# US 11,999,748 B2 · Exatecan derivatives, linker-payloads, and conjugates and thereof

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- Number: US 11,999,748 B2
- Document ID: US11999748B2
- Status: Granted
- Kind: B2
- Application number: 18/453,748
- Filed: 2023-08-22
- Published: 2024-01-18
- Granted: 2024-06-04
- Earliest claimed: 2021-11-16
- Assignees: Genequantum Healthcare (Suzhou) Co., Ltd.
- Applicants: Genequantum Healthcare (Suzhou) Co., Ltd.
- Inventors: Gang Qin; Tony Yantao Zhang; Guangming Chen; Paul H. Song; Boyu Zhong; Mingyu Hu
- Web page: https://patentgrep.com/patent/US11999748B2

## CPC

- C07D 491/22: in which the condensed system contains four or more hetero rings
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/66: the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
- A61K 47/68037: {the drug being a camptothecin [CPT] or derivatives}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6855: {the tumour determinant being from breast cancer cell}
- A61K 47/6889: {Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment}
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- C07K 5/1008: {the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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
- 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

The present disclosure relates to the biopharmaceutical field, in particular, Exatecan derivatives, linker-payloads, and conjugates and thereof antibody-drug conjugates, and the corresponding preparing process and use thereof.

## Claims

### Claim 1

A compound or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of formula (i):
wherein,
a is 0 or 1;
the carbon atoms marked with p1* and p2* each is asymmetric center, and the asymmetric center is S configured, R configured or racemic;
L1 is selected from C1-6 alkylene, which is unsubstituted or substituted with one substituent selected from halogen, —OH and —NH2;
M is —CH2—, —NH— or —O—;
L2 is C1-3 alkylene;
R1 is Cl; and
R2 is F.

### Claim 2 (depends on 1)

The compound of claim 1, which is selected from:
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The compound of claim 1, wherein L1 is selected from C1-6 linear alkylene, C1-6 branched alkylene, C3-6 cyclic alkylene and C3-4 cyclic alkyl-C1-2 linear alkylene group, which are each independently unsubstituted or substituted with one substituent selected from halogen, —OH and —NH2.

### Claim 4 (depends on 1)

The compound of claim 1, wherein L1 is selected from C1-4 linear alkylene, C1-4 branched alkylene, C3-4 cyclic alkylene and cyclopropyl-methylene, which are each independently unsubstituted or substituted with one substituent selected from halogen, —OH and —NH2.

### Claim 5 (depends on 1)

The compound of claim 1, wherein L1 is selected from —CH2—, —C2H4—,
which are each independently unsubstituted or substituted with at least one substituent selected from halogen, —OH and —NH2.

### Claim 6 (depends on 1)

The compound of claim 1, wherein L1 is selected from —CH2—,
wherein “#” marks the position attached to carbonyl.

### Claim 7 (depends on 1)

The compound of claim 1, wherein L1 is selected from —CH2—,
wherein “#” marks the position attached to carbonyl.

### Claim 8 (depends on 1)

The compound of claim 1, wherein L1 is selected from —CH2—,
wherein “#” marks the position attached to carbonyl.

### Claim 9 (depends on 1)

The compound of claim 1, wherein the halogen is selected from F, Cl and Br.

### Claim 10 (depends on 1)

The compound of claim 1, wherein M is —CH2—, —NH— or —O—; and L2 is —C2H4—; or M is —CH2—, and L2 is —CH2—.

### Claim 11 (depends on 1)

The compound of claim 1, wherein the carbon atom marked with p1* is S configured or racemic; and/or the carbon atom marked with p2* is S configured or racemic.

### Claim 12 (depends on 1)

The compound of claim 1, wherein
a is 0, R1 is Cl, R2 is F, and L1 is selected from —CH2—,

### Claim 13 (depends on 1)

The compound of claim 1, wherein the carbon atom marked with p1* is S configured; and/or the carbon atom marked with p2* is S configured.

### Claim 14 (depends on 1)

A method of inhibiting the proliferation of a tumor and/or cancel cell, comprising contacting the tumor and/or cancer cell with the compound of claim 1.

### Claim 15 (depends on 1, 14)

The method of claim 14, wherein the compound of claim 1 is delivered to the tumor and/or cancer cell using an ADC (antibody-drug conjugate) comprising the compound of claim 1.

### Claim 16 (depends on 2)

A method of inhibiting the proliferation of a tumor and/or cancer cell, comprising contacting the tumor and/or cancer cell with the compound of claim 2.

### Claim 17 (depends on 2, 16)

The method of claim 16, wherein the compound of claim 2 is delivered to the tumor and/or cancer cell using an ADC (antibody-drug conjugate) comprising the compound of claim 2.