86208-17-5Relevant academic research and scientific papers
Small tripeptide surrogates with low nanomolar affinity as potent inhibitors of the botulinum neurotoxin B metallo-proteolytic activity
Blommaert, Armand,Turcaud, Serge,Anne, Christine,Roques, Bernard P.
, p. 3055 - 3062 (2007/10/03)
Botulinum neurotoxin type B is a high-weight (150kDa) protein produced by the anaerobic bacillus Clostridium botulinum. This metallo-protease neurotoxin cleaves synaptobrevin, a protein, which is crucial to neurotransmission, resulting in the muscle paralysis, which characterizes botulism. Inhibition of the metallo-peptidase activity is a possible approach to obtain specific therapeutics to treat botulism. We have previously reported a successful attempt to block the proteolytic activity of this neurotoxin with new, selective amino-thiol inhibitors endowed with Ki values in the 15-20 nanomolar range. With the aim of increasing the affinity and bioavailability of this first series of inhibitors we have optimized the residue that fits the P1 subsite of the enzyme by comparing a series of ligands that contain subtle but significant variants of the parent structure. In addition, this strategy provided a simplification of the synthesis of BoNT/B inhibitors by reducing the possible number of stereoisomers. As such we were able to enhance the inhibitory potency whilst reducing the size as compared to the initial privileged structure yielding the first pseudo-tripeptide inhibitors with Ki values in the low nanomolar range.
Condensed pyrimidine derivative
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, (2008/06/13)
A novel pyrimidine derivative having an excellent antitumor activity, which is represented by the following general formula (I) or a pharmacologically acceptable salt thereof: STR1 wherein R1 represents a hydroxyl or amino group; R2 represents a phenylene, pyridinediyl, thiendiyl, furandiyl or thiazoldiyl group, --CO2 R5 and --CO2 R6 may be the same or different from each other and each represents a carboxyl group or a carboxylic acid ester, the part STR2 A represents an oxygen atom, a group represented by the formula: STR3 (wherein R3 and R4 may be the same or different from each other and each represents a hydrogen or halogen atom or a hydrocarbon group which may be substituted, or alternatively R3 and R4 may be united to form an alkylidene group which may be substituted) or a group represented by the formula: STR4 (wherein R70 represents a hydrogen atom or a hydrocarbon group), and n is an integer of 1 to 3, provided that the compound in which R1 represents oxygen, and hydrogen is attached to nitrogen at 3-position is included in the above shown definition, a process for preparation the same, and an antitumor drug containing the same.
Synthesis and antitumor activities of novel 6-5 fused ring heterocycle antifolates: N-[4-[ω-(2-amino-4-substituted-6,7- dihydrocyclopenta[d]pyrimidin-5-yl)alkyl]benzoyl]-L-glutamic acids
Kotake,Iijima,Yoshimatsu,Tamai,Ozawa,Koyanagi,Kitoh,Nomura
, p. 1616 - 1624 (2007/10/02)
Novel antifolates with a 6-5 fused ring system, 6,7- dihydrocyclopenta[d]pyrimidine, (3a,b and 4a,b) were synthesized on the basis of combined modification of the heterocycle and bridge regions of the folate molecule. The synthetic method involves (1) syn
Antibacterial β-lactam compounds
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, (2008/06/13)
Novel β-lactam compounds classified into penem compounds, a process for preparing the same and use of such β-lactam compounds are disclosed. These β-lactam compounds exhibit excellent antimicrobial activities useful as pharmaceuticals or they are important intermediates for the synthesis of compounds having antimicrobial activities.
