Resumen
[0000] The present invention provides derivatives of quinolylnitrones of formula I, wherein the meaning of the substituents is as described in the description, useful in treatment and/or prevention of hearing loss. [0000] Advantageously, these quinolylnitrones of formula (I) have a broad-spectrum effect, being efficient in the prevention and treatment of hearing loss regardless of its origin, whether caused by a physical agent, such as noise, or an ototoxic agent such as H<2>O<2>. [0000] <img class="EMIRef" id="574e5730-a1cb-4320-9d7e-7fcb4f07f980-EMI-C00001" />
Reivindicaciones
1. A compound of formula I: <img class="EMIRef" id="b3da2419-78f2-480f-a0a4-efcd79a93b42-ib0002" /> wherein: R<1> represents a -C<1-5> alkyl or a known aromatic ring having 5 or 6 members selected from: -CH-, - CR<12>-, -O-, -N-, and -S-; each one of R<2> to R<7> independently represents -H, halogen, -OR<8> or -NHR<8>; each one R<8> independently represents -H or -C<1-5> alkyl, wherein the -C<1-5> alkyl is optionally substituted with one or more R<9>; each one R<9> independently represents halogen, -OH, -O-C<1-5> alkyl, -NH<2>, -NH(C<1-5> alkyl) or Cyi; and Cy<1> represents a known ring system having from 5 to 8 members, saturated, partially unsaturated or aromatic, optionally containing from 1 to 3 heteroatoms selected from N, O, Se and S, Cy<1> being optionally bound to the remaining structure through any C or N atom, and optionally substituted by one or more R<10>; each one R<10> independently represents a -C<1-5> alkyl optionally substituted with one or more R<11>; and each R<11> independently represents -C<2-5> alkynyl ,provided that at least two of the R<2> to R<7> are other than -H; for use in a method for the prevention and/or treatment of hearing loss. 2. The compound for use according to claim 1, wherein: R<1> represents a -C<1-5> alkyl or a known aromatic ring having 5 or 6 members selected from: -CH-, - CR<12>-, -O-, -N-, and -S-; each one of R<2> to R<7> independently represents -H, halogen, -OR<8> or -NHR<8>; and each one R<8> independently represents -H or -C<1-5> alkyl. 3. The compound of formula (I) for use according to any one the preceding claims, wherein R<1> represents C<1-5> alkyl. 4. The compound of formula (I) for use according to any one of the preceding claims, wherein R<1> represents tert-butyl. 5. The compound of formula (I) for use according to any one of the preceding claims, wherein each one R<2> a R<7> independently represents-H, halogen or -OR<8>. 6. The compound of formula (I) for use according to any one of the preceding claims, wherein R<3>, R<4>, R<6> and R<7> represent -H. 7. The compound of formula (I) for use according to any one of the preceding claims, wherein R<2> represents halogen. 8. The compound of formula (I) for use according to any one of the preceding claims, wherein R<2> represents chlorine. 9. The compound of formula (I) for use according to any one of the preceding claims, wherein R<5> -OR<8>. 10. The compound of formula (I) for use according to any of the preceding claims, wherein R<8> represents -C<1-5> alkyl. 11. The compound of formula (I) for use according to any of the preceding claims, which is (Z)-N-tert-butyl-1-(2-chloro-6-metoxiquinolin-3-yl)methanimine oxide (QN23). 12. The compound of formula (I) for use according to any of the preceding claims, wherein the hearing loss is due to a physical agent, such as noise. 13. The compound of formula (I) for use according to any of the preceding claims, wherein the hearing loss is due to exposure to an ototoxic agent. 14. The compound of formula (I) for use according to any of the preceding claims, wherein the method of preventing or treating comprises administering the compound before the exposition to the physical or ototoxic agent; or alternatively the compound is administered after the exposition to the physical or ototoxic agent; or alternatively the compound is administered both before and after the exposition to the physical or ototoxic agent. 15. The compound of formula (I) for use according to any of the preceding claims, which is administered in the form of a pharmaceutical composition which comprises at least one pharmaceutically acceptable adjuvant, excipient and/or vehicle; particularly in the form of an oral, topical, intratympanic, or parenteral administration; particularly in the form of otic drops.
