- Chemo-Enzymatic One-Pot Two-Step Functionalization of 1,2,3,4-Tetrahydroisoquinolines by Monoamine Oxidase-Ugi-Joullié Reaction Sequence
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A one-pot two-step chemo-enzymatic approach for the functionalization of substituted 1,2,3,4-tetrahydroisoquinolines (THIQs) was developed. The system combines monoamine oxidase (MAO)-catalyzed imine formation with Ugi-type three-component reaction in an aqueous buffer without intermediate isolation. The two steps were separately optimized for buffer and pH to obtain the expected products. MAOs enabled the functionalization of fifteen THIQs by oxidation to imines, while the Ugi-Joullié-reaction was successfully carried out with eight carboxylic acids and eight isonitriles. 41 products were isolated giving access to valuable building blocks for medicinal chemistry applications. Gram-scale transformation demonstrated the utility of the described protocol for organic synthesis.
- Barna, Bence,Gáti, Tamás,Kotschy, András,Tasnádi, Gábor
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supporting information
(2022/03/01)
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- NOVEL TETRAHYDROISOQUINOLINES AND TERAHYDRONAPHTHYRIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
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The present invention provides novel compounds having the general formula (I): wherein R1, R 2, R 3, U, V, W, X and Y are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 33
(2018/05/24)
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- COMPLEMENT PATHWAY MODULATORS AND USES THEREOF
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The present invention provides a compound of formula I a method for manufacturing the compounds of the invention, and its therapeutic uses as inhibitor of the complement alternative pathway and particularly as inhibitor of Factor B for the treatment of e.g. age-related macular degeneration and diabetic retinopathy. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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Page/Page column 104; 105
(2014/01/09)
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- Decahydro-8H-isoquino[2,1-g][1,6]naphthyridine and decahydrobenzo[a]pyrrolo [2,3-e]quinolizine derivatives
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Compounds of the formula STR1 wherein: m is an integer of 1-6;n is an integer of 1 or 2;X and Y are independently hydrogen; hydroxy; lower alkyl; lower alkoxy; or halo; or X and Y when adjacent and taken together are methylenedioxy or ethylene-1,2-dioxy;R is STR2 wherein: R 1 and R 2 are independently hydrogen or lower alkyl, or when taken together with the carbon to which they are attached are cycloalkyl;R 3 is hydrogen, lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or halo; and STR3 and pharmaceutically acceptable acid addition salts thereof. The compounds and salts exhibit useful pharmacological properties, including selective α 2 -adrenoceptor antagonist properties and 5-HT 1A receptor partial agonist properties, and are particularly useful for the treatment of sexual dysfunction, depression and anxiety.
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- Process for the preparation of (8As,12AS,13AS)-decahydroisoquino ((2,1-G) (1,6)-naphthyridin-8-one derivatives
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The invention provides a process for preparing single enantiomers of compounds represented by the formula: STR1 and chiral acid addition salts thereof; wherein: X and Y are independently hydrogen; lower alkyl; lower alkoxy; or halo; or X and Y taken together is methylenedioxy or ethylene-1,2-dioxy; which includes reduction of a compound represented by the formula: STR2 to give a mixture of stereoisomers represented by the formula: STR3 wherein each wavy line independently represents a bond in either the α or β position; followed by dissolving the mixture of stereoisomers and a chiral resolving acid in a suitable solvent and allowing the solution to crystallize, giving a salt of the desired enantiomer.
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- Decahydro-8H-isoquino[2,1-g][1,6]naphthyridine and decahydrobenzo[a]pyrrolo[2,3-e]quinolizine derivatives
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Compounds of the formula ψψ ψwherein:ψ X and Y are independently hydrogen; hydroxy; lower alkyl of 1-6 carbon atoms; lower alkoxy of 1-6 carbon atoms; or halo; or X and Y when adjacent and taken together are methylenedioxy or ethylene-1,2-dioxy;ψ R is lower alkyl of 1-6 carbon atoms; cycloalkyl of 3-8 carbon atoms; phenyl or phenyl lower alkyl in which any phenyl group may be optionally substituted by one or two substituents chosen from the group consisting of halo, lower alkyl of 1-4 carbon atoms and lower alkoxy of 1-4 carbon atoms; or -ANHSO2R1; wherein A is lower alkylene of 1-6 carbon atoms; and R1 is lower alkyl of 1-6 carbon atoms or -NRyR3; whereinψ Ry and R3 are independently hydrogen or lower alkyl of 1-6 carbon atoms, or Ry and R3 taken together are cycloalkyl of 3-8 carbon atoms; andψ n is 1 or 2;ψ and the pharmaceutically acceptable salts thereof, are useful as à2-adrenoceptor antagonists, in particular as peripherally selective à2 -adrenoceptor antagonists.ψ
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