Pyrone-indole derivatives and process for their preparation

A method for alleviating neuropathy which comprises administering to an animal or human in need of such treatment a formulation comprising an effective amount of a compound having the formula

• Ar—B—Ar′ (I)
• wherein:
• —B— represents:
• —X—Y—Z—
• wherein
• X represents —(CH2)n (wherein n is 0-6);
• Y represents oxygen, sulphur, >NH or is absent;
• Z represents >C═O, >O or >COO or is absent;
• wherein at least one of X, Y and Z must be present;
• Ar represents an indole nucleus ring system:
• Ar′ represents an alpha-, beta- or gamma-pyrone nucleus ring system:
• wherein each of R1-4 substitutes the ring system Ar at any available position (including the N-position) and each of R1′-R2′ substitutes the ring system Ar′ at any available position and wherein each of R1-4 and R1′-2′ independently represents hydrogen, oxygen, halo, halo-C1-5 alkyl, aryl, acyl, a C5-7 heterocyclic group containing 1-3 hetero atoms independently selected from nitrogen, oxygen or sulphur;
• a C6-8 heteroaryl group containing 1-3 hetero atoms independently selected from nitrogen, oxygen or sulphur, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl- C1-5 alkyl, aryl- C2-5 alkenyl, aryl-C1-5 alkynyl, hydroxy-C1-5 alkyl, nitro, amino, cyano, cyanamide, guanidine, amidino, acylamido, C1-5 alkylamine, C1-5 alkylamido, hydroxy, thiol, acyloxy, azido, C1-5 alkoxy, carboxy, carbonylamido or styryl;
• wherein said arylalkyl, arylalkenyl, aralalkynyl, or styryl group optionally can be ring-substituted by one to four substituents independently selected from the group consisting of hydrogen, halo, halo-C1-5 alkyl, aryl, a C5-7 heterocyclic group containing 1-3 hetero atoms independently selected from nitrogen, oxygen and sulphur;
• a heteroaryl group containing 1-3 hetero atoms independently selected from nitrogen, oxygen and sulphur;
• C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl-C1-5 alkyl, aryl-C2-5 alkenyl, aryl-C2-5 alkynyl, hydroxy-C1-5 alkyl, nitro, amino, cyano, cyanamido, guanidino, amidino, acylamido, hydroxy, thiol, acyloxy, azido, aikoxy, carboxy, carbonylamido, S-alkyl or alkylthiol;
• and either of R3 or R4 further can include or represent a bond to B;
• wherein Ar can be bonded to B at any position on the five-membered ring portion of the Ar ring, including the N-position, and Ar′ can be bonded to B at any carbon on the Ar′ ring not substituted by R1′ and R2′;
• or a salt or stereoisomer thereof.