# US 9,040,498 B2 · 1,2,3-Triazolyl purine derivatives

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- Number: US 9,040,498 B2
- Document ID: US9040498B2
- Status: Granted
- Kind: B2
- Application number: 13/936,770
- Filed: 2013-07-08
- Published: 2014-01-09
- Granted: 2015-05-26
- Earliest claimed: 2012-07-06
- Assignees: Research Foundation of the City University of New York
- Applicants: Research Foundation of the City University of New York
- Inventors: Mahesh K. Lakshman
- Web page: https://patentgrep.com/patent/US9040498B2

## CPC

- C07H 23/00: Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12 (esters with inorganic acids C07H11/00)
- C07H 19/16: Purine radicals
- C07H 19/167: with ribosyl as the saccharide radical
- C07H 19/173: with 2-deoxyribosyl as the saccharide radical
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)

## Abstract

The present invention relates to novel 1,2,3-triazolyl purine derivatives. The invention also relates to using the derivatives to treat cancer and various viral infections. An example of a 1,2,3-triazolyl purine derivative of the invention is

## Claims

### Claim 1

A compound having Formula I,
wherein:
R1 represents an alkyl, an aryl, —SiR4, —SnR5, —B(R4)2, —B(OH)2, an amide, an imide, or an organometallic;
R2 and R3 independently represent N, CH, or CR6;
R4 independently represents —R5 or —OR5;
R5, R7 and R8, independently of each other and independently at each position, represent alkyl, cycloalkyl, or aryl;
R7 and R8 independently, may be combined to represent a heterocyclic alkyl or a heterocyclic aryl;
R6 independently represents an alkyl or an aryl;
Y represents H, an alkyl, an aryl, or a saccharide moiety;
alkyl groups are branched or unbranched, saturated or unsaturated, and have 1-18 carbon atoms in their longest chain;
cycloalkyl groups are carbocyclic or heterocyclic, fused or unfused, non-aromatic ring systems having a total of 5-16 ring members including substituent rings;
aryl groups are carbocyclic or heterocyclic;
carbocyclic aryl groups are fused or unfused ring systems having a total of 6-16 ring members including substituent rings;
heterocyclic aryl groups are fused or unfused ring systems having a total of 5-16 ring members including substituent rings;
halo substituents are fluoro, chloro, bromo, or iodo;
each alkyl, cycloalkyl, and aryl, independently, may be unsubstituted or substituted with one or more substituent at any position;
alkyl substituents are halo, hydroxyl, —OR5, —SR5, —S(O)R4, —S(O)2R4, —NH2, —NHR5, —NR7R8, cycloalkyl, or aryl;
cycloalkyl substituents are halo, hydroxyl, —OR5, —SR5, —NH2, —NHR5, —NR7R8, alkyl, cycloalkyl, or aryl;
aryl substituents are halo, hydroxyl, —OR5, —SR5, —NH2, —NHR5, —NR7R8, —CN, alkyl, cycloalkyl, aryl, nitro, or carboxyl; and
heterocyclic alkyl and heterocyclic aryl have at least one heteroatom selected from the group consisting of oxygen, nitrogen and sulfur.

### Claim 2 (depends on 1)

A compound according to claim 1, wherein Y represents a saccharide moiety, and the saccharide moiety has the following structure:
wherein:
Y1 represents C, N, or O;
R20 and R21 independently represent H, —OR23, —NR7R8, R6, or halo;
R22 represents H, OH, —CH2OR6, —CH2OR23, —NR7R8, —CH2NR7R8, R6; and
R23 represents H or a protecting group.

### Claim 3 (depends on 2)

A compound according to claim 2, wherein Y1 represents O.

### Claim 4 (depends on 2)

A compound according to claim 2, wherein R22 represents —CH2O(alkyl) or
—CH2OR23.

### Claim 5 (depends on 1)

A compound according to claim 1, wherein the saccharide moiety is selected from the group consisting of 1-ribosyl and 2′-deoxy-1-ribosyl.

### Claim 6 (depends on 1)

A compound according to claim 1, wherein R1 is an imide and the imide is represented by:
wherein:
R24 and R25 are independently an alkyl or an aryl; and
R24 and R25 independently, may be combined to represent a succinimidyl group that may be fused or unfused, and substituted or unsubstituted.

### Claim 7 (depends on 6)

A compound according to claim 6, wherein R1 is phthalimidyl.

### Claim 8 (depends on 1)

A compound according to claim 1, wherein R1 is an amide and the amide is represented by:
wherein:
R26 and R27 are independently an alkyl or an aryl.

### Claim 9 (depends on 1)

A compound according to claim 1, wherein R1 is an organometallic and the organometallic has a complex of Fe, Mo, Ru, or Pt.

### Claim 10 (depends on 9)

A compound according to claim 9, wherein R1 is ferrocenyl.

### Claim 11 (depends on 1)

A compound according to claim 1, wherein Y represents a saccharide moiety selected from the group consisting of 1-ribosyl and 2′-deoxy-1-ribosyl; R2 is N; R3 is CH; and R1 represents:

### Claim 12

A compound having Formula II,
wherein:
R1 represents an alkyl, an aryl, —SiR4, —SnR5, —B(R4)2, —B(OH)2, an amide, an imide, or an organometallic;
R2 and R3 independently represent N, CH, or CR6;
X represents —OR9, —SR9, or —NR9R10;
Y represents H, an alkyl, an aryl, or a saccharide moiety;
R4 independently represents —R5 or —OR5;
R5, R7 and R8, independently of each other and independently at each position, represent alkyl, cycloalkyl, or aryl; and
R6 independently represents an alkyl or an aryl;
R9 and R10 independently represent H, an alkyl, or an aryl;
R7 and R8, R9 and R10 independently, may be combined to represent a heterocyclic alkyl or a heterocyclic aryl;
alkyl groups are branched or unbranched, saturated or unsaturated, and have 1-18 carbon atoms in their longest chain;
cycloalkyl groups are carbocyclic or heterocyclic, fused or unfused, non-aromatic ring systems having a total of 5-16 ring members including substituent rings;
aryl groups are carbocyclic or heterocyclic;
carbocyclic aryl groups are fused or unfused ring systems having a total of 6-16 ring members including substituent rings;
heterocyclic aryl groups are fused or unfused ring systems having a total of 5-16 ring members including substituent rings;
halo substituents are fluoro, chloro, bromo, or iodo;
each alkyl, cycloalkyl, and aryl, independently, may be unsubstituted or substituted with one or more substituent at any position;
alkyl substituents are halo, hydroxyl, —OR5, —SR5, —S(O)R4, —S(O)2R4, —NH2, —NHR5, —NR7R8, cycloalkyl, or aryl;
cycloalkyl substituents are halo, hydroxyl, —OR5, —SR5, —NH2, —NHR5, —NR7R8, alkyl, cycloalkyl, or aryl;
aryl substituents are halo, hydroxyl, —OR5, —SR5, —NH2, —NHR5, —NR7R8, —CN, alkyl, cycloalkyl, aryl, nitro, or carboxyl; and
heterocyclic alkyl and heterocyclic aryl have at least one heteroatom selected from the group consisting of oxygen, nitrogen and sulfur.

### Claim 13 (depends on 12)

A compound according to claim 12, wherein X is —NR9R10 and R1 represents —SiR4, —SnR5, —B(R4)2, —B(OH)2, an imide, or an organometallic.

### Claim 14 (depends on 12)

A compound according to claim 12, wherein X is —NR9R10 and R9 and R10 independently represent an alkyl or an aryl.

### Claim 15 (depends on 12)

A compound according to claim 12, wherein R2 is N and R3 is CH.

### Claim 16 (depends on 12)

A compound according to claim 12, wherein R1 is phenyl.

### Claim 17 (depends on 12)

A compound according to claim 12, wherein R9 and R10 independently represent H or CH2Ph; or R9 and R10 are combined to represent CH2CH2OCH2CH2.

### Claim 18 (depends on 12)

A compound according to claim 12, wherein R1 is an imide and the imide is represented by:
wherein:
R24 and R25 are independently an alkyl or an aryl; and
R24 and R25 independently, may be combined to represent a succinimidyl group that may be fused or unfused, and substituted or unsubstituted.

### Claim 19 (depends on 18)

A compound according to claim 18, wherein R1 is phthalimidyl.

### Claim 20 (depends on 12)

A compound according to claim 12, wherein R1 is an amide and the amide is represented by:
wherein:
R26 and R27 are independently an alkyl or an aryl.

### Claim 21 (depends on 12)

A compound according to claim 12, wherein R1 is an organometallic and the organometallic has a complex of Fe, Mo, Ru, or Pt.

### Claim 22 (depends on 21)

A compound according to claim 21, wherein R1 is ferrocenyl.

### Claim 23 (depends on 12)

A compound according to claim 12, wherein Y represents a saccharide moiety, and the saccharide moiety has the following structure:
wherein:
Y1 represents C, N, or O;
R20 and R21 independently represent H, —OR23, —NR7R8, R6, or halo;
R22 represents H, OH, —CH2OR6, —CH2OR23, —NR7R8, —CH2NR7R8, R6; and
R23 represents H or a protecting group.

### Claim 24 (depends on 23)

A compound according to claim 23, wherein Y1 represents O.

### Claim 25 (depends on 23)

A compound according to claim 23, wherein R22 represents —CH2O(alkyl) or
—CH2OR23.

### Claim 26 (depends on 12)

A compound according to claim 12, wherein the saccharide moiety is selected from the group consisting of 1-ribosyl and 2′-deoxy-1-ribosyl.

### Claim 27

A compound having Formula III,
wherein:
R9, R10, R12, R13, R14, R15, R16, and R17 independently represent N or CR11;
R11 independently represents —R18, —OR19, —SR19, —N(R18)2, R18C(O)—, nitro, or halo;
R18 independently represents H, an alkyl group, or an aryl;
R19 independently represents R18 or a protecting group;
Y represents R18 or a saccharide moiety;
alkyl groups are branched or unbranched, saturated or unsaturated, and have 1-18 carbon atoms in their longest chain;
cycloalkyl groups are carbocyclic or heterocyclic, fused or unfused, non-aromatic ring systems having a total of 5-16 ring members including substituent rings;
aryl groups are carbocyclic or heterocyclic;
carbocyclic aryl groups are fused or unfused ring systems having a total of 6-16 ring members including substituent rings;
heterocyclic aryl groups are fused or unfused ring systems having a total of 5-16 ring members including substituent rings;
halo substituents are fluoro, chloro, bromo, or iodo;
each alkyl, cycloalkyl, and aryl, independently, may be unsubstituted or substituted with one or more substituent at any position;
alkyl substituents are halo, hydroxyl, —OR5, —SR5, —S(O)R4, —S(O)2R4, —NH2, —NHR5, —NR7R8, cycloalkyl, or aryl;
cycloalkyl substituents are halo, hydroxyl, —OR5, —SR5, —NH2, —NHR5, —NR7R8, alkyl, cycloalkyl, or aryl;
aryl substituents are halo, hydroxyl, —OR5, —SR5, —NH2, —NHR5, —NR7R8, —CN, alkyl, cycloalkyl, aryl, nitro, or carboxyl; and
heterocyclic alkyl and heterocyclic aryl have at least one heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R4 independently represents —R5 or —OR5;
R5, R7 and R8, independently of each other and independently at each position, represent alkyl, cycloalkyl, or aryl; and
R7 and R8 independently, may be combined to represent a heterocyclic alkyl or a heterocyclic aryl.

### Claim 28 (depends on 27)

A compound according to claim 27, wherein Y represents a saccharide moiety, and the saccharide moiety has the following structure:
wherein:
Y1 represents C, N, or O;
R20 and R21 independently represent H, —OR23, —NR7R8, R6, or halo;
R22 represents H, OH, —CH2OR6, —CH2OR23, —NR7R8, —CH2NR7R8, R6;
R23 represents H or a protecting group; and
R6 represents an alkyl or an aryl.

### Claim 29 (depends on 28)

A compound according to claim 28, wherein Y1 represents O.

### Claim 30 (depends on 28)

A compound according to claim 28, wherein R22 represents —CH2O(alkyl) or
—CH2OR23.

### Claim 31 (depends on 27)

A compound according to claim 27, wherein the saccharide moiety is selected from the group consisting of 1-ribosyl and 2′-deoxy-1-ribosyl.

### Claim 32 (depends on 27)

A compound according to claim 27, wherein no more than one of R14, R15, R16, and R17 represent N.

### Claim 33 (depends on 27)

A compound according to claim 27, wherein R9, R14, R15, R16, and R17 are CH; and R10, R12, and R13 are N.

### Claim 34 (depends on 27)

A compound according to claim 27, wherein R9, R14, R15, and R16 are CH; R10, R12, and R13 are N; and R17 is N or CH.

### Claim 35

A method of treating cancer, comprising administering to a patient in need thereof an effective amount of a compound of Formula I or a compound below: