Use of spiperone derivatives as immunosuppressant agents
AssigneeThe Beth Israel Hospital Association
InventorsRichard J. Sharpe, Kenenth A. Arndt, Stephen J. Galli
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Abstract
A method for suppressing an immune response in a mammal by treating the mammal with an effective amount of spiperone derivative that is without significant neuroleptic effect due to decreased binding to serotonin and/or dopamine receptors as compared with unmodified or uncomplexed spiperone, or due to topical application which maximizes local immunosuppression while limiting systemic absorption and neuroleptic effects. The spiperone derivatives are capable of inhibiting classic contact hypersensitivity reactions.
Claims8
A method for treating a mammal in need of immunosuppression, comprising administering to the mammal an effective amount of a spiperone derivative of the formula:
- ##STR7## wherein R.sub.1 =H, CH.sub.3 --, C.sub.6 H.sub.5 --, cyclohexyl, 4-(OCH.sub.3)C.sub.6 H.sub.4 --, 3-(CH.sub.3)C.sub.6 H.sub.4 --, 4-(CH.sub.3)C.sub.6 H.sub.4 --, 4-X--C.sub.6 H.sub.4 --, (CH.sub.3).sub.2 CH--, CH.sub.3 (CH.sub.2).sub.3 --, (CH.sub.3).sub.2 CHCH.sub.2 --, CH.sub.3 CH.sub.2 CH(CH.sub.3)--, (CH.sub.3).sub.3 C--;
- or Y--CH.sub.2 (CH.sub.2).sub.m --.
- R.sub.2 H or CH.sub.3 ;
- R.sub.3 =H, CH.sub.3, CH.sub.3 CH.sub.2 --, CH.sub.3 CH.sub.2 CH.sub.2 --, (CH.sub.3).sub.2 CH--, CN(CH.sub.2).sub.2 --, or CH.sub.3 (CH.sub.2).sub.s --;
- R.sub.4 =H, C.sub.6 H.sub.5 CH(CH.sub.2 CH.sub.3)CH.sub.2 --, C.sub.6 H.sub.5 CH(CH.sub.3)(CH.sub.2).sub.2 --, C.sub.6 H.sub.5 CH.sub.2 CH(CH.sub.3)CH.sub.2 --, C.sub.6 H.sub.5 CH.sub.2 CH.sub.2 CH(CH.sub.3)--, C.sub.6 H.sub.5 CH(CH.sub.3)(CH.sub.2).sub.3 --, 4-CH.sub.3 C.sub.6 H.sub.4 CH(CH.sub.3)(CH.sub.2).sub.3 --, 4-(CH.sub.3 O)C.sub.6 H.sub.4 CH(CH.sub.3)(CH.sub.2).sub.3, 4-X--C.sub.6 H.sub.4 CH(CH.sub.3)CH.sub.2 --, 4-X--C.sub.6 H.sub.4 CH(CH.sub.2 CH.sub.3)CH.sub.2 --, 4-X--C.sub.6 H.sub.4 CH(CH.sub.3)(CH.sub.2).sub.2 --, 4-X--C.sub.6 H.sub.4 --CH(CH.sub.3)(CH.sub.2).sub.3 --, C.sub.6 H.sub.5 CH(OCH.sub.3)(CH.sub.2).sub.2 --, ##STR8## C.sub.6 H.sub.5 CO(CH.sub.2).sub.3 --, C.sub.6 H.sub.5 CO(CH.sub.2).sub.4 --, 4-(CH.sub.3)C.sub.6 H.sub.4 CO(CH.sub.2).sub.3 --, 4-(CH.sub.3 O)C.sub.6 H.sub.4 CO(CH.sub.2).sub.3 --, 4-X--C.sub.6 H.sub.4 CO(CH.sub.2).sub.3 --, 4-X--C.sub.6 H.sub.4 CO(CH.sub.2).sub.3 --, 2-thienyl--CO(CH.sub.2).sub.3 --, ##STR9## 4-XC.sub.6 H.sub.4 C(CH.sub.3)CH(CH.sub.2).sup.-.sub.2, where the conformation about the double bond is cis or trans,
- 4-XC.sub.6 H.sub.4 C(CH.sub.3)CHCH.sub.2.sup.-, where the conformation about the double bond is cis or trans,
- 4-X--C.sub.6 H.sub.4 COCH.dbd.CHCH.sub.2, or
- --Y--CH.sub.2 (CH.sub.2).sub.s.
- wherein n=3 or 4;
- m is between 1 to 4;
- s is between 1 to 6;
- X=is a heteroatom or a substituted heteroatom such as F, Cl, Br, I, OCH.sub.3, SO.sub.3.sup.-, or NH.sub.2 ;
- Y=H or a heteroatom such as F, Cl, Br, I, SO.sub.3, PO.sub.4.sup.=, OH, SH, SCH.sub.3, CH.sub.3 SO.sub.2.sup.-, NH.sub.2, --CO.sub.2.sup.- ;
- and each of Ar and Ar.sub.1 is, independently, H, C.sub.6 H.sub.5 --, 4-(CH.sub.3)C.sub.6 H.sub.4 --, 4-(CH.sub.3 O)C.sub.6 H.sub.4 --, 4-X--C.sub.6 H.sub.4 --, 3-(CX.sub.3)C.sub.6 H.sub.4 --, 2-thienyl, or 4-X--C.sub.6 H.sub.4 CH.sub.2 --
- in a carrier selected from the group suitable for systemic pharmaceutical administration to immunosuppress the mammal.
Dependencies are inferred from the claim text.