The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Neal Castagnoli - One of the best experts on this subject based on the ideXlab platform.
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Novel 4-(aryloxy)Tetrahydropyridine analogs of MPTP as monoamine oxidase A and B substrates
Journal of Medicinal Chemistry, 1994Co-Authors: Amit S. Kalgutkar, Kay Castagnoli, Andrea Hall, Neal CastagnoliAbstract:Abstract The exceptionally good monoamine oxidase (MAO) substrate properties of several 4-(arylmethyl)-1-methyl-1,2,3,6-Tetrahydropyridine derivatives related to the neurotoxin MPTP have prompted studies to evaluate the corresponding properties of Tetrahydropyridine derivatives bearing heteroatom-linked groups at C-4. The expected dihydropyridinium metabolites generated from these MAO-A- and MAO-B-catalyzed oxidations of the 4-(aryloxy)Tetrahydropyridine analogs were found to undergo rapid hydrolytic cleavage to yield the corresponding arenol and 1-methyl-2,3-dihydro-4-pyridone, a species that could be monitored spectrophotometrically. We have exploited this reaction sequence to probe the active sites of beef liver MAO-B and human placental MAO-A with a variety of 4-(aryloxy)-1-methyl-1,2,3,6-Tetrahydropyridine derivatives. The results are discussed in relationship to recently published reports describing the MAO-A vs MAO-B selectivity of various 4-(arylmethyl)Tetrahydropyridine derivatives.
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Mechanistic studies on the monoamine oxidase B catalyzed oxidation of 1,4-disubstituted Tetrahydropyridines.
Chemical Research in Toxicology, 1994Co-Authors: Simon Kuttab, Amit S. Kalgutkar, Neal CastagnoliAbstract:Abstract Previous studies have established that 1-cyclopropyl-4-phenyl-1,2,3,6- Tetrahydropyridine (6) is an efficient time and concentration dependent inhibitor of the flavin containing enzyme monoamine oxidase B (MAO-B). This behavior is consistent with a proposed mechanism based inactivation pathway initiated by transfer of one of the nitrogen nonbonding pairs of electrons to the oxidized flavin cofactor to generate an amine radical cation intermediate. Subsequent opening of the strained cyclopropylamine ring is thought to lead to a primary carbon centered radical that inactivates the enzyme by covalent modification of the flavin or an essential active site functionality. We now have examined the MAO-B inactivator and substrate properties of 4-benzyl-1-cyclopropyl-1,2,3,6-Tetrahydropyridine (11). This compound also is a time and concentration dependent inhibitor of MAO-B. Unexpectedly, however, compound 11 proved to be an excellent MAO-B substrate. These results are discussed in terms of possible catalytic pathways for the MAO-B catalyzed oxidation of 1,4-disubstituted-1,2,3,6- Tetrahydropyridines.
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Design, synthesis, and biological evaluation of novel 4-substituted 1-methyl-1,2,3,6-Tetrahydropyridine analogs of MPTP.
Journal of Medicinal Chemistry, 1992Co-Authors: Zhiyang Zhao, Deepak Dalvie, Noreen Naiman, Kay Castagnoli, Neal CastagnoliAbstract:The exceptionally good MAO-B substrate properties of several 1-methyl-4-phenyl-1,2,3,6-Tetrahydropyridine (MPTP) derivatives have prompted studies to evaluate the corresponding properties of Tetrahydropyridines bearing heteroatom-linked groups at C-4. The 1-methyl-4-phenoxy-1,2,3,6-Tetrahydropyridine analog proved to be an excellent MAO-B substrate. Unlike analogs bearing hydrocarbon substituents at C-4, the resulting dihydropyridinium metabolite did not undergo further oxidation to the pyridinium compound but rather underwent hydrolytic cleavage. This observation has led to studies designed to explore the possibility of developing novel, nontoxic derivatives of MPTP bearing potential pharmacologically active leaving groups at C-4. In this paper we report the results of synthetic and metabolic studies on a series of Tetrahydropyridine analogs of MPTP with oxygen, sulfur, and carbamoyloxy derivatives on C-4 which serve as model compounds to evaluate the scope of this prodrug concept.
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Studies on 1,2,3,6-Tetrahydropyridine derivatives as potential monoamine oxidase inactivators.
Chemical Research in Toxicology, 1992Co-Authors: Larry Hall, Kay Castagnoli, Sam Murray, Neal CastagnoliAbstract:The Parkinsonian-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-Tetrahydropyridine (MPTP) and close structural analogs are the only known cyclic tertiary amines with good monoamine oxidase substrate properties. In addition to its excellent substrate properties, MPTP is a mechanism-based inactivator of monoamine oxidase B (MAO-B). In an attempt to exploit the special interactions between this cyclic tertiary allylamine and MAO-B, we have initiated studies to evaluate the enzymatic and biological properties of MPTP analogs bearing functional groups which are known to mediate the metabolism-dependent inactivation of this enzyme. This paper describes the synthesis, enzyme substrate/inhibitor properties, and neurotoxic/neuroprotective properties of 1-cyclopropyl-4-phenyl-1,2,3,6-Tetrahydropyridine, the corresponding acyclic secondary amine (E)-4-cyclopropyl-2-phenyl-2-butene, and 4-cyclopropyl-1-methyl-1,2,3,6-Tetrahydropyridine.
Marcos A. P. Martins - One of the best experts on this subject based on the ideXlab platform.
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Highly Chemoselective Synthesis of 6-Alkoxy-1-alkyl(aryl)-3-trifluoroacetyl-1,4,5,6-Tetrahydropyridines and 1-Alkyl(aryl)-6-amino-3-trifluoroacetyl-1,4,5,6-Tetrahydropyridines
European Journal of Organic Chemistry, 2009Co-Authors: Nilo Zanatta, Liana Da S. Fernandes, Fabiane M. Nachtigall, Helena S. Coelho, Simone S. Amaral, Alex F. C. Flores, Helio G. Bonacorso, Marcos A. P. MartinsAbstract:A simple and highly chemoselective method for the synthesis of a large series of novel 6-alkoxy-1-alkyl(aryl)-3-trifluoroacetyl-1,4,5,6-Tetrahydropyridines and 1-alkyl(aryl)-6-amino-3-trifluoroacetyl-1,4,5,6-Tetrahydropyridines, from the reaction of 6-alkoxy-3-trifluoroacetyl-4,5-dihydro-6H-pyrans with primary alkyl and arylamines, in good yields, is reported. Preliminary in vitro antimicrobial activity of the 1-alkyl(aryl)-6-amino-3-trifluoroacetyl-1,4,5,6-Tetrahydropyridine series was assessed against a variety of microorganisms including yeast-like fungi, bacteria and algae, and some of these compounds exhibit significant antimicrobial activity.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Meng-yang Chang - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of 1,2,4-trisubstituted-1,2,5,6-Tetrahydropyridines
Tetrahedron Letters, 2011Co-Authors: Meng-yang Chang, Ming-fang Lee, Nien-chia Lee, Yu-ping Huang, Chung-han LinAbstract:Abstract A novel method for the synthesis of 1,2,4-trisubstituted- or 1,2,3,4-tetrasubstituted-1,2,5,6-Tetrahydropyridine is presented. The process was carried out by the bromomethoxylation of 4-substituted-1,2,5,6-Tetrahydropyridines 1 with N-bromosuccinimide (NBS) in methanol, dehydrobromination with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and boron trifluoride etherate (BF3-OEt2)-catalyzed cross coupling of the corresponding enamine with trimethylsilyl-based nucleophiles. Homokainoid analogs were also synthesized via the protocol.
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Pd2(dba)3-promoted synthesis of 3-N-substituted 4-aryl-1,2,3,6-Tetrahydropyridine
Tetrahedron Letters, 2010Co-Authors: Meng-yang Chang, Chung-han Lin, Yeh-long Chen, Ru-ting Hsu, Ching-yao ChangAbstract:A novel method for the synthesis of 3-N-substituted 4-aryl-1,2,3,6-Tetrahydropyridine 3 is presented. The process is carried out by the allylic bromination of 4-aryl-1,2,3,6-Tetrahydropyridines 1 with N-bromosuccinimide in propanoic acid and palladium-catalyzed cross coupling of the corresponding bromide 2 with different N-based nucleophiles.
Chung-han Lin - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of 1,2,4-trisubstituted-1,2,5,6-Tetrahydropyridines
Tetrahedron Letters, 2011Co-Authors: Meng-yang Chang, Ming-fang Lee, Nien-chia Lee, Yu-ping Huang, Chung-han LinAbstract:Abstract A novel method for the synthesis of 1,2,4-trisubstituted- or 1,2,3,4-tetrasubstituted-1,2,5,6-Tetrahydropyridine is presented. The process was carried out by the bromomethoxylation of 4-substituted-1,2,5,6-Tetrahydropyridines 1 with N-bromosuccinimide (NBS) in methanol, dehydrobromination with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and boron trifluoride etherate (BF3-OEt2)-catalyzed cross coupling of the corresponding enamine with trimethylsilyl-based nucleophiles. Homokainoid analogs were also synthesized via the protocol.
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Pd2(dba)3-promoted synthesis of 3-N-substituted 4-aryl-1,2,3,6-Tetrahydropyridine
Tetrahedron Letters, 2010Co-Authors: Meng-yang Chang, Chung-han Lin, Yeh-long Chen, Ru-ting Hsu, Ching-yao ChangAbstract:A novel method for the synthesis of 3-N-substituted 4-aryl-1,2,3,6-Tetrahydropyridine 3 is presented. The process is carried out by the allylic bromination of 4-aryl-1,2,3,6-Tetrahydropyridines 1 with N-bromosuccinimide in propanoic acid and palladium-catalyzed cross coupling of the corresponding bromide 2 with different N-based nucleophiles.
Nilo Zanatta - One of the best experts on this subject based on the ideXlab platform.
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Highly Chemoselective Synthesis of 6-Alkoxy-1-alkyl(aryl)-3-trifluoroacetyl-1,4,5,6-Tetrahydropyridines and 1-Alkyl(aryl)-6-amino-3-trifluoroacetyl-1,4,5,6-Tetrahydropyridines
European Journal of Organic Chemistry, 2009Co-Authors: Nilo Zanatta, Liana Da S. Fernandes, Fabiane M. Nachtigall, Helena S. Coelho, Simone S. Amaral, Alex F. C. Flores, Helio G. Bonacorso, Marcos A. P. MartinsAbstract:A simple and highly chemoselective method for the synthesis of a large series of novel 6-alkoxy-1-alkyl(aryl)-3-trifluoroacetyl-1,4,5,6-Tetrahydropyridines and 1-alkyl(aryl)-6-amino-3-trifluoroacetyl-1,4,5,6-Tetrahydropyridines, from the reaction of 6-alkoxy-3-trifluoroacetyl-4,5-dihydro-6H-pyrans with primary alkyl and arylamines, in good yields, is reported. Preliminary in vitro antimicrobial activity of the 1-alkyl(aryl)-6-amino-3-trifluoroacetyl-1,4,5,6-Tetrahydropyridine series was assessed against a variety of microorganisms including yeast-like fungi, bacteria and algae, and some of these compounds exhibit significant antimicrobial activity.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
