Fused heterobicyclic kinase inhibitors

• US 20070208053A1
• Filed: 01/18/2007
• Published: 09/06/2007
• Est. Priority Date: 01/19/2006
• Status: Abandoned Application

• Current Assignee: Osi Pharmaceuticals Incorporated (Astellas Pharma Incorporated)
• Original Assignee: Osi Pharmaceuticals Incorporated (Astellas Pharma Incorporated)
• Inventors: Chen, Xin, Arnold, Lee, Wang, Jing, Dong, Hanqing, Mulvihill, Mark, Krulle, Thomas, Sambrook Smith, Colin, Garton, Andrew, Thomas, Gerard
• Application Number:
  US11/654,814
• Publication Number:
  US 20070208053A1
• Time in Patent Office: Days
• US Class Current: 514/300
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Compounds of the formula
and pharmaceutically acceptable salts thereof, wherein X₁, X₂, X₃, X₄, X₅, X₅, X₇, R¹, and Q¹ are defined herein, inhibit kinase enzymes and are useful for the treatment and/or prevention of hyperproliferative diseases such as cancer. The compounds are also useful in the treatment of inflammation, allergy, asthma, disease and conditions of the immune system, disease and conditions of the nervous system, cardiovascular diseases, disease and conditions of the eye, dermatological diseases, osteoporosis, diabetes, multiple sclerosis, and infections.

Claims

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein;

X¹ or X² are each independently N or —

C(E¹)-;

X³, X⁴ and X⁵ are each independently N, O, S, —

C(E¹)-, or ═

C(E¹)-;

provided that

X³ is O or S when X⁴ and X⁵ are combined to equal —

C(E^1a)=C(E¹)-;

X⁵ is NH, O, or S when X³ and X⁴ are combined to equal —

C(E^1a)=C(E¹)-;

X⁵ is NH when X³ and X⁴ are combined to equal —

N═

C(E¹)-;

X⁵ is NH when X³ and X⁴ are combined to equal —

C(E¹)=N—

;

Q¹ is C_0-10alkyl, C_2-10alkenyl, C_2-10alkynyl, C_1-10alkoxyC_1-10alkyl, C_1-10alkoxyC_2-10alkenyl, C_1-10alkoxyC_2-10alkynyl, C_1-10alkylthioC_1-10alkyl, C_1-10alkylthioC_2-10alkenyl, C_1-10alkylthioC_2-10alkynyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, cycloC_3-8alkylC_1-10alkyl, cycloC_3-8alkenylC_1-10alkyl, cycloC_3-8alkylC_2-10alkenyl, cycloC_3-8alkenylC_2-10alkenyl, cycloC_3-8alkylC_2-10alkynyl, cycloC_3-8alkenylC_2-10alkynyl, heterocyclyl-C_0-10alkyl, heterocyclyl-C_2-10alkenyl, heterocyclyl-C_2-10alkynyl, aryl-C_0-10alkyl, aryl-C_2-10alkenyl, aryl-C_2-10alkynyl, hetaryl-C_0-10alkyl, hetaryl-C_2-10alkenyl, hetaryl-C_2-10alkynyl, heterobicycloC_5-10alkyl, spiroalkyl, or heterospiroalkyl;

or -(Z¹)_n-(Y¹)_m—

R¹;

any of which is optionally substituted by one or more independent G¹ substituents;

E¹, E^1a, and G¹ are, in each instance, each independently equal to halo, —

CF₃, —

OCF₃, —

OR²—

NR²R³(R⁴)_j1, —

C(═

O)R², —

CO₂R², —

CONR²R³, —

NO₂, —

CN, —

S(O)_jR², —

SO₂NR²R³—

NR²C(═

O)R³—

NR²C(═

O)OR³, —

NR²C(═

O)NR³R⁴, —

NR²S(O)_j,R³, —

C(═

S)OR², —

C(═

O)SR², —

NR²C(═

NR³)NR⁴R⁵, —

NR²C(═

NR³)OR⁴, —

NR²C(═

NR³)SR⁴, —

OC(═

O)OR², —

OC(═

O)NR²R³, —

OC(═

O)SR², —

SC(═

O)OR², —

SC(═

O)NR²R³, C_0-10alkyl, C_2-10alkenyl, C_2-10alkynyl, C_1-10alkoxyC_1-10alkyl, C_1-10alkoxyC_2-10alkenyl, C_1-10alkoxyC_2-10alkynyl, C_1-10alkylthioC₁₀alkyl, C_1-10alkylthioC_2-10alkenyl, C_1-10alkylthioC_2-10alkynyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, cycloC_3-8alkylC_1-10alkyl, cycloC_3-8alkenylC_1-10alkyl, cycloC_3-8alkylC_2-10alkenyl, cycloC_3-8alkenylC_2-10alkenyl, cycloC_3-8alkylC_2-10alkynyl, cycloC_3-8alkenylC_2-10alkynyl, heterocyclyl-C_0-10alkyl, heterocyclyl-C_2-10alkenyl, heterocyclyl-C₂alkynyl, aryl-C_0-10alkyl, aryl-C_2-10alkenyl, aryl-C_2-10alkynyl, hetaryl-C_0-10alkyl, hetaryl-C_2-10alkenyl, or hetaryl-C_2-10alkynyl, any of which is optionally substituted with one or more independent halo, oxo, —

CF₃, —

OCF₃, —

OR²², NR²²R³³(R^22a)_j1a, —

C(═

O)R²², —

CO₂R²², —

C(═

O)NR²²R³³, —

NO₂, —

CN, —

S(═

O)_j1aR²², —

SO₂NR²²R³³, —

NR²²C(═

O)R³³, —

NR²²C(═

O)OR³³, —

NR²²C(═

O)NR³³R^22a, —

NR²²S(O)_j1aR²², —

C(═

S)OR²², —

C(═

O)SR²², —

NR²²C(═

NR³³)NR^22aR^33a, —

NR²²C(═

NR³³)OR^22a, —

NR²²C(═

NR³³)SR^22a, —

OC(═

O)OR²², —

OC(═

O)NR²²R³³, —

OC(═

O)SR²², —

SC(═

O)OR²², or —

SC(═

O)NR²²R³³ substituents;

Z¹ is cycloC_3-8alkyl, heterocyclyl-C_0-10alkyl, aryl-C_0-10alkyl, hetaryl-C_0-10alkyl, heterobicycloC_5-10alkyl, spiroalkyl, or heterospiroalkyl, any of which is optionally substituted by one or more independent G¹ substituents;

Y¹ is —

O—

, —

NR⁶—

, —

S(O)_j2—

, —

CR^6aR^7a—

, —

N(C(O)OR⁶)—

, —

N(C(O)R⁶)—

, —

N(SO₂R⁶)—

, —

(CR^6aR^7a)O—

, —

(CR^6aR^7a)S—

, —

(CR^6aR^7a)N(R⁶)—

, —

CR^6a(NR⁶)—

, —

(CR^6aR^7a)N(C(O)R⁶)—

, —

(CR^6aR^7a)N(C(O)OR⁶)—

, —

(CR^6aR^7a)N(SO₂R⁶)—

, —

(CR^6a)(NHR⁶)—

, —

(CR^6a)(NHC(O)R⁶)—

, —

(CR^6a)(NHSO₂R⁶)—

, —

(CR^6a)(NHC(O)OR⁶)—

, —

(CR^6a)(OC(O)R⁶)—

, —

(CR^6a)(OC(O)NHR⁶)—

, —

(CR^6a)═

(CR^6a)—

, —

C≡

C—

, —

C(═

NOR⁶)—

, —

C(O)—

, —

(CR^6a)(OR⁶)—

, —

C(O)N(R⁶)—

, —

N(R⁶)C(O)—

, —

N(R⁶)S(O)—

, —

N(R⁶)S(O)₂—

—

OC(O)N(R⁶)—

, N(R⁶)C(O)N(R^6a)—

, —

NR⁶C(O)O—

, —

S(O)N(R⁶)—

, —

S(O)₂N(R⁶)—

, —

N(C(O)R⁶)S(O)—

, —

N(C(O)R⁶)S(O)₂—

, —

N(R⁶)S(O)N(R⁷)—

, —

N(R⁶)S(O)₂N(R⁷)—

, —

C(O)N(R⁶)C(O)—

, —

S(O)N(R⁷)C(O)—

, —

S(O)₂N(R⁶)C(O)—

, —

OS(O)N(R⁶)—

, —

OS(O)₂N(R⁶)—

, —

N(R⁶)S(O)O—

, —

N(R⁶)S(O)₂O—

, —

N(R⁶)S(O)C(O)—

, —

N(R⁶)S(O)₂C(O)—

, —

SON(C(O)R⁶)—

, —

SO₂N(C(O)R⁶)—

, —

N(R⁶)SON(R⁷)—

, —

N(R⁶)SO₂N(R⁷)—

, —

C(O)O—

, —

N(R⁶)P(OR⁷)O—

, —

N(R⁶)P(OR⁷)—

, —

N(R⁶)P(O)(OR⁷)O—

, —

N(R⁶)P(O)(OR⁷)—

, —

N(C(O)R⁶)P(OR⁷)O—

, —

N(C(O)R⁶)P(OR⁷)—

, —

N(C(O)R⁶)P(O)(OR⁷)O—

, —

N(C(O)R⁶)P(OR⁷)—

, —

(CR^6aR^7a)S(O)—

, —

(CR^6aR^7a)S(O)₂—

, —

(CR^6aR^7a)N(C(O)OR⁷)—

, —

(CR^6aR^7a)N(C(O)R⁷)—

, —

(CR^6aR^7a)N(SO₂R⁷), —

(CR^6aR^7a)C(═

NOR⁷)—

, —

(CR^6aR^7a)C(O)—

, —

(CR^6aR^7a)(CR⁶aa)(OR⁷)—

, —

(CR^6aR^7a)C(O)N(R⁷)—

, —

(CR^6aR^7a)N(R⁶)C(O)—

, —

(CR^6aR^7a)N(R⁷)S(O)—

, —

(CR^6aR^7a)N(R⁷)S(O)₂—

, —

(CR^6aR^7a)OC(O)N(R⁷)—

, —

(CR^6aR^7a)N(R⁷)C(O)N(R)—

, —

(CR^6aR^7a)N(R⁷C(O)O—

, —

(CR^6aR^7a)S(O)N(R⁷)—

, —

(CR^6aR^7a)S(O)₂N(R⁷)—

, —

(CR^6aR^7a)N(C(O)R⁷)S(O)—

, —

(CR^6aR^7a)N(C(O)R⁷)S(O), —

(CR^6aR^7a)N(R⁷)S(O)N(R⁸)—

, —

(CR^6aR^7a)N(R⁷)S(O)₂N(R)—

, —

(CR^6aR^7a)C(O)N(R⁷)C(O)—

, —

(CR^6aR^7a)S(O)N(R⁷)C(O), —

(CR^6aR^7a)S(O)₂N(R⁷)C(O)—

, —

(CR^6aR^7a)OS(O)N(R⁷), —

(CR^6aR^7a)OS(O)₂N(R⁷)—

, (CR^6aR^7a)N(R⁷)S(O)O—

, —

(CR^6aR^7a)N(R⁷)S(O)₂O, —

(CR^6aR^7a)N(R⁷)S(O)C(O)—

, —

(CR^6aR^7a)N(R⁷)S(O)₂C(O)—

, —

(CR^6aR^7a)SO₂N(C(O)R⁷), —

(CR^6aR^7a)SO₂N(C(O)R⁷)—

, —

(CR^6aR^7a)N(R⁷)SON(R⁸)—

, —

(CR^6aR^7a)N(R⁷)SO₂N(R⁸)—

, —

(CR^6aR^7a)C(O)O—

, —

(CR^6aR^7a)N(R⁷)P(OR⁸)O—

, —

(CR^6aR^7a)N(R⁷)P(OR⁸)—

, —

(CR^6aR^7a)N(R⁷)P(O)(OR)O—

, —

(CR^6aR^7a)N(R⁷)P(O)(OR⁸)—

, —

(CR^6aR^7a)N(C(O)R⁷)P(OR⁸)O—

, —

(CR^6aR^7a)N(C(O)R⁷)P(OR⁸), —

(CR^6aR^7a)N(C(O)R⁷)P(O)(OR)O—

, or —

(CR^6aR^7a)N(C(O)R⁷)P(OR⁵);

R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R²², R^22a, R³³, and R^33a are, in each instance, each independently C_0-10alkyl, C_2-10alkenyl, C_2-10alkynyl, C_1-10alkoxyC_1-10alkyl, C_1-10alkoxyC_2-10alkenyl, C_1-10alkoxyC_2-10alkynyl, C_1-10alkylthioC_1-10alkyl, C_1-10alkylthioC_2-10alkenyl, C_1-10alkylthioC_2-10alkynyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, cycloC_3-8alkylC_1-10alkyl, cycloC_3-8alkenylC_1-10alkyl, cycloC_3-8alkylC_2-10alkenyl, cycloC_3-8alkenylC_2-10alkenyl, cycloC_3-8alkylC_2-10alkynyl, cycloC_3-8alkenylC_2-10alkynyl, heterocyclyl-C_0-10alkyl, heterocyclyl-C_2-10alkenyl, heterocyclyl-C_2-10alkynyl, aryl-C_0-10alkyl, aryl-C_2-10alkenyl, or aryl-C_2-10alkynyl, hetaryl-C_0-10alkyl, hetaryl-C_2-10alkenyl, or hetaryl-C_2-10alkynyl, any of which is optionally substituted by one or more independent G¹ substituents;

R^6a, R^6aa, and R^7a are, in each instance, each independently fluoro, trifluoromethyl, C_0-10alkyl, C_2-10alkenyl, C_2-10alkynyl, C_1-10alkoxyC_1-10alkyl, C_1-10alkoxyC_2-10alkenyl, C_1-10alkoxyC_2-10alkynyl, C_1-10alkylthioC_1-10alkyl, C_1-10alkylthioC_2-10alkenyl, C_1-10alkylthioC_2-10alkynyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, cycloC_3-8alkylC_1-10alkyl, cycloC_3-8alkenylC_1-10alkyl, cycloC_3-8alkylC_2-10alkenyl, cycloC_3-8alkenylC_2-10alkenyl, cycloC_3-8alkylC_2-10alkynyl, cycloC_3-8alkenylC_2-10alkynyl, heterocyclyl-C_0-10alkyl, heterocyclyl-C_2-10alkenyl, heterocyclyl-C_2-10alkynyl, aryl-C_0-10alkyl, aryl-C_2-10alkenyl, or aryl-C_2-10alkynyl, hetaryl-C_0-10alkyl, hetaryl-C_2-10alkenyl, or hetaryl-C_2-10alkynyl, any of which is optionally substituted by one or more independent G^11a substituents;

or in the case of —

NR²R³(R⁴)_j1b, —

NR³R⁴, —

NR⁴R⁵, —

NR^2bR^3b(R^4b)_j1b, —

NR^3bR^4b, —

NR^4bR^5b, —

NR⁹R¹⁰, —

NR¹⁰R¹¹, —

NR¹¹R¹², —

NR²²R³³(R^22a)_j1a, —

NR^22aR^33a, —

NR³³R^22a, —

NR⁶R¹, —

NR⁷R¹, and —

NR⁸R¹ then R² and R³, or R³ and R⁴, or R⁴ and R⁵, R^2b and R^3b, or R^3b and R^4b, or R^4b and R^5b, or R⁹ and R¹⁰, or R¹⁰ and R¹¹, or R¹¹ and R¹², or R²² and R³³, or R^22a and R^33a, or R³³ and R²², or R⁶ and R¹, or R⁷ and R¹, or R⁸ and R¹, respectively, are optionally taken together with the nitrogen atom to which they are attached to form a 3-10 membered saturated or unsaturated ring, wherein said ring is optionally substituted by one or more independent G¹¹¹ substituents and wherein said ring optionally includes one or more heteroatoms other than the nitrogen to which R² and R³, or R³ and R⁴, or R⁴ and R⁵, R^2b and R^3b, or R^3b and R^4b, or R^4b and R^5b, or R⁹ and R¹⁰, or R¹⁰ and R¹¹, or R¹¹ and R¹², or R²² and R³³, or R^22a and R^33a, or R³³ and R^22a, or R⁶ and R¹, or R⁷ and R¹, or R⁸ and R¹ are respectively attached;

or in the case of CR^6aR^7a, R^6a and R^7a can be taken together with the carbon to which they are attached to form a 3-10 membered saturated or unsaturated cycloalkyl or heterocycloalkyl ring, wherein said ring is optionally substituted by one or more independent G^111a substituents and wherein said ring optionally includes one or more heteroatoms;

G¹¹, G^11a, G¹¹¹, and G^111a are, in each instance, each independently halo, —

CF₃, —

OCF₃, —

OR^2b, —

NR^2bR^3b(R^4b)_j1b, —

C(═

O)R^2b, —

CO₂R^2b, CONR^2bR^3b, —

NO₂, —

CN, —

S(O)_j1bR^2b, —

SO₂NR^2bR^3b, —

NR^2bC(═

O)R^3b, —

NR^2bC(═

O)OR^3b, —

NR^2bC(═

O)NR^3bR^4b, —

NR^2bS(O)_j1bR^2b, —

C(═

S)OR^2b, C(═

O)SR^2b, —

NR^2bC(═

NR^3b)N(R^4bR^5b, —

NR^2bC(═

NR^3b)OR^4b, —

NR^2bC(═

NR^3b)SR^4b, OC(═

O)OR^2b, —

C(═

O)NR^2bR^3b, —

OC(═

O)SR^2b, SC(═

O)OR^2b, —

SC(═

O)NR^2bR^3b, C_0-10alkyl, C_2-10alkenyl, C_2-10alkynyl, C_1-10alkoxyC_1-10alkyl, C_1-10alkoxyC_2-10alkenyl, C_1-10alkoxyC_2-10alkynyl, C_1-10alkylthioC_1-10alkyl, C_1-10alkylthioC_2-10alkenyl, C_1-10alkylthioC_2-10alkynyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, cycloC_3-8alkylC_1-10alkyl, cycloC_3-8alkenylC_1-10alkyl, cycloC_3-8alkylC_2-10alkenyl, cycloC_3-8alkenylC_2-10alkenyl, cycloC_3-8alkylC_2-10alkynyl, cycloC_3-8alkenylC_2-10alkynyl, heterocyclyl-C_0-10alkyl, heterocyclyl-C_2-10alkenyl, heterocyclyl-C_2-10alkynyl, aryl-C_0-10alkyl, aryl-C_2-10alkenyl, aryl-C_2-10alkynyl, hetaryl-C_0-10alkyl, hetaryl-C_2-10alkenyl, or hetaryl-C_2-10alkynyl, any of which is optionally substituted with one or more independent halo, —

CF₃, —

OCF₃, —

OR⁹, —

NR⁹R¹⁰, —

C(O)R⁹, —

CO₂R⁹, —

CONR⁹R¹⁰, —

NO₂, —

CN, —

S(O)_j2aR⁹, —

SO₂NR⁹R¹⁰, —

NR⁹C(═

O)R¹⁰, —

NR⁹C(═

O)OR¹⁰, —

NR⁹C(═

O)NR¹¹R¹⁰, —

NR⁹S(O)_j2aR¹⁰, —

C(═

S)OR⁹, —

C(═

O)SR⁹, —

NR⁹C(═

NR¹⁰)NR¹¹R¹², —

NR⁹C(═

NR¹⁰)OR¹¹, —

NR⁹C(═

NR¹⁰)SR¹¹, —

OC(═

O)OR⁹, —

OC(═

O)NR⁹R¹⁰, —

OC(═

O)SR⁹, —

SC(═

O)OR⁹, —

P(O)OR⁹OR¹⁰, or —

SC(═

O)NR⁹R¹⁰ substituents;

R^2b, R^3b, R^4b, R^5b, R⁹, R¹⁰, R¹¹ and R¹² are, in each instance, each independently C_0-10alkyl, C_2-10alkenyl, C_2-10alkynyl, C_1-10alkoxyC_1-10alkyl, C_1-10alkoxyC_2-10alkenyl, C_1-10alkoxyC_2-10alkynyl, C_1-10alkylthioC_1-10alkyl, C_1-10alkylthioC_2-10alkenyl, C_1-10alkylthioC_2-10alkynyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, cycloC_3-8alkylC_1-10alkyl, cycloC_3-8alkenylC_1-10alkyl, cycloC_3-8alkylC_2-10alkenyl, cycloC_3-8alkenylC_2-10alkenyl, cycloC_3-8alkylC_2-10alkynyl, cycloC_3-8alkenylC_2-10alkynyl, heterocyclyl-C_0-10alkyl, heterocyclyl-C_2-10alkenyl, heterocyclyl-C_2-10alkynyl, C_1-10alkylcarbonyl, C_2-10alkenylcarbonyl, C_2-10alkynylcarbonyl, C_1-10alkoxycarbonyl, C_1-10alkoxycarbonylC_1-10alkyl, monoC_1-6alkylaminocarbonyl, diC_1-6alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl, or C_1-10alkyl(aryl)aminocarbonyl, any of which is optionally substituted with one or more independent halo, cyano, hydroxy, nitro, C_1-10alkoxy, —

SO₂N(C_0-4alkyl)(C_0-4alkyl), or —

N(C_0-4alkyl)(C_0-4alkyl) substituents;

or R^2b, R^3b, R^4b, R^5b, R⁹, R¹⁰, R¹¹ and R¹² are, in each instance, each independently aryl-C_0-10alkyl, aryl-C_2-10alkenyl, aryl-C_2-10alkynyl, hetaryl-C_0-10alkyl, hetaryl-C_2-10alkenyl, hetaryl-C_2-10alkynyl, mono(C_1-6alkyl)aminoC_1-6alkyl, di(C_1-6alkyl)aminoC_1-6alkyl, mono(aryl)aminoC_1-6alkyl, di(aryl)aminoC_1-6alkyl, or —

N(C_1-6alkyl)-C_1-6alkyl-aryl, any of which is optionally substituted with one or more independent halo, cyano, nitro, —

O(C_0-4alkyl), C_1-10alkyl, C_2-10alkenyl, C_2-10alkynyl, haloC_1-10alkyl, haloC_2-10alkenyl, haloC_2-10alkynyl, —

COOH, C_1-4alkoxycarbonyl, —

CON(C_0-4alkyl)(C_0-10alkyl), —

SO₂N(C_0-4alkyl)(C_0-4alkyl), or —

N(C_0-4alkyl)(C_0-4alkyl) substituents; and

j₁, j_1a, j_1b, j₂, j_2a, n, and m are, in each instance, each independently 0, 1, 2, or 3.

2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein:

X¹ or X² are each —

C(E¹)-;

X³ and X⁴ are combined to equal —

C(E^1a)=C(E¹)-;

X⁵ is NH; and

Q¹ is aryl-C_0-10alkyl optionally substituted by one or more independent G¹ substituents.

3. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein;

X¹ or X² are each —

C(E¹)-;

X³ and X⁴ are combined to equal —

C(E^1a)=C(E¹)-;

X⁵ is NH; and

Q¹ is heterocyclyl-C_0-10alkyl optionally substituted by one or more independent G¹ substituents.

4. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein:

X¹ or X² are each —

C(E¹)-;

X³ and X⁴ are combined to equal —

C(E^1a)=C(E¹)-;

X⁵ is NH; and

Q¹ is hetaryl-C_0-10alkyl optionally substituted by one or more independent G¹ substituents.

5. A composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

6. A composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof;

and an anti-neoplastic, anti-tumor, anti-angiogenic, or chemotherapeutic agent.

7. A composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a cytotoxic or angiogenesis inhibiting cancer therapeutic agent.

8. A composition comprising a compound according to claim 1 selected from

or a pharmaceutically acceptable salt thereof.

9. A composition comprising a compound of claim 1 selected from

or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 consisting of:

4-(4-morpholin-4-yl-phenyl)-1H-pyrrolo[2,3-b]pyridine;

N-phenyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-(4-fluoro-phenyl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-cyclohexyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N,N-dimethyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

piperidin-1]-yl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-methanone;

N-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

pyrrolidin-1-yl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-methanone;

N-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-acetamide;

N-ethyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-methyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

dimethyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-amine;

morpholin-4-yl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-methanone;

N-benzyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-(2-dimethylamino-ethyl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzonitrile;

1-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-ethanone;

4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester;

[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-carbamic acid tert-butyl ester;

4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenylamine;

2-phenyl-N-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-acetamide;

N-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-benzamide;

2-(4-fluoro-phenyl)-N-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-acetamide;

2-(3-fluoro-phenyl)-N-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-acetamide;

2-(2-fluoro-phenyl)-N-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-acetamide;

1-(2-fluoro-benzyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-urea;

1-phenyl-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-urea;

1-(3-fluoro-phenyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-urea;

1-(2-fluoro-phenyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-urea;

or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 1 consisting of:

1-(4-fluoro-phenyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-urea;

1-benzyl-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-urea;

1-(3-fluoro-benzyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-urea;

1-(4-fluoro-benzyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-urea;

4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzoic acid methyl ester;

N-(2-fluoro-benzyl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-(3-fluoro-benzyl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-(4-fluoro-benzyl)-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-pyridin-2-ylmethyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-Pyridin-3-ylmethyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-pyridin-4-ylmethyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-[2-(4-fluoro-phenyl)-ethyl]-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-carbamic acid tert-butyl ester;

4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamine;

N-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-benzamide;

2-phenyl-N-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-acetamide;

[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-methanol;

1-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-ethanol;

(2-fluoro-benzyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

4-(4-morpholin-4-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridine;

(4-chloro-benzyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

4-(4-pyrrolidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridine;

bis-(2-methoxy-ethyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

benzyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-(4-trifluoromethyl-benzyl)-amine;

(4-fluoro-phenyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(4-fluoro-benzyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

[2-(4-fluoro-phenyl)-ethyl]-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

4-(4-piperidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridine;

{3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-phenyl}-methanol;

pyridin-2-ylmethyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

pyridin-3-ylmethyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

4-(4-azocan-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridine;

1-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-piperidin-4-ol;

1-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-piperidin-3-ol;

4-[4-(4-butyl-piperazin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridine;

(4-methyl-benzyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

pyridin-4-ylmethyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

4-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridine;

dimethyl-(2-{4-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-piperazin-1-yl}-ethyl)-amine;

(3-fluoro-benzyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(2-methoxy-ethyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-thiophen-2-ylmethyl-amine;

(2-pyrrolidin-1-yl-ethyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

dimethyl-(4-{[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-methyl}-phenyl)-amine;

(s)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-(1,2,2-trimethyl-propyl)-amine;

(R)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-(1,2,2-trimethyl-propyl)-amine;

diethyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(1-phenyl-ethyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

cyclopentyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(2,6-dichloro-benzyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(1-methyl-1-phenyl-ethyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

ethyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(2,4-difluoro-benzyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(2-methoxy-benzyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

2-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-1,2,3,4-tetrahydro-isoquinoline;

(2-bromo-benzyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-benzoic acid methyl ester;

4-[4-(1,3-dihydro-isoindol-2-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridine;

(2-chloro-benzyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(2-fluoro-benzyl)-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(2-fluoro-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-thiophen-2-ylmethyl]-amine;

(2-fluoro-benzyl)-methyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(2-fluoro-benzyl)-methyl-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

2-{[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-methyl}-cyclohexanol;

N,N-dimethyl-N′

-[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-furan-2-ylmethyl]-ethane-1,2-diamine;

3-[4-(1H-pyrrolo[2,3-]pyridin-4-yl)-benzylamino]-benzamide;

2-{butyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amino}-ethanol;

3-{[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-thiophen-2-ylmethyl]-amino}-benzamide;

2-{4-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-phenyl-ethanol;

(2-pyridin-2-yl-ethyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

pyrrolidine-2-carboxylic acid 3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamide;

1-{3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-phenyl-ethanol;

4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenol;

methyl-(2-pyridin-2-yl-ethyl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(5-cyclopropyl-2-methyl-2H-pyrazol-3-yl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(6-methyl-pyridin-2-yl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

3-amino-N-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-propionamide;

3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamine;

4-thiophen-3-yl-1H-pyrrolo[2,3-b]pyridine;

4-{[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-thiophen-2-ylmethyl]-amino}-benzoic acid 2-diethylamino-ethyl ester;

4-p-tolyl-1H-pyrrolo[2,3-b]pyridine;

N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

4-(2-fluoro-3-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine;

1-[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-thiophen-2-yl]-ethanone;

{2-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylcarbamoyl]-ethyl}-carbamic acid tert-butyl ester;

1-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-ethanone;

4-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridine;

[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-methanol;

4-(6-methoxy-pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine;

4-[4-(5-thiophen-2-yl-1H-pyrazol-3-yl)-piperidin-1-yl]-1H-pyrrolo[2,3-b]pyridine;

4-(2-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridine;

4-(5-chloro-thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridine;

4-(3-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridine;

[3-(4-methyl-piperazin-1-yl)-propyl]-[5-(1H-pyrrolo[2,3 b]pyridin-4-yl)-furan-2-ylmethyl]-amine;

4-m-tolyl-1H-pyrrolo[2,3-b]pyridine;

N-(3-dimethylamino-propyl)-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

4-(5-methyl-thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridine;

(5-methyl-pyridin-2-yl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

4-{[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-thiophen-2-ylmethyl]-amino}-benzamide;

3-bromo-4-phenyl-1H-pyrrolo[2,3-b]pyridine;

2-{4-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-piperazin-1-yl}-ethanol;

ethyl-pyridin-4-ylmethyl-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

methyl-(1-methyl-piperidin-4-yl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

2-methyl-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-phenol;

phenyl-[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-furan-2-ylmethyl]-amine;

1-[4-(3-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-ethanone;

(5-ethyl-[1,3,4]thiadiazol-2-yl)-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

1-(4-naphthalen-2-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-ethanone;

2-{4-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-piperazin-1-yl}-ethanol;

2-{[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-methyl}-cyclohexanol;

(1H-benzotriazol-5-yl)-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

2-{4-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-phenyl}-ethanol;

4-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-benzamide;

(5-cyclopropyl-2-methyl-2H-pyrazol-3-yl)-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

(6-methyl-pyridin-2-yl)-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine;

1-[4-(3-Chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-ethanone;

4-benzo[1,3]dioxol-5-yl-3-bromo-1H-pyrrolo[2,3-b]pyridine;

N-(2,3-dihydroxy-propyl)-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

N-carbamoylmethyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

isoquinolin-5-yl-[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-thiophen-2-ylmethyl]-amine;

3-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-benzamide;

4-benzo[1,3]dioxol-5-yl-3-chloro-1H-pyrrolo[2,3-b]pyridine;

3-bromo-4-(4-vinyl-phenyl)-1H-pyrrolo[2,3-b]pyridine;

{3-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-phenyl}-methanol;

(E)-4-[4-(3-acetyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-but-3-en-2-one;

3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-benzoic acid;

3-chloro-4-phenyl-1H-pyrrolo[2,3-b]pyridine;

1-[4-(4-acetyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanone;

1-(4-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-ethanone;

1-[4-(3-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-ethanone;

4-biphenyl-4-yl-3-bromo-1H-pyrrolo[2,3-b]pyridine;

4-thiophen-2-yl-1H-pyrrolo[2,3-b]pyridine;

N-[2-(1H-imidazol-4-yl)-ethyl]-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

4-(4-methanesulfonyl-phenyl)-1H-pyrrolo[2,3-b]pyridine;

4-(3,5-difluoro-phenyl)-1H-pyrrolo[2,3-b]pyridine;

4-(6-methoxy-pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine;

4-(2-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine;

4-(3,4-dimethoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine;

4-(2,3-difluoro-phenyl)-1H-pyrrolo[2,3-b]pyridine;

5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-furan-2-carbaldehyde;

N,N-dimethyl-N′

-[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-furan-2-ylmethyl]-benzene-1,4-diamine;

N-(2-dimethylamino-ethyl)-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzamide;

1-{3-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzylamino]-phenyl}-ethanol;

(1-phenyl-ethyl)-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-amine; and

1-[3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-benzyl]-piperidine-3-carboxylic acid amide.

or a pharmaceutically acceptable salt thereof.

12. A method of treatment of hyperproliferative disorder comprising a step of administering an effective amount of the compound according to claim 1, or a pharmaceutically acceptable salt thereof.

13. The method of treatment according to claim 12, wherein the hyperproliferative disorder is breast cancer, lung cancer, non-small cell lung cancer, kidney cancer, renal cell carcinoma, prostate cancer, cancer of the blood, liver cancer, ovarian cancer, thyroid cancer, endometrial cancer, cancer of the GI tract, lymphoma, renal cell carcinoma, mantle cell lymphoma, or endometrial cancer.

14. A method of treatment of rheumatoid arthritis, hamartoma syndromes, transplant rejection, atherosclerosis, IBD, asthma, bacterial infection, viral infection, multiple sclerosis or immunosuppression diseases comprising a step of administering an effective amount of the compound according to claim 1, or a pharmaceutically acceptable salt thereof.