# US 2023/0056729 A1 · Replication protein a (rpa)-dna interaction inhibitors

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

- Number: US 2023/0056729 A1
- Document ID: US20230056729A1
- Status: Published application
- Kind: A1
- Application number: 17/782,876
- Filed: 2020-12-10
- Published: 2023-02-23
- Earliest claimed: 2019-12-10
- Assignees: The Trustees of Indiana University
- Applicants: The Trustees of Indiana University
- Inventors: John J. TURCHI; Navnath GAVANDE
- Web page: https://patentgrep.com/patent/US20230056729A1

## CPC

- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- A61P 35/00: Antineoplastic agents
- C07D 401/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to RPA compounds or pharmaceutically acceptable salts thereof, and for the use of the compounds to treat cancer.

## Claims

### Claim 1

A compound of the formula
wherein
R1 is selected from the group consisting of bromo, chloro, iodo, trifluoromethyl, OC(O)-morpholinyl, morpholinyl, furanyl, phenyl, pyridinyl, and isoxazolyl, wherein each hydrogen atom in furanyl, phenyl, pyridinyl, and isoxazolyl is independently optionally substituted with chloro, fluoro, bromo, iodo, C1-C6 haloalkyl, C1-C6 alkyl, or morpholinyl;
R2 is —OH, —NH—OH, —NH—SO2—R5, —NH(CH2)n-morpholinyl, —NH(CH2)n-piperazinyl, or —NH(CH2)n—(N-methyl-piperazinyl);
R3 is chloro, fluoro, bromo, or iodo;
R4 is C1-C6 alkyl;
R5 is C1-C6 haloalkyl, C1-C6 alkyl, or C3-C6 cycloalkyl, and
n is 1, 2, 3, or 4;
or a pharmaceutically acceptable salt thereof; and
with the proviso that the compound is not of the formula
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is pyridinyl having one hydrogen atom substituted with chloro, fluoro, bromo, iodo, C1C6 haloalkyl, or C1-C6 alkyl.

### Claim 3 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R1 is pyridinyl having one hydrogen atom in the para position relative to the point of attachment of R1 to the compound substituted with chloro, fluoro, bromo, iodo, C1C6 haloalkyl, or C1-C6 alkyl.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is furanyl or isoxazolyl.

### Claim 5

(canceled)

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is —NH(CH2)3-morpholinyl.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is bromo or iodo.

### Claim 8

(canceled)

### Claim 9 (depends on 7)

The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R1 is iodo.

### Claim 10 (depends on 9)

The compound of claim 9, or a pharmaceutically acceptable salt thereof, wherein R2 is NH(CH2)3-morpholinyl.

### Claim 11

A compound of the formula
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1, and at least one pharmaceutically acceptable carrier, diluent, or excipient.

### Claim 13 (depends on 1)

A method of treating cancer to a patient in need of such treatment, comprising administering a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 13)

The method of claim 13, wherein the compound interferes with the cell cycle of a cancer cell or is metabolized into a chemical that interferes with the cell cycle of a cancer cell.

### Claim 15 (depends on 1)

A method of treating a disease, comprising
a. administering a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof; and
b. administering a therapeutically effective amount of at least one additional therapeutic agent.

### Claim 16 (depends on 15)

The method of claim 15, wherein the at least one additional therapeutic agent is selected from the group consisting of BMN637, NU7441, VE821, MK1775, cisplatin, etoposide, busulfan, bendamustine, carboplatin, carmustine, chlorambucil, cyclophosphamide, dacarbazine, daunorubicin, decitabine, doxorubicin, epirubicin, etoposide, idarubicin, ifosfamide, paclitaxel, abraxane, pembrolizumab, nivolumab, olaparib, rucaparib, irinotecan, lomustine, mechlorethamine, melphalan, mitomycin C, mitoxantrone, oxaliplatin, temozolomide, and topotecan.

### Claim 17 (depends on 16)

The method of claim 16, wherein the cancer is ovarian cancer cell or nonsmall cell lung cancer.

### Claim at position 18

18-27. (canceled)

### Claim 28 (depends on 1)

A method of treating disease in a patient, the method comprising
administering a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof;
wherein the patient is previously identified as having a modulated expression of at least one gene selected from the group consisting of FEN1, APTX, PRKCG, POLE2, XRCC6, ATRX, TCEA1, IP6K3, FANCM, XAB2, ERCC2, DDB1, RRM2, BRE, PRPF19, UVRAG, DCLRE1C, KAT5, RNF168, and RTEL1.

### Claim 29 (depends on 28)

The method of claim 28, wherein the patient is previously identified as having more than one gene selected from the group consisting of FEN1, APTX, PRKCG, POLE2, XRCC6, ATRX, TCEA1, IP6K3, FANCM, XAB2, ERCC2, DDB1, RRM2, BRE, PRPF19, UVRAG, DCLRE1C, KAT5, RNF168, and RTEL1.

### Claim 30 (depends on 29)

The method of claim 29, wherein the disease is selected from the group consisting of cancer, pain, neurological diseases, autoimmune diseases, and inflammation.

### Claim 31 (depends on 30)

The method of claim 30, further comprising:
administering a therapeutically effective amount of at least one additional therapeutic agent.

### Claim 32 (depends on 31)

The method of claim 31, wherein the at least one additional therapeutic agent is selected from the group consisting of BMN637, NU7441, VE821, MK1775, cisplatin, etoposide, busulfan, bendamustine, carboplatin, carmustine, chlorambucil, cyclophosphamide, dacarbazine, daunorubicin, decitabine, doxorubicin, epirubicin, etoposide, idarubicin, ifosfamide, paclitaxel, abraxane, pembrolizumab, nivolumab, olaparib, rucaparib, irinotecan, lomustine, mechlorethamine, melphalan, mitomycin C, mitoxantrone, oxaliplatin, temozolomide, and topotecan.