| US 7,354,711 B2 | ||
| Methods for inhibiting immunostimulatory DNA associated responses | ||
| Donald E. Macfarlane, Iowa City, Iowa (US) | ||
| Assigned to University of Iowa Research Foundation, Iowa City, Iowa (US); and The Department of Veterans Affairs, as represented by the Secretary of United States of America, Washington, D.C. (US) | ||
| Filed on Jan. 03, 2003, as Appl. No. 10/336,635. | ||
| Application 10/336635 is a division of application No. 10/115421, filed on Apr. 02, 2002, granted, now 6,521,637, filed on Feb. 18, 2003. | ||
| Application 10/115421 is a division of application No. 09/768874, filed on Jan. 23, 2001, granted, now 6,399,630, filed on Jun. 04, 2002. | ||
| Application 09/768874 is a division of application No. 09/109513, filed on Jul. 02, 1998, granted, now 6,221,882, filed on Apr. 24, 2001. | ||
| Claims priority of provisional application 60/051666, filed on Jul. 03, 1997. | ||
| Prior Publication US 2003/0232856 A1, Dec. 18, 2003 | ||
| Int. Cl. C12Q 1/68 (2006.01); C08K 5/16 (2006.01) | ||
| U.S. Cl. 435—6 [524/187] | 4 Claims |
1. A method of identifying a compound that inhibits an immunostimulatory DNA-induced response, the method comprising contacting
a cell with an immunostimulatory DNA, thereby inducing a measurable immune response, and a test compound and detecting inhibition
of the immunostimulatory effect of the immunostimulatory DNA, wherein the test compound is selected from the group consisting
of: compounds, other than chloroquine, having the structural formula:
 wherein
RA is a hydrogen atom, a lower alkyl group, or linked to RB by a substituted or unsubstituted alkyl chain;
RB is a hydrogen atom, an alicyclic group, an alkyl secondary, tertiary or quarternary amine, or an alkenyl secondary, tertiary
or quarternary amine;
R2 is a hydrogen atom, a lower alkyl group, an aryl group, a heteroaromatic group, or a lower alkenyl group substituted with
an aryl group;
R3 is a hydrogen atom, a lower alkyl group, or an aromatic group;
R5 is a hydrogen atom, a lower alkyl group, or a halogen atom;
R6 is a hydrogen atom, a lower alkyl group, a lower alkoxy group, an aryloxy group, an aryl group, an amino group or a thioether
group;
R7 is a hydrogen atom, a lower alkyl group, a lower alkoxy group, an aryloxy group, a haloalkyl group, or a halogen atom; and
R8 is a hydrogen atom, or a lower alkoxy group, and pharmaceutically acceptable salts thereof, with the proviso that if R7 is a halogen, then at least one of R2, R3, R5, R6 or R8 is non-hydrogen and RB is not 4-[N,N-dialkyl-n-pentylamine] or 4-[N-alkyl-N-hydroxyalkyl-n-pentylamine],
compounds having the structural formula:
 wherein
RB is a hydrogen atom, or an alkyl secondary or tertiary amino substitutent selected from the group consisting of 2-[N,N-dimethyl
ethylamine], 2-[N-methyl ethylamine], 2-[ethyl-N,N-dialkyl amine], 2-[ethyl-N-alkyl amine], 2-[ethyl amine], 3-[propyl-N,N-dialkyl
amine], 3-[propyl-N-alkyl amine], 4-[pentyl-N,N-dialkyl amine], 4-[pentyl-N-alkyl amine], 4-[pentyl amine], 4-[butyl-N,N-dialkyl
amine], 4-[butyl-N-alkyl amine], 4-[butyl amine], 4-[N,N-diethyl pentylamine], 4-[N,N-diethyl butylamine], 4-[4-aryl-N,N-dialkyl
butylamine], 4-[4-heteroaromatic-N,N-dialkyl butylamine], 4-[4-aryl-N-alkyl butylamine], 4-[4-heteroaromatic-N-alkyl butylamine],
4-[N,N-dialkyl pentylamine], and 7-[hepta-4-methyl-4-azaamine];
R2 is a lower alkyl group;
R3 is a hydrogen atom or a lower alkoxy group; and
X is a halogen atom, and pharmaceutically acceptable salts thereof.
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