# US 9,872,852 B2 · Compounds useful as immunomodulators

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,872,852 B2
- Document ID: US9872852B2
- Status: Granted
- Kind: B2
- Application number: 14/915,782
- Filed: 2014-09-02
- Published: 2016-07-07
- Granted: 2018-01-23
- Earliest claimed: 2013-09-04
- Assignees: Bristol-Myers Squibb Company
- Applicants: Bristol-Myers Squibb Company
- Inventors: Louis S. Chupak; Xiaofan Zheng
- Web page: https://patentgrep.com/patent/US9872852B2

## CPC

- A61K 31/381: having five-membered rings
- A61K 31/396: having three-membered rings, e.g. aziridine
- A61K 31/397: having four-membered rings, e.g. azetidine
- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 31/4427: containing further heterocyclic ring systems
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/4523: containing further heterocyclic ring systems
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/5375: 1,4-Oxazines, e.g. morpholine
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 31/551: having two nitrogen atoms, e.g. dilazep
- A61P 31/04: Antibacterial agents
- A61P 31/12: Antivirals
- A61P 33/00: Antiparasitic agents
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/02: Immunomodulators
- C07C 217/58: with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
- C07C 229/14: to carbon atoms of carbon skeletons containing rings
- C07C 229/22: the carbon skeleton being further substituted by oxygen atoms
- C07C 233/36: having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
- C07C 233/38: having the carbon atom of the carboxamide group bound to a carbon atom of an acyclic unsaturated carbon skeleton
- C07C 233/47: having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
- C07C 233/78: with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C 235/76: of an unsaturated carbon skeleton
- C07C 237/06: having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C 255/54: containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
- C07C 271/20: to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
- C07C 275/40: being further substituted by nitrogen atoms not being part of nitro or nitroso groups
- C07C 279/12: being further substituted by nitrogen atoms not being part of nitro or nitroso groups
- C07C 279/14: being further substituted by carboxyl groups
- C07C 311/05: to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07D 205/04: having no double bonds between ring members or between ring members and non-ring members
- C07D 205/08: with one oxygen atom directly attached in position 2, e.g. beta-lactams
- C07D 207/08: with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D 207/14: Nitrogen atoms not forming part of a nitro radical
- C07D 207/16: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 207/27: with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C07D 211/32: by oxygen atoms
- C07D 211/34: with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 211/44: attached in position 4
- C07D 211/48: having an acyclic carbon atom attached in position 4
- C07D 211/56: Nitrogen atoms (nitro radicals C07D211/38)
- C07D 211/60: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 211/62: attached in position 4
- C07D 211/76: attached in position 2 or 6
- C07D 211/78: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D 213/57: Nitriles
- C07D 213/63: One oxygen atom
- C07D 213/64: attached in position 2 or 6
- C07D 213/65: attached in position 3 or 5
- C07D 213/69: Two or more oxygen atoms
- C07D 217/02: with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D 217/04: with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
- C07D 223/06: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms (halogen atoms C07D223/04)
- C07D 233/61: with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D 265/30: not condensed with other rings
- C07D 279/12: not condensed with other rings
- C07D 295/12: substituted by singly or doubly bound nitrogen atoms (nitro radicals C07D295/06)
- C07D 295/13: to an acyclic saturated chain
- C07D 295/14: substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 295/16: acylated on ring nitrogen atoms
- C07D 295/18: by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D 295/185: from aliphatic carboxylic acids
- C07D 309/14: Nitrogen atoms not forming part of a nitro radical
- C07D 311/08: not hydrogenated in the hetero ring
- C07D 311/14: substituted in position 6 and unsubstituted in position 7
- C07D 317/50: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D 319/18: Ethylenedioxybenzenes, not substituted on the hetero ring
- C07D 333/20: by nitrogen atoms (nitro, nitroso radicals C07D333/12)
- C07D 333/32: Oxygen atoms
- C07D 333/36: Nitrogen atoms
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 487/10: Spiro-condensed systems
- C07K 5/0806: {the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala}
- C07K 5/0808: {the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu}
- C07C 2601/02: with a three-membered ring
- C07C 2601/04: with a four-membered ring
- C07C 2601/08: the ring being saturated
- C07C 2601/14: The ring being saturated
- C07C 2602/08: the other ring being five-membered, e.g. indane
- C07C 2602/10: the other ring being six-membered, e.g. tetraline
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Disclosed are compounds of Formula (I): (I). Also disclosed are methods of using such compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of virological diseases or disorders and cancer.

## Claims

### Claim 1

A compound of Formula (I):
or salts thereof, wherein:
Ring B is phenyl or thienyl;
Ring A is:
wherein A″ is CH or N, and wherein one of R1 and R2 is Q and the other of R1 and R2 is Rb;
R3 is H or —CH2C(O)OH;
R4 is —NHCH2CH2NHC(O)CH3;
Q is:
(i)
wherein Ry is —OH, —CH3, —CH2OH, —C(O)OH, —CH2C(O)OH, or —C(O)NHCH2CH2OH, —C(O)NH2, —NHC(O)CH3, and Rz is —OH, —CH3, —OCH3, —OC(O)CH3, or —CH2CH═CH2 and Rh is —CH3 or —C(O)CH3;
(ii) —CH2NH—Rx wherein Rx is cyclobutyl, —(CH2)cyclobutyl optionally substituted with two fluorine atoms, cyclopropyl, hydroxycyclopentyl, cyclopentyl, cyclohexyl, hydroxycyclohexyl, hydroxytetrahydrofuranyl, N-methyl piperidinyl, N-ethyl piperidinyl, hydroxytetrahydrothienyl, or
(iii) —CH2NRa—CRaRa—(CH2)n—Rx wherein Rx is hydrogen, azetidinonyl, cyclohexyl, hydroxyphenyl, pyrrolidinonyl, piperidinonyl, piperazinonyl, morpholinyl, imidazolyl, N-methylimidazolyl, —C(O)(morpholinyl), piperazinyl optionally substituted with a methyl, phenyl, alkoxyphenyl, hydroxyphenyl, pyridinyl, pyrimidinyl, or —C(O)OC(CH3)3 group, pyrrolidinyl, pyridinyl, thiomorpholine dioxide, or methyl triazolyl; or
(iv) —CHRa—NRa—CRaRa—(CHRa)n—Rx wherein Rx is —OH, —OCH3, —C(O)OH, —OPh, —CH(CO2H)—NHC(O)CH3, —O(CH2)2O(CH2)2OH, —O(CH2)2O(CH2)2O(CH2)2OH, —O(CH2)2O(CH2)2O(CH2)2O(CH2)2CO2H—O(CH2)2O(CH2)2O(CH2)2O(CH2)2O(CH2)2O(CH2)2CO2H, —C(O)CH3, —C(O)NRaRa, —C(O)NRqRq, —N(CH3)2, —NHC(O)CH3, —NHC(O)Ph, —C(O)NH(CH2)2-imidazolyl, NHC(O)OCH2Ph, —N(CH3)S(O)2CH3, —NHC(O)CH═CH2, —NHC(O)CH═CHC(O)CH2CH3, —NHS(O)2CH3, or
each Ra is independently H, —CH(OH)CH3, OH, —(CH2)2OH, —CH2OH, —(CH2)2NH2, —CH2CH3, or —CH3; or, two Ra groups on the same carbon atom can form a four, five-, or six-membered carbocyclic ring, an N-methylpiperidinyl ring, or a pyranyl ring;
each Rb is independently H, F, Cl, Br, —CF3, —CN, CH3, or —OCH3;
each Rc is independently —OCH3, —OH, —OCH2CH3, —O(CH2)OCH3, —OCH2CH═CH2, —O(CH2)2CH3, —O(CH2)2-morpholinyl, or F;
or two Rc attached to adjacent carbon atoms form —O—(CH2)v—O—, wherein v is 1 or 2;
each Rq is selected from hydrogen, —CH2C(O)NHCH2CO2H, —(CH2)C(O)NHCH(CO2H)CH2CH(CH3)2, —CH(Bn)-C(O)NHCH(CO2H)(CH2)3NHC(NH)NH2;
m is zero or 1;
n is zero, 1, 2, or 3;
each p is independently zero or 1; and
q is zero, 1, or 2.

### Claim 2 (depends on 1)

The compound according to claim 1 or salts thereof, wherein Ring A is:

### Claim 3 (depends on 2)

The compound according to claim 2 or salts thereof, wherein Q is:

### Claim 4 (depends on 2)

The compound according to claim 2 or salts thereof, wherein Q is: —CH2NH—Rx wherein Rx is cyclobutyl, —(CH2)cyclobutyl optionally substituted with two fluorine atoms, cyclopropyl, hydroxycyclopentyl, cyclopentyl, cyclohexyl, hydroxycyclohexyl, hydroxytetrahydrofuranyl, N-methyl piperidinyl, N-ethyl piperidinyl, hydroxytetrahydrothienyl, or

### Claim 5 (depends on 2)

The compound according to claim 2 or salts thereof, wherein Q is: —CH2NRa—CRaRa—(CH2)n—Rx wherein Rx is hydrogen, azetidinonyl, cyclohexyl, hydroxyphenyl, pyrrolidinonyl, piperidinonyl, piperazinonyl, morpholinyl, imidazolyl, N-methylimidazolyl, —C(O)(morpholinyl), piperazinyl optionally substituted with a methyl, phenyl, alkoxyphenyl, hydroxyphenyl, pyridinyl, pyrimidinyl, or —C(O)OC(CH3)3 group, pyrrolidinyl, pyridinyl, thiomorpholine dioxide, or methyl triazolyl.

### Claim 6 (depends on 2)

The compound according to claim 2 or salts thereof, wherein Q is —CHRa—NRa—CRaRa—(CHRa)n—Rx wherein Rx is —OH, —OCH3, —C(O)OH, —OPh, —CH(CO2H)—NHC(O)CH3, —O(CH2)2O(CH2)2OH, —O(CH2)2O(CH2)2O(CH2)2OH, —O(CH2)2O(CH2)2O(CH2)2O(CH2)2CO2H—O(CH2)2O(CH2)2O(CH2)2O(CH2)2O(CH2)2O(CH2)2CO2H, —C(O)CH3, —C(O)NRaRa, —C(O)NRqRq, —N(CH3)2, —NHC(O)CH3, —NHC(O)Ph, —C(O)NH(CH2)2-imidazolyl, NHC(O)OCH2Ph, —N(CH3)S(O)2CH3, —NHC(O)CH═CH2, —NHC(O)CH═CHC(O)CH2CH3, —NHS(O)2CH3, or

### Claim 7 (depends on 1)

The compound according to claim 1 selected from: (S)-1-(2,6-dimethoxy-4-((2-methylbiphenyl-3-yl)methoxy)benzyl)piperidine-2-carboxylic acid (1); 1-(4-((2′-fluoro-2-methylbiphenyl-3-yl)methoxy)benzyl)azetidine (3); N-{2-[({3-bromo-2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}acetamide (4); ({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl) [2-methyl-1-(4-methylpiperazin-1-yl)propan-2-yl]amine (5); N-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}-N-methylmethanesulfonamide (6); 1-({3-bromo-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (7); 2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-1-(morpholin-4-yl)ethan-1-one (8); ({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)[2-(4-methylpiperazin-1-yl)ethyl]amine (9); 1-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}piperidin-2-one (10); 1-{3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propyl}pyrrolidin-2-one (11); 4-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}piperazin-2-one (12); ({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)[2-(morpholin-4-yl)ethyl]amine (13); 1-({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (14); 2-[methyl({3-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]acetic acid (15); N-({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)-1-ethylpiperidin-3-amine (16); 1-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}pyrrolidin-2-one (17); (2S,4R)-4-(acetyloxy)-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)pyrrolidine-2-carboxylic acid (18); N-(2-hydroxyethyl)-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl) piperidine-4-carboxamide (19); ({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)[1-(5-methyl-4H-1,2,4-triazol-3-yl)ethyl]amine (20); N-{2-[({3-bromo-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}acetamide (21); (2S,4R)-1-({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)-4-methoxypyrrolidine-2-carboxylic acid (22); N-{3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propyl}acetamide (23); (1R,2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]cyclohexan-1-ol (24); N-({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)-1-methylpiperidin-3-amine (25); (2S)-1-({2-methoxy-3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (26); (2S)-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)-2-(prop-2-en-1-yl)pyrrolidine-2-carboxylic acid (27); 3-[({3-bromo-4-[(2-methyl-3-phenylphenyl) methoxy]phenyl}methyl)amino]propanamide (28); 3-[({3-[(2-methyl-3-phenylphenyl) methoxy]phenyl}methyl)amino]propanamide (29); 4-({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)morpholine-3-carboxylic acid (30); 3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]butanoic acid (31); 1-({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-4-carboxylic acid (32); (2R)-1-({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (33); (2S)-1-({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (34); 2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-N,N-dimethylacetamide (35); N-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}acetamide (36); 1-({2-methoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (37); 1-({3-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)azetidine (38); (2S,4R)-4-methoxy-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl) pyrrolidine-2-carboxylic acid (39); 1-({2,6-dimethyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (40); 1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)azepane-2-carboxylic acid (41); 2-[1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidin-2-yl]acetic acid (42); 1-{3-[({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propyl}pyrrolidin-2-one (43); N-{2-[(1-{3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}ethyl)amino]ethyl}acetamide (44); 2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)(methyl)amino]acetic acid (45); 3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanamide (46); (2S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanoic acid (47); 1-({3-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl) piperidine-2-carboxylic acid (48); 1-({3-fluoro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (49); (2R,4R)-4-hydroxy-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)pyrrolidine-2-carboxylic acid (50); (2R,4S)-4-hydroxy-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl) pyrrolidine-2-carboxylic acid (51); 1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (52); 1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-3-carboxylic acid (53); (3R)-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-3-carboxylic acid (54); (2R,4R)-4-methyl-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)pyrrolidine-2-carboxylic acid (55); (2S)-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (56); 1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-4-carboxylic acid (57); (2R)-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (58); (2S)-1-({4-methyl-3-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (59); 1-{3-[({3-[(2-methyl-3-phenylphenyl) methoxy]phenyl}methyl)amino]propyl}pyrrolidin-2-one (60); 1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid (63); 2-[({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-methylpropanoic acid (64); N-{2-[({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}acetamide (65); 1-({3-bromo-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)azetidine (66); N-{2-[({2-methoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}acetamide (67); N-({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl) cyclobutanamine (68); N-{2-[({2,6-dimethyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}acetamide (69); N-{2-[(1-{3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}ethyl)amino]ethyl}acetamide (70); (2S)-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)pyrrolidine-2-carboxylic acid (71); 1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)pyrrolidine-2-carboxylic acid (72); (1R,2R)-2-[({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]cyclohexan-1-ol (73); 1-({4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)piperidine-2-carboxylic acid (74); (2R)-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)pyrrolidine-2-carboxylic acid (75); 5-{[({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]methyl}pyrrolidin-2-one (76); (2S)-2-[({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanoic acid (77); (2R)-2-[({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanoic acid (78); N-{2-[({3-fluoro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}acetamide (79); (2S)-2-[({2-methoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanoic acid (80); (2S)-2-[({3-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanoic acid (81); 3-[({2-methoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanamide (82); 1-({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)azetidine (83); 3-[({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]butanoic acid (84); (2R)-2-[methyl({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanoic acid (85); 3-[({2,6-dimethyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanamide (86); N-{2-[({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}acetamide (87); N-{2-[({4-methyl-3-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}acetamide (88); [(2S)-1-({3-methyl-4-[(2-methyl-3-phenylphenyl) methoxy]phenyl}methyl)pyrrolidin-2-yl]methanol (89); (2S)-1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)azetidine-2-carboxylic acid (90); 5-{[({4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]methyl}pyrrolidin-2-one (91); 5-{[({4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]methyl}pyrrolidin-2-one (92); (2S)-2-[({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanoic acid (93); 2-[methyl({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]acetic acid (94); 3-[({3-methyl-4-[(2-methyl-3-phenylphenyl) methoxy]phenyl}methyl)amino]propanamide (95); (2R)-2-[({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanoic acid (96); 1-({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)azetidine (97); 1-({2-methoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)azetidine (98); 1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)azetidine (99); 1-({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)azetidine (100); 2-[({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethan-1-ol (102); 2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl) methoxy]phenyl}methyl)amino]ethan-1-ol (103); (2S)-2-[({3-bromo-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanoic acid (104); (2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propanoic acid (105); (2R)-2-{[(2,6-dimethoxy-4-{[3-(3-methoxyphenyl)-2-methylphenyl]methoxy}phenyl)methyl]amino}propanoic acid (106); (2R)-2-{[(4-{[3-(3-fluoro-5-methoxyphenyl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl]amino}propanoic acid (107); (2R)-2-{[(4-{[3-(2H-1,3-benzodioxol-5-yl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl]amino}propanoic acid (108); 2-(6-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-3,4-dihydroisoquinolin-2(1H)-yl)acetic acid (2); N-[2-({5-[(2-methyl-3-phenylphenyl)methoxy]-1,2,3,4-tetrahydronaphthalen-1-yl}amino)ethyl]acetamide (61); N-[2-({6-[(2-methyl-3-phenylphenyl)methoxy]-1,2,3,4-tetrahydronaphthalen-1-yl}amino)ethyl]acetamide (62); or 6-[(2-methyl-3-phenylphenyl) methoxy]-1,2,3,4-tetrahydroisoquinoline (101); or salts thereof.

### Claim 8 (depends on 1)

The compound according to claim 1 or salts thereof, selected from
N-[2-({4-[(2-methyl-3-phenylphenyl)methoxy]-2,3-dihydro-1H-inden-1-yl}amino)ethyl]acetamide;
4-{[({3-methyl-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]methyl}azetidin-2-one;
(3S)-4-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-hydroxybutanoic acid;
(2S)-1-[(4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-3-(trifluoromethyl)phenyl)methyl]piperidine-2-carboxylic acid;
N-(2-{[(4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-3-(trifluoromethyl)phenyl)methyl]amino}ethyl)acetamide;
(3S)-4-{[(4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-3-(trifluoromethyl)phenyl)methyl]amino}-3-hydroxybutanoic acid;
(2R,3S)-2-[({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-hydroxybutanoic acid;
(2R,3R)-2-[({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-hydroxybutanoic acid;
(2S,3S)-2-[({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-hydroxybutanoic acid;
2-[({5-[(2-methyl-3-phenylphenyl)methoxy]thiophen-2-yl}methyl)amino]ethan-1-ol;
2-[({5-[(2-methyl-3-phenylphenyl)methoxy]pyridin-2-yl}methyl)amino]ethan-1-ol;
{1-[({5-[(2-methyl-3-phenylphenyl)methoxy]pyridin-2-yl}methyl)amino]cyclopentyl}methanol;
methyl({5-[(2-methyl-3-phenylphenyl)methoxy]pyridin-2-yl}methyl)amine;
5-{[({5-[(2-methyl-3-phenylphenyl)methoxy]pyridin-2-yl}methyl)amino]methyl}pyrrolidin-2-one;
2-(3,5-dimethoxy-4-{[(pyridin-2-ylmethyl)amino]methyl}phenoxymethyl)-6-phenylbenzonitrile;
2-{4-[(cyclopropylamino)methyl]-3,5-dimethoxyphenoxymethyl}-6-phenylbenzonitrile;
2-{3,5-dimethoxy-4-[(3-methylpiperidin-1-yl)methyl]phenoxymethyl}-6-phenylbenzonitrile;
2-[3,5-dimethoxy-4-({[2-(pyrrolidin-1-yl)ethyl]amino}methyl)phenoxymethyl]-6-phenylbenzonitrile;
2-{4-[(4-hydroxypiperidin-1-yl)methyl]-3,5-dimethoxyphenoxymethyl}-6-phenylbenzonitrile;
2-[3,5-dimethoxy-4-(morpholin-4-ylmethyl)phenoxymethyl]-6-phenylbenzonitrile;
2-(3,5-dimethoxy-4-{[(pyridin-3-ylmethyl)amino]methyl}phenoxymethyl)-6-phenylbenzonitrile;
2-(3,5-dimethoxy-4-{[(pyridin-4-ylmethyl)amino]methyl}phenoxymethyl)-6-phenylbenzonitrile;
2-[4-({[(3-hydroxyphenyl)methyl]amino}methyl)-3,5-dimethoxyphenoxymethyl]-6-phenylbenzonitrile;
2-[4-({[(2-hydroxyphenyl)methyl]amino}methyl)-3,5-dimethoxyphenoxymethyl]-6-phenylbenzonitrile;
2-[4-({[(4-hydroxyphenyl)methyl]amino}methyl)-3,5-dimethoxyphenoxymethyl]-6-phenylbenzonitrile;
2-{4-[(cyclobutylamino)methyl]-3,5-dimethoxyphenoxymethyl}-6-phenylbenzonitrile;
2-{4-[(cyclopentylamino)methyl]-3,5-dimethoxyphenoxymethyl}-6-phenylbenzonitrile;
2-{4-[(cyclohexylamino)methyl]-3,5-dimethoxyphenoxymethyl}-6-phenylbenzonitrile;
2-[3,5-dimethoxy-4-({[3-(2-oxopyrrolidin-1-yl)propyl]amino}methyl)phenoxymethyl]-6-phenylbenzonitrile;
2-(3,5-dimethoxy-4-{[(propan-2-yl)amino]methyl}phenoxymethyl)-6-phenylbenzonitrile;
N-{2-[({4-[(2-cyano-3-phenylphenyl)methoxy]-2,6-dimethoxyphenyl}methyl)amino]ethyl}acetamide;
2-[4-({[2-(dimethylamino)ethyl]amino}methyl)-3,5-dimethoxyphenoxymethyl]-6-phenylbenzonitrile;
2-(3,5-dimethoxy-4-{[(2-methoxyethyl)amino]methyl}phenoxymethyl)-6-phenylbenzonitrile;
2-(4-{[(2-hydroxyethyl)amino]methyl}-3,5-dimethoxyphenoxymethyl)-6-phenylbenzonitrile;
2-[4-({[1-(hydroxymethyl)cyclopentyl]amino}methyl)-3,5-dimethoxyphenoxymethyl]-6-phenylbenzonitrile;
2-(4-{[(4-hydroxycyclohexyl)amino]methyl}-3,5-dimethoxyphenoxymethyl)-6-phenylbenzonitrile;
3-[({4-[(2-cyano-3-phenylphenyl)methoxy]-2,6-dimethoxyphenyl}methyl)amino]propanamide;
2-{3,5-dimethoxy-4-[(methylamino)methyl]phenoxymethyl}-6-phenylbenzonitrile;
2-[3,5-dimethoxy-4-({[2-(pyridin-2-yl)ethyl]amino}methyl)phenoxymethyl]-6-phenylbenzonitrile;
2-{3,5-dimethoxy-4-[(2-methylpyrrolidin-1-yl)methyl]phenoxymethyl}-6-phenylbenzonitrile;
2-{4-[(4-acetylpiperazin-1-yl)methyl]-3,5-dimethoxyphenoxymethyl}-6-phenylbenzonitrile;
2-[3,5-dimethoxy-4-(pyrrolidin-1-ylmethyl)phenoxymethyl]-6-phenylbenzonitrile;
2-(4-{[3-(hydroxymethyl)piperidin-1-yl]methyl}-3,5-dimethoxyphenoxymethyl)-6-phenylbenzonitrile;
N-[(3S)-1-({4-[(2-cyano-3-phenylphenyl)methoxy]-2,6-dimethoxyphenyl}methyl)pyrrolidin-3-yl]acetamide;
2-[4-(azetidin-1-ylmethyl)-3,5-dimethoxyphenoxymethyl]-6-phenylbenzonitrile;
2-{4-[(4-acetyl-1,4-diazepan-1-yl)methyl]-3,5-dimethoxyphenoxymethyl}-6-phenylbenzonitrile;
2-(4-{[ethyl(pyridin-4-ylmethyl)amino]methyl}-3,5-dimethoxyphenoxymethyl)-6-phenylbenzonitrile;
2-(4-{[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-3,5-dimethoxyphenoxymethyl)-6-phenylbenzonitrile;
2-{4-[(2, 5-dimethylpyrrolidin-1-yl)methyl]-3,5-dimethoxyphenoxymethyl}-6-phenylbenzonitrile;
2-{4-[(3-hydroxypiperidin-1-yl)methyl]-3,5-dimethoxyphenoxymethyl}-6-phenylbenzonitrile;
1-({4-[(2-cyano-3-phenylphenyl)methoxy]-2,6-dimethoxyphenyl}methyl)piperidine-3-carboxylic acid;
(2S)-1-({4-[(2-cyano-3-phenylphenyl)methoxy]-2,6-dimethoxyphenyl}methyl)pyrrolidine-2-carboxamide;
(2S)-1-({4-[(2-cyano-3-phenylphenyl)methoxy]-2,6-dimethoxyphenyl}methyl)piperidine-2-carboxylic acid;
(6 S)-5-({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)-1,2,5-triazaspiro[2.4]hept-1-ene-6-carboxylic acid;
{2-[2-(2-aminoethoxy)ethoxy]ethyl}({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amine;
2-(2-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethoxy}ethoxy)ethan-1-ol;
({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)({2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl})amine;
({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)({2-[4-(pyridin-2-yl)piperazin-1-yl]ethyl})amine;
({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)({2-[4-(pyrimidin-2-yl)piperazin-1-yl]ethyl})amine;
tert-butyl 4-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}piperazine-1-carboxylate;
4-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}-1λ6,4-thiomorpholine-1,1-dione;
benzyl N-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}carbamate;
({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)[3-(4-methylpiperazin-1-yl)propyl]amine;
({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)[3-(morpholin-4-yl)propyl]amine;
({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)[3-(1H-imidazol-1-yl)propyl]amine;
4-{[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]methyl}azetidin-2-one;
3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-N-[2-(1H-imidazol-4-yl)ethyl]propanamide;
2-({3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propyl}(2-hydroxyethyl)amino)ethan-1-ol;
({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)(3-phenoxypropyl)amine;
4-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-hydroxybutanoic acid;
3-(4-{3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propyl}piperazin-1-yl)phenol;
[2-(benzyloxy)ethyl]({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amine;
1-{2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}-5,8,11-trioxa-2-azatridecan-13-ol;
1-{2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}-5,8,11,14,17,20-hexaoxa-2-azatricosan-23-oic acid;
1-{2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}-5,8,11,14-tetraoxa-2-azaheptadecan-17-oic acid;
(2S)-5-carbamimidamido-2-[(2R)-2-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]acetamido}-3-phenylpropanamido]pentanoic acid;
2-(2-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]acetamido}acetamido)acetic acid;
(2S)-5-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-acetamidopentanoic acid;
[(3,3-difluorocyclobutyl)methyl]({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amine;
(cyclobutylmethyl)({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amine;
(2S)-2-(2-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]acetamido}acetamido)-4-methylpentanoic acid;
(2-aminoethyl)({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)methylamine;
3-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)(methyl)amino]ethyl}-1-phenylurea;
N-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)(methyl)amino]ethyl}-2-oxo-2H-chromene-6-sulfonamide;
N-{2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)(methyl)amino]ethyl}prop-2-enamide;
ethyl (2E)-3-({2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)(methyl)amino]ethyl}carbamoyl)prop-2-enoate;
(6 S)-5-({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)-1,2,5-triazaspiro[2.4]hept-1-ene-6-carboxylic acid;
2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-(hydroxymethyl)propane-1,3-diol;
(3S)-4-[({3-chloro-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-hydroxybutanoic acid;
N-{2-[({3-cyano-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethyl}acetamide;
N-(2-{[(4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-2,5-difluorophenyl)methyl]amino}ethyl)acetamide;
(3S)-4-{[(4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-2, 5-difluorophenyl)methyl]amino}-3-hydroxybutanoic acid;
(2S)-1-[(4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-2, 5-difluorophenyl)methyl]piperidine-2-carboxylic acid;
N-{2-[({2-methoxy-6-[(2-methyl-3-phenylphenyl) methoxy]pyridin-3-yl}methyl)amino]ethyl}acetamide;
5-(azetidin-1-ylmethyl)-2-[(2-methyl-3-phenylphenyl)methoxy]pyridine;
N-({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)cyclobutanamine;
N-({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)cyclopentanamine;
1-{3-[({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amino]propyl}pyrrolidin-2-one;
({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)[2-(pyridin-2-yl)ethyl]amine;
2-[(2-methyl-3-phenylphenyl)methoxy]-5-(pyrrolidin-1-ylmethyl)pyridine;
[(2S)-1-({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)pyrrolidin-2-yl]methanol;
(2S)-1-({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)piperidine-2-carboxylic acid;
1-({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)piperidine-3-carboxylic acid;
[1-({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)piperidin-3-yl]methanol;
1-({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)piperidin-4-ol;
2-[(2-methyl-3-phenylphenyl)methoxy]-5-[(2-methylpyrrolidin-1-yl)methyl]pyridine;
({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)(propan-2-yl)amine;
methyl({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amine;
N-{2-[({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amino]ethyl}acetamide;
[2-(dimethylamino)ethyl]({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amine;
(2-methoxyethyl)({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amine;
2-[({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amino]ethan-1-ol;
{1-[({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amino]cyclopentyl}methanol;
4-[({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amino]cyclohexan-1-ol;
3-[({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amino]propanamide;
(2S)-2-[({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amino]propanoic acid;
5-{[({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)amino]methyl}pyrrolidin-2-one;
N-[(3S)-1-({6-[(2-methyl-3-phenylphenyl)methoxy]pyridin-3-yl}methyl)pyrrolidin-3-yl]acetamide;
(2R)-2-{[(4-{[3-(3-fluoro-5-methoxyphenyl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl]amino}propanoic acid;
(2R)-2-{[(4-{[3-(2H-1,3-benzodioxol-5-yl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl]amino}propanoic acid;
3-[3-(4-{[(2-hydroxyethyl)amino]methyl}-3,5-dimethoxyphenoxymethyl)-2-methylphenyl]phenol;
2-{[(4-{[3-(2H-1,3-benzodioxol-5-yl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl]amino}ethan-1-ol;
2-{[(4-{[3-(3-ethoxyphenyl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl]amino}ethan-1-ol;
2-[({2,6-dimethoxy-4-[(2-methyl-3-{3-[2-(piperidin-1-yl)ethoxy]phenyl}phenyl)methoxy]phenyl}methyl)amino]ethan-1-ol;
2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-methylpropane-1,3-diol;
(2S,3S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-methylpentan-1-ol;
(2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-4-methylpentan-1-ol;
1-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propan-2-ol;
{1-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]cyclopentyl}methanol;
2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propane-1,3-diol;
1-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]butan-2-ol;
(2S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-4-methylpentan-1-ol;
(2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-methylbutan-1-ol;
(2S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-methylbutan-1-ol;
(2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propan-1-ol;
(2S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]butan-1-ol;
2-{[(2,6-dimethoxy-4-{[2-methyl-3-(3-propoxyphenyl)phenyl]methoxy}phenyl)methyl]amino}ethan-1-ol;
(2S)-3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propane-1,2-diol;
(2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-methylbutanoic acid;
1-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-methylpropan-2-ol;
(2S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]pentan-1-ol;
3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]butan-2-ol;
(2R)-3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propane-1,2-diol;
(2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]butan-1-ol;
(2S)-1-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]propan-2-ol;
2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]cyclohexan-1-ol;
(1S,2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]cyclohexan-1-ol;
(3R,4S)-4-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]oxolan-3-ol;
1-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-methylbutan-2-ol;
({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)[3-(dimethylamino)-2-hydroxypropyl]amine;
(2R)-2-cyclopropyl-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethan-1-ol;
3-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-methylbutan-2-ol;
(2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-phenylethan-1-ol;
1-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2,3-dihydro-1H-inden-2-ol;
(1S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-1-phenylethan-1-ol;
(3S)-4-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-hydroxybutanoic acid;
4-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]thiolan-3-ol;
(1R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-1-phenylethan-1-ol;
2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-1-(pyridin-3-yl)ethan-1-ol;
2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-1-(pyridin-4-yl)ethan-1-ol;
(2S)-2-cyclohexyl-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]ethan-1-ol;
{4-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]oxan-4-yl}methanol;
2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-1-(1-methyl-1H-imidazol-2-yl)ethan-1-ol;
1-{[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]methyl}cyclohexan-1-ol;
(1R,2S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]cyclopentan-1-ol;
4-{[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]methyl}-1-methylpiperidin-4-ol;
(1R,2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]cyclohexan-1-ol;
(1S,2S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]cyclopentan-1-ol;
(1R,2R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]cyclopentan-1-ol;
(2R,3S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]butane-1,3-diol;
(2S,3R)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]butane-1,3-diol;
1-{[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]methyl}cyclobutan-1-ol;
(3R)-4-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-3-hydroxybutanoic acid;
2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-ethylpropane-1,3-diol;
(2S)-2-[({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)amino]-2-phenylethan-1-ol;
1-({2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl}methyl)-4-hydroxypiperidine-4-carboxamide;
N-(2-{[(2,6-dimethoxy-4-{[3-(3-methoxyphenyl)-2-methylphenyl]methoxy}phenyl)methyl]amino}ethyl)acetamide;
N-(2-{[(4-{[3-(3-ethoxyphenyl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl]amino}ethyl)acetamide;
N-(2-{[(4-{[3-(2H-1,3-benzodioxol-5-yl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl]amino}ethyl)acetamide;
[(4-{[3-(2H-1,3-benzodioxol-5-yl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl][2-methyl-1-(4-methylpiperazin-1-yl)propan-2-yl]amine;
N-(2-{[(4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl]amino}ethyl)acetamide;
[(4-{[3-(3-ethoxyphenyl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl][2-methyl-1-(4-methylpiperazin-1-yl)propan-2-yl]amine;
[(4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-2,6-dimethoxyphenyl)methyl][2-methyl-1-(4-methylpiperazin-1-yl)propan-2-yl]amine;
{[2,6-dimethoxy-4-({3-[3-(methoxymethoxy)phenyl]-2-methylphenyl}methoxy)phenyl]methyl}[2-methyl-1-(4-methylpiperazin-1-yl)propan-2-yl]amine;
{[2,6-dimethoxy-4-({2-methyl-3-[3-(prop-2-en-1-yloxy)phenyl]phenyl}methoxy)phenyl]methyl}[2-methyl-1-(4-methylpiperazin-1-yl)propan-2-yl]amine;
{[4-({3-[2-fluoro-5-(2-methoxyethoxy)phenyl]-2-methylphenyl}methoxy)-2,6-dimethoxyphenyl]methyl}[2-methyl-1-(4-methylpiperazin-1-yl)propan-2-yl]amine;
(3S)-4-[({4-[(2-cyano-3-phenylphenyl)methoxy]-2,6-dimethoxyphenyl}methyl)amino]-3-hydroxybutanoic acid;
(3S)-3-hydroxy-4-[({5-[(2-methyl-3-phenylphenyl)methoxy]pyridin-2-yl}methyl)amino]butanoic acid; and
N-(2-{[(3-chloro-4-{[2-methyl-3-(thiophen-3-yl)phenyl]methoxy}phenyl)methyl]amino}ethyl)acetamid.

### Claim 9 (depends on 1)

The compound according to claim 1 or salts thereof, wherein Ring A is:

### Claim 10 (depends on 1)

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

### Claim 11 (depends on 1)

A method of treating a disease or disorder associated with the inhibition of the PD-1/PD-L1 interaction, wherein said disease or disorder is a cancer selected from the group consisting of melanoma, renal cancer, prostate cancer, breast cancer, colon cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, uterine cancer, bladder cancer, ovarian cancer, brain cancer, kidney cancer, colon cancer, rectal cancer, stomach cancer, testicular cancer, Hodgkin's lymphoma, acute myeloid leukemia, chronic myeloid leukemia, myeloma, small intestine cancer, squamous cell cancer; or a virological infection selected from the group consisting of HPV, HBV, HCV, KHSV and HIV infections, the method comprising administering to a mammalian patient a compound according to claim 1 or a pharmaceutically acceptable salt.