Substituted 11-phenyl-dibenzazepine compounds useful for the treatment or prevention of diseases characterized by abnormal cell proliferation

A pharmaceutical composition comprising a compound and a pharmaceutically acceptable excipient, carrier or diluent, said compound having the formula:

• 12
• or a pharmaceutically acceptable salt or hydrate thereof, wherein:
• R1 is —R1, (C6-C20) aryl or substituted (C6-C20) aryl;
• R2 is —R1, —OR′, —SR′, halogen or trihalomethyl;
• R3 is —R1, —OR′, —SR′, halogen or trihalomethyl or, when taken together with R4, is (C6-C20) aryleno;
• R4 is —R1, —OR′, —SR′, halogen or trihalomethyl or, when taken together with R3, is (C6-C20) aryleno;
• each of R5, R6, R7, R8, R9, R10, R11, R12, R13, and R14 is independently selected from the group consisting of —R′, halogen and trihalomethyl;
• R15 is —R″, —C(O)R″, —C(S)R″, —C(O)OR″, —C(S)OR″, —C(O)SR″, —C(S)SR″, —C(O)N(R″)2, —C(S)N(R″)2, —C(O)C(O)R″, —C(S)C(O)R″, —C(O)C(S)R″, —C(S)C(S)R″, —C(O)C(O)OR″, —C(S)C(O)OR″, —C(O)C(S)OR″, —C(O)C(O)SR″, —C(S)C(S)OR″, —C(S)C(O)SR″, —C(O)C(S)SR″, —C(S)C(S)SR″, —C(O)C(O)N(R″)2, —C(S)C(O)N(R″)2, —C(O)C(S)N(R11)2 or —C(S)C(S)N(R″)2;
• each R′ is independently selected from the group consisting of —H, (C1-C6) alkyl, (C1-C6) alkenyl and (C,-c.) alkynyl;
• each R″ is independently selected from the group consisting of —H, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, (C6-C20) aryl, (C6-C20) substituted aryl, (C1-C20) alkaryl and substituted (C6-C26) alkaryl;
• and
• the aryl and alkaryl substituents are each independently selected from the group consisting of —CN, —OR′, —SR′, —NO2, —NR′R′, halogen, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl and trihalomethyl.

A method of inhibiting mammalian cell proliferation, said method comprising the step of contacting a mammalian cell in situ with an effective amount of a compound having the formula:

• 13
• or a pharmaceutically acceptable salt or hydrate thereof, wherein:
• R1 is —R′, (C6-C20) aryl or substituted (C6-C20) aryl;
• R2 is —R′, —OR′, —SR′, halogen or trihalomethyl;
• R3 is —R′, —OR′, —SR′, halogen or trihalomethyl or, when taken together with R4, is (C1-C20) aryleno;
• R4 is —R1, —OR′, —SR′, halogen or trihalomethyl or, when taken together with R3, is (C6-C20) aryleno;
• each of R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 is independently selected from the group consisting of —R′, halogen and trihalomethyl;
• R15 is —R″, —C(O)R″, —C(S)R″, —C(O)OR″, —C(S)OR″, —C(O)SR″, —C(S)SR″, —C(O)N(R″)2, —C(S)N(R″)2, —C(O)C(O)R″, —C(S)C(O)R″, —C(O)C(S)R″, —C(S)C(S)R″, —C(O)C(O)OR″, —C(S)C(O)OR″, —C(O)C(S)OR″, —C(O)C(O)SR″, —C(S)C(S)OR″, —C(S)C(O)SR″, —C(O)C(S)SR″, —C(S)C(S)SR″, —C(O)C(O)N(R″)2, —C(S)C(O)N(R″)2, —C(O)C(S)N(R″)2 or —C(S)C(S)N(R″)2;
• each R′ is independently selected from the group consisting of —H, (C1-C6) alkyl, (C1-C6) alkenyl and (C1-C6) alkynyl;
• each R″ is independently selected from the group consisting of —H, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, (C6-C20) aryl, (C6-C20) substituted aryl, (C6-C26) alkaryl and substituted (C6-C26) alkaryl;
• and
• the aryl and alkaryl substituents are each independently selected from the group consisting of —CN, —OR′, —SR′, —NO2, —NR′R′, halogen, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl and trihalomethyl.

A method of treating or preventing a disorder characterized by abnormal cell proliferation, said method comprising the step of administering to a subject in need thereof a therapeutically effective amount of a composition having the formula:

• 14
• or a pharmaceutically acceptable salt or hydrate thereof, wherein:
• R1 is —R′, (C6-C20) aryl or substituted (C6-C20) aryl;
• R2 is —R1, —OR′, —SR′, halogen or trihalomethyl;
• R2 is —R′, —OR′, —SR′, halogen or trihalomethyl or, when taken together with R4, is (C1-C20) aryleno;
• R4 is —R′, —OR′, —SR′, halogen or trihalomethyl or, when taken together with R3, is (C6-C20) aryleno;
• each of R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 is independently selected from the group consisting of —R′, halogen and trihalomethyl;
• R15 is —R″, —C(O)R″, —C(S)R10, —C(O)OR″, —C(S)OR″, —C(O)SR″, —C(S)SR″, —C(O)N(R″)2, —C(S)N(R″)2, —C(O)C(O)R″, —C(S)C(O)R″, —C(O)C(S)R″, —C(S)C(S)R″, —C(O)C(O)OR″, —C(S)C(O)OR″, —C(O)C(S)OR″, —C(O)C(O)SR″, —C(S)C(S)OR″, —C(S)C(O)SR″, —C(O)C(S)SR″, —C(S)C(S)SR″, —C(O)C(O)N(R″)2, —C(S)C(O)N(R″)2, —C(O)C(S)N(R″)2 or —C(S)C(S)N(R″)2;
• each R′ is independently selected from the group consisting of —H, (C1-C6) alkyl, (C1-C6) alkenyl and (C1-C6) alkynyl;
• each R″ is independently selected from the group consisting of —H, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, (C6-C20) aryl, (C6-C20) substituted aryl, (C6-C26) alkaryl and substituted (C6-C26) alkaryl;
• and
• the aryl and alkaryl substituents are each independently selected from the group consisting of —CN, —OR′, —SR′, —NO2, —NR′R′, halogen, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl and trihalomethyl.