112794-29-3

Usage

Uses

Used in Pharmaceutical Industry:
1,2,3,4-Tetrahydroisoquinoline-3-carboxamide is used as a reactant for the synthesis of 1,2-cyclohexanedicarboxamides, which are known as cathepsin inhibitors. These inhibitors play a crucial role in the development of drugs targeting various diseases, including cancer and neurodegenerative disorders, by modulating the activity of cathepsin enzymes involved in these pathological processes.

InChI:InChI=1/C10H12N2O/c11-10(13)9-5-7-3-1-2-4-8(7)6-12-9/h1-4,9,12H,5-6H2,(H2,11,13)/p+1/t9-/m0/s1

Upstream product

• 57060-86-3 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 
• 41994-51-8 1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid ; hydrochloride 
• 57060-88-5 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid,methyl ester hydrochloride 

Downstream Products

• 147557-04-8 3-aminomethyl-1,2,3,4-tetrahydroisoquinoline 
• 1003559-89-4 2-{[5-(4-methylphenyl)isoxazol-4-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 

Relevant academic research and scientific papers

Substituent-dependent negative hyperconjugation in 2-aryl-1,3-N,N-heterocycles. Fine-tuned anomeric effect?

The epimerization reactions of conformationally inflexible 2-aryl-1,3-N,N-heterocycles were used as model systems to study the role of the nitrogen lone pair-C2 associated antibonding orbital hyperconjugative interactions in the experimentally observed substituent-dependent generalized anomeric effect. The measured reaction free enthalpies were found to correlate well with the sum of the hyperconjugative stabilization energies of all the vicinal donor - acceptor orbital overlaps around C2, obtained from ab initio NBO analysis, and both quantities correlated linearly with the Hammett-Brown substituent constant. The individual stereoelectronic interactions (nN-σ*C2-N, nN-σ*C2-Ar, nN-σ*C2-H) were also observed to exhibit a substituent dependence, despite their distance from the 2-aryl substituent and their nonperiplanar arrangement. The higher the electron-withdrawing effect of the 2-aryl substituent, the larger was the stabilization for nN-σ*C2-Ar, while the overlaps nN-σ*C2-N and nN-σ*C2-H changed in the opposite sense. The different polarization of the acceptor σ* orbitals, caused by the 2-aryl substituent, accounted for the observed propagation of the substituent effect. These results promote a detailed explanation of the useful tautomeric behavior of the 2-aryl-1,3-X,N-heterocycles, and reveal the nature of the connection between the anomeric effect and the Hammett-type linear free energy relationship.

Synthesis and Evaluation of 3-Substituted Analogues of 1,2,3,4-Tetrahydroisoquinoline as Inhibitors of Phenylethanolamine N-Methyltransferase

1,2,3,4-Tetrahydroisoquinoline (THIQ) and aryl-substituted derivatives of THIQ are potent inhibitors of the enzyme that catalyzes the formation of epinephrine - phenylethanolamine N-methyltransferase (PNMT, E.C. 2.1.1.28).In previous studies, we found that substitution of the 3-position of THIQ with a methyl group resulted in enhanced activity as an inhibitor for 3-methyl-THIQ (8) with respect to THIQ itself.To more fully delineate this region of the PNMT active site, we have synthesized and evaluated other 3-substituted THIQ analogues that vary in both steric and electronic character.Extension of the methyl side chain in 8 by a single methylene unit results in diminished potency for 3-ethyl-THIQ (13), suggesting that this zone of the active site is spatially compact; furthermore, the region of steric intolerance may be located principally on only "one side" of the 3-position of bound THIQs, since the carbonyl containing (bent) analogues 3-(methoxycarbonyl)-THIQ (10) and 3-(aminocarbonyl)-THIQ (12) are much less capable of forming a strong enzyme-inhibitor dissociable complex compared to straight-chain derivatives possessing a similar steric component.The good activity of 3-(hydroxymethyl)-THIQ (11) as a PNMT inhibitor cannot be explained solely by steric tolerance for this side chain.We believe that an active-site amino acid residue capable of specific (i.e., hydrogen bond) interactions is located in close proximity to the 3-position of bound THIQs and that association of the OH functionality with this active-site residue results in the enhanced in vitro potency of this analogue (Ki = 2.4 μM) compared to that of THIQ (Ki = 10.3 μM).Incorporation of a hydroxymethyl substituent onto the 3-position of the potent PNMT inhibitor 7,8-dichloro-THIQ (SKF 64139, Ki = 0.24 μM) did not result in the same enhancement in inhibitor potency for 17 (Ki = 0.38 μM).This result suggests that simultaneous binding in an optional orientation of the aromatic halogens, secondary amine, and side-chain hydroxyl functionalities to the PNMT active site is not allowed in this analogue.