# US 2008/0188500 A1 · Substituted heterocycles as janus kinase inhibitors

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- Number: US 2008/0188500 A1
- Document ID: US20080188500A1
- Status: Published application
- Kind: A1
- Application number: 11/961,424
- Filed: 2007-12-20
- Published: 2008-08-07
- Earliest claimed: 2006-12-22
- Assignees: Incyte Corporation
- Inventors: Argyrios G. Arvanitis; James D. Rodgers; Louis Storace; Beverly Folmer
- Web page: https://patentgrep.com/patent/US20080188500A1

## CPC

- C07D 487/14: Ortho-condensed systems
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 11/06: Antiasthmatics
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/18: for HIV
- A61P 31/20: for DNA viruses
- A61P 31/22: for herpes viruses
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 471/14: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention provides substituted tricyclic heteroaryl compounds, including, for example, pyridoindoles, pyrimidinoindoles and triazinoindoles that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases such as immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

## Claims

### Claim 1

A compound of Formula I:
or a pharmaceutically acceptable salt form thereof, wherein:
Cya is selected from arylene, heteroarylene, cycloalkylene, and heterocycloalkylene, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, C(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1;
Cyb is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2 NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2C(O)NRc2Rd2, C(O)ORa2, OC(O)Ra2, OC(O)NRc2Rd1, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2R2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
L is a divalent moiety selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, (C1-6 alkylene)p-(C3-10 cycloalkylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-(C3-10 heterocycloalkylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-(C6-10 arylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-(C3-10 heteroarylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-O—(C1-6 alkylene)q, (C1-6 alkylene)p-S—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-C(O)—(C1-6 alkylene)q, (C1-6 alkylene)p-OC(O)—(C1-6 alkylene)q, (C1-6 alkylene)p-C(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-OC(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-S(O)—(C1-6 alkylene)q, (C1-6 alkylene)p-S(O)2—(C1-6 alkylene)q, (C1-6 alkylene)p-S(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-S(O)2NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3C(O)NRd3—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3S(O)NRd3—(C1-6 alkylene)q, and (C1-6 alkylene)p-NRc3S(O)2NRd3—(C1-6 alkylene)q, wherein each of the C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, cycloalkylene, arylene, heterocycloalkylene, and heteroarylene is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 hydroxyalkyl, C1-4 cyanoalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, CN, NO2, SCN, OH, C1-4 haloalkyl, halosulfanyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, and C2-8 dialkylamino;
wherein L is oriented in either direction with respect to its attachment to Cya and Cyb;
Y1 is selected from CR3 and N;
Y2 is selected from CR4 and N;
Y3 is selected from CR5 and N;
provided that at least one of Y1 and Y2 is other than N;
Z1 is selected from CR6 and N;
Z2 is selected from CR7 and N;
R1 is selected from H, C1-6 alkyl, C(O)C1-6 alkyl, and C(O)aryl;
R2, R3, R4, R5, R6, and R7 are independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy1, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, C(═NRi)NRc4Rd4, NRc4C(═NRi)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, NRc4S(O)R4, NRc4S(O)2Rb4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, and S(O)2NRc4Rd4; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from CN, NO2, Cγ1, Cy1-(C1-6 alkyl)-, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, C(═NRi)NRc4Rd4, NRc4C(═NRi)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2 b4, and S(O)2NRc4Rd4;
Cy, Cy1, and Cy2 are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halosulfanyl, CN, NO2, N3, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NR5C(O)ORa, C(═NRi)NRc5Rd5, NRc5C(═NRi)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5Rf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C1-6 haloalkyl, halosulfanyl, CN, NO2, N3, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi)NRc5Rd5, NRc5C(═NRi)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5Rf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5;
Ra1, Ra2, and Ra4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C(O)—C1-7 hydrocarbyl, wherein said C1-6 alkyl, C2-6 alkenyl, C1-7 hydrocarbyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rb1, Rb2, and Rb4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rc1, Rc2, and Rc4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rd1, Rd2, and Rd4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; or,
one or more of Rc1 and Rd1, Rc2 and Rd2, and Rc4 and Rd4 together with the N atom to which they are attached, optionally form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rc3 and Rd3 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Ra5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;
Rb5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;
Rc5 and Rd5 are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy; or
Rc5 and Rd5 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;
Re5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, (C1-6 alkoxy)-C1-6 alkyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocyclo-alkylalkyl;
Rf5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl;
Ri is H, CN, NO2, C(O)NH2, or C1-6 alkyl;
p is 0 or 1; and
q is 0 or 1;
provided that when Cya is a piperazine ring, R2 is other than halo.

### Claim 2 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Y1 is N and Y2 is CR4.

### Claim 3 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Y2 is N and Y1 is CR3.

### Claim 4 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Y2 is N.

### Claim 5 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Y2 is CR4.

### Claim 6 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Y3 is N.

### Claim 7 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Y3 is CR5.

### Claim 8 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Z1 is N.

### Claim 9 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Z1 is CR6.

### Claim 10 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Z2 is N.

### Claim 11 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Z2 is CR7.

### Claim 12 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R1 is H, C1-6 alkyl, or C(O)C1-6 alkyl.

### Claim 13 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R1 is H

### Claim 14 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R2 is H

### Claim 15 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cya is arylene or heteroarylene, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1.

### Claim 16 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cya is arylene optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Ra1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1.

### Claim 17 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cya is arylene optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORb1, SRb1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb, NRc1S(O)2Rb1, S(O)Rb1 S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1.

### Claim 18 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cya is arylene optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, CN, NO2, ORa1, SRa1, and NRc1Rd1.

### Claim 19 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cya is arylene optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyland ORa1.

### Claim 20 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cya is a substituted aryl or substituted heteroaryl ring according to Formula IA:
wherein:
R is selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halo-sulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1;
Q1, Q2 and Q3 are independently selected from CRQ and N; and
RQ is independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NR)NRc1Rd1, NRc1C(═NR)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Re1, S(O)Rb1, S(O)NRc1Rd, S(O)2Rb1, and S(O)2NRc1Rd1; wherein the point of attachment on the right hand side of the ring of Formula IA is attached to L.

### Claim 21 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cya is a substituted aryl or substituted heteroaryl ring according to Formula IB:
wherein:
R is selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halo-sulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORb1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Re1, and S(O)2NRc1Rd1;
Q1, Q2 and Q3 are independently selected from CRQ and N; and
RQ is independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NR)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1 wherein the point of attachment on the right hand side of the ring of Formula IB is attached to L.

### Claim 22 (depends on 21)

A compound of claim 21, or pharmaceutically acceptable salt thereof, wherein R is selected from H, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, and ORa1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1.

### Claim 23 (depends on 21)

A compound of claim 21, or pharmaceutically acceptable salt thereof, wherein R is selected from halosulfanyl, NO2, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1.

### Claim 24 (depends on 21)

A compound of claim 21, or pharmaceutically acceptable salt thereof, wherein R is selected from H, halo, CN, C1-6 alkyl and ORa1.

### Claim 25 (depends on 21)

A compound of claim 21, or pharmaceutically acceptable salt thereof, wherein Q1 is CRQ.

### Claim 26 (depends on 21)

A compound of claim 21, or pharmaceutically acceptable salt thereof, wherein Q2 is CRQ.

### Claim 27 (depends on 21)

A compound of claim 21, or pharmaceutically acceptable salt thereof, wherein Q3 is CRQ.

### Claim 28 (depends on 21)

A compound of claim 21, or pharmaceutically acceptable salt thereof, wherein Q3 is N.

### Claim 29 (depends on 21)

A compound of claim 21, or pharmaceutically acceptable salt thereof, wherein RQ is H.

### Claim 30 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cyb is aryl or heteroaryl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)OR2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)b2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2.

### Claim 31 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cyb is aryl or heteroaryl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2, S(O)b2 S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2.

### Claim 32 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cyb is aryl or heteroaryl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, and NRc2Rd2.

### Claim 33 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cyb is aryl, optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2.

### Claim 34 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Cyb is heteroaryl, optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2.

### Claim 35 (depends on 1)

A compound of claim 1, wherein Cyb is a substituted aryl or substituted heteroaryl ring according to Formula IF:
wherein:
W1 and W2 are independently selected from CRW and N;
A1 and A2 are independently selected from CRW and N; or the group, A1=A2, is S, O, or NH; and
each RW is independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, CY, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, CY, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2.

### Claim 36 (depends on 35)

A compound of claim 35, or pharmaceutically acceptable salt thereof, wherein W1 is CRW.

### Claim 37 (depends on 35)

A compound of claim 35, or pharmaceutically acceptable salt thereof, wherein W1 is N.

### Claim 38 (depends on 35)

A compound of claim 35, or pharmaceutically acceptable salt thereof, wherein W2 is CRW.

### Claim 39 (depends on 35)

A compound of claim 35, or pharmaceutically acceptable salt thereof, wherein W2 is N.

### Claim 40 (depends on 35)

A compound of claim 35, or pharmaceutically acceptable salt thereof, wherein A1 is CRW.

### Claim 41 (depends on 35)

A compound of claim 35, or pharmaceutically acceptable salt thereof, wherein A1 is N.

### Claim 42 (depends on 35)

A compound of claim 35, or pharmaceutically acceptable salt thereof, wherein A2 is CRW.

### Claim 43 (depends on 35)

A compound of claim 35, or pharmaceutically acceptable salt thereof, wherein A2 is N.

### Claim 44 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein L is a divalent moiety selected from C1-6 alkylene, (C1-6 alkylene)p-O—(C1-6 alkylene)q, (C1-6 alkylene)p-S—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-C(O)—(C1-6 alkylene)q, (C1-6 alkylene)p-OC(O)—(C1-6 alkylene)q, (C1-6 alkylene)p-C(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-OC(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-SO—(C1-6 alkylene)q, (C1-6 alkylene)p-SO2—(C1-6 alkylene)q, (C1-6 alkylene)p-SONRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-SO2NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3CONRd3—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3SONRd3—(C1-6 alkylene)q, and (C1-6 alkylene)p-NRc3SO2NRd3—(C1-6 alkylene)q, wherein the C1-6 alkylene is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 hydroxyalkyl, C1-4 cyanoalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, CN, NO2, SCN, OH, C1-4 haloalkyl, halosulfanyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, and C2-8 dialkylamino.

### Claim 45 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein L is a divalent moiety selected from (C1-6 alkylene)p-C(O)NRc3—(C1-6 alkylene)q and (C1-6 alkylene)p-NRc3CONRd3—(C1-6 alkylene)q, wherein the C1-6 alkylene is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 hydroxyalkyl, C1-4 cyanoalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, CN, NO2, SCN, OH, C1-4 haloalkyl, halosulfanyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, and C2-8 dialkylamino.

### Claim 46 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein L is a divalent moiety selected from (C1-6 alkylene)p-C(O)NRc3—(C1-6 alkylene)q and (C1-6 alkylene)p-NRc3CONRd3—(C1-6 alkylene)q.

### Claim 47 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein L is a divalent moiety selected from C(O)NH, C(O)NH—(C1-6 alkylene) and NHCONH.

### Claim 48 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein L is C(O)NH.

### Claim 49 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein L is C(O)NH—(C1-6 alkylene).

### Claim 50 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, wherein L is NHCONH.

### Claim 51 (depends on 1)

A compound of claim 1, or pharmaceutically acceptable salt thereof, having Formula II:

### Claim 52 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt thereof, having Formula III:

### Claim 53 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt thereof, having Formula IIIK:

### Claim 54 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt thereof, having Formula IVA or IVB:

### Claim 55 (depends on 1)

The compound of claim 1, selected from:
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-(trifluoromethyl)benzamide;
3-(4-Methyl-1H-imidazol-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(tri-fluoromethyl)benzamide;
3-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)-benzamide;
3-(4-formyl-1H-imidazol-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide;
3-[4-(hydroxymethyl)-1H-imidazol-1-yl]-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)-phenyl]-5-(trifluoromethyl)benzamide;
3-4-[(methylamino)methyl]-1H-imidazol-1-yl-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide;
3-(4-methylpiperazin-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)phenyl]-3-(trifluoromethyl)benzamide;
4-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)phenyl]-3-(trifluoromethyl)-benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-N′-[3-(trifluoromethyl)phenyl]urea;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)phenyl]-N′-[3-(trifluoromethyl)phenyl]urea;
4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)-N-[3-(trifluoromethyl)phenyl]benzamide;
4-chloro-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide;
4-cyano-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide;
2-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-(trifluoromethyl)-benzamide;
4-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-(trifluoromethyl)-benzamide;
2-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)-benzamide;
3-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)phenyl]benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-2,5-bis(trifluoromethyl)benzamide;
3-chloro-2-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)-benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3,5-bis(trifluoromethyl)benzamide;
4-methoxy-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-(trifluoromethyl)-benzamide;
3-methoxy-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-2-(trifluoromethyl)benzamide;
N-[4-fluoro-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-(trifluoromethyl)benzamide;
N-[3-(9H-pyrimido[4,5-b]-indol-7-yl)phenyl]-3-(trifluoromethyl)benzamide;
3-chloro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-(pentafluoro-λ(6)-sulfanyl)-benzamide;
N-[4-chloro-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-(trifluoromethyl)benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-4-(trifluoromethyl)pyridine-2-carboxamide;
3-(1H-imidazol-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoro-methyl)benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-(1H-1,2,4-triazol-1-yl)-5-(trifluoro-methyl)benzamide;
3-{4-[(dimethylamino)methyl]-1H-imidazol-1-yl}-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-morpholin-4-yl-5-(trifluoromethyl)-benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-piperazin-1-yl-5-(trifluoromethyl)-benzamide;
3-(4-hydroxypiperidin-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide;
3-(3-hydroxypiperidin-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-3-[(2-morpholin-4-ylethyl)amino]-5-(trifluoromethyl)benzamide;
3-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide;
3-{[3-(dimethylamino)propyl]amino}-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide;
3-(3-hydroxypyrrolidin-1-yl)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide;
3-{[3-(1H-imidazol-1-yl)-propyl]amino}-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)-phenyl]-5-(trifluoromethyl)benzamide;
3-(dimethylamino)-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoro-methyl)benzamide;
3-[3-(dimethylamino)-pyrrolidin-1-yl]-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)-phenyl]-5-(trifluoromethyl)benzamide;
3-{[2-(dimethylamino)ethyl]amino}-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)phenyl]-5-(trifluoromethyl)benzamide;
4-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)phenyl]-3-(trifluoromethyl)-benzamide;
3-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)phenyl]-5-(trifluoromethyl)-benzamide;
3-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)phenyl]benzamide;
N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)phenyl]-2,5-bis(trifluoromethyl)benzamide;
3-chloro-2-fluoro-N-[4-methyl-3-(9H-pyrimido[4,5-b]indol-6-yl)phenyl]-5-(trifluoromethyl)-benzamide;
4-methyl-3-(9H-pyrimido-[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide;
4-methyl-N-(3-methyl-phenyl)-3-(9H-pyrimido[4,5-b]indol-7-yl)benzamide;
4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethoxy)phenyl]benzamide;
N-(2,5-difluorobenzyl)-4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)benzamide;
4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)benzyl]benzamide;
4-methyl-N-(5-methyl-1,3-thiazol-2-yl)-3-(9H-pyrimido[4,5-b]indol-7-yl)benzamide;
4-chloro-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide;
3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide;
4-methoxy-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide;
4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]-benzamide;
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(9H-pyrimido[4,5-b]indol-7-yl)benzamide;
4-methyl-N-[(1R)-1-phenylethyl]-3-(9H-pyrimido[4,5-b]indol-7-yl)benzamide;
4-methyl-N-[(1S)-1-phenylethyl]-3-(9H-pyrimido[4,5-b]indol-7-yl)benzamide;
4-methyl-N-[3-(pentafluoro-λ(6)-sulfanyl)phenyl]-3-(9H-pyrimido[4,5-b]indol-7-yl)-benzamide;
4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[5-(trifluoromethyl)pyridin-3-yl]benzamide;
N-[3-(2-amino-9H-pyrimido[4,5-b]indol-7-yl)-4-methylphenyl]-3-(trifluoromethyl)-benzamide;
4-methyl-3-(9H-pyrido[2,3-b]indol-7-yl)-N-[3-(trifluoromethyl)phenyl]benzamide;
4-methyl-3-(9H-pyrido[3′,2′:4,5]pyrrolo[2,3-d]pyrimidin-7-yl)-N-[3-(trifluoromethyl)phenyl]-benzamide;
N-[6-methyl-5-(9H-pyrimido[4,5-b]indol-7-yl)pyridin-3-yl]-3-(trifluoromethyl)benzamide;
3-fluoro-N-[6-methyl-5-(9H-pyrimido[4,5-b]indol-7-yl)pyridin-3-yl]-5-(trifluoromethyl)benzamide;
3-(1H-imidazol-1-yl)-N-[6-methyl-5-(9H-pyrimido[4,5-b]indol-7-yl)pyridin-3-yl]-5-(trifluoromethyl)benzamide;
N-[6-methyl-5-(9H-pyrimido[4,5-b]indol-7-yl)pyridin-3-yl]-3-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethyl)benzamide;
3-(4-formyl-1H-imidazol-1-yl)-N-[6-methyl-5-(9H-pyrimido[4,5-b]indol-7-yl)pyridin-3-yl]-5-(trifluoromethyl)benzamide;
3-[4-(hydroxymethyl)-1H-imidazol-1-yl]-N-[6-methyl-5-(9H-pyrimido[4,5-b]indol-7-yl)pyridin-3-yl]-5-(trifluoromethyl)benzamide;
3-[2-(dimethylamino)ethyl]amino-N-[6-methyl-5-(9H-pyrimido[4,5-b]indol-7-yl)pyridin-3-yl]-5-(trifluoromethyl)benzamide;
3-[3-(dimethylamino)propyl]amino-N-[6-methyl-5-(9H-pyrimido[4,5-b]indol-7-yl)pyridin-3-yl]-5-(trifluoromethyl)benzamide; and
pharmaceutically acceptable salts thereof.

### Claim 56 (depends on 1)

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

### Claim 57 (depends on 56)

The composition of claim 56 which is suitable for topical administration.

### Claim 58

A method of treating a disease in a patient, wherein said disease is associated with abnormal activities of one or more kinases, comprising administering to said patient a therapeutically effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt form thereof, wherein:
Cya is selected from arylene, heteroarylene, cycloalkylene, and heterocycloalkylene, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa2, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRC(O)b1, NRc1C(O)ORb1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1;
Cyb is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rcd, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2R2, and S(O)2NRc2Rd2;
L is a divalent moiety selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, (C1-6 alkylene)p-(C3-10 cycloalkylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-(C3-10 heterocycloalkylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-(C6-10 arylene)-(C1-6 alkylene)q-(C1-6 alkylene)p-(C3-10 heteroarylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-O—(C1-6 alkylene)q, (C1-6 alkylene)p-S—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-C(O)—(C1-6 alkylene)q, (C1-6 alkylene)p-OC(O)—(C1-6 alkylene)q, (C1-6 alkylene)p-C(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-OC(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-SO—(C1-6 alkylene)q, (C1-6 alkylene)p-SO2—(C1-6 alkylene)q, (C1-6 alkylene)p-SONRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-SO2NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3CONRd3—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3SONRd3—(C1-6 alkylene)q, and (C1-6 alkylene)p-NRc3SO2NRd3—(C1-6 alkylene)q, wherein each of the C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, cycloalkylene, arylene, heterocycloalkylene, and heteroarylene is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 hydroxyalkyl, C1-4 cyanoalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, CN, NO2, SCN, OH, C1-4 haloalkyl, halosulfanyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, and C2-8 dialkylamino;
wherein L is oriented in either direction with respect to its attachment to Cya and Cyb;
Y1 is selected from CR3 and N;
Y2 is selected from CR4 and N;
Y3 is selected from CR5 and N;
provided that at least one of Y1 and Y2 is other than N;
Z1 is selected from CR6 and N;
Z2 is selected from CR7 and N;
R1 is selected from H, C1-6 alkyl, C(O)C1-6 alkyl, and C(O)aryl;
R2, R3, R4, R5, R6, and R7 are independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy1, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, C(═NRi)NRc4Rd4, NRc4C(═NRi)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, and S(O)2NRc4Rd4; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from CN, NO2, Cy1, Cy1—(C1-6 alkyl)-, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, C(═NRi)NRc4Rd4, NRc4C(═NRi)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, and S(O)2NRc4Rd4;
Cy, Cy1, and Cy2 are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halosulfanyl, CN, NO2, N3, ORa5, SRb5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi)NRc5Rd5, NRc5C(═NRi)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5ORf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C1-6 haloalkyl, halosulfanyl, CN, NO2, N3, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)b5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi)NRc5Rd5, NRc5C(═NR)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5ORf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5;
Ra1, Ra2, and Ra4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C(O)—C1-7 hydrocarbyl, wherein said C1-6 alkyl, C2-6 alkenyl, C1-7 hydrocarbyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rb1, Rb2, and Rb4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rc1, Rc2, and Rc4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rd1, Rd2, and Rd4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; or,
one or more of Rc1 and Rd1, Rc2 and Rd2, and Rc4 and Rd4 together with the N atom to which they are attached, optionally form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rc3 and Rd3 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Ra5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;
Rb5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;
Rc5 and Rd5 are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy; or
Rc5 and Rd5 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;
Re5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, (C1-6 alkoxy)-C1-6 alkyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocyclo-alkylalkyl;
Rf5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl;
R1 is H, CN, NO2, C(O)NH2, or C1-6 alkyl;
p is 0 or 1; and
q is 0 or 1.

### Claim 59 (depends on 58)

The method of claim 58 wherein the disease is characterized by the abnormal activity of ABL.

### Claim 60 (depends on 58)

The method of claim 58 wherein the disease is characterized by the abnormal activity of JAK.

### Claim 61 (depends on 58)

The method of claim 58 wherein the disease is characterized by the abnormal activity of ABL and JAK.

### Claim 62 (depends on 58)

The method of claim 58 wherein more than one compound of Formula I is administered

### Claim 63 (depends on 58)

The method of claim 58 wherein the compound is administered in combination with another kinase inhibitor.

### Claim 64 (depends on 58)

The method of claim 58 wherein said disease is allograft rejection or graft versus host disease.

### Claim 65 (depends on 58)

The method of claim 58 wherein said disease is an autoimmune disease.

### Claim 66 (depends on 65)

The method of claim 65 wherein said autoimmune disease is a skin disorder, multiple sclerosis, rheumatoid arthritis, juvenile arthritis, type I diabetes, lupus, inflammatory bowel disease, Crohn's disease, myasthenia gravis, immunoglobulin nephropathies, myocarditis, or autoimmune thyroid disorder.

### Claim 67 (depends on 65)

The method of claim 65 wherein said autoimmune disease is bullous skin disorder.

### Claim 68 (depends on 67)

The method of claim 67 wherein said bullous skin disorder is pemphigus vulgaris (PV) or bullous pemphigoid (BP).

### Claim 69 (depends on 65)

The method of claim 65 wherein said disease is a skin disorder.

### Claim 70 (depends on 69)

The method of claim 69 wherein said skin disorder is atopic dermatitis, psoriasis, skin sensitization, skin irritation, skin rash, contact dermatitis or allergic contact sensitization.

### Claim 71 (depends on 65)

The method of claim 65 wherein said disease is a viral disease.

### Claim 72 (depends on 71)

The method of claim 71 wherein said viral disease is Epstein Barr Virus (EBV), Hepatitis B, Hepatitis C, HIV, HTLV 1, Varicell-Zoster Virus (VZV) or Human Papilloma Virus (HPV).

### Claim 73 (depends on 65)

The method of claim 65 wherein said disease is cancer.

### Claim 74 (depends on 73)

The method of claim 73 wherein said cancer is a solid tumor.

### Claim 75 (depends on 73)

The method of claim 73 wherein said cancer is prostate cancer, renal cancer, hepatic cancer, breast cancer, lung cancer, thyroid cancer, Kaposi's sarcoma, Castleman's disease or pancreatic cancer.

### Claim 76 (depends on 73)

The method of claim 73 wherein said cancer is prostate cancer.

### Claim 77 (depends on 73)

The method of claim 73 wherein said cancer is hematological.

### Claim 78 (depends on 73)

The method of claim 73 wherein said cancer is lymphoma, leukemia, or multiple myeloma.

### Claim 79 (depends on 73)

The method of claim 73 wherein said cancer is acute lymphoblastic leukemia (ALL), chronic myelomonocytic leukemia (CMML), chronic myeloid leukemia (CML), atypical CML or CMML.

### Claim 80 (depends on 73)

The method of claim 73 wherein said cancer is a skin cancer.

### Claim 81 (depends on 80)

The method of claim 80 wherein said skin cancer is cutaneous T-cell lymphoma or cutaneous B-cell lymphoma.

### Claim 82 (depends on 73)

The method of claim 73 wherein said cancer is multiple myeloma.

### Claim 83 (depends on 65)

The method of claim 65 said disease is characterized by a mutant JAK2.

### Claim 84 (depends on 83)

The method of claim 83 wherein at least one mutation of said mutant JAK2 resides in the pseudo-kinase domain of said JAK2.

### Claim 85 (depends on 58)

The method of claim 58 wherein said disease is characterized by a mutant ABL.

### Claim 86 (depends on 85)

The method of claim 85 wherein at least one mutation of said mutant ABL resides in the kinase domain of said mutant ABL.

### Claim 87 (depends on 65)

The method of claim 65 wherein said disease is a myeloproliferative disorder.

### Claim 88 (depends on 87)

The method of claim 87 wherein said myeloproliferative disorder (MPD) is polycythemia vera (PV), essential thrombocythemia (ET), myeloid metaplasia with myelofibrosis (MMM), chronic myelogenous leukemia (CML), chronic myelomonocytic leukemia (CMML), hypereosinophilic syndrome (HES), idiopathic myelofibrosis (IMF), or systemic mast cell disease (SMCD).

### Claim 89 (depends on 65)

The method of claim 65 wherein said disease is an inflammatory disease.

### Claim 90 (depends on 89)

The method of claim 89 wherein said disease is an inflammatory disease of the eye.

### Claim 91 (depends on 90)

The method of claim 90 wherein said disease is iritis, uveitis, scleritis, or conjunctivitis.

### Claim 92 (depends on 89)

The method of claim 89 wherein said disease is an inflammatory disease of the respiratory tract.

### Claim 93 (depends on 92)

The method of claim 92 wherein said inflammatory disease concerns the upper respiratory tract.

### Claim 94 (depends on 92)

The method of claim 92 wherein said inflammatory disease concerns the lower respiratory tract.

### Claim 95 (depends on 89)

The method of claim 89 wherein said inflammatory disease is an inflammatory myopathy.

### Claim 96 (depends on 89)

The method of claim 89 wherein said inflammatory disease is myocarditis.

### Claim 97 (depends on 65)

The method of claim 65 wherein said disease is ischemia reperfusion or related to an ischemic event.

### Claim 98 (depends on 65)

The method of claim 65 wherein said disease is anorexia or cachexia resulting from or associated with cancer.

### Claim 99 (depends on 65)

The method of claim 65 wherein said disease is fatigue resulting from or associated with cancer.

### Claim 100

A method of treating autoimmune disease, skin disorder, viral disease, cancer, or myeloproliferative disorder in a patient, comprising administering to said patient a therapeutically effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt form thereof, wherein:
Cya is selected from arylene, heteroarylene, cycloalkylene, and heterocycloalkylene, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1 S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRi)NRc1Rd1, NRc1C(═NRi)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1;
Cyb is selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd1, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRi)NRc2Rd2, NRc2C(═NRi)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
L is a divalent moiety selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, (C1-6 alkylene)p-(C3-10 cycloalkylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-(C3-10 heterocycloalkylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-(C6-10 arylene)-(C1-6 alkylene)q-(C1-6 alkylene)p-(C3-10 heteroarylene)-(C1-6 alkylene)q, (C1-6 alkylene)p-O—(C1-6 alkylene)q, (C1-6 alkylene)p-S—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-C(O)—(C1-6 alkylene)q, (C1-6 alkylene)p-OC(O)—(C1-6 alkylene)q, (C1-6 alkylene)p-C(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-OC(O)NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-SO—(C1-6 alkylene)q, (C1-6 alkylene)p-SO2—(C1-6 alkylene)q, (C1-6 alkylene)p-SONRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-O2NRc3—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3CONRd3—(C1-6 alkylene)q, (C1-6 alkylene)p-NRc3SONRd3—(C1-6 alkylene)q, and (C1-6 alkylene)p-NRc3SO2NRd3—(C1-6 alkylene)q, wherein each of the C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, cycloalkylene, arylene, heterocycloalkylene, and heteroarylene is optionally substituted by 1, 2 or 3 substituents independently selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 hydroxyalkyl, C1-4 cyanoalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, CN, NO2, SCN, OH, C1-4 haloalkyl, halosulfanyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, and C2-8 dialkylamino;
wherein L is oriented in either direction with respect to its attachment to Cya and Cyb;
Y1 is selected from CR3 and N;
Y2 is selected from CR4 and N;
Y3 is selected from CR5 and N;
provided that at least one of Y1 and Y2 is other than N;
Z1 is selected from CR6 and N;
Z2 is selected from CR7 and N;
R1 is selected from H, C1-6 alkyl, C(O)C1-6 alkyl, and C(O)aryl;
R2, R3, R4, R5, R6, and R7 are independently selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cy1, C1-6 haloalkyl, halosulfanyl, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, C(═NRi)NRc4Rd4, NRc4C(═NRi)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Re, S(O)Rb4, S(O)NRc4Rd4, S(O)2Re, and S(O)2NRc4Rd4; wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from CN, NO2, Cy1, Cy1—(C1-6 alkyl)-, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, C(═NRi)NRc4Rd4, NRc4C(═NRi)NRc4Rd4, S(O)Rb4S(O)NRc4Rd4, S(O)2Rb4, and S(O)2NRc4Rd4;
Cy, Cy1, and Cy2 are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halosulfanyl, CN, NO2, N3, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi)NRc5Rd5, NRc5C(═NRi)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5ORf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd5, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C1-6 haloalkyl, halosulfanyl, CN, NO2, N3, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)NRc5Rd5, NRc5C(O)ORa5, C(═NRi)NRc5Rd5, NRc5C(═NRi)NRc5Rd5, P(Rf5)2, P(ORe5)2, P(O)Re5Rf5, P(O)ORe5ORf5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, NRc5S(O)2Rb5, and S(O)2NRc5Rd;
Ra1, Ra2, and Ra4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C(O)—C1-7 hydrocarbyl, wherein said C1-6 alkyl, C2-6 alkenyl, C1-7 hydrocarbyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rb1, Rb2, and Rb4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rc1, Rc2, and Rc4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Rd1, Rd2, and Rd4 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; or,
one or more of Rc1 and Rd1, Rc2 and Rd2, and Rc4 and Rd4 together with the N atom to which they are attached, optionally form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Re3 and Rd3 are independently selected from H, Cy2, —(C1-6 alkyl)-Cy2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, C1-6 alkoxy, CN, amino, alkylamino, dialkylamino, halo, C1-6 alkyl, C1-6 haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl;
Ra5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;
Rb5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;
Rc5 and Rd5 are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy; or
Rc5 and Rd5 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;
Re5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, (C1-6 alkoxy)-C1-6 alkyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl;
Rf5 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl;
Ri is H, CN, NO2, C(O)NH2, or C1-6 alkyl;
p is 0 or 1; and
q is 0 or 1.