122745-36-2Relevant academic research and scientific papers
CYTOTOXIC AGENTS
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, (2022/02/09)
The present invention provides a compound of formula (I): (T-X4)p-B1-X3-A-X2-L-X1-AM or pharmaceutically acceptable salts, tautomers, stereoisomers or mixtures thereof; wherein AM is (AM1); (AM2); or (AM3); with the proviso that the compound of formula (I) contains at least one sigma hole group; and with the proviso that no more than one of A, B1 and T is a sigma hole group; and each sigma hole group is independently: (SH1); (SH2); (SH3); (SH4); (SH5); (SH6); (SH7); (SH8); (SH9); or (SH10).
G-A CROSSLINKING CYTOTOXIC AGENTS
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, (2020/08/22)
The invention relates to a compound of formula (I): or salts, solvates, isomers or tautomers thereof, wherein; A is a group selected from: R1 is selected from H and halogen; either R2 is selected from -CH2-halogen, C1
ISOQUINOLIDINOBENZODIAZEPINE (IQB)-1(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI) DIMERS
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Paragraph 0011; 00241; 00249-00251, (2018/04/27)
Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.
SELF-IMMOLATIVE LINKERS CONTAINING MANDELIC ACID DERIVATIVES, DRUG-LIGAND CONJUGATES FOR TARGETED THERAPIES AND USES THEREOF
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Page/Page column 51; 86; 87; 91, (2015/03/28)
The invention provides a therapeutic drug and targeting conjugate, pharmaceutical compositions containing these conjugates in pharmaceutical composition, and uses of these conjugates in anti-neoplastic and other therapeutic regimens. Also provided are novel intermediates thereof. The conjugates provide a therapeutic drug fragment or prodrug fragment bound to a targeting moiety via a linker which comprises a substrate cleavable by a protease such as Cathepsin B. The targeting moiety is a ligand which targets a cell surface molecule, such as a cell surface receptor on an anti-neoplastic cell. The ligand may function solely as a targeting moiety or may itself have a therapeutic effect. Following administration of the therapeutic drug and targeting conjugate of formula I and exposure of the conjugate to the protease specific for the substrate, the linker is cleaved and the targeting moiety is separated from the conjugate, which causes the drug fragment or prodrug fragment to convert to the drug or prodrug. The recited conjugates are useful in anti-neoplastic therapies. Also provided are methods of making the therapeutic drug and targeting conjugates and intermediates thereof, and kits comprising the therapeutic drug and targeting conjugates.
CHEMICAL LINKERS AND CLEAVABLE SUBSTRATES AND CONJUGATES THEREOF
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Page/Page column 97; 98, (2010/06/19)
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.
Studies toward the duocarmycin prodrugs for the antibody prodrug therapy approach
Li, Lian-Sheng,Sinha, Subhash C.
scheme or table, p. 2932 - 2935 (2009/07/26)
A tricyclic precursor for the synthesis of the prodrugs of pro-1,2,9,9a-tetrahydrocyclopropa[c]benz-[e]indole-4-one tetramethoxyindolecarboxamide (CBI-TMI) was prepared using the ring-closing metathesis approach. The tricyclic intermediate was converted to an advanced precursor of a CBI-TMI prodrug equipped with a linker presumably suitable for activation using the aldolase catalytic antibody 38C2. An attempted 38C2-catalyzed two-step activation of the hydroxy-pro-CBI intermediate involving retro-aldol and the β-elimination reactions was also examined.
METHODS AND COMPOUNDS FOR PREPARING CC-1065 ANALOGS
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Page/Page column 28; Fig.1; Fig.2, (2010/11/27)
A method of forming a CBI CC- 1065 analog utilizes NH2 as a starting material, where R3 is H or alkyl and R6 is H, substituted or unsubstituted lower alkyl, cyano, or alkoxy. Intermediates (I) are used and are claimed.
An Improved Synthesis of 1,2,9,9a-Tetrahydrocyclopropabenzindol-4-one (CBI): A Simplified Analogue of the CC-1065 Alkylation Subunit
Boger, Dale L.,Yun, Weiya,Teegarden, Bradley R.
, p. 2873 - 2876 (2007/10/02)
A concise and improved synthesis of 11, the immediate precursor to N-BOC-CBI and related analogues of CC-1065 incorporating the 1,2,9,9a-tetrahydrocyclopropabenzindol-4-one alkylation subunit, is detailed based on a direct 5-exo-trig aryl radical-al
Synthesis of N-(tert-Butyloxycarbonyl)-CBI, CBI, CBI-CDPI1, and CBI-CDPI2: Enhanced Functional Analogues of CC-1065 Incorporating the 1,2,9,9a-Tetrahydrocyclopropabenzindol-4-one (CBI) Left-Hand Subunit
Boger, Dale L.,Ishizaki, Takayoshi,Kitos, Paul A.,Suntornwat, Oranart
, p. 5823 - 5832 (2007/10/02)
Full details of the synthesis of N-(tert-butyloxycarbonyl)-1,2,9,9a-tetrahydrocyclopropabenzindol-4-one constituting a more stable functional analogue of the CC-1065 left-hand subunit are described.The resolution of an immediate CBI
