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NLT HCl Crystalline Forms

IP.com Disclosure Number: IPCOM000187328D
Publication Date: 2009-Sep-02
Document File: 6 page(s) / 97K

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The IP.com Prior Art Database

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                 NLT HCl Crystalline Forms 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3- pyridinyl)-2-pyrimidinyl]amino]-benzamide, known as NLT. NLT has the molecular formula: C28H22F3N7O, a molecular weight of 529.52gr/mol and the following chemical structure:

N

CH3

NH

N

F3C

HN

N

O

N

N

H3C

    NLT is a tyrosine kinase inhibitor used for the treatment of drug resistant chronic myelogenous leukemia (CML), and in particular, for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myeloid leukemia (CML) in adult patients whose disease has progressed on or who cannot tolerate other therapies that included imatinib. NLT is administrated as a hydrochloride salt.

    Samples of NLT HCl crystalline forms T7, T8, T10 and T14-T16 were prepared according to the processes described below. The samples were analyzed by X-Ray Powder diffraction ("XRPD") and found to contain different crystalline forms as described in patterns 1-
6.

Pattern#1: XRPD of the Crystalline Form of NLT HCl Form T7

* The peak at 28.5 corresponds to Si

    The crystalline form T7 of NLT HCl is characterized by data selected from the group consisting of: an x-ray powder diffraction pattern having peaks at about 3.8, 7.5, 18.7, 19.9, and
25.4 degrees two theta ± 0.2 degrees two theta; an x-ray powder diffraction pattern substantially as depicted in Pattern 1; and a combination thereof. NLT HCl Form T7 may be further

1

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characterized by x-ray powder diffraction pattern having peaks at about 8.7, 11.4, 15.2, 19.4 and
22.3 degrees two theta ± 0.2 degrees two theta.

Pattern#2: XRPD of the Crystalline Form of NLT HCl Form T8

* The peak at 28.5 corresponds to Si

    The crystalline form T8 of NLT HCl is characterized by data selected from the group consisting of: an x-ray powder diffraction pattern having peaks at about 6.5, 7.4, 18.3, 23.1 and
24.3 degrees two theta ± 0.2 degrees two theta; an x-ray powder diffraction pattern substantially as depicted in Pattern 2; and a combination thereof. NLT HCl Form T8 may be further characterized by x-ray powder diffraction pattern having peaks at about 12.1, 13.5 and 27.2 degrees two theta ± 0.2 degrees two theta.

Pattern#3: XRPD of the Crystalline Form of NLT HCl Form T10

2400

2000

1600

1200

800

400

0

    The crystalline form T10 of NLT HCl is characterized by data selected from the group consisting of: an x-ray powder diffraction pattern having peaks at about 8.9, 14.0, 21.0, 23.8 and

2

2.0 6.0 10.0 14.0 18.0 22.0 26.0 30.0 34.0 38.0

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25.6 degrees two theta ± 0.2 degrees two theta; an x-ray powder diffraction pattern substantially as depicted in Pattern 3; and a combination thereof. NLT HCl Form T10 may be further characterized by x-ray powder diffraction pattern having peaks at about 8.0, 15.2, 16.9, 22.3 and
29.0 degrees two theta ± 0.2 degrees two theta.

Pattern#4: XRPD of the Crystalline Form of NLT HCl Form T14

3000

2000

1000

...