- Mustard Carbonate Analogues as Sustainable Reagents for the Aminoalkylation of Phenols
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N,N-dialkyl ethylamine moiety can be found in numerous scaffolds of macromolecules, catalysts, and especially pharmaceuticals. Common synthetic procedures for its incorporation in a substrate relies on the use of a nitrogen mustard gas or on multistep syntheses featuring chlorine hazardous/toxic chemistry. Reported herein is a one-pot synthetic approach for the easy introduction of aminoalkyl chain into different phenolic substrates through dialkyl carbonate (β-aminocarbonate) chemistry. This new direct alcohol substitution avoids the use of chlorine chemistry, and it is efficient on numerous pharmacophore scaffolds with good to quantitative yield. The cytotoxicity via MTT of the β-aminocarbonate, key intermediate of this synthetic approach, was also evaluated and compared with its alcohol precursor.
- Annatelli, Mattia,Trapasso, Giacomo,Salaris, Claudio,Salata, Cristiano,Castellano, Sabrina,Aricò, Fabio
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supporting information
p. 3459 - 3464
(2021/05/24)
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- Compound with dicationic quaternary ammonium salt structure and preparation method and application thereof
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The invention provides a diquaternary ammonium compound, or a crystal form thereof, or a solvate thereof, or a stereoisomer thereof, or an isotope label thereof, or a salt thereof. The structure of the diquaternary ammonium compound is as shown in formula (I). Experiments prove that the compound takes effect quickly after being taken once, can provide a complete muscle relaxation effect for 2-10 minutes, can realize a super-short-acting non-depolarized muscle relaxation effect only by depending on metabolism of an organism, and still shows quick fading of the muscle relaxation effect after being taken for a large dose and continuously. Compared with contrast muscle relaxants cisatracurium and succinylcholine, the compound provided by the invention has the advantages of smaller dosage, faster effect, complete recovery of muscular tension (TOF> 90%) and less time, and has a very good application prospect in preparation of skeletal muscle relaxation drugs which take effect quickly, recover quickly and have small toxic and side effects.
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Paragraph 0097-0100
(2021/05/29)
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- Biquaternary ammonium compound, and preparation method and application thereof
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The invention provides a diquaternary ammonium compound, or a crystal form, or a solvate, or a stereoisomer, or an isotope label or a salt thereof. The structure of the diquaternary ammonium compound is as shown in formula (I). Experiments prove that the compound disclosed by the invention takes effect quickly after being taken once, can provide a complete muscle relaxation effect for 2-10 minutes, can realize a super-short-acting non-depolarized muscle relaxation effect only by depending on metabolism of an organism, and still shows quick fading of the muscle relaxation effect after being taken for a large dose and continuously. Compared with contrast muscle relaxants cisatracurium and succinylcholine, the compound provided by the invention has the advantages of smaller dosage, faster effect, complete recovery of muscular tension (TOF > 90%), and has a very good application prospect in preparation of skeletal muscle relaxation drugs with low dosage, quick response, quick recovery and small toxic and side effects.
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Paragraph 0080-0083
(2021/06/13)
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- Diaminodiphosphine tetradentate ligand and ruthenium complex thereof, and preparation methods and applications of ligand and complex
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The invention discloses a diaminodiphosphine tetradentate ligand and a ruthenium complex thereof, and preparation methods and applications of the ligand and the complex, and provides a ruthenium complex represented by a formula I, wherein L is a diaminodiphosphine tetradentate ligand represented by a formula II, and X and Y are respectively and independently chlorine ion, bromine ion, iodine ion,hydrogen negative ion or BH4. According to the present invention, the ruthenium complex exhibits excellent catalytic activity in the catalytic hydrogenation reactions of ester compounds, has high yield and high chemical selectivity, is compatible with conjugated and non-conjugated carbon-carbon double bond, carbon-carbon triple bond, epoxy, halogen, carbonyl and other functional groups, and hasgreat application prospects.
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Paragraph 0301-0303; 0306
(2019/11/04)
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- Synthesis of novel and functionally selective non-competitive muscarinic antagonists as chemical probes
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Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug–receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non-competitive muscarinic ligands that strongly bind at a secondary receptor site. These compounds were found to be non-competitive antagonists that completely abolished carbachol activation in functional assays. Several of these compounds antagonized functional response to carbachol with great potency at M1 and M4 than at the rest of receptor subtypes.
- Boulos, John F.,Jakubik, Jan,Boulos, John M.,Randakova, Alena,Momirov, Jelena
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- Amino pyrimidine compound and preparation method and application thereof
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The invention relates to an amino pyrimidine compound and a preparation method and application thereof. The amino pyrimidine compound has a structure as shown in a formula I. The formula is shown in the description. The compound is an inhibitor of an epidermal growth factor receptor (EGFR) kinase. The invention further relates to a medicine composition comprising the compound, a preparation methodand application thereof in preparation of anti-tumor medicines.
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Paragraph 0514; 0515; 0516; 0517
(2018/11/22)
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- Novel indanone derivatives as MAO B/H3R dual-targeting ligands for treatment of Parkinson's disease
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The design of multi-targeting ligands was developed in the last decades as an innovative therapeutic concept for Parkinson's disease (PD) and other neurodegenerative disorders. As the monoamine oxidase B (MAO B) and the histamine H3 receptor (H3R) are promising targets for dopaminergic regulation, we synthetized dual-targeting ligands (DTLs) as non-dopaminergic receptor approach for the treatment of PD. Three series of compounds were developed by attaching the H3R pharmacophore to indanone-related MAO B motifs, leading to development of MAO B/H3R DTLs. Among synthesized indanone DTLs, compounds bearing the 2-benzylidene-1-indanone core structure showed MAO B preferring inhibition capabilities along with nanomolar hH3R affinity. Substitution of C5 and C6 position of the 2-benzylidene-1-indanones with lipophilic substituents revealed three promising candidates exhibiting inhibitory potencies for MAO B with IC50 values ranging from 1931 nM to 276 nM and high affinities at hH3R (Ki 50 = 276 nM, hH3R Ki = 6.5 nM) showed highest preference for MAO B over MAO A (SI > 36). Interestingly, IC50 determinations after preincubation of enzyme and DTLs revealed also nanomolar MAO B potency for 3e (MAO B IC50 = 232 nM), a structural isomer of 3f, and 3d (MAO B IC50 = 541 nM), suggesting time-dependent inhibition modes. Reversibility of inhibition for all three compounds were confirmed by dilution studies in excess of substrate. Thus, indanone-substituted derivatives are promising lead structures for the design of MAO B/hH3R DTLs as novel therapeutic approach of PD therapy.
- Affini, Anna,Hagenow, Stefanie,Zivkovic, Aleksandra,Marco-Contelles, Jose,Stark, Holger
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p. 487 - 497
(2018/02/28)
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- Catalytic Ester Metathesis Reaction and Its Application to Transfer Hydrogenation of Esters
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We report a Ru-complex-catalyzed ester metathesis reaction where an unsymmetrical ester such as ethyl hexanoate can be transformed to a mixture of starting material, hexyl ethanoate, ethyl acetate, and hexyl hexanoate in equal proportions, as expected from a classical metathesis reaction with 0.2 mol % catalyst. A 20× excess of low boiling alcohol, such as ethanol, allows for the transfer of an acyl moiety to the sacrificial low boiling ethyl acetate product, while significantly increasing the functional group tolerance and substrate scope; yields of alcohols can reach 90%, which represents an attractive alternative to current high H2 pressure hydrogenation protocols for Ru-based ester reduction chemistry. Both reactions have not been reported previously in the field of Ru-catalyzed transformations of the ester functionality.
- Dubey, Abhishek,Khaskin, Eugene
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p. 3998 - 4002
(2016/07/06)
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- BITOPIC MUSCARINIC AGONISTS AND ANTAGONISTS AND METHODS OF SYNTHESIS AND USE THEREOF
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Compositions for treating a condition associated with activity of a muscarinic receptor (e.g., one or more of M1, M2, M3, M4, M5) and for anesthetizing a subject include a bitopic muscarinic antagonist or agonist. A bitopic muscarinic antagonist named JB-D4 was discovered. This bitopic ligand and its structural analogs, as well as bitopic muscarinic agonists, may be used as neuromuscular blocking agents (e.g., for use in compositions for anesthetizing a subject) and for the treatment of central nervous system disorders (e.g., Parkinson's disease, Schizophrenia, etc.), Overactive Bladder Syndrome, Chronic Obstructive Pulmonary Disease, asthma, and many other diseases associated with the activation or inhibition of M1-M5 acetylcholine receptors.
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Paragraph 0064; 0074
(2014/02/15)
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- Catalytic hydrogenation of esters. Development of an efficient catalyst and processes for synthesising (R)-1,2-propanediol and 2-(l-Menthoxy)ethanol
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A ruthenium catalyst for the reduction of esters by hydrogenation has been developed. Processes for the hydrogenation of esters have also been developed for (R)-1,2-propanediol and 2-(l-menthoxy)ethanol. The catalyst shows good catalytic activity for the hydrogenation of esters in methanol. Methyl lactate was reduced at 30 °C and gave turnover numbers (TON) up to 4000. The optical purity of the (R)-1,2-propanediol made by the hydrogenation of methyl (R)-lactate was higher than that via the asymmetric hydrogenation of hydroxyacetone. A hydrogenation process to replace the lithium aluminum hydride (LAH) reduction used in the production of 2-(l-menthoxy)ethanol was developed.
- Kuriyama, Wataru,Matsumoto, Takaji,Ogata, Osamu,Ino, Yasunori,Aoki, Kunimori,Tanaka, Shigeru,Ishida, Kenya,Kobayashi, Tohru,Sayo, Noboru,Saito, Takao
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experimental part
p. 166 - 171
(2012/05/20)
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- Novel antagonists of serotonin-4 receptors: Synthesis and biological evaluation of pyrrolothienopyrazines
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Based on the definition of a 5-HT4 receptor antagonist pharmacophore, a series of pyrrolo[1,2-a]thieno[3,2-e] and pyrrolo[1,2-a]thieno[2,3-e] pyrazine derivatives were designed, prepared, and evaluated to determine the properties necessary for high-affinity binding to 5-HT4 receptors. The compounds were synthesized by substituting the chlorine atom of the pyrazine ring with various N-alkyl-4-piperidinylmethanolates. They were evaluated in binding assays with [3H]GR113808 (1) as the 5-HT4 receptor radioligand. The affinity values (Ki or inhibition percentages) were affected by both the substituent on the aromatic ring and the substituent on the lateral piperidine chain. A methyl group on the tricyclic ring produced a marked increase in affinity while an N-propyl or N-butyl group gave compounds with nanomolar affinities. Among the most potent ligands, 34d was selected for further pharmacological studies and evaluated in vivo. This compound acts as an antagonist/weak partial agonist in COS-7 cells stably expressing the 5-HT4(a) receptor and is of great interest as a peripheral antinociceptive agent.
- Lemaitre, Stephane,Lepailleur, Alban,Bureau, Ronan,Butt-Gueulle, Sabrina,Lelong-Boulouard, Veronique,Duchatelle, Pascal,Boulouard, Michel,Dumuis, Aline,Daveu, Cyril,Lezoualc'h, Frank,Pfeiffer, Bruno,Dauphin, Francois,Rault, Sylvain
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scheme or table
p. 2607 - 2622
(2009/09/06)
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- TETRAHYDRONAPHTHYRIDINES AND AZA DERIVATIVES THEREOF AS HISTAMINE H3 RECEPTOR ANTAGONISTS
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The invention relates to compounds of formula (I), wherein X1a, X1 to X5, Ra, Rb, n and R have the meaning as cited in the description and the claims. Said compounds are useful as Histamine H3 receptor antagonists. The invention also relates to pharmaceutical compositions, the preparation of such compounds as well as the production and use as medicament.
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Page/Page column 71
(2009/10/30)
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- A study of 2-piperidino-1-ethanol and its derivatives as antimicrobial additives to oils
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Some derivatives of 1-hydroxy-2-pyperidinoethane were studied as antimicrobial additives to lubricant oils.
- Gamzaeva,Mamedova, P. Sh.,Allakhverdieva,Velieva, G. Kh.,Akhundova,Allakhverdiev
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experimental part
p. 1577 - 1581
(2011/06/20)
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- Dialkylamino and nitrogen heterocyclic analogues of hexadecylphosphocholine and cetyltrimetylammonium bromide: Effect of phosphate group and environment of the ammonium cation on their biological activity
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A series of dialkylamino and nitrogen heterocyclic analogues of hexadecylphosphocholine and cetyltrimethylammonium bromide have been synthesized. The prepared compounds exhibit significant cytotoxic, antifungal and antiprotozoal activities. Alkylphosphocholines possess higher antifungal activity against Candida albicans in comparison with quaternary ammonium compounds. However, quaternary ammonium compounds exhibit significant higher activity against human tumor cells and Acanthamoeba lugdunensis compared to alkylphosphocholines. In addition, their haemolytic toxicity has been investigated. The relationship between structure and biological activity of the tested compounds is discussed.
- Lukac, Milos,Mojzis, Jan,Mojzisova, Gabriela,Mrva, Martin,Ondriska, Frantisek,Valentova, Jindra,Lacko, Ivan,Bukovsky, Marian,Devinsky, Ferdinand,Karlovska, Janka
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scheme or table
p. 4970 - 4977
(2010/02/27)
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- A new one-pot, four-component synthesis of 1,2-amino alcohols: TiCl 3/t-BuOOH-mediated radical hydroxymethylation of imines
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(Chemical Equation Presented) An amine, an aldehyde, and methanol can be readily assembled in one pot under very mild conditions through a free-radical multicomponent reaction by using an aqueous acidic TiCl3/t-BuOOH system to afford 1,2-amino alcohols in fair to excellent yields.
- Clerici, Angelo,Ghilardi, Alessandra,Pastori, Nadia,Punta, Carlo,Porta, Ombretta
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supporting information; experimental part
p. 5063 - 5066
(2009/05/31)
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- 2,3,4,5-TETRAHYDRO-1H-1,5-BENZODIAZEPINE DERIVATIVE AND MEDICINAL COMPOSITION
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The present invention has its object to provide a 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented with the Formula (1) , or the pharmaceutically acceptable salt, which is effective as a therapeutic and prophylactic agent for diabetes, diabetic nephropathy, or glomerulosclerosis.
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- Electrooxidative cyclization of hydroquinolyl alcohols, hydroquinolylamines, and dimethyl aminomalonates
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Several hydroquinolyl alcohols and amines were electrochemically oxidized in methanol in the presence of sodium methoxide and potassium iodide to afford the corresponding intramolecular cyclization products. Furthermore, several amino malonates were electrochemically oxidized to yield the corresponding heterocyclic compounds through an intramolecular carbon-carbon bond formation in the presence of sodium cyanide in methanol. CSIRO 2007.
- Okimoto, Mitsuhiro,Yoshida, Takashi,Hoshi, Masayuki,Hattori, Kazuyuki,Komata, Masashi,Numata, Kaori,Tomozawa, Kenta
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p. 236 - 242
(2008/02/11)
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- Effect of Topologically Controlled Coulombic Interactions on the Dynamic Behavior of Photoexcited Nitrophenyl Alkyl Ethers in the Presence of Tertiary Amines with Limited Motion Freedom
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Time-resolved electronic absorption spectroscopy has been successfully applied to clarify the mechanism of the "abnormal" photochemical cleavage of 4-nitrophenyl piperidinoaikyl ethers induced by controlled Coulombic disturbance of the "normal" electronic distribution of the radical anion intermediate. Thus, photolysis of 1-piperidino-2-(2-methoxy-4-nitrophenoxy)ethane (a system with an amine with limited freedom of motion) in acetonitrile leads to C-O bond photocleavage in a relatively slow process (k ≈ 4 × 105 s-1) from intermediate species that show radical-ion pair behavior. Systems with higher freedom of motion of the amine moiety, such as 1-piperidino-5-(2-methoxy-4-nitrophenoxy)pentane or 4-nitroveratrole 4- triethylamine, show the intermediate radicalion pairs mainly evolving to reduction products, probably a result of intermediates with geometries not allowed for the system with limited freedom of motion of the amine.
- Gonzalez-Blanco, Roberto,Bourdelande, Jose L.,Marquet, Jordi
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p. 6903 - 6910
(2007/10/03)
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- Quinolizinone type compounds
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Antibacterial compounds having the formula STR1 and the pharmaceutically acceptable salts, esters and amides thereof, preferred examples of which include those compounds wherein A is =CR6 --; R1 is cycloalkyl of from three to eight carbon atoms or substituted phenyl; R2 is selected from the group consisting of STR2 R3 is halogen; R4 is hydrogen, loweralkyl, a pharmaceutically acceptable cation, or a prodrug ester group; R5 is hydrogen, loweralkyl, halo(loweralkyl), or --NR13 R14 ; and R6 is halogen, loweralkyl, halo(loweralkyl), hydroxy-substituted loweralkyl, loweralkoxy(loweralkyl), loweralkoxy, or amino(loweralkyl), as well as pharmaceutical compositions containing such compounds and the use of the same in the treatment of bacterial infections.
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- Intramolecular Quenching of Iminium Ions Generated by Photooxidation of Aminoalcohols with Ketones. A New Synthesis of Oxazines and Oxazoles
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The irradiation of tertiary amines in the presence of ketones leads to a regioselective and stereoselective formation of iminium salts which then react to afford the corresponding oxazines or oxazoles. - Key words : Ammoniumyl ions, iminium ions, electron transfer, amines, ketones, tetrahydrooxazine tetrahydrooxazoles.
- Cossy, Janine,Guha, Madhumita
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p. 1715 - 1718
(2007/10/02)
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- KINETICS OF ALKALINE HYDROLYSIS AND CORRELETION STUDIES OF m- AND p-SUBSTITUTED PIPERIDINOETHYL PHENYLCARBAMATES
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Kinetics of alkaline hydrolysis have been studied with a series of 15 m- and p-substituted piperidinoethyl phenylcarbamates.The rate constants have been determined at 70, 60, 50, and 40 deg C and the activation parameters have been calculated.These values have been correlated with the substituent constants ?, , , F, R, ?.Validity of the Hammett equation and the Swain-Lupton equation has been confirmed in the series studied and for the p-derivatives, respectively.The lipophilicity parameter ? does not correlate with the values found.
- Stankovicova, Maria,Cizmarik, Jozef
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p. 1846 - 1853
(2007/10/02)
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- Omega-quaternary ammonium alkyl esters and thioesters of acidic nonsteroidal antiinflammatory drugs
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Quaternary ammonium alkyl esters and thioesters of acidic nonsteroidal anti-inflammatory drugs (NSAIDs) are disclosed. These esters and thioesters display the anti--inflammatory profile of the parent NSAIDs with greatly reduced gastrointestinal irritancy, providing a more favorable separation of therapeutic activity and toxicological side effects than the parent NSAIDs.
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- N-Alkylation d'amines en catalyse homogene. Synthese de mono- et de diamines cycliques
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Ruthenium compounds are appropriate catalysts in the N-alkylation of amines.The synthesis of N-alkylated cyclic amines from a cyclic amine and an alcohol or via the condensation between a diol and a primary amine are described.The reaction with cyclic amines is highly selective, especially in the presence of a phosphine, making it a high yielding preparative procedure.The catalytic condensation between cyclic amines and diols yields either an aminoalcohol (A) or a bicyclic diamine (B).The temperature, the presence of phosphine, and the ratio of amine to diol are decisive in directing the reaction toward A or B.The proposed mechanism involves the dehydrogenation of the alcohol followed by attack of the amine on the aldehyde intermediate.
- Bitsi, G.,Schleiffer, E.,Antoni, F.,Jenner, G.
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p. 343 - 352
(2007/10/02)
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