FREE BASE CRYSTALLINE FORM OF A COMPLEMENT COMPONENT C5a RECEPTOR

Abstract

Provided herein is a free base crystalline form of a complement component 5a receptor having the formula of Compound 1Also provided herein are pharmaceutical compositions and methods of treatment using the crystalline free base form of Compound 1 described herein.

1 .- 2 . (canceled) 
     
     
         3 . The method of  claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by XRPD peaks at 12.4, 15.2, 16.1, 24.4, and 24.7 degrees 2θ (±0.2 degrees 2θ) 
     
     
         4 . The method of  claim 11 , wherein the free base crystalline form of Compound 1 is characterized by an X-ray powder diffraction pattern substantially in accordance with  FIG. 1 . 
     
     
         5 . The method of  claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a differential scanning calorimetry thermogram (DSC) comprising an endothermic peak at around 216° C. 
     
     
         6 . The method of  claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a melting point onset of about 213° C. as determined by differential scanning calorimetry thermogram (DSC). 
     
     
         7 . The method of  claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a DSC substantially in accordance with  FIG. 2 . 
     
     
         8 .- 10 . (canceled) 
     
     
         11 . A method for treating an individual suffering from or susceptible to a disease or disorder involving pathologic activation of C5a receptors, comprising administering to the individual an effective amount of a free base crystalline form of Compound 1 
       
         
           
           
               
               
           
         
         characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 8.1, 8.4, 14.1, 16.9, and 19.0 degrees 2θ (±0.2 degrees 2θ). 
       
     
     
         12 . The method of  claim 11 , wherein the disease or disorder is an inflammatory disease or disorder. 
     
     
         13 . The method of  claim 12 , wherein the disease or disorder is selected from the group consisting of neutropenia, sepsis, septic shock, Alzheimer's disease, multiple sclerosis, stroke, inflammatory bowel disease, age-related macular degeneration, chronic obstructive pulmonary disorder, inflammation associated with burns, lung injury, osteoarthritis, atopic dermatitis, chronic urticaria, ischemia-reperfusion injury, acute respiratory distress syndrome, systemic inflammatory response syndrome, multiple organ dysfunction syndrome, tissue graft rejection, cancer and hyperacute rejection of transplanted organs. 
     
     
         14 . The method of  claim 11 , wherein the disease or disorder is a cardiovascular or cerebrovascular disorder. 
     
     
         15 . The method of  claim 14 , wherein the disease or disorder is selected from the group consisting of myocardial infarction, coronary thrombosis, vascular occlusion, post-surgical vascular reocclusion, artherosclerosis, traumatic central nervous system injury and ischemic heart disease. 
     
     
         16 . The method of  claim 11 , wherein the disease or disorder is an autoimmune disorder. 
     
     
         17 . The method of  claim 16 , wherein the disease or disorder is selected from the group consisting of rheumatoid arthritis, C3 glomerulopathy (C3G), hidradenitis suppurativa (HS), systemic lupus erythematosus, Guillain-Barre syndrome, pancreatitis, lupus nephritis, lupus glomerulonephritis, psoriasis, immunoglobulin A (IgA) nephropathy, Crohn's disease, vasculitis, irritable bowel syndrome, dermatomyositis, multiple sclerosis, bronchial asthma, pemphigus, pemphigoid, scleroderma, myasthenia gravis, autoimmune hemolytic and thrombocytopenic states, Goodpasture's syndrome, immunovasculitis, tissue graft rejection and hyperacute rejection of transplanted organs. 
     
     
         18 . The method of  claim 11 , wherein the disease or disorder is a pathologic sequelae associated with the group consisting of insulin-dependent diabetes, mellitus, lupus nephropathy, Heyman nephritis, membranous nephritis, glomerulonephritis, contact sensitivity responses, and inflammation resulting from contact of blood with artificial surfaces. 
     
     
         19 . The method of  claim 11 , wherein the disease or disorder is selected from the group consisting of anti-neutrophil cytoplasmic antibody associate (ANCA) vasculitis, C3 glomerulopathy, hidradenitis suppurativa, and lupus nephritis. 
     
     
         20 . The method of  claim 11 , wherein the disease or disorder is anti-neutrophil cytoplasmic antibody associate (ANCA) vasculitis. 
     
     
         21 . The method of  claim 11 , wherein the disease or disorder is granulomatosis with polyangiitis. 
     
     
         22 . The method of  claim 11 , wherein the disease or disorder is microscopic polyangiitis. 
     
     
         23 . The method of  claim 11 , wherein the disease or disorder is C3 glomerulopathy. 
     
     
         24 . The method of  claim 11 , wherein the disease or disorder is hidradenitis suppurativa. 
     
     
         25 . The method of  claim 11 , wherein the disease or disorder is lupus nephritis. 
     
     
         26 . The method of  claim 11 , further comprising administering to the individual an effective amount of one or more additional therapeutic agents. 
     
     
         27 . The method of  claim 26 , wherein the one or more additional therapeutic agent is rituximab. 
     
     
         28 . The method of  claim 26 , wherein the one or more additional therapeutic agent is cyclophosphamide.