1458033-48-1

Basic information

• Product Name: N¹,N³-bismethoxy-N¹,N³-dimethyl-1,3-benzenedicarboxamide
• Synonyms: N¹,N³-bismethoxy-N¹,N³-dimethyl-1,3-benzenedicarboxamide
• CAS NO: 1458033-48-1
• Molecular Weight: 252.27
• Mol File: 1458033-48-1.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: N¹,N³-bismethoxy-N¹,N³-dimethyl-1,3-benzenedicarboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: N¹,N³-bismethoxy-N¹,N³-dimethyl-1,3-benzenedicarboxamide(1458033-48-1)
• EPA Substance Registry System: N¹,N³-bismethoxy-N¹,N³-dimethyl-1,3-benzenedicarboxamide(1458033-48-1)

Safety Data

• Hazardous Substances Data: 1458033-48-1(Hazardous Substances Data)

Upstream product

• 121-91-5 isophthalic acid 
• 1117-97-1 N,0-dimethylhydroxylamine 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 

Downstream Products

• 1458033-37-8 1-(3-methylbenzoyl)-3-(3-methylbenzoyl)benzene thiosemicarbazone 
• 85566-05-8 <3-(3-methylbenzoyl)phenyl>(3-methylphenyl)methanone 

Relevant articles and documents

Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L

Upregulation of cathepsin L in a variety of tumors and its ability to promote cancer cell invasion and migration through degradation of the extracellular matrix suggest that cathepsin L is a promising biological target for the development of anti-metastatic agents. Based on encouraging results from studies on benzophenone thiosemicarbazone cathepsin inhibitors, a series of fourteen benzoylbenzophenone thiosemicarbazone analogues were designed, synthesized, and evaluated for their inhibitory activity against cathepsins L and B. Thiosemicarbazone inhibitors 3-benzoylbenzophenone thiosemicarbazone 1, 1,3-bis(4-fluorobenzoyl)benzene thiosemicarbazone 8, and 1,3-bis(2-fluorobenzoyl)-5-bromobenzene thiosemicarbazone 32 displayed the greatest potency against cathepsin L with low IC50 values of 9.9 nM, 14.4 nM, and 8.1 nM, respectively. The benzoylbenzophenone thiosemicarbazone analogues evaluated were selective in their inhibition of cathepsin L compared to cathepsin B. Thiosemicarbazone analogue 32 inhibited invasion through Matrigel of MDA-MB-231 breast cancer cells by 70% at 10 μM. Thiosemicarbazone analogue 8 significantly inhibited the invasive potential of PC-3ML prostate cancer cells by 92% at 5 μM. The most active cathepsin L inhibitors from this benzoylbenzophenone thiosemicarbazone series (1, 8, and 32) displayed low cytotoxicity toward normal primary cells [in this case human umbilical vein endothelial cells (HUVECs)]. In an initial in vivo study, 3-benzoylbenzophenone thiosemicarbazone (1) was well-tolerated in a CDF1 mouse model bearing an implanted C3H mammary carcinoma, and showed efficacy in tumor growth delay. Low cytotoxicity, inhibition of cell invasion, and in vivo tolerability are desirable characteristics for anti-metastatic agents functioning through an inhibition of cathepsin L. Active members of this structurally diverse group of benzoylbenzophenone thiosemicarbazone cathepsin L inhibitors show promise as potential anti-metastatic, pre-clinical drug candidates.

COMPOSITIONS AND METHODS FOR INHIBITION OF CATHEPSINS

This invention is directed to compound of Formula I and methods of using these compounds in the treatment of conditions in which modulation of a cathepsin, particularly cathepsin K or cathepsin L, will be therapeutically useful.