# US 9,751,864 B2 · Methods for preparing triazole agonists of the APJ receptor

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- Number: US 9,751,864 B2
- Document ID: US9751864B2
- Status: Granted
- Kind: B2
- Application number: 15/298,434
- Filed: 2016-10-20
- Published: 2017-02-16
- Granted: 2017-09-05
- Earliest claimed: 2015-05-20
- Assignees: Amgen Inc.
- Applicants: Amgen Inc.
- Inventors: Ning Chen; Xiaoqi Chen; Richard V. Connors; Jeffrey Deignan; Paul John Dransfield; Xiaohui Du; Zice Fu; Julie Anne Heath; Daniel B. Horne; Jonathan Houze; Matthew R. Kaller; David John Kopecky; Su-Jen Lai; Zhihua Ma; Lawrence R. McGee; Julio C. Medina; Jeffrey T. Mihalic; Nobuko Nishimura; Steven H. Olson; Vatee Pattaropong; Xiaodong Wang; Kevin Yang; Mikkel V. DeBenedetto; Robert P. Farrell; Simon J. Hedley; Ted C. Judd
- Web page: https://patentgrep.com/patent/US9751864B2

## CPC

- C07D 401/14: containing three or more hetero 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 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/497: containing further heterocyclic rings
- A61K 31/501: not condensed and containing further heterocyclic rings
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/695: Silicon compounds
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/12: Antihypertensives
- A61P 13/12: of the kidneys
- C07B 57/00: Separation of optically-active compounds
- C07B 59/002: {Heterocyclic compounds}
- C07C 311/13: the carbon skeleton containing six-membered aromatic rings
- C07D 211/54: Sulfur atoms
- C07D 213/61: Halogen atoms or nitro radicals
- C07D 213/71: to which a second hetero atom is attached
- C07D 213/82: in position 3
- C07D 239/26: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 239/30: Halogen atoms or nitro radicals
- C07D 239/34: One oxygen atom
- C07D 241/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 241/18: Oxygen or sulfur atoms
- C07D 241/24: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D 295/16: acylated on ring nitrogen atoms
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07F 7/08: Compounds having one or more C—Si linkages
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- C07B 2200/07: Optical isomers
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

Methods of preparing compounds of Formula VI, salts thereof, tautomers thereof, or salts of the tautomers include cyclizing compounds of Formula V, salts thereof, tautomers thereof, or salts of the tautomers. Compounds of Formula VI and Formula V have the following structures: where the definitions of the variables are provided herein.

## Claims

### Claim 1

A method for preparing a compound of Formula VI, a salt thereof, a tautomer thereof, or a salt of the tautomer:
the method comprising:
a) cyclizing a compound of Formula V, a salt thereof, a tautomer thereof, or a salt of the tautomer in the presence of an acid or a base to form the compound of Formula VI, the salt thereof, the tautomer thereof, or the salt of the tautomer,
wherein:
R1 is an unsubstituted pyridyl, pyridonyl, or pyridine N-oxide, or is a pyridyl, pyridonyl, or pyridine N-oxide substituted with 1, 2, 3, or 4 R1a substituents;
R1a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —C2-C6 alkenyl, —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl)-OH, —O—(C1-C6 haloalkyl)-O—(C1-C6 alkyl), —O—(C1-C6 perhaloalkyl)-OH, —O—(C1-C6 perhaloalkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(═O)—(C1-C6 alkyl), —C(═O)OH, —C(═O)—O—(C1-C6 alkyl), —C(═O)NH2, —C(═O)NH(C1-C6 alkyl), —C(═O)N(C1-C6 alkyl)2, phenyl, —C(═O)-(heterocyclyl), or a heterocyclyl group, wherein the heterocyclyl group of the —C(═O)-(heterocyclyl) or heterocyclyl group is a 3 to 7 membered ring containing 1, 2, or 3 heteroatoms selected from N, O, or S;
R3 is selected from an unsubstituted C1-C10 alkyl, a C1-C10 alkyl substituted with 1, 2, or 3 R3a substituents, a group of formula —(CR3bR3c)-Q, a group of formula NH—(CR3bR3c)-Q, a group of formula —(CR3bR3c)—C(═O)-Q, a group of formula —(CR3dR3e)—(CR3fR3g)-Q, a group of formula —(CR3b═CR3c)-Q, or a group of formula -(heterocyclyl)-Q, wherein the heterocyclyl of the -(heterocyclyl)-Q has 5 to 7 ring members of which 1, 2, or 3 are heteroatoms selected from N, O, or S and is unsubstituted or is substituted with 1, 2, or 3 R3h substituents;
R3a in each instance is independently selected from —F, —Cl, —CN, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
R3b and R3c are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
R3d and R3e are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
R3f and R3g are independently selected from —H, —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), or —N(C1-C6 alkyl)2;
R3h in each instance is independently selected from —F, —Cl, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —O—(C1-C6 alkyl)-OH, —O—(C1-C6 alkyl)-O—(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, or oxo;
Q is a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms selected from N, O, or S, a C3-C8 cycloalkyl group, or a 3 to 7 membered heterocyclyl group containing 1, 2, or 3 heteroatoms selected from N, O, or S, wherein the C6-C10 aryl group, the heteroaryl group, the cycloalkyl group, and the heterocyclyl group are unsubstituted or are substituted with 1, 2, 3, or 4 RQ substituent;
RQ in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(═O)—(C1-C6 alkyl), —C(═O)OH, —C(═O)—O—(C1-C6 alkyl), —C(═O)NH2, —C(═O)NH(C1-C6 alkyl), —C(═O)N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), phenyl, or a heteroaryl group, and the Q heterocyclyl group may be substituted with 1 oxo substituent;
R4 is selected from a monocyclic or bicyclic C6-C10 aryl group, a monocyclic or bicyclic heteroaryl group with 5 to 10 ring members containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a monocyclic or bicyclic heterocyclyl group with 5 to 10 ring members containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S, wherein the C6-C10 aryl group, the heteroaryl group, or the heterocyclyl group are unsubstituted or are substituted with 1, 2, or 3 R4a substituents; and
R4a in each instance is independently selected from —F, —Cl, —Br, —I, —CN, —C1-C6 alkyl, —C1-C6 haloalkyl, —C1-C6 perhaloalkyl, —OH, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), —O—(C1-C6 perhaloalkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —C(═O)—(C1-C6 alkyl), —C(═O)OH, —C(═O)—O—(C1-C6 alkyl), —C(═O)NH2, —C(═O)NH(C1-C6 alkyl), or —C(═O)N(C1-C6 alkyl)2, and the heterocyclyl R4 group may be further substituted with 1 oxo substituent.

### Claim 2 (depends on 1)

The method of claim 1, wherein cyclizing further comprises heating the compound of Formula V, the salt thereof, the tautomer thereof, or the salt of the tautomer in the presence of the acid or the base.

### Claim 3 (depends on 2)

The method of claim 2, wherein heating the compound of Formula V, the salt thereof, the tautomer thereof, or the salt of the tautomer comprises heating the compound to a temperature of from 50° C. to 100° C.

### Claim 4 (depends on 2)

The method of claim 2, wherein heating the compound of Formula V, the salt thereof, the tautomer thereof, or the salt of the tautomer comprises heating the compound to a temperature of from 60° C. to 85° C.

### Claim 5 (depends on 1)

The method of claim 1, wherein the cyclizing of the compound of Formula V, the salt thereof, the tautomer thereof, or the salt of the tautomer is performed in the presence of the base.

### Claim 6 (depends on 1)

The method of claim 1, wherein the base is a metal hydroxide.

### Claim 7 (depends on 6)

The method of claim 6, wherein the metal hydroxide is selected from NaOH or LiOH.

### Claim 8 (depends on 5)

The method of claim 5, wherein the cyclizing is carried out in an alcohol solvent.

### Claim 9 (depends on 8)

The method of claim 8, wherein the alcohol is isopropanol.

### Claim 10 (depends on 1)

The method of claim 1, wherein cyclizing further comprises heating the compound of Formula V, the salt thereof, the tautomer thereof, or the salt of the tautomer in the presence of the acid.

### Claim 11 (depends on 10)

The method of claim 10, wherein the acid is selected from a sulfonic acid, a carboxylic acid, polyphosphoric acid, phosphoric acid, sulfuric acid, or hydrochloric acid.

### Claim 12 (depends on 11)

The method of claim 11, wherein the sulfonic acid is methanesulfonic acid.

### Claim 13 (depends on 11)

The method of claim 11, wherein the acid is trifluoroacetic acid, acetic acid, or trichloroacetic acid.

### Claim 14 (depends on 10)

The method of claim 10, wherein the cyclizing is carried out in a cyclic ether, an acyclic ether, N,N-dimethylformamide, or acetonitrile.

### Claim 15 (depends on 14)

The method of claim 14, wherein the cyclizing is carried out in a cyclic ether.

### Claim 16 (depends on 15)

The method of claim 15, wherein the cyclic ether is selected from tetrahydrofuran, tetrahydropyran, or 1,4-dioxane.

### Claim 17 (depends on 15)

The method of claim 15, wherein the cyclic ether is 1,4-dioxane.

### Claim 18 (depends on 1)

The method of claim 1, wherein R1 is an unsubstituted pyridyl or is a pyridyl substituted with 1 or 2 R1a substituents, wherein R1a in each instance is independently selected from —CH3, —CH2CH3, —F, —Cl, —Br, —CN, —CF3, —CH═CH2, —C(═O)NH2, —C(═O)NH(CH3), —C(═O)N(CH3)2, —C(═O)NH(CH2CH3), —OH, —OCH3, —OCHF2, —OCH2CH3, —OCH2CF3, —OCH2CH2OH, —OCH2C(CH3)ZOH, —OCH2C(CF3)2OH, —OCH2CH2OCH3, —NH2, —NHCH3, —N(CH3)2, phenyl, or a group of formula
wherein the symbol , when drawn across a bond, indicates the point of attachment to the rest of the molecule.

### Claim 19 (depends on 1)

The method of claim 1, wherein R1 is selected from
wherein the symbol , when drawn across a bond, indicates the point of attachment to the rest of the molecule.

### Claim 20 (depends on 1)

The method of claim 1, wherein R4 is a phenyl, pyridyl, pyrimidinyl, isoxazolyl, indolyl, naphthyl, or pyridinyl any of which may be unsubstituted or substituted with 1, 2, or 3 R4a substituents wherein R4a is in each instance independently selected from —CH3, —F, —Cl, —Br, —CN, —CF3, —OCH3, —OCHF2, —OCH2CH3, —C(═O)OCH3, —C(═O)CH3, or —N(CH3)2.

### Claim 21 (depends on 1)

The method of claim 1, wherein R4 is selected from
wherein the symbol , when drawn across a bond, indicates the point of attachment to the rest of the molecule.

### Claim 22 (depends on 1)

The method of claim 1, wherein R4 is a phenyl substituted with 1 or 2 R4a substituents, wherein the 1 or 2 R4a substituents are —O—(C1-C2 alkyl) groups.

### Claim 23 (depends on 1)

The method of claim 1, wherein Q is selected from pyrimidinyl, pyridyl, isoxazolyl, thiazolyl, imidazolyl, phenyl, tetrahydropyrimidinonyl, cyclopropyl, cyclobutyl, cyclohexyl, morpholinyl, pyrrolidinyl, pyrazinyl, imidazo[1,2-a]pyridinyl, pyrazolyl, or oxetanyl any of which may be unsubstituted or substituted with 1, 2, or 3, RQ substituents.

### Claim 24 (depends on 1)

The method of claim 1, wherein Q is a monocyclic heteroaryl group with 5 or 6 ring members containing 1 or 2 heteroatoms selected from N, O, or S and Q is unsubstituted or is substituted with 1 or 2 RQ substituents.

### Claim 25 (depends on 1)

The method of claim 1, wherein Q is selected from
wherein the symbol , when drawn across a bond, indicates the point of attachment to the rest of the molecule.

### Claim 26 (depends on 1)

The method of claim 1, wherein R3 is a group of formula —(CR3dR3e)—(CR3fR3g)-Q.

### Claim 27 (depends on 1)

The method of claim 1, wherein R3 has the formula
wherein the symbol , when drawn across a bond, indicates the point of attachment to the rest of the molecule.

### Claim 28 (depends on 1)

The method of claim 1, wherein the compound of Formula VI is
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(6-methoxy-2-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;
(2S,3R)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-3-(5-methyl-2-pyrimidinyl)-2-butanesulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-hydroxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;
(1S,2R)-1-(5-chloro-2-pyrimidinyl)-N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-2-propanesulfonamide;
(1S,2R)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrazinyl)-2-propanesulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-hydroxy-1-(5-methyl-2-pyrazinyl)-2-propanesulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide;
(2S,3R)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-3-(5-methyl-2-pyrimidinyl)-2-butanesulfonamide;
(1R,2S)-1-(5-chloro-2-pyrimidinyl)-N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-2-propane sulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-1-(5-methyl-2-pyrimidinyl)-2-propane sulfonamide;
(1 S,2R)—N-(4-(2,6-dimethoxy phenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-145-methyl-2-pyrazinyl)-2-propane sulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(6-methyl-2-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-hydroxy-1-(5-methyl-2-pyrimidinyl)-2-propane sulfonamide;
(1R,2 S)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-1-(5-methyl-2-pyrimidinyl)-2-propane sulfonamide;
(1R,2 S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-(5-fluoro-2-pyrimidinyl)-1-methoxy-2-propane sulfonamide;
(2 S,3R)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-3-(5-methyl-2-pyrazinyl)-2-butane sulfonamide;
(1R,2 S)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-1-(5-fluoro-2-pyrimidinyl)-2-propane sulfonamide;
(1 S,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-(1-methylethoxy)-1-(5-methyl-2-pyrimidinyl)-2-propane sulfonamide;
(1R,2 S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-(1-methylethoxy)-1-(5-methyl-2-pyrimidinyl)-2-propane sulfonamide;
(1 S,2R)-1-(5-chloro-2-pyrimidinyl)-N-(4-(2, 6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-2-propane sulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-145-methoxy-2-pyrazinyl)-2-propane sulfonamide;
(2 S,3R)—N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-3-(5-methyl-2-pyrazinyl)-2-butane sulfonamide;
(1R,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-145-fluoro-2-pyrimidinyl)-2-propane sulfonamide;
(1R,2S)—N-(4-(4,6-dimethoxy-5-pyrimidinyl)-5-(6-methoxy-2-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-145-methyl-2-pyrimidinyl)-2-propane sulfonamide;
(1R,2R)-1-(5-chloro-2-pyrimidinyl)-N-(4-(2,6-dimethoxyphenyl)-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-2-propane sulfonamide; or
(1S,2S)—N-(4-(2,6-dimethoxyphenyl)-5-(5-methyl-3-pyridinyl)-4H-1,2,4-triazol-3-yl)-1-ethoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide, or
is the salt of any of the above compounds.