Methods and compositions for modulating fgf activity

A method of increasing spermatogenesis in a subject comprising administering to a subject a therapeutically effective amount of a compound, wherein the compound is a compound of formula (I):

• or a pharmaceutically acceptable salt or a tautomer thereof, wherein
• Q is optionally substituted C6-C10 aryl or optionally substituted 6- to 10-membered heterocyclyl;
• R1 is H, OH, optionally substituted C1-C6 alkyl, optionally substituted C6-C16 aryl, or optionally substituted 6- to 12-membered heteroaryl;
• and
• Z is O or NRc and is a double bond,
• wherein Rc is H;
• optionally substituted C1-C6 alkyl;
• optionally substituted C2-C6 alkenyl;
• optionally substituted C2-C6 alkynyl;
• optionally substituted C3-C8 cycloalkyl;
• optionally substituted C4-C13 cycloalkenyl;
• optionally substituted C1-C15 heterocyclyl;
• optionally substituted C6-C16 aryl;
• ORd;
• SRe;
• or NRfRg, wherein Ra and Re are independently H or C1-C6 alkyl and wherein Rf and Rg are independently H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted 6- to 10-membered heterocyclyl, or optionally substituted C6-C16 aryl, or Rf and Rg, together with the nitrogen atom to which they are attached, form an optionally substituted 6- to 10-membered heterocyclyl, or Rf and Rg, together with the nitrogen atom to which they are attached, form N═C(R1′)Q′, wherein R1′ is H, OH, optionally substituted C1-C6 alkyl, optionally substituted C6-C16 aryl, or optionally substituted 6- to 12-membered heteroaryl and Q′ is optionally substituted C6-C10 aryl or optionally substituted 6- to 10-membered heterocyclyl;
• or
• is a single bond, and R1 and Z, together with the carbon atom to which they are attached, form an optionally substituted oxazolidinyl or optionally substituted thiazolidinyl;
• or
• is a single bond, and Z is OH.

A compound of formula (I′):

• or a pharmaceutically acceptable salt or a tautomer thereof, wherein
• Q is optionally substituted C6-C10 aryl or optionally substituted 6- to 10-membered heterocyclyl;
• R1 is H;
• and
• Z is NRc and is a double bond,
• wherein Rc is a group of formula:
• wherein Rh is substituted C3-C8 cycloalkyl or optionally substituted C1-C15 heterocyclyl;
• or
• Rc is a group of formula N═C(R1′)Q′, wherein R1′ is H and Q′ is optionally substituted C6-C10 aryl or optionally substituted 6- to 10-membered heterocyclyl;
• or
• Rc is a group of formula:
• or
• is a single bond, and R1 and Z, together with the carbon atom to which they are attached, form an optionally substituted oxazolidinyl or optionally substituted thiazolidinyl.

A pharmaceutical composition comprising a compound of formula (I):

• wherein
• Q is optionally substituted C6-C10 aryl, or optionally substituted 6- to 10-membered heterocyclyl;
• R1 is H, OH, optionally substituted C1-C6 alkyl, optionally substituted C6-C16 aryl or optionally substituted 6- to 12-membered heteroaryl;
• and
• Z is O or NRc, and is a double bond,
• wherein Rc is H;
• optionally substituted C1-C6 alkyl;
• optionally substituted C2-C6 alkenyl;
• optionally substituted C2-C6 alkynyl;
• optionally substituted C3-C8 cycloalkyl;
• optionally substituted C4-C13 cycloalkenyl;
• optionally substituted C1-C15 heterocyclyl;
• optionally substituted C6-C16 aryl;
• ORd;
• SRe;
• or NRfRg, wherein Ra and Re are independently H or C1-C6 alkyl and wherein Rf and Rg are independently H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted 6- to 10-membered heterocyclyl, or optionally substituted C6-C16 aryl, or Rf and Rg, together with the nitrogen atom to which they are attached, forms an optionally substituted 6- to 10-membered heterocyclyl, or or Rf and Rg, together with the nitrogen atom to which they are attached, form N═C(R1′)Q′, wherein R1′ is H, OH, optionally substituted C1-C6 alkyl, optionally substituted C6-C16 aryl, or optionally substituted 6- to 12-membered heteroaryl and Q′ is optionally substituted C6-C10 aryl or optionally substituted 6- to 10-membered heterocyclyl;
• or
• is a single bond, and R1 and Z, together with the carbon atom to which they are attached, form an optionally substituted oxazolidinyl or optionally substituted thiazolidinyl,
• or a pharmaceutically acceptable salt or a tautomer thereof, and a pharmaceutically acceptable excipient.