Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome

A method for preventing or reducing adult respiratory distress syndrome (ARDS) in a patient at risk of ARDS which comprises administering to said patient an effective amount of a dehydroepiandrosterone (DHEA) derivative having the general formulas I and II and their pharmaceutically acceptable salts

• wherein
• R1, R2, R3, R4, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R19 are independently H, —OH, halogen, C1-10 alkyl or C1-10 alkoxy;
• R5 is H, —OH, halogen, C1-10 alkyl, C1-10 alkoxy or OSO2R20;
• R15 is
• (1) H, halogen, C1-10 alkyl or C1-10 alkoxy when R16 is —C(O)OR21 or
• (2) H, halogen, OH or C1-10 alkyl when R16 is H, halogen, OH or C1-10 alkyl or
• (3) H, halogen, C1-10 alkyl, C1-10 alkenyl, C1-10 alkynyl, formyl, C1-10 alkanoyl or epoxy when R16 is OH;
• or
• R15 and R16 taken together are ═O;
• R17 and R18 are independently
• (1) H, —OH, halogen, C1-10 alkyl or C1-10 alkoxy when R16 is H, OH, halogen, C1-10 alkyl or —C(O)OR21 or
• (2) H, (C1-10 alkyl)namino, (C1-10 alkyl)namino-C1-10 alkyl, C1-10 alkoxy, hydroxy-C1-10 alkyl, C1-10 alkoxy-C1-10 alkyl, (halogen)m-C1-10 alkyl, C1-10 alkanoyl, formyl, C1-10 carbalkoxy or C1-10 alkanoyloxy when R15 and R16 taken together are ═O;
• or
• R17 and R18 taken together are ═O or taken together with the carbon to which they are attached form a 3-6 member ring containing 0 or 1 oxygen atoms;
• or
• R15 and R17 taken together with the carbons to which they are attached form an epoxide ring;
• R20 is OH, pharmaceutically acceptable ester or pharmaceutically acceptable ether;
• R21 is H, (halogen)m-C1-10 alkyl or C1-10 alkyl;
• n is 0, 1 or 2;
• and
• m is 1,2 or 3,
• with the provisos that
• (a) R3 is not H, OH or halogen when R1, R2, R4, R6, R7, R9, R10, R12, R13, R14, R17 and R19 are H and R5 is OH or C1-10 alkoxy and R8 is H, OH or halogen and R11 is H or OH and R18 is H, halogen or methyl and R15 is H and R16 is OH;
• (b) R3 is not H, OH or halogen when R1, R2, R4, R6, R7, R9, R10, R12, R13, R14 and R19 are H and R5 is OH or C1-10 alkoxy and R8 is H, OH or halogen and R11 is H or OH and R18 is H, halogen or methyl and R15 and R16 taken together are ═O;
• (c) R5 is not H, halogen, C1-10 alkoxy or OSO2R20 when R1, R2, R3, R4, R6, R7, R8, R9, R10, R12, R13, R14 and R17 are H and R11 is H, halogen, OH or C1-10 alkoxy and R18 is H or halogen and R15 and R16 taken together are ═O;
• and
• (d) R5 is not H, halogen, C1-10 alkoxy or OSO2R20 when R1, R2, R3, R4, R6, R7, R8, R9, R10, R12, R13, R14 and R17 are H and R11 is H, halogen, OH or C1-10 alkoxy and R18 is H or halogen and R15 is H and R16 is H, OH or halogen.