79261-58-8

Basic information

• Product Name: (3S)-2-CARBOBENZOXY-1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID
• Synonyms: (S)-(+)-N-CBZ-1,2,3,4-TERTRAHYDRO ISOQUINOLINE-3-CARBOXYLIC ACID;N-ALPHA-CARBOBENZOXY-L-1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID;Z-L-1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID;Z-TIC-OH;Z-[3S]-1,2,3,4-TETRAHYDROISOQUINOLENE-3-CARBOXYLIC ACID;Z-D-[3S]-1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID;(S)-(+)-2-(BENZYLOXYCARBONYL)-TETRAHY-DR O-3-ISOQUINOLINECARBOXYLIC ACID, 97%;(S)-N-Benzyloxycarbonyl-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid
• CAS NO: 79261-58-8
• Molecular Formula: C₁₈H₁₇NO₄
• Molecular Weight: 311.33
• Product Categories: Building Blocks for HIV Protease InhibitorsChiral Building Blocks;Cell Signaling Enzymes;Heterocyclic Building Blocks;HIV Protease Reagents&Envelope Proteins;Isoquinolines
• Mol File: 79261-58-8.mol

Chemical Properties

• Melting Point: 137-141 °C
• Boiling Point: 451.38°C (rough estimate)
• Flash Point: 269.8oC
• Appearance: White to pale yellow/Solid
• Density: 1.2626 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 23.5 ° (C=2, MeOH)
• Storage Temp.: Store at 0-5°C
• PKA: 3.86±0.20(Predicted)
• CAS DataBase Reference: (3S)-2-CARBOBENZOXY-1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: (3S)-2-CARBOBENZOXY-1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID(79261-58-8)
• EPA Substance Registry System: (3S)-2-CARBOBENZOXY-1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID(79261-58-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 37/39-26-36-36/37/39
• Hazardous Substances Data: 79261-58-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research:
(3S)-2-Carbobenzoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is used as a reagent in the preparation of antibacterial studies. It plays a crucial role in the development and testing of peptide deformylase inhibitors, such as BB-3497 and its P2' and P3' analogs. These inhibitors are being studied for their potential to combat bacterial infections by targeting a key enzyme involved in protein synthesis in bacteria.
Used in Antibacterial Applications:
In the field of antibacterial research, (3S)-2-Carbobenzoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is utilized for the synthesis of peptide deformylase inhibitors. These inhibitors are designed to disrupt the process of protein synthesis in bacteria, thereby inhibiting their growth and helping to combat antibiotic-resistant strains. The development of such inhibitors is an important step towards creating new and effective antibacterial agents.

InChI:InChI=1/C18H17NO4/c20-17(21)16-10-14-8-4-5-9-15(14)11-19(16)18(22)23-12-13-6-2-1-3-7-13/h1-9,16H,10-12H2,(H,20,21)/t16-/m0/s1

Upstream product

• 501-53-1 benzyl chloroformate 
• 77497-95-1 (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride 
• 63-91-2 L-phenylalanine 
• 74163-81-8 L-Tic-OH 
• 13139-17-8 N-(Benzyloxycarbonyloxy)succinimide 

Downstream Products

• 781662-40-6 (S)-3-(2-aminophenylcarbamoyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester 
• 1238365-80-4 (S)-benzyl 3-((S)-1-phenylethylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1238365-78-0 (S)-benzyl 3-(isopropylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 254102-04-0 (S)-benzyl 3-(methylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1238365-76-8 (S)-benzyl 3-(benzhydrylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1430217-26-7 (S)-benzyl 3-(4-(tert-butoxycarbonyl)phenylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1430217-28-9 (S,E)-tert-butyl 4-(2-(3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acryloyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamido)benzoate 
• 1430217-27-8 (S)-tert-butyl 4-(1,2,3,4-tetrahydroisoquinoline-3-carboxamido)benzoate 
• 1430215-91-0 (S,E)-4-(2-(3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acryloyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamido)benzoic acid 
• 1394169-22-2 (S)-benzyl 3-(4-(2-oxopiperidin-1-yl)phenylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1394169-34-6 (S)-benzyl 3-(4-(3-oxomorpholino)phenylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1394169-58-4 (S,E)-2-(3-(2,4-dimethoxyphenyl)acryloyl)-N-methyl-N-(4-(3-oxomorpholino)phenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 
• 1394169-57-3 (S)-2-(3-(4-methoxyphenyl)propanoyl)-N-methyl-N-(4-(3-oxomorpholino)phenyl)-1,2,3,4-tetra-hydroisoquinoline-3-carboxamide 
• 1394169-56-2 (S)-2-(5-chloro-3-methylbenzo[b]thiophene-2-carbonyl)-N-(4-(3-oxomorpholino)phenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 

Relevant articles and documents

New approaches towards the synthesis of 1,2,3,4-tetrahydro isoquinoline-3-phosphonic acid (TicP)

Two new strategies for the efficient synthesis of racemic 1,2,3,4-tetrahydroisoquinoline-3-phosphonic acid (TicP) (±)-2 have been developed. The first strategy involves the electron-transfer reduction of the easily obtained α,β-dehydro phosphonophenylalanine followed by a Pictet–Spengler cyclization. The second strategy involves a radical decarboxylation–phosphorylation reaction on 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic). In both strategies, the highly electrophilic N-acyliminium ion is formed as a key intermediate, and the target compound is obtained in good yield using mild reaction conditions and readily available starting materials, complementing existing methodologies and contributing to the easy accessibility of (±)-2 for further research.

AGONISTS OF THE CHEMOKINE RECEPTOR CXCR3

The present invention relates to agonists of the chemokine receptor CXCR3, methods of their synthesis and uses thereof.

Discovery and Characterization of Biased Allosteric Agonists of the Chemokine Receptor CXCR3

In this work we report a design, synthesis, and detailed functional characterization of unique strongly biased allosteric agonists of CXCR3 that contain tetrahydroisoquinoline carboxamide cores. Compound 11 (FAUC1036) is the first strongly biased allosteric agonist of CXCR3 that selectively induces weak chemotaxis and leads to receptor internalization and the β-arrestin 2 recruitment with potency comparable to that of the chemokine CXCL11 without any activation of G proteins. A subtle structural change (addition of a methoxy group, 14 (FAUC1104)) led to a contrasting biased allosteric partial agonist that activated solely G proteins, induced chemotaxis, but failed to induce receptor internalization or β-arrestin 2 recruitment. Concomitant structure-activity relationship studies indicated very steep structure-activity relationships, which steer the ligand bias between the β-arrestin 2 and G protein pathway. Overall, the information presented provides a powerful platform for further development and rational design of strongly biased allosteric agonists of CXCR3.

Stereoselective synthesis of diazabicyclic β-lactams through intramolecular amination of unactivated C(sp3)-H bonds of carboxamides by palladium catalysis

An efficient C(sp3)-H bond activation and intramolecular amination reaction via palladium catalysis at the β-position of carboxyamides to make β-lactams was described. The investigation of the substrate scope showed that the current reaction conditions favored activation of the β-methylene group. Short sequences were developed for preparation of various diazabicyclic β-lactam compounds with this method as the key step from chiral proline and piperidine derivatives.

Microwave-assisted synthesis of guanidine organocatalysts bearing a tetrahydroisoquinoline framework and their evaluation in Michael addition reactions

The simple and practical syntheses of chiral guanidine organocatalysts and their evaluation in the asymmetric Michael addition reaction of malonates and β-keto esters with nitro-olefins is reported. These organocatalysts are the first of their kind based on a tetrahydroisoquinoline framework. In addition, a microwave-assisted procedure for introducing the guanidine unit onto amino amide derivatives is reported. The chiral products were obtained with quantitative chemical efficiency (up to 99 % yield) and excellent enantioselectivity (up to 97 % ee). Copyright

Synthesis of tetrahydroisoquinoline-diamine ligands and their application in asymmetric transfer hydrogenation

The use of the tetrahydroisoquinoline scaffold is well documented in biologically active compounds. However, reports of the utilisation of tetrahydroisoquinoline compounds in asymmetric catalysis are limited. The synthesis of novel diamine ligands possessing the tetrahydroisoquinoline (tetrahydroisoquinoline) backbone and evaluation of their activity in the asymmetric transfer hydrogenation of acetophenone are presented. The diamine ligands in conjunction with i-PrOH as the hydrogen source and [RhCl2(Cp*)]2 as the metal precursor proved to be the most effective of the tetrahydroisoquinoline derivatives for this catalytic system. Water was found to have a profound influence on the enantioselectivity of the reaction. Optimisation of the amount water, i-PrOH and catalytic loading content rendered the best result of 70% enantioselectivity for the (S)-1-phenylethanol isomer product.

Synthesis of a novel tetrahydroisoquinolino[2,1-c][1,4]benzodiazepine ring system with DNA recognition potential

The first stereospecific synthesis of a novel tetrahydroisoquinolino[2,1-c] [1,4]benzodiazepine ring system with DNA recognition potential starting from (S)-1,2,3,4-tetrahydroisoquinoline carboxylic acid has been reported. We report the first stereospecif

Tripeptidylpeptidase inhibitors

A compound of formula wherein the substituents are defined as in the specification and salts or hydrates thereof is disclosed as well as a method of treating disorders associated with the inactivation or excessive degradation of cholecystokinin.

Total syntheses of conformationally constrained didemnin B analogues. Replacements of N2O-dimethyltyrosine with L-1,2,3,4-tetrahydroisoquinoline and L-1,2,3,4-tetrahydro-7-methoxyisoquinoline

The design and synthesis of two conformationally constrained analogues of didemnin B are described. The [N,O-Me2Tyr5]residue of didemnin B was replaced with L-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) and L-1,2,3,4-tetrahydro-7-methoxyisoquinoline-3-carboxylic acid (MeO-Tic), which mimic the N,O-dimethylated tyrosine while constraining the conformation of the molecule. Preliminary results indicate that the conformation of the [N,O-Me2Tyr5]residue closely matches the conformation imposed by the Tic replacement.

Evolution of the Dmt-Tic pharmacophore: N-terminal methylated derivatives with extraordinary δ opioid antagonist activity

The δ opioid antagonist H-Dmt-Tic-OH (2',6'-dimethyl-L-tyrosyl-1,2,3,4- tetrahydroisoquinoline-3-carboxylic acid) exhibits extraordinary δ receptor binding characteristics [K(i)(δ) = 0.022 nM; K(i)(μ)/K(i)(δ) = 150 000] and δ antagonism (pA2 = 8.2; Ke = 5.7 nM). A change in chirality of Dmt at Cα (1, 2, 6, 8, 10, 13) curtailed δ receptor parameters, while replacement of its α-amino function by a methyl group (3) led to inactivity; Tyr-Tic analogues 4 and 11 weakly interacted with δ receptors. N-Alkylation of H- Dmt-Tic-OH and H-Dmt-Tic-Ala-OH with methyl groups produced potent δ-opioid ligands with high δ receptor binding capabilities and enhanced δ antagonism: (i) N-Me-Dmt-Tic-OH 5 had high δ opioid binding (K(i)(δ) = 0.2 nM), elevated δ antagonism on mouse vas deferens (MVD) (pA2 = 8.5; K(e) = 2.8 nM), and nondetectable μ activity with guinea pig ileum (GPI). (ii) N,N- Me2-Dmt-Tic-OH (12) was equally efficacious in δ receptor binding (K(i)(δ) = 0.12 nM; K(i)(μ)/K(i)(δ) = 20 000), but δ antagonism rose considerably (pA2 = 9.4; K(e) = 0.28 nM) with weak μ antagonism (pA2 = 5.8; K(e) = 1.58 μM; GPI/MVD = 1:5640). N-Me-(9) and N,N-Me2-Dmt-Tic-Ala-OH (15) also augmented δ opioid receptor binding, such that 15 demonstrated high affinity (K(i)(δ) = 0.0755 nM) and selectivity (K(i)(μ)/K(i)(δ) = 20 132) with exceptional antagonist activity on MVD (pA2 = 9.6; K(e) = 0.22 nM) and weak antagonism on GPI (pA2 = 5.8; K(e) = 1.58 μM; GPI/MVD = 1:7180). Although the amidated dimethylated dipeptide analogue 14 had high K(i)(δ) (0.31 nM) and excellent antagonist activity (pA2 = 9.9; K(e) = 0.12 nM), the increased activity toward μ receptors in the absence of a free acid function at the C- terminus revealed modest δ selectivity (K(i)(μ)/KK(i)(δ) = 1 655) and somewhat comparable bioactivity (GPI/MVD = 4500). Thus, the data demonstrate that N,N-(Me)2-Dmt-Tic-OH (12) and N,NMe2-Dmt-Tic-Ala-OH (15) retained high δ receptor affinities and δ selectivities and acquired enhanced potency in pharmacological bioassays on MVD greater than that of other peptide or non- peptide δ antagonists.