58322-72-8Relevant articles and documents
Design, Synthesis, and Monoamine Oxidase Inhibitory Activity of (+)-Cinchonaminone and Its Simplified Derivatives
Sato, Yuta,Oyobe, Naoko,Ogawa, Takao,Suzuki, Sayo,Aoyama, Hiroshi,Nakamura, Tomonori,Fujioka, Hiromichi,Shuto, Satoshi,Arisawa, Mitsuhiro
, p. 1464 - 1469 (2021)
The absolute structure of an indole alkaloid (+)-cinchonaminone by total synthesis of both (+)-cinchonaminone and its enantiomer was determined. The main focus of the study was the enantioselective synthesis of both enantiomers of a chiral cis-3,4-disubstituted piperidine. We also evaluated monoamine oxidase (MAO) inhibitory activities of these enantiomers. Furthermore, its structurally simplified derivatives were synthesized that did not have any chiral center. Two of these derivatives showed stronger MAO inhibitory activities than that of (+)-cinchonaminone.
COMPOUNDS ACTIVE TOWARDS NUCLEAR RECEPTORS
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Page/Page column 79, (2021/10/11)
Disclosed are compounds active towards nuclear receptors, pharmaceutical compositions containing the compounds and use of the compounds in therapy.
PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE
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, (2015/09/28)
The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7- diamine compounds (referred to herein as "PPDA compounds") that, inter alia, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.
Radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines and its application to new radiotracers for NR2B NMDA receptor visualization
Koudih, Radouane,Gilbert, Gwenaelle,Dhilly, Martine,Barre, Louisa,Debruyne, Daniele,Sobrio, Franck,Abbas, Ahmed
supporting information, p. 8493 - 8500,8 (2012/12/12)
In order to develop a novel and useful building block for the development of radiotracers for positron emission tomography (PET), we studied the radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines. Indeed, 3-fluoropiperidine became a useful building block in medicinal chemistry for the pharmacomodulation of piperidine-containing compounds. The radiofluorination was studied on substituted piperidines with electron-donating and electron-withdrawing N-substituents. In the instance of electron-donating N-substituents such as benzyl or butyl, configuration retention and satisfactory fluoride-18 incorporation yields up to 80% were observed. In the case of electron-withdrawing N-substituents leading to carbamate or amide functions, the incorporation yields depend on the 4-susbtitutent (2 to 63%). The radiolabelling of this building block was applied to the automated radiosynthesis of NR2B NMDA receptor antagonists and effected by a commercially available radiochemistry module. The in vivo evaluation of three radiotracers demonstrated minimal brain uptakes incompatible with the imaging of NR2B NMDA receptors in the living brain. Nevertheless, moderate radiometabolism was observed and, in particular, no radiodefluorination was observed which demonstrates the stability of the 3-position of the fluorine-18 atom. In conclusion, the 1,4-disubstituted 3-[18F]fluoropiperidine moiety could be of value in the development of other radiotracers for PET even if the evaluation of the NR2B NMDA receptor antagonists failed to demonstrate satisfactory properties for PET imaging of this receptor.
Radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines and its application to new radiotracers for NR2B NMDA receptor visualization
Koudih, Radouane,Gilbert, Gwéna?lle,Dhilly, Martine,Abbas, Ahmed,Barré, Louisa,Debruyne, Danièle,Sobrio, Franck
supporting information, p. 8493 - 8500 (2013/01/15)
In order to develop a novel and useful building block for the development of radiotracers for positron emission tomography (PET), we studied the radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines. Indeed, 3-fluoropiperidine became a useful building block in medicinal chemistry for the pharmacomodulation of piperidine-containing compounds. The radiofluorination was studied on substituted piperidines with electron-donating and electron-withdrawing N-substituents. In the instance of electron-donating N-substituents such as benzyl or butyl, configuration retention and satisfactory fluoride-18 incorporation yields up to 80% were observed. In the case of electron-withdrawing N-substituents leading to carbamate or amide functions, the incorporation yields depend on the 4-susbtitutent (2 to 63%). The radiolabelling of this building block was applied to the automated radiosynthesis of NR2B NMDA receptor antagonists and effected by a commercially available radiochemistry module. The in vivo evaluation of three radiotracers demonstrated minimal brain uptakes incompatible with the imaging of NR2B NMDA receptors in the living brain. Nevertheless, moderate radiometabolism was observed and, in particular, no radiodefluorination was observed which demonstrates the stability of the 3-position of the fluorine-18 atom. In conclusion, the 1,4-disubstituted 3-[18F]fluoropiperidine moiety could be of value in the development of other radiotracers for PET even if the evaluation of the NR2B NMDA receptor antagonists failed to demonstrate satisfactory properties for PET imaging of this receptor.
Synthesis and characterization of enantiomerically pure cis- and trans-3-fluoro-2,4-dioxa-9-aza-3-phosphadecalin 3-oxides as acetylcholine mimetics and inhibitors of acetylcholinesterase
Lorenzetto, Piergiorgio,Waechter, Michael,Rueedi, Peter
, p. 746 - 767 (2011/06/27)
The title compounds, the P(3)-axially and P(3)-equatorially substituted cis- and trans-configured 9-benzyl-3-fluoro-2,4-dioxa-9-aza-3-phosphadecalin 3-oxides (=9-benzyl-3-fluoro-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-oxides=7-benzyl-2-fluorohexah
Development of two diastereoselective routes towards trans-4-aminomethyl-piperidin-3-ol building blocks
Gijsen, Harrie J.M.,De Cleyn, Michel J.A.,Love, Christopher J.,Surkyn, Michel,Van Brandt, Sven F.A.,Verdonck, Marc G.C.,Moens, Luc,Cuypers, Jef,Bosmans, Jean-Paul R.M.A.
, p. 2456 - 2464 (2008/09/18)
Two diastereoselective, scaleable routes towards trans-3,4-disubstituted piperidines with a 4-hydroxymethyl-3-hydroxy or 4-aminomethyl-3-hydroxy substitution pattern are being described. In the first route, the 3,4-trans configuration was introduced regio- and diastereoselectively via a hydroboration/oxidation sequence starting from 4-hydroxymethylpyridine. In the second route, regioselective epoxide ring opening of N-benzyl-3,4-epoxy-piperidine was achieved with LiCN, in situ generated from acetocyanohydrin and LiNH2. The regioselectivity of both the hydroboration and the epoxide ring opening was positively influenced by the presence of the basic piperidine nitrogen. Both routes have been optimized to be performed at large scale.
Synthesis and pharmacological evaluation of benzamide derivatives as selective 5-HT4 receptor agonists
Sonda, Shuji,Kawahara, Toshio,Katayama, Kenichi,Sato, Noriko,Asano, Kiyoshi
, p. 3295 - 3308 (2007/10/03)
It is thought that selective 5-HT4 receptor agonists-such as 4-amino-5-chloro-2-methoxy-N-[1-(6-oxo-6-phenylhexyl)piperidin-4-ylmethyl] benzamide (2)-have the ability to enhance both upper and lower gastrointestinal motility without any significant adverse effects. Modification of 2 was performed. Variation of the piperidin-4-ylmethyl moiety of 2 led to a decrease in the binding affinity for the 5-HT4 receptor. Following conversion of the carbonyl group on the benzoyl part to a hydroxyl or sulfoxide group, the binding affinity for the 5-HT4 receptor was retained although the effect on defecation was reduced. Many of the 4-amino-5-chloro-2-methoxy-N- (piperidin-4-ylmethyl)benzamides that had a ether or sulfide moiety in the side-chain part at the 1-position of the piperidine exhibited high affinity for the 5-HT4 receptor. Among these, phenylthio 41c and benzylthio derivative 44 were selective 5-HT4 receptor agonists, and had a similar effect on defecation to compound 2.
2,4-Dioxa-7-aza-, 2,4-dioxa-8-aza-, and 2,4-dioxa-9-aza-3-phosphadecalins as rigid acetylcholine mimetics: Syntheses and characterization
Furegati, Stefan,Ganci, Walter,Gorla, Fabrizio,Ringeisen, Urs,Rueedi, Peter
, p. 2629 - 2661 (2007/10/03)
Phosphorylation of suitable piperidine precursors yielded a series of novel decalin-type O,N,P-heterocycles. The title compounds, P(3)-axially and P(3)-equatorially X-substituted, cis- and trans-configurated 2,4-dioxa-7-aza-, 2,4-dioxa-8-aza-, and 2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-oxides (X = Cl, F, 4-nitrophenoxy, and 2,4-dinitrophenoxy), are configuratively fixed and conformationally constrained P-analogues of acetylcholine and as such represent acetylcholine (7-aza and 9-aza isomers) or γ-homo-acetylcholine mimetics (8-aza isomers). Being irreversible inhibitors of acetylcholinesterase (AChE), the compounds are considered to be suitable probes for the investigation of the stereochemical course of the inhibition reaction by 31P-NMR spectroscopy. Moreover, the design of these mimetics will enable studies of molecular interactions with AChE, in particular, the recognition conformation of acetylcholine.
ESTERS OF 3-HYDROXY-PIPERIDINEMETHANOL DERIVATIVES
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, (2008/06/13)
The present invention of compounds of formula (I), a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, R is C1-6alkyloxy, C2-6alkenyloxy or C2-6alkynyloxy; R is hydrogen or C
