Novel imidazoquinolines with immunostimulatory effects
AssigneeSynovo GmbH
InventorsManuel Keppler, Simon Strass, Christiane Baeuerlein, Jan-Hinrich Guse, Mary Eggers, Martin Reisser, Michael W. Burnet, Sophia Geiger
Life of this patent
Estimating the term…
Abstract
Substituted imidazoquinoline ligands to TLR7 and 8 that up-regulate interferon production with improved specificity vs. existing ligands. The compounds exhibit improved pharmacokinetics and distribution properties and are well tolerated in vivo. They are suitable for use in therapeutics for infectious and neoplastic diseases.
Claims20
A compound of the Formula (I), or a salt thereof:
- Wherein n can be 0, 1, 2 or 3
- If n=0, X1 is CH and
- X2 is independently selected from N, O, and CH;
- X3 is independently selected from CH2, and O;
- X4 is independently selected from H, and (CH2)mCH3, wherein m can be 0, 1, 2, or 3;
- X5 is independently selected from H, and (CH2)mCH3 wherein k can be 0, 1, 2, or 3, or is absent;
- R is independently H, NH2, CH3, N(CH3)2, C2H5, C2H4—NH2, C2H4—N(CH3)2, or is absent;
- If n=1, X1 is CH and
- X2 is independently selected from N, and O;
- X3 is independently selected from CH2, and O;
- X4 is independently selected from H, or (CH2)mCH3 wherein m can be 0, 1, 2, or 3;
- X5 is independently selected from H, and (CH2)mCH3 wherein k can be 0, 1, 2, or 3, or is absent;
- R is independently H, NH2, CH3, N(CH3)2, C2H5, C2H4—NH2, C2H4—N(CH3)2, or is absent;
- In other embodiments X2 is independently selected from N, and CH;
- X3 is independently selected from CH2, and O;
- X4 is CH2 and X5 is CH2 with a single covalent bond between X4 and X5;
- R is independently H, NH2, CH3, N(CH3)2, C2H5, C2H4—NH2, C2H4—N(CH3)2, or is absent;
- If n=2 or 3, X1 is independently selected from CH, N, and O;
- X2 is independently selected from N, O, and CH;
- X3 is independently selected from CH2, and O, and
- If X1 is O;
- X4 is absent;
- X5 is independently selected from H, (CH2)mCH3 wherein k can be 0, 1, 2, or 3, or is absent;
- and R is independently H, NH2, CH3, N(CH3)2, C2H5, C2H4—NH2, C2H4—N(CH3)2, or is absent;
- If X1 is CH, then
- X4 is independently selected from H, and (CH2)mCH3 wherein m can be 0, 1, 2, or 3;
- X5 is independently selected from H, and (CH2)mCH3 wherein k can be 0, 1, 2, or 3, or is absent;
- R is independently H, NH2, CH3, N(CH3)2, C2H5, C2H4—NH2, C2H4—N(CH3)2, or is absent;
- or
- X4 is CH2 and X5 is CH2 with a single covalent bond between X4 and X5;
- R is independently H, NH2, CH3, N(CH3)2, C2H5, C2H4—NH2, C2H4—N(CH3)2, or is absent,
- or
- X4 is CH2 and X5 is NH with a single covalent bond between X4 and X5;
- R is H,
- or
- X4 is NH and X5 is CH2 with a single covalent bond between X4 and X5;
- R is H,
- If X1 is N, then
- X4 is independently selected from H, and (CH2)mCH3 wherein m can be 0, 1, 2, or 3;
- X5 is independently selected from H, and (CH2)mCH3 wherein k can be 0, 1, 2, or 3, or is absent;
- R is independently H, NH2, CH3, N(CH3)2, C2H5, C2H4—NH2, C2H4—N(CH3)2, or is absent;
- or
- X4 is CH2 and X5 is CH2 with a single covalent bond between X4 and X5;
- R is independently H, NH2, CH3, N(CH3)2, C2H5, C2H4—NH2, C2H4—N(CH3)2, or is absent.
A substance of Example 1 or 2, or a salt thereof, alone or in combination with another drug for use in a pharmaceutical composition.
A substance of Example 13 or 14, or a salt thereof, alone or in combination with another drug for use in a pharmaceutical composition.
A compound of the Formula X or a salt thereof:
- Formula X
- Wherein n can be 1, 2, 3, 4, 5 or 6
- X3 is independently selected from CH2, O;
- Y is a heterocycle independently selected from:
- wherein the attachment point of the carbon chain connecting nitrogen 1 of the imidazoquinoline to the heterocycle can be any carbon atom of the heterocycle and;
- if Y=Y−1, V1 is independently selected from H, CH3, C2H5, C2H4—NH2, C2H4—N(CH3)2, or a compound of Formula III
- if Y=Y−2, V1 or V2 are independently selected from H, CH3, C2H5, C2H4—NH2, C2H4—N(CH3)2, or a compound of Formula III
- if Y=Y−5 V1 is independently selected from H, CH3, C2H5, C2H4—NH2, C2H4—N(CH3)2, or a compound of Formula III
- In other embodiments, if 1<n<6, X3 is independently selected from CH2, O;
- Y is selected from Y−1, Y−2 and Y−5 and the attachment point connecting the substituted imidazoquinoline to the heterocycle substituent is a nitrogen atom of the heterocycle, V1 is absent in this case:
Dependencies are inferred from the claim text.