# US 8,541,391 B2 · Crystalline phases of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole

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- Number: US 8,541,391 B2
- Document ID: US8541391B2
- Status: Granted
- Kind: B2
- Application number: 13/282,504
- Filed: 2011-10-27
- Published: 2012-11-01
- Granted: 2013-09-24
- Earliest claimed: 2010-10-28
- Assignees: ViroPharma Incorporated
- Applicants: Eugene C. Amparo; Cristina Stoica; Mihaela Pop; Jaroslaw Mazurek
- Inventors: Eugene C. Amparo; Cristina Stoica; Mihaela Pop; Jaroslaw Mazurek
- Web page: https://patentgrep.com/patent/US8541391B2

## CPC

- C07H 19/052: Imidazole radicals
- A61K 31/7056: containing five-membered rings with nitrogen as a ring hetero atom
- A61P 31/22: for herpes viruses
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- 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

## Abstract

The invention relates to novel crystalline forms of 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole (Maribavir), pharmaceutical compositions thereof and their use in medical therapy.

## Claims

### Claim 1

Crystalline Form VIII of 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole having an X-ray powder diffraction pattern substantially as shown in FIG. 1.

### Claim 2

A crystalline form of 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole having an X-ray powder diffraction pattern selected from the group consisting of those substantially as shown in FIGS. 2-15.

### Claim 3

A crystalline solvate form of 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole, including a stoichiometric ratio of an organic solvent within at least one cavity of the crystal lattice, said solvent being selected from the group of methanol, ethyl formate, t-butylmethyl ether, acetonitrile, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, isopropyl ether, 1,2-dimethoxyethane, toluene, 2,2-dimethyl-3-butanone, hexafluorbenzene, nitrobenzene, 1,4-dioxane, tetrahydrofuran (THF), n-heptane, cyclohexane, methylbutyrate, or mixtures thereof.

### Claim 4 (depends on 1)

A pharmaceutical composition comprising a crystalline form of 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole according to claim 1 and at least one pharmaceutically acceptable carrier.

### Claim 5 (depends on 4)

A pharmaceutical composition according to claim 4 in the form of a powder, tablet, capsule or suspension.

### Claim 6

A composition comprising an admixture of crystalline Form VIII of 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole, together with at least one of Form I, Form II, ethanol solvate, Form IV, Form V, Form VI and amorphous 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole.

### Claim 7 (depends on 2)

A composition comprising an admixture of a crystalline form of 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole according to claim 2 together with at least one of Form I, Form II, ethanol solvate, Form IV, Form V, Form VI and amorphous 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole.

### Claim 8 (depends on 1)

A method for treatment or prophylaxis of a herpes viral infection in a patient in need thereof comprising administering to said patient an effective anti-viral amount of crystalline Form VIII of 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole according to claim 1.

### Claim 9 (depends on 8)

A method according to claim 8, wherein said herpes viral infection is cytomegalovirus (CMV).

### Claim 10 (depends on 2)

A method for treatment or prophylaxis of a herpes viral infection in a patient in need thereof comprising administering to said patient an effective anti-viral amount of a crystalline form of 5,6-dichloro-2-(isopropylamino)-1-(β-L-ribofuranosyl)-1H-benzimidazole according to claim 2.

### Claim 11 (depends on 10)

A method according to claim 10, wherein said herpes viral infection is cytomegalovirus (CMV).

### Claim 12 (depends on 3)

The crystalline solvate of claim 3, wherein said cavity (or cavities) including said solvent or solvent mixture occupies between about 3.3 to about 18.5% of the unit cell volume.

### Claim 13 (depends on 12)

The crystalline solvate of claim 12, wherein said cavity or cavities also includes water.