120-26-3

Transaminases (TAs) offer an environmentally and economically attractive method for the direct synthesis of pharmaceutically relevant disubstituted 1-phenylpropan-2-amine derivatives starting from prochiral ketones. In this work, we report the application of immobilised whole-cell biocatalysts with (R)-transaminase activity for the synthesis of novel disubstituted 1-phenylpropan-2-amines. After optimisation of the asymmetric synthesis, the (R)-enantiomers could be produced with 88-89% conversion and >99% ee, while the (S)-enantiomers could be selectively obtained as the unreacted fraction of the corresponding racemic amines in kinetic resolution with >48% conversion and >95% ee. This journal is

Herein, a sequential and selective chemoenzymatic approach is described involving the metal-catalysed Wacker-Tsuji oxidation of allylbenzenes followed by the amine transaminase-catalysed biotransamination of the resulting 1-arylpropan-2-ones. Thus, a series of nine optically active 1-arylpropan-2-amines were obtained with good to very high conversions (74–92%) and excellent selectivities (>99% enantiomeric excess) in aqueous medium. The Wacker-Tsuji reaction has been exhaustively optimised searching for compatible conditions with the biotransamination experiments, using palladium(II) complexes as catalysts and iron(III) salts as terminal oxidants in aqueous media. The compatibility of palladium/iron systems for the chemical oxidation with commercially available and made in house amine transaminases was analysed, finding ideal conditions for the development of a general and stereoselective cascade sequence. Depending on the selectivity displayed by selected amine transaminase, it was possible to produce both 1-arylpropan-2-amines enantiomers under mild reaction conditions, compounds that present therapeutic properties or can be employed as synthetic intermediates of chiral drugs from the amphetamine family. (Figure presented.).

The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5 and R6 are as described herein, compositions including the compounds and methods of using the compounds.

The invention provides novel compounds having the general formula (I) wherein R1, R2 R3, R4, R5 and R6 are as described herein, compositions including the compounds and methods of using the compounds in the treatment of the hepatitis B virus.

A rapid method for efficient reduction of nitroalkanes and α,β-unsaturated nitroalkenes using SmI2/H2O/amine has been developed.

The invention relates to novel pyrrolodihydroisoquinoline derivatives, which are efficacious inhibitors of PDE10.

Compounds of general formula (I) wherein D, E, R1, R2, R3, R4, R5, R6 and R7 are as defined in the specification, as well as salts, enantiomers thereof and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

Catalytic Sn(OTf)2-induced cyclization of linear, aryl-containing allylic N,O-acetals produced vinyl-substituted tetrahydroisoquinolines and tetrahydro-1H-β-carbolines. The usefulness of the vinyl moiety in the resulting products was demonstrated via the synthesis of various key building blocks for alkaloid structures. The α-vinyl moiety was utilized in a [2,3] sigmatropic rearrangement, in ring-closing metathesis and a cross-metathesis-based synthesis of vincantril, an antianoxia agent, and a synthetic member of the vincamine type natural products.

The present invention comprises novel analogs of ecstasy-class compounds and novel ecstasy-class immunogens leashed out of, i.e., derived from, the methylenedioxy position. The invention also comprises unique monoclonal antibodies generated using MDO-leashed MDMA immunogens as well as unique conjugates and tracers. These antibodies, conjugates, and tracers are useful in immunoassays for the detection of ecstasy-class compounds in biological fluids.

A series of ten novel phenyl ketone oxime ethers substituted on the terminal nitrogen by either 1,3 benzodioxole, alkyl, aralkyl or aryl moiety were synthesized and tested for their activity at bovine β3-adrenoceptors. The best compound, which was the benzodioxole dicarboxylate derivative, showed potent β3-adrenergic agonistic activities in Chinese hamster ovary cells expressing the bovine β3-adrenoceptors with Kact and Ki values better than compound CL 316,243 used as reference (14 ± 6 nM and 203 ± 71 nM, respectively). In this series three compounds showed an antagonistic activity. Structure-activity relationships in these ketone oxime ethers are discussed.

An (S)-1-phenyl-2-substituted propane derivative shown by the following formula (I) STR1 wherein R1 and R2 represent a lower alkyl group, etc., or R1 and R2 may form together an alkylene group, etc.; R3, R4 and R5 represent a hydrogen atom, etc.; and X represents a hydroxyl group which may be protected with a protective group, or a halogen atom etc., can readily be produced (i) by permitting a microorganism belonging to the genus Torulaspora, the genus Candida, the genus Pichia or the like to act on a phenylacetone derivative and asymmetrically reducing the compound, or (ii) by sterically inverting an (R)-enantiomer. (R,R)-1-phenyl-2-[(2-phenyl-1-methylethyl)amino]ethanol derivative having a high optical purity can easily be obtained from the compound of the formula (I). The ethanol derivative is useful as an anti-obesity agent and the like.

The photoamination of trans-1-arylpropenes (aryl = 2-methoxyphenyl), (1), 3-methoxyphenyl (2) 3,4-dimethoxyphenyl (3), and 4-methoxyphenyl (4) with NH3, i-PrNH2, and t-BuNH2 (RNH2), in the presence of p-dicyanobenzene (p-DCB) gave 2-alkylamino-1 arylpropanes (9) and/or 2-alkylamino-1-aryl-1-(4-cyanophenyl)propanes (10). The photoaminations of 1,2-dihydro-7-methoxynaphthalenes (6-8) with RNH2 in the presence of p-DCB gave mainly 2-alkylamino-1-(4-cyanophenyl)-6-methoxy-1,2,3,4-tetrahydronaphthalene s (13). The photoamination of trans-1-(3,5-dimethoxyphenyl)propene (5) with i-PrNH2 occurred at aromatic ring to give trans-1-(2-isopropylamino-3,5-dimethoxyphenyl)propene (11). The photoaminations of 1-4 and 6-8 with NH3 in the presence of m-dicyanobenzene gave the aminated products without incorporation of cyanophenyl group. Furthermore, the addition of 1,3,5-triphenylbenzene and m-terphenyl for these reactions improved the yields of the photoaminated products.

The photoaminations of trans-1-arylpropenes and 7-methoxy-1,2-dihydronaphthalenes with ammonia in the presence of dicyanobenzene gave 1-aryl-2-propylamines and 2-amino-6-methoxy-1,2,3,4-tetrahydronaphthalenes, respectively. The yields of the aminated compounds were improved by the addition of 1,3,5-triphenylbenzene or m-terphenyl.

New bronchospasmolytic compounds of the formula (X) and pharmaceutically acceptable salts thereof, wherein R1 and R2 are the same or different and are each H, OH, OCH3, OC2H5, halogen; or R1 and R2 together form the chain -O-CH2-O- or -O-CF2-O-;, R3 is H or CH3;, R5 is H or -CO-R7;, R6 is H, OH, OCH3, OC2H5 or halogen;, R7 is a straight or branched alkyl grup with 1-16 carbon atoms, aryl, -NHCH3 or -N(CH3)2, as well as their use and a process for their preparation.

The secondary amines R1R2C6H3CH2CH(CH3)NHCHR5CHR6(CH2)nC6H3R3R4 were synthesized by the reduction of the respective azomethines with sodium borohydride.The reaction was conducted in anhydrous methanol in the presence of hydrogen chloride with the azomethine and hydrogen chloride in a molar ratio of 1:1.The yield was 50-90percent.The erythro and threo isomers were isolated, and the data from the IR spectra of the isomers are given.

Novel substituted imidazoles and methods for their preparation are disclosed. These imidazoles, and their salts, exhibit pharmacological activity which includes antihypertensive activity and β-adrenergic blocking activity.

Substituted imidazoles and methods for their preparation are disclosed. These imidazoles, and their salts, exhibit pharmacological activity which includes antihypertensive activity and β-adrenergic blocking activity. STR1

Several N-(trifluoroacetyl)-α-amino acid chlorides have been reacted with benzene, anisole, and veratrole in the presence of AlCl3 or SnCl4 to produce the corresponding aromatic ketones in fair to high yields.The products are reductible under neutral or acidic conditions to the corresponding N-(trifluoroacetyl)-β-hydroxy-β-arylakylamines or N-(trifluoroacetyl)-β-arylalkylamines.The latter can be readily detrifluoroacetylated by mild basic hydrolysis and thence converted to the corresponding 3-substituted 1,2,3,4-tetrahydroisoquinolines by condensation with formaldehyde.

Novel substituted imidazoles of the formula STR1 and methods for their preparation are disclosed. These imidazoles, and their salts, exhibit pharmacological activity which includes antihypertensive activity and β-adrenergic blocking activity.

Reaction of 6,7-dialkoxy-1-alkyl-3,4-dihydro-3-methylisoquinolines (10 - 12) with sulphinamide anhydride (13) yields 2,3-dialkoxy-5,6,7,8-tetrahydro-6-methyl-8-oxoisoquinolinoquinazolines (14 and 19) and 2,3-dialkoxy-13a-alkyl-5,6,7,8,13,13a-hexahydro-6-methyl-8-oxoisoquinolinoquinazolines (15 - 17 and 20).Of the two possible geometrical isomers of the latter class of compounds, the cis-isomer predominates and the trans-isomer is found to be labile towards aerial oxidation.No evidence for the generation of iminoketene (21) is obtained in the reaction of sulphinamide anhydride (13) with various 3,4-dihydroisoquinoline derivatives.

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