1,721,234 research outputs found
New prospects for vinblastine analogues as anticancer agents.
No full textBoger et al. synthesized a series of C20' urea derivatives of vinblastine that matched or exceeded the potency of vinblastine in cell growth inhibition assays. The studies demonstrated the importance of the H-bond donor on the C20' position and revealed the presence of a space surrounding the C20' substituent that tolerates a wide variety of substituents, remarkably enhancing potency of vinblastine analogues
Boom in the development of non-peptidic beta-secretase (BACE1) inhibitors for the treatment of Alzheimer's disease
Full text linkb-Amyloid cleaving enzyme-1 (BACE1) has become a significant target for the therapy
of Alzheimer’s disease. After the discovery of the first non-peptidomimetic b-secretase inhibitors
by Takeda Chemicals in 2001, several research teams focused on SAR development of these
agents. The non-peptidic BACE1 inhibitors may potentially overcome the classical problems
associated with the peptide structure of first generation, such as blood–brain barrier crossing,
poor oral bioavailability and susceptibility to P-glycoprotein transport. In the past 6 years a
boom in research of non-peptidic BACE1 inhibitors has disseminated findings over hundreds
of publications and patents. The rapidly growing literature has been reviewed with particular emphasis on literature of pharmaceutical companies
Indolyl aryl Sulfones (IASs): Development of highly potent NNRTIs active against wt-HIV-1 and clinically relevant drug resistant mutants
No full textIndolyl aryl sulfones (IASs) are a potent class of NNRTIs developed from L-737,126, a lead agent discovered by Merck AG. IAS derivatives are endowed with inhibitory activities against wt HIV-1 in the low nanomolar concentration range. Introduction of two methyl groups at positions 3 and 5 of the phenyl ring of the aryl sulfonyl moiety furnished IAS derivatives such as 5-chloro- or 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamide, which showed very potent and selective anti-HIV-1 activity against some mutants carrying NNRTI resistant mutations at positions 103 and 181 of the reverse transcriptase. IAS derivatives bearing 2-hydroxyethylcarboxyamide or 2- hydroxyethylcarboxyhydrazide groups at position 2 of the indole nucleus were more active than L-737,126 against the K103N-Y181C double mutant. A great improvement of antiviral activity against wt HIV-1 and resistant mutants was obtained by coupling 1-3 simple amino acids, such as glycine and alanine, in sequence, with the 3-[(3,5- dimethylphenyl)sulfonyl]-1H-indole-2-carbonyl moiety. The transformation of the chain terminus into amide or hydrazide, produced short peptides with high selectivity and potent activity against wt HIV-1, and the viral mutants Y181C, K103N-Y181C and EFVR. IAS having two halogen atoms at the indole showed potent inhibitory activity against the Y181C and the EFVR resistant mutant strains. In particular, the introduction of a fluorine atom at position 4 of the indole ring notably contributed to improve the antiviral activities against both wt and the related resistant mutants. 5- Nitro-IASs were highly active against wt HIV-1 and exhibited low cytotoxicity. Experimental data highlighted the class IAS derivatives as promising candidates for clinical trials
Current state-of-the-art in preclinical and clinical development of novel non-nucleoside HIV-1 reverse transcriptase inhibitors
Full text linkIn spite of the tremendous advance in our understanding of the HIV-1 life cycle and of the molecular mechanisms underlying its pathogenesis, it is still not possible to fully control the HIV-1 infection for long periods of time, not to mention eradicate it. However, as it is still unclear whether an effective vaccine could be developed in a short time, therapeutic approaches based on the combination of different potent antiviral drugs are now thought to be the best option for the control of HIV-1 infection in patients. For this reason, development of novel molecules that are safer, more potent and less sensitive to drug resistance than available drugs is mandatory. Among the currently exploited anti-HIV drugs, non-nucleoside reverse transcriptase inhibitors play a major role. This review will summarise the most recent advances and evolutionary trends for this class of anti-HIV drugs
Indole, a Core Nucleus for Potent Inhibitors of Tubulin Polymerization.
Full text linkMicrotubules are the basic components of cell structure, which take part in a wide
number of pivotal cellular functions. Drugs that are able to modulate the microtubule assembly
either by inhibition of tubulin polymerization or by blocking microtubule disassembly are of great
interest in anti-cancer therapy. Several tubulin polymerization inhibitors characterized by the
presence of an indole nucleus have been obtained from natural sources or have been prepared by
semi-synthesis. In the last decade an ever increasing number of synthetic indoles have been
reported. We have reviewed anti-tubulin agents obtained by synthesis having an indole as core
nucleus. The synthesis, the biological activity, and the structure–activity relationship aspects of
3-formyl-2-phenylindoles, heterocombretastatins, diarylindoles, 2-aroylindoles, D-24851, 2-aryl-
3-aroylindoles, 3-aroyl- and 1-aroylindoles, and arylthioindoles are discussed
ChemInform Abstract: A Simplified Synthesis of Ethyl 5-Chloro-4-fluoro-1H-indole-2-carboxylate and Ethyl 5-Chloro-6-fluoro-1H-indole-2-carboxylate
No full textAn improved synthesis of ethyl 5-chloro-4-fluoro-1H-indole-2-carboxylate
No full text[No abstract available
Polymerization and MCF-7 Cell Growth Inhibitors. New Bioisosteres at the Sulfur Bridging Group.
No full textComunicazione Poster B1.P
A simplified synthesis of ethyl 5-chloro-6-fluro-1H-indole-2-carboxylate and ethyl 5-chloro-4-fluro-1H-indole-2-carboxylate
Full text linkArylthioindole tubulin polymerization inhibitors and their preparation, pharmaceutical compositions, and methods of treating or preventing cancer using them
No full text- …
