Chemokine Receptor Binding Heterocyclic Compounds With Enhanced Efficacy

Abstract

The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

1 . (canceled) 
     
     
         2 : A method to obtain isolated progenitor and/or stem cells from a subject, comprising:
 (a) administering to said subject a compound which is N 1 -(1H-Benzimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine, or a pharmaceutically acceptable salt thereof,   in an amount effective to elevate said progenitor and/or stem cell population in said subject, and wherein the compound is administered to said subject by an intravenous, subcutaneous or oral route; and   b) harvesting said progenitor and/or stem cells.   
     
     
         3 : The method of  claim 2 , wherein the subject undergoes chemotherapy or radiation therapy. 
     
     
         4 : The method of  claim 2 , wherein the subject is a healthy stem cell donor. 
     
     
         5 : The method of  claim 2 , wherein the compound is administered to said subject by an oral route. 
     
     
         6 : The method of  claim 2  wherein the compound is administered to said subject in the dosage range of about 0.1 μg/kg-5 mg/kg of body weight. 
     
     
         7 : The method of  claim 2 , further comprising: c) transplanting said progenitor and/or stem cells into said subject. 
     
     
         8 : The method of  claim 7 , wherein said subject exhibits a hematopoietic deficit from chemotherapy or radiation therapy at the time said cells are transplanted. 
     
     
         9 : The method of  claim 7 , wherein the subject has a condition selected from the group consisting of aplastic anemia, leukemia and drug-induced anemia at the time said cells are transplanted. 
     
     
         10 : The method of  claim 7 , wherein said progenitor and/or stem cells enhance wound healing. 
     
     
         11 : The method of  claim 7 , wherein said progenitor and/or stem cells ameliorate bacterial inflammation. 
     
     
         12 : The method of  claim 7 , wherein said progenitor and/or stem cells restore damaged organ tissue. 
     
     
         13 : The method of  claim 2 , further comprising: c) transplanting said progenitor and/or stem cells into a second subject. 
     
     
         14 : The method of  claim 2 , wherein the second subject exhibits a hematopoietic deficit from chemotherapy or radiation therapy. 
     
     
         15 : The method of  claim 13 , wherein second subject has a condition selected from the group consisting of aplastic anemia, leukemia and drug-induced anemia. 
     
     
         16 : The method of  claim 13 , wherein said progenitor and/or stem cells enhance wound healing. 
     
     
         17 : The method of  claim 13 , wherein said progenitor and/or stem cells ameliorate bacterial inflammation. 
     
     
         18 : The method of  claim 13 , wherein said progenitor and/or stem cells restore damaged organ tissue. 
     
     
         19 : A method to enhance the population of progenitor and/or stem cells in peripheral blood or bone marrow, which method comprises treating said peripheral blood or bone marrow with a compound which is N 1 -(1H-Benzimidazol-2-ylmethyl)-N 1 -(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine, or a pharmaceutically acceptable salt thereof, in an amount effective to elevate said progenitor and/or stem cell population in said peripheral blood or bone marrow. 
     
     
         20 : The method of  claim 19 , wherein said peripheral blood or bone marrow is derived from a subject who has been treated with G-CSF. 
     
     
         21 : The method of  claim 19 , wherein said peripheral blood or bone marrow is derived from a subject who is a healthy stem cell donor.