# US 11,078,232 B2 · Preparation and use of molecular site targeted and activated kinase inhibitor

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- Number: US 11,078,232 B2
- Document ID: US11078232B2
- Status: Granted
- Kind: B2
- Application number: 16/478,826
- Filed: 2018-01-16
- Published: 2020-05-07
- Granted: 2021-08-03
- Earliest claimed: 2017-01-17
- Assignees: Yafei Shanghai Biology Medicine Science & Technology Co. Ltd.
- Applicants: Yafei Shanghai Biology Medicine Science & Technology Co. Ltd.
- Inventors: Yuan Liu; Cheng Liu; Haiyang Wang
- Web page: https://patentgrep.com/patent/US11078232B2

## CPC

- A61K 47/549: {Sugars, nucleosides, nucleotides or nucleic acids}
- C07K 5/0806: {the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala}
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 47/54: the modifying agent being an organic compound
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- C07D 213/81: Amides; Imides
- C07K 5/0808: {the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu}
- C07K 5/081: {the side chain containing O or S as heteroatoms, e.g. Cys, Ser}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Disclosed are molecularly targeted and activated kinase inhibitors and use thereof. Specifically, a compound represented by the following formula A or a pharmaceutically acceptable salt thereof, wherein X is a polar and a non-polar uncharged amino acid such as alanine, proline or threonine; A is alanine; N is asparagine; PABC is —NH-phenyl-CH2-O—; and Z is a drug molecule; wherein the lactobionic acid residue, XAN and PABC are linked to each other by an amide bond; PABC is bonded to Z by an ester group, i.e., —OC(O)—.

## Claims

### Claim 1

A compound represented by the following formula A or a pharmaceutically acceptable salt thereof:
Lacto-XAN-PABC-Z (Formula A)
wherein,
X is alanine, proline or threonine;
A is alanine;
N is asparagine;
PABC is —NH-phenyl-CH2—O—;
Z is a drug molecule selected from the group consisting of doxorubicin, darafinib, dovetinib, motesanib and a sorafenib derivative represented by the following formula B:
wherein R is H or halogen;
Lacto is lactobionic acid residue;
wherein the lactobionic acid residue, XAN and PABC are linked to each other by an amide bond; PABC is bonded to Z by an ester group, namely —OC(O)—.

### Claim 2 (depends on 1)

The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein the compound of formula A has the structure of formula I:

### Claim 3 (depends on 1)

The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound of formula A or formula I has the structure of formula II, III or IV:

### Claim 4 (depends on 1)

The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein the compound is selected from the group consisting of:

### Claim 5 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 6 (depends on 1)

The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein the compound of formula B is selected from the group consisting of compound a and compound b, namely: