2,3-disubstituted chromen-4-one compounds as modulators of protein kinases

Patent metadata

Field	Value
Publication number	US-10442783-B2
Application number	US-93860910-A
Country	US
Kind code	B2
Filing date	Nov 3, 2010
Priority date	Nov 5, 2009
Publication date	Oct 15, 2019
Grant date	Oct 15, 2019

Abstract

The present invention provides PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of kinase mediated diseases or disorders with them.

First claim

We claim:

1. A compound of the formula:

or a tautomer thereof, N-oxide thereof, or pharmaceutically acceptable salt thereof, wherein
R is selected from −OR a , substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-8 cycloalkyl, and substituted or unsubstituted heterocyclic group; where R a is selected from hydrogen, and substituted or unsubstituted (C 1-6 )alkyl;
R 1 and R 2 may be the same or different and are independently selected from hydrogen, halogen, and substituted or unsubstituted C 1-6 alkyl, or both R 1 and R 2 directly bound to a common atom, may be joined to form a substituted or unsubstituted saturated or unsaturated 3-10 member ring (including the carbon atom to which R 1 and R 2 are bound), which may optionally include one or more heteroatoms which may be the same or different and are selected from O, NR a and S, where R a is selected from hydrogen and substituted or unsubstituted (C 1-6 )alkyl;
Cy 1 is a monocyclic group selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;
L 1 is absent or selected from —(CR a R b ) q — or —C(═Y)—, where each occurrence of R a and R b may be the same or different and are independently selected from hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted (C 1-6 )alkyl, and —OR c (wherein R c is substituted or unsubstituted (C 1-6 )alkyl) or when R a and R b are directly bound to a common atom, they may be joined to form an oxo group (═O) or form a substituted or unsubstituted saturated or unsaturated 3-10 member ring (including the common atom to which R a and R b are directly bound), which may optionally include one or more heteroatoms which may be the same or different and are selected from O, NR d (wherein R d is hydrogen or substituted or unsubstituted (C 1-6 )alkyl) or S;
Y is selected from O, S, and NR a , where R a is selected from hydrogen and substituted or unsubstituted (C 1-6 )alkyl;
q is 1 or 2; and
Cy 2 is substituted or unsubstituted heteroaryl.

2. A compound of claim 1 , wherein R is substituted or unsubstituted C 1-6 alkyl, or —O(unsubstituted C 1-6 alkyl).

3. A compound of claim 2 , wherein R is methoxy.

4. A compound of claim 1 , wherein Cy 1 is substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl.

5. A compound of claim 1 , wherein Cy 1 is selected from:

6. A compound of claim 1 , wherein R 1 and R 2 represent hydrogen or substituted or unsubstituted C 1-6 alkyl.

7. A compound of claim 1 , wherein L 1 is absent.

8. A compound of claim 1 , wherein Cy 2 is

wherein
X is CR 3 ; and
R 3 is independently selected from hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted heterocyclylalkyl ring, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted guanidine, —COOR x , —C(O)R x , —C(S)R x , —C(O)NR x R y , —C(O)ONR x R y , —NR y R z , —NR x CONR y R z , —N(R x )SOR y , —N(R x )SO 2 R y , —NR x C(O)OR y , —NR x R y , —NR x C(O)R y —, —NR x C(S)R y , —NR x C(S)NR y R z , —SONR x R y —, —SO 2 NR x R y —, —OR x , —OR x C(O)NR y R z , —OR x C(O)OR y —, —OC(O)R x , —OC(O)NR x R y , —R x NR y C(O)R z , —R x OR y , —R x C(O)OR y , —R x C(O)NR y R z , —R x C(O)R x , —R x OC(O)R y , —SR x , —SOR x , —SO 2 R x , —ONO 2 , wherein R x , R y and R z in each of the above groups can be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted heterocyclylalkyl ring, substituted or unsubstituted heteroarylalkyl, or substituted or unsubstituted heterocyclic ring, or any two of R x , R y and R z may be joined to form a substituted or unsubstituted saturated or unsaturated 3-10 membered ring, which may optionally include heteroatoms which may be the same or different and are selected from O, NR f (wherein R f is hydrogen or substituted or unsubstituted alkyl) or S.

9. A compound of the formula

or a tautomer thereof, N-oxide thereof, or pharmaceutically acceptable salt thereof, wherein
each occurrence of R is independently selected from −OR a , substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-8 cycloalkyl, and substituted or unsubstituted heterocyclic group, where R a is selected from hydrogen, and substituted or unsubstituted (C 1-6 )alkyl;
R 1 and R 2 may be the same or different and are independently selected from hydrogen, halogen, and substituted or unsubstituted C 1-6 alkyl, or both R 1 and R 2 directly bound to a common atom, may be joined to form a substituted or unsubstituted saturated or unsaturated 3-10 member ring (including the carbon atom to which R 1 and R 2 are bound), which may optionally include one or more heteroatoms which may be the same or different and are selected from O, NR a and S, where R a is selected from hydrogen and substituted or unsubstituted (C 1-6 )alkyl;
Cy 1 is a monocyclic group selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;
L 1 is absent or selected from —(CR a R b ) q — or —C(═Y)—, where each occurrence of R a and R b may be the same or different and are independently selected from hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted (C 1-6 )alkyl, and —OR c (wherein R c is substituted or unsubstituted (C 1-6 )alkyl) or when R a and R b are directly bound to a common atom, they may be joined to form an oxo group (═O) or form a substituted or unsubstituted saturated or unsaturated 3-10 member ring (including the common atom to which R a and R b are directly bound), which may optionally include one or more heteroatoms which may be the same or different and are selected from O, NR d (wherein R d is hydrogen or substituted or unsubstituted (C 1-6 )alkyl) or S;
Y is selected from O, S, and NR a , where R a is selected from hydrogen and substituted or unsubstituted (C 1-6 )alkyl;
q is 1 or 2; and
Cy 2 is

Assignees

• Muthuppalaniappan Meyyappan
• Viswanadha Srikant
• Babu Govindarajulu
• Vakkalanka Swaroop Kumar V S
• Rhizen Pharmaceuticals Sa

Inventors

• Muthuppalaniappan Meyyappan
• Viswanadha Srikant
• Babu Govindarajulu
• Vakkalanka Swaroop Kumar V S

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title