91523-50-1

Usage

Uses

Used in Pharmaceutical Research:
6-Hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid is used as a key intermediate in the synthesis of proline-containing peptides. These peptides have potential applications as caspase-2 inhibitors, which are important targets in the development of drugs for the treatment of various diseases, including cancer and neurodegenerative disorders.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, 6-Hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid serves as a valuable building block for the design and synthesis of novel bioactive compounds. Its unique structural features allow for the development of molecules with specific biological activities, making it a promising candidate for further research and drug discovery efforts.
Used in Drug Development:
6-Hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid is utilized in the development of new drugs targeting caspase-2, an enzyme involved in the regulation of apoptosis. Inhibition of caspase-2 has been shown to have potential therapeutic benefits in the treatment of diseases characterized by uncontrolled cell death, such as neurodegenerative disorders and certain types of cancer.
Used in Biochemical Studies:
6-Hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid is also used in biochemical studies to investigate the mechanisms of caspase-2 inhibition and its role in cellular processes. Understanding the interactions between 6-Hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid and caspase-2 can provide valuable insights into the development of more effective and targeted therapies for various diseases.

InChI:InChI=1/C10H11NO3/c12-7-1-2-8-6(5-7)3-4-11-9(8)10(13)14/h1-2,5,9,11-12H,3-4H2,(H,13,14)

Upstream product

• 588-05-6 m-tyramine 
• 298-12-4 Glyoxilic acid 
• 38449-59-1 2-(3-hydroxyphenyl)ethylamine hydrobromide 
• 2039-67-0 2-(3-methoxyphenyl)-1-ethanamine 
• 24550-32-1 1-(benzyloxy)-3-(2-nitrovinyl)benzene 
• 1700-37-4 3-Benzyloxybenzaldehyde 
• 24550-32-1 1-(benzyloxy)-3-[(E)-2-nitroethenyl]benzene 
• 3458-98-8 3-hydroxyphenylethylamine hydrochloride 
• 51061-22-4 2-(3-benzyloxyphenyl)ethylamine 
• 100-83-4 meta-hydroxybenzaldehyde 

Downstream Products

• 350014-18-5 1,2,3,4-Tetrahydro-6-hydroxy-1-isoquinolinecarboxylic acid methyl ester 
• 373633-78-4 C₂₂H₂₄NO₅^(1-)*Na⁽¹⁺⁾ 
• 531556-15-7 C₂₄H₂₃NO₃*ClH 
• 1068527-08-1 C₂₆H₂₅NO₄ 
• 499139-27-4 2-(tert-butoxycarbonyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid 
• 373634-57-2 C₂HF₃O₂*C₃₂H₄₅N₃O₄ 
• 373634-41-4 C₂HF₃O₂*C₃₁H₄₃N₃O₆ 
• 373637-03-7 C₂HF₃O₂*C₃₂H₄₀N₄O₃ 
• 373634-23-2 C₂HF₃O₂*C₃₀H₄₃N₃O₄ 
• 373636-62-5 C₂HF₃O₂*C₃₂H₃₉N₃O₃ 
• 373633-79-5 1-[[[2-[bis(1-methylethyl)amino]ethyl]amino]carbonyl]-3,4-dihydro-6-(phenylmethoxy)-2-(1H)-isoquinoline-carboxylic acid 1,1-dimethylethyl ester methanesulfonate 
• 531553-76-1 C₃₅H₃₇N₃O₃ 
• 373638-24-5 C₂₉H₄₁N₃O₄ 
• 373637-08-2 C₂₉H₄₁N₃O₄ 

Relevant academic research and scientific papers

Synthesis of novel (benzimidazolyl)isoquinolinols and evaluation as adenosine A1 receptor tools

G protein-coupled receptors (GPCRs) constitute the largest family of transmembrane receptors in eukaryotes. The adenosine A1 receptor (A1AR) is a class A GPCR that is of interest as a therapeutic target particularly in the treatment of cardiovascular disease and neuropathic pain. Increased knowledge of the role A1AR plays in mediating these pathophysiological processes will help realise the therapeutic potential of this receptor. There is a lack of enabling tools such as selective fluorescent probes to study A1AR, therefore we designed a series of (benzimidazolyl)isoquinolinols conjugated to a fluorescent dye (31-35, 42-43). An improved procedure for the synthesis of isoquinolinols from tetrahydroisoquinolinols via oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and atmospheric oxygen is reported. This synthetic method offers advantages over previous metal-based methods for the preparation of isoquinolinols and isoquinolines, which are important scaffolds found in many biologically active compounds and natural products. We report the first synthesis of the (benzimidazolyl)isoquinolinol compound class, however the fluorescent conjugates were not successful as A1AR fluorescent ligands.

Exploiting differences in caspase-2 and -3 S2 subsites for selectivity: Structure-based design, solid-phase synthesis and in vitro activity of novel substrate-based caspase-2 inhibitors

Several caspases have been implicated in the pathogenesis of Huntington's disease (HD); however, existing caspase inhibitors lack the selectivity required to investigate the specific involvement of individual caspases in the neuronal cell death associated with HD. In order to explore the potential role played by caspase-2, the potent but non-selective canonical Ac-VDVAD-CHO caspase-2 inhibitor 1 was rationally modified at the P2 residue in an attempt to decrease its activity against caspase-3. With the aid of structural information on the caspase-2, and -3 active sites and molecular modeling, a 3-(S)-substituted-l-proline along with four additional scaffold variants were selected as P2 elements for their predicted ability to clash sterically with a residue of the caspase-3 S2 pocket. These elements were then incorporated by solid-phase synthesis into pentapeptide aldehydes 33a-v. Proline-based compound 33h bearing a bulky 3-(S)-substituent displayed advantageous characteristics in biochemical and cellular assays with 20- to 60-fold increased selectivity for caspase-2 and ～200-fold decreased caspase-3 potency compared to the reference inhibitor 1. Further optimization of this prototype compound may lead to the discovery of valuable pharmacological tools for the study of caspase-2 mediated cell death, particularly as it relates to HD.

Tetrahydroisoquinoline 1-carboxamides as growth hormone secretagogues

Several novel series of tetrahydroisoquinoline 1-carboxamides were prepared and shown to be potent growth hormone (GH) secretagogues. Among them, carbamate 12a-E2 displays excellent in vivo activity by increasing plasma GH 10-fold in an anesthetized IV rat model.

Tetrahydroisoquinoline based sulfonamide hydroxamates as potent matrix metalloproteinase inhibitors

The synthesis and MMP inhibitory activity of a series of tetrahydroisoquinoline based sulfonamide hydroxamates are described. In nine MMPs tested, most of the compounds display potent inhibition activity except for MMP-7. Some subtle isozyme selectivity is observed by varying the substituents at the 6- and 7-positions and aromatic ring of arylsulfonyl groups.

Tetrahydroisoquinoline analogs as modulators of chemokine receptor activity

Tetrahydroisoquinoline analogs are provided which are modulators of chemokine receptor activity. The tetrahdroisoquinoline analogs thereof have the structure wherein R1, R2, R3, R3a, X1, X2, X3, X4, m, n and p are as described herein.

6-Substituted decahydroisoquinoline-3-carboxylic acids as potent and selective conformationally constrained NMDA receptor antagonists

We have prepared a series of 6-substituted decahydroisoquinoline-3- carboxylic acids, and structurally similar analogs, as potential N-methyl-D- aspartate receptor antagonists. There is a large body of evidence to support the use of such compounds as cerebroprotective agents in a variety of acute and chronic neurodegenerative disorders, where some component of glutamate- mediated excitotoxicity may exist. The compounds prepared were evaluated in vitro in both receptor binding assays ([3H]CGS19755, [3H]AMPA, and [3H]kainic acid) and in a cortical wedge preparation (versus NMDA, AMPA, and kainic acid) to determine affinity, potency, and selectivity. The new amino acids were also evaluated in vivo for their ability to block NMDA-induced lethality in mice. We synthesized many of the possible diastereomers of the decahydroisoquinoline nucleus in order to examine the spatial and steric requirements for affinity at the NMDA receptor and activity as NMDA antagonists. From our structure-activity relationship we identified two potent and selective NMDA receptor antagonists, the phosphonate- and tetrazole-substituted amino acids 31a and 32a, respectively, that show good activity in animals following systemic administration. For example, 31a and 32a selectively displaced [3H]CGS19755 binding with IC50s of 55 ± 14 and 856 ± 136 nM, respectively, and selectively antagonized responses due to NMDA in a cortical wedge preparation with IC50s of 0.15 ± 0.01 and 1.39 ± 0.29 μM, respectively. And compounds 31a and 32a blocked NMDA-induced lethality in mice with minimum effective doses of 1.25 and 2.5 mg/kg (intraperitoneal), respectively. These novel amino acids are among some of the most potent NMDA antagonists described thus far, and are excellent candidates for development as neuroprotective agents for a number of CNS disorders.

Synthesis and Murine Antineoplastic Activity of Bis Derivatives of Pyrroloisoquinoline

The synthesis of 4,5-dihydropyrroloisoquinolines is reported.A key intermediate in the synthesis of 8-methoxy-4,5-dihydropyrroloisoquinolines, 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (6), was prepared by using a regiospeci