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A simple protocol allows the synthesis of the title compounds (II) via intramolecular cyclization of substrates (I) in polyphosphoric acid.

Computational approaches have been increasingly applied to drug design over the past three decades and have already provided some useful results in the discovery of anticancer drugs. Given the increased availability of crystal structures in recent years, a growing number of molecular modeling studies on tubulin have been reported. Herein we present a brief overview of the role played by computational methods in anti-tubulin research, specifically in the context of colchicine binding agent research. An overview of current structures is reported, along with a brief discussion on the issues associated with the various tubulin isotypes. Finally, a summary of the most recent and relevant results is presented, highlighting the challenges and opportunities faced by researchers in this field.

A new microwave-assisted protocol for a very fast synthesis of pyridyl N-aryl hydrazones in open vessel mode, under cooling while heating conditions is developed.

New tetracyclic systems containing a pyrrolobenzodiazepine 5 or a pyrrolobenzotriazepine 6 moiety bounded by a spiro linkage to the piperidine nucleus are described. They have been synthesized by a simple reaction involving the interaction between proper aromatic amines and 4-oxopiperidines substituted or not at the 1-position in the presence of maleic acid as a catalyst. The synthesis of spiropyrrolo[1,2-a]quinoxaline-2,4′-piperidine 7 and its 1′-acyl derivatives by the same procedure is also reported.

Some 2-[4-(heteroarylmethyl)phenyl]propanoic acids and phenylacetic and benzoic analogues has been synthesized. All above acids were tested for their inhibitory activity on lipoxygenase and cyclooxygenase, in comparison with NDGA and tolmetin. 2-[4-(Thien-2-ylmethyl)phenyl]propanoic acid 2, strictly related with suprofen, was found the most interesting compound, giving rise to a 79% inhibition of the cyclooxygenase activity at 10(-4) M concentration.

Various aryl 1-pyrryl sulfones were synthesized and tested as inhibitors of HIV-1. 2-Nitrophenyl-2-ethoxycarbonyl-1-pyrryl sulfone, the most active among test derivatives, was selected as lead compound of the aryl pyrryl sulfone series. The in vitro anti-HIV-1 activity and cytotoxicity of 41 compounds is reported. Some structure-activity relationships are discussed also in comparison with the known NPPS (2-nitrophenyl phenyl sulfone).

The synthesis and the in vitro anti-HIV-1 activity of novel pyrrolo annulated benzothiadiazepine acetic acids and some related derivatives are reported. The new compounds share chemical features with pyrrolo[1,2-d][1,4]benzodiazepin-6-one 1 and Ro 5-3335 pyrrylbenzodiazepinone 4, two inhibitors of HIV-replication at the level of reverse transcriptase (RT) and transcriptional transactivation by Tat, respectively. Two derivatives, namely methyl 10,11-dihydropyrrolo[1,2-b][1,2,5]benzothiadiazepine-11-acetic-5,5 -dioxide (5a) and 1,12b-dihydro-2H-azeto[2,1-d]pyrrolo[1,2-b][1,2,5]benzoth iadiazepin-2-one 8,8-dioxide (7a), were found to exhibit a significant, although not very potent, activity against human immunodeficiency virus Type 1 (HIV-1).

A novel family of non-nucleoside reverse transcriptase inhibitors (NNRTIs) active at submicromolar concentrations was discovered. The new derivatives are 1-[2-(diarylmethoxy)ethyl]imidazoles bearing substituents both at benzene and imidazole rings. The most potent derivatives were those having nitro and methyl groups as substituents in the imidazole ring. Among 10 test derivatives compound 6d was found to be as potent as nevirapine and was selected as a lead for further studies.

β-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 β-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. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 2, 295–338, 2009