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CRYSTALLINE FORMS OF 4''-(PENTYLOXY)-[1,1':4',1''-TERPHENYL]-4-CARBOXYLIC ACID, 4-BROMO-4’-PENTYLOXYBIPHENYL, 4-IODO-4’-PENTYLOXYBIPHENYL, 4''-(PENTYLOXY)-[1,1':4',1''-TERPHENYL]-4-CARBOXYLIC ACID SUCCINIMIDE ESTER AND 4''-(PENTYLOXY)-[1,1':4',1''-TERPHENYL]-4-CARBOXYLIC ACID 2,4,5-TRICHLOROPHENYL ESTER

IP.com Disclosure Number: IPCOM000184440D
Publication Date: 2009-Jun-25

Publishing Venue

The IP.com Prior Art Database

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CRYSTALLINE FORMS OF 4''-(PENTYLOXY)-[1,1':4',1''-TERPHENYL]-4- CARBOXYLIC ACID, 4-BROMO-4'-PENTYLOXYBIPHENYL, 4-IODO-4'- PENTYLOXYBIPHENYL, 4''-(PENTYLOXY)-[1,1':4',1''-TERPHENYL]-4- CARBOXYLIC ACID SUCCINIMIDE ESTER AND 4''-(PENTYLOXY)-[1,1':4',1''-

TERPHENYL]-4-CARBOXYLIC ACID 2,4,5-TRICHLOROPHENYL ESTER

    4''-(pentyloxy)-[1,1':4',1''-Terphenyl]-4-carboxylic acid (referred as "CPOT") of the following chemical structure:

O

O

HO

   C24H24O3 Exact Mass: 360,17

Mol. Wt.: 360,45

    4-Bromo-4'-pentyloxybiphenyl (referred as pBrPOB) of the following chemical structure:

Br O

   C17H19BrO Exact Mass: 318,06

Mol. Wt.: 319,24

    4-Iodo-4'-pentyloxybiphenyl (referred as pIPOB) of the following chemical structure:

O

I

   C17H19IO Exact Mass: 366,05

Mol. Wt.: 366,24

4''-(pentyloxy)-[1,1':4',1''-Terphenyl]-4-carboxylic acid succinimide ester

(referred as Su-CPOT) of the following chemical structure:

O

O

O

O

O

N

   C28H27NO5 Exact Mass: 457,19

Mol. Wt.: 457,52

    4''-(pentyloxy)-[1,1':4',1''-Terphenyl]-4-carboxylic acid 2,4,5-trichlorophenyl ester (referred as TCP-CPOT)of the following chemical structure:

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Cl

Cl

O

O

O

  C30H25Cl3O3 Exact Mass: 538,09

Mol. Wt.: 539,88

are intermediates of synthesis of 1-((4R,5R)-4,5-Dihydroxy-N2-{[4"- (pentyloxy)(1,1':4',1"-terphenyl)-4-yl]carbonyl}-L-ornithine)-echinocandin B (referred as ADF) of the following chemical structure:

    which is a semi-synthetic cyclic lipopeptide of the echinocandin B class, synthesized from Echinocandin B, a fermentation product of Aspergillus nidulans. It is an antifungal drug that inhibits the synthesis of β (1,3)-D-glucan, an essential component of fungal cell walls. It is indicated for the treatment of candidemia, esophageal candidiasis, and other forms of candida infections.

    ADF is marketed under the trade name Ecalta (EU) and Eraxis (US) by Pfizer.Crystalline forms of CPOT, pBrPOB, pIPOB, Su-CPOT, and TCP-CPOT were found and are described herein below.

CPOT crystalline form

The crystalline form of CPOT, described herein has diffraction peaks at about 2.2,
4.3, 6.4, 8.6, 12.8, 17.1, 19.8, 20.5, 21.5, 22.7, 23.8, 25.8, 28.3, 28.7, 30.3, 32.2, 34.0 and
34.7 ± 0.2 degrees two-theta.

CPOT crystalline form can be further characterized by a PXRD pattern described

in Figure 1.

Cl

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Fig.1 PXRD pattern of CPOT crystalline form

     In addition the above crystalline form can be further characterized by FT-IR spectrometry having peaks at about 2958, 2936, 1687, 1599, 1515, 1492, 1434, 1289, 1281, 1256, 1221, 1180, 1130, 1026, 865, 823, 774, 621 and 482 cm-1 ± 4 cm-1 and a FT- IR spectrum described in Figure 2.

Fig.2 FT-IR spectrum of CPOT crystalline form

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pBrPOB crystalline form

The crystalline form of pBrPOB, described herein has diffraction pea...