138908-56-2

New tetrahydroisoquinolines were synthesized by the Pictet-Spengler reaction. Influence of a wide range of aryl and heteroaryl aldehydes, was investigated in the cyclization step with 3,4-dimethoxyphenylethylamine 1, L-DOPA 2 and L-3,4-dimethoxyphenylalan

WOBE437 ((2E,4E)-N-(3,4-dimethoxyphenethyl)dodeca-2,4-dienamide, 1) is a natural product-derived, highly potent inhibitor of endocannabinoid reuptake. In this study, we synthesized almost 80 analogues of 1 with different types of modifications in the dodecadienoyl domain as well as the dimethoxyphenylethyl head group, and we investigated their effects on anandamide uptake into U937 cells. Intriguingly, none of these analogues was a more potent inhibitor of anandamide uptake than WOBE437 (1). At the same time, a number of WOBE437 variants exhibited potencies in the sub-100 nM range, with high selectivity over inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase; two compounds were virtually equipotent with 1. Interestingly, profound activity differences were observed between analogues in which either of the two methoxy substituents in the head group had been replaced by the same bulkier alkoxy group. Some of the compounds described here could be interesting departure points for the development of potent endocannabinoid uptake inhibitors with more drug-like properties.

The invention discloses a polyphenol compound containing tetrahydropapaverine-3-methyl carboxylate, a preparation method and applications thereof, wherein the polyphenol compound has a structure represented by a formula I, and R is hydrogen, halogen, C1-8 alkyl, C1-8 cycloalkyl, C1-8 halogenated alkyl, C1-8 alkoxy, C1-8 halogenated alkoxy, C2-4 alkenyl, phenyl, halogenated phenyl, nitrophenyl, C1-4 alkyl substituted phenyl, C1-4 halogenated alkyl substituted phenyl, naphthalene or acylamino. According to the invention, the polyphenol compound is novel in structure and generally has relativelygood inhibitory activity on influenza A virus H1N1, and the inhibitory effect of most compounds is superior to the inhibitory effect of a positive control Perimivir, so that the results show that thecompound has obvious inhibiting effect on influenza A virus, can be prepared into anti-influenza A virus medicine to be applied, has good application prospects in prevention and treatment of influenzavirus infection, and expands the application of tetrahydropapaverine structures as anti-influenza virus medicine.

The invention belongs to the field of pharmacology, and relates to aza (oxa)-cyclopentane-2- ketone (thione) compounds shown in the formula I, medicine compositions thereof, a preparation method, applications in preparation of medicines treating diabetes and glucolipid metabolism, and especially applications in preparation of medicines treating II-type diabetes.

An Au(I)-catalysed intramolecular hydroarylation of an enantiopure allenamide has been achieved and has given access to a key α-vinyl- substititued tetrahydroisoquinoline. Additionally this has been accomplished in very high yield and high diastereoselectivity. Georg Thieme Verlag Stuttgart · New York.

A new organogelator with unique structural feature of a cyclic β-aminoalcohol is presented as the first example of gelation by aminoalcohol through hydrogen-bonding between hydroxy and amine.

(±)-3,4-Methylenedioxymethamphetamine (MDMA, also known as "ecstasy") is a chiral drug that is essentially metabolized in humans through O-demethylenation into 3,4-dihydroxymethamphetamine (HHMA). There has recently been a resurgence of interest in the po

Synthetic investigations of 1,3-dichloro-5,6-dicyanobenzoquinone-mediated benzylic oxidation is reported for the synthesis of natural alkaloid analogues. Extensive explorations of the oxidative nucleophilic substitution of the benzylic position of β-phenylethylamine derivatives and the synthesis of functionalized tetrahydroisoquinolines of ecteinascidin 743 precursors have been carried out. Starting from L-DOPA, a tunable oxazolidinone group was installed under oxidative benzylic conditions. This derivative 13 was submitted to benzylic oxidation reactions using a wide range of carboxylic acids and subsequent chemical transformations of these compounds were attempted. Moreover, an efficient synthesis of an aromatic ketone derivative 20 was achieved and gave rise to tetrahydroisoquinoline 24 through a direct Pictet-Spengler cyclisation reaction. Subsequently, 24 was transformed into functionahzed α-amino alcohols 31a and 31b, precursors of ecteinascidin 743 analogues. In addition, in order to assess the viability of our synthetic strategy, the reaction of 24 with methyl thioglycolate was performed and the stereoselectivity confirmed by X-ray analysis of 33a. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Stereocontrolled intramolecular α-amidoalkylation reactions of L-DOPA-derived succinimides have been studied. Addition of MeLi to nonracemic succinimides 9a-d yields oxoamides, which are cyclized upon treatment with Lewis or protic acids to afford (5S,10b

The pentacyclic core of ecteinascidins was constructed from two fundamental building blocks, the 1,2,3,4-tetrahydroisoquinoline derivative and the substituted phenylalanine derivative, via 8 steps using readily available L-Dopa as starting material. The k

Stereocontrolled N-acyliminium ion cyclisation of L-DOPA derived succinimide 5 has been investigated. Addition of organolithiums to chiral non-racemic 5 yields oxoamides, which are cyclised diastereoselectively upon treatment with BF3·OEt2, to afford 5,10b-trans pyrroloisoquinolones in moderate yields and high ee (99%).

To improve the in vitro and in vivo potency of our first low molecular weight GPIIb/IIIa antagonist 1 (TAK-029), a series of 2-[4-[2-(4-amidinobenzoylamino)-2-(substituted)acetyl]-3-(2-methoxy-2- oxoethyl)-2-oxopiperazinyl]acetic acids were synthesized th

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