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SALTS OF SUNITINIB

IP.com Disclosure Number: IPCOM000241097D
Publication Date: 2015-Mar-26

Publishing Venue

The IP.com Prior Art Database

Abstract

The present disclosure relates to salts of sunitinib and processes for their preparation. The present disclosure further provides crystalline forms of salts of sunitinib.

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SALTS OF SUNITINIB

Abstract

The present disclosure relates to salts of sunitinib and processes for their preparation.  The present disclosure further provides crystalline forms of salts of sunitinib.

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Sunitinib is chemically described as N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidine)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide and is represented by Formula I.

FORMULA I

Sunitinib is an oral multi-kinase inhibitor and is useful for the treatment of gastrointestinal stromal tumors and advanced renal cell carcinoma.  Sunitinib is commercially available as an L-malate salt, which is described chemically as butanedioic acid, hydroxy-, (2S)-, compound with N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidine)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (1:1).

Brief Description of the Drawings

Figure 1 depicts the X-ray powder diffraction (XRPD) pattern of crystalline Form I of an adipate salt of sunitinib prepared as per Example 1.  

Figure 1a depicts the associated values for the XRPD pattern depicted in Figure 1.

Figure 2 depicts the XRPD pattern of crystalline Form I of a glutarate salt of sunitinib prepared as per Example 2.

Figure 2a depicts the associated values for the XRPD pattern depicted in Figure 2.

Figure 3 depicts the XRPD pattern of crystalline Form I of a nicotinate salt of sunitinib prepared as per Example 3.

Figure 3a depicts the associated values for the XRPD pattern depicted in Figure 3.

Figure 4 depicts the XRPD pattern of crystalline Form I of a 4-hydroxybenzoate salt of sunitinib prepared as per Example 4.

Figure 4a depicts the associated values for the XRPD pattern depicted in Figure 4.

Figure 5 depicts the XRPD pattern of crystalline Form I of a saccharate salt of sunitinib prepared as per Example 5.

Figure 5a depicts the associated values for the XRPD pattern depicted in Figure 5.

Figure 6 depicts the Differential Scanning Calorimetry (DSC) thermogram of crystalline Form I of an adipate salt of sunitinib prepared as per Example 1.

Figure 7 depicts the DSC thermogram of crystalline Form I of a glutarate salt of sunitinib prepared as per Example 2.

Figure 8 depicts the DSC thermogram of crystalline Form I of a nicotinate salt of sunitinib prepared as per Example 3.

Figure 9 depicts the DSC thermogram of crystalline Form I of a 4-hydroxybenzoate salt of sunitinib prepared as per Example 4.

Figure 10 depicts the DSC thermogram of crystalline Form I of a saccharate salt of sunitinib prepared as per Example 5.

Reported herein is a salt of sunitinib selected from the group consisting of adipate, glutarate, nicotinate, 4-hydroxybenzoate, and saccharate.

Also reported herein is a crystalline Form I of an adipate salt of sunitinib.   

The crystalline Form I of an adipate salt of sunitinib is characterized by XRPD peaks at interplanar spacing (d) values at about 3.15, 3.34, 3.42, 3.50, 4.30,...