Showing papers on "Piperidine published in 1999"

Chiral non-racemic N -cyanomethyloxazolidines: the pivotal system of the CN( R,S ) method

Abstract: The α-cyanomethyloxazolidine ring system has been integrated into piperidine and pyrrolidine structures providing chiral non-racemic building blocks Reaction conditions have been determined for regio- and stereoselective substitution of the ring atoms This review highlights the applications of the methodology for the diastereoselective synthesis of both natural and unnatural derivatives containing either the piperidine or the pyrrolidine ring as a substructure

Material for organic electroluminescent element, and organic electroluminescent element using the same

Abstract: PROBLEM TO BE SOLVED: To obtain the subject material having a luminescent color from yellow to red, high emission luminance and long emission lifetime and useful in the emission layer of an organic electroluminescent element by desining the material to have a specific structure. SOLUTION: This material is obtained by designing itself to have a structure of formula I [R1 and R2 are each a monocyclic group or condensed polycyclic group; A is O or a methylene of formula II [R3 and R4 are each H or substituent selected from cyano, a halogen, alkylcarbonyl and alkoxycarbonyl, and both are not H at the same time); B is O or S], (e.g. a compound of formula III). The material of formula I is, for instance, produced by dehydrocondensation between a compound of formula IV and a formyl substitution product of (substituted) monocyclic compound or (substituted) condensed polycyclic compound in the presence of a catalyst comprising a base (e.g. piperidine) in a high-boiling solvent comprising a high-boiling alcohol (e.g. isopropanol).

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 2. Approaches to eliminate opioid agonist metabolites via modification of linker and 4-methoxycarbonyl-4-phenylpiperidine moiety.

Abstract: We have previously described compound 1a as a high-affinity subtype selective α1a antagonist. In vitro and in vivo evaluation of compound 1a showed its major metabolite to be a μ-opioid agonist, 4-methoxycarbonyl-4-phenylpiperidine (3). Several dihydropyrimidinone analogues were synthesized with the goal of either minimizing the formation of 3 by modification of the linker or finding alternative piperidine moieties which when cleaved as a consequence of metabolism would not give rise to μ-opioid activity. Modification of the linker gave several compounds with good α1a binding affinity (Ki = 300-fold over α1b and α1d). In vitro analysis in the microsomal assay revealed these modifications did not significantly affect N-dealkylation and the formation of the piperidine 3. The second approach, however, yielded several piperidine replacements for 3, which did not show significant μ-opioid activity. Several of these compounds maintained good affinity at the α1a adrenoceptor and selecti...

Asymmetric syntheses of n-boc 2-substituted pyrrolidines and piperidines by intramolecular cyclization

Abstract: Asymmetric lithiation-substitutions by n-BuLi/(−)-sparteine with the N-Boc-N-(3-halopropyl)allylamines 1−4 provide the N-Boc-2-alkenylpyrrolidines (S)-5, (S)-6, and (S)-7 in yields of 31−93% with enantiomeric ratios (ers) from 65:35 to 90:10. These reactions are shown to involve an initial asymmetric deprotonation, but the enantiodetermining step is a subsequent asymmetric cyclization under the influence of the chiral ligand. Extension to formation of a piperidine is illustrated by reaction of N-Boc-(4-chlorobutyl)cinnamylamine (9) to afford (S)-N-Boc-2-(trans-β-styryl)piperidine ((S)-10) in 68% yield with an enantiomeric ratio (er) of 84:16. Analogous reactions with epoxide ring openings of N-Boc-N-(oxaalkenyl)benzylamines 11 and 12 afford the corresponding N-Boc-2-phenyl-3-(hydroxymethyl)pyrrolidine (13) in 67% yield with a diastereomeric ratio (dr) of 50:50 and ers of 97:3 and 95:5 and the corresponding N-Boc-2-phenyl-3-(hydroxymethyl)piperidine (14) in 29% yield with a dr of 86:14 and ers of 81:19 and...

4-(2-keto-1-benzimidazolinyl)piperidine compounds as orl1-receptor agonists

Abstract: A compound of formula (I) or the pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 and R5 are defined above are useful as ORL1-receptor agonists, and useful as analgesics or the like in mammalian subjects.

A New Synthesis of All Four Stereoisomers of 2-(2,3-Dihydroxypropyl)piperidine via Iterative Asymmetric Dihydroxylation To Cause Enantiomeric Enhancement. Application to Asymmetric Synthesis of Naturally Occurring Piperidine-Related Alkaloids

Abstract: Both enantiomers of 2-(2-propenyl)piperidine 1 (76−88% ee), prepared via the first asymmetric dihydroxylation (AD) of 5-hexenyl azide, underwent the second AD to provide all four of the stereoisomeric 2-(2,3-dihydroxypropyl)piperidines 2 with enantiomeric enhancement (>98% ee). An asymmetric synthesis, starting from 2, of several 2-(2-hydroxyalkyl)piperidine alkaloids [(−)-halosaline, (+)-N-methylallosedridine, (+)-8-ethylnorlobelol, (+)-sedridine, (+)-allosedridine, (−)-allosedridine, and (+)-N-methylsedridine] and the ant defense alkaloids [(+)-tetraponerine-3 (T-3), T-4, T-7, and T-8] is demonstrated.

Quinoline derivatives and their use as antibacterial agents

Abstract: Piperidine derivatives and pharmaceutical derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly in man.

Farnesyl transferase inhibitors having a piperidine structure and process for preparation thereof

Abstract: The present invention relates to a novel piperidine derivative represented by formula (1) which shows an inhibitory activity against farnesyl transferase or pharmaceutically acceptable salts thereof, in which A, E and G are defined in the specification; to a process for preparation of the compound of formula (1); to an intermediate which is used in the preparation of the compound of formula (1); and to a pharmaceutical composition comprising the compound of formula (1) as an active ingredient.

Solid phase diels-alder reactions of amino acid derived trienes

Abstract: The known diethyl phosphonoacetyl-Wang resin 1 was treated with an Fmoc-protected amino aldehyde in the presence of Et3N and LiBr. The Fmoc group was then removed with piperidine to give primary amines 3. With or without N-benzylation, 3 was transformed to resin-bound trienes by either reductive alkylation with dienals or by acylation with activated dienocarboxylic acids. Trienes 5 cyclized at room temperature to give the predominant trans-fused bicyclic products 6. Trienes 10 containing a furan moiety were constructed similarly, and their cycloadditions also proceeded at room temperature to produce epoxyisohydroindolines 11, which were derived from an endo transition state pathway. Compounds 12 and 14 containing vinylfuran moieties reacted to form tricyclic products 13 and 15. These examples demonstrated that furan rings can be used in solid-phase Diels−Alder reactions to generate libraries of functionalized polycyclic compounds.

Naphthrydine compounds and their azaisosteric analogues as antibacterials

Abstract: Piperidine derivatives of formula (I) or a pharmaceutically acceptable derivative thereof and pharmaceutically acceptable derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly in man.

Piperidine ccr-3 receptor antagonists

Abstract: This invention relates to certain piperidine quaternary salts of formula (I), that are CCR-3 receptor antagonists, pharmaceutical compositions containing them, methods for their use and methods for preparing these compounds.

Piperidine derivatives having renin inhibiting activity

Abstract: Novel piperidine derivatives, their manufacture and use as medicaments, are disclosed. The invention is concerned with the novel piperidine derivatives of general formula I ##STR1## wherein R1, R2, R3, R4, Q, X, Z, m and n are as described herein.

Conformational Switching and the Synthesis of Spiro[2H-indol]-3(1H)-ones by Radical Cyclization.

Abstract: Radical cyclization of 1-(2-bromophenylamino)cyclohexanecarbonitriles (3, X = CH) and 4-(2-bromophenylamino)-4-piperidinecarbonitriles (3, X = N) provide spiro[2H-indole-2-cyclohexan]-3(1H)-imines (5, X = CH) and spiro[2H-indole-2,4'-piperidin]-3(1H)-imines (5, X = N), respectively, in 33-57% yields. This contradicts a recent report that 1-(2-bromophenylamino)cyclohexanecarbonitrile (3, X-R(2) = CH(2)), treated under apparently identical conditions, led only to nitrile transfer product 6 (X-R(2) = CH(2)). Acidic hydrolyses of the imines provide the corresponding ketones 2 in quantitative yields. Single-crystal X-ray analyses of ketone 2e and nitrile 3e indicate that the relative configuration of the aromatic nitrogen has been inverted during the cyclization. In addition, NOE NMR analyses of spiroindolepiperidine 2c and its aniline-nitrogen-methylated analogue 10a show that the relative conformation of the piperidine ring has inverted. Thus, methylation of 2c acts as a conformational "switch" for the spiroindolepiperidine ring system.

New Steric Hindrance Approach Employing the Hybrid Ligand 2-Aminomethylpiperidine for Diminishing Dynamic Motion Problems of Platinum Anticancer Drug Adducts Containing Guanine Derivatives.

Abstract: A fundamental problem obscuring the role of the ammine and primary amine groups in the activity of clinically used Pt anticancer drugs is the dynamic character of the adducts with DNA and DNA constituents. Dynamic motion is slower in analogues containing only secondary or tertiary amines, but such agents are not used clinically. Recently we found that enclosing the N center within a piperidine (pip) ring greatly reduces dynamic motion. In this work, we test the hypothesis that a diamine with only one pip ring, 2-aminomethylpiperidine (pipen), would slow dynamic motion enough for insightful study of adducts with one site (cis to the primary amine) closely reflecting the coordination environment of clinically used drugs. Racemic pipen was prepared and resolved by improved methods. PtCl(2)(pipen) synthesized with the pipen enantiomer having an R configuration of the asymmetric carbon (determined on the basis of the [alpha](D) sign) has the S stereochemistry at the N asymmetric center. In the adduct (S,R)-pipenPt(5'-GMP)(2), restricted rotation of the two nonequivalent N7-coordinated 5'-GMP's about the Pt-N7 bonds potentially could lead to two head-to-tail (LambdaHT and DeltaHT) and two head-to-head (HH(1) and HH(2)) atropisomers. However, 1D and 2D NOESY NMR data at pH approximately 3 indicated the dominance of the two HT atropisomers in a LambdaHT:DeltaHT ratio of 2:1. Deprotonation of the phosphate group (pH 7) further stabilized the LambdaHT form, and the CD signal had the shape characteristic of a LambdaHT form with a positive peak at approximately 280 nm. However, at pH 9.5, where the 5'-GMP N1H was largely deprotonated, the NMR spectrum and the approximately 280 nm CD peak both revealed that the LambdaHT form had decreased. When the pH was jumped down to 6.9, the NMR signals of the LambdaHT form and the approximately 280 nm CD peak increased with a half-time of approximately 3 min. Thus, the pip ring lengthens the atropisomerization time from seconds for ethylenediaminePt(5'-GMP)(2) to minutes for (S,R)-pipenPt(5'-GMP)(2). This pH jump experiment indicates that the signs of the CD signal are opposite for the LambdaHT and DeltaHT forms. Changes with pH in both the relative abundance and shifts of the H8 signals of the LambdaHT and DeltaHT forms correlated with an increase in hydrogen bonding by the phosphate group of the 5'-GMP cis to the primary amine. The hydrogen bonding changes the 5'-GMP base tilt and hence the H8 chemical shift. Such information is not obtainable on 5'-GMP adducts of clinically used anticancer drugs.

A novel palladium complex catalyst for carbonylation of alkynes under mild conditions

Abstract: Carbonylation of alkynes has been carried out using a catalyst system consisting of Pd(OAc)2, a monophosphine, p‐toluene sulphonic acid and semilabile anionic bidentate ligands such as pyridine or piperidine carboxylic acids. Turnover frequencies (TOF) upto 3500 h−1 and 98% selectivity to 2‐substituted 2‐propenoic acid/ester have been achieved under mild CO pressures of 1–3 atm at 373 K.

Organic luminous element, organic luminous element using the same and triarylamine compound

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound being a triarylamine compound containing a specific substituent, useful as an organic luminous element material capable of being luminous in high brightness in high efficiency from green to red at a low applied voltage. SOLUTION: This compound is shown by formula I [R1 and R2 are each a (substituted) aryl, a heterocyclic group, an aliphatic hydrocarbon group, at least one of R1 and R2 is an aryl or a heterocyclic group; R3 is a substituent; m is 0-4; R4 to R6 are each H or a substituent; Z127 is a 5- to 7-membered ring-forming atomic group (e.g. substituted 1,3-indanedione nucleus or the like; n is 0-2) such as a triarylamine compound of formula II. The compound of formula II is obtained by dissolving 4-(N,N-diphenylamino)benzaldehyde and 5-phenylindane-1,3-dione 2 in ethanol, adding piperidine, refluxing the solution under heating, cooling the reaction solution, purifying precipitated crude crystal by silica gel chromatography and crystallizing the compound by ethanol- chloroform.

Piperidine analogues of D-galactose as potent inhibitors of α-galactosidase: Synthesis by stannane-mediated hydroxymethylation of 5-azido-1,4-lactones. Structural relationships between D-galactosidase and L-rhamnosidase inhibitors

Abstract: The syntheses of the polyhydroxylated piperidines deoxygalactonojirimycin 2, homogalactonojirimycins 7 and 9, and other 2,6-iminoheptitol derivatives, including an analogue of L-altropyranose, are reported 5-Azidoaldono-1,4-lactones undergo chain extension to afford azido lactols by the addition of a hydroxymethyllithium species 18, generated by transmetallation of a protected stannylmethanol derivative 17 Hydrogenation results in azide reduction with subsequent intramolecular reductive amination to give piperidine ring systems The deprotected iminogalactopyranose analogues are potent and selective α-galactosidase inhibitors Observations on the structural features determining selectivity of inhibition of α-galactosidases over naringinase (L-rhamnosidase) are also reported

New piperazine and piperidine compounds

Abstract: The invention relates to a group of novel piperazine and piperidine derivatives of formula (I), wherein: S1 is hydrogen, halogen, alkyl (1-3C), CN, CF3, OCF3, SCF3, alkoxy (1-3C), amino or mono- or dialkyl (1-3C) substituted amino, or hydroxy; X represents NR3, S, CH2, O, SO or SO2, wherein R3 is H or alkyl (1-3C);.......Z represents =C or -N; - R1 and R2 independently represent H or alkyl (1-3C), or R1 and R2 together can form a bridge of 2 or 3 C-atoms; R4 is hydrogen or alkyl (1-3C); Q is methyl, ethyl, ethyl substituted with one or more fluorine atoms, cyclopropyl - methyl, optionally substituted with one or more fluorine atoms, and salts and prodrugs thereof. It has been found that these compounds have both partial dopamine D2-receptor agonism and partial serotonin 5-HT1A-receptor agonism mediated activities.