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US 2014/0234216 A1Published application
Folate conjugates of albumin-binding entities
AssigneeMerck & Cie
InventorsRoger Schibli, Rudolf Moser, Cristina Magdalena Muller, Harriet Struthers, Viola Groehn, Simon Mensah Ametamey, Cindy Ramona Fischer
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Abstract
The present invention is directed towards new trifunctional folate-conjugates comprising a folate, an albumin binder and a radionuclide-based therapeutic or diagnostic moiety as well as pharmaceutical compositions thereof, their method of production and their use in diagnostic and therapeutic medical applications, such as diagnostic nuclear imaging and radionuclide therapy.
Claims34
Compounds of formula I,
- wherein
- Z is a pteroate or derivative thereof,
- L1,L4 are independently of each other a covalent bond or a straight-chain or branched C(1-8)alkyl, which is unsubstituted or substituted by at least one CN, Hal, OR′, NHR′, CO2R′ or NO2, wherein R′ represents H or C(1-8)alkyl,
- L2 is a covalent bond or a linking group, such as straight-chain or branched C(1-8)alkyl, which is unsubstituted or substituted by at least one OR′, NHR′, or CO2R′, and wherein one or more of the non-adjacent CH2 groups may independently be replaced by a group selected from —O—, —CO—, —CO—O—, —O—CO—, —NR′—, —NR′—CO—, —CO—NR′, wherein R′ represents H or C(1-8)alkyl,
- L3 is a covalent bond or a linking group, such as straight-chain or branched C(1-8)alkyl, which is unsubstituted or substituted by at least one CN, Hal, OR′, NHR′, CO2R′ or NO2, and wherein one or more of the non-adjacent CH2 groups may independently be replaced by a group selected from —O—, —CO—, —CO—O—, —O—CO—, —NR′—, —NR′—CO—, —CO—NR′—, —NR′—CO—O—, —O—CO—NR′—, —NR′—CO—NR′—, —CH═CH—, —C≡C—, —O—CO—O—, —S—R′—, —SO3R′—, and a five-membered azaheterocycle, wherein R′ represents H or C(1-8)alkyl,
- Y1,Y3 are independently of each other O, N or S,
- A1, A2, A3 are independently of each other H, a capping group, or an albumin binder,
- M is a radionuclide-based therapeutic or diagnostic moiety,
- m1, m2 are independently of each other 0, 1, 2 or 3,
- with the proviso that at least one, preferably one, of A1, A2 and A3 is an albumin binder.
7 more elements
(canceled)
(canceled)
Dependencies are inferred from the claim text.