1140-81-4

Usage

Uses

Used in Pharmaceutical Synthesis:
6-ACETAMIDO-4-HYDROXY-2-METHYLQUINOLINE is used as an intermediate in the synthesis of NSC 23766 (N900280), a highly soluble and membrane permeable Rac GTPase inhibitor. It plays a vital role in the development of 6-ACETAMIDO-4-HYDROXY-2-METHYLQUINOLINE, which has potential applications in the treatment of various diseases and conditions.
Used in Cancer Research and Treatment:
In the field of cancer research, 6-ACETAMIDO-4-HYDROXY-2-METHYLQUINOLINE is used as a precursor for the synthesis of NSC 23766, which has demonstrated the ability to inhibit the anchorage-independent growth and invasion phenotypes of human prostate cancer PC-3 cells. This makes it a promising candidate for further research and development in the fight against prostate cancer.
Used in Drug Design and Development:
The unique molecular structure of 6-ACETAMIDO-4-HYDROXY-2-METHYLQUINOLINE allows it to be used as a building block in the design and development of new drugs and therapeutic agents. Its reactivity and chemical properties can be exploited to create novel compounds with potential applications in various therapeutic areas, including oncology, cardiovascular disease, and neurological disorders.

Synthesis Reference(s)

Journal of the American Chemical Society, 70, p. 4065, 1948 DOI: 10.1021/ja01192a031

InChI:InChI=1/C12H12N2O2/c1-7-5-12(16)10-6-9(14-8(2)15)3-4-11(10)13-7/h3-6H,1-2H3,(H,13,16)(H,14,15)

Upstream product

• 244219-89-4 methyl 3-{[4-(acetylamino) phenyl]amino}but-2-enoate 
• 122-80-5 N-acetyl-p-phenylenediamine 
• 63304-45-0 (E)-ethyl 3-((4-acetamidophenyl)amino)but-2-enoate 
• 1131-34-6 6-amino-2-methylquinolin-4-ol 
• 108-24-7 acetic anhydride 

Downstream Products

• 100795-23-1 N-(4-methoxy-2-methyl-6-quinolyl)acetamide 
• 1131-34-6 6-amino-2-methylquinolin-4-ol 
• 59611-57-3 6-acetamide-4-chloro-2-methylquinoline 

Relevant academic research and scientific papers

Design, synthesis and anti leukemia cells proliferation activities of pyrimidylaminoquinoline derivatives as DOT1L inhibitors

A series of novel pyrimidylaminoquinoline derivatives 8(a-i) and 9(a-i) containing amino side chain, and the bisaminoquinoline analogs 3(b-e) have been designed and synthesized by structural modifications on a lead DOT1L inhibitor, 3a. All the compounds have been evaluated for their DOT1L inhibitory activities. The results showed that most of the compounds have strong anti DOT1L activities. Compounds 3e, 8h and 9e are the most potential ones from each category with the IC50 values of 1.06 ± 0.35 μM, 5.72 ± 1.56 μM and 3.55 ± 1.28 μM, respectively. Such inhibitors expressed significant binding interactions with DOT1L by surface plasmon resonance (SPR)-based binding assay. The results of molecular docking experiments suggested that they could occupy the SAM binding pocket of DOT1L. Compounds 8h and 9e exhibited better inhibitory activities but poor selectivities against the both MLL-rearranged MV4-11 cells and the non MLL-rearranged Kasumi-1 cells than those of 3a and 3e, which suggested that the introduction of the amino side chain would be beneficial for their anti leukemia cells proliferation activities, possibly due to the improvement of the fat solubility. Additionally, the direct cellular inhibition activities were found that compound 9e could effectively down-regulate both the level of H3k79 methylation and MLL-rearranged leukemia gene expression of Hoxa9 and Meis1 in MV4-11 in the qRT-PCR and western blot studies. These observations suggested DOT1L was one of the potential targets but perhaps not the most pivotal one for these compounds, which made their poor selectivities against leukemia cells proliferation.

Small molecule antagonists of cell-surface heparan sulfate and heparin-protein interactions

Surfen, bis-2-methyl-4-amino-quinolyl-6-carbamide, was previously reported as a small molecule antagonist of heparan sulfate (HS), a key cell-surface glycosaminoglycan found on all mammalian cells. To generate structure-activity relationships, a series of rationally designed surfen analogs was synthesized, where its dimeric structure, exocyclic amines, and urea linker region were modified to probe the role of each moiety in recognizing HS. An in vitro assay monitoring inhibition of fibroblast growth factor 2 binding to wild-type CHO cells was utilized to quantify interactions with cell surface HS. The dimeric molecular structure of surfen and its aminoquinoline ring systems was essential for its interaction with HS, and certain dimeric analogs displayed higher inhibitory potency than surfen and were also shown to block downstream FGF signaling in mouse embryonic fibroblast cells. These molecules were also able to antagonize other HS-protein interactions including the binding of soluble RAGE to HS. Importantly, selected molecules were shown to neutralize heparin and other heparinoids, including the synthetic pentasaccharide fondaparinux, in a factor Xa chromogenic assay and in vivo in mice. These results suggest that small molecule antagonists of heparan sulfate and heparin can be of therapeutic potential for the treatment of disorders involving glycosaminoglycan-protein interactions.

GTPase inhibitors and methods of use and crystal structure of RAC-1 GTPase

The preferred embodiments generally relate to methods and compositions that affect the GTP-binding activity of members of the Rho family GTPases, preferably Rac (Rac1, Rac2 and/or Rac3), such compositions include compounds that modulate the GTP/GDP exchan

GTPASE INHIBITORS AND USE THEREOF FOR CONTROLLING PLATELET HYPERACTIVITY

The preferred embodiments generally relate to methods and compositions that affect the GTP-binding activity of members of the Rho family GTPases, preferably Rac (Rac1, Rac2 and/or Rac3), such compositions include compounds that modulate the GTP/GDP exchan

GTPASE INHIBITORS AND METHODS OF USE

The preferred embodiments generally relate to methods and compositions that affect the GTP-binding activity of members of the Rho family GTPases, preferably Rac (Rac1, Rac2 and/or Rac3), such compositions include compounds that modulate the GTP/GDP exchan

Amide derivatives and nociceptin antagonists

The present invention relates to a compound of the formula [1′] wherein R2is lower alkyl optionally substituted by hydroxy, amino and the like, ring B is phenyl, thienyl and the like, E is a single bond, —O—, —S— and the like, ring G is aryl, heterocyclic group and the like, R5is halogen atom, hydroxy, lower alkyl optionally substituted by halogen atom etc., and the like, t is 0 or an integer of 1 to 5, when t is an integer of 2 to 5, each R5may be the same or different, m is 0 or an integer of 1 to 8, and n is 0 or an integer of 1 to 4, and a nociceptin antagonist containing compound [1′] as an active ingredient. The compound [1′] shows, due to nociceptin antagonistic action, analgesic effect against sharp pain such as postoperative pain and the like. The present invention also relates to the use of certain amide derivative inclusive of compound [1′] as a nociceptin antagonist or analgesic.

4-Aminoquinolines: Novel nociceptin antagonists with analgesic activity

Small-molecule nociceptin antagonists were synthesized to examine their therapeutic potential. After a 4-aminoquinoline derivative was found to bind with the human ORL1 receptor, a series of 4-aminoquinolines and related compounds were synthesized and their binding was evaluated. Elucidation of structure - Activity relationships eventually led to the optimum compounds. One of these compounds, N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamide hydrochloride (11) not only antagonized nociceptin-induced allodynia in mice but also showed analgesic effect in a hot plate test using mice and in a formalin test using rats. Its analgesic effect was not antagonized by the opioid antagonist naloxone. These results indicate that this nociceptin antagonist has the potential to become a novel type of analgesic that differs from μ-opioid agonists.