- SMAC MIMETICS USED AS IAP INHIBITORS AND USE THEREOF
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Disclosed are a class of SMAC mimetics used as IAP inhibitors, and in particular disclosed are compounds as shown in formula (I), isomers thereof, and pharmaceutically acceptable salts thereof. The IAP inhibitors are drugs for treating cancers, in particu
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- Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists
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A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12 ml/min/kg and 11p, 9 ml/min/kg).
- Chiba, Jun,Takayama, Gensuke,Takashi, Tohru,Yokoyama, Mika,Nakayama, Atsushi,Baldwin, John J.,McDonald, Edward,Moriarty, Kevin J.,Sarko, Christopher R.,Saionz, Kurt W.,Swanson, Robert,Hussain, Zahid,Wong, Angela,MacHinaga, Nobuo
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p. 2725 - 2746
(2007/10/03)
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- VLA-4 INHIBITORS
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The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.
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- Synthesis and biological properties of new constrained CCK-B antagonists: Discrimination of two affinity states of the CCK-B receptor on transfected CHO cells
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To improve our knowledge of the bioactive conformation of CCK-B antagonists, we have developed a new series of constrained dipeptoids whose synthesis and biochemical properties are reported here. These compounds, of general structure N(α)-[(2-adamantyloxy
- Bellier, Bruno,McCort-Tranchepain, Isabelle,Ducos, Bertrand,Danascimento, Sophie,Meudal, Hervé,Noble, Florence,Garbay, Christiane,Roques, Bernard P.
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p. 3947 - 3956
(2007/10/03)
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