US 11,731,981 B2
CCR2 receptor antagonists and uses thereof
Heiner Ebel, Biberach an der Riss (DE); Sara Frattini, Castelleone (IT); Kai Gerlach, Mittelbiberach (DE); Riccardo Giovannini, Verona (IT); Christoph Hoenke, Biberach an der Riss (DE); Rocco Mazzaferro, San Giuliano Milanese (IT); Marco Santagostino, Mittelbiberach (DE); Stefan Scheuerer, Warthausen (DE); Christofer Tautermann, Biberach (DE); and Thomas Trieselmann, Mettenberg (DE)
Assigned to Centrexion Therapeutics Corporation, Boston, MA (US)
Filed by Centrexion Therapeutics Corporation, Boston, MA (US)
Filed on Jun. 11, 2021, as Appl. No. 17/345,110.
Application 14/260,552 is a division of application No. 12/969,745, filed on Dec. 16, 2010, granted, now 8,765,949, issued on Jul. 1, 2014.
Application 17/345,110 is a continuation of application No. 16/233,315, filed on Dec. 27, 2018, granted, now 11,046,706.
Application 16/233,315 is a continuation of application No. 15/606,749, filed on May 26, 2017, granted, now 10,196,402, issued on Feb. 5, 2019.
Application 15/606,749 is a continuation of application No. 14/260,552, filed on Apr. 24, 2014, granted, now 9,670,222, issued on Jun. 6, 2017.
Claims priority of application No. 09179555 (EP), filed on Dec. 17, 2009; and application No. 10162621 (EP), filed on May 12, 2010.
Prior Publication US 2022/0002310 A1, Jan. 6, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 491/107 (2006.01); A61P 25/02 (2006.01); A61P 25/00 (2006.01); A61P 25/04 (2006.01); A61P 29/00 (2006.01); C07D 405/14 (2006.01)
CPC C07D 491/107 (2013.01) [A61P 25/00 (2018.01); A61P 25/02 (2018.01); A61P 25/04 (2018.01); A61P 29/00 (2018.01); C07D 405/14 (2013.01)] 20 Claims
 
1. A method for treating a neurologic disease selected from inflammatory and neuropathic pain, comprising administering to a human patient an effective amount of a pharmaceutical formulation containing a compound of Formula I to treat the neurologic disease, wherein Formula I is represented by:

OG Complex Work Unit Chemistry
or a salt thereof; wherein:
R1 is a group selected from among —H, -halogen, —CN, —O—C1-C4-alkyl, —C1-C4-alkyl, —CH═CH2, —C≡CH, —CF3, —OCF3, —OCF2H, and —OCFH2;
R7 is a ring selected from among —C3-C5-cycloalkyl, —C5-C10-aryl, and —C5-C10-heteroaryl,
wherein the ring R7 is optionally substituted with one or more groups selected from among —CF3, —O—CF3, —S—CF3, —CN, —C1-C6-alkyl, —C(CH3)2—CN, and -halogen, or wherein the ring R7 is optionally substituted with one or more groups selected from among —O—C1-C6-alkyl and —C3-C8-cycloalkyl;
R2 is selected from among —H, -halogen, —CN, —O—C2-C4-alkyl, —C1-C4-alkyl, —CH═CH2, —C≡CH, —CF3, —OCF3, —OCF2H, and —OCFH2;
R3 is selected from among —H, -methyl, -ethyl, -propyl, -i-propyl, -cyclopropyl, —OCH3, —CF3, and —CN;
n is 1, 2, or 3;
G and E are N;
Z is C;
R4 denotes —H, and R5 is -L1-R18, wherein L1 is selected from among —NH—, —N(C1-C4-alkyl)-, and a bond, and R18 is —C3-C8-cycloalkyl or —C3-C8-heterocyclyl, wherein R18 is optionally substituted by one or more groups selected from among halogen, —CF3, —OCF3, —CN, —OH, —O—C1-C4-alkyl, —C1-C6-alkyl, —NH—C(O)—C1-C6-alkyl, —N(C1-C4-alkyl)-C(O)—C1-C6-alkyl, and —C(O)—C1-C6-alkyl; and
R6 is selected from among —H, —C1-C4-alkyl, —OH, —O—C1-C4-alkyl, -halogen, —CN, —CF3, and —OCF3.