19889-77-1Relevant articles and documents
Semi-rigid (Aminomethyl) piperidine-based pentadentate ligands for Mn(II) complexation
Baranyai, Zsolt,Callegari, Edoardo,Cossi, Maurizio,Fraccarollo, Alberto,Martinelli, Jonathan,Tei, Lorenzo
, (2021/10/12)
Two pentadentate ligands built on the 2-aminomethylpiperidine structure and bearing two tertiary amino and three oxygen donors (three carboxylates in the case of AMPTA and two carboxylates and one phenolate for AMPDA-HB) were developed for Mn(II) complexation. Equilibrium studies on the ligands and the Mn(II) complexes were carried out using pH potentiometry,1H-NMR spectroscopy and UV-vis spectrophotometry. The Mn complexes that were formed by the two ligands were more stable than the Mn complexes of other pentadentate ligands but with a lower pMn than Mn(EDTA) and Mn(CDTA) (pMn for Mn(AMPTA) = 7.89 and for Mn(AMPDA-HB) = 7.07).1H and17O-NMR relaxometric studies showed that the two Mn-complexes were q = 1 with a relaxivity value of 3.3 mM?1 s?1 for Mn(AMPTA) and 3.4 mM?1 s?1 for Mn(AMPDA-HB) at 20 MHz and 298 K. Finally, the geometries of the two complexes were optimized at the DFT level, finding an octahedral coordination environment around the Mn2+ ion, and MD simulations were performed to monitor the distance between the Mn2+ ion and the oxygen of the coordinated water molecule to estimate its residence time, which was in good agreement with that determined using the17O NMR data.
Characterization of an enantioselective amidase from Cupriavidus sp. KNK-J915 (FERM BP-10739) useful for enzymatic resolution of racemic 3-piperidinecarboxamide
Nojiri, Masutoshi,Taoka, Naoaki,Yasohara, Yoshihiko
, p. 136 - 142 (2014/12/10)
A novel amidase (CsAM) acting on (R,S)-N-benzyl-3-piperidinecarboxamide was purified from Cupriavidus sp. KNK-J915 (FERM BP-10739) and characterized. The enzyme acts on (R,S)-N-benzyl-3-piperidinecarboxamide S-selectively to yield (R)-N-benzyl-3-piperidinecarboxamide. Analytical gel filtration column chromatography and SDS-PAGE revealed that the enzyme is a tetramer with a subunit of approximately 47 kDa. It has a broad substrate spectrum against nitrogen-containing heterocyclic amides. Its optimal pH and temperature are 8.0-9.0 and 50 °C, respectively. The CsAM gene was cloned and sequenced, and it was found to comprise 1341 bp and encode a polypeptide of 46,388 Da. The deduced amino acid sequence exhibited 78% identity to that of a putative amidase (CnAM) from Cupriavidus necator JMP134. The cultured cells of recombinant Escherichia coli producing CnAM could be used for the S-selective hydrolysis of (R,S)-N-benzyl-3-piperidinecarboxamide but could not be used for the S-selective hydrolysis of (R,S)-3-piperidinecarboxamide because of its very low level of selectivity. In contrast, the cultured cells of recombinant E. coli producing CsAM could hydrolyze both (R,S)-N-benzyl-3-piperidinecarboxamide and (R,S)-3-piperidinecarboxamide with high S-selectivity.
Core refinement toward permeable β-secretase (BACE-1) inhibitors with low hERG activity
Ginman, Tobias,Viklund, Jenny,Malmstr?m, Jonas,Blid, Jan,Emond, Rikard,Forsblom, Rickard,Johansson, Anh,Kers, Annika,Lake, Fredrik,Sehgelmeble, Fernando,Sterky, Karin J.,Bergh, Margareta,Lindgren, Anders,Johansson, Patrik,Jeppsson, Fredrik,F?lting, Johanna,Gravenfors, Ylva,Rahm, Fredrik
supporting information, p. 4181 - 4205 (2013/07/19)
By use of iterative design aided by predictive models for target affinity, brain permeability, and hERG activity, novel and diverse compounds based on cyclic amidine and guanidine cores were synthesized with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. Since synthesis feasibility had low priority in the design of the cores, an extensive synthesis effort was needed to make the relevant compounds. Syntheses of these compounds are reported, together with physicochemical properties and structure-activity relationships based on in vitro data. Four crystal structures of diverse amidines binding in the active site are deposited and discussed. Inhibitors of BACE-1 with 3 μM to 32 nM potencies in cells are shown, together with data on in vivo brain exposure levels for four compounds. The results presented show the importance of the core structure for the profile of the final compounds.
Synthesis and anticonvulsant activity of novel 2,6-diketopiperazine derivatives. Part 2: Perhydropyrido[1,2-a]pyrazines
Dawidowski, MacIej,Herold, Franciszek,Chodkowski, Andrzej,Kleps, Jerzy
scheme or table, p. 347 - 353 (2012/03/22)
A new series of chiral pyrido[1,2-a]pyrazine derivatives was synthesised and evaluated in in vivo animal models of epilepsy. A significant influence of the stereochemistry of the pyrido[1,2-a]pyrazine framework on the pharmacological activity was observed
The synthesis and conformational analysis of optical isomers of 4-phenyl-perhydropyrido[1,2-a]pyrazine-1,3-dione: an example of 'solid state-frozen' dynamics in nitrogen-bridged bicyclic 2,6-diketopiperazines
Dawidowski, Maciej,Herold, Franciszek,Wilczek, Marcin,Kleps, Jerzy,Wolska, Irena,Turlo, Jadwiga,Chodkowski, Andrzej,Widomski, Pawel,Bielejewska, Anna
experimental part, p. 1759 - 1766 (2009/12/28)
The synthesis, chemical properties, and conformational analysis of enantiopure (4R,9aS)-, (4S,9aR)-, (4S,9aS)-, and (4R,9aR)-4-phenyl-perhydropyrido[1,2-a]pyrazine-1,3-diones having potential biological activity are described. An interesting example of the coexistence of two invertomers of the (4R,9aR)-diastereomer in a single crystal unit cell is reported. The invertomers differ in the cis/trans-relationship between the fused rings and in the absolute configuration at the chiral nitrogen atom. The structure and equilibrium distributions of the respective conformers have been determined by NMR spectroscopy in both polar and non-polar solvents at various temperatures. The NMR spectra show that dynamic processes in the imide parts of the interconverting species are restrained by self-aggregation. The (4S,9aR)-diastereomer exists in a single conformation with insignificant dynamic effects.
Design and synthesis of peripherally restricted transient receptor potential vanilloid 1 (TRPV1) antagonists
Tamayo, Nuria,Liao, Hongyu,Stec, Markian M.,Wang, Xianghong,Chakrabarti, Partha,Retz, Dan,Doherty, Elizabeth M.,Surapaneni, Sekhar,Tamir, Rami,Bannon, Anthony W.,Gavva, Narender R.,Norman, Mark H.
, p. 2744 - 2757 (2008/12/22)
Transient receptor potential vanilloid 1 (TRPV1) channel antagonists may have clinical utility for the treatment of chronic nociceptive and neuropathic pain. We recently advanced a TRPV1 antagonist, 3 (AMG 517), into clinical trials as a new therapy for t
PYRAZOLE DERIVATIVES
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Page/Page column 37-38, (2010/11/26)
A compound represented by formula (I): (wherein Ar1 represents a phenyl group which may have 1 to 3 substituents, or a non-substituted 5- or 6-membered aromatic heterocyclic group; Ar2 represents (i) a non-substituted phenyl group, (ii) a phenyl group which has been substituted by a lower alkyl group having 1 to 3 groups or atoms selected from among a carbamoyl group, an amino group, a hydroxyl group, a lower alkoxy group, and a halogen atom, or (iii) a 5- or 6-membered nitrogen-containing aromatic heterocyclic group which has been substituted by 1 to 3 groups or atoms selected from among a lower alkyl group, a lower alkynyl group, a lower alkanoyl group, a carbamoyl group, a cyano group, an amino group, a hydroxyl group, a lower alkoxy group, and a halogen atom; and X represents a group represented by formula (II): (wherein the ring structure represents a 4- to 7-membered heterocyclic group which may have, in addition to the nitrogen atom shown in formula (II), one heteroatom selected from among nitrogen, oxygen, and sulfur, and which may be substituted by 1 to 4 groups or atoms selected from among a lower alkyl group, a carbamoyl group, an amino group, a hydroxyl group, a lower alkoxy group, an oxo group, a lower alkanoyl group, a lower alkylsulfonyl group, and a halogen atom)), a salt thereof, a solvate of the compound or the salt, and a drug.
An efficient synthesis of enantiomerically pure (R)-pipecolic acid, (S)-proline, and their N-alkylated derivatives
Fadel, Antoine,Lahrache, Nabil
, p. 1780 - 1784 (2007/10/03)
Enantiomerically pure (R)-(+)-pipecolic acid was synthesized in four steps and 42% overall yield starting from dihydropyran and (R)-α- methylbenzylamine. A general short strategy is also described for preparing (S)-proline (47.5% overall yield) and derivatives.
Vanilloid receptor ligands and their use in treatments
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Page/Page column 67, (2010/10/20)
Substituted pyridines and pyrimidines and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.
Vanilloid receptor ligands and their use in treatments
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Page/Page column 32, (2010/10/20)
Therapeutic benzimidazoles and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.
