134388-87-7

Usage

Chemical Properties

white to yellow crystalline powder

InChI:InChI=1/C10H11NO3/c12-8-2-1-6-5-11-9(10(13)14)4-7(6)3-8/h1-3,9,11-12H,4-5H2,(H,13,14)/t9-/m0/s1

Upstream product

• 76824-99-2 6-hydroxy-1,2,3,4-tetrahydro-3-isoquinoline carboxylic acid 
• 50-00-0 formaldehyd 
• 587-33-7 m-tyrosine 
• 6720-12-3 rac-N-methyl-meta-tyrosine 
• 775-06-4 D/L-3-hydroxy-phenylalanine 

Downstream Products

• 152495-61-9 methyl 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 
• 1541189-76-7 C₁₂H₁₁NO₃ 
• 942076-85-9 methyl 6-hydroxyisoquinoline-3-carboxylate 
• 845552-56-9 2-(tert-butoxycarbonyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 
• 134388-88-8 ethyl 6-hydroxy-2-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 
• 128073-41-6 ethyl decahydro-6-hydroxy-2-methoxycarbonyl-3-isoquinolinecarboxylate 

Relevant academic research and scientific papers

Optimized Opioid-Neurotensin Multitarget Peptides: From Design to Structure-Activity Relationship Studies

Fusion of nonopioid pharmacophores, such as neurotensin, with opioid ligands represents an attractive approach for pain treatment. Herein, the μ-/δ-opioid agonist tetrapeptide H-Dmt-d-Arg-Aba-β-Ala-NH2(KGOP01) was fused to NT(8-13) analogues. Since the NTS1 receptor has been linked to adverse effects, selective MOR-NTS2 ligands are preferred. Modifications were introduced within the native NT sequence, particularly a β3-homo amino acid in position 8 and Tyr11substitutions. Combination of β3hArg and Dmt led to peptide 7, a MOR agonist, showing the highest NTS2 affinity described to date (Ki= 3 pM) and good NTS1 affinity (Ki= 4 nM), providing a >1300-fold NTS2 selectivity. The (6-OH)Tic-containing analogue 9 also exhibited high NTS2 affinity (Ki= 1.7 nM), with low NTS1 affinity (Ki= 4.7 μM), resulting in an excellent NTS2 selectivity (>2700). In mice, hybrid 7 produced significant and prolonged antinociception (up to 8 h), as compared to the KGOP01 opioid parent compound.

Oxidative cyclization of N-methyl-dopa by a fungal flavoenzyme of the amine oxidase family

Flavin-dependent enzymes catalyze many oxidations, including formation of ring structures in natural products. The gene cluster for biosynthesis of fumisoquins, secondary metabolites structurally related to isoquinolines, in the filamentous fungus Aspergillus fumigatus harbors a gene that encodes a flavoprotein of the amine oxidase family, termed fsqB (fumisoquin biosynthesis gene B). This enzyme catalyzes an oxidative ring closure reaction that leads to the formation of isoquinoline products. This reaction is reminiscent of the oxidative cyclization reported for berberine bridge enzyme and tetrahydrocannabinol synthase. Despite these similarities, amine oxidases and berberine bridge enzyme–like enzymes possess distinct structural properties, prompting us to investigate the structure–function relationships of FsqB. Here, we report the recombinant production and purification of FsqB, elucidation of its crystal structure, and kinetic analysis employing five putative substrates. The crystal structure at 2.6 ? resolution revealed that FsqB is a member of the amine oxidase family with a covalently bound FAD cofactor. N-methyl-dopa was the best substrate for FsqB and was completely converted to the cyclic isoquinoline product. The absence of the meta-hydroxyl group, as e.g. in L-Nmethyl-tyrosine, resulted in a 25-fold lower rate of reduction and the formation of the demethylated product L-tyrosine, instead of a cyclic product. Surprisingly, FsqB did not accept the D-stereoisomer of N-methyltyrosine, in contrast to N-methyl-dopa, for which both stereoisomers were oxidized with similar rates. On the basis of the crystal structure and docking calculations, we postulate a substrate-dependent population of distinct binding modes that rationalizes stereospecific oxidation in the FsqB active site.

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.

Chemoenzymatic Approach to (S)-1,2,3,4-Tetrahydroisoquinoline Carboxylic Acids Employing D-Amino Acid Oxidase

Optically pure 1,2,3,4-tetrahydroisoquinoline carboxylic acids constitute an important class of building blocks for the synthesis of natural products and synthetic pharmaceuticals. However, redox deracemization of racemic 1,2,3,4-tetrahydroisoquinoline carboxylic acids as an attractive method is still challenging for the lack of suitable oxidoreductases. Herein, a D-amino acid oxidase from Fusarium solani M-0718 (FsDAAO) with broad substrate scope and excellent enantioselectivity was exploited through genome mining, and applied for the kinetic resolution of a number of racemic 1- and 3-carboxyl substituted tetrahydroisoquinolines to yield the corresponding (S)-enantiomers with excellent enantiomeric excess (ee) values (up to >99%). By using FsDAAO in combination with ammonia-borane in one pot, deracemization of these racemic carboxyl-substituted tetrahydroisoquinolines was achieved with conversions up to >98% and >99% ee. Preparative-scale deracemization of racemic 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid and 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was also demonstrated with good isolated yields (82% and 73%, respectively) and ee>99%. Our study provides an effective method for the synthesis of enantiomeric pure 1,2,3,4-tetrahydroisoquinoline carboxylic acids. This method is expected to provide access to chiral carboxyl-substituted 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydro-?-carbolines. (Figure presented.).

MODULATORS OF REV-ERB

The subject matter herein concerns the identification and development of potent synthetic REV-ERB ligands, such as in vivo agonists and antagonists. These compounds allow for characterization of the effects of modulation of this receptor in vivo specifically on circadian behavior and metabolism, and have suitable characteristics for development of medicinal compounds useful for treatment of malconditions such as diabetes, obesity, atherosclerosis, dyslipidemia, a circadian rhythm disorder, coronary artery disease, bipolar disorder, depression, cancer, a sleep disorder, an anxiety disorder, an addiction disorder, a bone-related disorder such osteoporosis, a skeletal muscle disease, e.g., with compromised exercise capacity, or an autoimmune disorder such as psoriasis, multiple sclerosis, inflammatory bowel disease, and others.

6-Hydroxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid mimics active conformation of tyrosine in opioid peptides

6-Hydroxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (6Htc) has been proposed as a rigid mimic of tyrosine conformation in opioid ligand-receptor complex. The significant receptor binding to mu and delta opioid receptors of respective analogues of

TETRAHYDROISOQUINOLINE OR ISOCHROMAN COMPOUNDS AS ORL-1 RECEPTOR LIGANDS FOR THE TREATMENT OF PAIN AND CNS DISORDERS

This invention provides the compounds of formula (I), or its a pharmaceutically acceptable ester or amide of such compound, or a pharmaceutically acceptable salt thereof, wherein X1 is NH; R1, R2, R4 through Rs

Process for producing tetrahydroisoquinoline-3-carboxylic acid compounds

The present invention relates to a process for producing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid compounds or salts thereof represented by the following formula (II): STR1 wherein R1, R2 and R3 independently represent hydrogen, hydroxy or lower alkoxy, and R4 represent hydrogen, lower alkyl, aryl or aralkyl, the process comprising, allowing phenylalanine compounds to react with formaldehyde or paraformaldehyde in the presence of sulfuric acid or hydrobromic acid, the phenylalanine compounds being represented by the following formula (I): STR2 wherein R1, R2, R3 and R4 have the same meaning as defined above.

DECAHYDROISOQUINOLINE COMPOUNDS AS EXCITATORY AMINO ACID RECEPTOR ANTAGONISTS

This invention provides novel decahydroisoquinoline compounds which are useful as excitatory amino acid receptor antagonists and in the treatment of neurological disorders.

A Novel Series of Selective, Non-Peptide Inhibitors of Angiotensin II Binding to the AT2 Site

The availability of peptide and non-peptide Ang II receptor antagonists has permitted the study of Ang II receptor heterogeneity.It is now widely recognized that there are at least two distinct Ang II receptor subtypes.AT1 receptors are selective in their recognition of agents such as losartan, DuP 532,L-158,809,SKF108566, and similar non-peptides.To date, all of the well-known actions of Ang II in mammals are blocked by the AT1 selective antagonists such as losartan and are thus designated as being mediated by the AT1 receptor.Although there have been reports of functional activity mediated through AT2 sites, the pharmacological role for the AT2 receptor has not yet been elucidated.Herein, we report the chemistry and SAR on a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids which have selective affinity for AT2 receptors.The most potent of which (19) has an IC50 of 30 nM for the AT2 receptor in the rat adrenal radioligand binding assay.