CCR2 receptor antagonists and uses thereof
Inventors
Ebel, Heiner • Frattini, Sara • Gerlach, Kai • Giovannini, Riccardo • Hoenke, Christoph • Mazzaferro, Rocco • Santagostino, Marco • Scheuerer, Stefan • Tautermann, Christofer • Trieselmann, Thomas
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11731981-B2
Publication Date
2023-08-22
Expiration Date
Abstract
The present invention relates to novel antagonists for CCR2 (CC chemokine receptor 2) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD.
Core Innovation
The invention relates to a method for treating a neurologic disease selected from inflammatory and neuropathic pain in a human patient by administering an effective amount of a pharmaceutical formulation containing a compound of Formula I, or a salt thereof. Formula I is defined by structural variables including R1, R2, R3, R4, R5, R6, R7, n, G, E, and Z, with G and E as N, Z as C, and n as 1, 2, or 3. The compounds are further characterized by R4 denoting H and R5 being -L1-R18, with L1 selected from -NH-, -N(C1-C4-alkyl)-, or a bond, and R18 selected from C3-C8-cycloalkyl or C3-C8-heterocyclyl with optional substitution patterns.
R7 is selected from C3-C5-cycloalkyl, C5-C10-aryl, or C5-C10-heteroaryl, with optional substitution by groups including CF3, OCF3, SCF3, CN, alkyl, C(CH3)2-CN, halogen, O-C1-C6-alkyl, and C3-C8-cycloalkyl. The disclosed content further defines preferred Formula (I) embodiments by specified substituent selections for R1, R2, R3, and R6, including halogen, CN, alkyl, and oxygen-containing groups such as OCF3, OCF2H, and OCFH2.
The specification additionally describes compound intermediates and related chemical structures with stereochemical assignments, including cis and relative cis stereochemistry, and labeled intermediate series. It provides synthetic descriptions linking intermediates to product examples, together with analytical characterization by HPLC, GC/MS retention time, chiral HPLC separation, and X-ray crystallography in some examples.
Claims Coverage
The consolidated independent-claim coverage centers on one method claim for treating a neurologic disease selected from inflammatory and neuropathic pain in a human patient by administering an effective amount of a pharmaceutical formulation containing a compound of Formula I, or a salt thereof. The inventive features combine the treatment purpose with a highly defined Formula I scaffold and variable selections; several inputs repeat this claim while some add dependent claim refinements.
Treatment of inflammatory and neuropathic pain with Formula I pharmaceutical formulation
A method for treating a neurologic disease selected from inflammatory and neuropathic pain by administering to a human patient an effective amount of a pharmaceutical formulation containing a compound of Formula I, or a salt thereof.
Defined Formula I chemical structure variables
Formula I is represented with structural variables where R1, R2, R3, R4 denoting H, R5, R6, and R7 have specified selectable groups; G and E are N; Z is C; and n is 1, 2, or 3. The scope also includes R5 as -L1-R18 with L1 selected from -NH-, -N(C1-C4-alkyl)-, or a bond, and R18 selected from C3-C8-cycloalkyl or C3-C8-heterocyclyl with optional substitution.
R7 ring selection and optional substitution
R7 is a ring selected from C3-C5-cycloalkyl, C5-C10-aryl, or C5-C10-heteroaryl, optionally substituted with groups including CF3, OCF3, SCF3, CN, alkyl, C(CH3)2-CN, halogen, O-C1-C6-alkyl, and C3-C8-cycloalkyl.
The claim coverage is anchored by a method of treatment for inflammatory and/or neuropathic pain in a human patient using a pharmaceutical formulation comprising a Formula I compound or salt, with the scope constrained by defined substituent and ring-variable selections across the Formula I scaffold.
Stated Advantages
Modulating or treating MCP-1 related diseases via CCR2 antagonists that bind the CCR2/MCP-1 pathway.
Documented Applications
Treating a neurologic disease selected from inflammatory and neuropathic pain in a human patient by administering a pharmaceutical formulation containing a compound of Formula I, or a salt thereof.
Treating inflammatory diseases including respiratory inflammation such as COPD, asthma, and cystic fibrosis using a medicament formulated with a compound of Formula (I).
Treating immune-related diabetes mellitus using a medicament formulated with a compound of Formula (I).
Treating cardiovascular peripheral atherosclerotic disease using a medicament formulated with a compound of Formula (I).
Treating diabetic nephropathy using a medicament formulated with a compound of Formula (I).
Inflammatory/immune disease categories and MCP-1 related disease examples including rheumatoid arthritis.
Pulmonary disease categories and MCP-1 related disease examples including COPD and idiopathic pulmonary fibrosis.
Cardiovascular disease categories and MCP-1 related disease examples including atherosclerosis and restenosis.
Neurologic disease examples listed include multiple sclerosis, Alzheimer’s disease, inflammatory pain, neuropathic pain, and chronic pain.
Fibrotic disease categories including idiopathic pulmonary fibrosis.
Wound/trauma disease categories including wound healing.
Infectious disease categories are referenced as part of infectious indications.
Interested in licensing this patent?