3040-44-6Relevant articles and documents
Compound with dicationic quaternary ammonium salt structure and preparation method and application thereof
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Paragraph 0097-0100, (2021/05/29)
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.
Biquaternary ammonium compound, and preparation method and application thereof
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Paragraph 0080-0083, (2021/06/13)
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.
Mustard Carbonate Analogues as Sustainable Reagents for the Aminoalkylation of Phenols
Annatelli, Mattia,Trapasso, Giacomo,Salaris, Claudio,Salata, Cristiano,Castellano, Sabrina,Aricò, Fabio
supporting information, p. 3459 - 3464 (2021/05/24)
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.
Diaminodiphosphine tetradentate ligand and ruthenium complex thereof, and preparation methods and applications of ligand and complex
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Paragraph 0301-0303; 0306, (2019/11/04)
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.
Novel indanone derivatives as MAO B/H3R dual-targeting ligands for treatment of Parkinson's disease
Affini, Anna,Hagenow, Stefanie,Zivkovic, Aleksandra,Marco-Contelles, Jose,Stark, Holger
, p. 487 - 497 (2018/02/28)
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.
Synthesis of novel and functionally selective non-competitive muscarinic antagonists as chemical probes
Boulos, John F.,Jakubik, Jan,Boulos, John M.,Randakova, Alena,Momirov, Jelena
, p. 93 - 104 (2017/10/06)
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.
Amino pyrimidine compound and preparation method and application thereof
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Paragraph 0514; 0515; 0516; 0517, (2018/11/22)
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.
Catalytic Ester Metathesis Reaction and Its Application to Transfer Hydrogenation of Esters
Dubey, Abhishek,Khaskin, Eugene
, p. 3998 - 4002 (2016/07/06)
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.
BITOPIC MUSCARINIC AGONISTS AND ANTAGONISTS AND METHODS OF SYNTHESIS AND USE THEREOF
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Paragraph 0064; 0074, (2014/02/15)
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.
Catalytic hydrogenation of esters. Development of an efficient catalyst and processes for synthesising (R)-1,2-propanediol and 2-(l-Menthoxy)ethanol
Kuriyama, Wataru,Matsumoto, Takaji,Ogata, Osamu,Ino, Yasunori,Aoki, Kunimori,Tanaka, Shigeru,Ishida, Kenya,Kobayashi, Tohru,Sayo, Noboru,Saito, Takao
experimental part, p. 166 - 171 (2012/05/20)
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.
