Heterocyclic Building Blocks-Tetrahydroisoquinoline

Charton, Julie published the artcileOptimized synthesis of tetrahydroisoquinoline-hydantoins, HPLC of Formula: 142335-42-0, the publication is Tetrahedron Letters (2004), 45(38), 7081-7085, database is CAplus.

Several methods have been developed and compared for the solution synthesis of tetrahydroisoquinoline-hydantoin (Tic-hydantoin) derivatives Starting materials were Tic-OH and amines readily available from com. sources. The best yields were observed when the imidazolidine-2,4-dione ring was synthesized in two steps, i.e., reaction of Tic-OH with the appropriate amine and cyclization with 1,1′-carbonyldiimidazole.

Tetrahedron Letters published new progress about 142335-42-0. 142335-42-0 belongs to tetrahydroisoquinoline, auxiliary class Tetrahydroisoquinoline,Chiral,Carboxylic acid,Amide,Alcohol, name is (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, and the molecular formula is C15H19NO5, HPLC of Formula: 142335-42-0.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Zhang, Yingjie published the artcileDesign, synthesis and preliminary activity assay of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as novel Histone deacetylases (HDACs) inhibitors, Recommanded Product: (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, the publication is Bioorganic & Medicinal Chemistry (2010), 18(5), 1761-1772, database is CAplus and MEDLINE.

Histone deacetylases (HDACs) are enzymes involved in tumor genesis and development. Herein, we report a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDACs inhibitors. The preliminary biol. screening showed that most of our compounds exhibited potent inhibitory activity against HDACs. Within this series, five compounds, 13a (IC₅₀ = 0.58±0.10 μM), 7d (IC₅₀ = 1.00±0.16 μM), 8l (IC₅₀ = 1.06±0.14 μM), 7i (IC₅₀ = 1.17±0.19 μM) and 7a (IC₅₀ = 1.29±0.15 μM) possessed better HDACs inhibitory activity than Vorinostat (IC₅₀ = 1.48±0.20 μM). So these five compounds could be used as novel lead compounds for further design of HDACs inhibitors. The anti-proliferative activities of a few compounds and the structure-activity relationships are also briefly discussed.

Bioorganic & Medicinal Chemistry published new progress about 142335-42-0. 142335-42-0 belongs to tetrahydroisoquinoline, auxiliary class Tetrahydroisoquinoline,Chiral,Carboxylic acid,Amide,Alcohol, name is (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, and the molecular formula is C6H17NO3Si, Recommanded Product: (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Zhang, Yingjie published the artcileDevelopment of Tetrahydroisoquinoline-Based Hydroxamic Acid Derivatives: Potent Histone Deacetylase Inhibitors with Marked in Vitro and in Vivo Antitumor Activities, Application of (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, the publication is Journal of Medicinal Chemistry (2011), 54(8), 2823-2838, database is CAplus and MEDLINE.

Inhibition of histone deacetylase (HDAC) results in growth arrest, differentiation, and apoptosis in nearly all tumor cell lines, promoting HDACs as promising targets for antitumor therapy. In our previous study we developed a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDAC inhibitors (HDACi), among which compound 7d (I) exhibited promising HDAC8 inhibitory and antiproliferative activities. Herein, we report the design and development of a new class of tetrahydroisoquinoline-bearing hydroxamic acid analogs as potential HDACi and anticancer agents. In vitro biol. evaluation of these compounds showed improved HDAC8 inhibition (compounds 31a and 31b exhibited mid-nM IC₅₀ values against HDAC8) and potent growth inhibition in multiple tumor cell lines. Most importantly, compounds 25e, 34a, and 34b exhibited excellent in vivo anticancer activities in a human breast carcinoma (MDA-MB-231) xenograft model compared with suberoylanilide hydroxamic acid (SAHA), an approved HDACi. Collectively, our results indicate that tetrahydroisoquinoline bearing a hydroxamic acid is an excellent template to develop novel HDACi as potential anticancer agents.

Journal of Medicinal Chemistry published new progress about 142335-42-0. 142335-42-0 belongs to tetrahydroisoquinoline, auxiliary class Tetrahydroisoquinoline,Chiral,Carboxylic acid,Amide,Alcohol, name is (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, and the molecular formula is C14H10O4S2, Application of (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Zhang, Yingjie published the artcileDiscovery of a Tetrahydroisoquinoline-Based Hydroxamic Acid Derivative (ZYJ-34c) as Histone Deacetylase Inhibitor with Potent Oral Antitumor Activities, Formula: C15H19NO5, the publication is Journal of Medicinal Chemistry (2011), 54(15), 5532-5539, database is CAplus and MEDLINE.

Histone deacetylase (HDAC) has emerged as an attractive target for the development of antitumor agents during the past decade. Previously tetrahydroisoquinoline-bearing hydroxamic acid analog, ZYJ-25e (1), was identified and validated as a potent histone deacetylase inhibitor (HDACi) with marked in vitro and in vivo antitumor potency. In the present study, further modification of 1 led to another more potent, orally active HDACi, ZYJ-34c (4). Compared to FDA-approved drug suberoylanilide hydroxamic acid (SAHA), compound 4 exhibited higher in vivo antitumor potency in a human breast carcinoma (MDA-MB-231) xenograft model and in a mouse hepatoma-22 (H22) pulmonary metastasis model and similar in vivo antitumor potency in a human colon tumor (HCT116) xenograft model.

Journal of Medicinal Chemistry published new progress about 142335-42-0. 142335-42-0 belongs to tetrahydroisoquinoline, auxiliary class Tetrahydroisoquinoline,Chiral,Carboxylic acid,Amide,Alcohol, name is (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, and the molecular formula is C9H6FNO2, Formula: C15H19NO5.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Perez, Heidi L. published the artcileDiscovery of Potent Heterodimeric Antagonists of Inhibitor of Apoptosis Proteins (IAPs) with Sustained Antitumor Activity, Application of (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, the publication is Journal of Medicinal Chemistry (2015), 58(3), 1556-1562, database is CAplus and MEDLINE.

The prominent role of IAPs in controlling cell death and their overexpression in a variety of cancers has prompted the development of IAP antagonists as potential antitumor therapies. The authors describe the identification of a series of heterodimeric antagonists with highly potent antiproliferative activities in cIAP- and XIAP-dependent cell lines. Compounds I (L = none) and I (L = NH) further demonstrate curative efficacy in human melanoma and lung cancer xenograft models and are promising candidates for advanced studies.

Journal of Medicinal Chemistry published new progress about 142335-42-0. 142335-42-0 belongs to tetrahydroisoquinoline, auxiliary class Tetrahydroisoquinoline,Chiral,Carboxylic acid,Amide,Alcohol, name is (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, and the molecular formula is C15H19NO5, Application of (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Li, Yangmei published the artcilePotent μ-opioid receptor agonists from cyclic peptides Tyr-c[D-Lys-Xxx-Tyr-Gly]: Synthesis, biological, and structural evaluation, COA of Formula: C15H19NO5, the publication is Journal of Medicinal Chemistry (2016), 59(3), 1239-1245, database is CAplus and MEDLINE.

To optimize the structure of a μ-opioid receptor ligand, analogs H-Tyr-c[D-Lys-Xxx-Tyr-Gly] were synthesized and their biol. activity was tested. The analog containing a Phe³ was identified as not only exhibiting binding affinity 14-fold higher than the original hit but also producing agonist activity 3-fold more potent than morphine. NMR study suggested that a trans conformation at D-Lys²-Xxx³ is crucial for these cyclic peptides to maintain high affinity, selectivity, and functional activity toward the μ-opioid receptor.

Journal of Medicinal Chemistry published new progress about 142335-42-0. 142335-42-0 belongs to tetrahydroisoquinoline, auxiliary class Tetrahydroisoquinoline,Chiral,Carboxylic acid,Amide,Alcohol, name is (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, and the molecular formula is C15H19NO5, COA of Formula: C15H19NO5.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Thomas, James B. published the artcileIdentification of (3R)-7-Hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)- 3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro- 3-isoquinolinecarboxamide as a Novel Potent and Selective Opioid κ Receptor Antagonist, Name: (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, the publication is Journal of Medicinal Chemistry (2003), 46(14), 3127-3137, database is CAplus and MEDLINE.

(3R)-7-Hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic) was identified as a potent and selective κ opioid receptor antagonist. Structure-activity relation (SAR) studies on JDTic analogs revealed that the 3R,4R stereochem. of the 3,4-dimethyl-4-(3-hydroxyphenyl)piperidine core structure, the 3R attachment of the 7-hydroxy-1,2,3,4-tetrahydroisoquinoline group, and the 1S configuration of the 2-methylpropyl (isopropyl) group were all important to its κ potency and selectivity. The results suggest that, like other κ opioid antagonists such as nor-BNI and GNTI, JDTic requires a second basic amino group to express potent and selective κ antagonist activity in the [³⁵S]GTPγS functional assay. However, unlike previously reported κ antagonists, JDTic also requires a second phenol group in rigid proximity to this second basic amino group. The potent and selective κ antagonist properties of JDTic can be rationalized using the “message-address” concept wherein the (3R,4R)-3,4-dimethyl-4-(hydroxyphenyl)piperidinyl group represents the message, and the basic amino and phenol group in the N substituent constitutes the address. It is interesting to note the structural commonality (an amino and phenol groups) in both the message and address components of JDTic. The unique structural features of JDTic will make this compound highly useful in further characterization of the κ receptor.

Journal of Medicinal Chemistry published new progress about 142335-42-0. 142335-42-0 belongs to tetrahydroisoquinoline, auxiliary class Tetrahydroisoquinoline,Chiral,Carboxylic acid,Amide,Alcohol, name is (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, and the molecular formula is C2H2N4O2, Name: (S)-2-(tert-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem