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Henk Timmerman - One of the best experts on this subject based on the ideXlab platform.
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Non-imidazole histamine H3 ligands. Part III. New 4-n-propylPiperazines as non-imidazole histamine H3-antagonists.
European journal of medicinal chemistry, 2005Co-Authors: Krzysztof Walczyński, Obbe P. Zuiderveld, Henk TimmermanAbstract:In search for a new lead of non-imidazole histamine H3-receptor antagonists, a series of 1[(2-thiazolopyridine)-4-n-propyl]Piperazines, the analogous 1-[(2-oxazolopyridine)-4-npropyl]Piperazines, 1-[(2-benzothiazole)-4-n-propyl]Piperazine and 1-[(2-benzooxazole)4-n-propyl]Piperazine were prepared and in vitro tested as H3-receptor antagonists (the electrically evoked contraction of the guinea-pig jejunum). It appeared that by comparison of homologous pairs the thiazolo derivatives have slightly higher activity than their oxazolo analogues. The most potent compound of these series is the 1-(2-thiazolo[4,5-c]pyridine)-4-n-propylPiperazine (3c) with pA2 = 7.25 (its oxazole analogue (4g) showed pA2 = 6.9). The structure–activity relationships for compounds with various positions of the nitrogen in the benzene ring for the thiazoles compared with oxazoles are discussed. © 2004 Elsevier SAS. All rights reserved.
Glidewell Christopher - One of the best experts on this subject based on the ideXlab platform.
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Six 1-halobenzoyl-4-(2-methoxyphenyl)Piperazines having Z′ values of one, two or four; disorder, pseudosymmetry, twinning and supramolecular assembly in one, two or three dimensions
'International Union of Crystallography (IUCr)', 2021Co-Authors: Harish Chinthal Chayanna, Yathirajan H. S., Foro Sabine, Kavitha, Channappa N., Glidewell ChristopherAbstract:Six 1-halobenzoyl-4-(2-methoxyphenyl)Piperazines have been prepared using carbodiimide-mediated coupling reactions between halobenzoic acids and N-(2-methoxyphenyl)Piperazine. The molecules of 1-(4-fluorobenzoyl)-4-(2-methoxyphenyl)Piperazine, C18H19FN2O2 (I), are linked into a chain of rings by a combination of C—H⋯O and C—H⋯π(arene) hydrogen bonds. 1-(4-Chlorobenzoyl)-4-(2-methoxyphenyl)Piperazine, C18H19ClN2O2 (II), crystallizes in the space group Pca21 with Z′ = 4 and it exhibits both pseudosymmetry and inversion twinning: a combination of six C—H⋯O and two C—H⋯π(arene) hydrogen bonds generate a three-dimensional assembly. In 1-(4-bromobenzoyl)-4-(2-methoxyphenyl)Piperazine, C18H19BrN2O2 (III), which also crystallizes in space group Pca21 but with Z′ = 2, the bromobenzoyl unit in one of the molecules is disordered. Pseudosymmetry and inversion twinning are again present, and a combination of three C—H⋯O and one C—H⋯π(arene) hydrogen bonds generate a two-dimensional assembly. A single C—H⋯O hydrogen bond links the molecules of 1-(4-iodobenzoyl)-4-(2-methoxyphenyl)Piperazine, C18H19IN2O2 (IV), into simple chains but in the isomeric 3-iodobenzoyl analogue (V), which crystallizes in space group P212121 with Z′ = 2, a two-dimensional assembly is generated by a combination of four C—H⋯O and two C—H⋯π(arene) hydrogen bonds; pseudosymmetry and inversion twinning are again present. A single C—H⋯O hydrogen bond links the molecules of 1-(2-fluorobenzoyl)-4-(2-methoxyphenyl)Piperazine, C18H19FN2O2 (VI), into simple chains. Comparisons are made with the structures of some related compounds
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Six 1-aroyl-4-(4-methoxyphenyl)Piperazines: similar molecular structures but different patterns of supramolecular assembly
'International Union of Crystallography (IUCr)', 2019Co-Authors: Kiran Kumar H., Yathirajan H. S., Sagar B. K., Foro Sabine, Glidewell ChristopherAbstract:Six new 1-aroyl-4-(4-methoxyphenyl)Piperazines have been prepared, using coupling reactions between benzoic acids and N-(4-methoxyphenyl)Piperazine. There are no significant hydrogen bonds in the structure of 1-benzoyl-4-(4-methoxyphenyl)Piperazine, C18H20N2O2, (I). The molecules of 1-(2-fluorobenzoyl)-4-(4-methoxyphenyl)Piperazine, C18H19FN2O2, (II), are linked by two C—H⋯O hydrogen bonds to form chains of rings, which are linked into sheets by an aromatic π–π stacking interaction. 1-(2-Chlorobenzoyl)-4-(4-methoxyphenyl)Piperazine, C18H19ClN2O2, (III), 1-(2-bromobenzoyl)-4-(4-methoxyphenyl)Piperazine, C18H19BrN2O2, (IV), and 1-(2-iodobenzoyl)-4-(4-methoxyphenyl)Piperazine, C18H19IN2O2, (V), are isomorphous, but in (III) the aroyl ring is disordered over two sets of atomic sites having occupancies of 0.942 (2) and 0.058 (2). In each of (III)–(V), a combination of two C—H⋯π(arene) hydrogen bonds links the molecules into sheets. A single O—H⋯O hydrogen bond links the molecules of 1-(2-hydroxybenzoyl)-4-(4-methoxyphenyl)Piperazine, C18H20N2O3, (VI), into simple chains. Comparisons are made with the structures of some related compounds
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Six 1-aroyl-4-(4-methoxyphenyl)Piperazines : similar molecular structures but different patterns of supramolecular assembly
'International Union of Crystallography (IUCr)', 2019Co-Authors: Kiran Kumar Haruvegowda, Yathirajan H. S., Sagar B. K., Foro Sabine, Glidewell ChristopherAbstract:HSY thanks the University Grants Commission, New Delhi, for the award of a BSR Faculty Fellowship for three years.Six new 1-aroyl-4-(4-methoxyphenyl)Piperazines have been prepared, using coupling reactions between benzoic acids and N-(4-methoxyphenyl)Piperazine. There are no significant hydrogen bonds in the structure of 1-benzoyl-4-(4-methoxyphenyl)Piperazine, C18H20N2O2, (I). The molecules of 1-(2-fluorobenzoyl)-4-(4-methoxyphenyl)Piperazine, C18H19FN2O2, (II), are linked by two C—H⋯O hydrogen bonds to form chains of rings, which are linked into sheets by an aromatic π–π stacking interaction. 1-(2-Chlorobenzoyl)-4-(4-methoxyphenyl)Piperazine, C18H19ClN2O2, (III), 1-(2-bromobenzoyl)-4-(4-methoxyphenyl)Piperazine, C18H19BrN2O2, (IV), and 1-(2-iodobenzoyl)-4-(4-methoxyphenyl)Piperazine, C18H19IN2O2, (V), are isomorphous, but in (III) the aroyl ring is disordered over two sets of atomic sites having occupancies of 0.942 (2) and 0.058 (2). In each of (III)–(V), a combination of two C—H⋯π(arene) hydrogen bonds links the molecules into sheets. A single O—H⋯O hydrogen bond links the molecules of 1-(2-hydroxybenzoyl)-4-(4-methoxyphenyl)Piperazine, C18H20N2O3, (VI), into simple chains. Comparisons are made with the structures of some related compounds.Publisher PDFPeer reviewe
Leigh Ferris - One of the best experts on this subject based on the ideXlab platform.
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synthesis of enantiopure Piperazines via asymmetric lithiation trapping of n boc Piperazines unexpected role of the electrophile and distal n substituent
Journal of the American Chemical Society, 2016Co-Authors: James D Firth, Peter Obrien, Leigh FerrisAbstract:A new method for the synthesis of enantiopure α-substituted Piperazines via direct functionalization of the intact Piperazine ring is described. The approach utilizes the asymmetric lithiation–substitution of an α-methylbenzyl-functionalized N-Boc Piperazine using s-BuLi/(−)-sparteine or (+)-sparteine surrogate and provides access to a range of Piperazines (as single stereoisomers). Optimization of the new methodology required a detailed mechanistic study. Surprisingly, it was found that the main culprits affecting the yield and enantioselectivity were the electrophile (the last reagent to be added to the reaction flask) and the distal N-substituent. The mechanistic studies included optimization of lithiation times using in situ IR spectroscopy, identification of a ring-fragmentation of the lithiated Piperazines (that could be minimized with sterically hindered N-alkyl groups), and use of a novel “diamine switch” strategy to improve enantioselectivity with certain electrophiles. The methodology was showca...
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Synthesis of Enantiopure Piperazines via Asymmetric Lithiation–Trapping of N‑Boc Piperazines: Unexpected Role of the Electrophile and Distal N‑Substituent
2016Co-Authors: James D. Firth, Peter O’brien, Leigh FerrisAbstract:A new method for the synthesis of enantiopure α-substituted Piperazines via direct functionalization of the intact Piperazine ring is described. The approach utilizes the asymmetric lithiation–substitution of an α-methylbenzyl-functionalized N-Boc Piperazine using s-BuLi/(−)-sparteine or (+)-sparteine surrogate and provides access to a range of Piperazines (as single stereoisomers). Optimization of the new methodology required a detailed mechanistic study. Surprisingly, it was found that the main culprits affecting the yield and enantioselectivity were the electrophile (the last reagent to be added to the reaction flask) and the distal N-substituent. The mechanistic studies included optimization of lithiation times using in situ IR spectroscopy, identification of a ring-fragmentation of the lithiated Piperazines (that could be minimized with sterically hindered N-alkyl groups), and use of a novel “diamine switch” strategy to improve enantioselectivity with certain electrophiles. The methodology was showcased with the preparation of an intermediate for Indinavir synthesis and the stereoselective synthesis of 2,5-trans- and 2,6-trans-Piperazines
Stefano Manfredini - One of the best experts on this subject based on the ideXlab platform.
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Rapid Access to 1‐Benzyl 2‐Substituted Piperazines: Application to the Synthesis of 1‐Benzyl‐2‐difluoromethyl‐Piperazine.
ChemInform, 2011Co-Authors: Carmela Napolitano, Manuela Borriello, Francesca Cardullo, Daniele Donati, Alfredo Paio, Stefano ManfrediniAbstract:Abstract A rapid and efficient synthesis of 1-benzyl-2-difluoromethyl-Piperazine is herein described. The new pathway has the advantage of avoiding orthogonal protection at the two Piperazine nitrogen atoms; therefore it is suitable for access to several 1-benzyl 2-substituted Piperazines starting from the simple commercially available N,N′-dibenzylethylendiamine.
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Rapid Access to 1-Benzyl 2-Substituted Piperazines: Application to the Synthesis of 1-Benzyl-2-difluoromethyl-Piperazine
Synthetic Communications, 2011Co-Authors: Carmela Napolitano, Manuela Borriello, Francesca Cardullo, Daniele Donati, Alfredo Paio, Stefano ManfrediniAbstract:Abstract A rapid and efficient synthesis of 1-benzyl-2-difluoromethyl-Piperazine is herein described. The new pathway has the advantage of avoiding orthogonal protection at the two Piperazine nitrogen atoms; therefore it is suitable for access to several 1-benzyl 2-substituted Piperazines starting from the simple commercially available N,N′-dibenzylethylendiamine.
Krzysztof Walczyński - One of the best experts on this subject based on the ideXlab platform.
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Non-imidazole histamine H3 ligands. Part III. New 4-n-propylPiperazines as non-imidazole histamine H3-antagonists.
European journal of medicinal chemistry, 2005Co-Authors: Krzysztof Walczyński, Obbe P. Zuiderveld, Henk TimmermanAbstract:In search for a new lead of non-imidazole histamine H3-receptor antagonists, a series of 1[(2-thiazolopyridine)-4-n-propyl]Piperazines, the analogous 1-[(2-oxazolopyridine)-4-npropyl]Piperazines, 1-[(2-benzothiazole)-4-n-propyl]Piperazine and 1-[(2-benzooxazole)4-n-propyl]Piperazine were prepared and in vitro tested as H3-receptor antagonists (the electrically evoked contraction of the guinea-pig jejunum). It appeared that by comparison of homologous pairs the thiazolo derivatives have slightly higher activity than their oxazolo analogues. The most potent compound of these series is the 1-(2-thiazolo[4,5-c]pyridine)-4-n-propylPiperazine (3c) with pA2 = 7.25 (its oxazole analogue (4g) showed pA2 = 6.9). The structure–activity relationships for compounds with various positions of the nitrogen in the benzene ring for the thiazoles compared with oxazoles are discussed. © 2004 Elsevier SAS. All rights reserved.
