- ADJUVANTED CONJUGATE OPIOID VACCINE
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The adjuvanted conjugate opioid vaccine described herein is a conjugate of a protein carrier and at least one opioid backbone component or hapten conjugated thereto, admixed with at least one adjuvant. Anti-opioid effects are demonstrated after administration of a vaccine made up of the CRM197 protein carrier linked to a FEN backbone, combined with adjuvants such as dmLT or LTA1.
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Paragraph 0038-0040
(2021/12/08)
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- Carbon isotope labeling of carbamates by late-stage [11C], [13C] and [14C]carbon dioxide incorporation
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A general procedure for the late-stage [11C], [13C] and [14C]carbon isotope labeling of cyclic carbamates is reported. This protocol allows the incorporation of carbon dioxide, the primary source of carbon-14 and carbon-11 radioisotopes, in a direct, cost-effective and sustainable manner. A disconnection/reconnection strategy, involving ring opening/isotopic closure, was also implemented.
- Del Vecchio, Antonio,Talbot, Alex,Caillé, Fabien,Chevalier, Arnaud,Sallustrau, Antoine,Loreau, Olivier,Destro, Gianluca,Taran, Frédéric,Audisio, Davide
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supporting information
p. 11677 - 11680
(2020/10/19)
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- Nitro-Aldol Approach for Commercial Manufacturing of Fenspiride Hydrochloride
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An efficient, short manufacturing process for fenspiride hydrochloride is reported. Nitro-aldol condensation is the key reaction in the developed process. Improved routes to key building blocks are demonstrated by expedient multikilogram production. Hazardous reactions are avoided. API produced following this new route meets the quality requirement NLT 99.70% purity by HPLC with any individual impurity NMT 0.10% with very good yield.
- Pramanik, Chinmoy,Bapat, Kiran,Patil, Pradip,Kotharkar, Sandeep,More, Yogesh,Gotrane, Dinkar,Chaskar, Sudhir P.,Mahajan, Ulhas,Tripathy, Narendra K.
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p. 1252 - 1256
(2019/06/13)
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- Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine N-benzylpiperidine fragments
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Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62 nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain substitution indicates a new binding mode of inhibitor with AChE. This finding provides new insights into the binding mechanism and is helpful for discovery of novel high-activity AChE inhibitors.
- Zhou, Yeheng,Sun, Wei,Peng, Jiale,Yan, Hui,Zhang, Li,Liu, Xingyong,Zuo, Zhili
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supporting information
(2019/10/08)
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- PEGYLATED OPIOID WITH LOW ADDICTIVE EFFECT
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Provided in the present invention are a conjugate of polyethylene glycol and opioid as shown in general formula (I), and a pharmaceutical composition comprising the conjugate. By means of covalently bonding a plurality of opioids to a polyethylene glycol derivative, the present invention improves water solubility and pharmacokinetic property of the drug with a low addictive effect. ????????PEG-(X-OP)m?????(I)
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- A process for preparing 3 - methyl - 1 - phenethyl piperidine - 4 - one or 1 - phenethyl piperidine - 4 - one method
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The invention discloses a method for preparing 3-mehtyl-1-phenethyl piperidine-4-ketone or 1-phenethyl piperidine-4-ketone. The method starts from easily-obtained 3-substituted pyridine-4-alcohol, sodium borohydride is selectively reduced into allyl alcohol after 3-substituted pyridine-4-alcohol forms quaternary ammonium together with phenethyl-2-halide, and 3-substitute-1-phenethyl piperidine-4-ketone is obtained then after isomerization. The synthetic method is easy, convenient to use, practical, high in operability and beneficial to further large-scale production.
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Paragraph 0040-0041
(2017/08/23)
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- N-phenethyl-4-aniline-based process for preparation of piperidines
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The invention relates to a method for preparing N-phenethyl-4-phenylaminopiperidine. The method comprises the main steps of carrying out hydrogenation and amination on N-phenethyl-4-piperidone (structural formula as shown in a formula (II)) and aniline (structural formula as shown in a formula (III)) in ethanol in the presence of Raney Ni at the temperature of 50-100 DEG C so as to obtain the target product. The method for preparing N-phenethyl-4-phenylaminopiperidine has the advantages of cheap and available raw material, less byproduct, good product purity, high yield, low cost and the like.
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- An efficient, optimized synthesis of fentanyl and related analogs
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The alternate and optimized syntheses of the parent opioid fentanyl and its analogs are described. The routes presented exhibit high-yielding transformations leading to these powerful analgesics after optimization studies were carried out for each synthetic step. The general three-step strategy produced a panel of four fentanyls in excellent yields (73-78%) along with their more commonly encountered hydrochloride and citric acid salts. The following strategy offers the opportunity for the gram-scale, efficient production of this interesting class of opioid alkaloids.
- Valdez, Carlos A.,Leif, Roald N.,Mayer, Brian P.
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- Novel symmetrical trans-bis-Schiff bases of N-substituted-4- piperidones: Synthesis, characterization, and preliminary antileukemia activity mensurations
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A series of novel symmetrical trans-bis-Schiff bases (11a, 11b, 11c, 11d, 11e, 11f, 11g, 11h, 11i, 11j, 11k, 11l, 11m) were designed and prepared as novel anticancer analogues, with the trans-configuration confirmed by X-ray diffraction. Preliminary inhibitory effects of these compounds on CML K562 cell growth were investigated, and the potential analogue 11e showed an excellent anti-leukemia activity (IC50=6.35 μg/mL), which is higher than that of the clinical drug 5-fluorouracil (IC50=8.48 μg/mL). Complete assignments had been achieved for the title compounds by spectroscopic techniques, and their structure-activity relationships have been studied.
- Sun, Chuan-Wen,Wang, Hai-Feng,Zhu, Jun,Yang, Ding-Rong,Xing, Jiahua,Jin, Jia
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p. 1374 - 1380
(2014/01/06)
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- SUBSTITUTED 4-AMINO-PIPERIDINES
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The present invention relates to new substituted 4-amino-piperidine opioid receptor modulators, pharmaceutical compositions thereof, and methods of use thereof
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Page/Page column 19
(2010/02/17)
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- Synthesis and anti-leukemia activity mensuration of 1-phenethyl-4-hydroxy-4-substituted piperidinium hydrochlorides: Structure of bis[1-phenethyl-4-hydroxy-4-(3-fluorophenyl) piperidinium hydrochloride] studied by X-ray and DFT methods
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Four unknown compounds have been synthesized based on the molecular motif of 1-phenethyl-4-hydroxy piperidinium hydrochloride with a variety of the substituted groups R on the same carbon atom bearing the hydroxy group, such as 3-fluorophenyl (3a), 4-methoxyphenyl (3b), 4-methylphenyl (3c) and cyclohexanyl (3d), and their molecular structures were characterized by 1H NMR, MS and IR. To account for the stereo structure and provide more information on the effect of counter ions, hydrogen bonds on molecular conformation, the structure of [1-phenethyl-4-hydroxy-4-(3-fluorophenyl) piperidinium hydrochloride] [PHFPH.Cl] 3a was determined by the single-crystal X-ray analysis and optimized by the B3LYP/6-31G (d, p) calculations. Two chloride anions, two PHFPH cations and a dichloromethane molecule formed a five-membered structure ([(PHFPH)2Cl2]·CH2Cl2) via the intermolecular hydrogen bonds. The core of the five-membered structure ([(PHFPH)2Cl2]·CH2Cl2) is formed by two PHFPH cations linked by N(1B)-H(2)?Cl(2) hydrogen bonds of lengths 3.033(4), which is engaged in two hydrogen bonds: N(1A)-H(1)?Cl(1) of 3.110(4) A? and O(1B)-H(2B)?Cl(1) of 3.099(4) A?. The anti-tumor activity tests indicated that these compounds could inhibit the growth of the K562 cells to some extent and have the potential bioactivity of anti-leukemia.
- Yang, Dingrong,Xue, Sijia,Wang, Haifeng,Zhu, Jun,Jin, Jia,Chen, Jun
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experimental part
p. 97 - 104
(2009/12/03)
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- PESTICIDAL SUBSTITUTED PIPERIDINES
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The invention relates to the use of piperidine derivatives encompassed from the general formula (I) for the control of pests, including arthropods and helminths, and a method for the control of pests.
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Page/Page column 51; 55
(2008/06/13)
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- A convenient one pot synthesis of fentanyl
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Fentanyl, N-(1-phenethyl-4-piperidyl) propionanilide, was prepared by performing three successive one pot reactions at room temparature.
- Gupta, Pradeep Kumar,Ganesan, Kumaran,Pande, Ambuja,Malhotra, Ramesh Chandra
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p. 452 - 453
(2007/10/03)
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- Concise and versatile syntheses of N-arylalkylpiperidines as potential intermediates for 4-anilidopiperidine analgesics
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N-Arylalkylpiperidones and N-arylalkylspiroepoxypiperidine as potential intermediates for 4-anilidopiperidine analgesics and their structural analogues have been efficiently synthesized from the simple arylalkylamines by two and three step sequences respectively.
- Suh, Young-Ger,Shin, Dong-Yun,Cho, Kyung-Ho,Ryu, Jae-Sang
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p. 239 - 242
(2007/10/03)
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- Structure-activity relationship studies of novel 4-[2-[bis(4- fluorophenyl)methoxy]ethyl]-1-(3-phenylpropyl)piperidine analogs: Synthesis and biological evaluation at the dopamine and serotonin transporter sites
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Several analogs of the potent dopamine (DA) transporter ligand 4-[2- [bis(4-fluorophenyl)-methoxy]ethyl]-1-(3-phenylpropyl)piperidine, 1b, were made and biologically evaluated for their binding at the DA and serotonin (5HT) transporters in rat striatal membranes. Different alkyl chain lengths and substitutions were introduced in these molecules to generate an optimum activity and selectivity for the DA transporter. In general, unsubstituted and fluoro-substituted compounds were the most active and selective for the DA transporter. The compound 4-[2(diphenylmethoxy)ethyl]-1-benzylpiperidine, 9a, showed high potency and was the most selective for the DA transporter (5HT/DA = 49) in this series of compounds. Some of these novel analogs were found to be more selective in binding at the DA transporter than the original GBR 12909 molecule, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperidine.
- Dutta,Xu,Reith
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p. 749 - 756
(2007/10/03)
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- Novel 1,4 substituted piperidine derivatives. Synthesis and correlation of antioxidant activity with structure and lipophilicity
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A series of novel piperidine derivatives was prepared and their lipophilicity was determined (as R(M) values). These compounds as well as two intermediate α-keto-esters were tested for antioxidant activity. It was found that the cysteamine derivatives were efficient antioxidants, i.e. they could inhibit lipid peroxidation, act as hydroxyl radical scavengers and interact with 2,2-diphenyl-1-picrylhydrazyl radicals. This interaction could be attributed to the free SH group and this activity seemed to be favoured by increased lipophilicity. Replacement of SH by NH2 or OH resulted in a decreased antioxidant activity of the compounds. However, the described activities seem not to be connected with any O2- scavenging ability, at least under the experimental conditions applied. Furthermore, cysteamine derivatives seem to induce O2- generation, a phenomenon often observed with thiol compounds. The antioxidant activity of the intermediate α-keto-esters varied and is probably mediated by different mechanisms.
- Alexidis,Rekka,Demopoulos,Kourounakis
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p. 131 - 137
(2007/10/02)
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- New antihistaminic N-heterocyclic 4-piperidinamines. 1. Synthesis and antihistaminic activity of N-(4-piperidinyl)-1H-benzimidazol-2-amines
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The synthesis of a series N-(4-piperidinyl)-1H-benzimidazol-2-amines and the preliminary evaluation of their in vitro and in vivo antihistaminic activity are described. Cyclodesulfurization of (2-aminophenyl) thioureas with mercury(II) oxide resulted in 2-aminobenzimidazole intermediates, which were monoalkylated on the endo-nitrogen atom. After deprotection of the piperideine nitrogen atom with 48% aqueous hydrobromic acid solution, the title compounds were obtained by three different methods, viz. alkylation, reductive amination, or oxirane ring-opening reactions. The in vivo antihistaminic activity was evaluated by the compound 48/80 induced lethality test in rats and histamine-induced lethality test in guinea pigs after oral and/or subcutaneous administration. The duration of action, for a selected number of compounds, was studied in the guinea pig. The phenylethyl derivatives showed the most potent antihistamine properties after oral administration in both animal species.
- Janssens,Torremans,Janssen,Stokbroekx,Luyckx
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p. 1925 - 1933
(2007/10/02)
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