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ENZYME INHIBITORS

Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R1 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R2is the side chain of a natural or non-natural alpha amino acid; Y is a bond, -C(=O)-, -S(=O)2-, -C(=O)O-, -C(O)NR3-, -C(=S)-NR3 , -C(=NH)NR3 or -S(=O)2NR3- wherein R3 is hydrogen or optionally substituted C1-C6 alkyl; L1 is a divalent radical of formula -(Alk1)m(Q)n(Alk2)p- wherein m, n and p are independently 0 or 1 , Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 – 13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula -X2-Q1- or -Q1-X2- wherein X2 is -O-, S- or NRA- wherein RA is hydrogen or optionally substituted C1-C3 alkyl, and Q1 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 – 13 ring members, AIk1 and AIk2 independently represent optionally substituted divalent C3-C7 cycloalkyl radicals, or optionally substituted straight or branched, C1-C6 alkylene, C2-C6 alkenylene ,or C2-C6 alkynylene radicals which may optionally contain or terminate in an ether (-O-), thioether (-S-) or amino (-NRA-) link wherein RA is hydrogen or optionally substituted C1-C3 alkyl; X1 represents a bond; -C(=O); or -S(=O)2-; -NR4C(=O)-, -C(=O)NR4-, -NR4C(=O)NR5- , -NR4S(=O)2-, or -S(=O)2NR4-wherein R4 and R5 are independently hydrogen or optionally substituted C1-C6 alkyl; z is 0 or 1 ; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R1R2NH-Y-L1-X1-[CH2]Z- and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONHOH, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

-The following derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid have been prepared in their (S)-form and as racemates: hydrochloride of methyl ester, N-carboxy anhydride, and N-acetyl derivative. All the substances were fully characterised by elemental analyses, 1H and 13C NMR spectra, and optical rotation, as the case may be; the N-carboxy anhydride was also characterised by means of X-Ray diffraction. Also identified was the intermediate of the reaction of the title acid with phosgene, the N-chlorocarbonyl derivative, and the respective methyl ester was prepared. The dioxopiperazine of the title acid was prepared and characterised both in pure (S,S)-form and in the form of a mixture of two racemates. The optically pure dioxopiperazine was prepared by a reaction of the N-carboxy anhydride in solid phase.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Cascade and RCM syntheses of chiral tricyclic alkaloids from (S)-1,2,3,4-tetrahydro isoquinoline carboxylic acid

Concise syntheses of novel chiral pyrroloazacyclo and chiral tricyclic isoquinoline alkaloids, starting from the readily available (S)-1,2,3,4-tetrahydroisoquinoline carboxylic acid methyl ester, by utilizing cascade spiro-to fused and RCM protocols, are reported.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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TETRAHYDROISOQUINOLINE DERIVATIVES

A compound of the formula: STR1 wherein R 1 is hydrogen or methyl, is prepared by condensing a compound of the formula: STR2 wherein R 2 is alkyl, aryl or aralkyl and R 1 is same as above, or a reactive derivative thereof with 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid or an ester thereof to give a compound of the formula: STR3 wherein R 3 is an ester residue and R 1 and R 2 are same as above, followed by hydrolysis or ammonolysis of said compound (IV) . The compound (I) is useful as a diagnostic or therapeutic agent for angiotensin-related hypertension.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Coordination compounds based on 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

Syntheses of 2,6-bis[((3S)-3-(methoxycarbonyl)-1,2,3,4- tetrahydroisoquinolin-2-yl)carbonyl]pyridine and its coordination compounds with Cu2+, Co2+, Co3+, or Fe3+ are described. By means of 1H- and 13C-NMR spectra it was proved that 2,6-bis[((3S)-3-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-2- yl)carbonyl]pyridine as well as its coordination compound with Co3+ exist in the form of a mixture of three conformers, differing in the conformations at the two amide groups present. The prepared coordination compounds were tested in the enantioselective catalysis of the nitroaldol addition of nitromethane with 2-nitrobenzaldehyde or 4-nitrobenzaldehyde, and in the Michael addition of ethyl 2-oxocyclohexanecarboxylate to but-3-en-2-one.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Discovery of (S)-Methyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate hydrochloride

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78183-55-8, Name is (S)-Methyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate hydrochloride, belongs to tetrahydroisoquinoline compound, is a common compound. COA of Formula: C11H14ClNO2In an article, once mentioned the new application about 78183-55-8.

Hydantoins and thiohydantoins derived from 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

The reaction of methyl (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate with isocyanates (phenyl, naphthalen-l-yl, cyclohexyl, (S)-1-methylbenzyl) in ether has been used to prepare N-substituted methyl (3S)-2-aminocarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylates. These compounds were cyclised by action of CF3COOH to give the corresponding 2-substituted (10aS)-10,10a-dihydroimidazo[1,5-b]isoquinoline-1,3(2H,5H)-diones (hydantoins Tic-H). Hydantoins Tic-H were also prepared by the reaction of methyl (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate with isocyanates (methyl, (1S)-1-methylbenzyl, 4-methylphenyl, 3-methylphenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 4-methoxyphenyl, 5-chloro-2-methoxyphenyl, 3-chloro-4-ethoxyphenyl) and triethylamine in CH2Cl2. 2-Substituted (10aS)-3-thioxo-1,2,3,5, 10, 10a-hexahydroimidazo[ 1,5-b]isoquinolin-1-ones (thiohydantoins Tic-TH) were prepared analogously by the reaction of methyl (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate with isothiocyanates (methyl, ethyl, allyl, phenyl). The optical purity of selected substances was determined chromatographically.{A figure is presented}. Tic Acid Hydantoin Thiodantoin Atropoisomer NMR Spectrum, X-Ray and Chiral HPLC.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Synthesis of 1-(m-hydroxybenzyl)-substituted 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as opioid peptide mimetics – Unexpected amide bond cleavages under mild conditions

N-Glycyl-(1R,3S)-1-(m-hydroxybenzyl)-1,2,3, 4-tetrahydroisoquinoline-3-carboxylic acid (Tic) was prepared as a Tyr-Tic dipeptide mimetic for exploration of its potential as a delta opioid receptor selective ligand. The compound was successfully obtained by a stereoselective synthesis starting from L-Tic. In the course of the reactions, unusual peptide bond cleavages were observed under mild conditions, and reaction mechanisms have been proposed. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

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Tetrahydroisoquinoline – Wikipedia,
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Potent, cell active, non-thiol tetrapeptide inhibitors of farnesyltransferase.

All previously reported CAAX-based farnesyltransferase inhibitors contain a thiol functionality. We report that attachment of the 4-imidazolyl group, via 1-, 2-, or 3-carbon alkyl or alkanoyl spacers, to Val-Tic-Met or tLeu-Tic-Gln provides potent FT inhibitors. (R*)-N-[[1,2,3,4-Tetrahydro-2-[N-[2-(1H-imidazol-4-yl)ethyl] -L-valyl]-3-isoquinolinyl]carbonyl]-L-methionine ([imidazol- 4-yl-ethyl]-Val-Tic-Met), with FT IC50 = 0.79 nM, displayed potent cell activity in the absence of prodrug formation (SAG EC50 = 3.8 muM).

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Tetrahydroisoquinoline – Wikipedia,
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SUBSTITUTED SULFONAMIDES USEFUL AS ANTIAPOPTOTIC BCL INHIBITORS

Disclosed are compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein: W and Q and G are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bcl-2 family antiapoptotic proteins for the treatment of cancer; and pharmaceutical compositions comprising such compounds

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Tetrahydroisoquinoline – Wikipedia,
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Synthesis of tetrahydroisoquinoline-diamine ligands and their application in asymmetric transfer hydrogenation

The use of the tetrahydroisoquinoline scaffold is well documented in biologically active compounds. However, reports of the utilisation of tetrahydroisoquinoline compounds in asymmetric catalysis are limited. The synthesis of novel diamine ligands possessing the tetrahydroisoquinoline (tetrahydroisoquinoline) backbone and evaluation of their activity in the asymmetric transfer hydrogenation of acetophenone are presented. The diamine ligands in conjunction with i-PrOH as the hydrogen source and [RhCl2(Cp*)]2 as the metal precursor proved to be the most effective of the tetrahydroisoquinoline derivatives for this catalytic system. Water was found to have a profound influence on the enantioselectivity of the reaction. Optimisation of the amount water, i-PrOH and catalytic loading content rendered the best result of 70% enantioselectivity for the (S)-1-phenylethanol isomer product.

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Tetrahydroisoquinoline – Wikipedia,
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