Semicarbazide-sensitive amine oxidase inhibitors for use as analgesics in traumatic neuropathy and neurogenic inflammation

A method for the treatment of hyperalgesia and allodynia implicated in traumatic neuropathy or neurogenic inflammation, said method comprising administering a compound having SSAO/VAP-1 inhibitor activity to a subject in need of said treatment, wherein the compound has the general formula of Ar—(CH2)n-CR1=N—OR2 (I′) or salt, hydrate or solvate thereof—wherein

• Ar is a group of the formula:
• R1 is H or lower alkyl;
• R2 is H, lower alkyl, benzyl, —(CH2)k-COOR13, —(CH2)m-N(R14R15) or —CO—NH—R16,
• wherein R13 is lower alkyl,
• k is 1, 2 or 3;
• m is 1, 2 or 3;
• R14 and R15 are independently from each other lower alkyl, or R14 and R15 together with the nitrogen they are atteched form a 5 to 7 membered heteroring, optionally containing 1 to 3 further heteroatom(s) selected from nitrogen, oxygen and sulfur atoms,
• R16 is phenyl, optionally substituted with one or more group selected from halogen, lower alkyl and lower alkoxy;
• R3 and R4 together with the carbons they are attached to form a 5 to 7 membered heteroring containing one or two oxygen(s), preferably 1,3-dioxolane, optionally substituted with lower alkyl;
• or
• R3 is H, halogen, lower alkyl or OR17, wherein R17 is H, lower alkyl, lower alkenyl, optionally substituted with phenyl;
• R4 is H or OR19, wherein R19 is lower alkyl;
• R5 is H or halogen;
• R6 is H or halogen;
• R7 is H, halogen, OH, OR20 or a phenyl substituted with Z
• wherein R20 is lower alkyl or lower alkenyl, and Z is —CH═N—OH or halogen;
• X is a 5 to 7 membered heteroring containing 1 or 3 heteroatom(s) selected from nitrogen, oxygen and sulfur atoms;
• Y is SR21, OR22, 5 to 7 membered heteroring containing 1 to 3 heteroatom(s) selected from nitrogen, oxygen and sulfur atoms, optionally substituted with phenyl or a (lower alkenyl)amino, optionally N-substituted with lower alkyl;
• wherein R21 is lower alkyl or phenyl and R22 is lower alkyl;
• R8 is lower alkyl or optionally substituted benzyl, wherein the substituent is 1 or 2 lower alkoxy;
• R9 is H or phenyl;
• R10 is di(lower alkyl)amino, preferably dimethylamino, 5 to 7 membered heteroring containing 1 or 3 heteroatom(s) selected from nitrogen, oxygen and sulfur atoms, optionally substituted with one or more group selected from lower alkyl, lower alkenyl and phenyl;
• or R9 and R10 together with the attached carbon atoms form an optionally substituted 5 to 8 membered heteroring containing 1 or 3 heteroatom(s) selected from nitrogen, oxygen and sulfur atoms, optionally substituted with one or more group selected from lower alkyl and benzyl, and optionally together with lower alkylene form a fused bicyclic group;
• W is a bond or a phenylene group;
• R11 is lower alkyl;
• R12 is phenyl, optionally substituted with halogen;
• n is integer of 0 to 4;
• Ar1 and Ar2 are the same or different and stand for phenyl, optionally substituted with one or more group selected from halogen, lower alkyl and lower alkoxy;
• and any stereoisomer, mixture of stereoisomers, E or Z forms, mixture of E and Z forms, crystalline form, non-crystalline form thereof;
• wherein
• “lower alkyl” refers to aliphatic and alicyclic groups including straight-chain (linear), branched-chain or cyclic groups having up to 6 carbon atoms;
• “lower alkenyl” refers to unsaturated aliphatic and alicyclic groups including straight-chain (linear), branched-chain, cyclic groups, and combinations thereof, having up to 6 carbon atoms, which contain at least one double bond (—C═C—);
• “lower alkoxy”refers to a “(lower alkyl)-O—“group, where the “lower alkyl”has the above-defined meaning.