contacting adherent neutrophils with an effective amount of a chemical compound, wherein the compound has the formula: [chemical expression included] wherein: R 1 is substituted or unsubstituted phenyl; R 2 is C 1 -C 4 alkyl; and R 3 is substituted or unsubstituted benzoylhydrazino. |
| Claim: | 4. The method according to claim 3 , wherein the compound has the formula: [chemical expression included] |
| Claim: | 5. The method according to claim 3 , wherein the compound has the formula: [chemical expression included] |
| Claim: | 6. The method according to claim 3 , wherein the compound has the formula: [chemical expression included] |
| Claim: | 7. The method according to claim 3 , wherein the compound has the formula: [chemical expression included] |
| Claim: | 8. The method according to claim 3 , wherein the compound has the formula: [chemical expression included] |
| Claim: | 9. The method according to claim 3 , wherein the compound has the formula: [chemical expression included] |
| Claim: | 10. The method according to claim 3 , wherein the compound has the formula: [chemical expression included] |
| Claim: | 11. The method according to claim 1 , wherein said contacting neutrophils is carried out in vitro. |
| Claim: | 12. The method according to claim 1 , wherein said contacting neutrophils is carried out in vivo. |
| Claim: | 13. The method according to claim 1 , wherein said contacting with a compound inhibits respiratory burst in adherent neutrophils triggered by an agent selected from the group consisting of a chemokine, a cytokine, bacteria, and a bacterial factor. |
| Claim: | 14. The method according to claim 13 , wherein said contacting with a compound inhibits respiratory burst in adherent neutrophils triggered by a chemokine selected from the group consisting of macrophage inflammatory protein-1 (MIP-1), interleukin-8 (IL-8), and chemoattractant complement component C5a. |
| Claim: | 15. The method according to claim 13 , wherein said contacting with a compound inhibits respiratory burst in adherent neutrophils triggered by a cytokine selected from the group consisting of tumor necrosis factor (TNF), lymphotoxin, granulocyte-specific colony stimulating factor (G-CSF), and granulocyte/macrophage-specific colony stimulating factor (GM-CSF). |
| Claim: | 16. The method according to claim 13 , wherein said contacting with a compound inhibits respiratory burst in adherent neutrophils triggered by bacteria selected from the group consisting of whole bacteria, bacterial cell wall components, and secreted or shed bacterial products. |
| Claim: | 17. The method according to claim 13 , wherein said contacting with a compound inhibits respiratory burst in adherent neutrophils triggered by a bacterial factor that is a soluble bacterial complement protein. |
| Claim: | 18. The method according to claim 3 , wherein said contacting neutrophils is carried out in vitro. |
| Claim: | 19. The method according to claim 3 , wherein said contacting neutrophils is carried out in vivo. |
| Claim: | 20. The method according to claim 3 , wherein said contacting with a compound inhibits respiratory burst in adherent neutrophils triggered by an agent selected from the group consisting of a chemokine, a cytokine, bacteria, and a bacterial factor. |
| Claim: | 21. The method according to claim 20 , wherein said contacting with a compound inhibits respiratory burst in adherent neutrophils triggered by a chemokine selected from the group consisting of macrophage inflammatory protein-1 (MIP-1), interleukin-8 (IL-8), and chemoattractant complement component C5a. |
| Claim: | 22. The method according to claim 20 , wherein said contacting with a compound inhibits respiratory burst in adherent neutrophils triggered by a cytokine selected from the group consisting of tumor necrosis factor (TNF), lymphotoxin, granulocyte-specific colony stimulating factor (G-CSF), and granulocyte/macrophage-specific colony stimulating factor (GM-CSF). |
| Claim: | 23. The method according to claim 20 , wherein said contacting with a compound inhibits respiratory burst in adherent neutrophils triggered by bacteria selected from the group consisting of whole bacteria, bacterial cell wall components, and secreted or shed bacterial products. |
| Claim: | 24. The method according to claim 20 , wherein said contacting with a compound inhibits respiratory burst in adherent neutrophils triggered by a bacterial factor that is a soluble bacterial complement protein. |
| Current U.S. Class: | 514/396 |
| Patent References Cited: | 5462946 October 1995 Mitchell et al. 5475017 December 1995 Wuest et al. 2002/0119988 August 2002 Sneddon et al. 2003/0073712 April 2003 Wang et al. WO 2003024446 March 2003 |
| Other References: | Ram et al.“Thieno[2,3-d]pyrimidines as Potential Chemotherapeutic Agents. II.”, J Het Chem, 1981, 18, 1227-1280. cited by examiner http://www.medilexicon.com/medicaldictionary.php?t=13063Test. cited by examiner Picciola et al., “Composti Eterociclici a Potenziale Attivita Antiinflammatoria Contenenti il Residuo di un Acido 4-Amminofenilalcanoico,” Farmaco 39:371-378 (1984). cited by other Short & Schoeb, “Synthesis and Structure of 5-Oxo-1-Phenylpyrazoline-3- and 4-Alkanoic Acids. Antiinflammatory Agents,” J. Heterocyclic Chem. 6:723-728 (1969). cited by other International Search Report for PCT/US04/33914 (May 26, 2006). cited by other Written Opinion for PCT/US2004/033914 (May 26, 2006). cited by other Han et al., “Critical Role of the Carboxyl Terminus of Proline-Rich Tyrosine Kinase (Pyk2) in the Activation of Human Neutrophils by Tumor Necrosis Factor: Separation of Signals for the Respiratory Burst and Degranulation,” J. Exp. Med. 197(1):63-75 (2003). cited by other Han et al., “Chemical Inhibitors of TNF Signal Transduction in Human Neutrophils Point to Distinct Steps in Cell Activation,” J. Leukoc. Biol. 79:147-154 (2006). cited by other Han et al., “Calcium-Sensing Soluble Adenylyl Cyclase Mediates TNF Signal Transduction in Human Neutrophils,” J. Exp. Med. 202(3):353-361 (2005). cited by other Han, “Tumor Necrosis Factor Triggered Signaling Cascades in Adherent Human Neutrophils: Separation of Signals for the Respiratory Burst and Degranulation,” Dissertation Presented to the Faculty of the Joan and Sanford I. Weill Graduate School of Biomedical Sciences of Cornell University (Indexed Feb. 2004). cited by other Parsons, “Focal Adhesion Kinase: The First Ten Years,” J. Cell Sci. 116:1409-1416 (2003). cited by other Sadhu et al., “Essential Role of Phosphoinositide 3-Kinase Delta in Neutrophil Directional Movement,” J. Immunol. 170:2647-2654 (2003). cited by other Nathan, “Inflammation as a Flow of Information,” Oral Presentation, Weill Medical College, Cornell University (Oct. 15, 2003). cited by other |
| Assistant Examiner: | Javanmard, Sahar |
| Primary Examiner: | Padmanabhan, Sreeni |
| Attorney, Agent or Firm: | LeClairRyan |
| رقم الانضمام: | edspgr.07977366 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |