Compounds effective in the treatment of circadian rhythms and related disorders, the novel pharmaceutical preparations and novel method of application
First Claim
1. A compound having the ability to combat chronopathology of jet lag or delayed sleep phase syndrome of the formula:
- ##STR7## wherein a) R=isopropyl R1 =CH3 R2 =Hb) R=cyclohexyl R1 =CH3 R2 =Hc) R=methyl R1 =cyclopropyl R2 =Hd) R=phenyl R1 =cyclopropyl R2 =He) R=Br R1 =cyclopropyl R2 =Hf) R=Br R1 =CH3 R2 =Br(g) R=I R1 =cyclopropyl R2 =Hor(h) R=Br R1 =CH3 R2 =H.
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Accused Products
Abstract
The novel compounds of formula: ##STR1## in which R is isopropyl, cyclohexyl, phenyl, CH3, Br or I; or H R1 is CH3 or cyclopropyl and R2 is H or Br, and when R1 is cyclopropyl and R2 is H, R is other than H, and when R1 is CH3 and R2 is H, R is other than H, and when R1 is CH3 and R2 is H, R is other than I, and when R is CH3 and R2 is H, R1 is other than CH3, and when R is phenyl and R2 is H, R1 is other than CH3, 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.
15 Citations
22 Claims
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1. A compound having the ability to combat chronopathology of jet lag or delayed sleep phase syndrome of the formula:
- ##STR7## wherein a) R=isopropyl R1 =CH3 R2 =H
b) R=cyclohexyl R1 =CH3 R2 =H c) R=methyl R1 =cyclopropyl R2 =H d) R=phenyl R1 =cyclopropyl R2 =H e) R=Br R1 =cyclopropyl R2 =H f) R=Br R1 =CH3 R2 =Br (g) R=I R1 =cyclopropyl R2 =H or (h) R=Br R1 =CH3 R2 =H.
- ##STR7## wherein a) R=isopropyl R1 =CH3 R2 =H
- 2. A method of treatment of a living subject affected by chronopathology of jet lag or delayed sleep phase syndrome, which consists of administering by the transdermal route to said living subject a composition containing as the active ingredient 0.1-5% of a compound which is a member selected from the group consisting of melatonin, 2-methylmelatonin, 2-bromomelatonin, 2-iodomelatonin, 2,6-dibromomelatonin, 2-cyclohexylmelatonin, 2-bromo-N-cyclopropanoyl-5-methoxytryptamine, and 2-iodo-N-cyclopropanoyl-5-methoxytryptamine.
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8. A pharmaceutical composition in the form of a gel, a paste, a cream or an emulsion for transdermal administration which contains as the active component melatonin or a melatonin agonist of formula:
- ##STR8## wherein;
R is cyclohexyl, CH3, Br, I, or HR1 is CH3 or cyclopropyl and R2 is H or Br, in the amount of 0.1-5% of the total composition and pharmaceutically acceptable carriers and excipients. - View Dependent Claims (9, 10, 11, 12, 13, 14, 15, 16)
- ##STR8## wherein;
- 17. A method of treatment of a living subject to achieve sustained peripheral blood levels for a period of 6-8 hours which consists of administering by the transdermal route to said living subject a composition containing as the active ingredient 0.1-5% of a compound which is a member selected from the group consisting of melatonin, 2-methylmelatonin, 2-bromomelatonin, 2-iodomelatonin, 2,6-dibromomelatonin, 2-cyclohexylmelatonin, 2-bromo-N-cyclopropanoyl-5-methoxytryptamine and 2-iodo-N-cyclopropanoyl-5-methoxytryptamine.
Specification