Browse Prior Art Database

Crystalline forms of Racemic 3-(Carbamoylmethyl)-5-methylhexanoic acid and of R-(+)-3-(Carbamoylmethyl)-5-methylhexanoic acid and process for preparation thereof

IP.com Disclosure Number: IPCOM000146904D
Publication Date: 2007-Feb-27
Document File: 4 page(s) / 21K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
At least one non-text object (such as an image or picture) has been suppressed.
This is the abbreviated version, containing approximately 55% of the total text.

Page 1 of 4

Crystalline forms of Racemic 3-(Carbamoylmethyl)-5-methylhexanoic acid and of R-(+)-3-(Carbamoylmethyl)-5-methylhexanoic acid and process for preparation thereof

    Racemic 3-(Carbamoylmethyl)-5-methylhexanoic acid (referred to as CMH) and its R enantiomer, R-(+)-3-(Carbamoylmethyl)-5- methylhexanoic acid (referred to as R- CMH) of the following structure:

H2N

O

CO2H

are key intermediates in the synthesis of (S)-(+)-3-(aminomethyl)-5-methylhexanoic acid (referred to as PRG) of the follo wing structure.

H2N

PRG is known also as ?-amino butyric acid or (S)-3-isobutyl GABA. PRG has been found to activate GAD (L- glutamic acid decarboxylase). PRG has a dose dependent protective effect on-seizure, and is a CNS-active compound. PRG is useful in anticonvulsant therapy, due to its activation of GAD, promoting the production of GABA, one of the brain's major inhibitory neurotransmitters, which is released at 30 percent of the brains synapses. PRG has analgesic, anticonvulsant, and anxiolytic activity.

    Crystalline forms of CMH and of R-CMH were found and are described herein below.

Form a of R-CMH

The crystalline form, designated form a, is characterized by PXRD pattern with peaks at
9.0, 13.0, 13.8, 14.4, 18.2, 19.3, 20.4 ± 0.2 degrees 2-theta.

1

O

OH

[This page contains 3 pictures or other non-text objects]

Page 2 of 4

34400

36000

31200

32800

29600

26400

28000

23200

24800

20000

21600

16800

18400

13600

15200

10400

12000

7200

8800

5600

2400

4000

800

2.0 5.0 8.0 11.0 14.0 17.0 20.0 23.0 26.0 29.0 32.0 35.0 38.0
Deg.

Form b of CMH

    The crystalline form, designated form b, is characterized by PXRD pattern with peaks at 6.3, 12.6, 15.7, 19.2, 21.7 ± 0.2 degrees 2-theta.

86000

82000

78000

74000

70000

66000

62000

58000

50000

54000

46000

42000

34000

38000

30000

26000

22000

18000

14000

10000

6000

2000

2.0 5.0 8.0 11.0 14.0 17.0 20.0 23.0 26.0 29.0 32.0 35.0 38.0
Deg.

X-Ray Powder Diffractions were performed on ARL (Scintag) X-Ray powder diffractometer model X'TRA, Cu-tube, solid state detector. A round standard aluminum sample holder with

2

[This page contains 1 picture or other non-text object]

Page 3 of 4

round zero background quartz plat...