- Synthesis and Stereochemistry of Some 3-Azabicyclo[3.3.1]nonane Derivatives
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Michael reactions of methyl (ethyl) 1-benzyl-4-oxopiperidine-3- carboxylates with a number of α,β-unsaturated carbonyl compounds result in formation of 6- and 6,8-substituted methyl (ethyl) 3-benzyl-9-oxo-3-azabicyclo[3.3.1]nonane-1-carboxylates. Stereochemical aspects of these reactions were studied, and some further transformations of the products were performed.
- Vafina,Yakhina,Khakimova,Spirikhin,Galin,Yunusov
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- Asymmetric synthetic method for Capromorelin chiral intermediate
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The invention discloses an asymmetric synthetic method for a Capromorelin chiral intermediate. The method comprises the following steps: enabling 3-ethoxycarbonyl-4-piperidone hydrochloride to react with benzyl bromide in the action of alkalinity, under the action of a cinchona alkaloid phase transfer catalyst, performing an asymmetric alkylation reaction on an obtained compound of 1-benzyl-4-oxopiperidine-3-carboxylic acid ethyl ester and the benzyl bromide, to obtain 1,3-dibenzyl-4-oxopiperidine-3-ethyl formate, through a two-step reaction of removing a Bn protecting group and loading a Bocprotecting group, under a heating condition, to obtain a compound of 3alphaR-benzyl-1-(tert-butyl)oxocarbonyl-2-methyl-4,5,6,7-tetrahydro-2H-pyrazole[4,3-c]pyridine-3-(3H)-ketone, wherein the compoundis an important intermediate of Capromorelin. The method is cheap and easily obtained in raw material, lower in cost, simple and convenient in operation, moderate in reaction condition, and capable of avoiding using chiral resolution or an enzymatic catalysis method to construct a chiral quaternary carbon center, and using cinchona alkaloid as the phase transfer catalyst, wherein a yield is apparently higher than that of a chiral product obtained by using a resolution method, and environmentally friendly without danger.
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Paragraph 0025-0031
(2019/02/25)
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- AZA-DIHYDRO-ACRIDONE DERIVATIVES
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Aza-dihydro-acridone derivatives of formula I, wherein the meaning of R1, R'1, R2 and R3 is that specified in the description, to be used as T cells proliferation inhibitors.
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Paragraph 0245; 0246
(2018/10/19)
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- ANTI-PULMONARY TUBERCULOSIS NITROIMIDAZOLE DERIVATIVE
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Disclosed is a substituted nitroimidazole derivative, which is mainly used for treating related diseases caused by mycobacterial infections, such as Mycobacterium tuberculosis, especially being suitable for diseases caused by resistant Mycobacterium tuberculosis.
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Paragraph 0429-0431
(2017/12/31)
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- New P2X3 receptor antagonists. Part 2: Identification and SAR of quinazolinones
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Numerous potent P2X3 antagonists have been discovered and the therapeutic potential of P2X3 antagonism already comprises proof-of-concept data obtained in clinical trials with the most advanced compound. We have lately reported the discovery and optimization of thia-triaza-tricycle compounds with potent P2X3 antagonistic properties. This Letter describes the SAR of a back-up series containing a 4-oxo-quinazoline central ring. The discovery of the highly potent compounds 51 is presented.
- Szántó, Gábor,Makó, Attila,Vágó, István,Hergert, Tamás,Bata, Imre,Farkas, Bence,Kolok, Sándor,Vastag, Mónika
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p. 3905 - 3912
(2016/08/01)
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- Synthesis and antiproliferative activity of cyclic arylidene ketones: a direct comparison of monobenzylidene and dibenzylidene derivatives
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Abstract To give further insight into the influence of the structural modifications of enones and dienones on their antiproliferative properties, 25 derivatives of enones: (E)-2-benzylidene-1-cyclohexanones, (E)-2-benzylidene-1-tetralones, (E)-2-benzylidene-1-indanone, and dienones: (E,E)-2,5- or 2,6-dibenzylidene-1-cyclanones, (E,E)-3,5-dibenzylidene-4-piperidones were synthesized using a newly developed "one-pot" synthetic method. Due to the fact that all of them have the same aryl substituents (phenyl or 4-chlorophenyl) in the arylidene moiety, it is possible to compare the relevant contribution of the single-point structural modifications (type of ring or N-substitution) on their potency on the basis of their IC 50 values. Their antiproliferative activity was evaluated against the following four human adherent cancer cell lines: HeLa, A431, A2780, and MCF7. The cytotoxicity screen has revealed that the dibenzylidene dienones in general dominate the monobenzylidene enones in this respect. The nitrogen-containing heterocyclic dienones at the same time displayed higher inhibitory properties toward these human carcinoma cell lines compared with their homocyclic dienone analogs. One of the eight newly prepared 4-piperidone derivatives, N-(γ-oxobutyl)-(E,E)-3,5-bis(p-chlorobenzylidene)-4-piperidone is as potent a cell growth inhibitor (IC 50 of 0.438-1.409 μM) as the N-methyl-(E,E)-3,5-bis(p-chlorobenzylidene)-4-piperidone (IC 50 of 0.447-1.048 μM), one of the most active among the previously described compounds in this series. Catalytic hydrogen-transfer isomerization of compounds with two exocyclic benzylidene double bonds to derivatives with endocyclic double bonds results in the complete loss of antiproliferative activity. The structural modifications and 50 % inhibitory concentration (IC 50) values resulted in correlations which can promote the design of more potent derivatives of the 4-piperidone dienones.
- Huber, Imre,Zupk, Istvn,Kovcs, Ida J.,Minorics, Renta,Gulys-Fekete, Gergely,Masz, Gbor,Perjsi, Pl
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p. 973 - 981
(2015/02/19)
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- KINASE INHIBITORS
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The present invention relates to compounds of formulae I and II wherein the variables are as defined herein. These compounds are capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.
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Paragraph 0422
(2013/09/26)
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- METHOD OF TREATING CONDITIIONS WITH KINASE INHIBITORS
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The present invention relates to a method of treating ophthalmic diseases and conditions, e.g. diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, etc., in a subject comprising administering to said subject a therapeutically effective amount of at least one compound of formula I or a prodrug, pharmaceutically acceptable salt, racemic mixtures or enantiomers of said compound. The compounds of formula I are capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.
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Paragraph 0426-0427
(2013/09/26)
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- Synthesis of 7-benzyl-5-(piperidin-1-yl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-1-ylamine and its analogs as bombesin receptor subtype-3 agonists
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The original structure of a high-throughput screening hit obtained from an external vendor was revised based on multiple NMR studies. The active compound was re-synthesized via a novel route and its structure and biological activity as a BRS-3 agonist were unambiguously confirmed. Multi-gram quantities of the hit were prepared for pharmacokinetic and efficacy studies. The synthetic strategy allowed for the preparation of multiple analogs for SAR exploration.
- Guo, Cheng,Guzzo, Peter R.,Hadden, Mark,Sargent, Bruce J.,Yet, Larry,Kan, Yanqing,Palyha, Oksana,Kelly, Theresa M.,Guan, Xiaoming,Rosko, Kim,Gagen, Karen,Metzger, Joseph M.,Dragovic, Jasminka,Lyons, Kathryn,Lin, Linus S.,Nargund, Ravi P.
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scheme or table
p. 2785 - 2789
(2010/07/08)
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- SULFONAMIDES AND PHARMACEUTICAL COMPOSITIONS THEREOF
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The invention is directed to a class of compounds, including the pharmaceutically acceptable salts of the compounds, having the structure of formula (I), as defined in the specification. The invention is also directed to compositions containing the compounds of formula (I).
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Page/Page column 65-66
(2008/12/04)
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- Synthesis and in-vitro activity of new 1β-methylcarbapenem derivatives as antibacterial agents
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The synthesis of a new series of 1β-methylcarbapenems having pyrrolidine and piperidine moieties is described. Their in-vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the pyrrolidine ring was investigated. A particular compound III b having an oxime-pyrrolidine moiety showed the most potent antibacterial activity.
- Jung, Myung-Ho,Joon, Hee Hong,Cho, Jung-Hyuck,Oh, Chang-Hyun
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scheme or table
p. 780 - 786
(2009/04/07)
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- Clay catalyzed chemoselective Michael type addition of aliphatic amines to α,β-ethylenic compounds
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Application of acidic clays as heterogeneous catalysts for the Michael type addition reaction of aliphatic amines to α,β-ethylenic compounds is presented. Aromatic amines do not participate in this transformation.
- Shaikh, Nadim S.,Deshpande, Vishnu H.,Bedekar, Ashutosh V.
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p. 9045 - 9048
(2007/10/03)
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- Titanium mediated cyclization of N-substituted di(β-carbethoxyethyl)amines: Preparation of 1-substituted-3-carbethoxy-4-piperidones
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Dieckmann cyclisation of N-substituted di(β-carbethoxyethyl)amines with titanium tetrachloride in DCM in the presence of triethylamine leads to the formation of 3-carbethoxy-4-piperidones.
- Deshmukh,Sampath Kumar,Rama Rao
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p. 177 - 182
(2007/10/02)
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