180468-42-2Relevant academic research and scientific papers
Study on synthesis and biological effects of a series of 3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives
Fu, Zhi-Yang,Jin, Qing-Hao,Xia, Ya-Nan,Jiang, Hai-Ying,Guan, Li-Ping
, p. 52 - 61 (2019)
In this paper, we have reported the synthesis and biological evaluation of nineteen (S)-N-substituted-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives as novel candidate antidepressant and anticonvulsant agents. Compounds 2h, 2k, 2r, and 2s exhibited better potent antidepressant activity and displayed the antidepressant effects in a dose-dependent manner from 10 to 30 mg/kg in the FST and TST. And, we found that the best antidepressant effect of compounds 2r and 2s are likely mediated by an increase in central nervous system 5-HT and NE. In addition, compounds 2r and 2s also exhibited the anticonvulsant activity against MES-induced seizures. Thus, compounds 2r and 2s may be a useful antidepressant adjunct therapy for treating depression in patients with epilepsy. In addition, compounds 2r and 2s showed the anti-inflammatory activity and the excellent analgesic activity. Several scholars have postulated the anti-inflammatory and analgesic effects of antidepressant drugs, suggesting that they may be possess a similar mechanism of action.
Synthesis, potential anti-inflammatory and analgesic activities study of (S)-N-substituted-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamides
Guan, Li-Ping,Xia, Ya-Nan,Jin, Qing-Hao,Liu, Bing-Yu,Wang, Si-Hong
, p. 3378 - 3381 (2017)
A series of (S)-N-substitued-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives were designed, synthesized and evaluated for their anti-inflammatory and analgesic effects in vivo. Among the synthesized compounds 2a and 2n showed the best anti-inflammatory activity (inhibition rate: 95% and 92.7%, respectively) and analgesic effect (inhibition rate: 100% and 100%, respectively), which was greater than that or nearly equivalent to that of indomethacin. Compounds 2a and 2n were selected to test their inhibitory effects against ovine COX-1 and COX-2 using the cyclooxygenase inhibition assay in vitro. Compounds 2a and 2n are weak inhibitors of COX-1 isozyme but displayed moderate COX-2 isozyme inhibitory effects (IC50?=?0.47?μM and 1.63?μM, respectively) and COX-2 selectivity indexes (SI?=?11.5 and 4.8). Furthermore, compound 2a was more inhibitors of COX-2 isozyme active than the reference drug celecoxib.
Asymmetric synthesis method for preparation of solifenacin
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, (2018/07/10)
The invention relates to an asymmetric synthesis method for preparation of solifenacin and specifically, discloses a preparation method of solifenacin. The method comprises that ortho-substituted aldehyde as a raw material undergoes a reaction under catalysis of rhodium and a chiral sulfoxide-olefin ligand to produce a key intermediate for high enantioselective addition, and the intermediate is further functionalized and cyclized to form solifenacin. The method is easy to operate, needs mild reaction conditions and has high efficiency and high selectivity.
Preparation method and application of solifenacin derivative
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Paragraph 0015; 0016; 0019; 0022, (2018/09/08)
The invention relates to a preparation method of a solifenacin derivative. The preparation method includes the steps of: (a) using a solifenacin EP impurity A shown as formula 1, adding chlorine dioxide shown as formula 2 in the presence of potassium carb
Highly Enantioselective Arylation of N,N-Dimethylsulfamoyl-Protected Aldimines Using Simple Sulfur-Olefin Ligands: Access to Solifenacin and (S)-(+)-Cryptostyline II
Jiang, Tao,Chen, Wen-Wen,Xu, Ming-Hua
, p. 2138 - 2141 (2017/04/27)
With the use of a simple sulfur-olefin ligand, a highly enantioselective rhodium-catalyzed addition of arylboroxines to N,N-dimethylsulfamoyl-protected aldimines has been achieved, allowing access to a broad range of chiral diarylmethylamines in high yields (up to 98%) with uniformly excellent enantioselectivities (up to 99% ee). This catalyst system is also applicable to the arylation of N-tosyl arylimines. By utilizing this method, some biologically active molecules possessing a chiral 1-aryl-1,2,3,4-tetrahydroisoquinoline core such as Solifenacin and (S)-(+)-Cryptostyline II are facilely constructed.
A process for the preparation of new thorley that succinic acid
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Paragraph 0053, (2016/10/07)
The invention relates to a method for preparing a solifenacin succinate ((3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate succinate). The method comprises the following steps: 1) preparing a compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline carboxylic acid ethyl ester of formula III from a compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline, serving as a raw material, of formula IV; 2) synthesizing a compound (3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate of formula II in an ionic liquid by using the compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline carboxylic acid ethyl ester of formula III; and 3) salifying the compound (3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate of formula II in an organic solvent to obtain the compound solifenacin succinate ((3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate succinate) of formula I. The preparation method has the advantages that the process is simple, the method is suitable for industrialized production, the yield of the product is high and the purity of the product is high.
PROCESS FOR PREPARING (1S)-1-PHENYL-3,4-DIHYDRO-2(1H)-ISOQUINOLINE-CARBOXYLATE
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Paragraph 0034, (2015/09/22)
A process for preparation of (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline-carboxylate (Formula I), comprising reacting (1S)-1-phenyl-3,4-dihydro-2(1H)isoquinoline (Formula II) with carbon dioxide and an alkylating agent R-LG in the presence of a base to obtain the compound of Formula I in an organic solvent. In Formula I and II, R is an alkyl or a substituted alkyl; LG is a leaving group.
Stereoselective Total Syntheses of Solifenacin and N -Acetyl-1-(4-chloro-phenyl)-6,7-dimethoxytetrahydroisoquinoline
Babu, R. Anji,Reddy, N. Siva Senkar,Reddy, B. Jagan Mohan,Reddy, B. V. Subba
, p. 2794 - 2798 (2015/11/02)
A highly stereoselective synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinoline drugs such as solefinacin (muscarinic acetylcholine receptor antagonist) and N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxytetrahydroisoquinoline (AMPA receptor antagonist) has been accomplished using (R)-tert-butanesulfinamide as a chiral source. Chiral tetrahydroisoquinolines have been prepared through the aryl Grignard addition to chiral N-sulfinylimines followed by haloamide cyclization.
An improved process for the preparation of highly pure solifenacin succinate via resolution through diastereomeric crystallisation
Trinadhachari, Ganala Naga,Kamat, Anand Gopalkrishna,Venkata Balaji, Boddu,Prabahar, Koilpillai Joseph,Naidu, Kolukuluru Mohan,Babu, Korupolu Raghu,Sanasi, Paul Douglas
, p. 934 - 940 (2014/10/15)
An improved process for the preparation of solifenacin succinate (1) involving resolution through diastereomeric crystallization is described. (1S)-IQL derivative (5) is esterified to form (1S)-ethoxycarbonyl IQL derivative (6) which is condensed with (RS)-3-quinuclidinol (7) to form a solifenacin diastereomeric mixture (8); this is subjected to resolution through diastereomeric crystallization to produce solifenacin succinate (1), which is used for the treatment of an overactive bladder.
Enantioselective iridium-catalyzed hydrogenation of 1- and 3-substituted isoquinolinium salts
Ye, Zhi-Shi,Guo, Ran-Ning,Cai, Xian-Feng,Chen, Mu-Wang,Shi, Lei,Zhou, Yong-Gui
supporting information, p. 3685 - 3689 (2013/04/24)
Asymmetric hydrogenation: The title reaction provides an efficient and rapid access to chiral 1- and 3-substituted 1,2,3,4-tetrahydroisoquinolines with excellent enantioselectivity (see scheme; L=ligand). A preliminary mechanistic study indicates that the 1,2-hydride addition might be the initial step in the reaction. The method has been used in the synthesis of urinary antispasmodic drug (+)-solifenacin. Copyright
