Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
2003-02-11
2004-10-12
Killos, Paul (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
C514S616000, C514S315000, 65
Reexamination Certificate
active
06803481
ABSTRACT:
FIELD OF THE INVENTION
The present invention is directed to the novel use of a peptide class of compound for treating different types and symptoms of acute and chronic pain, especially non neurophathic inflammatory pain.
BACKGROUND OF THE INVENTION
Certain peptides are known to exhibit central nervous system (CNS) activity and are useful in the treatment of epilepsy and other CNS disorders. These peptides which are described in the U.S. Pat. No. 5,378,729 have the Formula (I):
wherein
R is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, aryl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, and R is unsubstituted or is substituted with at least one electron withdrawing group or electron donating group;
R
1
is hydrogen or lower alkyl, lower alkenyl, lower alkynyl, aryl lower alkyl, aryl, heterocyclic lower alkyl, heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, each unsubstituted or substituted with an electron donating group or an electron withdrawing group; and
R
2
and R
3
are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl lower alkyl, aryl, heterocyclic, heterocyclic lower alkyl, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, or Z-Y wherein R
2
and R
3
may be unsubstituted or substituted with at least one electron withdrawing group or electron donating group;
Z is O, S, S(O)
2
, NR
4
, PR
4
or a chemical bond;
Y is hydrogen, lower alkyl, aryl, aryl lower alkyl, lower alkenyl, lower alkynyl, halo, heterocyclic, heterocyclic lower alkyl, and Y may be unsubstituted or substituted with an electron donating group or an electron withdrawing group, provided that when Y is halo, Z is a chemical bond, or
ZY taken together is NR
4
NR
5
R
7
, NR
4
OR
5
, ONR
4
R
7
, OPR
4
R
5
, PR
4
OR
5
, SNR
4
R
7
, NR
4
SR
7
, SPR
4
R
5
or PR
4
SR
7
, NR
4
PR
5
R
6
or PR
4
NR
5
R
7
,
R
4
, R
5
and R
6
are independently hydrogen, lower alkyl, aryl, aryl lower alkyl, lower alkenyl, or lower alkynyl, wherein R
4
, R
5
and R
6
may be unsubstituted or substituted with an electron withdrawing group or an electron donating group; and
R
7
is R
6
or COOR
8
or COR
8
;
R
8
is hydrogen or lower alkyl, or aryl lower alkyl, and the aryl or alkyl group may be unsubstituted or substituted with an electron withdrawing group or an electron donating group; and
n is 1-4; and
a is 1-3.
U.S. Pat. No. 5,773,475 also discloses additional compounds useful for treating CNS disorders. These compounds are N-benzyl-2-amino-3-methoxy-propionamide having the Formula (II):
wherein
Ar is aryl which is unsubstituted or substituted with halo; R
3
is lower alkoxy; and R
1
is lower alkyl especially methyl.
The patents are hereby incorporated by reference. However neither of these patents describe the use of these compounds as specific analgesics for the treatment of acute and chronic pain, especially rheumatic inflammatory pain. Particularly the antinociceptive profile and properties of this class of compounds are not disclosed.
SUMMARY OF THE INVENTION
Accordingly, the present invention relates to the novel use of a compound having Formula (I) and/or Formula (II) showing antinociceptive properties for treating different types and symptoms of acute and chronic pain, especially non neuropathic inflammatory pain.
Particularly the present invention concerns the use of said compounds of Formulae (I) and/or (II) for the preparation of a pharmaceutical composition for the treatment of different types and symptoms of acute and chronic pain, especially non neuropathic inflammatory pain. This include chronic inflammatory pain e.g. rheumatoid arthritis pain and/or secondary inflammatory osteoarthritic pain.
A compound according to the invention has the general Formula (I)
wherein
R is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, aryl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, and R is unsubstituted or is substituted with at least one electron withdrawing group, or electron donating group;
R
1
is hydrogen or lower alkyl, lower alkenyl, lower alkynyl, aryl lower alkyl, aryl, heterocyclic lower alkyl, heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, each unsubstituted or substituted with an electron donating group or an electron withdrawing group; and
R
2
and R
3
are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl lower alkyl, aryl, heterocyclic, heterocyclic lower alkyl, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, or Z-Y wherein R
2
and R
3
may be unsubstituted or substituted with at least one electron withdrawing group or electron donating group;
Z is O, S, S(O)
2
, NR
4
, PR
4
or a chemical bond;
Y is hydrogen, lower alkyl, aryl, aryl lower alkyl, lower alkenyl, lower alkynyl, halo, heterocyclic, heterocyclic lower alkyl, lower alkyl, and Y may be unsubstituted or substituted with an electron donating group or an electron withdrawing group, provided that when Y is halo, Z is a chemical bond, or
ZY taken together is NR
4
NR
5
R
7
, NR
4
OR
5
, ONR
4
R
7
, OPR
4
R
5
, PR
4
OR
5
, SNR
4
R
7
, NR
4
SR
7
, SPR
4
R
5
or PR
4
SR
7
, NR
4
PR
5
R
6
or PR
4
NR
5
R
7
,
R
4
, R
5
and R
6
are independently hydrogen, lower alkyl, aryl, aryl lower alkyl, lower alkenyl, or lower alkynyl, wherein R
4
, R
5
and R
6
may be unsubstituted or substituted with an electron withdrawing group or an electron donating group;
R
7
is independently R
6
or COOR
8
or COR
8
;
R
8
is hydrogen or lower alkyl, or aryl lower alkyl, and the aryl or alkyl group may be unsubstituted or substituted with an electron withdrawing group or an electron donating group; and
n is 1-4; and
a is 1-3.
Furthermore a compound according to the invention has the general Formula (II)
wherein
Ar is aryl which is unsubstituted or substituted with halo; R
3
is lower alkoxy; and R
1
is lower alkyl, especially methyl.
The present invention is also directed to the preparation of pharmaceutical compositions comprising a compound according to Formula (I) and/or Formula (II) useful for the treatment of rheumatic inflammatory pain.
DETAILED DESCRIPTION OF THE INVENTION
As indicated hereinabove, the compounds of Formula I are useful for treating pain, particularly non neuropathic inflammatory pain. This type of pain includes chronic inflammatory pain e.g. rheumatoid arthritis pain and/or secondary inflammatory osteoarthritic pain. They show an anti-nociceptive effectiveness.
These compounds are described in U.S. Pat. No. 5,378,729, the contents of which are incorporated by reference.
As defined herein, the “alkyl” groups when used alone or in combination with other groups, are lower alkyl containing from 1 to 6 carbon atoms and may be straight chain or branched. These groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, amyl, hexyl, and the like.
The “aryl lower alkyl” groups include, for example, benzyl, phenethyl, phenpropyl, phenisopropyl, phenbutyl, diphenylmethyl, 1,1-diphenylethyl, 1,2-diphenylethyl, and the like.
The term “aryl”, when used alone or in combination, refers to an aromatic group which contains from 6 up to 18 ring carbon atoms and up to a total of 25 carbon atoms and includes the polynuclear aromatics. These aryl groups may be monocyclic, bicyclic, tricyclic or polycyclic and are fused rings. A polynuclear aromatic compound as used herein, is meant to encompass bicyclic and tricyclic fused aromatic ring systems containing from 10-18 ring carbon atoms and up to a total of 25 carbon atoms. The aryl group includes phenyl, and the polynuclear aromatics e.g., naphthyl, anthracenyl, phenanthrenyl, azulenyl and the like. The aryl group also includes groups like ferrocyenyl. “Lower alkenyl” is an alkenyl group containing from 2 to 6 carbon atoms and at least one double bond.
These groups may be straight chained or branched and may be in the Z or E form. Such groups include vinyl, propenyl, 1-butenyl, isobutenyl, 2-bute
Hsi Jeffrey D.
Killos Paul
Reyes Hector M.
Schwarz Pharma AG
LandOfFree
Use of peptide class of compound for treating non... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of peptide class of compound for treating non..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of peptide class of compound for treating non... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3323769