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Crystalline form of 4-[5-[Bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoic acid hydrochloride

IP.com Disclosure Number: IPCOM000184385D
Publication Date: 2009-Jun-23
Document File: 3 page(s) / 98K

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The IP.com Prior Art Database

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Crystalline form of 4-[5-[Bis(2-chloroethyl)amino]-1-methylbenzimidazol-2- yl]butanoic acid hydrochloride

    4-[5-[Bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoic acid hydrochloride (referred as "BNT HCl"), having the following formula;

O

    belongs to the family of drugs called alkylating agents. BNT HCl is the substance in the treatment of leukemia, chronic lymphocytic leukemia (CLL) and also being studied for the treatment of sarcoma.

    BNT HCl received first marketing approval in Germany under the trade name Ribomustin, by Astellas Pharma GmbH's licensee, Mundipharma International Corporation Limited, which it is indicated as a single-agent or in combination with other anticancer agents for indolent NHL, multiple myeloma, and chronic lymphocytic leukemia (CLL).

A crystalline form of BNT HCl was found and it is described herein below.

BNT HCl crystalline form

    The crystalline form of BNT HCl is characterized by data selected from the group consisting of: a powder XRD pattern with peaks at about 7.0, 9.8, 14.8, 19.7 and 21.6 ±
0.1 degrees 2-theta; a powder XRD pattern as depicted in figure 1; and a combination thereof.

Cl

OH

HCl

N

N

N

Cl

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Figure 1 shows a powder XRD pattern of crystalline BNT HCl (the peak marked with "Si" belongs to silicon internal standard; the amorphous bump is a result of presence of n-dodecane used for sample preparation)

Si

    The above crystalline form of BNT HCl can be further characterized by data selected from the group consisting of: a powder XRD pattern with peaks at about 10.2,
10.6, 12.4, 22.0 and 30.1 ± 0.1 degrees 2-theta.

Experimental

PXRD
XRD analysis was performed on X-Ray powder diffractometer: Philips X'pert Pro powder diffractometer, CuKα radiation, λ = 1.5418 Å. X'Celerator detector active length (2 theta) = 2.122°, laboratory temperature 22-25 °C. Zero background sample holders were used. Prior to analysis the samples were gently g...