# US 2010/0168076 A1 · Diphenyl substituted alkanes

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- Number: US 2010/0168076 A1
- Document ID: US20100168076A1
- Status: Published application
- Kind: A1
- Application number: 12/377,136
- Filed: 2007-08-29
- Published: 2010-07-01
- Earliest claimed: 2006-09-01
- Assignees: Merck Sharp & Dohme Corp.
- Inventors: Anthony Ogawa; Feroze Ujjainwalla; Ellenk Vande Bunte; Lin Chu; Debra Ondeyka; Ihor Kopka; Bing Li; Hyun Ok; Minal J. Patel; Jinyou Xu; Rosemary Sisco
- Web page: https://patentgrep.com/patent/US20100168076A1

## CPC

- C07D 413/14: containing three or more hetero rings
- 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 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The instant invention provides compounds of Formula I which are 5-lipoxygenase activating protein inhibitors. Compounds of Formula (I) are useful as anti-atherosclerotic, anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective agents.

## Claims

### Claim 1

A compound represented by structural Formula I:
or a pharmaceutically acceptable salt thereof wherein:
q is an integer selected from 0 (zero) and 1 (one);
R1 is selected from the group consisting of:
(a) a 5-membered aromatic or partially unsaturated heterocyclic ring containing 2 to 4 heteroatoms selected from N, S and O, wherein the heterocyclic ring is optionally substituted with R6,
(b) a 6-membered aromatic or partially unsaturated heterocyclic ring containing 1 to 2 heteroatoms selected from N and O, wherein the heterocyclic ring is optionally substituted with R6;
(c) an 8-membered aromatic or partially unsaturated ortho-fused bicyclic ring system containing 3-5 heteroatoms selected from one sulfur and 2-4 of nitrogen wherein one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4-alkyl, —CN and 1-3 of fluoro, and
(d) a 9-membered aromatic or partially unsaturated ortho-fused bicyclic ring system containing 3-4 nitrogen atoms, wherein one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4alkyl, —CN and 1-3 of fluoro;
(e) —C1-6alkyl, —C2-6alkenyl, and —C2-6alkynyl, said alkyl, alkenyl and alkynyl groups being optionally substituted with R12 and optionally substituted with R13;
(f) —C3-6 cycloalkyl optionally substituted with 1-3 substituents selected from the group consisting of fluoro, —NH2, —OH and —C1-3alkyl optionally substituted with 1-3 of fluoro;
(g) —O—R6a wherein R6a is selected from the group consisting of (1) —C1-6alkyl optionally substituted with R12 and optionally substituted with R13, (2) —C3-6 cycloalkyl optionally substituted with R12 and optionally substituted with R13 and (3) —C2-6alkyl-R10; with the proviso that when q is 0, R6a is not —C1-6alkyl substituted with Z1; and
(h) —H, —OH, —CN, —CO2R4a, —C(O)NR7R8, —NR7R8, —NRbSOpRa, —NRbC(O)Ra, —NRbC(O)NRaRb, —S(O)pRa, and —S(O)pNRaRb;
p is an integer selected from 0, 1 and 2;
R2 is selected from the group consisting of (a) —C1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —OH and fluoro, (b) —C3-6 cycloalkyl optionally substituted with 1-3 of fluoro, and
n is an integer selected from 0, 1, 2 and 3;
R3 is selected from the group consisting of —H, —F, —OH, and —C1-3alkyl optionally substituted with 1-5 fluoro; or
R2 and R3 are taken in combination and represent a mono- or bi-cyclic ring system containing 3 to 8 carbon atoms, said system being optionally substituted with 1-2 groups selected from: C1-3alkyl, OC1-3alkyl, F, OH, mono-, di- or tri-fluoroC1-3alkyl and mono-, di- and tri-fluoroC1-3alkoxy;
X is selected from the group consisting of —O—, —S— and —C(R14)2—;
R4a is selected from the group consisting of —H, —C1-6alkyl and —C3-6 cycloalkyl;
R4 is selected from the group consisting of —H, —C1-6alkyl and —C3-6 cycloalkyl;
R5 is selected from the group consisting of —H, —F, and —CH3;
R6 is selected from the group consisting of (a) —C1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2, —CN, —O—C1-4alkyl and fluoro, (b) —C1-6alkyl-R10, (c) —OC1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2 and fluoro, (d) —C3-6 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of methyl, —OH, —NH2, —CF3 and fluoro, (e) —NR7R8, (f) —SO2C1-3alkyl, (g) —CO2—R8, (h) —OH, (i) ═O (oxo), (j) —SH, (k) ═S, (l) —SMe, (m) —Cl, (n) —CF3, (o) —CN and (p) R10;
R7 is selected from the group consisting of (a) —H, (b) —C1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —F, —NH2 and —OH, (c) —C3-6 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of methyl, —CF3, —F, —NH2 and —OH, (d) —COC1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —F and —OH, (e) —COC3-6cycloalkyl optionally substituted with one or more substituents selected from the group consisting of methyl, —CF3, —F, —NH2 and —OH, and (f) a 4-6 membered saturated heterocyclic ring containing one N, wherein the ring is bonded to the nitrogen in —NR7R8 through a carbon atom in the ring, and wherein the ring is optionally substituted with one or more substituents selected from the group consisting of methyl, —CF3, —F, —NH2 and —OH;
R8 is selected from the group consisting of (a) —H, (b) —C1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —F, —NH2 and —OH, and (c) —C3-6cycloalkyl optionally substituted with one or more substituents selected from the group consisting of methyl, —CF3, —F, —NH2 and —OH;
R9 is selected from the group consisting of —H, —OH, —C1-3alkyl and —F;
R10 is a heterocyclic ring selected from the group consisting of (a) azetidinyl optionally substituted with one or more of methyl, —F and —OH, (b) pyrrolidinyl optionally substituted with one or more of methyl, —F and —OH, (c) piperidinyl optionally substituted with one or more of methyl, —F and —OH and (d) morpholinyl optionally substituted with one or more of methyl, —F and —OH; and
Y is selected from the group consisting of (a) a 5-membered aromatic or partially unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from 1 to 4 of N and zero to 1 of S, wherein the heterocyclic ring is optionally substituted with R11, (b) a 6-membered aromatic or partially unsaturated heterocyclic ring containing 1 to 2 N heteroatoms, wherein the heterocyclic ring is optionally substituted with R11, (c) a 9-membered bicyclic aromatic or partially unsaturated heterocyclic ring containing 1 to 4 N heteroatoms, wherein the heterocyclic ring is optionally substituted with R11 and (d) a 10-membered bicyclic aromatic or partially unsaturated heterocyclic ring containing 1 to 4 N heteroatoms, wherein the heterocyclic ring is optionally substituted with R11; and
R11 is selected from the group consisting of —F, —NH2, —OH, —OC3-4cycloalkyl, —C1-3alkyl optionally substituted with 1-3 fluoro, and —OC1-3alkyl optionally substituted with phenyl or 1-3 fluoro.
R12 is selected from the group consisting of: —CO2R4a, —C(O)NR7R8, —N(Ra)2, —NRbSOpRa, —NRbC(O)Ra, —NRbC(O)NRaRb, —S(O)pNRaRb, —S(O)pRa, —F, —CF3, phenyl, Hetcy and Z1,
R13 is selected from the group consisting of —OH, —NH2 and 1-5 of —F;
R14 is selected from the group consisting of —H and —C1-4alkyl optionally substituted with 1-3 fluoro groups;
each Ra is independently selected from the group consisting of
a) —H,
b) —C1-4alkyl, —C2-4alkenyl and —C2-4alkynyl, wherein each is optionally substituted with 1-2 substituents selected from the group consisting of: —OH, —OC1-4alkyl, —CN, —NH2, —NHC1-4alkyl, and —N(C1-4alkyl)2, and —CF3, and optionally with 1-3 of fluoro,
c) Hetcy and Hetcy-C1-4alkyl-, the Hetcy moieties being optionally substituted on carbon with 1-2 substituents selected from the group consisting of —F, —OH, —CO2H, —C1-4alkyl, —CO2C1-4alkyl, —OC1-4alkyl, —NH2, —NHC1-4alkyl, —N(C1-4alkyl)2, —NHC(O)C1-4alkyl, oxo, —C(O)NH1-4alkyl and —C(O)N(C1-4alkyl)2; and optionally substituted on nitrogen when present with a group selected from —C1-4alkyl and —C1-4acyl; and the alkyl portion of Hetcy-C1-4alkyl- being optionally substituted with a member selected from the group consisting of —OH, —CN, —OC1-4alkyl, —NH2, —NHC1-4alkyl, —N(C1-4alkyl)2 and 1-3 of fluoro,
d) Z2 and Z2—C1-4alkyl-, the alkyl portion of Z2—C1-4alkyl- being optionally substituted with a substituent selected from the group consisting of —OH, —CN, —OC1-4alkyl, —NH2, —NHC1-4alkyl, —N(C1-4alkyl)2 and 1-3 of fluoro;
each Rb is independently selected from the group consisting of —H and —C1-3alkyl optionally substituted with 1-2 members selected from the group consisting of NH2, —OH, —F, —CN and —CF3;
Rc, Rd, and Re are each independently selected from —H, —F, —Cl, —OH, —CN, —C1-4alkyl optionally substituted with 1-3 of fluoro, and —OC1-4alkyl optionally substituted with 1-3 of fluoro;
Hetcy is selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, tetraydrofuranyl and β-lactamyl, δ-lactamyl, γ-lactamyl and tetrahydropyranyl;
Z1 is selected from the group consisting of:
a) Z2,
b) an 8-membered aromatic or partially unsaturated ortho-fused bicyclic ring system containing 3-5 heteroatoms selected from one sulfur and 2-4 of nitrogen wherein one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4-alkyl, —CN and 1-3 of fluoro, and
c) a 9-membered aromatic or partially unsaturated ortho-fused bicyclic ring system containing 3-4 nitrogen atoms, wherein one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4alkyl, —CN and 1-3 of fluoro; and
Z2 is selected from the group consisting of:
a) a 5-membered aromatic or partially unsaturated heterocyclic ring containing 2-4 nitrogen atoms, wherein one nitrogen in the ring is optionally substituted with a group selected from —C1-4alkyl and —C1-4alkyl substituted with a group selected from —NH2, —OH, —CN and 1-3 of fluoro, and one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and —C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4alkyl, —CN and 1-3 of fluoro,
b) a 5-membered aromatic or partially unsaturated heterocyclic ring containing 2-3 heteroatoms selected from one oxygen or one sulfur and 1-2 of nitrogen, wherein one nitrogen in the ring is optionally substituted with a group selected from C1-4alkyl and C1-4alkyl substituted with a group selected from —NH2, —OH, —CN and 1-3 of fluoro, and one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, and C1-4alkyl optionally substituted with a group selected from —NH2, —OH, —OC1-4alkyl, —CN and 1-3 of fluoro, and
c) a 6-membered aromatic or partially unsaturated heterocyclic ring containing 1-2 nitrogen atoms, wherein one nitrogen in the ring is optionally substituted with a group selected from —C1-4alkyl and —C1-4alkyl substituted with a group selected from —NH2, —OH, —CN and 1-3 of fluoro, and one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and —C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4alkyl, —CN and 1-3 of fluoro.

### Claim 2 (depends on 1)

The compound of claim 1 wherein Y is selected from (a) a 5-membered aromatic heterocyclic ring containing 1 to 2 heteroatoms selected from 1 to 2 of N and zero to 1 of S, wherein the heterocyclic ring is optionally substituted with R11, and (b) a 6-membered aromatic heterocyclic ring containing 1 to 2 N heteroatoms, wherein the heterocyclic ring is optionally substituted with R11.

### Claim 3 (depends on 2)

The compound of claim 2 wherein Y is selected from:

### Claim 4 (depends on 2)

The compound of claim 2 wherein R2 is selected from the group consisting of i-propyl, t-butyl, cyclopropyl, cyclobutyl,
and R3 is selected from the group consisting of —H and —CH3.

### Claim 5 (depends on 4)

The compound of claim 4 wherein R4 is selected from the group consisting of —H, —CH3 and —CH2CH3 and R5 is —H.

### Claim 6 (depends on 5)

The compound of claim 5 wherein R1 is selected from the group consisting of:
(a) a 5-membered aromatic or partially unsaturated heterocyclic ring containing a total of 2 to 4 heteroatoms selected from two to four of N, zero to one of O, and zero to one of S, wherein the heterocyclic ring is optionally substituted with R6,
(b) a 6-membered aromatic or partially unsaturated heterocyclic ring containing 1 to 2 heteroatoms selected from N and O, wherein the heterocyclic ring is optionally substituted with R6,
(c) —C1-4alkyl optionally substituted with R12 and optionally substituted with R13,
(d) —OR6a wherein R6a is —C1-4alkyl optionally substituted with R13, (e) —CO2C1-6alkyl, (f) —C(O)NR7R8, (g) —CN, and (h) —C3-6 cycloalkyl optionally substituted with R12 and optionally substituted with R13.

### Claim 7 (depends on 6)

The compound of claim 6 wherein R1 is selected from the group consisting of:
(a) —C(CH3)2OH, (b) —C(CH3)2NH2 (c) —C3-6 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of —OH and —NH2, (d) —OCH3 optionally substituted with 1-3 of fluoro, (e) —CN, (f) —CO2C1-6alkyl, and (g) —C(O)NR7R8 wherein R8 is —H and R7 is selected from (i) —H, (ii) —C1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —F and —OH, (iii) —C3-6 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of —F and —OH, and (iv) a 4-6 membered saturated heterocyclic ring containing one N, wherein the ring is bonded to the nitrogen in —NR7R8 through a carbon atom in the ring, and wherein the ring is optionally substituted with one or more substituents selected from the group consisting of methyl, —CF3, —F, —NH2 and —OH,
(h) a 5-membered aromatic or partially unsaturated heterocyclic ring optionally substituted with R6, wherein the ring is selected from:
and (i) a 6-membered aromatic heterocyclic ring optionally substituted with R6, wherein the ring is selected from:

### Claim 8 (depends on 6)

The compound of claim 6 wherein R6, when present, is selected from the group consisting of:
(a) —CRxRyRz wherein Rx is selected from —H, —C1-3alkyl and —F, Ry is selected from —H, —C1-3alkyl and —F, and Rz is selected from —H, —C1-3alkyl, —OC1-3alkyl, —F, —NH2 and —OH; or Rx and Ry are joined together with the carbon to which they are attached to form a cyclopropyl ring the following structure
(b)—C1-3 alkyl-R10,
(c) —R10,
(d) —OC1-4alkyl optionally substituted with 1-5 fluoro,
(e) —NR7R8,
(f) —SO2CH3,
(g) oxo and
(h) —CO2C1-6alkyl.

### Claim 9 (depends on 6)

The compound of claim 6 wherein R10 is selected from
and is optionally substituted with a substituent selected from methyl, —OH and 1-2 of fluoro.

### Claim 10 (depends on 6)

The compound of claim 6 wherein Rc, Rd and Re are each —H.

### Claim 11 (depends on 1)

The compound of claim 1 having structural Formula Ia:
or a pharmaceutically acceptable salt thereof wherein Y is a 6-membered aromatic heterocyclic ring containing 1 to 2 N heteroatoms wherein the heterocyclic ring is optionally substituted with R11.

### Claim 12 (depends on 11)

The compound of claim 11 wherein Y is selected from:

### Claim 13 (depends on 12)

The compound of claim 12 wherein R2 is selected from the group consisting of i-propyl, t-butyl, cyclopropyl, cyclobutyl,
and R3 is selected from the group consisting of —H and —CH3.

### Claim 14 (depends on 13)

The compound of claim 13 wherein R1 is selected from the group consisting of:
(a) a 5-membered aromatic or partially unsaturated heterocyclic ring containing a total of 2 to 4 heteroatoms selected from two to four of N, zero to one of O, and zero to one of S, wherein the heterocyclic ring is optionally substituted with R6,
(b) a 6-membered aromatic or partially unsaturated heterocyclic ring containing 1 to 2 heteroatoms selected from N and O, wherein the heterocyclic ring is optionally substituted with R6,
(c) —C1-4alkyl optionally substituted with R12 and optionally substituted with R13,
(d) —OR6a wherein R6a is —C1-4alkyl optionally substituted with R13, (e) —CO2C1-6alkyl, (f) —C(O)NR7R8, (g) —CN, and
(h) —C3-6 cycloalkyl optionally substituted with R12 and optionally substituted with R13.

### Claim 15 (depends on 1)

The compound of claim 1 having structural Formula Ib:
or a pharmaceutically acceptable salt thereof wherein Y is selected from (a) a 5-membered aromatic heterocyclic ring containing 1 to 2 heteroatoms selected from 1 to 2 of N and zero to 1 of S, wherein the heterocyclic ring is optionally substituted with R11, and (b) a 6-membered aromatic heterocyclic ring containing 1 to 2 N heteroatoms, wherein the heterocyclic ring is optionally substituted with R11.

### Claim 16 (depends on 15)

The compound of claim 15 wherein Y is selected from:

### Claim 17 (depends on 16)

The compound of claim 16 wherein R2 is selected from the group consisting of i-propyl, t-butyl, cyclopropyl, cyclobutyl,
and R3 is selected from the group consisting of —H and —CH3.

### Claim 18 (depends on 17)

The compound of claim 17 wherein R1 is selected from the group consisting of:
(a) a 5-membered aromatic or partially unsaturated heterocyclic ring containing a total of 2 to 4 heteroatoms selected from two to four of N, zero to one of O, and zero to one of S, wherein the heterocyclic ring is optionally substituted with R6,
(b) a 6-membered aromatic or partially unsaturated heterocyclic ring containing 1 to 2 heteroatoms selected from N and O, wherein the heterocyclic ring is optionally substituted with R6,
(c) —C1-4alkyl optionally substituted with R12 and optionally substituted with R13,
(d) —OR6a wherein R6a is —C1-4alkyl optionally substituted with R13, (e) —CO2C1-6alkyl, (f) —C(O)NR7R8, (g) —CN, and
(h) —C3-6 cycloalkyl optionally substituted with R12 and optionally substituted with R13.

### Claim 19 (depends on 1)

The compound of claim 1 selected from the group consisting of:
4-{[3-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]methyl}morpholine;
2-[3-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]propan-2-ol;
2-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}-5-[5-(piperidin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]pyridine;
5-{5-[(4-fluoropiperidin-1-yl)methyl]-1,2,4-oxadiazol-3-yl}-2-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridine;
2-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}-5-[5-(pyrrolidin-1-ylmethyl)-1,2,4-oxadiazol-3-yl]pyridine;
5-(5-{[(3S)-3-fluoropyrrolidin-1-yl]methyl}-1,2,4-oxadiazol-3-yl)-2-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridine;
5-(5-{[(3R)-3-fluoropyrrolidin-1-yl]methyl}-1,2,4-oxadiazol-3-yl)-2-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridine;
tert-butyl {1-[3-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]-1-methylethyl}carbamate;
tert-butyl {1-[3-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropyl}carbamate;
2-[3-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]propan-2-amine;
1-[3-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropanamine;
2-[5-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)isoxazol-3-yl]propan-2-ol;
2-[6-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)pyridazin-3-yl]propan-2-ol;
2-{6-[6-(1-{4-[2-(2,5-dimethyl-1H-pyrrol-1-yl)pyrimidin-5-yl]phenyl}-1,2-dimethylpropyl)pyridin-3-yl]pyridazin-3-yl}propan-2-ol;
2-[6-(6-{1-[4-(2-aminopyrimidin-5-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)pyridazin-3-yl]propan-2-ol;
2-[6-(6-{1-[4-(6-aminopyridazin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)pyridazin-3-yl]propan-2-ol;
3-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)-6-methylpyridazine;
3-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)-6-(trifluoromethyl)pyridazine;
3-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)-6-(methylsulfonyl)pyridazine;
3-[6-(1-{-4-[5-(fluoromethoxy)pyridin-3-yl]phenyl}-1,2-dimethylpropyl)pyridin-3-yl]-6-(trifluoromethyl)pyridazine;
3-[6-(1-{4-[5-(difluoromethoxy)pyridin-3-yl]phenyl}-1,2-dimethylpropyl)pyridin-3-yl]-6-(trifluoromethyl)pyridazine;
3-(6-{1-[4-(5-ethoxypyridin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)-6-(trifluoromethyl)pyridazine;
3-[6-(1-{-4-[5-(benzyloxy)pyridin-3-yl]phenyl}-1,2-dimethylpropyl)pyridin-3-yl]-6-(trifluoromethyl)pyridazine;
2-(6-{1-[4-(2-aminopyrimidin-5-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)propan-2-ol;
methyl 6-{1-[4-(2-aminopyrimidin-5-yl)phenyl]-1,2-dimethylpropyl}nicotinate;
6-{1-[4-(2-aminopyrimidin-5-yl)phenyl]-1,2-dimethylpropyl}nicotinonitrile;
2-(6-{1-[4-(6-aminopyridazin-3-yl)phenyl]-1,2-dimethylpropyl}pyridin-3-yl)propan-2-ol;
5-(6-{2,2-dimethyl-1-[4-(pyridin-2-ylmethoxy)phenyl]propyl}pyridin-3-yl)-1,3,4-oxadiazol-2-amine;
2-{2,2-dimethyl-1-[4-(pyridin-2-ylmethoxy)phenyl]propyl}-5-(2-methyl-2H-tetrazol-5-yl)pyridine;
2-[3-(6-{1,2-dimethyl-1-[4-(pyridin-2-ylmethoxy)phenyl]propyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]propan-2-ol;
1-[3-(6-{1,2-dimethyl-1-[4-(pyridin-2-ylmethoxy)phenyl]propyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropanamine;
4-{[3-(6-{1,2-dimethyl-1-[4-(pyridin-2-ylmethoxy)phenyl]propyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]methyl}morpholine;
3-chloro-6-(6-{1,2-dimethyl-1-[4-(pyridin-2-ylmethoxy)phenyl]propyl}pyridin-3-yl)pyridazine;
6-(6-{1,2-dimethyl-1-[4-(pyridin-2-ylmethoxy)phenyl]propyl}pyridin-3-yl)pyridazine-3-carboxylate;
2-[6-(6-{1,2-dimethyl-1-[4-(pyridin-2-ylmethoxy)phenyl]propyl}pyridin-3-yl)pyridazin-3-yl]propan-2-ol;
2-[3-(6-{1,2-dimethyl-1-[4-(1,3-thiazol-2-ylmethoxy)phenyl]propyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]propan-2-ol;
1-[3-(6-{1,2-dimethyl-1-[4-(1,3-thiazol-2-ylmethoxy)phenyl]propyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]cyclopropanamine;
and the pharmaceutically acceptable salts thereof.

### Claim 20 (depends on 1)

The compound of claim 1 which is 2-[3-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-(1R)-1,2-dimethylpropyl}pyridin-3-yl)-1,2,4-oxadiazol-5-yl]propan-2-ol, or a pharmaceutically acceptable salt thereof.

### Claim 21 (depends on 1)

The compound of claim 1 which is 2-[5-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-(1R)-1,2-dimethylpropyl}pyridin-3-yl)isoxazol-3-yl]propan-2-ol,
or a pharmaceutically acceptable salt thereof.

### Claim 22 (depends on 1)

The compound of claim 1 which is 2-[6-(6-{1-[4-(5-methoxypyridin-3-yl)phenyl]-(1R)-1,2-dimethylpropyl}pyridin-3-yl)pyridazin-3-yl]propan-2-ol,
or a pharmaceutically acceptable salt thereof

### Claim 23 (depends on 1)

The compound of claim 1 which is 2-[6-(6-{1-[4-(2-aminopyrimidin-5-yl)phenyl]-(1R)-1,2-dimethylpropyl}pyridin-3-yl)pyridazin-3-yl]propan-2-ol,
or a pharmaceutically acceptable salt thereof.

### Claim 24 (depends on 1)

The compound of claim 1 which is 2-[6-(6-{1-[4-(6-aminopyridazin-3-yl)phenyl]-(1R)-1,2-dimethylpropyl}pyridin-3-yl)pyridazin-3-yl]propan-2-ol,
or a pharmaceutically acceptable salt thereof.

### Claim 25 (depends on 1)

The compound of claim 1 which is 2-(6-{1-[4-(2-aminopyrimidin-5-yl)phenyl]-(1R)-1,2-dimethylpropyl}pyridin-3-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

### Claim 26 (depends on 1)

The compound of claim 1 which is 2-(6-{1-[4-(6-aminopyridazin-3-yl)phenyl]-(1R)-1,2-dimethylpropyl}pyridin-3-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

### Claim 27 (depends on 1)

A pharmaceutical composition comprised of a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

### Claim 28 (depends on 1)

A method of treating atherosclerosis comprising administering a therapeutically effective amount of a compound of claim 1 to a patient in need of such treatment.

### Claim 29 (depends on 1)

A method for prevention or treatment of asthma, allergic rhinitis or COPD comprising administering a therapeutically effective amount of a compound of claim 1 to a patient in need of such treatment.

### Claim at position 30

30-35. (canceled)