- Preparation method of neuromuscular blocking agent intermediate
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The invention relates to a preparation method of a neuromuscular blocking agent intermediate. The method includes: a compound as shown in formula (II) and a cyclization reagent are allowed to have reaction in a reaction solvent to generate a compound as s
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Paragraph 0037-058
(2018/07/30)
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- Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor
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Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (Ke) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats. (Chemical Equation Presented).
- Perrey, David A.,German, Nadezhda A.,Decker, Ann M.,Thorn, David,Li, Jun-Xu,Gilmour, Brian P.,Thomas, Brian F.,Harris, Danni L.,Runyon, Scott P.,Zhang, Yanan
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p. 599 - 614
(2015/04/27)
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- Molecular structure effects in the asymmetric transfer hydrogenation of functionalized dihydroisoquinolines on (S,S)-[RuCl(η 6-p-cymene) TsDPEN]
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The asymmetric transfer hydrogenation of five dihydroisoquinolines (DHIQs) was studied by NMR spectroscopy. The DHIQs differed by substitution with methoxy groups, which had a significant effect upon the reaction performance in terms of reaction rate and enantioselectivity. The differences are most probably related to the basicity of DHIQs.
- Vaclavik, Jiri,Pechacek, Jan,Vilhanova, Beata,Sot, Petr,Januscak, Jakub,Matousek, Vaclav,Prech, Jan,Bartova, Simona,Kuzma, Marek,Kacer, Petr
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p. 555 - 562
(2013/07/19)
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- Two optimized synthetic pathways toward a chiral precursor of Mivacurium chloride and other skeletal muscle relaxants
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A chiral precursor of Mivacurium chloride, (R)-5′-methoxylaudanosine, was prepared using two different methods. The chiral resolution of racemic 5′-methoxylaudanosine, typically used in industry, was carried out in parallel with a procedure consisting of
- Vilhanová, Beáta,Matou?ek, Václav,Václavík, Ji?í,Syslová, Kamila,P?ech, Jan,Pechá?ek, Jan,?ot, Petr,Janu??ák, Jakub,Toman, Jaromír,Zápal, Jakub,Kuzma, Marek,Ka?er, Petr
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- Synthesis of 8-oxoberbines and related benzolactams by Pd(OAc) 2-catalyzed direct aromatic carbonylation
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A variety of alkoxy-substituted benzolactams with a berbine or yohimbane skeleton were prepared from 1-benzyl-1,2,3,4-tetrahydroisoquinolines or 1-benzyl-1,2,3,4-tetrahydro-β-carbolines by a phosphine-free Pd(II)-catalyzed direct aromatic carbonylation in a Pd(OAc)2-Cu(OAc) 2 catalytic system. The site selectivity was compared with that of the carbonylation with Pd(OAc)2 or Pd(OAc)2·2 PPh3, respectively.
- Miyazawa, Mamoru,Tokuhashi, Takashi,Horibata, Akiyoshi,Nakamura, Takatoshi,Onozaki, Yu,Kurono, Nobuhito,Senboku, Hisanori,Tokuda, Masao,Ohkuma, Takeshi,Orito, Kazuhiko
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- Neuromuscular blocking agents
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Short acting reversible neuromuscular blocking agents of the formula (I) STR1 where B and C is preferably meta or maybe para STR2 where m is 2, 3 or 4 and is preferably 2, R1, R2, R3, R4, R5, R6 and R7 are the same or different and are hydrogen or lower alkoxy of 1 to 4 carbon atoms Y is lower alkyl of 1 to 4 carbon atoms n is 2, 3 or 4, most preferably 3, provided that at least one of R1 to R4 and one of R5 to R7 is lower alkoxy and X is a pharmaceutically acceptable anion. These neuromuscular blocking agents of formula I are useful upon administration to a patient in providing muscular relaxation in the patient during surgery and are normally intravenously administered in a pharmaceutically acceptable carrier.
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- Bis-isoquinolinium compounds, compositions and methods of use
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Intermediate-duration reversible neuromuscular blocking agents of the formula (I) STR1 where B and C are preferably para or may be meta and are each STR2 where W is CH2 or most preferably CH=CH R1, R2, R3 and R
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