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A novel and original protocol for the preparation of complex framework compounds containing a vinylcyclopropane (VCP) fragment is presented by means of UV conversion of cyclopentene (CP) derivatives under standard conditions, providing high yields of target products in an unprecedented atom economical reversible step. The reverse transformation of compounds with vinylcyclopropyl moieties into CP derivatives takes place in the presence of trifluoroacetic acid at room temperature. A one-pot approach for the synthesis of VCPs from the corresponding benzoazacyclic allenes has also been developed and the mechanisms of mutual rearrangements of both VCP and CP have been rationalized by DFT calculations.

Marine alkaloids belonging to the lamellarins family, which incorporate a 5,6-dihydro-1-phenylpyrrolo[2,1-a]isoquinoline (DHPPIQ) moiety, possess various biological activities, spanning from antiviral and antibiotic activities to cytotoxicity against tumor cells and the reversal of multidrug resistance. Expanding a series of previously reported imino adducts of DHPPIQ 2-carbaldehyde, novel aliphatic and aromatic Schiff bases were synthesized and evaluated herein for their cytotoxicity in five diverse tumor cell lines. Most of the newly synthesized compounds were found noncytotoxic in the low micromolar range (&lt, 30 &mu, M). Based on a Multi-fingerprint Similarity Search aLgorithm (MuSSeL), mainly conceived for making protein drug target prediction, some DHPPIQ derivatives, especially bis-DHPPIQ Schiff bases linked by a phenylene bridge, were prioritized as potential hits addressing Alzheimer&rsquo, s disease-related target proteins, such as cholinesterases (ChEs) and monoamine oxidases (MAOs). In agreement with MuSSeL predictions, homobivalent para-phenylene DHPPIQ Schiff base 14 exhibited a noncompetitive/mixed inhibition of human acetylcholinesterase (AChE) with Ki in the low micromolar range (4.69 &mu, M). Interestingly, besides a certain inhibition of MAO A (50% inhibition of the cell population growth (IC50) = 12 &mu, M), the bis-DHPPIQ 14 showed a good inhibitory activity on self-induced &beta, amyloid (A&beta, )1&ndash, 40 aggregation (IC50 = 13 &mu, M), which resulted 3.5-fold stronger than the respective mono-DHPPIQ Schiff base 9.

1-(p-Methoxyphenyl)tetrazolyl-substituted 6,7-dimethoxy(6,7-methylenedioxy)-1,2,3,4-tetrahydroisoquinolines formed tetrazolyl-substituted azocines in high yields by using activated alkynes. Unsubstituted at 6,7,8-aromatic fragment 1-tetrazolylisoquinoline interacted in several pathways forming tetrazolyl-substituted azocines, 1-tetrazolyl-1-R-vinylisoquinolines and 3-azaspiro[5.5]undeca-1,7,9-triene. ispartof: MOLECULES vol:23 issue:11 ispartof: location:Switzerland status: published

Heating 1-vinyl-4,5,6,7-tetrahydro-5-methyl-4,6-ethanopyrrolo(3,2-c)pyridine (1) in the presence of acetic or trifluoroacetic anhydride resulted in bicyclic saturated fragment cleavage, affording cyclohepteno(b)pyrroles 2a,b in low yields. In the case of trifluoroacetic anhydride, the major product of the reaction, -trifluoroacetylsubstituted tetrahydropyrrolo(3,2-c)pyridine 3 was isolated in 34% yield.

A series of ester derivatives of annulated tetrahydroazocines, namely 2,3,6,11-tetrahydro-1 H -azocino[4,5- b ]indoles ( 5 – 10 ), 2,3,6,7-tetrahydro-1 H -azocino[5,4- b ]indoles ( 11 – 14 ), and 4,7,8,9-tetrahydro-1 H -pyrrolo[2,3- d ]azocines ( 15 – 18 ), synthesized through an efficient 6 → 8 membered ring expansion procedure, were investigated for their acetylcholinesterase (AChE) inhibitory activities. Most of the compounds acted as AChE inhibitors in vitro, with IC 50 values ranging from 5 to 40 μM. The most potent compounds 11 and 15 , both as racemic mixtures, proved selective toward AChE, exhibiting selectivity ratios versus butyrylcholinesterase (BuChE) of ca. 15 and more than 20, respectively. Structure–activity studies highlighted, among other factors, lipophilicity as a property modulating the AChE inhibition potency, as shown by a reasonable parabolic correlation between pIC 50 and experimental 1-octanol/water partition coefficient (log P ), which described the prevailing behavior of the examined compounds ( r 2 = 0.665). Molecular docking simulations using the X-ray crystal structure of AChE from Torpedo californica suggested possible binding modes of the tetrahydroazocine ester derivatives 11 and 15 .