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(6Aalpha,10Aalpha,11Aalpha)-2-(2-PYRIDINYL)-1,3,4,6,6A,7,8,9,10,10A,11,11A-DODECAHYDRO-2H-PYRAZINO]1,2-B] ISOQUINOLINE AND DERIVATIVES

(6aalpha,10aalpha,11aalpha)-2-(2-pyridinyl)-1,3,4,6,6a,7,8,9, 10, 10 a, 11 ,11a-dodecahydro-2H-pyrazino[1,2-b]isoquinoline and derivatives or acid addition salts thereof are selective alpha 2-adrenergic receptor antagonists and thereby useful as antidepressant agents and for treating sedation caused by antihypertensive therapy.

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

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N2 -naphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof, and antithrombotic compositions and methods employing them

N2 -naphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof have been found to be effective as pharmaceutical agents for the inhibition and suppression of thrombosis.

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Design and synthesis of N-(5-chloro-2,4-dihydroxybenzoyl)-(R)-1,2,3,4-tetrahydroisoquinoline-3-carboxamides as novel Hsp90 inhibitors

Heat shock protein 90 (Hsp90) is an attractive chemotherapeutic target for antitumor drug development. Herein, we reported the design and synthesis of two series of novel N-(5-chloro-2,4-dihydroxybenzoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamides as Hsp90 inhibitors using (S)-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) (A1-13) and (R)-Tic (B1-13) as scaffold, respectively. Cellular thermal shift assay (CETSA) screening showed that compounds B1-13 with (R)-Tic scaffold exhibited potent ability to stabilize Hsp90alpha. Compound B7 showed not only the most potent ability to induce thermal stabilization of Hsp90alpha but also the strongest cytotoxicity. The IC50 values of B7 were 0.98 muM and 1.74 muM against the proliferation of human breast cancer MDA-MB-231 and human cervical cancer HeLa cell lines, respectively. Moreover, CETSA melt and ITDRFCETSA (isothermal dose-response fingerprint) curves confirmed that B7 bound to Hsp90alpha in 293T cells. Western blotting results indicated that B7 induced the degradation of Hsp90 clients CDK4, Her2, Cdc-2 and C-raf. In addition, docking and Molecular dynamics (MD) refinement of the B7-Hsp90 complex showed that the binding model of B7 to Hsp90 was similar with that of 8-benzyladenines. The overall properties warrant compound B7 a promising lead for the development of Hsp90 inhibitor antitumor drugs.

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Tetrahydroisoquinoline – Wikipedia,
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HETEROCYCLES FROM NITRILE IMINES. PART IV. CHIRAL 4,5-DIHYDRO-1,2,4-TRIAZIN-6-ONES

The reaction of nitrile imines (II) with alpha-amino esters (III) proceeds with no detectable racemization and constitutes a convenient synthetic route to 4,5-dihydro-1,2,4-triazin-6-ones (IV).Permangamate oxidation of heterocycles (IV) affords the corresponding 1,2,4-triazin-6-ones (V).The reaction of (II) with beta-amino esters gives the respective acyclic amidrazone adducts (VI).

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

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LXR INVERSE AGONISTS FOR TREATMENT OF CANCER

In some aspects, the present disclosure provides compounds of the formula: (I) or (II) wherein the variables are as defined herein. In some embodiments, these compounds may be used to treat cancer or other hyperproliferative diseases, as well as atherosclerosis and coronary artery disease.

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Tetrahydroisoquinoline – Wikipedia,
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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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ACYL ISOINDOLINE DERIVATIVES AND ACYL ISOQUINOLINE DERIVATIVES AS ANTI-VIRAL AGENTS

Anti viral agents of Formula (I) where in R3 represents aryl or heteroaryl R4 represents one or two substituents independently selected from hydrogen, C 1-6alkyl, halo, ORA , C(O)NRBRC, C(O)RD, CO2H, CO2RD, NRBRC, NRE C(O)RD, NRECO2RD, NREC(O)NRFRG, NRESO2RD, SO2NRFRG, SO2RD, nitro, cyano, heterocyclyl, heteroaryl, aryl, arylalkyl heteroarylalkyl or CF3 R5 and R6 independently represent hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl n represents 0 or 1 when n represents 0, R1 represents C(O)RH and R2 represents C1-6alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl when n represents 1, either i) R1 represents C(O)RH R2 represents C1-6alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl; and R7 and R8 independently represent hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; or ii) R1 and R2 independently represent hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; R7 represents C(O)RH; and R8 represents C1-6alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl; RA represents hydrogen, C1-6alkyl, arylalkyl, heteroarylalkyl, aryl or heteroaryl; RB and RC independently represent hydrogen, C1-6alkyl, aryl or heteroaryl; or RB and RC together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group RDis selected from the group consisting of C1-6alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl RE represents hydrogen or C1-6alkyl; RF and RG are independently selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl or RF and RG together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group RH represents hydroxy or NRBRC and salts, solvates and esters there of provided that when RH is hydroxy, which is esterified to form -OR where R is selected from straight or branched chain alkyl, aralkyl, aryloxyalkyl, or aryl, then R is other than tert-butyl. Processes for their preparation and methods of using them in HCV treatment are provided.

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Tetrahydroisoquinoline – Wikipedia,
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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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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.57060-88-5,Methyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate hydrochloride,as a common compound, the synthetic route is as follows.

57060-88-5, A mixture of 2,4-bis(benzyloxy)-5-chlorobenzoic acid 4 (2.213 g, 6 mmol), EDCI (1.38 g, 7.2 mmol), HOBt (0.973 g, 7.2 mmol), NMM (2.012 mL, 18 mmol) and hydrochloride 6 (1.639 g, 7.2 mmol) in CH2Cl2 (30 mL) was stirred for overnight at room temperature. The organic layer was washed successively with 2 M HCl and 2 M NaOH, then dried over anhydrous Na2SO4, filtered and evaporated under vacuum. The residue was purified by column chromatography over silica gel eluted with PE-EtOAc (4: 1, v/v) to give 7 (2.89 g) as a white foam with the yield 81%. HR ESIMS: m/z 542.1731 [M + H]+ (calcd. 542.1734). The structure of compound 7 was confirmed by the 1H NMR spectra of its debenzylation product obtained by boron trichloride-mediated deprotection. 1H NMR (600 MHz, acetone-d6, r.t.) delta 7.38 (s, 1H), 7.23-7.20 (m, 4H), 6.62 (s, 1H), 5.15 (br s, 1H), 4.97 (d, J = 16.3 Hz, 1H), 4.72 (br s, 1H), 3.62 (s, 3H), 3.34 (dd, J = 15.7, 5.4 Hz, 2H), 3.28 (dd, J = 15.9, 4.3 Hz, 1H). HR ESIMS: m/z 384.0618 [M + Na]+ (calcd. 384.0615).

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Reference£º
Article; Liang, Chuanpeng; Hao, Huilin; Wu, Xingkang; Li, Zhenyu; Zhu, Jing; Lu, Chunhua; Shen, Yuemao; European Journal of Medicinal Chemistry; vol. 121; (2016); p. 272 – 282;,
Tetrahydroisoquinoline – Wikipedia
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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As a common heterocyclic compound, it belongs to tetrahydroisoquinoline compound, name is Methyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate hydrochloride, and cas is 57060-88-5, its synthesis route is as follows.,57060-88-5

Step A: Preparation of Methyl 1,2,3,4,4a,5,6,7,8,8a-Decahydroisoquinoline-3-carboxylate Methyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate hydrochloride (2.3 g, 10 mmol) in 200 ml absolute ethanol is hydrogenated at 50 psi, room temperature, using 0.6 g 5% Rh/C catalyst. After the theoretical amount of hydrogen is taken up (36 hours), the catalyst is filtered and the filtrate is evaporated to dryness. The residue is dissolved in methylene chloride and washed with a saturated solution of sodium carbonate. The organic phase is dried (Na2 SO4) and acidified with ethanolic HCl. Evaporation of the solvent yields 2.0 g of the product as a diastereomeric mixture which is used without further separation.

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Reference£º
Patent; Merck & Co., Inc.; US4381302; (1983); A;,
Tetrahydroisoquinoline – Wikipedia
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem