char = E;code = 69
char = ,;code = 44
char = E;code = 69
char = ,;code = 44
char = E;code = 69
char = -;code = 45
char = 1;code = 49
char = -;code = 45
char = (;code = 40
char = 4;code = 52
char = -;code = 45
char = A;code = 65
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = -;code = 45
char = 4;code = 52
char = -;code = 45
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = -;code = 45
char = 2;code = 50
char = -;code = 45
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = y;code = 121
char = l;code = 108
char = );code = 41
char = -;code = 45
char = 3;code = 51
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 = a;code = 97
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = );code = 41
char = -;code = 45
char = 4;code = 52
char = -;code = 45
char = p;code = 112
char = i;code = 105
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = :;code = 58
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = p;code = 112
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
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 = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
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 = n;code = 110
char = s;code = 115
char = .;code = 46
result sql = E,E,E-1-(4-Arylamino-4-oxo-2-butenoyl)-3,5-bis(arylidene)-4-piperidones: a topographical study of some novel potent cytotoxins.
E,E,E-1-(4-Arylamino-4-oxo-2-butenoyl)-3,5-bis(arylidene)-4-piperidones: a topographical study of some novel potent cytotoxins.
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 = E;code = 69
char = ,;code = 44
char = E;code = 69
char = ,;code = 44
char = E;code = 69
char = -;code = 45
char = 3;code = 51
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 = a;code = 97
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = );code = 41
char = -;code = 45
char = 1;code = 49
char = -;code = 45
char = (;code = 40
char = 4;code = 52
char = -;code = 45
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = -;code = 45
char = 4;code = 52
char = -;code = 45
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = -;code = 45
char = 2;code = 50
char = -;code = 45
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = y;code = 121
char = l;code = 108
char = );code = 41
char = -;code = 45
char = 4;code = 52
char = -;code = 45
char = p;code = 112
char = i;code = 105
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = (;code = 40
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 5;code = 53
char = ;code = 32
char = (;code = 40
char = 4;code = 52
char = -;code = 45
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = );code = 41
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = l;code = 108
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = N;code = 78
char = -;code = 45
char = a;code = 97
char = c;code = 99
char = y;code = 121
char = l;code = 108
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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 = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = E;code = 69
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = o;code = 111
char = l;code = 108
char = t;code = 116
char = ;code = 32
char = 4;code = 52
char = /;code = 47
char = C;code = 67
char = 8;code = 56
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = E;code = 69
char = M;code = 77
char = ;code = 32
char = T;code = 84
char = -;code = 45
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = I;code = 73
char = C;code = 67
char = (;code = 40
char = 5;code = 53
char = 0;code = 48
char = );code = 41
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = g;code = 103
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = L;code = 76
char = 1;code = 49
char = 2;code = 50
char = 1;code = 49
char = 0;code = 48
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 = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
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 = a;code = 97
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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 = i;code = 105
char = n;code = 110
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 = 4;code = 52
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = y;code = 121
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
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 = t;code = 116
char = o;code = 111
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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 = i;code = 105
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
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 = 4;code = 52
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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 = s;code = 115
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result sql = A series of E,E,E-3,5-bis(arylidene)-1-(4-arylamino-4-oxo-2-butenoyl)-4-piperidones 4 (phenylidene) and 5 (4-nitrophenylidene) were prepared in order to explore the structural features of the N-acyl group which affects the cytotoxic potency. Evaluation toward human Molt 4/C8 and CEM T-lymphocytes revealed that many of the IC(50) figures were submicromolar and lower than melphalan. Marked inhibitory potencies toward murine leukemia L1210 cells were also noted. When evaluated against a panel of human tumor cell lines, three representative compounds in series 4 displayed selective toxicity to leukemia and colon cancer cell lines and were significantly more potent than the reference drug melphalan. Molecular modeling of representative compounds in both series 4 and the analogs, in which the configuration of the olefinic double bond was changed from E to Z (series 3), revealed that the torsion angles of the arylidene aryl rings and locations of the terminal arylaminocarbonyl groups may have contributed to the greater cytotoxic properties displayed in 3. Compounds 4c (3,4-dichlorophenylamino), d (4-methylphenylamino) and 5c (3,4-dichlorophenylamino), d (4-methylphenylamino) inhibited the activity of human N-myristoyltransferase by approximately 50% at concentrations of 50-100 microM. The compounds in series 4 and 5 were well tolerated in a short-term toxicity study in mice.

Publication: Bioorg. Med. Chem. 2007 Sep 1 ;15(17)::5854-65.
Publication Date: 2007 Sep 1
Study Author(s): Jha, Amitabh;Mukherjee, Chandrani;Prasad, Ashok K;Parmar, Virinder S;Clercq, Erik De;Balzarini, Jan;Stables, James P;Manavathu, Elias K;Shrivastav, Anuraag;Sharma, Rajendra K;Nienaber, Kurt H;Zello, Gordon A;Dimmock, Jonathan R;
Institution: Department of Chemistry, Acadia University, Wolfville, NS, Canada. [email protected]
Shortcut link to this study:
A series of E,E,E-3,5-bis(arylidene)-1-(4-arylamino-4-oxo-2-butenoyl)-4-piperidones 4 (phenylidene) and 5 (4-nitrophenylidene) were prepared in order to explore the structural features of the N-acyl group which affects the cytotoxic potency. Evaluation toward human Molt 4/C8 and CEM T-lymphocytes revealed that many of the IC(50) figures were submicromolar and lower than melphalan. Marked inhibitory potencies toward murine leukemia L1210 cells were also noted. When evaluated against a panel of human tumor cell lines, three representative compounds in series 4 displayed selective toxicity to leukemia and colon cancer cell lines and were significantly more potent than the reference drug melphalan. Molecular modeling of representative compounds in both series 4 and the analogs, in which the configuration of the olefinic double bond was changed from E to Z (series 3), revealed that the torsion angles of the arylidene aryl rings and locations of the terminal arylaminocarbonyl groups may have contributed to the greater cytotoxic properties displayed in 3. Compounds 4c (3,4-dichlorophenylamino), d (4-methylphenylamino) and 5c (3,4-dichlorophenylamino), d (4-methylphenylamino) inhibited the activity of human N-myristoyltransferase by approximately 50% at concentrations of 50-100 microM. The compounds in series 4 and 5 were well tolerated in a short-term toxicity study in mice.
PMID: 17562365

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