Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1993-02-19
1994-04-05
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514365, 514381, 514383, A61K 31415, A61K 3141
Patent
active
053005198
DESCRIPTION:
BRIEF SUMMARY
This invention relates to immunosuppressive agents.
The purine derivative azathioprine interfers with cell replication, and has immunosuppressive and antileukamic properties. It is used extensively as a drug to treat a wide range of chronic inflammatory diseases in which immune mechanisms are involved such as rheumatoid arthritis; chronic active hepatitis; kidney disease; skin disease; and multiple sclerosis. It is also used to inhibit the rejection of transplanted organs such as kidneys. However, its beneficial therapeutic effects are compromised by the fact that it is toxic to bone marrow. It is the object of the present invention to provide an immunosuppressive agent which does not have this disadvantage.
According to one aspect of the invention there is provided a compound for use as an immunosuppressive agent, said compound having the formula: ##STR1## in which R.sup.1 comprises a heterocyclic ring system, a homocyclic ring system, a combined heterocyclic and homocyclic ring system, alkoxycarbonylalkyl or aryloxycarbonylalkyl group and wherein ##STR2## or isomers thereof. R.sup.1 is alkyl, aryl or hydrogen and
According to a preferred embodiment of the invention said compounds which are used as immunosupressive agents have the following formula: ##STR3## in which R.sup.2 is hydrogen, or methyl or ethyl or propyl; and one of the following: ##STR4## in which R.sup.4 is hydrogen or methyl or ethyl or propyl or phenyl or 1-naphthyl 2. ##STR5## in which R.sup.5 is hydrogen or trifluoromethyl or phenyl or 4-chlorophenyl or 4-methoxyphenyl or 3-pyridyl 3. ##STR6## in which R.sup.6 hydrogen or phenyl or chlorophenyl or 4-methoxyphenyl 4. ##STR7## in which R.sup.10 is hydrogen or an alkoxy group; and ##STR8## in which R.sup.11 is hydrogen, methyl, or hydroxyl; and ##STR9## in which Z is oxygen or sulphur or N--H; and ##STR10## in which R.sup.13 is hydrogen or an amino or carboxyl group; and ##STR11## in which R.sup.16 is alkyl or aryl 9. ##STR12## 10. in which ##STR13## 12. in which R.sup.18 is alkyl or aryl 13. ##STR14##
Specific illustrative examples of the first embodiment of the invention are as follows: ##STR15##
Some of the compounds, as referred to above are previously unknown.
Therefore, according to a further aspect of the invention there are provided compounds comprising the following formula: ##STR16## wherein the molecular groups R.sup.1, R.sup.2, and R.sup.3 are defined as one of the following:
1. R.sup.1 is defined as the following: ##STR17## in which R.sup.4 is hydrogen or methyl;
2. R.sup.1 is defined as the following: ##STR18## in which R.sup.2,R.sup.3, and R.sup.5 are one of the following combinations:
3. R.sup.1 is defined as the following: ##STR19## in which R.sup.2 is methyl; and
4. R.sup.1 is defined as the following: ##STR20## in which R.sup.2 is methyl; and or chlorine; or methoxy groups; or methoxy groups OR
5. R.sup.1 is defined as the following: ##STR21## in which R.sup.2 is methyl; and
6. R.sup.1 is defined as the following: ##STR22## in which R.sup.2 is methyl; and
7. R.sup.1 is defined as the following: ##STR23## in which R.sup.2 is methyl; and combinations:
8. R.sup.1 is defined as the following: ##STR24## in which R.sup.2 is methyl; and
9. R.sup.1 is defined as the following: ##STR25## OR
10. R.sup.1 is defined as the following: ##STR26## OR
11. R.sup.1 is defined as the following: ##STR27##
Referring now to Reaction Scheme 1, azathioprine I was originally designed as a "pro-drug" for 6-mercaptopurine II, to which it is rapidly converted by red blood cells. 6-mercaptopurine II has immunosupressive properties, but the mechanism of its action is unclear. ##STR28##
It would appear that the immunosuppressive action of azathioprine I is due not solely to prior conversion of 6-mercaptopurine II in the body, but to the immunosuppressive action of azathioprine I itself. The mechanism of action of azathioprine I differs from that of 6-mercaptopurine II. There is strong evidence to suggest that 6-mercaptopurine II is converted in vivo into a nucleotide metabolite that is associated with b
REFERENCES:
Chan et al., "Chemical Abstract" 107(13), 1987 #111843Z.
Startford et al., "Chemical Abstract" 102(19), 1985 #163025a.
Van Caneghem et al. Chemical Abstract, 105(3), #21069f, 1986.
Jones David N.
Maddocks John L.
Gupta Y. N.
Shah Mukund J.
The University of Sheffield
LandOfFree
Immunosuppressive agents does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Immunosuppressive agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Immunosuppressive agents will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-511303