142335-41-9

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 300-39-0 3,5-diiodo-l-tyrosine 
• 142335-40-8 (S)-1,2,3,4-Tetrahydro-7-hydroxy-6,8-diiodoisoquinoline-3-carboxylic acid 

Downstream Products

• 1314556-93-8 (S)-2-((2S,3S)-2-(3,3-dimethylbutanamido)-3-methylpentanoyl)-7-(2-(hydroxyamino)-2-oxoethoxy)-N-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 
• 1287261-10-2 (S)-7-(2-(hydroxyamino)-2-oxoethoxy)-N-(4-methoxypheny)-2-(4-phenylbutanoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 
• 1287261-09-9 (S)-2-benzoyl-7-(2-(hydroxyamino)-2-oxoethoxy)-N-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 
• 1287261-08-8 (S)-7-(2-(hydroxyamino)-2-oxoethoxy)-N-(4-methoxyphenyl)-2-(2-phenylacetyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 
• 1287261-48-6 (S)-methyl 2-(2-benzyl-3-(4-methoxyphenylcarbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yloxy)acetate 
• 1287261-49-7 (S)-methyl 2-(3-(4-methoxyphenylcarbamoyl)-2-phenethyl-1,2,3,4-tetrahydroisoquinolin-7-yloxy)acetate 
• 1287261-47-5 (S)-methyl 2-(3-(4-methoxyphenylcarbamoyl)-2-(3-phenylpropyl)-1,2,3,4-tetrahydroisoquinolin-7-yloxy)acetate 
• 1287261-46-4 (S)-methyl 2-(3-(4-methoxyphenylcarbamoyl)-2-(4-phenylbutanoyl)-1,2,3,4-tetrahydroisoquinolin-7-yloxy)acetate 
• 1287261-45-3 (S)-methyl 2-(2-benzoyl-3-(4-methoxyphenylcarbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yloxy)acetate 
• 1287261-44-2 (S)-methyl 2-(3-(4-methoxyphenylcarbamoyl)-2-(2-phenylacetyl)-1,2,3,4-tetrahydroisoquinolin-7-yloxy)acetate 
• 1287261-21-5 (S)-2-((S)-2-amino-3-methylbutanoyl)-7-(2-(hydroxyamino)-2-oxoethoxy)-N-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide hydrochloride 
• 1287261-20-4 (S)-2-((S)-2-aminopropanoyl)-7-(2-(hydroxyamino)-2-oxoethoxy)-N-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide hydrochloride 
• 1287261-19-1 (S)-2-((S)-2-amino-4-methylpentanoyl)-7-(2-(hydroxyamino)-2-oxoethoxy)-N-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide hydrochloride 
• 1287261-18-0 (S)-2-((2S,3S)-2-amino-3-methylpentanoyl)-7-(2-(hydroxyamino)-2-oxoethoxy)-N-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide hydrochloride 

Relevant academic research and scientific papers

Synthesis and pharmacological evaluation of Tic-hydantoin derivatives as selective σ1 ligands. Part 1

Herein is described a new class of selective σ1 ligands consisting of tetrahydroisoquinoline-hydantoin (Tic-hydantoin) derivatives. Compound 3a has high affinity (IC50 = 16 nM) for the σ1 receptor and is selective in a large panel of therapeutic targets. This first study presents structural changes around the Tic-hydantoin core, leading to a Tic-hydantoin analogue with a higher σ1 affinity (IC50 ≈ 1 nM).

MDM2 DEGRADERS AND USES THEREOF

The present invention relates to compounds and methods useful for the modulation of mouse double minute 2 homolog ("MDM2") protein via ubiquitination and/or degradation by compounds according to the present invention.

IRAK DEGRADERS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

IRAK DEGRADERS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same. The compounds include an IRAK binding moiety capable of binding to IRAK4 and a degradation inducing moiety (DIM). The DIM could be DTM a ligase binding moiety (LBM) or lysine mimetic. The compounds could be useful as IRAK protein kinase inhibitors and applied to IRAK mediated disorders.

IRAK DEGRADERS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

TETRAHYDROISOQUINOLINES AS PRMT5 INHIBITORS

A compound of formula (I) wherein: n is 1 or 2; p is 0 or 1; R1a, R1b, R1c and R1d are independently selected from the group consisiting of H, halo, C1-4 alkoxy, C1-4 alkyl, C1-4 fluoroalkyl, C3-4 cycloalkyl, NH-C1-4 alkyl and cyano; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2e is H or Me; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted C5-12 heteroaryl; wherein when R2e is H, at least one of R1a, R1b, R1c and R1d is selected from C1-4 alkoxy, C2-4 alkyl, C1-4 fluoroalkyl, C3-4 cycloalkyl, NH-C1-4 alkyl and cyano.

Development of tetrahydroisoquinoline-based hydroxamic acid derivatives: Potent histone deacetylase inhibitors with marked in vitro and in vivo antitumor activities

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 exhibited promising HDAC8 inhibitory and antiproliferative activities. Herein, we report the design and development of a new class of tetrahydroisoquinoline-bearing hydroxamic acid analogues as potential HDACi and anticancer agents. In vitro biological 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.

Discovery of a tetrahydroisoquinoline-based hydroxamic acid derivative (ZYJ-34c) as histone deacetylase inhibitor with potent oral antitumor activities

Histone deacetylase (HDAC) has emerged as an attractive target for the development of antitumor agents during the past decade. Previously tetrahydroisoquinoline-bearing hydroxamic acid analogue, 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.

Design, synthesis and preliminary activity assay of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as novel Histone deacetylases (HDACs) inhibitors

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 biological screening showed that most

Comparison of the inhibition of human and Trypanosoma cruzi prolyl endopeptidases

Prolyl endopeptidases (PEPs) have been found in numerous species. Inhibitors of human enzyme could correct cognitive deficits in Alzheimer patients while inhibition of Trypanosoma cruzi PEP could prevent invasion phase in Chagas disease. A structure-activity relationship study carried out in a tetrahydroisoquinoline series allowed to obtain potent competitive inhibitors superior to SUAM-1221. Besides, inhibitors expected to act according to an irreversible mechanism revealed to be superior to JPT-4819, for applications linked to human enzyme inhibition.