193902-98-6

Upstream product

• 127-19-5 N,N-dimethyl acetamide 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 2369-11-1 5-fluoro-2-nitroaniline 
• 1635-61-6 5-chloro-2-nitroaniline 

Downstream Products

• 668432-44-8 4-amino-5-fluoro-3-(6-piperazin-1-yl-1H-benzimidazol-2-yl)quinolin-2(1H)-one 
• 1820703-82-9 tert-butyl 4-(4-bromo-3-chlorophenyl)piperazine-1-carboxylate 
• 1386950-73-7 tert-butyl 4-(4-amino-3-chlorophenyl)piperazine-1-carboxylate 
• 1621399-60-7 C₁₉H₁₉FN₆O 
• 1621399-82-3 tert-butyl 4-(2-(2-amino-5-fluorophenylcarbamoyl)quinoxalin-6-yl)piperazine-1-carboxylate 
• 1621399-59-4 C₁₉H₁₉FN₆O 
• 1621399-81-2 tert-butyl 4-(2-(2-(tert-butoxycarbonylamino)-4-fluorophenylcarbamoyl)-quinoxalin-6-yl)-piperazine-1-carboxylate 
• 1339046-76-2 4-[2-(3,4-diamino-phenyl)-1H-benzoimidazol-5-yl]-piperazine-1-carboxylic acid dimethylamide 
• 1339046-74-0 4-[2-(4-amino-3-nitro-phenyl)-1H-benzoimidazol-5-yl]-piperazine-1-carboxylic acid dimethylamide 
• 1339046-72-8 4-(3-amino-4-nitro-phenyl)-piperazine-1-carboxylic acid dimethylamide 
• 96103-52-5 2-nitro-5-piperazin-1-yl-phenylamine 
• 193902-99-7 tert-butyl 4-(3,4-diaminophenyl)piperazine-1-carboxylate 
• 885232-22-4 4-[4-nitro-3-(2-phenoxy-acetylamino)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

Synthesis of 7-amino-6-halogeno-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides: A way forward for targeting hypoxia and drug resistance of cancer cells

To establish a new approach for the synthesis of quinoxaline 1,4-dioxides as hypoxia-selective cytotoxic agents, an original multi-step preparation of derivatives possessing the diamine moiety at position 7 was evaluated. Herein, we present the synthesis of a series of novel 7-amino-6-halogeno-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides 13a-h, 14a,b,g based on the regioselective Beirut reaction. Comparison of antitumor properties of derivatives possessing the diamine moiety at position 7 with structurally close congeners possessing the corresponding amino groups at position 6 revealed key differences in the cytotoxicity profiles and HIF-1α inhibition. All the synthesized 7-amino-6-halogeno derivatives 13a-h, 14a,b,g demonstrated significant cytotoxic activities against breast cancer cell lines (MCF7, MDA-MB-231) in normoxia and hypoxia with IC50 values ranging from 0.1 to 7.6 μM. Most of these novel derivatives can circumvent the multidrug resistance of tumor cells caused by P-glycoprotein over expression. The lead compounds 13a, 14a and 14b can suppress the expression of HIF-1α at low micromolar concentrations and induce apoptosis in breast cancer MCF7 cells. In addition, compound 14b effectively inhibits BCL2 and ERα expression in MCF7 cells. The current research opens a new direction for targeting hypoxia and drug resistance of cancer cells. This journal is

Protein hydrolysis target chimera and pharmaceutical composition and application thereof

The invention discloses a protein hydrolysis target chimera which can effectively induce degradation of FLT3-ITD in MOM - 13-MV - 4 - 11 positive cells FLT3 and ITD in a dose-dependent manner and a time-dependent manner. The in vivo study shows that the internal CD45 of the acute myelogenous leukemia mouse can be remarkably reduced. + The positive cell level shows a better treatment effect on acute myelogenous leukemia.

Proteolysis-Targeting Chimera (PROTAC) Modification of Dovitinib Enhances the Antiproliferative Effect against FLT3-ITD-Positive Acute Myeloid Leukemia Cells

Acute myeloid leukemia (AML) refers to one of the most lethal blood malignancies worldwide. FLT3-ITD mutation is recognized as the most common one that predicted a poorer prognosis. There have been many prominent FLT3-ITD inhibitors approved by the FDA for clinical therapies. However, as impacted by undesirable off-target effects, differentiated metabolic issues, and clinical drug resistance problems, it remains challenging to discover alternative and promising solutions for treating FLT3-ITD+ AML. In this study, dovitinib was chemically modified and converted into CRBN-recruiting PROTACs. Two active compounds were identified, which showed enhanced antiproliferative effects against FLT3-ITD+ AML cells, both in vitro and in vivo. As demonstrated from further biological evaluation, the compounds could induce the degradation of the FLT3-ITD and KIT proteins in a ubiquitin-proteasome-dependent manner and completely block their downstream signaling pathway. The findings of this study would provide another promising strategy to develop novel therapies for FLT3-ITD+ AML.

Multi-target active compound and application thereof

The invention relates to a multi-target active compound and application thereof. The multi-target active compound is a compound shown as a formula I or a pharmaceutically acceptable salt thereof. Themulti-target active compound provided by the invention h

HETEROCYCLIC COMPOUNDS

The present invention provides a heterocyclic compound a TLR7 and/or TLR9 and/or TLR-7/8/9 and/or TLR-7/8 and/or TLR-7/9 inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases and/or inflammatory diseases and the like, in particular, acute decompensated heart failure, non-alcoholic steatohepatitis (NASH), IgA nephropathy, Duchenne muscular dystrophy (DMD), systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, inflammatory bowel disease, asthma, type 1 diabetes, myasthenia gravis, hematopoetic disfunction, B-cell malignancies, transplant rejection and graft-versus-host disease, hepatocellular carcinoma (HCC) and the like. The present invention is a compound represented by the formula (1) : wherein each symbol is as described in the specification, or a salt thereof.

HPK1 INHIBITORS AND METHODS OF USING SAME

Thienopyridinone compounds of Formula (I) and pharmaceutically acceptable salts thereof are described. In these compounds, one of X1; X2, and X3 is S and the other two are each independently CR, wherein R and all other variables are as defined herein. The compounds are shown to inhibit HPK1 kinase activity and to have in vivo antitumor activity. The compounds can be effectively combined with pharmaceutically acceptable carriers and also with other immunomodulatory approaches, such as checkpoint inhibition or inhibitors of tryptophan oxidation. Formula (I).

NOVEL 5-HYDROXYTRYPTAMINE RECEPTOR 7 ACTIVITY MODULATORS AND THEIR METHOD OF USE

Pharmaceutical compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity.

NOVEL SIGMA-2 RECEPTOR BINDERS AND THEIR METHOD OF USE

Pharmaceutical compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of sigma-2 receptor activity.

SELECTIVE HDAC3 INHIBITORS

Provided herein are HDAC3 inhibitors, as well as methods of treatment comprising administering these compounds to a subject in need thereof.

RADIOPROTECTOR COMPOUNDS AND METHODS

The invention relates to novel compounds, processes for their preparation and their use in protecting biological materials from radiation damage (radioprotection). Preferred compounds of the invention are those of Formula (II), as follows: wherein W represents -N(R1R2) where R1 and R2 are not both hydrogen and where they may together form a 5, 6 or 7 membered ring structure, -NHN(R1R2), NHR3N(R1R2), -NHR3OR2, -N(R3)R3OR2, -N(R1)R3OR3OR3, OR3NR1R2, -OR3 or W represents piperidyl, piperazinyl, morpholinyl, thiomorpholinyl or diazepanyl each of which may be optionally substituted by C1 to C4 alkyl, C2 to C4 alkenyl, -N(CO)N(R1R2), -N(CO)OR1, -N(CO)OR3OH, -(CO)NR1R2, -R3(CO)NR1R2, -R3OR1, -OR1, -N(R1R2) OR -NH-; R1 and R2 are the or different and are selected from hydrogen, C1 to C4 alkyl or C2 to C4 alkenyl; group or chain; Z is the same or different and represents N or CH; Z' is the same or different and represents N or C; X represents CH, N or NH, where .. is a double bond when X is CH or N and a single bond when X is NH; X' represents N or NH, wherein when X is CH or N X' is NH and wherein X and X' are different and further where ～～～is a double bond when X' is N and a single bond when X' is NH; Q represents H, alkoxyl, -NR1R2, F or Cl; Q1 is absent when Z' is N and when Z' is C it represents H, alkoxyl, -NR1R2, F or Cl; A represents a five to ten membered single or multiple ring structure with heterocyclic N or O located at the ortho position, said ring including optional double bonds, substitutions and/or other heteroatoms and pharmaceutically acceptable derivatives thereof.