107474-63-5

Upstream product

• 107474-65-7 methyl pyrrolo<3,2-e>indole-2-carboxylate 
• 107474-66-8 methyl 3-(tert-butyloxycarbonyl)-1,2-dihydro-3H-pyrrolo<3,2-e>indole-7-carboxylate 
• 1074-86-8 4-formyl indole 
• 1037796-08-9 C₁₂H₁₀N₄O₂ 
• 107474-64-6 methyl 2-azido-3-(1H-indol-4-yl)acrylate 

Downstream Products

• 105518-47-6 3-carbamoyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylic acid 
• 1049812-54-5 C₄₃H₄₆ClN₉O₆ 
• 1049812-57-8 C₂HF₃O₂*C₅₃H₅₇ClN₁₀O₉ 
• 107474-66-8 methyl 3-(tert-butyloxycarbonyl)-1,2-dihydro-3H-pyrrolo<3,2-e>indole-7-carboxylate 

Relevant academic research and scientific papers

CHEMICAL LINKERS AND CLEAVABLE SUBSTRATES AND CONJUGATES THEREOF

The present disclosure provides drug-ligand conjugates and drug-cleavable substrate conjugates that are potent cytotoxins. The disclosure is also directed to compositions containing the drug-ligand conjugates, and to methods of treatment using them.

CHEMICAL LINKERS WITH SINGLE AMINO ACIDS AND CONJUGATES THEREOF

The present disclosure provides drug-ligand conjugates that are potent cytotoxins and include a linker between the drug and ligand where the linker has a single amino acid. The disclosure is also directed to compositions containing the drug-ligand conjugates, and to methods of treatment using them.

Systematic exploration of the structural features of yatakemycin impacting DNA alkylation and biological activity

A systematic examination of the impact of the yatakemycin left and right subunits and their substituents is detailed along with a study of its unique three subunit arrangement (sandwiched vs extended and reversed analogues). The examination of the ca. 50 analogues prepared illustrate that within the yatakemycin three subunit structure, the subunit substituents are relatively unimportant and that it is the unique sandwiched arrangement that substantially increases the rate and optimizes the efficiency of its DNA alkylation reaction. This potentiates the cytotoxic activity of yatakemycin and its analogues overcoming limitations typically observed with more traditional compounds in the series (CC-1065, duocarmycins). Moreover, a study of the placement of the alkylation subunit within the three subunit arrangement (sandwiched vs extended and reversed analogues) indicates that it not only has a profound impact on the rate and efficiency of DNA alkylation but also controls and establishes the DNA alkylation selectivity as well, where both enantiomers of such sandwiched agents alkylate the same adenine sites exhibiting the same DNA alkylation selectivity independent of their absolute configuration.

Studies on the Total Synthesis of CC-1065: Preparation of a Synthetic, Simplified 3-Carbamoyl-1,2-dihydro-3H-pyrroloindole Dimer/Trimer/Tetramer (CDPI Dimer/Trimer/Tetramer) and Development of Methodolodgy for PDE-I Dimer Methyl Ester Formation

Two synthetic preparations of 3-carbamaoyl-1,2-dihydro-3H-pyrroloindole-7-carboxylic acid (2b, CDPI) and the investigation and development of methodology for the preparation of 3-carbamoyl-1,2-dihydro-3H-pyrroloindole dimer 3 (CDPI dimer) constituting the simplified and stable PDE-I dimer skeleton possessing the B-DNA minor groove complementary shape of the natural product CC-1065 are detailed.The extension of this methodology to the preparation of 3-carbamoyl-1,2-dihydro-3H-pyrroloindole trimer 4 and tetramer 5 (CDPI trimer and tetramer) are described and constitute synthetic, potentially selective, high affinity, noncovalent B-DNA minor groove binding agents.