Mcgill University

Universita′ Degli Studi Di Milano

Università Degli Studi Di Parma

Universita Degli Studi Di Urbino

Iflo-Istituto Farmacologico Lombardo S.a.s. Di Giorgio E Ald. Laguzzi

Instituto Farmacologico Lombardo-Iflo, S.a.s.

Franco Fraschini

Bojidar Stankov

Marco Mor

Giorgio Tarzia

Gilberto Spadoni

Silvia Rivara

Gabriele Biella

Luigi F Strambi

Annalida Bedini

Maria T Moni, Heir

Ermanno Duranti, Deceased

Aldo Laguzzi

Carlo Introini

Gabriella Gobbi

Valeria Lucini

Margherita Borgonovo

Novel melatonin ligands of Formula I: or pharmaceutically acceptable salts thereof wherein: n is 1 or 2; m is 0, 1 or 2; p is 0, 1, 2, 3, 4, 5, 6, 7 or 8; v is 2 or 3; A is aryl or heteroaryl; Z is O, S or NR; Y is selected from the group consisting of hydrogen, aryl, heteroaryl, C-Calkyl, C-Ccycloalkyl, and R is selected from the group consisting of hydrogen, hydroxyl, &#x2014;OCF, CF, C-Calkyl, C-Calkyloxy, C-Calkylthio, halogen and &#x2014;Z&#x2014;(CH)-A; Ris selected from the group consisting of C-Calkyl, C-Ccycloalkyl, CF, hydroxy-substituted C-Calkyl, hydroxy-substituted C-Ccycloalkyl, and NHR, wherein Ris C-Calkyl or C-Ccycloalkyl; Ris selected from the group consisting of: hydrogen, C-Calkyl, C-Calkyloxy, OCF, CF, hydroxyl, and halogen; Ris selected from the group consisting of hydrogen, C-Calkyl, C-Calkyloxy, OCF, CF, hydroxyl, and halogen; R and Rmay be connected together to form an &#x2014;O&#x2014;(CH)bridge representing with the carbon atoms to which they are attached a 5- or 6-membered heterocyclic ring system; Ris selected from the group consisting of hydrogen, C-Calkyl, C-Calkyloxy, OCF, CF, hydroxyl, and halogen; Ris selected from the group consisting of hydrogen and C-Calkyl; Ris selected from the group consisting of hydrogen, C-Calkyl, C-Calkyloxy, OCF, CF, hydroxyl, and halogen; and Ris selected from the group consisting of hydrogen and C-Calkyl.

Melatonin ligands having antidepressant activity as well as sleep inducing properties

The novel compounds of formula: ##STR1## in which R is isopropyl, cyclohexyl, phenyl, CH.sub.3, Br or I; or H R.sub.1 is CH.sub.3 or cyclopropyl and R.sub.2 is H or Br, and when R.sub.1 is cyclopropyl and R.sub.2 is H, R is other than H, and when R.sub.1 is CH.sub.3 and R.sub.2 is H, R is other than H, and when R.sub.1 is CH.sub.3 and R.sub.2 is H, R is other than I, and when R is CH.sub.3 and R.sub.2 is H, R.sub.1 is other than CH.sub.3, and when R is phenyl and R.sub.2 is H, R.sub.1 is other than CH.sub.3, exhibit superior activity in the treatment of pathologies which interfere with the circadian rhythm. A novel method of preparation is described according to which the pharmaceutical compositions containing the novel compounds, as well as compounds already known, are administered transdermally. The novel method of administration results in sustained peripheral blood level. Novel pharmaceutical compositions are described suitable for transdermal administration.

Compounds effective in the treatment of circadian rhythms and related

The present invention relates to new pharmaceutical compositions active in the therapy of sleep disorders comprising N-acetyl-5-methoxy-triptamine (melatonin) or one of its derivatives, preferably 2-iodo-N-acetyl-5-methoxy-triptamine (2-iodomelatonin), 2-bromo-N-acetyl-5-methoxy-triptamine (2-bromomelatonin), 2-chloro-N-acetyl-5-methoxy-triptamine (2-chloromelatonin) or 6-chloro-N-acetyl-5-methoxy-triptamine (6-chloromelatonin), at a dosage comprised between 10 and 100 mg, preferably comprised respectively between 20 and 80 mg between 10 and 20 mg and between 10 and 40 mg alone or in association with a benzodiazepinic derivative at a dosage comprised between 0.06 and 25 mg.

Pharmaceutical compositions active in the therapy of sleep disorders

Growing community of inventors

Milan, Italy

Franco Fraschini