- A Convenient One-Pot Synthesis of 1,5-Disubstituted Tetrazoles Containing an Amino or a Carboxy Group
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Abstract: A convenient method is proposed for constructing the tetrazole ring by a one-pot reaction of amides with phosphorus oxychloride and sodium azide. A series of 1,5-disubstituted tetrazoles containing an amino or a carboxy group, which present interest as buildings blocks for the synthesis of biologically active substances, were obtained.
- Obushak, M. D.,Pokhodylo, N. T.,Shyyka, O. Ya.
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p. 802 - 812
(2020/07/03)
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- SUBSTITUTED PYRIMIDINYL-AMINES AS PROTEIN KINASE INHIBITORS
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The present invention provides novel substituted pyrimidinyl-amines that are useful as inhibitors of protein kinases, especially c-Jun N-terminal kinases (JNK) and pharmaceutical compositions thereof and methods of using the same for treating conditions responsive to the inhibition of the JNK pathway.
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Page/Page column 122
(2009/04/25)
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- Discovery of CC chemokine receptor-3 (CCR3) antagonists with picomolar potency
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Starting with our previously described20 class of CC chemokine receptor-3 (CCR3) antagonist, we improved the potency by replacing the phenyl linker of 1 with a cyclohexyl linker and by replacing the 4-benzylpiperidine with a 3-benzylpiperidine. The resulting compound, 32, is a potent and selective antagonist of CCR3. SAR studies showed that the 3-acetylphenyl urea of 32 could be replaced with heterocyclic ureas or heterocyclic-substituted phenyl ureas and still maintain the potency (inhibition of eotaxin-induced chemotaxis) of this class of compounds in the low-picomolar range (IC50 = 10-60 pM), representing some of the most potent CCR3 antagonists reported to date. The potency of 32 for mouse CCR3 (chemotaxis IC50 = 41 nM) and its oral bioavailability in mice (20% F) were adequate to assess the efficacy in animal models of allergic airway inflammation. Oral administration of 32 reduced eosinophil recruitment into the lungs in a dose-dependent manner in these animal models. On the basis of its overall potency, selectivity, efficacy, and safety profile, the benzenesulfonate salt of 32, designated DPC168, entered phase I clinical trials.
- De Lucca, George V.,Ui, Tae Kim,Vargo, Brian J.,Duncia, John V.,Santella III, Joseph B.,Gardner, Daniel S.,Zheng, Changsheng,Liauw, Ann,Wang, Zhang,Emmett, George,Wacker, Dean A.,Welch, Patricia K.,Covington, Maryanne,Stowell, Nicole C.,Wadman, Eric A.,Das, Anuk M.,Davies, Paul,Yeleswaram, Swamy,Graden, Danielle M.,Solomon, Kimberly A.,Newton, Robert C.,Trainor, George L.,Decicco, Carl P.,Ko, Soo S.
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p. 2194 - 2211
(2007/10/03)
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- N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
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The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
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- N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
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The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
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- Piperidine amides as modulators of chemo kine receptor activity
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The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
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