# US 9,040,558 B2 · Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors

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- Number: US 9,040,558 B2
- Document ID: US9040558B2
- Status: Granted
- Kind: B2
- Application number: 11/320,120
- Filed: 2005-12-28
- Published: 2006-08-10
- Granted: 2015-05-26
- Earliest claimed: 2004-12-31
- Assignees: Dr. Reddy's Laboratories, Inc.
- Applicants: Anima Baruah; Dibyendu De; Ish Kumar Khanna; Sivaram Pillarisetti; Santanu Maitra; Christopher W. Alexander; Jennepalli Sreenu; Indu Dager; Shanavas Alikunju
- Inventors: Anima Baruah; Dibyendu De; Ish Kumar Khanna; Sivaram Pillarisetti; Santanu Maitra; Christopher W. Alexander; Jennepalli Sreenu; Indu Dager; Shanavas Alikunju
- Web page: https://patentgrep.com/patent/US9040558B2

## CPC

- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/438: The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
- A61K 31/47: Quinolines; Isoquinolines
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 213/73: Unsubstituted amino or imino radicals
- C07D 213/74: Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C07D 215/38: Nitrogen atoms (nitro radicals C07D215/18)
- C07D 221/04: Ortho- or peri-condensed ring systems
- C07D 239/78: with hetero atoms directly attached in position 2
- C07D 241/20: Nitrogen atoms (nitro radicals C07D241/16)
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 471/04: Ortho-condensed systems
- C07D 498/04: Ortho-condensed systems
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention is directed to novel substituted benzylamino quinolines, compounds comprising substituted benzylamino quinolines, methods of making substituted benzylamino quinolines, the use of substituted benzylamino quinolines for treating or preventing a variety of conditions or diseases associated with lipoprotein metabolism, and the use of substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors.

## Claims

### Claim 1

A compound having the formula:
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein:
A is a substituted or an unsubstituted quinoline moiety having the formula:
wherein Ra, in each occurrence, is selected independently from: 1) a halogen; a hydroxyl, or a cyano; 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms; or 3) CO2R6; and p is an integer from 0 to 3, inclusive;
R1 and R2 are selected independently from: 1) hydrogen; 2) a substituted or an unsubstituted alkyl, cycloalkyl, haloalkyl, aryl, heterocyclyl, heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; 3) CO2R6, COR8, SO2R8, SO2NR6R7, or CONR6R7; or 4) (CHRx)nR5 or (CH2)nRdCO2Re, wherein n, in each occurrence, is 1, 2, or 3; Rx, in each occurrence, is selected independently from an alkyl or an alkoxy, either of which having up to 12 carbon atoms, or hydrogen; Rd, in each occurrence, is selected independently from an alkyl, a cycloalkyl, an aryl, a heterocyclyl, or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; and Re, in each occurrence, is selected independently from an alkyl or a cycloalkyl, either of which having up to 12 carbon atoms, or hydrogen;
or R1 and R2 together with the diradical Z to which they are attached form a substituted or an unsubstituted monocyclic or bicyclic moiety comprising up to 12 carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms or heterogroups in addition to Z, selected independently from O, N, S, NR10, SO2, or CO;
R3 is selected from: 1) cyano; 2) a substituted alkyl having up to 12 carbon atoms; 3) a substituted or an unsubstituted aryl, or a substituted or an unsubstituted 5-, 6-, or 7-membered heterocyclyl or heteroaryl, any of which having up to 12 carbon atoms, comprising 1, 2, or 3 heteroatoms or heterogroups selected independently from O, N, S, NR10, SO2, or CO; or 4) CO2R6, COR8, SO2R8, SO2NR6R7, CONR6R7, C(S)NR6R7, C(S)NHC(O)OR8, or C(S)SR8; or 5) a substituted or an unsubstituted group selected from 4,5-dihydro-oxazolyl, tetrazolyl, isoxazolyl, pyridyl, pyrimidinyl, oxadiazolyl, thiazolyl, or oxazolyl; wherein any optional substituents is selected independently from a) an alkyl or a haloalkyl, any of which having up to 12 carbon atoms; or b) CO2R9, wherein R9 is an alkyl having up to 12 carbon atoms;
wherein when R3 is an aryl, a heterocyclyl, or a heteroaryl, R3 is optionally substituted with up to three substituents selected independently from a halide, a hydroxyl, a cyano, an alkoxy having up to 12 carbon atoms, or R11;
R4, in each occurrence, is selected independently from: 1) halogen, cyano, or hydroxy; 2) an alkyl, a cycloalkyl, a cycloalkoxy, an alkoxy, a haloalkyl, or a haloalkoxy, any of which having up to 12 carbon atoms; 3) a substituted or an unsubstituted aryl, aralkyl, aryloxy, heteroaryl, or heteroaryloxy, any of which having up to 12 carbon atoms, wherein any heteroaryl or heteroaryloxy comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 4) CO2R6, COR8, SO2R8, SO2NR6R7, CONR6R7, or (CH2)qNR6R7, wherein q is an integer from 0 to 5, inclusive;
m is an integer from 0 to 3, inclusive;
or R4m is a fused cyclic moiety comprising from 3 to 5 additional ring carbon atoms, inclusive, and optionally comprising at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R5, in each occurrence, is selected independently from: 1) an alkoxy, a haloalkoxy, or a cycloalkyl, any of which having up to 12 carbon atoms; 2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; 3) hydroxyl, NR6R7, CO2R6, COR8, or SO2R8; or 4) a substituted or an unsubstituted heterocycloalkyl comprising from 3 to 7 ring carbon atoms, and from 1 to 3 heteroatoms or heterogroups, inclusive, selected independently from O, N, S, NR10, SO2, or CO;
R6 and R7, in each occurrence, are selected independently from: 1) hydrogen; 2) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 3) a substituted or an unsubstituted aryl, aralkyl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; or R6 and R7 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety having from 3 to 7 ring carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms in addition to the nitrogen atom to which R6 and R7 are bonded, selected independently from O, N, S, or NR10;
R8, in each occurrence, is selected independently from: 1) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R10, in each occurrence, is selected independently from: 1) hydrogen; or 2) an alkyl, a cycloalkyl, a haloalkyl, an aryl, or an aralkyl, any of which having up to 12 carbon atoms;
Z is N; or the ZR1 moiety is S, CO, or SO2;
R11 is selected independently from:
1) an alkyl, a haloalkyl, a cycloalkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms;
2) a substituted or an unsubstituted heteroaryl or heterocyclyl, any of which having up to 12 carbon atoms, comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heteroaryl or heterocyclyl is substituted with up to three substituents selected independently from an alkyl having up to 12 carbon atoms or a hydroxyl; or
3) —CO—Z2—R13, —CO—R12, —CO—Z2—(CH2)r—CO—Z2—R13, —NR15R16, —Z2—CO—(CH2)r—Z2—R13, —Z2—CO—(CH2)r—CO—Z2—R13, —O—(CH2)r—CO—Z2—R13, —O—(CH2)r—R14, —O—R12—(CH2)r—R13, —O—R14—CO—O—R13, —O—(CH2)r—R12, —O—(CH2)r—NR′R″, —O—(CH2)r—CO2—(CH2)r—R13, —O—(CH2)r—CONR′R″, —O—(CH2)r—SR8, —O—(CH2)r—CO2—R13, —O—(CH2)r—O—(CH2)r—OR13, —O—(CH2)r—CONH—(CH2)r—OR13, —O—(CH2)r—SO2R8, —O—(CH2)r—R13, —O—(CH2)r—OR13, —S—(CH2)r—CONR′R″, —SO2—(CH2)r—OR13, —SO2—(CH2)r—CONR′R″, —(CH2)r—O—CO—R8, —(CH2)r—R12, —(CH2)r—R13, —(CH2)r—CO—Z2—R13, —(CH2)r—Z2—R13, or -alkenylene-CO2—(CH2)r—R13;
r, in each occurrence, is independently 1, 2, or 3;
R12, in each occurrence, is independently selected from a substituted or an unsubstituted heterocyclyl having up to 12 carbon atoms, comprising at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heterocyclyl is substituted with up to three substituents selected independently from an acyl, an alkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms, or —COOH;
R13, in each occurrence, is independently selected from: 1) hydrogen; or 2) a cycloalkyl, an aryl, a haloalkyl, a heterocyclyl, or an alkyl group optionally substituted with at least one hydroxyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R14, in each occurrence, is independently selected from a heterocyclyl, a cycloalkyl, or an aryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
Z2, in each occurrence, is selected independently from NR10 or O;
R′ and R″, in each occurrence, are independently selected from hydrogen or an alkyl having up to 12 carbon atoms; and
R15 and R16, in each occurrence, are independently selected from: 1) hydrogen; 2) an alkyl having up to 12 carbon atoms; or 3) —(CH2)r—O—R13, —(CH2)r—R14, —COR13, —(CH2)r—CO—Z2—R13, —CO2R13, —CO2—(CH2)r—R13, —CO2—(CH2)r—R12, —CO2—(CH2)r—CO—Z2—R13, —CO2—(CH2)r—OR13, —CO—(CH2)r—O—(CH2)r—O—(CH2)r—R13, —CO—(CH2)r—O(CH2)r—OR13, or —CO—NH—(CH2)r—OR13; or
R15 and R16 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety comprising up to 12 carbon atoms, optionally comprising at least one additional heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; wherein any substituted cyclic moiety is substituted with up to three substituents selected independently from: 1) hydroxyl; 2) an alkyl or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 3) COOR13, —Z2—(CH2)r—R13, —COR13, —CO2—(CH2)r—R13, —CO(CH2)r—O—R13, —(CH2)r—CO2—R13, —SO2R8, —SO2NR′R″, or —NR′R″;
wherein the —(CH2)r— linking moiety, in any occurrence, is optionally substituted with at least one group selected independently from hydroxyl, amino, or an alkyl having up to 3 carbon atoms;
when R1 and R2 do not form a monocyclic or bicyclic moiety, R1 and R2 are optionally substituted with 1 or 2 substituents, and when substituted, the substituents are selected independently from: 1) an alkyl, a cycloalkyl, a haloalkyl, an alkoxy, an aryl, a heteroaryl, or a heterocyclyl, any of which having up to 12 carbon atoms, wherein any heteroaryl or heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; or 2) halogen, cyano, or hydroxyl;
when R1 and R2 together with the diradical Z to which they are attached form a monocyclic or a bicyclic moiety, the cyclic moiety is optionally substituted with at least one substituent selected independently from: 1) halogen, cyano, or hydroxyl; 2) an alkyl, a haloalkyl, a cycloalkyl, an alkoxy, a cycloalkyl-substituted alkyl, an alkoxyalkyl, a cycloalkoxy, a haloalkoxy, an aryl, an aryloxy, an aralkyl, a heteroaryl or a heteroaryloxy, any of which having up to 12 carbon atoms, wherein any heteroaryl or heteroaryloxy comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 3) CO2R6, COR8, SO2R8, SO2NR6R7, or CONR6R7;
R4, R6, R7, and R8 are optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms;
and R5 is optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl having up to 12 carbon atoms.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein Z is N.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein:
R1 and R2 are selected independently from: an alkyl having up to 6 carbon atoms; a cycloalkyl having up to 6 carbon atoms; COR8; (CH2)nR5, or (CH2)nRdCO2Re, wherein n, in each occurrence, is 1 or 2;
or R1 and R2 together with the diradical Z to which they are attached form a substituted or an unsubstituted monocyclic or bicyclic moiety comprising up to 12 carbon atoms, and optionally comprising 1 or 2 heteroatoms or heterogroups selected independently from O, N, or NR10; wherein any optional substituent on the cyclic moiety selected from: 1) a cycloalkyl having up to 6 carbon atoms; or 2) an alkyl having up to 2 carbon atoms.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein: R3 is selected from:
1) cyano; 2) a substituted alkyl having up to 12 carbon atoms; 3) a substituted or an unsubstituted aryl, or a substituted or an unsubstituted 5-, 6-, or 7-membered heterocyclyl or heteroaryl, comprising 1, 2, or 3 heteroatoms or heterogroups selected independently from O, N, S, NR10, SO2, or CO, any of which having up to 12 carbon atoms; or 4) CO2R6, COR8, SO2R8, SO2NR6R7, CONR6R7, C(S)NR6R7, C(S)NHC(O)OR8, or C(S)SR8; or 5) a substituted or an unsubstituted group selected from 4,5-dihydro-oxazolyl, tetrazolyl, isoxazolyl, pyridyl, pyrimidinyl, oxadiazolyl, thiazolyl, or oxazolyl; wherein any optional substituents is selected independently from a) an alkyl or a haloalkyl, any of which having up to 12 carbon atoms; or b) CO2R9, wherein R9 is an alkyl having up to 12 carbon atoms;
wherein when R3 is an aryl, a heterocyclyl, or a heteroaryl, R3 is optionally substituted with up to three substituents selected independently from a halide, a hydroxyl, a cyano, an alkoxy having up to 12 carbon atoms, or R11;
R11 is selected independently from:
1) an alkyl, a haloalkyl, a cycloalkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms;
2) a substituted or an unsubstituted heteroaryl or heterocyclyl, any of which having up to 12 carbon atoms, comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heteroaryl or heterocyclyl is substituted with up to three substituents selected independently from an alkyl having up to 12 carbon atoms or a hydroxyl; or
3) —CO—Z2—R13, —CO—R12, —CO—Z2—(CH2)r—CO—Z2—R13, —NR15R16, —Z2—CO—(CH2)r—Z2—R13, —Z2—CO—(CH2)r—CO—Z2—R13, —O—(CH2)r—CO—Z2—R13, —O—(CH2)r—R14, —O—R12—(CH2)r—R13, —O—R14—CO—O—R13, —O—(CH2)r—R12, —O—(CH2)r—NR′R″, —O—(CH2)r—CO2—(CH2)r—R13, —O—(CH2)r—SR8, —O—(CH2)r—CO2—R13, —O—(CH2)r—CONR′R″, —O—(CH2)r—CONH—(CH2)r—OR13, —O—(CH2)r—SO2R8, —O—(CH2)r—R13, —O—(CH2)r—OR13, —O—(CH2)r—O—(CH2)r—OR13, —S—(CH2)r—CONR′R″, —SO2—(CH2)r—OR13, —SO2—(CH2)r—CONR′R″, —(CH2)r—O—CO—R8, —(CH2)r—R12, —(CH2)r—R13, —(CH2)r—CO—Z2—R13, —(CH2)r—Z2—R13, or -alkenylene-CO2—(CH2)r—R13;
r, in each occurrence, is independently 1, 2, or 3;
R12, in each occurrence, is independently selected from a substituted or an unsubstituted heterocyclyl having up to 12 carbon atoms, comprising at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heterocyclyl is substituted with up to three substituents selected independently from an acyl, an alkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms, or —COOH;
R13, in each occurrence, is independently selected from: 1) hydrogen; or 2) a cycloalkyl, an aryl, a haloalkyl, a heterocyclyl, or an alkyl group optionally substituted with at least one hydroxyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R14, in each occurrence, is independently selected from a heterocyclyl, a cycloalkyl, or an aryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
Z2, in each occurrence, is selected independently from NR10 or O;
R′ and R″, in each occurrence, are independently selected from hydrogen or an alkyl having up to 12 carbon atoms; and
R15 and R16, in each occurrence, are independently selected from: 1) hydrogen; 2) an alkyl having up to 12 carbon atoms; or 3) —(CH2)r—O—R13, —(CH2)r—R14, —COR13, —(CH2)r—CO—Z2—R13, —CO2R13, —CO2—(CH2)r—R13, —CO2—(CH2)r—R12, —CO2—(CH2)r—CO—Z2—R13, —CO2—(CH2)r—OR13, —CO—(CH2)r—O—(CH2)r—O—(CH2)r—R13, —CO—(CH2)r—O(CH2)r—OR13, or —CO—NH—(CH2)r—OR13;
or R15 and R16 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety comprising up to 12 carbon atoms, optionally comprising at least one additional heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; wherein any substituted cyclic moiety is substituted with up to three substituents selected independently from: 1) hydroxyl; 2) an alkyl or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 3) COOR13, —Z2—(CH2)r—R13, —COR13, —CO2—(CH2)r—R13, —CO(CH2)r—O—R13, —(CH2)r—CO2—R13, —SO2R8, —SO2NR′R″, or —NR′R″; and
wherein the —(CH2)r— linking moiety, in any occurrence, is optionally substituted with at least one group selected independently from hydroxyl, amino, or an alkyl having up to 3 carbon atoms.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein: R4, in each occurrence, is selected independently from: 1) a halogen or cyano; or 2) an alkyl or a haloalkyl, either of which having up to 4 carbon atoms; and m is 2 or 3.

### Claim 6

A compound having the formula:
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein:
A is:
wherein Ra, in each occurrence, is selected independently from: 1) a halogen; a hydroxyl, or a cyano; 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms; or 3) CO2R6; and p is an integer from 0 to 3, inclusive;
R1 and R2 are selected independently from: 1) a substituted or an unsubstituted alkyl, cycloalkyl, haloalkyl, aryl, heterocyclyl, heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; 2) CO2R6, COR8, SO2R8, SO2NR6R7, or CONR6R7; or 3) (CHRx)nR5 or (CH2)nRdCO2Re, wherein n, in each occurrence, is 1, 2, or 3; Rx, in each occurrence, is selected independently from an alkyl or an alkoxy, either of which having up to 12 carbon atoms, or hydrogen; Rd, in each occurrence, is selected independently from an alkyl, a cycloalkyl, an aryl, a heterocyclyl, or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; and Re, in each occurrence, is selected independently from an alkyl or a cycloalkyl, either of which having up to 12 carbon atoms, or hydrogen;
or R1 and R2 together with the diradical Z to which they are attached form a substituted or an unsubstituted monocyclic or bicyclic moiety comprising up to 12 carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms or heterogroups in addition to Z, selected independently from O, N, S, NR10, SO2, or CO;
R3 is selected from: 1) cyano; 2) a substituted or an unsubstituted aryl, or a substituted or an unsubstituted 5-, 6-, or 7-membered heterocyclyl or heteroaryl, any of which having up to 12 carbon atoms, comprising 1, 2, or 3 heteroatoms or heterogroups selected independently from O, N, S, NR10, SO2, or CO; or 3) CO2R6, COR8, SO2R8, SO2NR6R7, CONR6R7, C(S)NR6R7, C(S)NHC(O)OR8, or C(S)SR8; or 4) a substituted or an unsubstituted group selected from 4,5-dihydro-oxazolyl, tetrazolyl, isoxazolyl, pyridyl, pyrimidinyl, oxadiazolyl, thiazolyl, or oxazolyl; wherein any optional substituents is selected independently from a) an alkyl or a haloalkyl, any of which having up to 12 carbon atoms; or b) CO2R9, wherein R9 is an alkyl having up to 12 carbon atoms;
wherein when R3 is an aryl, a heterocyclyl, or a heteroaryl, R3 is optionally substituted with up to three substituents selected independently from a halide, a hydroxyl, a cyano, an alkoxy having up to 12 carbon atoms, or R11;
R4, in each occurrence, is selected independently from: 1) halogen, cyano, or hydroxy; 2) an alkyl, a cycloalkyl, a cycloalkoxy, an alkoxy, a haloalkyl, or a haloalkoxy, any of which having up to 12 carbon atoms; 3) a substituted or an unsubstituted aryl, aralkyl, aryloxy, heteroaryl, or heteroaryloxy, any of which having up to 12 carbon atoms, wherein any heteroaryl or heteroaryloxy comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 4) CO2R6, COR8, SO2R8, SO2NR6R7, CONR6R7, or (CH2)qNR6R7, wherein q is an integer from 0 to 5, inclusive;
m is an integer from 0 to 3, inclusive;
or R4m is a fused cyclic moiety comprising from 3 to 5 additional ring carbon atoms, inclusive, and optionally comprising at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R5, in each occurrence, is selected independently from: 1) an alkoxy, a haloalkoxy, or a cycloalkyl, any of which having up to 12 carbon atoms; 2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; 3) hydroxyl, NR6R7, CO2R6, COR8, or SO2R8; or 4) a substituted or an unsubstituted heterocycloalkyl comprising from 3 to 7 ring carbon atoms, and from 1 to 3 heteroatoms or heterogroups, inclusive, selected independently from O, N, S, NR10, SO2, or CO;
R6 and R7, in each occurrence, are selected independently from: 1) hydrogen; 2) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 3) a substituted or an unsubstituted aryl, aralkyl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; or R6 and R7 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety having from 3 to 7 ring carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms in addition to the nitrogen atom to which R6 and R7 are bonded, selected independently from O, N, S, or NR10;
R8, in each occurrence, is selected independently from: 1) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R10, in each occurrence, is selected independently from: 1) hydrogen; or 2) an alkyl, a cycloalkyl, a haloalkyl, an aryl, or an aralkyl, any of which having up to 12 carbon atoms;
Z is N
R11 is selected independently from:
1) an alkyl, a haloalkyl, a cycloalkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms;
2) a substituted or an unsubstituted heteroaryl or heterocyclyl, any of which having up to 12 carbon atoms, comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heteroaryl or heterocyclyl is substituted with up to three substituents selected independently from an alkyl having up to 12 carbon atoms or a hydroxyl; or
3) —CO—Z2—R13, —CO—R12, —CO—Z2—(CH2)r—CO—Z2—R13, —NR15R16, —Z2—CO—(CH2)r—Z2—R13, —Z2—CO—(CH2)r—CO—Z2—R13, —O—(CH2)r—CO—Z2—R13, —O—(CH2)r—R14, —O—R12—(CH2)r—R13, —O—R14—CO—O—R13, —O—(CH2)r—R12, —O—(CH2)r—NR′R″, —O—(CH2)r—CO2—(CH2)r—R13, —O—(CH2)r—CONR′R″, —O—(CH2)r—SR8, —O—(CH2)r—CO2—R13, —O—(CH2)r—O—(CH2)r—OR13, —O—(CH2)r—CONH—(CH2)r—OR13, —O—(CH2)r—SO2R8, —O—(CH2)r—R13, —O—(CH2)r—OR13, —S—(CH2)r—CONR′R″, —SO2—(CH2)r—OR13, —SO2—(CH2)r—CONR′R″, —(CH2)r—O—CO—R8, —(CH2)r—R12, —(CH2)r—R13, —(CH2)r—CO—Z2—R13, —(CH2)r—Z2—R13, or -alkenylene-CO2—(CH2)r—R13;
r, in each occurrence, is independently 1, 2, or 3;
R12, in each occurrence, is independently selected from a substituted or an unsubstituted heterocyclyl having up to 12 carbon atoms, comprising at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heterocyclyl is substituted with up to three substituents selected independently from an acyl, an alkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms, or —COOH;
R13, in each occurrence, is independently selected from: 1) hydrogen; or 2) a cycloalkyl, an aryl, a haloalkyl, a heterocyclyl, or an alkyl group optionally substituted with at least one hydroxyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R14, in each occurrence, is independently selected from a heterocyclyl, a cycloalkyl, or an aryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
Z2, in each occurrence, is selected independently from NR10 or O;
R′ and R″, in each occurrence, are independently selected from hydrogen or an alkyl having up to 12 carbon atoms; and
R15 and R16, in each occurrence, are independently selected from: 1) hydrogen; 2) an alkyl having up to 12 carbon atoms; or 3) —(CH2)r—O—R13, —(CH2)r—R14, —COR13, —(CH2)r—CO—Z2—R13, —CO2R13, —CO2—(CH2)r—R13, —CO2—(CH2)r—R12, —CO2—(CH2)r—CO—Z2—R13, —CO2—(CH2)r—OR13, —CO—(CH2)r—O—(CH2)r—O—(CH2)r—R13, —CO—(CH2)r—O(CH2)r—OR13, or —CO—NH—(CH2)r—OR13; or
R15 and R16 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety comprising up to 12 carbon atoms, optionally comprising at least one additional heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; wherein any substituted cyclic moiety is substituted with up to three substituents selected independently from: 1) hydroxyl; 2) an alkyl or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 3) COOR13, —Z2—(CH2)r—R13, —COR13, —CO2—(CH2)r—R13, —CO(CH2)r—O—R13, —(CH2)r—CO2—R13, —SO2R8, —SO2NR′R″, or —NR′R″;
wherein the —(CH2)r— linking moiety, in any occurrence, is optionally substituted with at least one group selected independently from hydroxyl, amino, or an alkyl having up to 3 carbon atoms;
when R1 and R2 do not form a monocyclic or bicyclic moiety, R1 and R2 are optionally substituted with 1 or 2 substituents, and when substituted, the substituents are selected independently from: 1) an alkyl, a cycloalkyl, a haloalkyl, an alkoxy, an aryl, a heteroaryl, or a heterocyclyl, any of which having up to 12 carbon atoms, wherein any heteroaryl or heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; or 2) halogen, cyano, or hydroxyl;
when R1 and R2 together with the diradical Z to which they are attached form a monocyclic or a bicyclic moiety, the cyclic moiety is optionally substituted with at least one substituent selected independently from: 1) halogen, cyano, or hydroxyl; 2) an alkyl, a haloalkyl, a cycloalkyl, an alkoxy, a cycloalkyl-substituted alkyl, an alkoxyalkyl, a cycloalkoxy, a haloalkoxy, an aryl, an aryloxy, an aralkyl, a heteroaryl or a heteroaryloxy, any of which having up to 12 carbon atoms, wherein any heteroaryl or heteroaryloxy comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 3) CO2R6, COR8, SO2R8, SO2NR6R7, or CONR6R7;
R4, R6, R7, and R8 are optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms;
and R5 is optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl having up to 12 carbon atoms.

### Claim 7 (depends on 6)

The compound according to claim 6, wherein Z is N.

### Claim 8 (depends on 6)

The compound according to claim 6, wherein:
R1 and R2 are selected independently from: 1) an alkyl having up to 6 carbon atoms; 2) a cycloalkyl having up to 6 carbon atoms; 3) COR8; or 4) (CH2)nR5 or (CH2)nRdCO2Re, wherein n, in each occurrence, is 1 or 2; Rd, in each occurrence, is selected independently from an alkyl, a cycloalkyl, an aryl, a heterocyclyl, or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; and Re, in each occurrence, is selected independently from an alkyl or a cycloalkyl, either of which having up to 12 carbon atoms, or hydrogen;
or R1 and R2 together with the diradical Z to which they are attached form a substituted or an unsubstituted monocyclic or bicyclic moiety comprising up to 12 carbon atoms, and optionally comprising 1 or 2 heteroatoms or heterogroups selected independently from O, N, or NR10; wherein any optional substituent on the cyclic moiety selected from: 1) a cycloalkyl having up to 6 carbon atoms; or 2) an alkyl having up to 2 carbon atoms.

### Claim 9 (depends on 6)

The compound according to claim 6, wherein:
R3 is selected from: 1) cyano; 2) a substituted or an unsubstituted aryl, or a substituted or an unsubstituted 5-, 6-, or 7-membered heterocyclyl or heteroaryl, comprising 1, 2, or 3 heteroatoms or heterogroups selected independently from O, N, S, NR10, SO2, or CO, any of which having up to 12 carbon atoms; or 3) CO2R6, CORS, SO2R8, SO2NR6R7, CONR6R7, C(S)NR6R7, C(S)NHC(O)OR8, or C(S)SR8; or 4) a substituted or an unsubstituted group selected from 4,5-dihydro-oxazolyl, tetrazolyl, isoxazolyl, pyridyl, pyrimidinyl, oxadiazolyl, thiazolyl, or oxazolyl; wherein any optional substituents is selected independently from a) an alkyl or a haloalkyl, any of which having up to 12 carbon atoms; or b) CO2R9, wherein R9 is an alkyl having up to 12 carbon atoms;
wherein when R3 is an aryl, a heterocyclyl, or a heteroaryl, R3 is optionally substituted with up to three substituents selected independently from a halide, a hydroxyl, a cyano, an alkoxy having up to 12 carbon atoms, or R11;
R11 is selected independently from:
1) an alkyl, a haloalkyl, a cycloalkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms;
2) a substituted or an unsubstituted heteroaryl or heterocyclyl, any of which having up to 12 carbon atoms, comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heteroaryl or heterocyclyl is substituted with up to three substituents selected independently from an alkyl having up to 12 carbon atoms or a hydroxyl; or
3) —CO—Z2—R13, —CO—R12, —CO—Z2—(CH2)r—CO—Z2—R13, —NR15R16, —Z2—CO—(CH2)r—Z2—R13, —Z2—CO—(CH2)r—CO—Z2—R13, —O—(CH2)r—CO—Z2—R13, —O—(CH2)r—R14, —O—R12—(CH2)r—R13, —O—R14—CO—O—R13, —O—(CH2)r—R12, —O—(CH2)r—NR′R″, —O—(CH2)r—CO2—(CH2)r—R13, —O—(CH2)r—SR8, —O—(CH2)r—CO2—R13, —O—(CH2)r—CONR′R″, —O—(CH2)r—CONH—(CH2)r—OR13, —O—(CH2)r—SO2R8, —O—(CH2)r—R13, —O—(CH2)r—OR13, —O—(CH2)r—O—(CH2)r—OR13, —S—(CH2)r—CONR′R″, —SO2—(CH2)r—OR13, —SO2—(CH2)r—CONR′R″, —(CH2)r—O—CO—R8, —(CH2)r—R12, —(CH2)r—R13, —(CH2)r—CO—Z2—R13, —(CH2)r—Z2—R13, or -alkenylene-CO2—(CH2)r—R13;
r, in each occurrence, is independently 1, 2, or 3;
R12, in each occurrence, is independently selected from a substituted or an unsubstituted heterocyclyl having up to 12 carbon atoms, comprising at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heterocyclyl is substituted with up to three substituents selected independently from an acyl, an alkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms, or —COOH;
R13, in each occurrence, is independently selected from: 1) hydrogen; or 2) a cycloalkyl, an aryl, a haloalkyl, a heterocyclyl, or an alkyl group optionally substituted with at least one hydroxyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R14, in each occurrence, is independently selected from a heterocyclyl, a cycloalkyl, or an aryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
Z2, in each occurrence, is selected independently from NR10 or O;
R′ and R″, in each occurrence, are independently selected from hydrogen or an alkyl having up to 12 carbon atoms; and
R15 and R16, in each occurrence, are independently selected from: 1) hydrogen; 2) an alkyl having up to 12 carbon atoms; or 3) —(CH2)r—O—R13, —(CH2)r—R14, —COR13, —(CH2)r—CO—Z2—R13, —CO2R13, —CO2—(CH2)r—R13, —CO2—(CH2)r—R12, —CO2—(CH2)r—CO—Z2—R13, —CO2—(CH2)r—OR13, —CO—(CH2)r—O—(CH2)r—O—(CH2)r—R13, —CO—(CH2)r—O(CH2)r—OR13, or —CO—NH—(CH2)r—OR13;
or R15 and R16 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety comprising up to 12 carbon atoms, optionally comprising at least one additional heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; wherein any substituted cyclic moiety is substituted with up to three substituents selected independently from: 1) hydroxyl; 2) an alkyl or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 3) COOR13, —Z2—(CH2)r—R13, —COR13, —CO2—(CH2)r—R13, —CO(CH2)r—O—R13, —(CH2)r—CO2—R13, —SO2R8, —SO2NR′R″, or —NR′R″; and
wherein the —(CH2)r— linking moiety, in any occurrence, is optionally substituted with at least one group selected independently from hydroxyl, amino, or an alkyl having up to 3 carbon atoms.

### Claim 10 (depends on 6)

The compound according to claim 6, wherein: R4, in each occurrence, is selected independently from: 1) halogen or cyano; or 2) an alkyl or a haloalkyl, any of which having up to 4 carbon atoms; and m is 2 or 3.

### Claim 11 (depends on 6)

The compound according to claim 6, having the formula:
(II);
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein:
R1 and R2 are selected independently from: 1) a substituted or an unsubstituted alkyl or a substituted or an unsubstituted cycloalkyl, either of which having up to 12 carbon atoms; 2) COR8 or CO2R6; or 3) (CH2)nR5 or (CH2)nRdCO2Re, wherein n, in each occurrence, is 1 or 2; Rd, in each occurrence, is selected independently from an alkyl, a cycloalkyl, an aryl, a heterocyclyl, or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; and Re, in each occurrence, is selected independently from an alkyl or a cycloalkyl, either of which having up to 12 carbon atoms, or hydrogen;
R3 is selected from: 1) cyano; 2) a substituted or an unsubstituted, 5-, 6-, or 7-membered heterocyclyl or heteroaryl, any of which having up to 12 carbon atoms, comprising 1, 2, or 3 heteroatoms or heterogroups selected independently from O, N, S, NR10, SO2, or CO; or 3) CO2R6, C(S)SR8, or C(S)NHC(O)OR8; or 4) a substituted or an unsubstituted group selected from 4,5-dihydro-oxazolyl, tetrazolyl, isoxazolyl, pyridyl, pyrimidinyl, oxadiazolyl, thiazolyl, or oxazolyl; wherein any optional substituents is selected independently from a) an alkyl or a haloalkyl, any of which having up to 12 carbon atoms; or b) CO2R9, wherein R9 is an alkyl having up to 12 carbon atoms;
R4, in each occurrence, is selected independently from: 1) halogen or cyano; or 2) an alkyl or a haloalkyl, either of which having up to 12 carbon atoms; m is an integer from 0 to 3, inclusive;
R5, in each occurrence, is selected independently from: 1) a cycloalkyl having up to 12 carbon atoms; or (2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R6 is selected from: 1) hydrogen; 2) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 3) a substituted or an unsubstituted aryl, aralkyl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R8, in each occurrence, is selected independently from an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms or a substituted or an unsubstituted aryl, heteroaryl, or heterocyclyl, any of which having up to 12 carbon atoms, wherein any heteroaryl or heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R10, in each occurrence, is selected independently from: 1) hydrogen; or 2) an alkyl, a cycloalkyl, a haloalkyl, an aryl, or an aralkyl, any of which having up to 12 carbon atoms;
Ra, in each occurrence, is selected independently from: 1) halogen, hydroxyl, or cyano; 2) an alkyl, or an alkoxy, any of which having up to 12 carbon atoms; or 3) CO2R6; and
p is an integer from 0 to 3, inclusive.

### Claim 12 (depends on 11)

The compound according to claim 11, having the formula:
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein: Rb is selected independently from: 1) hydrogen; or 2) an alkyl or a cycloalkyl, either of which having up to 12 carbon atoms.

### Claim 13 (depends on 6)

The compound according to claim 6 having the formula:
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein:
R1 and R2 are selected independently from: 1) a substituted or an unsubstituted alkyl, cycloalkyl, haloalkyl, aryl, heterocyclyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, NR10, or CO; 2) COR8, or 3) (CH)nR5, wherein n, in each occurrence, is 1, 2, or 3; Rx, in each occurrence, is selected independently from an alkyl or an alkoxy, either of which having up to 12 carbon atoms, or hydrogen;
or R1 and R2 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted monocyclic or bicyclic moiety comprising up to 12 carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms or heterogroups in addition to N, selected independently from O, N, —NR10 or CO;
R3 is selected from a substituted or an unsubstituted group selected from tetrazolyl, 1,3,4-oxadiazolyl, oxazolyl, pyrimidinyl, 4,5-dihydro-oxazolyl, pyridyl, thiazolyl, or isoxazolyl; wherein any optional substituent on R3 is selected independently from an alkyl or a haloalkyl, any of which having up to 12 carbon atoms;
R5, in each occurrence, is selected independently from: 1) an alkoxy, a haloalkoxy, or a cycloalkyl, any of which having up to 12 carbon atoms; 2) a substituted or an unsubstituted aryl, or heterocyclyl any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, NR10, or CO; 3) hydroxyl, NR6R7, COR8, or 4) a substituted or an unsubstituted heterocycloalkyl comprising from 3 to 7 ring carbon atoms, and from 1 to 3 heteroatoms or heterogroups, inclusive, selected independently from O, N, NR10, or CO;
R6 and R7, in each occurrence, are selected independently from: 1) hydrogen; 2) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 3) a substituted or an unsubstituted aryl, aralkyl, heterocyclyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, NR10, or CO; or
R6 and R7 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety having from 3 to 7 ring carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms in addition to the nitrogen atom to which R6 and R7 are bonded, selected independently from O, N, or NR10;
R8, in each occurrence, is selected independently from: 1) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, NR10, or CO;
R10, in each occurrence, is selected independently from: 1) hydrogen; or 2) an alkyl, a cycloalkyl, a haloalkyl, an aryl, or an aralkyl, any of which having up to 12 carbon atoms;
when R1 and R2 do not form a monocyclic or bicyclic moiety, R1 and R2 are optionally substituted with 1 or 2 substituents, and when substituted, the substituents are selected independently from: 1) an alkyl, a cycloalkyl, a haloalkyl, an alkoxy, an aryl, a heteroaryl, or a heterocyclyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, NR10, or CO; or 2) halogen, cyano, or hydroxyl;
when R1 and R2 together with the nitrogen atom to which they are attached form a monocyclic or a bicyclic moiety, the cyclic moiety is optionally substituted with at least one substituent selected independently from: 1) halogen, cyano, or hydroxyl; 2) an alkyl, a haloalkyl, a cycloalkyl, an alkoxy, a cycloalkyl-substituted alkyl, an alkoxyalkyl, a cycloalkoxy, a haloalkoxy, an aryl, an aryloxy, or an aralkyl, any of which having up to 12 carbon atoms;
R4, R6, R7, and R8 are optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms;
R5 is optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl having up to 12 carbon atoms;
wherein Ra, in each occurrence, is selected independently from: 1) a halogen; a hydroxyl, or a cyano; 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms; or 3) CO2R6; and
p is an integer from 0 to 3, inclusive.

### Claim 14 (depends on 13)

The compound according to claim 13, having the formula:
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein: Ra is selected from methyl, ethyl, or methoxy.

### Claim 15

A compound wherein the compound is selected from:
and combinations thereof.

### Claim 16

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound having the formula:
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein:
A is a substituted or an unsubstituted quinoline moiety having the formula:
wherein Ra, in each occurrence, is selected independently from: 1) a halogen; a hydroxyl, or a cyano; 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms; or 3) CO2R6; and p is an integer from 0 to 3, inclusive;
R1 and R2 are selected independently from: 1) hydrogen; 2) a substituted or an unsubstituted alkyl, cycloalkyl, haloalkyl, aryl, heterocyclyl, heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; 3) CO2R6, COR8, SO2R8, SO2NR6R7, or CONR6R7; or 4) (CHRx)nR5 or (CH2)nRdCO2Re, wherein n, in each occurrence, is 1, 2, or 3; Rx, in each occurrence, is selected independently from an alkyl or an alkoxy, either of which having up to 12 carbon atoms, or hydrogen; Rd, in each occurrence, is selected independently from an alkyl, a cycloalkyl, an aryl, a heterocyclyl, or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; and Re, in each occurrence, is selected independently from an alkyl or a cycloalkyl, either of which having up to 12 carbon atoms, or hydrogen;
or R1 and R2 together with the diradical Z to which they are attached form a substituted or an unsubstituted monocyclic or bicyclic moiety comprising up to 12 carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms or heterogroups in addition to Z, selected independently from O, N, S, NR10, SO2, or CO;
R3 is selected from: 1) hydrogen or cyano; 2) a substituted alkyl having up to 12 carbon atoms; 3) a substituted or an unsubstituted aryl, or a substituted or an unsubstituted 5-, 6-, or 7-membered heterocyclyl or heteroaryl, any of which having up to 12 carbon atoms, comprising 1, 2, or 3 heteroatoms or heterogroups selected independently from O, N, S, NR10, SO2, or CO; or 4) CO2R6, COR8, SO2R8, SO2NR6R7, CONR6R7, C(S)NR6R7, C(S)NHC(O)OR8, or C(S)SR8; or 5) a substituted or an unsubstituted group selected from 4,5-dihydro-oxazolyl, tetrazolyl, isoxazolyl, pyridyl, pyrimidinyl, oxadiazolyl, thiazolyl, or oxazolyl; wherein any optional substituent is selected independently from: a) an alkyl or haloalkyl, any of which having up to 12 carbon atoms; or b) CO2R9, wherein R9 is an alkyl having up to 12 carbon atoms;
wherein when R3 is an aryl, a heterocyclyl, or a heteroaryl, R3 is optionally substituted with up to three substituents selected independently from a halide, a hydroxyl, a cyano, an alkoxy having up to 12 carbon atoms, or R11;
R4, in each occurrence, is selected independently from: 1) halogen, cyano, or hydroxy; 2) an alkyl, a cycloalkyl, a cycloalkoxy, an alkoxy, a haloalkyl, or a haloalkoxy, any of which having up to 12 carbon atoms; 3) a substituted or an unsubstituted aryl, aralkyl, aryloxy, heteroaryl, or heteroaryloxy, any of which having up to 12 carbon atoms, wherein any heteroaryl or heteroaryloxy comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 4) CO2R6, COR8, SO2R8, SO2NR6R7, CONR6R7, or (CH2)qNR6R7, wherein q is an integer from 0 to 5, inclusive;
m is an integer from 0 to 3, inclusive;
or R4m is a fused cyclic moiety comprising from 3 to 5 additional ring carbon atoms, inclusive, and optionally comprising at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R5, in each occurrence, is selected independently from: 1) an alkoxy, a haloalkoxy, or a cycloalkyl, any of which having up to 12 carbon atoms; 2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; 3) hydroxyl, NR6R7, CO2R6, COR8, or SO2R8; or 4) a substituted or an unsubstituted heterocycloalkyl comprising from 3 to 7 ring carbon atoms, and from 1 to 3 heteroatoms or heterogroups, inclusive, selected independently from O, N, S, NR10, SO2, or CO;
R6 and R7, in each occurrence, are selected independently from: 1) hydrogen; 2) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 3) a substituted or an unsubstituted aryl, aralkyl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
or R6 and R7 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety having from 3 to 7 ring carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms in addition to the nitrogen atom to which R6 and R7 are bonded, selected independently from O, N, S, or NR10;
R8, in each occurrence, is selected independently from: 1) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R10, in each occurrence, is selected independently from: 1) hydrogen; or 2) an alkyl, a cycloalkyl, a haloalkyl, an aryl, or an aralkyl, any of which having up to 12 carbon atoms;
Z is N; or the ZR1 moiety is S, CO, or SO2;
R11 is selected independently from:
1) an alkyl, a haloalkyl, a cycloalkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms;
2) a substituted or an unsubstituted heteroaryl or heterocyclyl, any of which having up to 12 carbon atoms, comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heteroaryl or heterocyclyl is substituted with up to three substituents selected independently from an alkyl having up to 12 carbon atoms or a hydroxyl; or
3) —CO—Z2—R13, —CO—R12, —CO—Z2—(CH2)r—CO—Z2—R13, —NR15R16, —Z2—CO—(CH2)r—Z2—R13, —Z2—CO—(CH2)r—CO—Z2—R13, —O—(CH2)r—CO—Z2—R13, —O—(CH2)r—R14, —O—R12—(CH2)r—R13, —O—R14—CO—O—R13, —O—(CH2)r—R12, —O—(CH2)r—NR′R″, —O—(CH2)r—CO2—(CH2)r—R13, —O—(CH2)r—SR8, —O—(CH2)r—CO2—R13, —O—(CH2)r—CON′R″, —O—(CH2)r—CONH—(CH2)r—OR13, —O—(CH2)r—SO2R8, —O—(CH2)r—R13, —O—(CH2)r—OR13, —O—(CH2)r—O—(CH2)r—OR13, —S—(CH2)r—CONR′R″, —SO2—(CH2)r—OR13, —SO2—(CH2)r—CON′R″, —(CH2)r—O—CO—R8, —(CH2)r—R12, —(CH2)r—R13, —(CH2)r—CO—Z2—R13, —(CH2)r—Z2—R13, or -alkenylene-CO2—(CH2)r—R13;
r, in each occurrence, is independently 1, 2, or 3;
R12, in each occurrence, is independently selected from a substituted or an unsubstituted heterocyclyl having up to 12 carbon atoms, comprising at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heterocyclyl is substituted with up to three substituents selected independently from an acyl, an alkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms, or —COOH;
R13, in each occurrence, is independently selected from: 1) hydrogen; or 2) a cycloalkyl, an aryl, a haloalkyl, a heterocyclyl, or an alkyl group optionally substituted with at least one hydroxyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R14, in each occurrence, is independently selected from a heterocyclyl, a cycloalkyl, or an aryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
Z2, in each occurrence, is selected independently from NR10 or O;
R′ and R″, in each occurrence, are independently selected from hydrogen or an alkyl having up to 12 carbon atoms; and
R15 and R16, in each occurrence, are independently selected from: 1) hydrogen; 2) an alkyl having up to 12 carbon atoms; or 3) —(CH2)r—O—R13, —(CH2)r—R14, —COR13, —(CH2)r—CO—Z2—R13, —CO2R13, —CO2—(CH2)r—R13, —CO2—(CH2)r—R12, —CO2—(CH2)r—CO—Z2—R13, —CO2—(CH2)r—OR13, —CO—(CH2)r—O—(CH2)r—O—(CH2)r—R13, —CO—(CH2)r—O(CH2)r—OR13, or —CO—NH—(CH2)r—OR13;
or R15 and R16 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety comprising up to 12 carbon atoms, optionally comprising at least one additional heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; wherein any substituted cyclic moiety is substituted with up to three substituents selected independently from: 1) hydroxyl; 2) an alkyl or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 3) COOR13, —Z2—(CH2)r—R13, —COR13, —CO2—(CH2)r—R13, —CO(CH2)r—O—R13, —(CH2)r—CO2—R13, —SO2R8, —SO2NR′R″, or —NR′R″;
wherein the —(CH2)r— linking moiety, in any occurrence, is optionally substituted with at least one group selected independently from hydroxyl, amino, or an alkyl having up to 3 carbon atoms;
when R1 and R2 do not form a monocyclic or bicyclic moiety, R1 and R2 are optionally substituted with 1 or 2 substituents, and when substituted, the substituents are selected independently from: 1) an alkyl, a cycloalkyl, a haloalkyl, an alkoxy, an aryl, a heteroaryl, or a heterocyclyl, any of which having up to 12 carbon atoms, wherein any heteroaryl or heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; or 2) halogen, cyano, or hydroxyl;
when R1 and R2 together with the diradical Z to which they are attached form a monocyclic or a bicyclic moiety, the cyclic moiety is optionally substituted with at least one substituent selected independently from: 1) halogen, cyano, or hydroxyl; 2) an alkyl, a haloalkyl, a cycloalkyl, an alkoxy, a cycloalkyl-substituted alkyl, an alkoxyalkyl, a cycloalkoxy, a haloalkoxy, an aryl, an aryloxy, an aralkyl, a heteroaryl or a heteroaryloxy, any of which having up to 12 carbon atoms, wherein any heteroaryl or heteroaryloxy comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 3) CO2R6, COR8, SO2R8, SO2NR6R7, or CONR6R7;
R4, R6, R7, and R8 are optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms;
and R5 is optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl having up to 12 carbon atoms.

### Claim 17 (depends on 16)

The pharmaceutical composition according to claim 16, further comprising: optionally, a pharmaceutically acceptable auxiliary; optionally, a pharmaceutically acceptable preservative; optionally, a pharmaceutically acceptable excipient; and optionally, a pharmaceutically acceptable diluent.

### Claim 18 (depends on 16)

The pharmaceutical composition according to claim 16, wherein the composition is in the form of a tablet, a capsule, a cachet, a powder, a granule, a solution, a suspension, an emulsion, a bolus, a lozenge, a suppository, a pessary, a tampon, a cream, a gel, a paste, a foam, a spray, an aerosol, a microcapsule, a liposome, a transdermal patch, a pastille, a paste, or a mouthwash.

### Claim 19

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound that has the formula:
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein:
A is:
wherein Ra, in each occurrence, is selected independently from: 1) a halogen; a hydroxyl, or a cyano; 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms; or 3) CO2R6; and p is an integer from 0 to 3, inclusive;
R1 and R2 are selected independently from: 1) a substituted or an unsubstituted alkyl, cycloalkyl, haloalkyl, aryl, heterocyclyl, heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; 2) CO2R6, COR8, SO2R8, SO2NR6R7, or CONR6R7; or 3) (CHRx)nR5 or (CH2)nRdCO2Re, wherein n, in each occurrence, is 1, 2, or 3; Rx, in each occurrence, is selected independently from an alkyl or an alkoxy, either of which having up to 12 carbon atoms, or hydrogen; Rd, in each occurrence, is selected independently from an alkyl, a cycloalkyl, an aryl, a heterocyclyl, or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; and Re, in each occurrence, is selected independently from an alkyl or a cycloalkyl, either of which having up to 12 carbon atoms, or hydrogen;
or R1 and R2 together with the diradical Z to which they are attached form a substituted or an unsubstituted monocyclic or bicyclic moiety comprising up to 12 carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms or heterogroups in addition to Z, selected independently from O, N, S, NR10, SO2, or CO;
R3 is selected from: 1) hydrogen or cyano; 2) a substituted or an unsubstituted aryl, or a substituted or an unsubstituted 5-, 6-, or 7-membered heterocyclyl or heteroaryl, any of which having up to 12 carbon atoms, comprising 1, 2, or 3 heteroatoms or heterogroups selected independently from O, N, S, NR10, SO2, or CO; or 3) CO2R6, COR8, SO2R8, SO2NR6R7, CONR6R7, C(S)NR6R7, C(S)NHC(O)OR8, or C(S)SR8; or 4) a substituted or an unsubstituted group selected from 4,5-dihydro-oxazolyl, tetrazolyl, isoxazolyl, pyridyl, pyrimidinyl, oxadiazolyl, thiazolyl, or oxazolyl; wherein any optional substituent is selected independently from: a) an alkyl or haloalkyl, any of which having up to 12 carbon atoms; or b) CO2R9, wherein R9 is an alkyl having up to 12 carbon atoms;
wherein when R3 is an aryl, a heterocyclyl, or a heteroaryl, R3 is optionally substituted with up to three substituents selected independently from a halide, a hydroxyl, a cyano, an alkoxy having up to 12 carbon atoms, or R11;
R4, in each occurrence, is selected independently from: 1) halogen, cyano, or hydroxy; 2) an alkyl, a cycloalkyl, a cycloalkoxy, an alkoxy, a haloalkyl, or a haloalkoxy, any of which having up to 12 carbon atoms; 3) a substituted or an unsubstituted aryl, aralkyl, aryloxy, heteroaryl, or heteroaryloxy, any of which having up to 12 carbon atoms, wherein any heteroaryl or heteroaryloxy comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10; or 4) CO2R6, COR8, SO2R8, SO2NR6R7, CONR6R7, or (CH2)qNR6R7, wherein q is an integer from 0 to 5, inclusive;
m is an integer from 0 to 3, inclusive;
R5, in each occurrence, is selected independently from: 1) an alkoxy, a haloalkoxy, or a cycloalkyl, any of which having up to 12 carbon atoms; 2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; 3) hydroxyl, NR6R7, CO2R6, COR8, or SO2R8; or 4) a substituted or an unsubstituted heterocycloalkyl comprising from 3 to 7 ring carbon atoms, and from 1 to 3 heteroatoms or heterogroups, inclusive, selected independently from O, N, S, NR10, SO2, or CO;
R6 and R7, in each occurrence, are selected independently from: 1) hydrogen; 2) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 3) a substituted or an unsubstituted aryl, aralkyl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
or R6 and R7 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety having from 3 to 7 ring carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms in addition to the nitrogen atom to which R6 and R7 are bonded, selected independently from O, N, S, or NR10;
R8, in each occurrence, is selected independently from: 1) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R10, in each occurrence, is selected independently from: 1) hydrogen; or 2) an alkyl, a cycloalkyl, a haloalkyl, an aryl, or an aralkyl, any of which having up to 12 carbon atoms;
Z is N; or the ZR1 moiety is S, CO, or SO2;
R11 is selected independently from:
1) an alkyl, a haloalkyl, a cycloalkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms;
2) a substituted or an unsubstituted heteroaryl or heterocyclyl, any of which having up to 12 carbon atoms, comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heteroaryl or heterocyclyl is substituted with up to three substituents selected independently from an alkyl having up to 12 carbon atoms or a hydroxyl; or
3) —CO—Z2—R13, —CO—R12, —CO—Z2—(CH2)r—CO—Z2—R13, —NR15R16, —Z2—CO—(CH2)r—Z2—R13, —Z2—CO—(CH2)r—CO—Z2—R13, —O—(CH2)r—CO—Z2—R13, —O—(CH2)r—R14, —O—R12—(CH2)r—R13, —O—R14—CO—O—R13, —O—(CH2)r—R12, —O—(CH2)r—NR′R″, —O—(CH2)r—CO2—(CH2)r—R13, —O—(CH2)r—SR8, —O—(CH2)r—CO2—R13, —O—(CH2)r—CONR′R″, —O—(CH2)r—CONH—(CH2)r—OR13, —O—(CH2)r—SO2R8, —O—(CH2)r—R13, —O—(CH2)r—OR13, —O—(CH2)r—O—(CH2)r—OR13, —S—(CH2)r—CONR′R″, —SO2—(CH2)r—OR13, —SO2—(CH2)r—CONR′R″, —(CH2)r—O—CO—R8, —(CH2)r—R12, —(CH2)r—R13, —(CH2)r—CO—Z2—R13, —(CH2)r—Z2—R13, or -alkenylene-CO2—(CH2)r—R13;
r, in each occurrence, is independently 1, 2, or 3;
R12, in each occurrence, is independently selected from a substituted or an unsubstituted heterocyclyl having up to 12 carbon atoms, comprising at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO, wherein any substituted heterocyclyl is substituted with up to three substituents selected independently from an acyl, an alkyl, or an alkoxycarbonyl, any of which having up to 12 carbon atoms, or —COOH;
R13, in each occurrence, is independently selected from: 1) hydrogen; or 2) a cycloalkyl, an aryl, a haloalkyl, a heterocyclyl, or an alkyl group optionally substituted with at least one hydroxyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R14, in each occurrence, is independently selected from a heterocyclyl, a cycloalkyl, or an aryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
Z2, in each occurrence, is selected independently from NR10 or O;
R′ and R″, in each occurrence, are independently selected from hydrogen or an alkyl having up to 12 carbon atoms; and
R15 and R16, in each occurrence, are independently selected from: 1) hydrogen; 2) an alkyl having up to 12 carbon atoms; or 3) —(CH2)r—O—R13, —(CH2)r—R14, —COR13, —(CH2)r—CO—Z2—R13, —CO2R13, —CO2—(CH2)r—R13, —CO2—(CH2)r—R12, —CO2—(CH2)r—CO—Z2—R13, —CO2—(CH2)r—OR13, —CO—(CH2)r—O—(CH2)r—O—(CH2)r—R13, —CO—(CH2)r—O(CH2)r—OR13, or —CO—NH—(CH2)r—OR13;
or R15 and R16 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety comprising up to 12 carbon atoms, optionally comprising at least one additional heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; wherein any substituted cyclic moiety is substituted with up to three substituents selected independently from: 1) hydroxyl; 2) an alkyl or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 3) COOR13, —Z2—(CH2)r—R13, —COR13, —CO2—(CH2)r—R13, —CO(CH2)r—O—R13, —(CH2)r—CO2—R13, —SO2R8, —SO2NR′R″, or —NR′R″;
wherein the —(CH2)r— linking moiety, in any occurrence, is optionally substituted with at least one group selected independently from hydroxyl, amino, or an alkyl having up to 3 carbon atoms;
when R1 and R2 do not form a monocyclic or bicyclic moiety, R1 and R2 are optionally substituted with 1 or 2 substituents, and when substituted, the substituents are selected independently from: 1) an alkyl, a cycloalkyl, a haloalkyl, an alkoxy, an aryl, a heteroaryl, or a heterocyclyl, any of which having up to 12 carbon atoms, wherein any heteroaryl or heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; or 2) halogen, cyano, or hydroxyl;
when R1 and R2 together with the diradical Z to which they are attached form a monocyclic or a bicyclic moiety, the cyclic moiety is optionally substituted with at least one substituent selected independently from: 1) halogen, cyano, or hydroxyl; 2) an alkyl, a haloalkyl, a cycloalkyl, an alkoxy, a cycloalkyl-substituted alkyl, an alkoxyalkyl, a cycloalkoxy, a haloalkoxy, an aryl, an aryloxy, an aralkyl, a heteroaryl or a heteroaryloxy, any of which having up to 12 carbon atoms, wherein any heteroaryl or heteroaryloxy comprises at least one heteroatom or heterogroup selected independently from O, N, S, or NR10; or 3) CO2R6, COR8, SO2R8, SO2NR6R7, or CONR6R7;
R4, R6, R7, and R8 are optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms; and
R5 is optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl having up to 12 carbon atoms.

### Claim 20 (depends on 19)

The pharmaceutical composition according to claim 19,
wherein the at least one compound has the formula:
(II);
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein:
R1 and R2 are selected independently from: 1) a substituted or an unsubstituted alkyl or a substituted or an unsubstituted cycloalkyl, either of which having up to 12 carbon atoms; 2) COR8 or CO2R6; or 3) (CH2)nR5 or (CH2)nRdCO2Re, wherein n, in each occurrence, is 1 or 2; Rd, in each occurrence, is selected independently from an alkyl, a cycloalkyl, an aryl, a heterocyclyl, or a heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO; and Re, in each occurrence, is selected independently from an alkyl or a cycloalkyl, either of which having up to 12 carbon atoms, or hydrogen;
R3 is selected from: 1) hydrogen or cyano; 2) a substituted or an unsubstituted, 5-, 6-, or 7-membered heterocyclyl or heteroaryl, any of which having up to 12 carbon atoms, comprising 1, 2, or 3 heteroatoms or heterogroups selected independently from O, N, S, NR10, SO2, or CO; or 3) CO2R6, C(S)SR8, or C(S)NHC(O)OR8; or 5) a substituted or an unsubstituted group selected from 4,5-dihydro-oxazolyl, tetrazolyl, isoxazolyl, pyridyl, pyrimidinyl, oxadiazolyl, thiazolyl, or oxazolyl; wherein any optional substituent is selected independently from: a) an alkyl or haloalkyl, any of which having up to 12 carbon atoms; or b) CO2R9, wherein R9 is an alkyl having up to 12 carbon atoms;
R4, in each occurrence, is selected independently from: 1) halogen or cyano; or 2) an alkyl or a haloalkyl, either of which having up to 12 carbon atoms; m is an integer from 0 to 3, inclusive;
R5, in each occurrence, is selected independently from: 1) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R6 is selected from: 1) hydrogen; 2) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 3) a substituted or an unsubstituted aryl, aralkyl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R8, in each occurrence, is selected independently from an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms or a substituted or an unsubstituted aryl, heteroaryl, or heterocyclyl, any of which having up to 12 carbon atoms, wherein any heteroaryl or heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, S, NR10, SO2, or CO;
R10, in each occurrence, is selected independently from: 1) hydrogen; or 2) an alkyl, a cycloalkyl, a haloalkyl, an aryl, or an aralkyl, any of which having up to 12 carbon atoms;
Ra, in each occurrence, is selected independently from: 1) halogen, hydroxyl, or cyano; 2) an alkyl, or an alkoxy, any of which having up to 12 carbon atoms; or 3) CO2R6; and
p is an integer from 0 to 3, inclusive.

### Claim 21 (depends on 19)

The pharmaceutical composition according to claim 19, wherein the at least one compound has the formula:
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein: Rb is selected independently from: 1) hydrogen; or 2) an alkyl or a cycloalkyl, either of which having up to 12 carbon atoms.

### Claim 22

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound having the formula:
or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein:
R1 and R2 are selected independently from: 1) a substituted or an unsubstituted alkyl, cycloalkyl, haloalkyl, aryl, heterocyclyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, NR10, or CO; 2) COR8, or 3) (CHRx)nR5, wherein n, in each occurrence, is 1, 2, or 3; Rx, in each occurrence, is selected independently from an alkyl or an alkoxy, either of which having up to 12 carbon atoms, or hydrogen;
or R1 and R2 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted monocyclic or bicyclic moiety comprising up to 12 carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms or heterogroups in addition to Z, selected independently from O, N, —NR10 or CO;
R3 is selected from a substituted or an unsubstituted group selected from tetrazolyl, 1,3,4-oxadiazolyl, oxazolyl, pyrimidinyl, 4,5-dihydro-oxazolyl, pyridyl, thiazolyl, or isoxazolyl; wherein any optional substituent on R3 is selected independently from an alkyl or a haloalkyl, any of which having up to 12 carbon atoms;
R5, in each occurrence, is selected independently from: 1) an alkoxy, a haloalkoxy, or a cycloalkyl, any of which having up to 12 carbon atoms; 2) a substituted or an unsubstituted aryl, or heterocyclyl any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, NR10, or CO; 3) hydroxyl, NR6R7, COR8, or 4) a substituted or an unsubstituted heterocycloalkyl comprising from 3 to 7 ring carbon atoms, and from 1 to 3 heteroatoms or heterogroups, inclusive, selected independently from O, N, NR10, or CO;
R6 and R7, in each occurrence, are selected independently from: 1) hydrogen; 2) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 3) a substituted or an unsubstituted aryl, aralkyl, heterocyclyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, NR10, or CO; or
R6 and R7 together with the nitrogen atom to which they are attached form a substituted or an unsubstituted cyclic moiety having from 3 to 7 ring carbon atoms, and optionally comprising 1, 2, or 3 heteroatoms in addition to the nitrogen atom to which R6 and R7 are bonded, selected independently from O, N, or NR10;
R8, in each occurrence, is selected independently from: 1) an alkyl, a cycloalkyl, or a haloalkyl, any of which having up to 12 carbon atoms; or 2) a substituted or an unsubstituted aryl, heterocyclyl, or heteroaryl, any of which having up to 12 carbon atoms, wherein any heterocyclyl or heteroaryl comprises at least one heteroatom or heterogroup selected independently from O, N, NR10, or CO;
R10, in each occurrence, is selected independently from: 1) hydrogen; or 2) an alkyl, a cycloalkyl, a haloalkyl, an aryl, or an aralkyl, any of which having up to 12 carbon atoms;
Z is N;
when R1 and R2 do not form a monocyclic or bicyclic moiety, R1 and R2 are optionally substituted with 1 or 2 substituents, and when substituted, the substituents are selected independently from: 1) an alkyl, a cycloalkyl, a haloalkyl, an alkoxy, an aryl, a heteroaryl, or a heterocyclyl, any of which having up to 12 carbon atoms, wherein any heterocyclyl comprises at least one heteroatom or heterogroup selected independently from O, N, NR10, or CO; or 2) halogen, cyano, or hydroxyl;
when R1 and R2 together with the nitrogen atom to which they are attached form a monocyclic or a bicyclic moiety, the cyclic moiety is optionally substituted with at least one substituent selected independently from: 1) halogen, cyano, or hydroxyl; 2) an alkyl, a haloalkyl, a cycloalkyl, an alkoxy, a cycloalkyl-substituted alkyl, an alkoxyalkyl, a cycloalkoxy, a haloalkoxy, an aryl, an aryloxy, or an aralkyl, any of which having up to 12 carbon atoms;
R4, R6, R7, and R8 are optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms;
R5 is optionally substituted with at least one substituent, and when substituted, the substituents are selected independently from: 1) halide, hydroxy, cyano, or NR6R7; or 2) an alkyl having up to 12 carbon atoms; and
wherein Ra, in each occurrence, is selected independently from: 1) a halogen; a hydroxyl, or a cyano; 2) an alkyl or an alkoxy, any of which having up to 12 carbon atoms; or 3) CO2R6; and
p is an integer from 0 to 3, inclusive.

### Claim 23 (depends on 22)

The pharmaceutical composition according to claim 22, wherein the at least one compound has the formula: or a salt, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof, or any combination thereof, wherein: Ra is selected from methyl, ethyl, or methoxy.

### Claim 24

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound, wherein the compound is:
and combinations thereof.

### Claim 25 (depends on 24)

The pharmaceutical composition according to claim 24, further comprising:
optionally, a pharmaceutically acceptable auxiliary;
optionally, a pharmaceutically acceptable preservative;
optionally, a pharmaceutically acceptable excipient; and
optionally, a pharmaceutically acceptable diluent.

### Claim 26 (depends on 25)

The pharmaceutical composition according to claim 25, wherein the composition is in the form of a tablet, a capsule, a cachet, a powder, a granule, a solution, a suspension, an emulsion, a bolus, a lozenge, a suppository, a pessary, a tampon, a cream, a gel, a paste, a foam, a spray, an aerosol, a microcapsule, a liposome, a transdermal patch, a pastille, a paste, or a mouthwash.

### Claim 27

A compound selected from the group consisting of:

### Claim 28

A pharmaceutical composition comprising one or more compounds selected from the group consisting of: