char = S;code = 83
char = u;code = 117
char = g;code = 103
char = a;code = 97
char = r;code = 114
char = -;code = 45
char = b;code = 98
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = c;code = 99
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 = n;code = 110
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = y;code = 121
char = r;code = 114
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = [;code = 91
char = 2;code = 50
char = ,;code = 44
char = 1;code = 49
char = -;code = 45
char = c;code = 99
char = ];code = 93
char = [;code = 91
char = 1;code = 49
char = ,;code = 44
char = 4;code = 52
char = ];code = 93
char = -;code = 45
char = b;code = 98
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = z;code = 122
char = e;code = 101
char = p;code = 112
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
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 = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = G;code = 71
char = A;code = 65
char = B;code = 66
char = A;code = 65
char = A;code = 65
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = s;code = 115
char = .;code = 46
result sql = Sugar-based enantiomeric and conformationally constrained pyrrolo[2,1-c][1,4]-benzodiazepines as potential GABAA ligands.
Sugar-based enantiomeric and conformationally constrained pyrrolo[2,1-c][1,4]-benzodiazepines as potential GABAA ligands.
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = r;code = 114
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char = l;code = 108
char = o;code = 111
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char = ,;code = 44
char = 1;code = 49
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char = c;code = 99
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char = [;code = 91
char = 1;code = 49
char = ,;code = 44
char = 4;code = 52
char = ];code = 93
char = -;code = 45
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char = o;code = 111
char = d;code = 100
char = i;code = 105
char = a;code = 97
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char = e;code = 101
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char = r;code = 114
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char = ;code = 32
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char = i;code = 105
char = c;code = 99
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char = c;code = 99
char = l;code = 108
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char = c;code = 99
char = ;code = 32
char = D;code = 68
char = -;code = 45
char = ;code = 32
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char = ;code = 32
char = L;code = 76
char = -;code = 45
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = o;code = 111
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char = u;code = 117
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char = s;code = 115
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char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
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char = D;code = 68
char = -;code = 45
char = ;code = 32
char = o;code = 111
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char = ;code = 32
char = L;code = 76
char = -;code = 45
char = f;code = 102
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = i;code = 105
char = e;code = 101
char = t;code = 116
char = y;code = 121
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
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char = e;code = 101
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char = o;code = 111
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char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = f;code = 102
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = i;code = 105
char = e;code = 101
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char = y;code = 121
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = w;code = 119
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 = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = r;code = 114
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char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
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char = L;code = 76
char = -;code = 45
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char = a;code = 97
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
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char = x;code = 120
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char = s;code = 115
char = t;code = 116
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char = s;code = 115
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char = i;code = 105
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 1;code = 49
char = 8;code = 56
char = %;code = 37
char = ;code = 32
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = y;code = 121
char = i;code = 105
char = e;code = 101
char = l;code = 108
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = M;code = 77
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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
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char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = i;code = 105
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char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
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char = ;code = 32
char = D;code = 68
char = N;code = 78
char = M;code = 77
char = R;code = 82
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
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 = 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 = D;code = 68
char = -;code = 45
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = L;code = 76
char = -;code = 45
char = f;code = 102
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = b;code = 98
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = y;code = 121
char = r;code = 114
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = b;code = 98
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = a;code = 97
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char = e;code = 101
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char = h;code = 104
char = i;code = 105
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char = ;code = 32
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char = ;code = 32
char = r;code = 114
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char = g;code = 103
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char = d;code = 100
char = ;code = 32
char = (;code = 40
char = P;code = 80
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char = d;code = 100
char = ;code = 32
char = (;code = 40
char = M;code = 77
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char = -;code = 45
char = h;code = 104
char = e;code = 101
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char = i;code = 105
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char = l;code = 108
char = ;code = 32
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char = ,;code = 44
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char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = C;code = 67
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char = 1;code = 49
char = 1;code = 49
char = a;code = 97
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char = i;code = 105
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char = a;code = 97
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char = e;code = 101
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char = q;code = 113
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char = a;code = 97
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char = g;code = 103
char = ,;code = 44
char = ;code = 32
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = o;code = 111
char = r;code = 114
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = N;code = 78
char = -;code = 45
char = m;code = 109
char = e;code = 101
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = o;code = 111
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char = h;code = 104
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char = p;code = 112
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char = c;code = 99
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char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
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char = ;code = 32
char = s;code = 115
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char = g;code = 103
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = c;code = 99
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char = o;code = 111
char = l;code = 108
char = ;code = 32
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char = r;code = 114
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char = s;code = 115
char = ,;code = 44
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = e;code = 101
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char = m;code = 109
char = o;code = 111
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result sql = Synthesis of a library of pyrrolo[2,1-c][1,4]-benzodiazepines derived from spiro bicyclic D- or L-proline analogues containing a D- or L-fructose moiety was developed. The L-fructose moiety was obtained by using a new synthetic pathway starting from L-arabinose through a six steps synthesis in 18% overall yield. Molecular modeling calculations and DNMR studies showed that D- and L-fructose-based pyrrolobenzodiazepines exhibit a rigid (P)- and (M)-helical conformation, respectively, in which the C-11a substituent was always pseudoequatorial. Additionally, pyrrolobenzodiazepines functionalized with a chloride, bromide, nitro, or amino group in the benzene ring, with or without N-methylation and with or without protection of sugar alcohol groups, allowed a relationship between the molecular structure and biological activity to be established. The conformation of the diazepam ring was not the sole key player influencing binding affinities, and the sugar moiety can in some cases increase the binding activity, possibly by participating in the binding event. Finally, these compounds have increased the understanding of the differential recognition of (M)-/(P)-helical benzodiazepines on GABA(A) receptor.

Publication: J. Med. Chem. 2011 Mar 10 ;54(5)::1266-75. :doi: 10.1021/jm101244n.
Publication Date: 2011 Mar 10
Study Author(s): Araújo, Ana C;Rauter, Amélia P;Nicotra, Francesco;Airoldi, Cristina;Costa, Barbara;Cipolla, Laura;
Institution: Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Centro de Química e Bioquímica, Lisboa, Portugal. [email protected]
Shortcut link to this study:
Synthesis of a library of pyrrolo[2,1-c][1,4]-benzodiazepines derived from spiro bicyclic D- or L-proline analogues containing a D- or L-fructose moiety was developed. The L-fructose moiety was obtained by using a new synthetic pathway starting from L-arabinose through a six steps synthesis in 18% overall yield. Molecular modeling calculations and DNMR studies showed that D- and L-fructose-based pyrrolobenzodiazepines exhibit a rigid (P)- and (M)-helical conformation, respectively, in which the C-11a substituent was always pseudoequatorial. Additionally, pyrrolobenzodiazepines functionalized with a chloride, bromide, nitro, or amino group in the benzene ring, with or without N-methylation and with or without protection of sugar alcohol groups, allowed a relationship between the molecular structure and biological activity to be established. The conformation of the diazepam ring was not the sole key player influencing binding affinities, and the sugar moiety can in some cases increase the binding activity, possibly by participating in the binding event. Finally, these compounds have increased the understanding of the differential recognition of (M)-/(P)-helical benzodiazepines on GABA(A) receptor.
PMID: 21314193

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