A5036707660- HER2/EGFR in Cancer Research
- Synthetic Organic Chemistry Methods
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Marine Toxins and Detection Methods
- Cancer Treatment and Pharmacology
- Crystallization and Solubility Studies
- Radiopharmaceutical Chemistry and Applications
- X-ray Diffraction in Crystallography
- Marine Sponges and Natural Products
- Glycosylation and Glycoproteins Research
- interferon and immune responses
- Monoclonal and Polyclonal Antibodies Research
- Synthesis and Characterization of Heterocyclic Compounds
- Asymmetric Synthesis and Catalysis
- Crystallography and molecular interactions
- Carbohydrate Chemistry and Synthesis
- Fluorine in Organic Chemistry
- Microwave-Assisted Synthesis and Applications
- Angiogenesis and VEGF in Cancer
- Advanced Synthetic Organic Chemistry
- Alkaloids: synthesis and pharmacology
- Synthesis and Reactions of Organic Compounds
- Synthesis and biological activity
- Inorganic Fluorides and Related Compounds
Eisai (United States)
2018-2024
Eisai (Japan)
2024
Chemical Synthesis Lab
2007-2009
Scripps Research Institute
2008-2009
University of California, San Diego
2008-2009
Institute of Chemical and Engineering Sciences
2007
Agency for Science, Technology and Research
2007
University of Utah
2003-2006
University of Arizona
2003
University of Idaho
2001-2002
A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation cyclic dinucleotides by introducing transannular macrocyclic bridge between the nucleic acid bases leads to topologically novel macrocycle-bridged STING agonist (MBSA). In addition substantially enhanced potency, newly designed MBSAs, exemplified clinical candidate E7766, exhibit broad activity in all major human variants. E7766 shown have...
Microtubule-targeting agents (MTA) have been investigated for many years as payloads antibody-drug conjugates (ADC). In cases, these ADCs shown limited benefits due to lack of efficacy or significant toxicity, which has spurred continued investigation into novel MTA next-generation ADCs. this study, we developed using the eribulin, a derivative macrocyclic polyether natural product halichondrin B, payload. Eribulin demonstrated in vitro potency and specificity various linkers two different...
This communication describes the total synthesis of marine polyether toxin, gambierol. work couples our iterative C-glycoside/enol ether−olefin metathesis strategy to subunits with a unique olefin metathesis/carbonyl olefination reaction bring together.
An expedient asymmetric total synthesis of aspidophytine is reported. A highly convergent strategy involving the sequential annulation vinyl iodide 5 with indole 6 exploits varying modes reactivity to provide in 23% over six steps from 5.
Abstract Gambierol, a representative of the marine ladder toxin family, consists eight ether rings, 18 stereocenters, and two challenging pyranyl rings having methyl groups that are in 1,3‐diaxial orientation to one another. Herein we describe generation gambierol's A–C F–H ring systems demonstrate versatility glycosyl anhydride, enol ether–olefin RCM strategy fused polycyclic ethers. This work has both enabled us generate sufficient quantities gambierol precursors better understand chemical...
Reactions of various diketo compounds with Deoxofluor [(CH(3)OCH(2)CH(2))(2)NSF(3)] have been investigated. When reacted Deoxofluor, alpha-diketones, R(1)COCOR(2) (R(1) = R(2) Ph; R(1) 4-Me-C(6)H(4); Ph, Me; Me, Et) (1a-d) formed difluoro derivatives (2a-d) in the presence a catalytic amount HF and/or tetrafluoro (3a-d) products depending on reaction conditions and stoichiometry used. beta-diketones, R(3)COCH(2)COR(4) (R(3) R(4) R(3) Ph) (4e-g), led to formation difluoroalkenones as mixture...
New synthetic methods for the construction of novel heterocycles and tryptamines are described. Thus, N-Boc anilines (I) sequentially converted to II ((3-(2-aminophenyl)pyrrolidin-3-ol) derivatives), III (substituted 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3′-pyrrolidines), VI (2-(4,5-dihydro-1H-pyrrol-3-yl)aniline) derivatives through a route involving t-BuLi induced ortho-metalation/LaCl3·2LiCl metal exchange, reaction with pyrrolidin-3-one (5), subsequent decarboxylative...
This manuscript describes our synthesis of the F−H subunit gambierol. In addition to tricycle, note is an interesting protecting group influence on generation a C(23) C-glycoside as well use ring-closing metathesis generate tetrasubstituted enol ether.
The preceding manuscript detailed our synthesis of the gambierol A-C and F-H ring precursors. Reported herein is a description coupling two precursors conversion coupled material into gambierol. Coupling subunits involved ester formation, enol ether RCM, mixed thioketal formation reduction. By employing this strategy we were able to bring highly advanced and, as result, minimize number post-coupling transformations required complete At completion synthesis, generated 7.5 mg (1.5 % overall...
Chlorotoxin (Cltx) isolated from scorpion venom is an established tumor targeting and antiangiogenic peptide. Radiolabeled Cltx therapeutic (131I-TM601) yielded promising results in human glioma clinical studies, the imaging agent tozuleristide, under investigation CNS cancer studies. Several binding targets have previously been proposed for but none effectively explain its pleiotropic effects; true target remains ambiguous focus of this study. A peptide-drug conjugate (ER-472) composed...
Links von der Mitte: Die Synthese „linken“ Strukturdomäne (2) Haplophytin (1) gelang durch stereoselektiven Aufbau sterisch überfrachteten C-C-Bindung (C9′-C15) und eine effiziente Kaskadensequenz, zu Gerüstumlagerung eines vermuteten Epoxidintermediats gehört.
Abstract Introduction STING (stimulator of interferon genes) is an emerging target for cancer immunotherapy. 2’,3'-cGAMP, a natural cyclic dinucleotide (CDN) agonist, and its phosphorothioate analogs, have drawn broad attention as lead molecules targeted drug discovery. These CDNs, however, lack efficacy in some common genotypes disproportionally represented non-Caucasians. Moreover, such CDNs not fully addressed liability chemical/metabolic stability. Here we report our chemistry approach...
IntroductionSTING (stimulator of interferon genes) is an emerging target for cancer immunotherapy. 2',3'-cGAMP, a natural cyclic dinucleotide (CDN) STING agonist, and its phosphorothioate analogs, have drawn broad attention as lead molecules targeted drug discovery. These CDNs, however, lack efficacy in some common genotypes disproportionally represented non-Caucasians. Moreover, such CDNs not fully addressed liability chemical/metabolic stability. Here we report our chemistry approach to...
The synthesis and characterization of the first stable trialkyl(difluoroamino)silane, R3SiNF2, as well R3SiNHF R3SiN(CH3)F in moderate yields are reported. (difluoroamino)silane has promise a new synthon for introduction -NF2 group into variety electrophilic inorganic organic substrates. Activation barriers relative energies were calculated unimolecular decompositions Me3SiCF3 t-Bu3SiNF2 using density functional theory (B3LYP/6-31G). activation confirm long-assumed kinetic stability Me3SiCF3.
Linkers with disulfide bonds are the only cleavable linkers that utilize physiological thiol gradients as a trigger to initiate intracellular drug release cascade. Herein, we present novel concept exploiting gradient phenomena design new class of linker no bond. To support concept, an electron-deficient sulfonamide-based amenable conjugation molecules targeting agents, was developed. Modulating electron-withdrawing nature aryl sulfonamide critical balance between stability and release....
Abstract Chlorotoxin is an established tumor targeting peptide that naturally occurs in scorpion venom. 131I-labelled chlorotoxin assessed early phase human glioma clinical trials achieved promising results. A drug conjugate (PDC) composed of linked to a cytotoxic payload (cryptophycin analog) was used as tool probe the mechanism chlorotoxin. The PDC proved efficacious, yet differential sensitivity observed multiple models. Previously described targets did not align with activity; therefore,...
<div>Abstract<p>Microtubule-targeting agents (MTA) have been investigated for many years as payloads antibody–drug conjugates (ADC). In cases, these ADCs shown limited benefits due to lack of efficacy or significant toxicity, which has spurred continued investigation into novel MTA next-generation ADCs. this study, we developed using the eribulin, a derivative macrocyclic polyether natural product halichondrin B, payload. Eribulin demonstrated <i>in vitro</i> potency...
<p>Biophysical analyses of MORAb-202 large-scale conjugation.</p>
<p>Specificity of MORAb-202 cytotoxicity</p>
<p>Eribulin compound structures and synthetic methods</p>
<p>Analyses of faletuzumab and amatuximab ADCs</p>