char = S;code = 83 char = y;code = 121 char = n;code = 110 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = s;code = 115 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = t;code = 116 char = o;code = 111 char = z;code = 122 char = o;code = 111 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = p;code = 112 char = y;code = 121 char = r;code = 114 char = i;code = 105 char = d;code = 100 char = y;code = 121 char = l;code = 108 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = u;code = 117 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = .;code = 46 result sql = Synthesis and antiprotozoal activity of pyridyl analogues of pentamidine.
Synthesis and antiprotozoal activity of pyridyl analogues of pentamidine.char = A;code = 65 char = ;code = 32 char = s;code = 115 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = n;code = 110 char = o;code = 111 char = v;code = 118 char = e;code = 101 char = l;code = 108 char = ;code = 32 char = p;code = 112 char = y;code = 121 char = r;code = 114 char = i;code = 105 char = d;code = 100 char = y;code = 121 char = l;code = 108 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = u;code = 117 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = 1;code = 49 char = -;code = 45 char = 1;code = 49 char = 8;code = 56 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = t;code = 116 char = o;code = 111 char = z;code = 122 char = o;code = 111 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = d;code = 100 char = r;code = 114 char = u;code = 117 char = g;code = 103 char = ;code = 32 char = 1;code = 49 char = ,;code = 44 char = 5;code = 53 char = -;code = 45 char = b;code = 98 char = i;code = 105 char = s;code = 115 char = (;code = 40 char = 4;code = 52 char = -;code = 45 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = o;code = 111 char = p;code = 112 char = h;code = 104 char = e;code = 101 char = n;code = 110 char = o;code = 111 char = x;code = 120 char = y;code = 121 char = );code = 41 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = a;code = 97 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = (;code = 40 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = );code = 41 char = ;code = 32 char = h;code = 104 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = s;code = 115 char = y;code = 121 char = n;code = 110 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = s;code = 115 char = i;code = 105 char = z;code = 122 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = i;code = 105 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = g;code = 103 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = s;code = 115 char = t;code = 116 char = ;code = 32 char = T;code = 84 char = r;code = 114 char = y;code = 121 char = p;code = 112 char = a;code = 97 char = n;code = 110 char = o;code = 111 char = s;code = 115 char = o;code = 111 char = m;code = 109 char = a;code = 97 char = ;code = 32 char = b;code = 98 char = r;code = 114 char = u;code = 117 char = c;code = 99 char = e;code = 101 char = i;code = 105 char = ;code = 32 char = r;code = 114 char = h;code = 104 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = s;code = 115 char = i;code = 105 char = e;code = 101 char = n;code = 110 char = s;code = 115 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = P;code = 80 char = l;code = 108 char = a;code = 97 char = s;code = 115 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = i;code = 105 char = u;code = 117 char = m;code = 109 char = ;code = 32 char = f;code = 102 char = a;code = 97 char = l;code = 108 char = c;code = 99 char = i;code = 105 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = u;code = 117 char = m;code = 109 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = L;code = 76 char = e;code = 101 char = i;code = 105 char = s;code = 115 char = h;code = 104 char = m;code = 109 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = a;code = 97 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = n;code = 110 char = o;code = 111 char = v;code = 118 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = c;code = 99 char = y;code = 121 char = t;code = 116 char = o;code = 111 char = t;code = 116 char = o;code = 111 char = x;code = 120 char = i;code = 105 char = c;code = 99 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = g;code = 103 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = s;code = 115 char = t;code = 116 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = m;code = 109 char = m;code = 109 char = a;code = 97 char = l;code = 108 char = i;code = 105 char = a;code = 97 char = n;code = 110 char = ;code = 32 char = c;code = 99 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = s;code = 115 char = .;code = 46 char = ;code = 32 char = A;code = 65 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = t;code = 116 char = o;code = 111 char = z;code = 122 char = o;code = 111 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = r;code = 114 char = t;code = 116 char = i;code = 105 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = o;code = 111 char = u;code = 117 char = n;code = 110 char = d;code = 100 char = s;code = 115 char = ;code = 32 char = 1;code = 49 char = -;code = 45 char = 1;code = 49 char = 8;code = 56 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = d;code = 100 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = l;code = 108 char = a;code = 97 char = c;code = 99 char = e;code = 101 char = m;code = 109 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = c;code = 99 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = i;code = 105 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = y;code = 121 char = r;code = 114 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = r;code = 114 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = w;code = 119 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = ;code = 32 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = n;code = 110 char = a;code = 97 char = t;code = 116 char = u;code = 117 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = s;code = 115 char = u;code = 117 char = b;code = 98 char = s;code = 115 char = t;code = 116 char = i;code = 105 char = t;code = 116 char = u;code = 117 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = g;code = 103 char = r;code = 114 char = o;code = 111 char = u;code = 117 char = p;code = 112 char = s;code = 115 char = .;code = 46 char = ;code = 32 char = D;code = 68 char = i;code = 105 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = 6;code = 54 char = ;code = 32 char = w;code = 119 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = c;code = 99 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = i;code = 105 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = d;code = 100 char = j;code = 106 char = a;code = 97 char = c;code = 99 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = p;code = 112 char = y;code = 121 char = r;code = 114 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = n;code = 110 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = o;code = 111 char = m;code = 109 char = s;code = 115 char = ;code = 32 char = w;code = 119 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = s;code = 115 char = t;code = 116 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = m;code = 109 char = i;code = 105 char = s;code = 115 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = o;code = 111 char = u;code = 117 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = s;code = 115 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = s;code = 115 char = h;code = 104 char = o;code = 111 char = w;code = 119 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = s;code = 115 char = u;code = 117 char = p;code = 112 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = i;code = 105 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = g;code = 103 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = s;code = 115 char = t;code = 116 char = ;code = 32 char = T;code = 84 char = .;code = 46 char = ;code = 32 char = b;code = 98 char = r;code = 114 char = u;code = 117 char = c;code = 99 char = e;code = 101 char = i;code = 105 char = ;code = 32 char = r;code = 114 char = h;code = 104 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = s;code = 115 char = i;code = 105 char = e;code = 101 char = n;code = 110 char = s;code = 115 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = P;code = 80 char = .;code = 46 char = ;code = 32 char = f;code = 102 char = a;code = 97 char = l;code = 108 char = c;code = 99 char = i;code = 105 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = u;code = 117 char = m;code = 109 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = L;code = 76 char = .;code = 46 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = n;code = 110 char = o;code = 111 char = v;code = 118 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = .;code = 46 char = ;code = 32 char = A;code = 65 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = r;code = 114 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = d;code = 100 char = r;code = 114 char = u;code = 117 char = g;code = 103 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = d;code = 100 char = i;code = 105 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = 6;code = 54 char = ,;code = 44 char = ;code = 32 char = d;code = 100 char = i;code = 105 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = o;code = 111 char = x;code = 120 char = i;code = 105 char = m;code = 109 char = e;code = 101 char = ;code = 32 char = 9;code = 57 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = d;code = 100 char = m;code = 109 char = i;code = 105 char = n;code = 110 char = i;code = 105 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = 2;code = 50 char = 5;code = 53 char = ;code = 32 char = m;code = 109 char = g;code = 103 char = /;code = 47 char = k;code = 107 char = g;code = 103 char = ;code = 32 char = d;code = 100 char = a;code = 97 char = i;code = 105 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = 4;code = 52 char = ;code = 32 char = d;code = 100 char = a;code = 97 char = y;code = 121 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = h;code = 104 char = i;code = 105 char = b;code = 98 char = i;code = 105 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = c;code = 99 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = y;code = 121 char = p;code = 112 char = a;code = 97 char = n;code = 110 char = o;code = 111 char = s;code = 115 char = o;code = 111 char = m;code = 109 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = c;code = 99 char = y;code = 121 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = v;code = 118 char = i;code = 105 char = v;code = 118 char = o;code = 111 char = ;code = 32 char = c;code = 99 char = u;code = 117 char = r;code = 114 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = l;code = 108 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = f;code = 102 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = m;code = 109 char = a;code = 97 char = l;code = 108 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = S;code = 83 char = T;code = 84 char = I;code = 73 char = B;code = 66 char = 9;code = 57 char = 0;code = 48 char = 0;code = 48 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = u;code = 117 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = u;code = 117 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = l;code = 108 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = y;code = 121 char = p;code = 112 char = a;code = 97 char = n;code = 110 char = o;code = 111 char = s;code = 115 char = o;code = 111 char = m;code = 109 char = i;code = 105 char = a;code = 97 char = s;code = 115 char = i;code = 105 char = s;code = 115 char = .;code = 46 char = <;code = 60 char = b;code = 98 char = r;code = 114 char = /;code = 47 char = >;code = 62 result sql = A series of novel pyridyl analogues 1-18 of antiprotozoal drug 1,5-bis(4-amidinophenoxy)pentane (pentamidine) has been synthesized and tested for in vitro activities against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani, and for cytotoxicity against mammalian cells. Antiprotozoal properties of compounds 1-18 depended on the placement of cationic moieties on the pyridine rings as well as the nature of substituents on the amidine groups. Diamidine 6 with cationic moieties adjacent to pyridine nitrogen atoms was the most promising compound in the series showing superior in vitro activities against T. brucei rhodesiense, P. falciparum, and L. donovani compared to pentamidine. An oral prodrug of diamidine 6, diamidoxime 9, administered at 25 mg/kg daily for 4 days, exhibited excellent antitrypanosomal efficacy in vivo curing all infected animals in the STIB900 acute mouse model of trypanosomiasis.
Publication: J. Med. Chem. 2009 Aug 13 ;52(15)::4657-67. :doi: 10.1021/jm900805v.
Publication Date: 2009 Aug 13
Study Author(s): Bakunova, Svetlana M;Bakunov, Stanislav A;Wenzler, Tanja;Barszcz, Todd;Werbovetz, Karl A;Brun, Reto;Tidwell, Richard R;
Institution: Department of Pathology and Laboratory Medicine, School of Medicine, The University of North Carolina, Chapel Hill, North Carolina 27599-7525, USA.
Shortcut link to this study:
A series of novel pyridyl analogues 1-18 of antiprotozoal drug 1,5-bis(4-amidinophenoxy)pentane (pentamidine) has been synthesized and tested for in vitro activities against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani, and for cytotoxicity against mammalian cells. Antiprotozoal properties of compounds 1-18 depended on the placement of cationic moieties on the pyridine rings as well as the nature of substituents on the amidine groups. Diamidine 6 with cationic moieties adjacent to pyridine nitrogen atoms was the most promising compound in the series showing superior in vitro activities against T. brucei rhodesiense, P. falciparum, and L. donovani compared to pentamidine. An oral prodrug of diamidine 6, diamidoxime 9, administered at 25 mg/kg daily for 4 days, exhibited excellent antitrypanosomal efficacy in vivo curing all infected animals in the STIB900 acute mouse model of trypanosomiasis.
PMID: 19606902