|
|
char = N;code = 78
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 = r;code = 114
char = o;code = 111
char = l;code = 108
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char = d;code = 100
char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = u;code = 117
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char = e;code = 101
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = C;code = 67
char = -;code = 45
char = C;code = 67
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char = e;code = 101
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char = c;code = 99
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char = 1;code = 49
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char = (;code = 40
char = C;code = 67
char = C;code = 67
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char = a;code = 97
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char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = .;code = 46
result sql = Novel pyrrolidine ureas as C-C chemokine receptor 1 (CCR1) antagonists.
Novel pyrrolidine ureas as C-C chemokine receptor 1 (CCR1) antagonists.char = M;code = 77
char = o;code = 111
char = n;code = 110
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char = c;code = 99
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char = e;code = 101
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char = i;code = 105
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char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = i;code = 105
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char = i;code = 105
char = m;code = 109
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char = l;code = 108
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char = e;code = 101
char = d;code = 100
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char = r;code = 114
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char = e;code = 101
char = t;code = 116
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char = a;code = 97
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char = h;code = 104
char = r;code = 114
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char = t;code = 116
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char = ,;code = 44
char = ;code = 32
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char = d;code = 100
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char = m;code = 109
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char = c;code = 99
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char = e;code = 101
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = -;code = 45
char = C;code = 67
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = (;code = 40
char = C;code = 67
char = C;code = 67
char = R;code = 82
char = 1;code = 49
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char = i;code = 105
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char = ;code = 32
char = a;code = 97
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char = c;code = 99
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char = c;code = 99
char = e;code = 101
char = p;code = 112
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char = r;code = 114
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = ;code = 32
char = u;code = 117
char = p;code = 112
char = o;code = 111
char = n;code = 110
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char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
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char = l;code = 108
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char = y;code = 121
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char = m;code = 109
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char = I;code = 73
char = P;code = 80
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char = 1;code = 49
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char = );code = 41
char = ;code = 32
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char = d;code = 100
char = ;code = 32
char = r;code = 114
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char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = e;code = 101
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char = n;code = 110
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char = T;code = 84
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char = l;code = 108
char = ;code = 32
char = e;code = 101
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char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = A;code = 65
char = N;code = 78
char = T;code = 84
char = E;code = 69
char = S;code = 83
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = m;code = 109
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char = d;code = 100
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char = n;code = 110
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char = a;code = 97
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char = f;code = 102
char = i;code = 105
char = c;code = 99
char = k;code = 107
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char = n;code = 110
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char = s;code = 115
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char = o;code = 111
char = f;code = 102
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char = i;code = 105
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char = l;code = 108
char = a;code = 97
char = m;code = 109
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 = .;code = 46
char = ;code = 32
char = H;code = 72
char = i;code = 105
char = g;code = 103
char = h;code = 104
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 = p;code = 112
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = n;code = 110
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char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
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char = r;code = 114
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char = b;code = 98
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char = a;code = 97
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char = l;code = 108
char = l;code = 108
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char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = i;code = 105
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char = i;code = 105
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char = e;code = 101
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char = t;code = 116
char = ;code = 32
char = C;code = 67
char = C;code = 67
char = R;code = 82
char = 1;code = 49
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char = a;code = 97
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char = C;code = 67
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char = i;code = 105
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result sql = Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1alpha (MIP-1alpha) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC(50) of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.
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char = C;code = 67
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char = .;code = 46
result sql = Novel pyrrolidine ureas as C-C chemokine receptor 1 (CCR1) antagonists.
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result sql = Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1alpha (MIP-1alpha) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC(50) of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.
Publication: J. Med. Chem. 2009 Mar 12 ;52(5)::1295-301. :doi: 10.1021/jm801416q.
Publication Date: 2009 Mar 12
Study Author(s): Merritt, J Robert;Liu, Jinqi;Quadros, Elizabeth;Morris, Michelle L;Liu, Ruiyan;Zhang, Rui;Jacob, Biji;Postelnek, Jennifer;Hicks, Catherine M;Chen, Weiqing;Kimble, Earl F;Rogers, W Lynn;O'Brien, Linda;White, Nicole;Desai, Hema;Bansal, Shalini;King, George;Ohlmeyer, Michael J;Appell, Kenneth C;Webb, Maria L;
Institution: Pharmacopeia, Inc., Cranbury, New Jersey 08512, USA. [email protected]
Shortcut link to this study:
Publication Date: 2009 Mar 12
Study Author(s): Merritt, J Robert;Liu, Jinqi;Quadros, Elizabeth;Morris, Michelle L;Liu, Ruiyan;Zhang, Rui;Jacob, Biji;Postelnek, Jennifer;Hicks, Catherine M;Chen, Weiqing;Kimble, Earl F;Rogers, W Lynn;O'Brien, Linda;White, Nicole;Desai, Hema;Bansal, Shalini;King, George;Ohlmeyer, Michael J;Appell, Kenneth C;Webb, Maria L;
Institution: Pharmacopeia, Inc., Cranbury, New Jersey 08512, USA. [email protected]
Shortcut link to this study:
Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1alpha (MIP-1alpha) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC(50) of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.
PMID: 19183043
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