160446-15-1

Upstream product

• 39684-80-5 2-(tert-butoxycarbonylamino)ethyl bromide 
• 2328-12-3 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline monohydrochloride 
• 574-98-1 2-(2-bromoethyl)isoindoline-1,3-dione 
• 1745-07-9 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 849675-80-5 2-chloro-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethanone 
• 15365-56-7 6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride 
• 120-20-7 2-(3,4-dimethoxyphenyl)-ethylamine 
• 136918-14-4 phthalimide 
• 160446-14-0 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)acetonitrile 

Downstream Products

• 1609428-57-0 N-(2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl)-1-(2-methoxybenzyl)-1H-1,2,3-triazole-4-carboxamide 
• 1609428-58-1 N-(2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl)-1-(3-methoxybenzyl)-1H-1,2,3-triazole-4-carboxamide 
• 1609428-59-2 N-(2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl)-1-(4-methoxybenzyl)-1H-1,2,3-triazole-4-carboxamide 
• 1609428-56-9 N-(2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl)-1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide 
• 1609428-55-8 N-(2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl)-1-(3-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide 

Relevant academic research and scientific papers

Preparation and application of Sigma-2 fluorescent ligand

The invention mainly relates to synthesis of a series of sigma-2 fluorescent ligands and application of the sigma-2 fluorescent ligands in the fields of pharmacy and medicine, specifically to a series of compounds containing benzopyran structures, wherein the compounds have high affinity activity and selectivity to a sigma-2 receptor, have good affinity activity to the sigma-2 receptor, and have diagnosis and treatment effects on tumor cells, brain cells of patients with Alzheimer's disease, and other cells highly expressing the sigma-2 receptor.

Antitumor effect of 2, 4, 7-trisubstituted pyrimidino indole compound

The invention relates to a series of compounds with 2, 4, 7-trisubstituted pyrimidino indole structures, and the compounds can inhibit the growth of various tumor cells, and particularly, the compounds can efficiently inhibit the proliferation of breast cancer, cervical cancer, gastric adenocarcinoma and liver cancer cells. In addition, the compound can inhibit tumor cell clone formation at a very low concentration and promote tumor cell apoptosis. The invention also relates to a preparation method of the compound and application of the compound in marking, diagnosis, prevention and treatment or adjuvant therapy of tumors.

2, 4, 7 -substituted pyrimido indole compound antitumor drug resistance effect

The invention relates to 2, 4 and 7 - tri-substituted pyrimido-indole structural compounds which can inhibit the growth of various drug-resistant tumor cells, and in particular, can efficiently inhibit doxorubicin resistant breast cancer. Cisplatin-resistant lung cancer and cisplatin liver cancer cell proliferation. In addition, the compounds of the present invention can inhibit the formation of drug-resistant tumor cell clones at very low concentrations and inhibit P glycoprotein and ABCG2 transport in vitro functions. The invention also relates to a preparation method of the compound and an application of the compound in tumor treatment or adjuvant therapy.

Anti-tumor metastasis effect of 2, 4, 7-trisubstituted pyrimidino indole compound

The invention relates to a compound with a 2, 4, 7-trisubstituted pyrimidino indole structure. The compound can inhibit tumor cell migration and invasion at a very low concentration, and has an effect superior to that of a clinically common drug cis-platinum. In addition, the compound can also inhibit the expression of matrix metalloproteinase related protein which plays an important role in tumor migration and invasion processes. The invention also relates to a preparation method of the compound and application of the compound in marking, diagnosis, prevention and treatment or adjuvant therapy of tumors.

Structure-Based Discovery of Pyrimidine Aminobenzene Derivatives as Potent Oral Reversal Agents against P-gp- And BCRP-Mediated Multidrug Resistance

Overexpression of ATP binding cassette (ABC) transporters, including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), is an important factor leading to multidrug resistance (MDR) in cancer treatments. Three subclasses of dual inhibitors of P-gp and BCRP were designed based on the active moieties of BCRP inhibitors, tyrosine kinase inhibitors, and P-gp inhibitors, of which compound 21 possessed low cytotoxicity, high reversal potency, and good lipid distribution coefficient. 21 also increased the accumulation of Adriamycin (ADM) and Mitoxantrone (MX), blocked Rh123 efflux, and made no change in the protein expression of P-gp and BCRP. Importantly, coadministration of 21 can significantly improve the oral bioavailability of paclitaxel (PTX). It was also demonstrated that 21 significantly inhibited the growth of K562/A02 xenograft tumors by increasing the sensitivity of ADM in vivo. In summary, 21 has the potential to overcome MDR caused by P-gp and BCRP and to improve the oral bioavailability of PTX.

Impact of N-Alkylamino Substituents on Serotonin Receptor (5-HTR) Affinity and Phosphodiesterase 10A (PDE10A) Inhibition of Isoindole-1,3-dione Derivatives

In this study, a series of compounds derived from 4-methoxy-1H-isoindole-1,3(2H)-dione, potential ligands of phosphodiesterase 10A and serotonin receptors, were investigated as potential antipsychotics. A library of 4-methoxy-1H-isoindole-1,3(2H)-dione derivatives with various amine moieties was synthesized and examined for their phosphodiesterase 10A (PDE10A)-inhibiting properties and their 5-HT1A and 5-HT7 receptor affinities. Based on in vitro studies, the most potent compound, 18 (2-[4-(1H-benzimidazol-2-yl)butyl]-4-methoxy-1H-isoindole-1,3(2H)-dione), was selected and its safety in vitro was evaluated. In order to explain the binding mode of compound 18 in the active site of the PDE10A enzyme and describe the molecular interactions responsible for its inhibition, computer-aided docking studies were performed. The potential antipsychotic properties of compound 18 in a behavioral model of schizophrenia were also investigated.

Synthesis and evaluation of pyrimidoindole analogs in umbilical cord blood ex vivo expansion

The scarcity of hematopoietic stem cells (HSCs)significantly hindered their clinical potentials. Umbilical cord blood (UCB)has become the leading source of HSCs for both research and clinical applications. But the low content of HSCs in a single UCB unit limited its use only to pediatric patients. Various cytokines and small molecules have demonstrated strong abilities in promoting HSC ex vivo expansion, of which UM171 is the newest and by far the most potent HSC ex vivo expansion agent. In this study, we synthesized 37 pyrimidoindole analogs and identified 6 compounds to be potent in promoting HSC ex vivo expansion. In particular, analog 11 was found to be the most effective in stimulating ex vivo expansion of UCB CD34+ cells and CD34+CD38? cells. Initial data indicated that compound 11 promoted the absolute number of long term HSCs and inhibited their differentiation. UCB HSCs expanded with 11 retained adequate multi-lineage differentiation capacity. In addition, compound 11 is not cytotoxic at its test concentrations, suggesting that it merits further investigation for potential clinical applications.

99mTc-Cyclopentadienyl Tricarbonyl Chelate-Labeled Compounds as Selective Sigma-2 Receptor Ligands for Tumor Imaging

We have designed and synthesized a series of cyclopentadienyl tricarbonyl rhenium complexes containing a 5,6-dimethoxyisoindoline or a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline pharmacophore as σ2 receptor ligands. Rhenium compound 20a posse

Synthesis and structure-activity relationship studies of conformationally flexible tetrahydroisoquinolinyl triazole carboxamide and triazole substituted benzamide analogues as σ2 receptor ligands

Two novel classes of compounds targeting the sigma-2 (σ2) receptor were synthesized, and their bioactivities to binding σ1 and σ2 receptors were measured. Four novel triazole carboxamide analogues, 24d, 24e, 24f, and 39c, demonstrated high affinity and selectivity for the σ2 receptor. These data suggest 11C-labeled versions of these compounds may be potential σ2-selective radiotracers for imaging the proliferative status of solid tumors.

Identification of dipeptidyl peptidase IV inhibitors: Virtual screening, synthesis and biological evaluation

Inhibition of dipeptidyl peptidase IV is an important approach for the treatment of type-2 diabetes. In this study, we reported a multistage virtual screening workflow that integrated 3D pharmacophore models, structural consensus docking, and molecular mechanics/generalized Born surface area binding energy calculation to identify novel dipeptidyl peptidase IV inhibitors. After screening our in-house database, two hit compounds, HWL-405 and HWL-892, having persistent high performance in all stages of virtual screening were identified. These two hit compounds together with several analogs were synthesized and evaluated for in vitro inhibition of dipeptidyl peptidase IV. The experimental data indicated that most designed compounds exhibited significant dipeptidyl peptidase IV inhibitory activity. Among them, compounds 35f displayed the greatest potency against dipeptidyl peptidase IV in vitro with the IC 50 value of 78 nm. In an oral glucose tolerance test in normal male Kunming mice, compound 35f reduced blood glucose excursion in a dose-dependent manner. Several compounds with Tetrahydroisoquinoline scaffold were identified by multi-stage virtual screening as the antidiabetic drugs candidates against DPP-4.