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The present invention relates to compds. I [Cy = aryl or heteroaryl; A = CR3 or N; X = O, S, NH, SO, SO2 or a single bond; Y, Y1-​Y3 = (independently) (un)​substituted alkanediyl or alkenediyl, or a single bond; R1 = H or alkyl; R2 = H, OH, halo and alkyl; R3 = H, alkyl, cycloalkyl, haloalkyl, halo; R5 = H or alkyl; or R2 and R5 taken together form alkanediyl bridge; R6 = H, alkyl, cycloalkyl, heterocycloalkyl, etc.; each of R7 and R8 = (independently) H, (un)​substituted alkyl, aryl, heteroaryl, etc.; or R7 and R8 form together with the nitrogen atom to which they are attached a cyclic amine selected from aziridine, azetidine, pyrrolidine, etc.; R, Ra, Rb, Rc = (independently) H, halo, CN, alkyl, etc.] or pharmaceutically acceptable salts, tautomers, solvates or stereoisomers thereof, that are inhibitors of hepatitis B virus (HBV)​. For example, reacting cis-​7-​methyl-​N-​(3,​4,​5-​trifluorophenyl)​-​2,​3,​3a,​4,​10,​10a-​hexahydro-​1H,​7H-​dipyrrolo[3,​4-​b:3',​4'-​f]​[1,​4,​5]​oxathiazocine-​8-​carboxamide 5,​5-​dioxide hydroiodide with N,​N-​dimethyloxamic acid afforded cis-​II. The exemplified compds. I were tested for HBV inhibition (data given)​. Compds. I are useful alone or in combination with other agents for treating, ameliorating, preventing or curing HBV infection and related conditions. The present invention also relates to pharmaceutical compns. contg. said compds. I.

Improved sanitary conditions, disease prevention (e.g., vaccinations) and treatment (e.g., antibiotics) have increased life expectancy, up to the 67.2 years value in 2010. Unfortunately, living longer a poor life does not represent anyone?s dream, mostly due to neurodegenerative diseases (NDDs). Alzheimer?s Disease International (ADI) estimates in its 2013 report that there are more than 35 million people with dementia worldwide as of 2010, and that this number will double by 2030 and triplicate by 2050. In industrialized countries the prevalence of Parkinson?s disease (PD) is about 1% for people over 60, with estimates of up to 4% for people in the highest age groups. In 2016 the Centres for Disease Control and Prevention estimated that between 14,000 - 15,000 Americans suffered from Amyotrophic Lateral Sclerosis (ALS). These and other NDDs are the result of neurodegenerative processes, that entail the progressive loss of structure or function of neurons, eventually causing their death. Symptomatic treatment strategies available on the market for NDDs are inadequate, as they offer only temporary relief without changing the ultimate NDD outcome. Effective treatment of NDDs should be based on small molecules able to modulate disease-modifying pathways involved in the development and/or the progression of NDDs, to cause their remission. In my Ph.D. work I focused on four different pathways (each described in a dedicated Chapter) involved in the development of multiple NDDs. With the aim to therapeutically modulate them by promoting and/or inhibiting those targets, I?ve rationally designed and synthetized several classes of compounds. My research group established a multi-disciplinary approach in collaboration with bioinformatics, biologists, pharmacologists and clinicians; thus, my putative NDD treatments were tested by our collaborators in different Universities and Institutes (CIBIO, University of Trento; San Raffaele Research Institute, Milan; Department of Neuroscience, Federico II University, Naples).

A new series of in vitro potent and highly selective histone methyl transferase enzyme G9a inhibitors was obtained. In particular, compound 2a, one the most potent G9a inhibitor identified, was endowed with >130-fold selectivity over GLP and excellent ligand efficiency. Therefore, it may represent a valuable tool compound to validate the role of highly selective G9a inhibitors in different pathological conditions. When 2a was characterized in vitro in cellular models of skeletal muscle differentiation, a relevant increase of myofibers’ size and reduction of the fibroadipogenic infiltration were observed, further confirming the therapeutic potential of selective G9a inhibitors for the treatment of Duchenne muscle dystrophy.

Acid-sensitive ion channels (ASICs) are sodium channels partially permeable to Ca2+ ions, listed among putative targets in central nervous system (CNS) diseases in which a pH modification occurs. We targeted novel compounds able to modulate ASIC1 and to reduce the progression of ischemic brain injury. We rationally designed and synthesized several diminazene-inspired diaryl mono- and bis-guanyl hydrazones. A correlation between their predicted docking affinities for the acidic pocket (AcP site) in chicken ASIC1 and their inhibition of homo- and heteromeric hASIC1 channels in HEK-293 cells was found. Their activity on murine ASIC1a currents and their selectivity vs mASIC2a were assessed in engineered CHO-K1 cells, highlighting a limited isoform selectivity. Neuroprotective effects were confirmed in vitro, on primary rat cortical neurons exposed to oxygen-glucose deprivation followed by reoxygenation, and in vivo, in ischemic mice. Early lead 3b, showing a good selectivity for hASIC1 in human neurons, was neuroprotective against focal ischemia induced in mice.