Substituted pyrazolo[1,5-a]pyrimidines as Bruton's tyrosine kinase modulators

An oral dosage form comprising a pharmaceutically acceptable carrier and a compound of formula I:

• or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
• A is a 5- or 6-membered aromatic ring, wherein the 5- or 6-membered aromatic ring comprises 0, 1, 2, or 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• L is a bond, —CH2—, —NR12—, —O—, or —S—;
• R1 is H, halogen, CN, alkyl, heteroalkyl, alkenyl, alkynyl, C(NR13)NR14R15, C(O)R13, C(O)NR13R14, C(O)OR13, NR13R14, NR13C(O)R14, NR13C(O)NR14R15, NR13C(O)OR14, NR13S(O)2R14, NR13S(O)2NR14R15, OR13, S(O)2R13, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more independently selected R16 substituents;
• each R2 is independently halogen, CN, alkyl, C(NR13)NR14R15, C(O)R13, C(O)NR13R14, C(O)OR13, NR13R14, NR13C(O)R14, NR13C(O)NR14R15, NR13C(O)OR14, NR13S(O)2R14, NR13S(O)2NR14R15, OR13, S-alkyl, or S(O)2R13;
• R4 is H, halogen, CN, alkyl, heteroalkyl, alkenyl, alkynyl, C(NR13)NR14R15, C(O)R13, C(O)NR13R14, C(O)OR13, NR13R14, NR13C(O)R14, NR13C(O)NR14R15, NR13C(O)OR14, NR13S(O)2R14, NR13S(O)2NR14R15, OR13, S(O)2R13, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more independently selected R16 substituents;
• R5 is H, halogen, CN, alkyl, heteroalkyl, alkenyl, alkynyl, C(NR13)NR14R15, C(O)R13, C(O)NR13R14, C(O)OR13, NR13R14, NR13C(O)R14, NR13C(O)NR14R15, NR13C(O)OR14, NR13S(O)2R14, NR13S(O)2NR14R15, OR13, S(O)2R13, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more independently selected R16 substituents;
• R6 is H, halogen, CN, alkyl, heteroalkyl, alkenyl, alkynyl, C(NR13)NR14R15, C(O)R13, C(O)NR13R14, C(O)OR13, NR13R14, NR13C(O)R14, NR13C(O)NR14R15, NR13C(O)OR14, NR13S(O)2R14, NR13S(O)2NR14R15, OR13, S(O)2R13, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more independently selected R16 substituents;
• R7 is H, halogen, CN, alkyl, heteroalkyl, alkenyl, alkynyl, C(NR13)NR14R15, C(O)R13, C(O)NR13R14, C(O)OR13, NR13R14, NR13C(O)R14, NR13C(O)NR14R15, NR13C(O)OR14, NR13S(O)2R14, NR13S(O)2NR14R15, OR13, S(O)2R13, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more independently selected R16 substituents;
• R12 is H or lower alkyl;
• each R13 is independently H, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• each R14 is independently H, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• each R15 is independently H, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• or
• each R13 and R14, together with the atom(s) to which they are attached, independently forms a cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally and independently substituted with one or more independently selected R16 substituents;
• or
• each R14 and R15, together with the atom(s) to which they are attached, independently forms a cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally and independently substituted with one or more independently selected R16 substituents;
• each R16 is independently halogen, CN, oxo, alkyl, alkenyl, alkynyl, C(NR′)NR″R′″, C(O)R′, C(O)NR′R″, C(O)OR′, NR′R″, NR′C(O)R″, NR′C(O)NR′R″, NR′C(O)OR″, NR'S(O)2R″, NR'S(O)2NR″R′″, OR′, S(O)2R′, S(O)2aryl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• each R′ is independently H, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• each R″ is independently H, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• each R′″ is independently H, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• or
• each R′ and R″, together with the atom(s) to which they are attached, independently forms a cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• or
• each R″ and R′″, together with the atom(s) to which they are attached, independently forms a cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• W is —CH2— or —C(O)—;
• m is 1;
• n is 0, 1, 2, 3, or 4;
• p is 1;
• and
• — is a single or double bond;
• wherein each alkyl, alkenyl, and alkynyl of each R16, R′, R″, and R′″ is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, oxo, C(NRa)NRbRc, C(O)Ra, C(O)NRaRb, C(O)ORa, NRaRb, NRaC(O)Rb, NRaC(O)NRaRb, NRaC(O)ORb, NRaS(O)2Rb, NRaS(O)2NRbRc, ORa, S(O)2Ra, S(O)2aryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl of each R16, R′, R″, and R′″ is optionally and independently substituted with one or more substituents independently selected from the group consisting of halogen, CN, oxo, alkyl, alkenyl, alkynyl, C(NRa)NRbRc, C(O)Ra, C(O)NRaRb, C(O)ORa, NRaRb, NRaC(O)Rb, NRaC(O)NRaRb, NRaC(O)ORb, NRaS(O)2Rb, NRaS(O)2NRbRc, ORa, S(O)2Ra, S(O)2aryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• and
• wherein each Ra, Rb, and Rc is independently H, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• with the proviso that when ═ is a double bond, R5 and R7 are absent.