Claims for Patent: 10,570,139

Summary for Patent: 10,570,139

Title:	Substituted pyrazolo[1,5-a]pyrimidines as Bruton's tyrosine kinase modulators
Abstract:	The invention is fused heterocyclic compounds of formula (I), and salts thereof, compositions thereof, and methods of use therefor. In particular, disclosed herein are certain fused heterocyclic compounds that can be useful for inhibiting protein kinase, including Bruton's tyrosine kinase (Btk), and for treating disorders mediated thereby.
Inventor(s):	Zhiwei Wang, Yunhang Guo
Assignee:	Beone Medicines I GmbH
Application Number:	US15/969,864
Patent Claims:	1. A method for modulating Bruton's tyrosine kinase activity in a patient suffering from a B-cell proliferative disorder, comprising administering to the patient a therapeutically effective amount of a compound of formula I: or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein: A is a 5- or 6-membered aromatic ring comprising 0, 1, 2, or 3 heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen; W is —(CH2)— or —C(O)—; L is a bond, CH2, NR12, O, or S; S/D is a single or double bond, wherein when S/D is a double bond, R5 and R7 are absent; m is 1; n is 0, 1, 2, 3, or 4, wherein when n is 2, 3, or 4, each R2 may be different; p is 1; R1, R4, R5, R6 and R7 are each independently H, halogen, heteroalkyl, alkyl, alkenyl, cycloalkyl, aryl, saturated or unsaturated heterocyclyl, heteroaryl, alkynyl, —CN, —NR13R14, —OR13, —COR13, —CO2R13, —CONR13R14, —C(═NR13)NR14R15, —NR13COR14, —NR13CONR14R15, —NR13CO2R14, —SO2R13, —NR13SO2NR14R15, or —NR13SO2R14, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, aryl, and saturated or unsaturated heterocyclyl are optionally substituted with at least one substituent R16; R2 is halogen, alkyl, —S-alkyl, —CN, —NR13R14, —OR13, —COR13, —CO2R13, —CONR13R14, —C(═NR13)NR14R15, —NR13COR14, —NR13CONR14R15, —NR13CO2R14, —SO2R13, —NR13SO2NR14R15, or —NR13SO2R14; R12 is H or lower alkyl; R13, R14 and R15 are each independently H, heteroalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, saturated or unsaturated heterocyclyl, aryl, or heteroaryl; wherein (R13 and R14), and/or (R14 and R15) together with the atom(s) to which they are attached, may independently form a ring selected from cycloalkyl, saturated or unsaturated heterocyclyl, aryl, and heteroaryl, each optionally substituted with at least one substituent R16; and R16 is halogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, oxo, —CN, —OR′, —NR′R″, —COR′, —CO2R′, —CONR′R″, —C(=NR′)NR″R″′, —NR′COR″, —NR′CONR′R″, —NR′CO2R″, —SO2R′, —SO2aryl, —NR′SO2NR″R″′, or —NR′SO2R″, wherein R′, R″, and R″′ are independently H, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein (R′ and R″) and/or (R″ and R″′) together with the atom(s) to which they are attached, may independently form a ring selected from cycloalkyl, heterocyclyl, aryl, and heteroaryl; wherein each alkyl, alkenyl and alkynyl of R16, R′, R″, and R′″ is optionally substituted with at least one substituent selected from the group consisting of halogen, cycloalkyl, aryl, heteroaryl, heterocyclyl, oxo, —CN, —ORa, —NRaRb, —CORa, —CO2Ra, —CONRaRb, —C(═NRa)NRbRc, —NRaCORb, —NRaCONRaRb, —NRaCO2Rb, —SO2Ra, —SO2aryl, —NRaSO2NRbRc, and —NRaSO2Rb; wherein each cycloalkyl, aryl, heteroaryl, and heterocyclyl of R16, R′, R″, and R″′ is optionally substituted with at least one substituent selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, oxo, —CN, —ORa, —NRaRb, —CORa, —CO2Ra, —CONRaRb, —C(═NRa)NRbRc, —NRaCORb, —NRaCONRaRb, —NRaCO2Rb, —SO2Ra, —SO2aryl, —NRaSO2NRbRc, and —NRaSO2Rb; and wherein each Ra, Rb, and Rc is independently selected from the group consisting of H, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl. 2. The method of claim 1, wherein the B-cell proliferative disorder is selected from a chronic lymphocytic lymphoma, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma or chronic lymphocytic leukemia. 3. The method of claim 1, wherein S/D is a single bond. 4. The method of claim 1, wherein A is a phenyl. 5. The method of claim 1, wherein L is O. 6. The method of claim 1, wherein R1 is aryl, optionally substituted with at least one substituent R16. 7. The method of claim 1, wherein each R2 is independently halogen, lower alkyl, or lower alkoxy. 8. The method of claim 1, wherein R4 is 9. The method of claim 1, wherein R4 is 10. The method of claim 1, wherein R5, R6 and R7 are each independently H. 11. The method of claim 1, wherein W is —(CH2)—. 12. The method of claim 1, wherein the compound is of formula II: 13. The method of claim 1, wherein the compound is 14. The method of claim 1, wherein the compound is 15. The method of claim 1, wherein the compound is