# US 2010/0168142 A1 · Salts of 4-aniline quinazoline derivative

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- Number: US 2010/0168142 A1
- Document ID: US20100168142A1
- Status: Published application
- Kind: A1
- Application number: 12/527,345
- Filed: 2008-02-04
- Published: 2010-07-01
- Earliest claimed: 2007-02-14
- Assignees: Shanghai Allist Pharmaceuticals, Inc.
- Inventors: Jianhui Guo; Yong Jiang
- Web page: https://patentgrep.com/patent/US20100168142A1

## CPC

- C07D 239/94: Nitrogen atoms
- A61P 35/00: Antineoplastic agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to salt forms of N-{4-[3-chloro-4-(3-fluoro-benzyloxy)phenylamino]-quinazolin-6-yl}-acrylamide, methods for preparation thereof, pharmaceutical compositions comprising the same and their use thereof. The salt forms of the present invention, which possess excellent tumor inhibitory activity, good bioavailability and low toxicity in an animal body, are suitable for the use of preparation of anti-tumor medicaments.

## Claims

### Claim 1

A pharmaceutically acceptable salt of the compound of formula (I):

### Claim 2 (depends on 1)

The salt of claim 1, wherein the salt is an acid addition salt formed from the compound of formula (I) with an inorganic or organic acid, or a base addition salt formed from the compound of formula (I) with an inorganic or organic base.

### Claim 3 (depends on 2)

The salt of claim 2, wherein the salt is the acid addition salt.

### Claim 4 (depends on 3)

The salt of claim 3, wherein the acid addition salt is selected from the group consisting of hydrobromide, hydrochloride, sulfate, bisulfate, carbonate, bicarbonate, sulfite, phosphate, biphosphate, borate, acetate, oxalate, malonate, valerate, benzoate, p-toluenesulfonate, methanesulfonate, tartrate, lactate, benzoate, toluate, citrate, maleate, fumarate, malate, pamoate, salicylate, vanillate, mandelate and succinate.

### Claim 5 (depends on 4)

The salt of claim 4, wherein the acid addition salt is selected from the group consisting of hydrochloride, sulfate, phosphate, carbonate, p-toluenesulfonate, methanesulfonate, benzoate, salicylate, oxalate, acetate, valerate, malonate and tartrate.

### Claim 6 (depends on 5)

The salt of claim 5, wherein the acid addition salt is hydrochloride or p-toluenesulfonate.

### Claim 7 (depends on 2)

The salt of claim 2, wherein the salt is a base addition salt.

### Claim 8 (depends on 7)

The salt of claim 7, wherein the base addition salt is selected from the group consisting of alkali metal salt, alkali earth metal salt, quaternary ammonium cation salt and amine salt.

### Claim 9 (depends on 8)

The salt of claim 8, wherein the base addition salt is selected from the group consisting of sodium salt, potassium salt, calcium salt, magnesium salt, tetramethyl quaternary ammonium salt, tetraethyl quaternary ammonium salt, methylamine salt, dimethylamine salt, trimethylamine salt, triethylamine salt and ethylamine salt.

### Claim 10 (depends on 9)

The salt of claim 9, wherein the base addition salt is triethylamine salt.

### Claim 11 (depends on 1)

The salt as defined in claim 1 for treatment or prevention of the mammalian tumors.

### Claim 12 (depends on 1)

A process for preparing the salt as defined in claim 1 comprising the steps of:
(a) dissolving the compound of formula (I) in an organic solvent, and adding dropwise an acid-containing solvent or a base-containing solvent with stir; and
(b) filtering the resulting mixture directly or after concentrating, to obtain a solid; water-washing, and drying the solid to obtain the salt.

### Claim 13 (depends on 12)

A process of claim 12, wherein the organic solvent is selected from the group consisting of methanol, ethanol, ethyl acetate, tetrahydrofuran, triethylamine, diethyl ether, 1,4-dioxane and a combination thereof.

### Claim 14 (depends on 1)

A pharmaceutical composition comprising the salt as defined in claim 1 and a pharmaceutically acceptable carrier.

### Claim 15 (depends on 14)

The pharmaceutical composition of claim 14, which further comprises additional anti-tumor drugs.

### Claim 16 (depends on 1)

Use of the salt as defined in claim 1 in preparation of anti-tumor drugs.

### Claim 17 (depends on 16)

The use of claim 16, wherein the tumor is selected from the group consisting of breast cancer, non-small cell lung cancer, ovarian cancer, gastric cancer, colonic cancer, pancreatic cancer and epidermatoid squamous cancer.

### Claim 18 (depends on 1)

A method for treating or preventing mammalian tumors, comprising the administration of an effective amount of the salt as defined in claim 1 to the mammalian which needs such treatment or prevention.

### Claim 19 (depends on 18)

The method of claim 18, wherein the tumor is selected from the group consisting of breast cancer, non-small cell lung cancer, ovarian cancer, gastric cancer, colonic cancer, pancreatic cancer and epidermatoid squamous cancer.

### Claim 20 (depends on 1, 19)

The method of claim 19, further comprising the administration of additional anti-tumor drugs in combination with the salt as defined in claim 1 simultaneously or in sequence to the mammalian which needs such treatment.