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PDBsum entry 4lko
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References listed in PDB file
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Key reference
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Title
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Optimization of activity, Selectivity, And liability profiles in 5-Oxopyrrolopyridine dpp4 inhibitors leading to clinical candidate (sa)-2-(3-(Aminomethyl)-4-(2,4-Dichlorophenyl)-2-Methyl-5-Oxo-5h-Pyrrolo[3,4-B]pyridin-6(7h)-Yl)-N,N-Dimethylacetamide (bms-767778).
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Authors
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P.Devasthale,
Y.Wang,
W.Wang,
J.Fevig,
J.Feng,
A.Wang,
T.Harrity,
D.Egan,
N.Morgan,
M.Cap,
A.Fura,
H.E.Klei,
K.Kish,
C.Weigelt,
L.Sun,
P.Levesque,
F.Moulin,
Y.X.Li,
R.Zahler,
M.S.Kirby,
L.G.Hamann.
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Ref.
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J Med Chem, 2013,
56,
7343-7357.
[DOI no: ]
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PubMed id
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Abstract
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Optimization of a 5-oxopyrrolopyridine series based upon structure-activity
relationships (SARs) developed from our previous efforts on a number of related
bicyclic series yielded compound 2s (BMS-767778) with an overall activity,
selectivity, efficacy, PK, and developability profile suitable for progression
into the clinic. SAR in the series and characterization of 2s are described.
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Secondary reference #1
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Title
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Structural basis of proline-Specific exopeptidase activity as observed in human dipeptidyl peptidase-Iv.
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Authors
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R.Thoma,
B.Löffler,
M.Stihle,
W.Huber,
A.Ruf,
M.Hennig.
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Ref.
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Structure, 2003,
11,
947-959.
[DOI no: ]
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PubMed id
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Figure 4.
Figure 4. Access to the Active SiteSchematic view on the
subunit of DPP-IV with the active site surface colored according
to the atom types. The substrate diprotin A is shown with white
carbons indicating the substrate binding site. Arrows illustrate
that the substrate may enter the active site at the
well-accessible and open active site cleft and that the
dipeptidic product of the catalytic reaction may leave the
active site cavity via the narrower tunnel that is formed by the
b propeller.
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The above figure is
reproduced from the cited reference
with permission from Cell Press
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