# US 2020/0399305 A1 · Prodrug-type anticancer agent using cancer-specific enzymatic activity

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- Number: US 2020/0399305 A1
- Document ID: US20200399305A1
- Status: Published application
- Kind: A1
- Application number: 16/977,607
- Filed: 2019-03-04
- Published: 2020-12-24
- Earliest claimed: 2018-03-03
- Assignees: The University of Tokyo
- Applicants: The University of Tokyo
- Inventors: Yasuteru URANO; Mako KAMIYA; Kento HAYASHI
- Web page: https://patentgrep.com/patent/US20200399305A1

## CPC

- C07H 23/00: Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12 (esters with inorganic acids C07H11/00)
- A61P 35/00: Antineoplastic agents
- C07C 237/04: the carbon skeleton being acyclic and saturated
- C07C 271/22: to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
- 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
- C07F 7/081: {comprising at least one atom selected from the elements N, O, halogen, S, Se or Te}
- C07F 7/0812: {comprising a heterocyclic ring}
- C07H 15/203: Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
- C07K 5/06026: {the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala}
- C07B 2200/07: Optical isomers
- C07F 7/1804: {Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896)}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- 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)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

To provide novel compounds that are promising as prodrug-type anticancer agents, a compound represented by general formula (I) or a salt thereof is provided.

## Claims

### Claim 1

A compound represented by general formula (I) or a salt thereof,
(wherein,
X is selected from the group consisting of a fluorine atom, ester group (—OC(═O)—R′), carbonate group (—OCO2—R′), carbamate group (—OCONH—R′), phosphoric acid and ester groups thereof (—OP(═O)(—OR′)(—OR″), and sulfuric acid and ester groups thereof (—OSO2—OR′),
where R′ and R″ are each independently selected from substituted or unsubstituted alkyl groups or substituted or unsubstituted aryl groups;
Y is —NH—CO-L, —NH-L′, or —OL′,
where L is a partial structure of an amino acid,
L′ is a saccharide or a partial structure of a saccharide, a saccharide having a self-cleaving linker, an amino acid or a peptide having a self-cleaving linker;
R1 and R2 are each independently selected from a hydrogen atom or a monovalent substituent;
R3 represents a hydrogen atom or one to four monovalent substituents present on a benzene ring, which are the same or different).

### Claim 2 (depends on 1)

The compound or a salt thereof according to claim 1, wherein the partial structure of an amino acid of L, together with the C═O to which L bonds, constitutes an amino acid, an amino acid residue, a peptide, or part of an amino acid.

### Claim 3 (depends on 1)

The compound or a salt thereof according to claim 1, wherein the partial structure of a saccharide of L′, together with the O to which L′ bonds, constitutes a saccharide or part of a saccharide.

### Claim 4 (depends on 1)

The compound or salt thereof according to claim 1, wherein —Y in general formula (I) bonds to —C(R1)(R2)X on the ortho position or para position of the benzene ring.

### Claim 5 (depends on 1)

The compound or salt thereof according to claim 1, wherein Y has a structure selected from the following:

### Claim 6 (depends on 1)

The compound or salt thereof according to claim 1, wherein X is a fluorine atom or an ester group (—OCO—R′).

### Claim 7 (depends on 1)

The compound or salt thereof according to claim 1, wherein R1 and R2 are each independently selected from a hydrogen atom or a fluorine atom.

### Claim 8 (depends on 1)

The compound or salt thereof according to claim 1, wherein the monovalent substituent of R3 is selected from the group consisting of an alkyl group, an alkoxycarbonyl group, a nitro group, an amino group, a hydroxyl group, an alkylamino group (—NHR′, —NHCOR′), an alkoxy group (—OR′, —OCOR′), a halogen atom, a boryl group, and a cyano group (R′ is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group).

### Claim 9 (depends on 8)

The compound or salt thereof according to claim 8, wherein the monovalent substituent of R3 is an alkyl group such as a methyl group or an alkoxycarbonyl group such as a methoxycarbonyl group.

### Claim 10 (depends on 1)

A prodrug-type anticancer agent comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

A prodrug-type anticancer agent that acts cell-selectively by cancer cell-specific enzyme activity comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 11)

The prodrug-type anticancer agent according to claim 11, wherein the enzyme is a peptidase or a glycosidase.