Histamine derivatives as immune modulators
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsKenneth L. Melmon, Murray Goodman, Manzoor M. Khan, Debra Marr-Leisy, Michael Verlander
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Abstract
Histamine derivatives are disclosed which find use as effect and tissue-specific immune modulators. Specifically, the primary terminal nitrogen in histamine is derivatized to introduce a variable length side chain having 0 to 1 branch of from 1 to 3 carbons; 0 to 2 non-oxo-carbonyl groups; 0 to 4 heteroatoms, other than the non-oxo carbonyl oxygen; 0 to 1 aryl or alkylaryl group; and 0 to 1 functionally bound amino acid, polypeptide, or protein or derivative thereof.
Claims12
Histamine derivatives having binding specificity for H.sub.1 or H.sub.2 receptors of lymphocytes being characterized by being mono-substituted at the side chain amine of a histamine molecule with a substituent having an aliphatic chain of from 2 to 10 carbon atoms, wherein the alpha-carbon of the chain is substituted with oxo or alkyl of from 1 to 3 carbon atoms, said chain terminating in . .hydrogen or.!. carboxamido, wherein the carboxamido nitrogen is substituted with alkyl of from 1 to 6 . .amido.!. carbon atoms, tolyl or trifluoromethylphenyl. ., with the proviso that when said chain terminates in hydrogen, the chain length is 5 or 6 atoms.!..
Histamine derivatives having binding specificity for H.sub.1 or H.sub.2 receptors of lymphocytes and of the formula ##STR11## wherein:
- X is CO or CHR, where R is an alkyl group of from 1 to 3 carbon atoms;
- n is an integer of from 2 to 6;
- Y is .!.CH.sub.3 or.!.CONHZ, wherein Z is H;
- (CH.sub.2).sub.m CH.sub.3, where m is .Badd.1 to 4;
- or substituted phenyl, where the substituent is methyl or trifluoromethyl;
- A is a physiologically acceptable counterion;
- and
- b is an integer of from 0 to 2. . .
Histamine derivatives having binding specificity for H.sub.1 or H.sub.2 receptors of lymphocytes and of the following formula
- His--NH--X--(CH.sub.2).sub.n --Y(HA).sub.b
- His--NH is a histaminyl residue;
- X is CO, CH.sub.2, or CHR, where R is an alkyl group of from 1 to 3 carbon atoms;
- n is an integer from 0 to 10;
- Y is CONHZ wherein Z is H;
- (CH.sub.2).sub.m CH.sub.3, where
- m is 0 to 10;
- phenyl;
- or a phenyl group substituted with methyl or halomethyl;
- A is a physiologically acceptable counterion;
- and
- b is an integer from 0 to 2.
Dependencies are inferred from the claim text.