55649-51-9

Usage

InChI:InChI=1/C11H10F3NO/c12-11(13,14)10(16)15-6-5-8-3-1-2-4-9(8)7-15/h1-4H,5-7H2

Upstream product

• 91-21-4 1,2,3,4-tetrahydroisoquinoline 
• 407-25-0 trifluoroacetic anhydride 
• 50-00-0 formaldehyd 
• 458-85-5 2,2,2-trifluoro-N-(2-phenylethyl)acetamide 
• 383-63-1 ethyl trifluoroacetate, 
• 672949-77-8 2-bromo-1-(3,4-dihydroisoquinolin-2(1H)-yl)-2,2-difluoroethan-1-one 
• 354-58-5 1,1,1-Trichloro-2,2,2-trifluoroethane 
• 64-04-0 phenethylamine 

Downstream Products

• 74291-57-9 2-(2,2,2-trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinoline-7-sulfonyl chloride 
• 74291-58-0 2-(2,2,2-Trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid (2,3-dichloro-phenyl)-amide 
• 74291-33-1 1,2,3,4-Tetrahydro-isoquinoline-7-sulfonic acid (2,3-dichloro-phenyl)-amide; hydrochloride 
• 82771-27-5 7-acetyl-1,2,3,4-tetrahydroisoquinoline hydrochloride 
• 1400651-18-4 N-(4-fluorophenyl)-2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide 
• 1400651-19-5 N-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide 
• 1400648-43-2 2-[2-(4-tert-Butylphenyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide 
• 31404-61-2 1,2,3,4-tetrahydroisoquinoline-7-sulfonamide 
• 186390-77-2 6-nitro-1,2,3,4-tetrahydro-isoquinoline 
• 42923-79-5 7-nitro-1,2,3,4-tetrahydroisoquinoline 
• 186390-79-4 6-Nitro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 
• 171049-42-6 tert-butyl 3,4-dihydro-7-nitroisoquinoline-2(1H)-carboxylate 
• 164148-92-9 tert-butyl 6-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate 

Relevant academic research and scientific papers

New 1,2,3,4-tetrahydroisoquinoline derivatives as modulators of proteolytic cleavage of amyloid precursor proteins

A type of new 1,2,3,4-tetrahydroisoquinoline derivatives was synthesized via concise procedure from commercially available tetrahydroisoquinoline. These derivatives were delicately designed to possess propargyl-related pharmacophores simulated with a monoamine oxidase inhibitor rasagiline. We investigated the effect of these synthetic tetrahydroisoquinoline derivatives on the regulation of proteolytic processing of amyloid precursor protein (APP) by an ERK-dependent signaling pathway. Additionally, these compounds were also evaluated on the prevention of the proteolytic processing of C99 as γ-secretase inhibitors by using a highly efficient cell-based reporter gene assay for γ-secretase. The results suggested that certain compounds might be explored to possess both sAPPα-releasing stimulation and γ-secretase inhibitory potency, which may reflect the synergetic potential of neuroprotective activities for the treatment of Alzheimer's disease as they possessed both ERK activation and inhibition of amyloidogenic Aβ release.

Electrochemical approach to trifluoroacetamide synthesis from 1,1,1-trichloro-2,2,2-trifluoroethane (CFC-113a) catalyzed by B12complex

One-pot synthetic approach to produce trifluoroacetamide has been developed using an electrochemical method with the B12 complex as a catalyst under mild conditions, in open air at room temperature. Thirty examples of trifluoroacetamide were synthesized from 1,1,1-trichloro-2,2,2-trifluoroethane (CFC-113a) in moderate to good yields. This user-friendly strategy is compatible with a broad range of trifluoroacetamide syntheses.

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 AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured.The variables shown in Formula AA are as defined in the claims. The compounds of formula AA are NLRP3 activity modulators and, as such, can be used in the treatment of metabolic disorders (e.g. Type 2 diabetes, atherosclerosis, obesity or gout), a disease of the central nervous system (e.g. Alzheimer's disease, multiple sclerosis, Amyotrophic Lateral Sclerosis or Parkinson's disease), lung disease (e.g. asthma, COPD or pulmonary idiopathic fibrosis), liver disease (e.g. NASH syndrome, viral hepatitis or cirrhosis), pancreatic disease (e.g. acute pancreatitis or chronic pancreatitis), kidney disease (e.g. acute kidney injury or chronic kidney injury), intestinal disease (e.g. Crohn's disease or Ulcerative Colitis), skin disease (e.g. psoriasis), musculoskeletal disease (e.g. scleroderma), a vessel disorder (e.g. giant cell arteritis), a disorder of the bones (e.g. osteoarthritis, osteoporosis or osteopetrosis disorders), eye disease (e.g. glaucoma or macular degeneration), a disease caused by viral infection (e.g. HIV or AIDS), an autoimmune disease (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus or Autoimmune Thyroiditis), cancer or aging.

Synthesis of trifluoromethyl moieties by late-stage copper (I) mediated nucleophilic fluorination

The nucleophilic fluorination of bromodifluoromethyl derivatives mediated by the complex (PPh3)3CuF is described. Under the reaction conditions, different trifluoroacetates, trifluoroketones, trifluoroarenes and trifluoroacetamides were obtained in good yields.

An efficient and convenient synthesis of acyl coa: Monoacylglycerol acyltransferase 2 inhibitor, 2-[2-(4-tert-butylphenyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide

An efficient and convenient synthesis of MGAT2 inhibitor, 2-[2-(4-tert-butylphenyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-1,2,3, 4-tetrahydroisoquinoline-6-sulfonamide (1), is reported. The optimized route consists of an effective chlorosulfonylation and debromination, resulting in an increase in the total yield from 6.8% to 45%, compared with our previous method. This synthetic approach enabled the synthesis of 1 to be scaled-up to a multi-gram scale.

Efficient DBU accelerated synthesis of 18F-labelled trifluoroacetamides

Nucleophilic 18F-fluorination of bromodifluoromethyl derivatives was performed using [18F]Bu4NF in the presence of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene). This novel procedure provided a diverse set of [18F]trifluoroacetamides in good to excellent radiochemical conversions. A mechanism where DBU acts as organomediator in this transformation is proposed.

Identification of 2-[2-(4-tert-butylphenyl)ethyl]-N-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (29) as an orally available MGAT2 inhibitor

MGAT2 (monoacylglycerol acyltransferase 2) is expected to be an attractive target for the drug treatment of obesity, diabetes, and other disease. We describe our exploration and structure-activity relationship (SAR) study of 2,3-dihydro-1H-isoindole-5-sul

S1P RECEPTORS MODULATORS

The invention relates to novel compounds that have S1P receptor modulating activity and, preferably, apoptotic activity and/or anti proliferative activity against cancer cells and other cell types. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, cancer. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as cancer.

1,2,3,4-Tetrahydroisoquinoline Derivatives, Preparation Process therefor and Pharmaceutical Composition Containing the Same

The invention provides a type of novel 1,2,3,4-tetrahydroisoquinoline derivatives with a structure of formula (I): wherein R1 represents propargyl or cyclopropylmethyl; wherein R2 represents N-ethyl-N-methylamino, 1-Pyrrolidyl, 1-Piperidinyl, or 1-Morpholinyl. The invention provides further a process for preparing said derivatives and a pharmaceutical composition containing the same. Said derivatives can be used to modulate the proteolytic process of amyloid precursor proteins (APP), and provides further novel compounds useful for treating Alzheimer's disease (AD).