US 12,214,059 B2
Cleavable radioligands for targeting cell surface receptors and uses thereof
Fa Liu, Watchung, NJ (US); and Alla Darwish, Kitchener (CA)
Assigned to FULL-LIFE TECHNOLOGIES HK LIMITED, Hong Kong (CN)
Filed by Full-Life Technologies HK Limited, Hong Kong (CN)
Filed on Mar. 13, 2024, as Appl. No. 18/604,400.
Application 18/604,400 is a continuation of application No. PCT/US2022/050952, filed on Nov. 23, 2022.
Claims priority of provisional application 63/283,361, filed on Nov. 26, 2021.
Prior Publication US 2024/0382630 A1, Nov. 21, 2024
Int. Cl. A61K 51/04 (2006.01); A61K 51/02 (2006.01); A61K 51/06 (2006.01); A61K 51/08 (2006.01)
CPC A61K 51/0482 (2013.01) [A61K 51/02 (2013.01); A61K 51/06 (2013.01); A61K 51/088 (2013.01); A61K 51/081 (2013.01)] 13 Claims
 
1. A compound, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is:
 
I.D Compound Name Structure
 
 
I- 1 4pIBA- Glu- SSL1- Lys (DOTA)- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 2 4pIBA- Glu- ESL1- Lys (DOTA)- Trx- 2Na1- eKuE
 

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I- 3 4pIBA- Glu- Lys (-ESL1- DOTA)- Trx- 2Na1- eKuE
 

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I- 4 4pIBA- Glu- Lys (-SSL1- DOTA)- Trx- 2Nal- eKuE
 

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I- 5 4pIBA- Glu- Lys (-ESL2- DOTA)- Aun- Trx- 2Nal- eKuE
 

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I- 6 DOTA- ESL2- Lys (-Glu- 4pIBA)- Trx- 2Nal- eKuE
 

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I- 7 4pIBA- Glu- OEG- OEG- Lys (-OEG- OEG- Glu- 4pIBA)- Lys (-ESL1- DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 8 4pIBA- Glu- OEG- OEG- Lys (-OEG- OEG- Glu- 4pIBA)- OEG- ESL1- Lys (DOTA)- Trx- 2Nal- eKuE
 

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I- 9 4pIBA- Glu- Lys [-Suc- eLys- Val- Met- Gly- DOTA]- Trx- 2Nal- eKuE
 

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I- 10 HO- C18 -gGlu- Lys (-ESL1- DOTA) -OEG- OEG- OEG- Trx- 2Nal- eKuE
 

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I- 11 HO- C18- gGlu- Lys (-ESL1- DOTA)- OEG- OEG- OEG- OEG- OEG- OEG- Trx- 2Nal- eKuE
 

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I- 12 HO- C18- gGlu- Lys (-ESL2- DOTA)- OEG- OEG- Trx- 2Nal- eKuE
 

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I- 13 HO- C18- gGlu- Lys (-ESL2- DOTA)- OEG- OEG- OEG- Trx- 2Nal- eKuE
 

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I- 14 HO- C20- gGlu- Lys (-ESL2- DOTA)- OEG- OEG- OEG- Trx- 2Nal- eKuE
 

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I- 15 HO- C18- gGlu- Lys (-ESL2- DOTA)- OEG- OEG- OEG- OEG- Trx- 2Nal- eKuE
 

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I- 16 HO- C18- gGlu- OEG- OEG- Lys (-ESL2- DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 17 HO- C20- gGlu- OEG- Lys (-ESL1- DOTA)- OEG- OEG- Trx- 2Nal- eKuE
 

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I- 18 HO- C18- gGlu- OEG- OEG- Lys (-ESL1- DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 19 HO- C18- gGlu- OEG- OEG- OEG- OEG- OEG- OEG- ESL1- Lys (DOTA)- Trx- 2Nal- eKuE
 

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I- 20 HO- C18- gGlu- OEG- OEG- ESL2- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 21 HO- C18- gGlu- OEG- OEG- ESL1- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 22 HO- C18- gGlu- OEG- ESL1- ESL1- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 23 HO- C18- gGlu- ESL1- ESL1- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 24 HO- C18- gGlu- OEG- OEG- OEG- OEG- OEG- ESL1- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 25 HO- C20- gGlu- OEG- OEG- ESL1- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 26 HO- C18- gGlu- OEG- OEG- ESL1- OEG- Lys (DOTA)- Trx- 2Nal- eKuE
 

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I- 27 HO- C18- gGlu- ESL1- OEG- OEG- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 28 HO- C18- gGlu- gGlu- gGlu- OEG- OEG- ESL1- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 29 HO- C20- gGlu- OEG- ESL1- ESL1- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 30 HO- C16- gGlu- OEG- OEG- ESL1- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 31 HO- C18- gGlu- OEG- OEG- ESL3- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 32 (HO- C18)- gGlu- OEG- OEG- OEG- OEG- OEG- Glu- Arg- Gly- Glu- Thr- Gly- Pro- Ser- Gly- OEG- Lys (-ESL1- DOTA)- Trx- 2Nal- eKuE
 

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I- 33 4pIBA- Glu- OEG- NH2CH2- CH2NH- TMA [-ESL1- Tys (DOTA)- Trx- 2Nal -eKuE]2
 

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I- 34 HO -C18- gGlu- Lys (-ESL1- DOTA)- OEG- OEG- OEG- NH2CH2- CH2NH- TMA (-OEG- Trx- 2Nal- eKuE)2
 

OG Complex Work Unit Chemistry
 
I- 35 HO- C20- gGlu- OEG- OEG- Lys (ESL1- DOTA)- OEG- NH2CH2- CH2NH- TMA (-OEG- Trx- 2Nal- eKuE)2
 

OG Complex Work Unit Chemistry
 
I- 36 HO- C20- gGlu- Lys (-ESL2- DOTA)- OEG- OEG- OEG- NH2CH2- CH2NH- TMA (-OEG- Trx- 2Nal- eKuE)2
 

OG Complex Work Unit Chemistry
 
I- 37 HO- C20- gGlu- Lys (-ESL1- ESL1- DOTA)- OEG- OEG- OEG- NH2CH2- CH2NH- TMA (-OEG- Trx- 2Nal- eKuE)2
 

OG Complex Work Unit Chemistry
 
I- 38 HO- C18- gGlu- OEG- OEG- Lys (-ESL1- DOTA) -OEG- NH2CH2- CH2NH- TMA (-OEG- Trx- 2Nal- eKuE)2
 

OG Complex Work Unit Chemistry
 
I- 39 HO- C18- gGlu- Lys (-ESL2- DOTA)- OEG- OEG- OEG- NH2CH2- CH2NH- TMA (-OEG- Trx- 2Nal- eKuE)2
 

OG Complex Work Unit Chemistry
 
I- 40 HO- C18- gGlu -OEG- Lys (-ESL1- DOTA)- OEG- NH2CH2- CH2NH- TMA (-OEG- Trx- 2Nal- eKuE)2
 

OG Complex Work Unit Chemistry
 
I- 41 HO- C18- gGlu- OEG- OEG- NH2CH2- CH2NH- TMA [-ESL1- Lys (DOTA)- Trx- 2Nal- eKuE]2
 

OG Complex Work Unit Chemistry
 
I- 42 HO- C20- gGlu- OEG- OEG- NH2CH2- CH2NH- TMA [-ESL1- Lys (DOTA)- Trx- 2Nal- eKuE]2
 

OG Complex Work Unit Chemistry
 
I- 43 [HO- C18- gGlu- OEG- OEG- ESL1- Lys (DOTA)- OEG- NH2CH2- CH2NH-]- TMA- (-OEG- Trx- 2Nal- eKuE)2
 

OG Complex Work Unit Chemistry
 
I- 44 [HO- C20- gGlu- Lys (-ESL1- ESL1- ESL1- DOTA)- OEG- OEG- OEG- NH2CH2- CH2NH-]- TMA- (-OEG- Trx- 2Nal- eKuE)2
 

OG Complex Work Unit Chemistry
 
I- 45 HO- C18- gGlu- OEG- OEG- Lys (-ESL1- Gly- Gly- DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 46 HO- C18- gGlu- OEG- OEG- Lys (-ESL1- Gly- Gly- Gly- DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 47 HO- C18- gGlu- OEG- OEG- Lys (-ESL1- OEG- DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 48 HO- C18- gGlu- OEG- OEG- Lys (-ESL1- Gly- OEG- DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 49 HO- C18- gGlu- OEG- OEG- Gly- 5hPA- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 50 HO- C18- gGlu- OEG- OEG- Gly- 6hHA- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 51 HO- C18- gGlu- OEG- OEG- ESL1- Gly- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 52 HO- C18- gGlu- OEG- OEG- ESL1- Gly- Gly- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 53 HO- C18- gGlu- OEG- OEG- Gly- 4hPA- OEG- Lys (DOTA)- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 54 HO- C18- gGlu- OEG- OEG- Leu- 4hBA- OEG- Lys (DOTA)- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 55 (a) (R)-HO- C18- gGlu- OEG- OEG- Leu- 4hPA- OEG- Lys (DOTA)- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 55 (b) (S)-HO- C18- gGlu- OEG- OEG- Leu- 4hPA- OEG- Lys (DOTA)- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 56 HO- C18- gGlu- OEG- OEG- OEG- ESL1- Lys (DOTA)- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 57 HO- C18- gGlu- OEG- OEG- Gly- OCH2CO- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 58 HO- C18- gGlu- OEG- OEG- ESL1- Gly- Gly- Gly- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 59 HO- C18- gGlu- OEG- OEG- Dab- 4hBA- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

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I- 60 HO- C18- gGlu- OEG- OEG- Leu- 4hBA- Lys (DOTA)- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 61 HO- C18- gGlu- OEG- OEG- ESL1- Lys (DOTA)- OEG- Gly- Tyr- Phe- eKuE
 

OG Complex Work Unit Chemistry
 
I- 62 HO- C18- gGlu- OEG- OEG- ESL1- k(DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 63 HO- C18- gGlu- OEG- OEG- ESL1- Dab (DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 64 HO- C18- gGlu- OEG- OEG- ESL1- Gly- Gly- Lys (DOTA)- OEG- Gly- Tyr- Phe- eKuE
 

OG Complex Work Unit Chemistry
 
I- 65 HO- C18- gGlu- OEG- OEG- ESL1- Gly- Gly- Gly- Lys (DOTA)- OEG- Gly- Tyr- Phe- eKuE
 

OG Complex Work Unit Chemistry
 
I- 66 HO- C18- gGlu- OEG- OEG- Gly- 5hPA- Lys (DOTA)- OEG- Gly- Tyr- Phe- eKuE
 

OG Complex Work Unit Chemistry
 
I- 67 4pIBA- gGlu- OEG- OEG- ESL1- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
I- 68 C18- gGlu- OEG- OEG- ESL1- Lys (DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
 
 
 or
 
I- 69 4pIBA- gGlu- OEG- OEG- Lys (-ESL1- DOTA)- OEG- Trx- 2Nal- eKuE
 

OG Complex Work Unit Chemistry
 
or a pharmaceutically acceptable salt or solvate thereof.