# US 2010/0168153 A1 · Salts and crystall forms of 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile

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- Number: US 2010/0168153 A1
- Document ID: US20100168153A1
- Status: Published application
- Kind: A1
- Application number: 12/514,976
- Filed: 2007-11-16
- Published: 2010-07-01
- Earliest claimed: 2006-11-20
- Assignees: Novartis AG
- Inventors: Frank Stowasser; Markus Banziger; Sudhakar Devidasrao Garad
- Web page: https://patentgrep.com/patent/US20100168153A1

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 13/08: of the prostate
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 309/30: of six-membered aromatic rings substituted by alkyl groups
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The invention relates to particular crystalline forms of 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile, its hydrates and solvates, its salts and hydrates and solvates of its salts, certain processes for their preparation, pharmaceutical compositions containing these crystalline forms, and their use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans, and their use as an intermediate or for the preparation of pharmaceutical preparations for use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans.

## Claims

### Claim 1

A crystalline form of the compound of formula I
or of a hydrate or solvate of the compound of formula I, or of a salt of the compound of formula I, or of a hydrate or solvate of a salt of the compound of formula I.

### Claim 2 (depends on 1)

Compound I according to claim 1 in crystalline form A.

### Claim 3 (depends on 2)

A compound according to claim 2 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 8.4°+/−0.3°.

### Claim 4 (depends on 1)

Compound I according to claim 1 in crystalline form B.

### Claim 5 (depends on 3)

A compound according to claim 3 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 6.9°+/−0.3°.

### Claim 6 (depends on 1)

Compound I according to claim 1 in crystalline form C.

### Claim 7 (depends on 6)

A compound according to claim 6 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 14.7°+/−0.3°.

### Claim 8 (depends on 1)

Compound I according to claim 1 in crystalline form

### Claim 9 (depends on 8)

A compound according to claim 8 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 23.9°+/−0.3°.

### Claim 10 (depends on 1)

A monohydrate of compound I according to claim 1 in crystalline form HA.

### Claim 11 (depends on 10)

A compound according to claim 10 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 17.6°+/−0.3°.

### Claim 12 (depends on 1)

A monotosylate salt of compound I according to claim 1 in crystalline form.

### Claim 13 (depends on 12)

A monotosylate salt of compound I according to claim 12 in crystalline form A.

### Claim 14 (depends on 12, 13)

A compound according to claim 12 or 13 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.7°+/−0.3°.

### Claim 15 (depends on 12, 13, 14)

A compound according to claim 12, 13 or 14 which shows on X-ray diffraction peaks at an angle of diffraction 2Theta of 5.4°+/31 0.3°; 5.7°+/−0.3° and 17.2°+/−0.3°.

### Claim 16 (depends on 12, 13)

A compound according to claim 12 or 13 which shows an X-ray diffraction diagram essentially as outlined in FIG. 6.

### Claim 17 (depends on 12)

A monotosylate salt of compound I according to claim 12 in crystalline form B.

### Claim 18 (depends on 12, 17)

A compound according to claim 12 or 17 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.8°+/−0.3°.

### Claim 19 (depends on 12, 17, 18)

A compound according to claim 12, 17 or 18 which shows on X-ray diffraction peaks at an angle of diffraction 2Theta of 5.8°+/−0.3°; 17.8°+/−0.3° and 18.7°+/−0.3°.

### Claim 20 (depends on 1)

A monohydrate of the monotosylate salt of compound I according to claim 1 in crystalline form HA.

### Claim 21 (depends on 20)

A compound according to claim 20 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 6.5°+/−0.3°.

### Claim 22 (depends on 1)

A dihydrate of the monotosylate salt of compound I according to claim 1 in crystalline form HB.

### Claim 23 (depends on 22)

A compound according to claim 22 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 6.9°+/−0.3°.

### Claim 24 (depends on 1)

A diformic acid solvate of the monotosylate salt of compound I according to claim 1 in crystalline form SA.

### Claim 25 (depends on 24)

A compound according to claim 24 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.8°+/−0.3°.

### Claim 26 (depends on 1)

A ditosylate salt of compound I according to claim 1 in crystalline form.

### Claim 27 (depends on 26)

A ditosylate salt of compound I according to claim 26 in crystalline form A.

### Claim 28 (depends on 26, 27)

A compound according to claim 26 or 27 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 22.4°+/−0.3°.

### Claim 29 (depends on 1)

A trihydrate of the ditosylate salt of compound I according to claim 1 in crystalline form HA.

### Claim 30 (depends on 29)

A compound according to claim 29 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 4.7°+/−0.3°.

### Claim 31 (depends on 1)

An amorphous monotosylate salt of compound I according to claim 1.

### Claim 32 (depends on 1)

A monohydrate of the diformic acid solvate of the monotosylate salt of compound I according to claim 1 in crystalline form SC.

### Claim 33 (depends on 32)

A compound according to claim 32 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.6°+/−0.3°.

### Claim 34 (depends on 1)

A diacetic acid solvate of the monotosylate salt of compound I according to claim 1 in crystalline form SB.

### Claim 35 (depends on 34)

A compound according to claim 34 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.7°+/−0.3°.

### Claim 36 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

The solid form of the compound of formula I or of a hydrate or solvate of the compound of formula I, or of a salt of the compound of formula I, or of a hydrate or solvate of a salt of the compound of formula I according to any one of the claims 1 to 35, which is present in essentially pure form.

### Claim 37 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A pharmaceutical composition comprising a solid form of the compound of formula I, its hydrates or solvates, its salts and hydrates or solvates of its salts according to any one of the claims 1 to 35, and optionally at least one pharmaceutically acceptable carrier.

### Claim 38 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

The use of a solid form of the compound of formula I, its hydrates or solvates, its salts and hydrates or solvates of its salts according to any one of the claims 1 to 35 for the preparation of a medicament for the treatment of treatment of a proliferative disease selected from a benign or malignant tumor, carcinoma of the brain, kidney, liver, adrenal gland, bladder, breast, stomach, gastric tumors, ovaries, colon, rectum, prostate, pancreas, lung, vagina or thyroid, sarcoma, glioblastomas, multiple myeloma or gastrointestinal cancer, especially colon carcinoma or colorectal adenoma or a tumor of the neck and head, an epidermal hyperproliferation, psoriasis, prostate hyperplasia, a neoplasia, a neoplasia of epithelial character, lymphomas, a mammary carcinoma or a leukemia. Other diseases include Cowden syndrome, Lhermitte-Dudos disease and Bannayan-Zonana syndrome, or diseases in which the PI3K/PKB pathway is aberrantly activated.

### Claim 39 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

Method of treating a disease selected from a benign or malignant tumor, carcinoma of the brain, kidney, liver, adrenal gland, bladder, breast, stomach, gastric tumors, ovaries, colon, rectum, prostate, pancreas, lung, vagina or thyroid, sarcoma, glioblastomas, multiple myeloma or gastrointestinal cancer, especially colon carcinoma or colorectal adenoma or a tumor of the neck and head, an epidermal hyperproliferation, psoriasis, prostate hyperplasia, a neoplasia, a neoplasia of epithelial character, lymphomas, a mammary carcinoma or a leukemia. Other diseases include Cowden syndrome, Lhermitte-Dudos disease and Bannayan-Zonana syndrome, or diseases in which the PI3K/PKB pathway is aberrantly activated in a warm-blooded animal in need thereof comprising administering to the animal a crystalline form of the compound of formula I, its hydrates or solvates, its salts or hydrates or solvates of its salts according to any one of the claims 1 to 35 in a quantity which is therapeutically effective against the respective disease.