Chloride channel opener
AssigneeSucampo AG
InventorsRyuji Ueno, John Cuppoletti
Life of this patent
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Abstract
Disclosed is a novel use of a prostaglandin compound as a chloride channel opener. According to the instant invention, chloride channels in a mammalian subject can be opened by a prostaglandin compound to facilitate chloride ion transportation.
Claims25
A method for treating disease by opening ClC channels in a mammalian subject, wherein the disease is selected from the group consisting of myotonia atrophica, calculus renum, constipation, anxiety, insomnia, epilepsia, anesthesia, asthma, bronchitis and neuropathy, which comprises administering an effective amount of a prostaglandin compound to the subject, wherein said prostaglandin compound is the compound as shown by the following general formula (I):
- wherein L, M and N are hydrogen atom, hydroxy, halogen atom, lower alkyl, hydroxy(lower)alkyl, or oxo, wherein at least one of L and M is a group other than hydrogen, and the five-membered ring of formula (I) may have one or more double bonds;
- A is —CH2OH, —COCH2OH, —COOH or a pharmaceutically acceptable salt, ether, ester or amide thereof;
- B is —CH2—CH2—, —CH═CH— or —C≡C—;
- Zis
- wherein R4 and R5 are hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or hydroxy(lower)alkyl, wherein R4 and R5 are not hydroxy and lower alkoxy at the same time;
- R1 is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, alkyl, hydroxy, oxo, or aryl, and at least one carbon atom in the aliphatic hydrocarbon is optionally substituted by oxygen, nitrogen or sulfur;
- and
- Ra is a saturated or unsaturated lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, oxo, hydroxy, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, cyclo(lower)alkyloxy, aryl, or aryloxy;
- cyclo(lower)alkyl;
- cyclo(lower)alkyloxy;
- aryl;
- or aryloxy.
A method for treating cystic fibrosis, which comprises by administrating an effective amount of a prostaglandin compound to a subject in need of such treatment, wherein said prostaglandin compound is a compound as shown by the following general formula (I):
- wherein L, M and N are hydrogen atom, hydroxy, halogen atom, lower alkyl, hydroxy(lower)alkyl, or oxo, wherein at least one of L and M is a group other than hydrogen, and the five-membered ring of formula (I) may have one or more double bonds;
- A is —CH2OH, —COCH2OH, —COOH or a pharmaceutically acceptable salt, ether, ester or amide thereof;
- B is —CH2—CH2—, —CH═CH— or —C≡C—;
- Z is
- wherein R4 and R5 are hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or hydroxy(lower)alkyl, wherein R4 and R5 are not hydroxy and lower alkoxy at the same time;
- R1 is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, alkyl, hydroxy, oxo, or aryl, and at least one carbon atom in the aliphatic hydrocarbon is optionally substituted by oxygen, nitrogen or sulfur;
- and
- Ra is a saturated or unsaturated lower or medium aliphatic hydrocarbon residue, which is substituted with halogen, oxo, hydroxy, lower alkoxy, or lower aryloxy;
- cyclo(lower)alkyl;
- cyclo(lower)alkyloxy;
- aryl;
- or aryloxy, provided that Ra is substituted by halogen.
A method for treating a condition associated with reduced chloride ion permeability wherein the condition is selected from the group consisting of myotonia atrophica, calculus renum, anxiety, insomnia, epilepsia, anesthesia and neuropathy, which comprises administering to a subject in need thereof an effective amount of a prostaglandin compound as shown by the following general formula (I):
- wherein L, M and N are hydrogen atom, hydroxy, halogen atom, lower alkyl, hydroxy(lower)alkyl, or oxo, wherein at least one of L and M is a group other than hydrogen, and the five-membered ring of formula (I) may have one or more double bonds;
- A is —CH2OH, —COCH2OH, —COGH or a pharmaceutically acceptable salt, ether, ester or amide thereof;
- B is —CH2—CH2—, —CH═CH— or —C≡C—;
- Z is
- wherein R4 and R5 are hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or hydroxy(lower)alkyl, wherein R4 and R5 are not hydroxy and lower alkoxy at the same time;
- R1 is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, alkyl, hydroxy, oxo or aryl, and at least one carbon atom in the aliphatic hydrocarbon is optionally substituted by oxygen, nitrogen or sulfur;
- and
- Ra is a saturated or unsaturated lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, oxo, hydroxy, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, cyclo(lower)alkyloxy, aryl, or aryloxy;
- cyclo(lower)alkyl;
- cyclo(lower)alkyloxy;
- aryl;
- or aryloxy.
Dependencies are inferred from the claim text.