- Solid phase parallel synthesis of highly substituted thiophene derivatives and identification of novel phosphodiesterase-4 (PDE-4) inhibitors
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A versatile protocol for solid phase synthesis of highly substituted thiophene derivatives and their activity against the PDE-4 enzyme are discussed. This protocol employs 3-hydroxymethylthiophene-2-boronic acid (5) as the scaffold and sequential palladium catalyzed cross-coupling reactions as the C-C bond forming step. This methodology allows convenient modification of the thiophene core from three directions, giving rise to structurally diverse derivatives with overall high chemical purity and yield. A novel series of potent PDE-4 inhibitors have been identified from these compounds.
- Han, Yongxin,Giroux, Andre,Lepine, Carole,Laliberte, France,Huang, Zheng,Perrier, Helene,Bayly, Christopher I.,Young, Robert N.
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- Co-catalyzed reductive cyclization of azido and cyano substituted α,β-unsaturated esters with NaBH4: enantioselective synthesis of (R)-baclofen and (R)-rolipram
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Sodium borohydride in combination with a catalytic amount of CoCl2 has been found to be an excellent catalytic system in reductive cyclizations of suitably substituted azido and cyano groups of α,β-unsaturated esters to afford γ and δ-lactams in high yields. The process has been demonstrated for the enantioselective synthesis of (R)-baclofen, (R)-rolipram, and (R)-4-fluorophenylpiperidinone, a key intermediate for (-)-paroxetine.
- Paraskar, Abhimanyu S.,Sudalai, Arumugam
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p. 4907 - 4916
(2007/10/03)
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- Enantioselective Syntheses of (-)-(R)-Rolipram, (-)-(R)-Baclofen and Other GABA Analogues via Rhodium-Catalyzed Conjugate Addition of Arylboronic Acids
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Highly enantioselective syntheses of two important γ-aminobutyric acid (GABA) analogues, the antispastic drug (-)-(R)-Baclofen and the antidepressant agent (-)-(R)-Rolipram, are reported. Key-steps in both syntheses are the Rh-catalyzed asymmetric 1,4-additions of arylboronic acids to 4-aminobut-2,3-enoic acid derivatives.
- Becht, Jean-Michel,Meyer, Oliver,Helmchen, Guenter
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p. 2805 - 2810
(2007/10/03)
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- Aryl thiophene derivatives as PDE IV inhibitors
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The invention encompasses the novel compound of Formula I useful in the treatment of diseases, including asthma, by raising the level of cyclic adenosine-3',5'-monophosphate (cAMP) through the inhibition of phosphodiesterase IV (PDE IV). The invention als
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- Substituted biphenyl derivatives
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A compound of the following structure: STR1 wherein, when R8 =H: R1 =alkyl, cycloalkyl, arylalkyl, aryl; R2 =cycloalkyl, aryl, C3 -C10 alkyl; X,Y=O, S(O)n, NH; Z=CHO, CO2 R3
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- Substituted biphenyl derivatives
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A compound of the following structure: STR1 wherein R8 =H: R1 =alkyl, cycloalkyl, arylalkyl, aryl; R2 =cycloalkyl, aryl, C3 -C10 alkyl; X,Y=O, S(O)n, NH; Z=CO2 R3, C(O
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