Imidazopyrazine tyrosine kinase inhibitors

• US 7,459,554 B2
• Filed: 10/14/2004
• Issued: 12/02/2008
• Est. Priority Date: 10/15/2003
• Status: Active Grant

• Current Assignee: Acerta Pharma B.V. (Astrazeneca PLC)
• Original Assignee: Osi Pharmaceuticals Incorporated (Astellas Pharma Incorporated)
• Inventors: Dong, Han-Qing, Mulvihill, Mark Joseph, Steinig, Arno G., Foreman, Kenneth, Werner, Douglas, Wilkes, Robin, Nigro, Anthony Innocenzo
• Primary Examiner(s): Tucker; Zachary C
• Application Number:
  US10/965,182
• Publication Number:
  US 20060084654A1
• Time in Patent Office: 1,510 Days
• Field of Search: 544/120, 544/350, 540/599
• US Class Current: 544/120
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• 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: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems

Abstract

Compounds of the formula

and pharmaceutically acceptable salts thereof, wherein Q¹ and R¹ are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of various diseases and conditions that respond to treatment by inhibition of tyrosine kinases.

Claims

1. A compound represented by Formula I:

2. The compound or salt of claim 1, wherein Q¹ is aryl¹ or heteroaryl¹, any of which is optionally substituted by one or more independent G¹ substituents.

3. The compound or salt of claim 2, wherein Q¹ is heteroaryl¹, any of which is optionally substituted by one or more independent G¹ substituents.

4. The compound or salt of claim 3, wherein Q¹ is aryl¹, any of which is optionally substituted by one or more independent G¹ substituents.

5. The compound or salt of claim 1, wherein G¹ is halo, —

CF₃, —

OCF₃, —

OR², —

NR²R³, —

C(O)R², —

CO₂R², —

CONR²R³, —

S(O)_j1R², —

SO₂NR²R³, NR²(C═

O)R³, NR²(C═

O)OR³, NR²(C═

O)NR²R³, NR²S(O)_j1R³, —

O(C═

O)OR², —

O(C═

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_1-10alkylthioC_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, or heterocyclyl-C_2-10alkynyl, any of which is optionally substituted with one or more independent halo, oxo, —

CF₃, —

OCF₃, —

OR²²², —

NR²²²R³³³(R^333a)_j1a, —

C(O)R²²², —

CO₂R²²², —

CONR²²²R³³³, —

NO₂, —

CN, —

S(O)_j1aR²²², —

SO₂NR²²²R³³³, NR²²²(C═

O)R³³³, NR²²²(C═

O)OR³³³, NR²²²(C═

O)NR²²²R³³³, NR²²²S(O)_j1aR³³³, —

(C═

S)OR²²², —

(C═

O)SR²²², —

NR²²²(C═

NR³³³)NR^222aR^333a, —

NR²²²(C═

NR³³³)OR^222a, —

NR²²²(C═

NR³³³)SR^333a, —

O(C═

O)OR²²², —

O(C═

O)NR²²²R³³³, —

O(C═

O)SR²²², —

S(C═

O)OR²²², or —

S(C═

O)NR²²²R³³³ substituents;

or —

(X¹)_n—

(Y¹)_m—

R⁴;

or aryl-C_0-10alkyl, aryl-C_2-10alkenyl, or aryl-C_2-10alkynyl, any of which is optionally substituted with one or more independent halo, —

CF₃, —

OCF₃, —

OR²²², —

NR²²²R³³³(R^333a)_j2a, —

C(O)R²²², —

CO₂R²²², —

CONR²²²R³³³, —

NO₂, —

CN, —

S(O)_j2aR²²², —

SO₂NR²²²R³³³, NR²²²(C═

O)R³³³, NR²²²(C═

O)OR³³³, NR²²²(C═

O)NR²²²R³³³, NR²²²S(O)_j2aR³³³, —

(C═

S)OR²²², —

(C═

O)SR²²², —

NR²²²(C═

NR³³³)NR^222aR^333a, —

NR²²²(C═

NR³³³)OR^222a, —

NR²²²(C═

NR³³³)SR^333a, —

O(C═

O)OR²²², —

O(C═

O)NR²²²R³³³, —

O(C═

O)SR²²², —

S(C═

O)OR²²², or —

S(C═

O)NR²²²R³³³ substituents;

or 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, —

OR²²², —

NR²²²R³³³(R^333a)_j3a, —

C(O)R²²², —

CO₂R²²², —

CONR²²²R³³³, —

NO₂, —

CN, —

S(O)_j3aR²²², —

SO₂NR²²²R³³³, NR²²²(C═

O)R³³³, NR²²² (C═

O)OR³³³, NR²²²(C═

O)NR²²²R³³³, NR²²²S(O)_j3aR³³³, —

(C═

S)OR²²², —

(C═

O)SR²²², —

NR²²²(C═

NR³³³)NR^222aR^333a, —

NR²²²(C═

NR³³³)OR^222a, —

NR²²²(C═

NR³³³)SR^333a, —

O(C═

O)OR²²², —

O(C═

O)NR²²²R³³³, —

O(C═

O)SR²²², —

S(C═

O)OR²²², or —

S(C═

O)NR²²²R³³³ substituents.

6. The compound or salt of claim 1, wherein G¹ is halo, —

OR², —

NR²R³, —

C(O)R², —

CO₂R², —

CONR²R³, —

SO₂NR²R³, NR²(C═

O)R³, NR²(C═

O)OR³, NR²(C═

O)NR²R³, NR²S(O)_j1R³, —

O(C═

O)OR², —

O(C═

O)NR²R³, C_0-10alkyl, C_2-10alkenyl, C_1-10alkoxyC_1-10alkyl, C_1-10alkoxyC_2-10alkenyl, C_1-10alkylthioC_1-10alkyl, C_1-10alkylthioC_2-10alkenyl, 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, or heterocyclyl-C_0-10alkyl, or heterocyclyl-C_2-10alkenyl, any of which is optionally substituted with one or more independent oxo, —

CF₃, —

OCF₃, —

OR²²², —

NR²²²R³³³, —

C(O)R²²², —

CO₂R²²², —

CONR²²²R³³³, —

SO₂NR²²²R³³³, NR²²²(C═

O)R³³³, NR²²²(C═

O)OR³³³, NR²²²(C═

O)NR²²²R³³³, NR²²S(O)_j1aR³³³, —

NR²²²(C═

NR³³³)NR^222aR^333a, or —

O(C═

O)NR²²²R³³³ substituents;

or —

(X¹)_n—

(Y¹)_m—

R⁴;

or aryl-C_0-10alkyl optionally substituted with one or more independent halo, —

CF₃, —

OCF₃, —

OR²²², —

NR²²²R³³³, —

C(O)R²²², —

CO₂R²²², —

CONR²²²R³³³, —

SO₂NR²²²R³³³, NR²²²(C═

O)R³³³, NR²²²(C═

O)OR³³³, NR²²²(C═

O)NR²²²R³³³, NR²²²S(O)_j2aR³³³, —

NR²²²(C═

NR³³³)NR^222aR^333a, or —

O(C═

O)NR²²²R³³³ substituents;

or hetaryl-C_0-10alkyl, optionally substituted with one or more independent halo, —

CF₃, —

OCF₃, —

OR²²², —

NR²²²R³³³, —

C(O)R²²², —

CO₂R²²², —

CONR²²²R³³³, —

SO₂NR²²²R³³³, NR²²²(C═

O)R³³³, NR²²²(C═

O)OR³³³, NR²²²(C═

O)NR²²²R³³³, NR²²²S(O)_j3aR³³³, —

NR²²²(C═

NR³³³)NR^222aR^333a, or —

O(C═

O)NR²²²R³³³ substituents.

7. The compound or salt of claim 1, wherein G¹ is halo, —

OR², —

NR²R³, —

C(O)R², —

CO₂R², —

CONR²R³, —

SO₂NR²R³, NR²(C═

O)R³, NR²(C═

O)OR³, NR²(C═

O)NR²R³, NR²S(O)_j1R³, —

O(C═

O)OR², —

O(C═

O)NR²R³, C_0-10alkyl, C_2-10alkenyl, C_1-10alkoxyC_1-10alkyl, C_1-10alkylthioC_1-10alkyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, or heterocyclyl-C_0-10alkyl, or heterocyclyl-C_2-10alkenyl, any of which is optionally substituted with one or more independent oxo, —

CF₃, —

OCF₃, —

OR²²², —

NR²²²R³³³, —

C(O)R²²², —

CO₂R²²², —

CONR²²²R³³³, —

SO₂NR²²²R³³³, NR²²²(C═

O)R³³³, NR²²²(C═

O)OR³³³, NR²²²(C═

O)NR²²²R³³³, NR²²²S(O)_j1aR³³³, —

NR²²²(C═

NR³³³)NR^222aR^333a, or —

O(C═

O)NR²²²R³³³ substituents;

or —

(X¹)_n—

(Y¹)_m—

R⁴;

or aryl-C_0-10alkyl, optionally substituted with one or more independent halo, —

CF₃, —

OCF₃, —

OR²²², —

NR²²²R³³³, —

C(O)R²²², —

CO₂R²²², —

CONR²²²R³³³, —

SO₂NR²²²R³³³, NR²²²(C═

O)R³³³, NR²²²(C═

O)OR³³³, NR²²²(C═

O)NR²²²R³³³, NR²²²S(O)_j2aR³³³, —

NR²²²(C═

NR³³³)NR^222aR_333a, or —

O(C═

O)NR²²²R³³³ substituents;

or hetaryl-C_0-10alkyl, optionally substituted with one or more independent halo, —

CF₃, —

OCF₃, —

OR²²², —

NR²²²R³³³, —

C(O)R²²², —

CO₂R²²², —

CONR²²²R³³³, —

SO₂NR²²²R³³³, NR²²²(C═

O)R³³³, NR²²²(C═

O)OR³³³, NR²²²(C═

O)NR²²²R³³³, NR²²²S(O)_j3aR³³³, —

NR²²²(C═

NR³³³)NR^222aR^333a, or —

O(C═

O)NR²²²R³³³ substituents.

8. The compound or salt of claim 1, wherein G¹ is halo, —

OR², —

NR²R³, —

C(O)R², —

CO₂R², —

CONR²R³, —

SO₂NR²R³, NR²(C═

O)R³, NR²(C═

O)OR³, NR²(C═

O)NR²R³, NR²S(O)_j1R³, —

O(C═

O)OR², —

O(C═

O)NR²R³, C_0-10alkyl, C_2-10alkenyl, C_1-10alkoxyC_1-10alkyl, C_1-10alkylthioC_1-10alkyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, or heterocyclyl-C_0-10alkyl, or heterocyclyl-C_2-10alkenyl, any of which is optionally substituted with one or more independent oxo, —

CF₃, —

OCF₃, —

OR²²², —

NR²²²R³³³, —

C(O)R²²², —

CO₂R²²², —

CONR²²²R³³³, —

SO₂ NR²²²R³³³, NR²²²(C═

O)R³³³, NR²²²(C═

O)OR³³³, NR²²²(C═

O)NR²²²R³³³, NR²²²S(O)_j1aR³³³, —

NR²²²(C═

NR³³³)NR^222aR^333a, or —

O(C═

O)NR²²²R³³³ substituents;

or —

(X¹)_n—

(Y¹)_m—

R⁴.

9. The compound or salt of claim 1, wherein X¹ and Y¹ are each independently —

O—

, —

NR⁷—

, —

S(O)_j7—

, —

CR⁵R⁶—

, —

N(C(O)OR⁷)—

, —

N(C(O)R⁷)—

, —

N(SO₂R⁷)—

, —

CH₂O—

, —

CH₂S—

, —

CH₂N(R⁷)—

, —

CH(NR⁷)—

, —

CH₂N(C(O)R⁷)—

, —

CH₂N(C(O)OR⁷)—

, —

CH₂N(SO₂R⁷)—

, —

CH(NHR⁷)—

, —

CH(NHC(O)R⁷)—

, —

CH(NHSO₂R⁷)—

, —

CH(NHC(O)OR⁷)—

, —

CH(OC(O)R⁷)—

, —

CH(OC(O)NHR⁷)—

, —

C(O)—

, —

CH(OR⁷)—

, —

C(O)N(R⁷)—

, —

N(R⁷)C(O)—

, —

N(R⁷)S(O)—

, —

N(R⁷)S(O)₂—

—

OC(O)N(R⁷)—

, —

N(R⁷)C(O)N(R⁷)—

, —

NR⁷C(O)O—

, —

S(O)N(R⁷)—

, —

S(O)₂N(R⁷)—

, —

N(C(O)R⁷)S(O)—

, —

N(C(O)R⁷)S(O)₂—

, —

N(R⁷)S(O)N(R⁷)—

, —

N(R⁷)S(O)₂N(R⁷)—

, —

C(O)N(R⁷)C(O)—

, —

S(O)N(R⁷)C(O)—

, —

S(O)₂N(R⁷)C(O)—

, —

OS(O)N(R⁷)—

, —

OS(O)₂N(R⁷)—

, —

N(R⁷)S(O)O—

, —

N(R⁷)S(O)₂O—

, —

N(R⁷)S(O)C(O)—

, —

N(R⁷)S(O)₂C(O)—

, —

SON(C(O)R⁷)—

, —

SO₂N(C(O)R⁷)—

, —

N(R⁷)SON(R⁷)—

, —

N(R⁷)SO₂N(R⁷)—

, —

C(O)O—

, —

CH(R⁷)S(O)—

, —

CH(R⁷)S(O)₂—

, —

CH(R⁷)N(C(O)OR⁷)—

, —

CH(R⁷)N(C(O)R⁷)—

, —

CH(R⁷)N(SO₂R⁷)—

, —

CH(R⁷)O—

, —

CH(R⁷)S—

, —

CH(R⁷)N(R⁷)—

, —

CH(R⁷)N(C(O)R⁷)—

, —

CH(R⁷)N(C(O)OR⁷)—

, —

CH(R⁷)N(SO₂R⁷)—

, —

CH(R⁷)C(═

NOR⁷)—

, —

CH(R⁷)C(O)—

, —

CH(R⁷)CH(OR⁷)—

, —

CH(R⁷)C(O)N(R⁷)—

, —

CH(R⁷)N(R⁷)C(O)—

, —

CH(R⁷)N(R⁷)S(O)—

, —

CH(R⁷)N(R⁷)S(O)₂—

, —

CH(R⁷)OC(O)N(R⁷)—

, —

CH(R⁷)N(R⁷)C(O)N(R⁷)—

, —

CH(R⁷)NR⁷C(O)O—

, —

CH(R⁷)S(O)N(R⁷)—

, —

CH(R⁷)S(O)₂N(R⁷)—

, —

CH(R⁷)N(C(O)R⁷)S(O)—

, —

CH(R⁷)N(C(O)R⁷)S(O)—

, —

CH(R⁷)N(R⁷)S(O)N(R⁷)—

, —

CH(R⁷)N(R⁷)S(O)₂N(R⁷)—

, —

CH(R⁷)C(O)N(R⁷)C(O)—

, —

CH(R⁷)S(O)N(R⁷)C(O)—

, —

CH(R⁷)S(O)₂N(R⁷)C(O)—

, —

CH(R⁷)OS(O)N(R⁷)—

, —

CH(R⁷)OS(O)₂N(R⁷)—

, —

CH(R⁷)N(R⁷)S(O)O—

, —

CH(R⁷)N(R⁷)S(O)₂O—

, —

CH(R⁷)N(R⁷)S(O)C(O)—

, —

CH(R⁷)N(R⁷)S(O)₂C(O)—

, —

CH(R⁷)SON(C(O)R⁷)—

, —

CH(R⁷)SO₂N(C(O)R⁷)—

, —

CH(R⁷)N(R⁷)SON(R⁷)—

, —

CH(R⁷)N(R⁷)SO₂N(R⁷)—

, or —

CH(R⁷)C(O)O—

.

10. The compound or salt of claim 1 wherein Q¹ is substituted by said one to five independent G¹ substituents wherein at least one of said G¹ substituents is —

(X¹)_n—

(Y¹)_m—

R⁴, and wherein X¹ and Y¹ are each independently equal to —

O—

, —

NR⁷—

, —

CR⁵R⁶—

, —

S(O)_j7—

, or —

C(O)—

, and wherein n and m are both equal to 1 and j7 is equal to 1 or 2.

11. The compound or salt of claim 1 wherein Q¹ is substituted by said one to five independent G¹ substituents wherein at least one of said G¹ substituents is —

(X¹)_n—

(Y¹)_m—

R⁴, and wherein X¹ and Y¹ are each independently —

O—

or —

CR⁵R⁶—

, and wherein n and m are equal to 1.

12. The compound or salt of claim 1 wherein R¹ is cycloalkyl, bicycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, or heterobicycloalkyl, any of which is optionally substituted by one or more independent G¹¹ substituents.

13. The compound or salt of claim 1 wherein R¹ is cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, or heterocyclyl, any of which is optionally substituted by one or more independent G¹¹ substituents.

14. The compound or salt of claim 1 wherein R¹ is cycloalkyl or heterocyclyl, any of which is optionally substituted by one or more independent G¹¹ substituents.

15. The compound or salt of claim 1 wherein R¹ is cycloalkyl optionally substituted by one or more independent G¹¹ substituents.

16. The compound or salt of claim 1 wherein R¹ is heterocyclyl optionally substituted by one or more independent G¹¹ substituents.

17. The compound or salt of claim 1 wherein R¹ is aryl, heteroaryl, aralkyl, or heteroaralkyl, any of which is optionally substituted by one or more independent G¹¹ substituents.

18. The compound or salt of claim 1 wherein R¹ is aryl or heteroaryl, any of which is optionally substituted by one or more independent G¹¹ substituents.

19. The compound or salt of claim 1 wherein G¹¹ is —

OR²¹, —

NR²¹R³¹(R^31a)_j4, —

C(O)R²¹, —

CO₂R²¹, —

CONR²¹R³¹, NR²¹(C═

O)R³¹, NR²¹(C═

O)OR³¹, NR²¹(C═

O)NR²¹R³¹, NR²¹S(O)_j4R³¹, —

O(C═

O)OR²¹, —

O(C═

O)NR²¹R³¹, C_0-10alkyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, heterocyclyl-C_0-10alkyl, or heterocyclyl-C_2-10alkenyl, any of which is optionally substituted with one or more independent halo, oxo, —

CF₃, —

OCF₃, —

OR²²²¹, —

NR²²²¹R³³³¹(R^333a)_j4a, —

C(O)R²²²¹, —

CO₂R²²²¹, —

CONR²²²¹R³³³¹, —

NO₂, —

CN, —

S(O)_j4aR²²²¹, —

SO₂NR²²²¹R³³³¹, NR²²²¹(C═

O)R³³³¹, NR²²²¹(C═

O)OR³³³¹, NR²²²¹(C═

O)NR²²²¹R³³³¹, NR²²²¹S(O)_j4aR³³³¹, —

(C═

S)OR²²²¹, —

(C═

O)SR²²²¹, —

NR²²²¹(C═

NR³³³¹)NR^222a1R^333a1, —

NR²²²¹(C═

NR³³³¹)OR^222a1, —

NR²²²¹(C═

NR³³³¹)SR^333a1, —

O(C═

O)OR²²²¹, —

O(C═

O)NR²²²¹R³³³¹, —

O(C═

O)SR²²²¹, —

S(C═

O)OR²²²¹, or —

S(C═

O)NR²²²¹R³³³¹ substituents;

or aryl-C_0-10alkyl, aryl-C_2-10alkenyl, or aryl-C_2-10alkynyl, any of which is optionally substituted with one or more independent halo, —

CF₃, —

OCF₃, —

OR²²²¹, —

NR²²²¹R³³³¹(R^333a1)_j5a, —

C(O)R²²²¹, —

CO₂R²²²¹, —

CONR²²²¹R³³³¹, —

NO₂, —

CN, —

S(O)_j5aR²²²¹, —

SO₂NR²²²¹R³³³¹, NR²²²¹(C═

O)R³³³¹, NR²²²¹(C═

O)OR³³³¹, NR²²²¹(C═

O)NR²²²¹R³³³¹, NR²²²¹S(O)_j5aR³³³¹, —

(C═

S)OR²²²¹, —

(C═

O)SR²²²¹, —

NR²²²¹(C═

NR³³³¹)NR^222a1R^333a1, —

NR²²²¹(C═

NR³³³¹)OR^222a1, —

NR²²²¹(C═

NR³³³¹)SR^333a1, —

O(C═

O)OR²²²¹, —

O(C═

O)NR²²²¹R³³³¹, —

O(C═

O)SR²²²¹, —

S(C═

O)OR²²²¹, or —

S(C═

O)NR²²²¹R³³³¹ substituents;

or 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, —

OR²²²¹, —

NR²²²¹R³³³¹(R^333a1)_j6a, —

C(O)R²²²¹, —

CO₂R²²²¹, —

CONR²²²¹R³³³¹, —

NO₂, —

CN, —

S(O)_j6aR²²²¹, —

SO₂NR²²²¹R³³³¹, NR²²²¹(C═

O)R³³³¹, NR²²²¹(C═

O)OR³³³¹, NR²²²¹(C═

O)NR²²²¹R³³³¹, NR²²²¹S(O)_j6aR³³³¹, —

(C═

S)OR²²²¹, —

(C═

O)SR²²²¹, —

NR²²²¹(C═

NR³³³¹)NR^222a1R^333a1, —

NR²²²¹(C═

NR³³³¹)OR^222a1, —

NR²²²¹(C═

NR³³³¹)SR^333a1, —

O(C═

O)OR²²²¹, —

O(C═

O)NR²²²¹R³³³¹, —

O(C═

O)SR²²²¹, —

S(C═

O)OR²²²¹, or —

S(C═

O)NR²²²¹R³³³¹ substituents.

20. The compound or salt of claim 1 wherein G¹¹ is —

OR²¹, —

NR²¹R³¹, —

CO₂R²¹, —

C(O)R²¹, —

CONR²¹R³¹, NR²¹(C═

O)R³¹, NR²¹(C═

O)OR³¹, NR²¹(C═

O)NR²¹R³¹, NR²¹S(O)_j4R³¹, —

O(C═

O)OR²¹, —

O(C═

O)NR²¹R³¹, C_0-10alkyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, heterocyclyl-C_0-10alkyl, or heterocyclyl-C_2-10alkenyl, any of which is optionally substituted with one or more independent halo, oxo, —

CF₃, —

OCF₃, —

OR²²²¹, —

NR²²²¹R³³³¹(R^333a1)_j4a, —

C(O)R²²²¹, —

CO₂R²²²¹, —

CONR²²²¹R³³³¹, —

NO₂, —

CN, —

S(O)_j4aR²²²¹, —

SO₂NR²²²¹R³³³¹, NR²²²¹(C═

O)R³³³¹, NR²²²¹(C═

O)OR³³³¹, NR²²²¹(C═

O)NR²²²¹R³³³¹, NR²²²¹S(O)_j4aR³³³¹, —

(C═

S)OR²²²¹, —

(C═

O)SR²²²¹, —

NR²²²¹(C═

NR³³³¹)NR^222a1R^333a1, —

NR²²²¹(C═

NR³³³¹)OR^222a1, —

NR²²²¹(C═

NR³³³¹)SR^333a1, —

O(C═

O)OR²²²¹, —

O(C═

O)NR²²²¹R³³³¹, —

O(C═

O)SR²²²¹, —

S(C═

O)OR²²²¹, or —

S(C═

O)NR²²²¹R³³³¹ substituents.

21. The compound or salt of claim 1 wherein R⁴ is H, alkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, cycloalkenyl, or heterocycloalkenyl, any of which is optionally substituted by one or more independent G⁴¹ substituents.

22. The compound or salt of claim 10 wherein R⁴ is alkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, cycloalkenyl, or heterocycloalkenyl, any of which is optionally substituted by one or more independent G⁴¹ substituents.

23. The compound or salt of claim 11 wherein R⁴ is alkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, cycloalkenyl, or heterocycloalkenyl, any of which is optionally substituted by one or more independent G⁴¹ substituents.

24. The compound or salt of claim 1 wherein Q¹ is phenyl substituted by said one to five independent G¹ substituents wherein at least one of said G¹ substituents is —

(X¹)_n—

(Y¹)_m—

R⁴, and wherein n=1 and X¹ is 3-(—

O—

), m=1 and Y¹ is —

(—

CH₂—

), and R⁴ is aryl optionally substituted by one or more independent G⁴¹ substituents.

25. The compound or salt of claim 24 wherein R¹ is aryl, heteroaryl, cycloalkyl or heterocyclyl, optionally substituted by one or more independent G¹¹ substituents.

26. The compound or salt of claim 25 wherein R¹ is cycloalkyl or heterocyclyl, optionally substituted by one or more independent G¹¹ substituents.

27. The compound or salt of claim 26 wherein R¹ is cycloalkyl, optionally substituted by one or more independent G¹¹ substituents.

28. The compound or salt of claim 27 wherein R¹ is cyclobutyl, cyclopentyl or cyclohexyl, optionally substituted by one or more independent G¹¹ substituents.

29. The compound or salt of claim 27 wherein G¹¹ is —

OR²¹, —

NR²¹R³¹, —

CO₂R²¹, —

C(O)R²¹, —

CONR²¹R³¹, NR²¹(C═

O)R³¹, NR²¹(C═

O)OR³¹, NR²¹(C═

O)NR²¹R³¹, NR²¹S(O)_j4R³¹, —

O(C═

O)OR²¹, —

O(C═

O)NR²¹R³¹, C_0-10alkyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, heterocyclyl-C_0-10alkyl, or heterocyclyl-C_2-10alkenyl, any of which is optionally substituted with one or more independent halo, oxo, —

CF₃, —

OCF₃, —

OR²²²¹, —

NR²²²¹R³³³¹(R^333a1)_j4a, —

C(O)R²²²¹, —

CO₂R²²²¹, —

CONR²²²¹R³³³¹, —

NO₂, —

CN, —

S(O)_j4aR²²²¹, —

SO₂NR²²²¹R³³³¹, NR²²²¹(C═

O)R³³³¹, NR²²²¹(C═

O)OR³³³¹, NR²²²¹(C═

O)NR²²²¹R³³³¹, NR²²²¹S(O)_j4aR³³³¹, —

(C═

S)OR²²²¹, —

(C═

O)SR²²²¹, —

NR²²²¹(C═

NR³³³¹)NR^222a1R^333a1, —

NR²²²¹(C═

NR³³³¹)OR^222a1, —

NR²²²¹(C═

NR³³³¹)SR^333a1, —

O(C═

O)OR²²²¹, —

O(C═

O)NR²²²¹R³³³¹, —

O(C═

O)SR²²²¹, —

S(C═

O)OR²²²¹, or —

S(C═

O)NR²²²¹R³³³¹ substituents.

30. The compound or salt of claim 1 wherein Q¹ is phenyl substituted by said one to five independent G¹ substituents wherein at least one of said G¹ substituents is —

(X¹)_n—

(Y¹)_m—

R⁴, and wherein n=1 and X¹ is 4-(—

O—

), m=1 and Y¹ is —

(—

CH₂—

), and R⁴ is aryl optionally substituted by one or more independent G⁴¹ substituents.

31. The compound or salt of claim 30 wherein R¹ is aryl, heteroaryl, cycloalkyl or heterocyclyl, optionally substituted by one or more independent G¹¹ substituents.

32. The compound or salt of claim 31 wherein R¹ is cycloalkyl or heterocyclyl, optionally substituted by one or more independent G¹¹ substituents.

33. The compound or salt of claim 32 wherein R¹ is cycloalkyl, optionally substituted by one or more independent G¹¹ substituents.

34. The compound or salt of claim 33 wherein R¹ is cyclobutyl, cyclopentyl or cyclohexyl, optionally substituted by one or more independent G¹¹ substituents.

35. The compound or salt of claim 33 wherein G¹¹ is —

OR²¹, —

NR²¹R³¹, —

CO₂R²¹, —

C(O)R²¹, —

CONR²¹R³¹, NR²¹(C═

O)R³¹, NR²¹(C═

O)OR³¹, NR²¹(C═

O)NR²¹R³¹, NR²¹S(O)_j4R³¹, —

O(C═

O)OR²¹, —

O(C═

O)NR²¹R³¹, C_0-10alkyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, heterocyclyl-C_0-10alkyl, or heterocyclyl-C_2-10alkenyl, any of which is optionally substituted with one or more independent halo, oxo, —

CF₃, —

OCF₃, —

OR²²²¹, —

NR²²²¹R³³³¹(R^333a1)_j4a, —

C(O)R²²²¹, —

CO₂R²²²¹, —

CONR²²²¹R³³³¹, —

NO₂, —

CN, —

S(O)_j4aR²²²¹, —

SO₂NR²²²¹R³³³¹, NR²²²¹(C═

O)R³³³¹, NR²²²¹(C═

O)OR³³³¹, NR²²²¹(C═

O)NR²²²¹R³³³¹, NR²²²¹S(O)_j4aR³³³¹, —

(C═

S)OR²²²¹, —

(C═

O)SR²²²¹, —

NR²²²¹(C═

NR³³³¹)NR^222a1R^333a1, —

NR²²²¹(C═

NR³³³¹)OR^222a1, —

NR²²²¹(C═

NR³³³¹)SR^333a1, —

O(C═

O)OR²²²¹, —

O(C═

O)NR²²²¹R³³³¹, —

O(C═

O)SR²²²¹, —

S(C═

O)OR²²²¹, or —

S(C═

O)NR²²²¹R³³³¹ substituents.

36. The compound or salt of claim 1 wherein Q¹ is phenyl substituted by said one to five independent G¹ substituents wherein at least one of said G¹ substituents is —

(X¹)_n—

(Y¹)_m—

R⁴, and wherein n=1 and X¹ is 3-(—

O—

), m=0, and R⁴ is (C₀-C₈)alkyl or cycloalkyl optionally substituted by one or more independent G⁴¹ substituents.

37. The compound or salt of claim 36 wherein R¹ is aryl, heteroaryl, cycloalkyl or heterocyclyl, optionally substituted by one or more independent G¹¹ substituents.

38. The compound or salt of claim 37 wherein R¹ is cycloalkyl or heterocyclyl, optionally substituted by one or more independent G¹¹ substituents.

39. The compound or salt of claim 38 wherein R¹ is cycloalkyl, optionally substituted by one or more independent G¹¹ substituents.

40. The compound or salt of claim 39 wherein R¹ is cyclobutyl, cyclopentyl or cyclohexyl, optionally substituted by one or more independent G¹¹ substituents.

41. The compound or salt of claim 39 wherein G¹¹ is —

OR²¹, —

NR²¹R³¹, —

CO₂R²¹, —

C(O)R²¹, —

CONR²¹R³¹, NR²¹(C═

O)R³¹, NR²¹(C═

O)OR³¹, NR²¹(C═

O)NR²¹R³¹, NR²¹S(O)_j4R³¹, —

O(C═

O)OR²¹, —

O(C═

O)NR²¹R³¹, C_0-10alkyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, heterocyclyl-C_0-10alkyl, or heterocyclyl-C_2-10alkenyl, any of which is optionally substituted with one or more independent halo, oxo, —

CF₃, —

OCF₃, —

OR²²²¹, —

NR²²²¹R³³³¹(R^333a1)_j4a, —

C(O)R²²²¹, —

CO₂R²²²¹, —

CONR²²²¹R³³³¹, —

NO₂, —

CN, —

S(O)_j4aR²²²¹, —

SO₂NR²²²¹R³³³¹, NR²²²¹(C═

O)R³³³¹, NR²²²¹(C═

O)OR³³³¹, NR²²²¹(C═

O)NR²²²¹R³³³¹, NR²²²¹S(O)_j4aR³³³¹, —

(C═

S)OR²²²¹, —

(C═

O)SR²²²¹, —

NR²²²¹(C═

NR³³³¹)NR^222a1R^333a1, —

NR²²²¹(C═

NR³³³¹)OR^222a1, —

NR²²²¹(C═

NR³³³¹)SR^333a1, —

O(C═

O)OR²²²¹, —

O(C═

O)NR²²²¹R³³³¹, —

O(C═

O)SR²²²¹, —

S(C═

O)OR²²²¹, or —

S(C═

O)NR²²²¹R³³³¹ substituents.

42. The compound or salt of claim 36 wherein R⁴ is (C₀-C₆)alkyl.

43. The compound or salt of claim 41 wherein R⁴ is (C₀-C₆)alkyl.

44. The compounds or salts of claim 36 wherein R⁴ is H or methyl.

45. The compound or salt of claim 43 wherein R⁴ is H or methyl.

46. The compound or salt of claim 1 wherein Q¹ is phenyl substituted by said one to five independent G¹ substituents wherein at least one of said G¹ substituents is —

(X¹)_n—

(Y¹)_m—

R⁴, and wherein n=1 and X¹ is 3-(—

O—

), m=0, and R⁴ is aryl optionally substituted by one or more independent G⁴¹ substituents.

47. The compound or salt of claim 46 wherein R¹ is aryl, heteroaryl, cycloalkyl or heterocyclyl, optionally substituted by one or more independent G¹¹ substituents.

48. The compound or salt of claim 46 wherein R¹ is cycloalkyl or heterocyclyl, optionally substituted by one or more independent G¹¹ substituents.

49. The compound or salt of claim 48 wherein R¹ is cyclobutyl, cyclopentyl or cyclohexyl, optionally substituted by one or more independent G¹¹ substituents.

50. The compound or salt of claim 48 wherein G¹¹ is —

OR²¹, —

NR²¹R³¹, —

CO₂R²¹, —

C(O)R²¹, —

CONR²¹R³¹, NR²¹(C═

O)R³¹, NR²¹(C═

O)OR³¹, NR²¹(C═

O)NR²¹R³¹, NR²¹S(O)_j4R³¹, —

O(C═

O)OR²¹, —

O(C═

O)NR²¹R³¹, C_0-10alkyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, heterocyclyl-C_0-10alkyl, or heterocyclyl-C_2-10alkenyl, any of which is optionally substituted with one or more independent halo, oxo, —

CF₃, —

OCF₃, —

OR²²²¹, —

NR²²²¹R³³³¹(R^333a1)_j4a, —

C(O)R²²²¹, —

CO₂R²²²¹, —

CONR²²²¹R³³³¹, —

NO₂, —

CN, —

S(O)_j4aR²²²¹, —

SO₂NR²²²¹R³³³¹, NR²²²¹(C═

O)R³³³¹, NR²²²¹(C═

O)OR³³³¹, NR²²²¹(C═

O)NR²²²¹R³³³¹, NR²²²¹S(O)_j4aR³³³¹, —

(C═

S)OR²²²¹, —

(C═

O)SR²²²¹, —

NR²²²¹(C═

NR³³³¹)NR^222a1R^333a1, —

NR²²²¹(C═

NR³³³¹)OR^222a1, —

NR²²²¹(C═

NR³³³¹)SR^333a1, —

O(C═

O)OR²²²¹, —

O(C═

O)NR²²²¹R³³³¹, —

O(C═

O)SR²²²¹, —

S(C═

O)OR²²²¹, or —

S(C═

O)NR²²²¹R³³³¹ substituents.

51. The compound or salt of claim 46 wherein R⁴ is phenyl optionally substituted with G⁴¹.

52. The compound or salt of claim 1 wherein Q¹ is phenyl substituted by said one to five independent G¹ substituents wherein at least one of said G¹ substituents is —

(X¹)_n—

(Y¹)_m—

R⁴, and wherein n=1 and X¹ is 3- or 4-(—

NH—

), m=1 and Y¹ is —

(—

SO₂—

), and R⁴ is aryl optionally substituted by one or more independent G⁴¹ substituents.

53. The compound or salt of claim 52 wherein R¹ is aryl, heteroaryl, cycloalkyl or heterocyclyl, optionally substituted by one or more independent G¹¹ substituents.

54. The compound or salt of claim 53 wherein R¹ is cycloalkyl or heterocyclyl, optionally substituted by one or more independent G¹¹ substituents.

55. The compound or salt of claim 54 wherein R¹ is cyclobutyl, cyclopentyl or cyclohexyl, optionally substituted by one or more independent G¹¹ substituents.

56. The compound or salt of claim 54 wherein G¹¹ is —

OR²¹, —

NR²¹R³¹, —

CO₂R²¹, —

C(O)R²¹, —

CONR²¹R³¹, NR²¹(C═

O)R³¹, NR²¹(C═

O)OR³¹, NR²¹(C═

O)NR²¹R³¹, NR²¹S(O)_j4R³¹, —

O(C═

O)OR²¹, —

O(C═

O)NR²¹R³¹, C_0-10alkyl, cycloC_3-8alkyl, cycloC_3-8alkenyl, heterocyclyl-C_0-10alkyl, or heterocyclyl-C_2-10alkenyl, any of which is optionally substituted with one or more independent halo, oxo, —

CF₃, —

OCF₃, —

OR²²²¹, —

NR²²²¹R³³³¹(R^333a1)_j4a, —

C(O)R²²²¹, —

CO₂R²²²¹, —

CONR²²²¹R³³³¹, —

NO₂, —

CN, —

S(O)_j4aR²²²¹, —

SO₂NR²²²¹R³³³¹, NR²²²¹(C═

O)R³³³¹, NR²²²¹(C═

O)R³³³¹, NR²²²¹(C═

O)NR²²²¹R³³³¹, NR²²²¹S(O)_j4aR³³³¹, —

(C═

S)OR²²²¹, —

(C═

O)SR²²²¹, —

NR²²²¹(C═

NR³³³¹)NR^222a1R^333a1, —

NR²²²¹(C═

NR³³³¹)OR^222a1, —

NR²²²¹(C═

NR³³³¹)SR^333a1, —

O(C═

O)OR²²²¹, —

O(C═

O)NR²²²¹R³³³¹, —

O(C═

O)SR²²²¹, —

S(C═

O)OR²²²¹, or —

S(C═

O)NR²²²¹R³³³¹ substituents.

57. The compound or salt of claim 56 wherein R¹ is cis- or trans-cyclobutyl substituted at the 3-position by G¹¹ wherein G¹¹ is —

OH, —

NH₂, —

N(CH₃)₂, —

NHAc, —

NH(CO)NHCH₃, —

NH(CO)OCH₃, —

CH₂OH, —

CH₂NH₂, —

CH₂NHAc, CO₂H, CONH₂, —

CH₂N(CH₃)₂, —

CH₂NH(CO)NHMe, —

CH₂NH(CO)OCH₃, CO₂CH₃, CONHCH₃,

58. The compound or salt of claim 56 wherein R¹ is cis- or trans-cyclohexyl substituted at the 4-position by G¹¹ wherein G¹¹ is —

OH, —

NH₂, —

N(CH₃)₂, —

NHAc, —

NH(CO)NHCH₃, —

NH(CO)OCH₃, —

CH₂OH, —

CH₂NH₂, —

CH₂NHAc, CO₂H, CONH₂, —

CH₂N(CH₃)₂, —

CH₂NH(CO)NHMe, —

CH₂NH(CO)OCH₃, CO₂CH₃, CONHCH₃,

59. A compound selected from the group consisting of:

[1-(3-Benzyloxy-phenyl)-3-cyclobutyl-imidazo[1,5-a]pyrazin-8-ylamine],

1-(3-Benzyloxyphenyl)-3-phenyl-imidazo[1,5-a]pyrazin-8-ylamine,

3-Benzyl-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxyphenyl)-3-naphthalen-1-yl-imidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxyphenyl)-3-naphthalen-2-yl-imidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxy-phenyl)-3-cyclopentyl-imidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxy-phenyl)-3-cyclohexyl-imidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxy-phenyl)-3-cycloheptyl-imidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxy-phenyl)-3-(tetrahydro-furan-3-yl)-imidazo[1,5-a]pyrazin-8-ylamine,

trans-3-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclobutanol,

1-(3-Benzyloxy-phenyl)-3-(1-methyl-piperidin-4-yl)-imidazo[1,5-a]pyrazin-8-ylamine,

cis-4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide,

trans-4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid amide,

cis-{4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexyl}-methanol,

trans-{4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexyl}-methanol,

cis-2-{4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexylmethyl}-isoindole-1,3-dione,

trans-2-{4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexylmethyl}-isoindole-1,3-dione,

cis-3-(4-Aminomethyl-cyclohexyl)-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

trans-3-(4-Aminomethyl-cyclohexyl)-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

cis-N-{4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexylmethyl}-acetamide, or

trans-N-{4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexylmethyl}-acetamide.

or pharmaceutically acceptable salts thereof.

60. A compound selected from the group consisting of:

trans-N-{4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexylmethyl}-acetamide,

1-Biphenyl-3-yl-3-cyclobutylimidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Bromo-phenyl)-3-cyclobutylimidazo[1,5-a]pyrazin-8-ylamine,

1-(4′

-t-Butylbiphenyl-3-yl)-3-cyclobutylimidazo[1,5-a]pyrazin-8-ylamine,

3-Cyclobutyl-1-(4′

-methylbiphenyl-3-yl)-imidazo[1,5-a]pyrazin-8-ylamine,

3-Cyclobutyl-1-(4′

-methoxybiphenyl-3-yl)-imidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxyphenyl)-3-cyclopentylmethylimidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxyphenyl)-3-cyclohexylmethylimidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxyphenyl)-3-trifluoromethylimidazo[1,5-a]pyrazin-8-ylamine,

4-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]-benzamide,

3-Cyclobutyl-1-phenylimidazo[1,5-a]pyrazin-8-ylamine,

(trans-3-(4-Azetidin-1-ylmethyl-cyclohexyl)-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

trans-1-(3-Benzyloxy-phenyl)-3-(4-pyrrolidin-1-ylmethyl-cyclohexyl)-imidazo[1,5-a]pyrazin-8-ylamine),

trans-4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methyl ester,

(trans-4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid,

(trans-4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methylamide,

4-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid ethylamide,

trans-1-(3-Benzyloxy-phenyl)-3-(3-pyrrolidin-1-ylmethyl-cyclobutyl)-imidazo[1,5-a]pyrazin-8-ylamine,

cis-1-(3-Benzyloxy-phenyl)-3-(3-pyrrolidin-1-ylmethyl-cyclobutyl)-imidazo[1,5-a]pyrazin-8-ylamine,

trans-3-(3-Azetidin-1-ylmethylcyclobutyl)-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

cis-3-(3-Azetidin-1-ylmethylcyclobutyl)-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

toluene-4-sulfonic acid 3-[8-amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutylmethyl ester,

{3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol,

3-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-1-methyl-cyclobutanol,

3-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-1-ethyl-cyclobutanol,

1-Allyl-3-[8-amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclobutanol,

1-(3-Benzyloxyphenyl)-3-tert-butylimidazo[1,5-a]pyrazin-8-ylamine,

cis-1-[3-(Benzyloxy)phenyl]-3-[3-(dimethylamino) cyclobutyl]imidazo[1,5-a]pyrazin-8-amine,

3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenol,

3-Cyclobutyl-1-[3-(4-fluoro-benzyloxy)-phenyl]-imidazo[1,5-a]pyrazin-8-ylamine,

trans-4-[8-Amino-1-(3-hydroxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclohexanecarboxylic acid methyl ester,

3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]-benzamide,

{3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]-phenyl}-methanol,

3-(3-Aminomethylphenyl)-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

2-{3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]-benzyl}-isoindole-1,3-dione,

4-{8-Amino-1-[3-(2,6-difluoro-benzyloxy)-phenyl]-imidazo[1,5-a]pyrazin-3-yl}-cyclohexanecarboxylic acid,

cis-3-(3-Dimethylaminomethyl-cyclobutyl)-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

cis-3-(3-Azetidin-1-ylmethylcyclobutyl)-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

cis-3-(3-Pyrrolidin-1-ylmethylcyclobutyl)-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

cis-3-(3-Azidomethyl-cyclobutyl)-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

cis-3-(3-aminomethyl-cyclobutyl)-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-8-ylamine,

cis-3-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclobutane-carboxylic acid amide,

trans-3-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclobutane-carboxylic acid amide,

3-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-1-hydroxymethyl-cyclobutanol,

cis-Toluene-4-sulfonic acid 3-[8-amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-1-hydroxy-cyclobutylmethyl ester,

trans-Toluene-4-sulfonic acid 3-[8-amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-1-hydroxy-cyclobutylmethyl ester,

trans-3-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-1-azetidin-1-ylmethyl-cyclobutanol,

cis-3-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]-1-azetidin-1-ylmethyl-cyclobutanol,

1-[3-(4-tert-Butoxy-benzyloxy)-phenyl]-3-cyclobutyl-imidazo[1,5-a]pyrazin-8-ylamine,

2-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-benzonitrile,

3-Cyclobutyl-1-[3-(2-nitro-benzyloxy)-phenyl]-imidazo[1,5-a]pyrazin-8-ylamine,

1-[3-(2-Bromo-benzyloxy)-phenyl]-3-cyclobutyl-imidazo[1,5-a]pyrazin-8-ylamine,

1-[3-(3-Aminomethyl-benzyloxy)-phenyl]-3-cyclobutyl-imidazo[1,5-a]pyrazin-8-ylamine,

3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-benzoic acid methyl ester,

3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-benzamide,

{3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-phenyl}-methanol,

2-{3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-benzyl}-isoindole-1,3-dione,

3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-benzoic acid,

3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-N-methyl-benzamide,

1-(3-Benzyloxy-phenyl)-3-(3-methoxymethylene-cyclobutyl)-imidazo[1,5-a]pyrazin-8-ylamine,

3-[8-Amino-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutanecarbaldehyde,

cis-1-(3-Benzyloxy-phenyl)-3-(4-methoxy-cyclohexyl)-imidazo[1,5-a]pyrazin-8-ylamine,

trans-1-(3-Benzyloxy-phenyl)-3-(4-methoxy-cyclohexyl)-imidazo[1,5-a]pyrazin-8-ylamine,

cis-tert-Butyl ({3-[8-amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]-cyclobutyl}oxy)acetate,

cis-2-{3-[8-Amino-1-(3-benzyloxyphenyl)imidazo[1,5-a]pyrazin-3-yl]cyclobutoxy}ethanol,

cis-Toluene-4-sulfonic acid 2-{3-[8-amino-1-(3-benzyloxyphenyl)imidazo[1,5-a]pyrazin-3-yl]cyclobutoxy}ethyl ester,

cis-1-(3-Benzyloxyphenyl)-3-[3-(2-dimethylaminoethoxy)-cyclobutyl]imidazo[1,5-a]pyrazin-8-yl amine,

cis-{3-[8-Amino-1-(3-benzyloxyphenyl)imidazo[1,5-a]pyrazin-3-yl]-cyclobutoxy}acetic acid,

cis-2-{3-[8-Amino-1-(3-benzyloxyphenyl)imidazo[1,5-a]pyrazin-3-yl]cyclobutoxy}-N-methylacetamide,

cis-2-{3-[8-Amino-1-(3-benzyloxy-phenyl)imidazo[1,5-a]pyrazin-3-yl]cyclobutoxy}acetamide,

1-(3-benzyloxy-4-methoxyphenyl)-3-cyclobutyl-imidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxy-4-fluorophenyl)-3-cyclobutyl-imidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxy-4-isopropoxyphenyl)-3-cyclobutylimidazo[1,5-a]pyrazin-8-ylamine,

1-(3-Benzyloxy-4-ethoxyphenyl)-3-cyclobutylimidazo[1,5-a]pyrazin-8-ylamine,

4-(8-Amino-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-2-benzyloxyphenol,

4-{8-Amino-1-[3-(2,6-difluoro-benzyloxy)-phenyl]-imidazo[1,5-a]pyrazin-3-yl}-cyclohexanecarboxylic acid amide,

4-{8-Amino-1-[3-(2,6-difluoro-benzyloxy)-phenyl]-imidazo[1,5-a]pyrazin-3-yl}-cyclohexanecarboxylic acid methylamide,

N-{3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-phenyl}-acetamide,

or pharmaceutically acceptable salts thereof.

61. A compound selected from the group consisting of:

62. A compound selected from the group consisting of:

63. A compound selected from the group consisting of:

64. A compound selected from the group consisting of:

65. A compound selected from the group consisting of:

66. A compound selected from the group consisting of:

67. A compound selected from the group consisting of:

68. A compound selected from the group consisting of: