# US 10,870,634 B2 · Histone demethylase inhibitors

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- Number: US 10,870,634 B2
- Document ID: US10870634B2
- Status: Granted
- Kind: B2
- Application number: 16/819,875
- Filed: 2020-03-16
- Published: 2020-07-09
- Granted: 2020-12-22
- Earliest claimed: 2016-04-19
- Assignees: Celgene Quanticel Research, Inc.
- Applicants: Celgene Quanticel Research, Inc.
- Inventors: Zhe Nie; Jeffrey Alan Stafford; James Marvin Veal; Michael Brennan Wallace
- Web page: https://patentgrep.com/patent/US10870634B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 35/00: Antineoplastic agents
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present embodiments provide for substituted triazolylpyridine derivative compounds, and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for modulating the activity of histone demethylase enzymes. Additionally, the subject compounds and compositions are useful for the treatment of cancer or other neoplastic diseases, or maladies associated with abnormal histone demethylase activity. Accordingly, the substituted triazolylpyridine derivative compounds described herein are useful in methods and medicaments for treating cancer.

## Claims

### Claim 1

A method inhibiting a histone demethylase enzyme selected from a group comprising FBXL10, JARID1B, JMJD2C and JMJD3 comprising contacting a histone demethylase enzyme with an effective amount of a compound of Formula I
wherein a compound of Formula I is optionally a pharmaceutically acceptable salt thereof, and wherein:
R1 is halogen, CH2G, NHG, or OG, wherein
G is hydrogen, alkyl, or XY, in which
X is a bond, hydrogen, or C1 alkyl, and
Y is carbocyclyl optionally substituted with aralkyl, carbocyclylalkyl, aryl optionally substituted with halogen, alkyl or carbocyclyl, —Rb—ORa, —Rb—OC(O)—Ra, —Rb—OC(O)—ORa, —Rb—OC(O)—N(Ra)2, —Rb—N(Ra)2, —Rb—C(O)Ra, —Rb—C(O)ORa, —Rb—O—Rc—C(O)N(Ra)2, —Rb—N(Ra)C(O)ORa, —Rb—N(Ra)C(O)Ra, —Rb—N(Ra)S(O)tRa, —Rb—S(O)tORa, —Rb—S(O)tORa, or —Rb—S(O)tN(Ra)2, wherein
each Ra is independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl,
each Rb is independently a direct bond or a straight or branched alkylene, alkenylene chain, carbocyclyl, or aryl optionally substituted by halogen,
each Rc is a straight or branched alkylene or alkenylene chain; and
t is 1 or 2; and
R2 is halogen or CF3; and
R5 is hydrogen, methyl, ethyl, isoproplyl, t-butyl, CHF2, CH2F, CF3, CH2OH, CHCH3OH, or C(CH3)2OH.

### Claim 2 (depends on 1)

The method of claim 1, wherein R1 is fluoro.

### Claim 3 (depends on 1)

The method of claim 1, wherein R2 is chloro or fluoro.

### Claim 4 (depends on 1)

The method of claim 1, wherein R2 is CF3; and R1 is NHG, wherein G is —X—Y wherein X is methyl.

### Claim 5 (depends on 1)

The method of claim 1, wherein G is —X—Y, and wherein Y is adamantyl, indanyl, naphthyl, 1,2-dihydronaphthyl, phenyl optionally substituted with halogen or carbocyclyl, or tetralinyl optionally substituted with aralkyl.

### Claim 6 (depends on 5)

The method of claim 5, wherein Y is phenyl substituted with alkyl, alkynyl, chloro, fluoro, fluoroalkyl, nitro, aralkyl, aralkenyl, aralkynyl, carbocyclyl, carbocyclylalkyl, —Rb—ORa, —Rb—OC(O)—Ra, —Rb—OC(O)—ORa, —Rb—OC(O)—N(Ra)2, —Rb—N(Ra)2, —Rb—C(O)Ra, —Rb—C(O)ORa, —Rb—O—Rc—C(O)N(Ra)2, —Rb—N(Ra)C(O)ORa, —Rb—N(Ra)C(O)Ra, —Rb—N(Ra)S(O)tRa, —Rb—S(O)tORa, —Rb—S(O)tORa, or —Rb—S(O)tN(Ra)2; wherein
each Ra is independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl;
each Rb is independently a direct bond or a straight or branched alkyl or alkenyl chain;
each Rc is a straight or branched alkyl or alkenyl chain; and
t is 1 or 2.

### Claim 7 (depends on 1)

The method of claim 1, wherein the compound has the structure:
wherein R2, R5, and G are as described in claim 1.

### Claim 8 (depends on 1)

The method of claim 1, wherein the compound has the structure:
wherein R2, and R5 are as described in claim 1; and
Z is independently at least one hydrogen, hydroxy, halogen, cyano, NH2, alkyl, alkenyl, alkynyl, alkoxy, aryl, aryl—S—, aralkyl, aryloxy, aralkoxy, carbocyclyl, carbocyclylalkyl, or NHRd, N(Rd)2, NHC(O)Rd, NHC(O)ORd, NHC(O)NHRd, NHC(O)N(Rd)2, NHS(O)2Rd, NRdC(O)Rd, NRdC(O)ORd, NRdC(O)NHRd, NRdC(O)N(Rd)2, or NRdS(O)2Rd, wherein
each Rd is independently alkyl, aryl, aralkyl, carbocyclyl, or carbocyclylalkyl.

### Claim 9 (depends on 8)

The method of claim 8, wherein R2 is CF3; and Z is independently at least one fluoro, phenylmethoxy, trifluoromethyloxy, straight, branched or cyclic C1− C6 alkyl.

### Claim 10 (depends on 8)

The method of claim 8, wherein R2 is CF3, one of Z is fluoro, and one of Z is NHRd or N(Rd)2.

### Claim 11 (depends on 1)

The method of claim 1, wherein the compound has the structure: