Stereoisomers of...

Details Stereoisomers of... Stereoisomers of...

2002-06-27

2004-02-10

Killos, Paul J. (Department: 1625)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acids and salts thereof

Reexamination Certificate

active

06689905

ABSTRACT:

This invention concerns novel stereoisomers of 3-amino-2,6-dimethyl-bicyclo[2.2.1]-heptane-1,3-dicarboxylic acid, as well as methods for their preparation, isolation and use.
BACKGROUND OF THE INVENTION
The Journal of Medicinal Chemistry (1999) 42, 1027-1040 describes the synthesis and pharmacological activity of a series of 4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acids (ABHDA's) as group 11 metabotropic glutamate (mGlu) receptor agonists. The (−)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acid (ABHDA-I) is reported as a mGlu2 agonist with an EC
50
value of 2.69 nM while the (−)-2-thia-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acid (ABHDA-II) displayed an EC
50
value of 3.91 nM at the mGlu2 site.
The synthesis and the pharmacological profile of a series of amino-bicyclo[2.2.1]heptane dicarboxylic acids (ABHD's) as rigid analogues of 1-amino-cyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) is described in Bioorganic and Medicinal Chemistry (1998) 6, 195-208. 2-endo-aminobicyclo[2.2.1]heptane-2-exo-7-anti-dicarboxylic acid (ABHD-I) is reported as a competitive antagonist at the mGlu1a receptor with a K
b
value of 300 &mgr;M.
Both compounds (ABHD-I & ABHD-II) are described as agonists at the type 2 mGlu receptors.
Tocris Cookson Inc., 16144 Westwoods Business Park, Ellisville, Mis., 63021 (www.tocris.com) offers lists two isomers of aminotricyclo[2.2.1.0(2,6)]heptane-dicarboxylic acid.
WO 9947490 claims a series of compounds described by the formula below in which n is 0-6, X is CH
2
, CH
2
CH or O, Z is CHR
2
or NR
2
and R
1
and R
2
are hydrogen, alkyl, aryl or heteroaryl as metabotropic glutamate receptor ligands useful for the treatment of a variety of neurological and psychiatric disorders.
U.S. Pat. No. 6,124,361 (Chenard) teaches substituted bicyclo[3.1.0]hexane compounds of the formula:
wherein n is an integer from 0 to 6; Z is (C
1
-C
4
) alkylene, oxygen, sulfur, NH or N(C
1
-C
6
)alkyl; and R
1
is H or optionally substituted aryl or heteroaryl; which are metabotropic glutamate receptor ligands useful in the treatment of a variety of neurological and psychiatric disorders.


REFERENCES:
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patent: WO 99/47490 (1999-09-01), None
U.S. patent application Ser. No. 10/185,489, Stack et al., Not Published.
U.S. patent application Ser. No. 10/185,445, Greenfield et al., Not Published.
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