Nitroxide radicals for the treatment of diseases of the respiratory tract

A method of treating a disease or disorder associated with respiratory tract remodeling, the method comprising administering by oral and/or intranasal administration to a subject in need thereof a cyclic nitroxide compound having the general formula I:

• wherein:
• the dashed line denotes a saturated bond or an unsaturated bond, wherein when the dashed line denotes an unsaturated bond, R7 and R8 are absent;
• R1-R4 are each independently a C1-4-alkyl, or alternatively, R1 and R2, and/or R3 and R4, together form a 3-7-membered alicyclic ring;
• and
• R5-R8 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, —S(═O)—R′, —S(═O)2—R′, —S(═O)2—O—R′, —O—S(═O)2—O—R′, cyano, nitro, azide, —P(═O)(OR′)(OR″), —C(═O)—R′, —C(═S)—R′, —N(R′)—C(═O)—NR″R″′, —N(R′)—C(═S)—NR″R″′, —OC(═O)—NR′R″, —N(R″)—C(═O)OR′, —OC(═S)—NR′R″, —N(R″)—C(═S)OR′, —C(═O)—NR′R″, —NR″—C(═O)R′, —C(═O)—OR′, —O—C(═O)R′, —S(═O)2—NR′R″, —NR″—S(═O)2R′, —N(R′)—N(R″)R″′, —N+R′R″R″′ and —NR′R″, wherein R′, R″ and R″′ are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalicyclic, aryl and/or heteroaryl,
• each of said alkyl, said alkenyl, said alkynyl, said cycloalkyl, said heteroalicyclic, said aryl, said heteroaryl, said alkoxy, said aryloxy, said thiohydroxy and said thioaryloxy being unsubstituted,
• wherein said disease or disorder is selected from the group consisting of idiopathic interstitial pneumonia, autoimmune-related pulmonary fibrosis, drug-induced interstitial lung disease, chronic obstructive pulmonary disease (COPD), chronic asthma, emphysema, acute lung injury, acute respiratory distress syndrome, and Birt-Hogg-Dube syndrome,
• thereby treating the disease or disorder.

A method of treating asthma, chronic obstructive pulmonary disease (COPD), and/or lung cancer, the method comprising administering to a subject in need thereof a cyclic nitroxide compound having the general formula I:

• wherein:
• the dashed line denotes a saturated bond or an unsaturated bond, wherein when the dashed line denotes an unsaturated bond, R7 and R8 are absent;
• R1-R4 are each independently a C1-4-alkyl, or alternatively, R1 and R2, and/or R3 and R4, together form a 3-7-membered alicyclic ring;
• and
• R5-R8 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, —S(═O)—R′, —S(═O)2—R′, —S(═O)2—O—R′, —O—S(═O)2—O—R′, cyano, nitro, azide, —P(═O)(OR′)(OR″), —C(═O)—R′, —C(═S)—R′, —N(R′)—C(═O)—NR″R″′, —N(R′)—C(═S)—NR″R″′, —OC(═O)—NR′R″, —N(R″)—C(═O)OR′, —OC(═S)—NR′R″, —N(R″)—C(═S)OR′, —C(═O)—NR′R″, —NR″—C(═O)R′, —C(═O)—OR′, —O—C(═O)R′, —S(═O)2—NR′R″, —NR″—S(═O)2R′, —N(R′)—N(R″)R″′, —N+R′R″R″′ and —NR′R″, wherein R′, R″ and R″′ are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalicyclic, aryl and/or heteroaryl,
• each of said alkyl, said alkenyl, said alkynyl, said cycloalkyl, said heteroalicyclic, said aryl, said heteroaryl, said alkoxy, said aryloxy, said thiohydroxy and said thioaryloxy being unsubstituted,
• thereby treating the asthma, chronic obstructive pulmonary disease (COPD), and/or lung cancer.