| US 7,544,814 B2 | ||
| [3.2.0] Heterocyclic compounds and methods of using the same | ||
| Barbara Christine Potts, Escondido, Calif. (US); Venkat Macherla, San Diego, Calif. (US); Scott Sherman Mitchell, San Carlos, Calif. (US); Ram Rao Manam, San Diego, Calif. (US); Katherine A. McArthur, San Diego, Calif. (US); Kin Sing Lam, San Diego, Calif. (US); Saskia Neuteboom, La Jolla, Calif. (US); Ta-Hsiang Chao, San Diego, Calif. (US); Benjamin Nicholson, Merion Station, Pa. (US); and Cheryl L. Billstrom, San Diego, Calif. (US) | ||
| Assigned to Nereus Pharmaceuticals, Inc., San Diego, Calif. (US) | ||
| Filed on Oct. 01, 2007, as Appl. No. 11/865,704. | ||
| Application 11/865704 is a continuation of application No. 11/118260, filed on Apr. 29, 2005, granted, now 7,276,530. | ||
| Claims priority of provisional application 60/659385, filed on Mar. 04, 2005. | ||
| Claims priority of provisional application 60/644132, filed on Jan. 13, 2005. | ||
| Claims priority of provisional application 60/627462, filed on Nov. 12, 2004. | ||
| Claims priority of provisional application 60/591190, filed on Jul. 26, 2004. | ||
| Claims priority of provisional application 60/580838, filed on Jun. 18, 2004. | ||
| Claims priority of provisional application 60/567336, filed on Apr. 30, 2004. | ||
| Prior Publication US 2008/0070969 A1, Mar. 20, 2008 | ||
| This patent is subject to a terminal disclaimer. | ||
| Int. Cl. A61K 31/407 (2006.01); C07D 491/044 (2006.01) | ||
| U.S. Cl. 548—453 [514/421] | 26 Claims |
1. A compound having the structure of Formula I, and pharmaceutically acceptable salts and pro-drug esters thereof:
 wherein the dashed line indicates that the designated bond is either a single bond or a double bond, and wherein R1 is separately selected from the group consisting of a hydrogen, a mono-substituted or poly-substituted saturated C1-C24 alkyl, mono-substituted, poly-substituted or unsubstituted variants of the following residues: C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, cycloalkoxy, aryl, heteroaryl,
arylalkoxy carbonyl, alkoxy carbonylacyl, aminocarbonyl, aminocarbonyloxy, nitro, azido, phenyl, cycloalkylacyl, arylthio,
oxysulfonyl, carboxy, cyano, thio, sulfoxide, sulfone, sulfonate ester, thiocyano, boronic acid, boronic ester, and halogenated
alkyl including polyhalogenated alkyl,
wherein the mono-substituted or poly-substituted saturated C1-C24 alkyl in R1 is substituted with one or more substituents selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl,
substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, amino, substituted amino, aminoacyl, aminoacyloxy,
oxyacylamino, cyano, halogen, carboxyl, carboxylalkyl, keto, thioketo, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy,
heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, —SO-alkyl, —SO-substituted alkyl,
—SO-aryl, —SO-heteroaryl, —SO2-alkyl, —SO2-substituted alkyl, —SO2-aryl and —SO2-heteroaryl;
wherein the halogenated alkyl in R1 is a C1-24-alkyl poly-halogenated with fluorine, bromine, chlorine or iodine; or
the halogenated alkyl is methyl or C3-24-alkyl mono-or poly-halogenated with fluorine, bromine, or iodine;
where n is equal to 1 or 2, and if n is equal to 2, then R1 can be the same or different, and at least one R1 is not hydrogen;
wherein R2 is selected from the group consisting of hydrogen, a halogen, mono-substituted, poly-substituted or unsubstituted variants
of the following residues: saturated C1-C24 alkyl, unsaturated C2-C24 alkenyl, C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl,
arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, cycloalkylacyl, hydroxy,
alkylthio, arylthio, oxysulfonyl, carboxy, cyano, thio, sulfoxide, sulfone, sulfonate ester, thiocyano, boronic acid, boronic
ester, and halogenated alkyl including polyhalogenated alkyl;
wherein R3 is selected from the group consisting of a halogen, mono-substituted, poly-substituted or unsubstituted variants of the following
residues: saturated C1-C24 alkyl, unsaturated C2-C24 alkenyl, C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl,
arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, cycloalkylacyl, hydroxy,
alkylthio, arylthio, oxysulfonyl, carboxy, cyano, thio, sulfoxide, sulfone, sulfonate esters, thiocyano, boronic acid, boronic
ester, and halogenated alkyl including polyhalogenated alkyl;
wherein each of E1 and E3 is a substituted or unsubstituted heteroatom selected from the group consisting of O and S, E2 is a substituted or unsubstituted N, and E4 is a substituted or unsubstituted heteroatom selected from the group consisting of O, S, and N; and
with the proviso that Formula I is not Compound II-16,
wherein Compound II-16 has the structure:
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