Nucleoside analog libraries

The compound having the formula:

• 32
• wherein:
• X1 is an optionally substituted azidyl or hydroxyl;
• X2 is chloro, or together with a double bond attached to the ring form a carbonyl;
• R1 is a linker moiety;
• R2 is selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocycloalkyl, or is absent;
• the dashed bonds denoted by a and b are single or double bonds wherein a is a single bond when b is a double bond and a is a double bond when b is a single bond;
• and
• S is a solid phase.

A library of at least 500 compounds having the formula:

• 34
• wherein:
• R3 is —SR5, —NR6R7, —NR8—NR9R10, —NR11—OR12 or —OR13,
• wherein R5, R6, R7, R8, R9, R10, R11, R12 and R13 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• R4 is —CH2—OH, —CH2—NR14R15, —CH2—Cl, —CH2—N3, —CH2—COOH,
• 35
• wherein R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, and R28 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• Z is an oxygen or sulfur;
• Y is an oxygen or a secondary amine;
• the dashed bonds denoted by e, f and g are single bonds or absent wherein if e is a single bond then f is absent and g is absent, and if e is absent then f is a single bond and g is a single bond;
• L1 is a linker moiety or hydrogen wherein L1 is hydrogen when e is a single bond and L1 is a linker moiety when e is absent;
• L2 is hydrogen or absent wherein L2 is hydrogen when e is a single bond and L2 is absent when e absent;
• and
• S is an optionally present solid phase.

A library of at least 500 compounds having the formula:

• 36
• wherein:
• R3 is —SR5, —NR6R7, —NR8—NR9R10, —NR11—OR12 or —OR13,
• wherein R5, R6, R7, R8, R9, R10, R11, R12 and R13 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• R4 is —CH2—OH, —CH2—NR14R15, —CH2—Cl, —CH2—N3, —CH2—COOH,
• 37
• wherein R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, and R28 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• Z is an oxygen or sulfur;
• Y is an oxygen or a secondary amine;
• the dashed bonds denoted by e, f and g are single bonds or absent wherein if e is a single bond then f is absent and g is absent, and if e is absent then f is a single bond and g is a single bond;
• L1 is a linker moiety or hydrogen wherein L1 is hydrogen when e is a single bond and L1 is a linker moiety when e is absent;
• L2 is hydrogen or absent wherein L2 is hydrogen when e is a single bond and L2 is absent when e absent;
• and
• S is an optionally present solid phase.

A method for the preparation of a combinatorial chemistry library of compounds having the formula:

• 38
• wherein:
• R3 is —SR5, —NR6R7, —NR8—NR9R10, —NR11—OR12 or —OR13,
• wherein R4, R5, R6, R7, R8, R9, R10, R11, R12 and R13 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• R4 is —CH2—OH, —CH2—NR14R15, —CH2—Cl, —CH2—N3, —CH2—COOH,
• 39
• wherein R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, and R26 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• Z is an oxygen or sulfur;
• Y is an oxygen or a secondary amine;
• the dashed bonds denoted by e, f and g are single bonds or absent wherein if e is a single bond then f is absent and g is absent, and if e is absent then f is a single bond and g is a single bond;
• L1 is a linker moiety or hydrogen wherein L1 is hydrogen when e is a single bond and L1 is a linker moiety when e is absent;
• L2 is hydrogen or absent wherein L2 is hydrogen when e is a single bond and L2 is absent when e absent;
• and
• S is an optionally present solid phase;
• the method comprising subjecting a combinatorial chemistry intermediate to at least one diversity generating reaction to form the combinatorial chemistry library of compounds, the combinatorial chemistry intermediate having the formula:
• 40
• wherein:
• X1 is an optionally substituted azidyl or hydroxyl;
• X2 is an optionally substituted triazolyl, or together with a double bond attached to the ring form a carbonyl;
• R1 is a linker moiety;
• R2 is hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocycloalkyl, or is absent;
• the dashed bonds denoted by a and b are single or double bonds wherein a is a single bond when b is a double bond and a is a double bond when b is a single bond;
• and
• S is a solid phase.

A method for the preparation of a combinatorial chemistry library of compounds having the formula:

• 41
• wherein:
• R3 is —SR5, —NR6R7, —NR8—NR9R10, —NR11—OR12 or —OR13,
• wherein R5, R6, R7, R8, R9, R10, R11, R12 and R13 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• R4 is —CH2—OH, —CH2—NR14R15, —CH2—Cl, —CH2—N3, —CH2—COOH,
• 42
• wherein R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, and R28 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• Z is an oxygen or sulfur;
• Y is an oxygen or a secondary amine;
• the dashed bonds denoted by e, f and g are single bonds or absent wherein if e is a single bond then f is absent and g is absent, and if e is absent then f is a single bond and g is a single bond;
• L1 is a linker moiety or hydrogen wherein L1 is hydrogen when e is a single bond and L1 is a linker moiety when e is absent;
• L2 is hydrogen or absent wherein L2 is hydrogen when e is a single bond and L2 is absent when e absent;
• and
• S is an optionally present solid phase;
• the method comprising subjecting a combinatorial chemistry intermediate to at least one diversity generating reaction to form the combinatorial chemistry library of compounds, the combinatorial chemistry intermediate having the formula:
• 43
• wherein:
• X1 is an optionally substituted azidyl or hydroxyl;
• X2 is an optionally substituted triazolyl, or together with a double bond attached to the ring form a carbonyl;
• R1 is a linker moiety;
• R2 is hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocycloalkyl, or is absent;
• the dashed bonds denoted by a and b are single or double bonds wherein a is a single bond when b is a double bond and a is a double bond when b is a single bond;
• and
• S is a solid phase.

A method of screening a library of compounds for an agonist of a purine receptor, the method comprising:

• (i) preparing a library of compounds having the formula:
• 44
• wherein:
• R3 is —SR5, —NR6R7, —NR8—NR9R10, —NR11—OR12 or —OR13,
• wherein R5, R6, R7, R8, R9, R10, R11, R12 and R13 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• R4 is —CH2—OH, —CH2—NR14R15, —CH2—Cl, —CH2—N3, —CH2—COOH,
• 45
• wherein R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, and R28 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• Z is an oxygen or sulfur;
• Y is an oxygen or a secondary amine;
• the dashed bonds denoted by e, f and g are single bonds or absent wherein if e is a single bond then f is absent and g is absent, and if e is absent then f is a single bond and g is a single bond;
• L1 is a linker moiety or hydrogen wherein L1 is hydrogen when e is a single bond and L1 is a linker moiety when e is absent;
• L2 is hydrogen or absent wherein L2 is hydrogen when e is a single bond and L2 is absent when e absent;
• and
• S is an optionally present solid phase;
• and
• (ii) screening the library by contacting the purine receptor with the library.

A method of screening a library of compounds for an agonist of a purine receptor, the comprising:

• (i) preparing a library of compounds having the formula:
• 46
• wherein:
• R3 is —SR5, —NR6R7, —NR8—NR9R10, —NR11—OR12 or —OR13,
• wherein R5, R6, R7, R8, R9, R10, R11, R12 and R13 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• R4 is —CH2—OH, —CH2—NR14R15, —CH2—Cl, —CH2—N3, —CH2—COOH,
• 47
• wherein R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, and R28 are each members independently selected from hydrogen, an optionally substituted alkyl, an optionally substituted heteroalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted heterocycloalkyl;
• Z is an oxygen or sulfur;
• Y is an oxygen or a secondary amine;
• the dashed bonds denoted by e, f and g are single bonds or absent wherein if e is a single bond then f is absent and g is absent, and if e is absent then f is a single bond and g is a single bond;
• L1 is a linker moiety or hydrogen wherein L1 is hydrogen when e is a single bond and L1 is a linker moiety when e is absent;
• L2 is hydrogen or absent wherein L2 is hydrogen when e is a single bond and L2 is absent when e absent;
• and
• S is an optionally present solid phase;
• and
• (ii) screening the library by contacting the purine receptor with the library.