186390-77-2

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 63, p. 4116, 1998 DOI: 10.1021/jo972184e

InChI:InChI=1/C9H10N2O2/c12-11(13)9-2-1-8-6-10-4-3-7(8)5-9/h1-2,5,10H,3-4,6H2

Upstream product

• 174648-97-6 1-(3,4-dihydro-6-nitroisoquinolin-2(1H)-yl)ethanone 
• 124-63-0 methanesulfonyl chloride 
• 186390-74-9 2-(2-Hydroxymethyl-5-nitro-phenyl)-ethanol 
• 55649-51-9 2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline 
• 458-85-5 2,2,2-trifluoro-N-(2-phenylethyl)acetamide 
• 64-04-0 phenethylamine 
• 273405-00-8 N-methylsulfonyl-m-nitrophenylethylamine 
• 19008-62-9 1-(3-nitrophenyl)-2-ethanamine hydrochloride 
• 91-21-4 1,2,3,4-tetrahydroisoquinoline 
• 174648-94-3 N-acetyl-8-nitro-1,2,3,4-tetrahydroisoquinoline 
• 186390-71-6 2-(carboxy-5-nitro-phenyl)malonic acid dimethyl ester 
• 1025823-76-0 2-(2-Carboxy-5-nitro-phenyl)-malonic acid 
• 39585-32-5 2-carboxymethyl-4-nitro-benzoic acid 
• 99-60-5 2-chloro-4-nitrobenzoic acid 

Downstream Products

• 186390-79-4 6-Nitro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 
• 72299-68-4 1,2,3,4-Tetrahydro-isoquinolin-7-ylamine 
• 72299-67-3 1,2,3,4-tetrahydroisoquinolin-6-amine 
• 164148-92-9 tert-butyl 6-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1422041-04-0 C₁₆H₁₅N₃O₄ 
• 1422040-85-4 C₄₀H₄₂N₆O₄ 

Relevant academic research and scientific papers

N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine Derivatives as Selective Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms

In this study, we described a series of N-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine derivatives as selective JAK2 (Janus kinase 2) inhibitors. Systematic exploration of the structure-activity relationship though cyclization modification based on previously reported compound 18e led to the discovery of the superior derivative 13ac. Compound 13ac showed excellent potency on JAK2 kinase, SET-2, and Ba/F3V617F cells (high expression of JAK2V617F mutation) with IC50 values of 3, 11.7, and 41 nM, respectively. Further mechanistic studies demonstrated that compound 13ac could downregulate the phosphorylation of downstream proteins of JAK2 kinase in cells. Compound 13ac also showed good selectivity in kinase scanning and potent in vivo antitumor efficacy with 82.3% tumor growth inhibition in the SET-2 xenograft model. Moreover, 13ac significantly ameliorated the disease symptoms in a Ba/F3-JAK2V617F allograft model, with 77.1% normalization of spleen weight, which was more potent than Ruxolitinib.

COMPOUNDS FOR TREATMENT OF CARDIAC ARRHYTHMIAS AND HEART FAILURE

This disclosure concerns compounds and a method for modulating the activity of calcium ion channels, including Ca2+-induced (or Ca2+-activated) calcium release channels and conformationally coupled calcium release channels such as ryanodine receptors. Some of the compounds have a structure according to formula I, or a stereoisomer, tautomer, hydrate, solvate, prodrug, or pharmaceutically acceptable salt thereof.

METHODS FOR IDENTIFICATION OF JAK KINASE INTERACTING MOLECULES AND FOR THE PURIFICATION OF JAK KINASES

The present invention relates to immobilization compounds and methods useful for the identification of JAK interacting compounds or for the purification or identification of JAK.

NOVEL NUCLEOSIDE TRANSPORT INHIBITORS

Compounds or compositions that are inhibitors and/or ligands of nucleoside transporters; and methods of treating cancer, heart disease and stroke, as well as AIDS and other infectious diseases

Synthesis and flow cytometric evaluation of novel 1,2,3,4-tetrahydroisoquinoline conformationally constrained analogues of nitrobenzylmercaptopurine riboside (NBMPR) designed for probing its conformation when bound to the es nucleoside transporter

Novel regioisomers of conformationally constrained analogues of the potent es nucleoside transporter ligand, nitrobenzylmercaptopurine riboside (NBMPR), designed for probing its bound (bioactive) conformation, were synthesized and evaluated as es transporter ligands by flow cytometry. Purine 6-position 5, 6, 7, or 8-nitro-1,2,3,4-tetrahydroisoquinolylpurine ribosides, in which the nitrobenzyl moiety in NBMPR has been locked into the nitro-1,2,3,4-tetrahydroisoquinoline system, were synthesized by reaction of the appropriate nitro-1,2,3,4-tetrahydroisoquinoline with 6-chloropurine riboside. Flow cytometry was performed using 5-(SAENTA)-X8-fluorescein as the competitive ligand. A high degree of variation in the es transporter binding capacity of the target compounds was observed, with the Ki values ranging from 0.45 nM for the most tightly bound compound (4) to 300 nM for the least tightly bound compound (5). The Ki of NBMPR was 0.70 nM, a little higher than that of compound 4. Compound 4 is the isomer that has the nitro group in the best orientation at the es transporter binding site compared to the other three compounds, 2, 3, and 5.

Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein B (ApoB) secretion

Compositions comprising a lipid lowering agent selected from cholesterol biosynthesis inhibitors, bile acid sequestrants, fibrates, cholesterol absorption inhibitors, and niacin; and an inhibitor of microsomal triglyceride transfer protein for treating atherosclerosis, obesity and related diseases.

Apo B-secretion/MTP inhibitory amides

PCT No. PCT/IB97/01368 Sec. 371 Date Apr. 20, 1999 Sec. 102(e) Date Apr. 20, 1999 PCT Filed Nov. 3, 1997 PCT Pub. No. WO98/23593 PCT Pub. Date Jun. 4, 1998This invention is directed to compounds of formula (I) or the stereoisomers, pharmaceutically accept

Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and their use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein B (Apo B) secretion

Compounds of formula (I), STR1 wherin X is CH2, CO, CS or SO2 ; Y is selected from: a direct link, aliphatic hydrocarbylene radicals having up to 20 carbon atoms, which radical may be mono-substituted by hydroxy, (C1 -C10)alkoxy, (C1 -C10)acyl, (C1 -C10)acyloxy, or (C6 -C10)aryl, NH, and O, provided that if X is CH2,Y is a direct link; Z is selected from the following groups: (1) H, halo, cyano, (2) hydroxy, (C1 -C10)alkoxy, (C1 -C10)a1kylthio, (C1 -C10)acyl, thiophenylcaronyl (C1 -C10)alkoxycarbonyl, (3) (C1 -C10)aklkyammo, di(C1 -C10)alylamino, (C6 -C10)aryl(C1 -C10)alkylamino, provided that Y is not O or NH, (4) unsubstituted vinyl, (C6 -C10)aryl, (C3 -C8)cycloalkyl and fused benz derivatives thereof, (C7 -C10)polycycloalkyl, (C4 -C8)cycloalkenyl, (C7 -C10)polycycloalkenyl, (5) (C6 -C10)aryloxy, (C6 -C10)aryltio, (C6 -C10)aryl(C1 -C10)alkoxy, (C6 -C10)aryl(C1 -C10)alkylthio, (C3 -C8)cycloalkyloxy, (C4 -C8)cycloalkenyloxy, (6) heterocyclyl sclected from the group consisting of monocyclic radicals and fused polycycuic radicals, wherein said radicals contain a total of from 5 to 14 ring atoms, wherein said radicals contain a total of from 1 to 4 ring heteroatoms independently selocted from oxygen, nitrogen, and sulfur, and wherein the individual rings of said radicals may be independendy satated, partally unsaturated, or aromatic, provided that if X is CH2, Z is H or is selected from groups (4) and (6), wherein, when Z contains one or more rings, said rings may each independently bear 0 to 4 substituents independently selected from halo, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyl, phenyl phenoxy, phenylthio, halophenylthio, benzyl, benzyloxy, (C1 -C10)alkyl, (C1 -C10)alkoxy, (C1 -C10)alkoxycarbonyl, (C1 -C10)althyltio, (C1 -C10)altylamino, (C1 -C10)alkylaminocarbonyl, di(C1 -C10)alkylamino, di(C1 -C10)alkylaminocarbonyl, di(C1 -C10)alkyo(C1 -C10)alkoxy, (C1 -C3)perfluoroalkyl, (C1 -C3)perfluoroalkoxy, (C1 -C10)acyl, (C1 -C10)acyloxy, (C1 -C10)acyloxy(C1 -C10)alkyl, and pyrrolidinyl; and pharmaceutically acceptable salts thereof.