# US 2026/0061084 A1 · Fibroblast activation protein (fap) inhibitors, fap conjugates, and diagnostic and therapeutic uses thereof

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- Number: US 2026/0061084 A1
- Document ID: US20260061084A1
- Status: Published application
- Kind: A1
- Application number: 19/278,501
- Filed: 2025-07-23
- Published: 2026-03-05
- Earliest claimed: 2022-09-23
- Assignees: Nuclidium AG; University of Basel
- Applicants: Nuclidium AG; University of Basel
- Inventors: Leila JAAFAR-THIEL; Melpomeni FANI; Jacopo MILLUL; Francesco DE ROSE
- Web page: https://patentgrep.com/patent/US20260061084A1

## CPC

- A61K 47/545: {Heterocyclic compounds (A61K47/558 takes precedence)}
- A61K 51/0482: {chelates from cyclic ligands, e.g. DOTA}
- A61K 51/0455: {having six-membered rings with one nitrogen as the only ring hetero atom}
- A61K 51/0497: {conjugates with a carrier being an organic compounds}
- A61P 35/00: Antineoplastic agents
- C07B 59/004: {Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur, selenium or tellurium}
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07F 1/08: Copper compounds
- A61K 2121/00: Preparations for use in therapy
- A61K 2123/00: Preparations for testing in vivo
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The present disclosure relates to the field of fibroblast activation protein (FAP) inhibitors, conjugates comprising the novel FAP inhibitors, including radiotracers, for the imaging, diagnosis and treatment of conditions characterized by overexpression of FAP.

## Claims

### Claim 1

A compound, wherein the compound is of Formula I:
wherein:
R1 is Ra;
R2 and R3 are each Ra or together form a C2-9 heterocycle with the nitrogen atoms to which they are attached;
R4 is H or an amine protecting group;
Ra, independently for each occurrence, is selected from H, C1-10 alkyl, C2-10 alkenyl, C3-10 alkynyl, C3-10 cycloalkyl, C6-10 aryl, C2-9 heterocyclyl, or C5-9 heteroaryl, optionally substituted by one or more substituents selected from —OH, —OR′, ═O, ═S, —SH, —SR′, —NH2, —NHR′, —N(R′)2, —NHCOR′, —NR′COR′, halogen, —CN, —CO2H, —CO2R′, —CHO, —COR′, —CONH2, —CONHR′, —CON(R′)2, —NO2, —OP(O)(OH)2, —SO3H, —SO3R′, —SOR′, and —SO2R′, wherein R′, independently for each occurrence, is C1-10 alkyl or C3-10 cycloalkyl;
n is an integer from 1 to 20; and
m is an integer from 1 to 20;
or is a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R1 is C1-10 alkyl.

### Claim 3 (depends on 2)

The compound of claim 2, wherein R1 is methyl.

### Claim 4 (depends on 1)

The compound of claim 1, wherein R1 is H.

### Claim 5 (depends on 1)

The compound of claim 1, wherein R2 is H.

### Claim 6 (depends on 1)

The compound of claim 1, wherein R3 is H.

### Claim 7 (depends on 1)

The compound of claim 1, wherein R2 and R3 together form a C2-9 heterocycle with the nitrogen atoms to which they are attached.

### Claim 8 (depends on 7)

The compound of claim 7, wherein the C2-9 heterocycle is a 5-, 6-, or 7-membered heterocycle.

### Claim 9 (depends on 8)

The compound of claim 8, wherein the C2-9 heterocycle is a 6-membered heterocycle selected from a piperazine, hexahydropyrimidine, hexahydropyridazine, 1,2,3-triazinane, 1,2,4-triazinane, and 1,3,5-triazinane.

### Claim 10 (depends on 9)

The compound of claim 9, wherein the 6-membered heterocycle is a piperazine.

### Claim 11

(canceled)

### Claim 12 (depends on 1)

The compound of claim 1, wherein R4 is H.

### Claim 13 (depends on 1)

The compound of am claim 1, wherein R4 is an amine protecting group.

### Claim 14 (depends on 13)

The compound of claim 13, wherein the amine protecting group is selected from carbobenzyloxy (Cbz), p-methoxybenzyl carbonyl (Moz or MeOZ), tert-butyloxycarbonyl (Boc), 9-fluorenylmethyloxycarbonyl (FMOC), acetyl (Ac), benzoyl (Bz), benzyl (Bn), a carbamate, p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), a succinimide (i.e., a cyclic imide), and tosyl (Ts).

### Claim at position 15

-54. (canceled)

### Claim 55 (depends on 1)

The compound of claim 1, wherein n is an integer from 1 to 10.

### Claim 56

(canceled)

### Claim 57 (depends on 55)

The compound of claim 55, wherein n is 2.

### Claim 58 (depends on 1)

The compound of claim 1, wherein m is an integer from 1 to 10.

### Claim 59

(canceled)

### Claim 60 (depends on 58)

The compound of claim 58, wherein m is 2.

### Claim 61 (depends on 1)

The compound of claim 1, wherein the compound is of Formula Ia:
wherein R1 is H or C1-10 alkyl.

### Claim 62 (depends on 1)

The compound of claim 1, wherein the compound is of Formula Ib:
wherein R1 is H or C1-10 alkyl.

### Claim at position 24

-65. (canceled)

### Claim 66 (depends on 61)

The compound of claim 61, wherein R4 is H.

### Claim 67 (depends on 61)

The compound of claim 61, wherein R4 is an amine protecting group.

### Claim 68 (depends on 67)

The compound of claim 67, wherein the amine protecting group is selected from carbobenzyloxy (Cbz), p-methoxybenzyl carbonyl (Moz or MeOZ), tert-butyloxycarbonyl (Boc), 9-fluorenylmethyloxycarbonyl (FMOC), acetyl (Ac), benzoyl (Bz), benzyl (Bn), a carbamate, p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), a succinimide (i.e., a cyclic imide), and tosyl (Ts).

### Claim at position 28

-70. (canceled)

### Claim 71 (depends on 1)

The compound of claim 1, wherein the compound is selected from:
Compound
Structure
1
2
3
and
4
or is a pharmaceutically acceptable salt thereof.

### Claim at position 30

-140. (canceled)

### Claim 141 (depends on 62)

The compound of claim 62, wherein R4 is H.

### Claim 142 (depends on 62)

The compound of claim 62, wherein R4 is an amine protecting group.

### Claim 143 (depends on 142)

The compound of claim 142, wherein the amine protecting group is selected from carbobenzyloxy (Cbz), p-methoxybenzyl carbonyl (Moz or MeOZ), tert-butyloxycarbonyl (Boc), 9-fluorenylmethyloxycarbonyl (FMOC), acetyl (Ac), benzoyl (Bz), benzyl (Bn), a carbamate, p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), a succinimide (i.e., a cyclic imide), and tosyl (Ts).