| US 7,485,654 B2 | ||
| Corneal perception recovery drug containing amide compound | ||
| Yoshiko Takayama, Kobe (Japan); Yoshikuni Nakamura, Kobe (Japan); Jun Inoue, Kobe (Japan); and Mitsuyoshi Azuma, Nishinomiya (Japan) | ||
| Assigned to Senju Pharmaceutical Co., Ltd., Osaka (Japan); and Mitsubishi Tanabe Pharma Corporation, Osaka (Japan) | ||
| Appl. No. 10/557,415 PCT Filed Jun. 03, 2005, PCT No. PCT/JP2005/010624 § 371(c)(1), (2), (4) Date Dec. 12, 2005, PCT Pub. No. WO2005/118582, PCT Pub. Date Dec. 15, 2005. |
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| Claims priority of application No. 2004-166445 (JP), filed on Jun. 03, 2004. | ||
| Prior Publication US 2006/0252765 A1, Nov. 09, 2006 | ||
| Int. Cl. A61K 31/445 (2006.01); A61K 31/44 (2006.01) | ||
| U.S. Cl. 514—352 [514/243; 514/245; 514/256] | 3 Claims |
1. A method of recovering corneal sensitivity after corneal surgery, which comprises administering after corneal surgery and
topically to the eye of a patient in need thereof an effective amount of an amide compound represented by the formula (I):
 Ra is a formula:
 in the formulas (a) and (b),
R is hydrogen, alkyl, or cycloalkyl, cycloalkylalkyl, phenyl or aralkyl, each optionally having substituent(s) on the ring,
or a formula:
 wherein
R6 is hydrogen, alkyl or a formula: —NR8R9 wherein R8 and R9 are the same or different and each is hydrogen, alkyl, aralkyl or phenyl, and
R7 is hydrogen, alkyl, aralkyl, phenyl, nitro or cyano,
or R6 and R7 in combination form a heterocyclic group further optionally containing, in the ring, an oxygen atom, a sulfur atom, or a nitrogen
atom optionally having a substituent,
R1 is hydrogen, alkyl, or cycloalkyl, cycloalkylalkyl, phenyl or aralkyl, each optionally having substituent(s) on the ring,
or R and R1 in combination form, together with the adjacent nitrogen atom, a heterocyclic group further optionally containing, in the
ring, an oxygen atom, a sulfur atom, or a nitrogen atom optionally having a substituent,
R2 is hydrogen or alkyl,
R3 and R4 are the same or different and each is hydrogen, alkyl, aralkyl, halogen, nitro, amino, alkylamino, acylamino, hydroxy, alkoxy,
aralkyloxy, cyano, acyl, mercapto, alkylthio, aralkylthio, carboxy, alkoxycarbonyl, carbamoyl, mono- or di-alkylcarbamoyl
or azido, and
A is a formula:
 wherein
R10 and R11 are the same or different and each is hydrogen, alkyl, haloalkyl, aralkyl, hydroxyalkyl, carboxy or alkoxycarbonyl, or R10 and R11 in combination form cycloalkyl, and
l, m, n are each 0 or an integer of 1-3, and
in the formula (c),
L is hydrogen, alkyl, aminoalkyl, mono- or di-alkylaminoalkyl, tetrahydrofurfuryl, carbamoylalkyl, phthalimidoalkyl, amidino,
or a formula:
 wherein
B is hydrogen, alkyl, alkoxy, aralkyl, aralkyloxy, aminoalkyl, hydroxyalkyl, alkanoyloxyalkyl, alkoxycarbonylalkyl, α-aminobenzyl,
furyl, pyridyl, phenyl, phenylamino, styryl or imidazopyridyl,
Q1 is hydrogen, halogen, a hydroxyl group, aralkyloxy or thienylmethyl,
W is alkylene,
Q2 is hydrogen, halogen, a hydroxyl group or aralkyloxy,
X is alkylene,
Q3 is hydrogen, halogen, a hydroxyl group, alkoxy, nitro, amino, 2,3-dihydrofuryl or 5-methyl-3-oxo-2,3,4,5-tetrahydropyridazin-6-yl,
and
Y is a single bond, alkylene or alkenylene,
a bond shown by a broken line and a solid line in the formula (c) is a single bond or a double bond, and
R5 is hydrogen, a hydroxyl group, alkoxy, alkoxycarbonyloxy, alkanoyloxy or aralkyloxycarbonyloxy,
Rb is hydrogen, alkyl, aralkyl, aminoalkyl or mono- or di-alkylaminoalkyl, and
Rc is a nitrogen-containing heterocycle optionally having substituent(s), an isomer thereof and/or a pharmaceutically acceptable
acid addition salt thereof.
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