Radiolabeled Fibroblast Activation Protein Inhibitors and Methods of Making Same

A method of preparing a fibroblast activation protein inhibitor comprising:

• admixing a compound having a structure according to formula (IV) with a salt, MX, to form a compound having a structure according to formula (I):
• wherein
• M is selected from the group of K, Li, Na, Rb, Cs, tetraethylammonium, and tetrabutylammonium;
• in the salt, KX, and in formula (I), X is selected from the group of 123I, 124I, 125I, 131I, 211At, 76Br, 77Br, 18F, H311CO, CF218F, CHF18F, OCF218F, OCHF18F, SCF218F, SCHF18F, 11CN, 11CH3, and H311CS;
• and X is the same in the salt and in formula (I);
• Q is selected from trialkyl stannyl, trialkyl germyl, and trialkyl silyl;
• in formula (IV) and formula (I), Q and X are located at carbon 1′, 2′, or 3′, and the location of Q in formula (IV) and the location of X in formula (I) are the same;
• and
• each R is independently selected from H, F, 2H, CH3, and cyclopentyl, and the R in formula (I) are the same as the R in formula (IV).

A method of preparing a fibroblast activation protein inhibitor comprising:

• admixing a compound having a structure according to formula (VI) with a salt, MX, to form a compound having a structure according to formula (II):
• wherein
• M is selected from the group of K, Li, Na, Rb, Cs, tetraethylammonium, and tetrabutylammonium;
• in the salt, KX, and in formula (II), X is selected from the group of 123I, 124I, 125I, 131I, 211At, 76Br, 77Br, 18F, H311CO, CF218F, CHF18F, OCF218F, OCHF18F, SCF218F, SCHF18F, 11CN, 11CH3, and H311CS, and X is the same in the salt and in formula (II);
• Q is selected from trialkyl stannyl, trialkyl germyl, or trialkyl silyl;
• in formula (VI) and formula (II), Q and X are located at carbon 1′, 2′, or 3′, and the location of Q in formula (VI) and the location of X in formula (II) are the same;
• and
• each R is independently selected from H, F, 2H, CH3, and cyclopentyl, and the R in formula (II) are the same as the R in formula (VI).

A method of preparing a fibroblast activation protein inhibitor comprising:

• admixing a compound having a structure according to formula (VII) with a salt, MX, to form a compound having a structure according to formula (III):
• wherein
• M is selected from the group of K, Li, Na, Rb, Cs, tetraethylammonium, and tetrabutylammonium;
• in the salt, MX, and in formula (III), X is selected from the group of 123I, 124I, 125I, 131I, 211At, 76Br, 77Br, 18F, H311CO, CF218F, CHF18F, OCF218F, OCHF18F, SCF218F, SCHF18F, 11CN, 11CH3, and H311CS, and X is the same in the salt and in formula (III);
• Q is selected from trialkyl stannyl, trialkyl germyl, or trialkyl silyl;
• in formula (VII) and formula (III), Q and X are located at carbon 1′, 2′, or 3′, and the location of Q in formula (VII) and the location of X in formula (III) are the same;
• and
• each R is independently selected from H, F, 2H, CH3, and cyclopentyl, and the R in formula (III) are the same as the R in formula (VII).

A method of preparing a fibroblast activation protein inhibitor comprising:

• admixing a compound having a structure according to formula (VIII) with a radiolabeled salt, MX, to form a compound having a structure according to formula (I):
• wherein
• Z has a structure according selected from the group of:
• in formula (VIII) and formula (I), Z and X are located at carbon 1′, 2′, or 3′, and the location of Z in formula (VIII) and the location of X in formula (I) are the same;
• M is selected from the group of K, Li, Na, Rb, Cs, tetraethylammonium, and tetrabutylammonium;
• in the salt, MX, and in formula (I), X is selected from the group of 18F, 211At, 123I, 124I, 125I, 131I, 76Br, 77Br;
• and
• each R is independently selected from H, F, 2H, CH3, and cyclopentyl, and the R in formula (I) are the same as the R in formula (VIII).

A method of preparing a fibroblast activation protein inhibitor comprising:

• admixing a compound having a structure according to formula (X) with a radiolabeled salt, MX, to form a compound having a structure according to formula (II):
• wherein
• Z has a structure selected from the group of:
• in formula (X) and formula (II), Z and X are located at carbon 1′, 2′, or 3′, and the location of Z in formula (X) and the location of X in formula (II) are the same;
• M is selected from the group of K, Li, Na, Rb, Cs, tetraethylammonium, and tetrabutylammonium;
• in the salt, MX, and in formula (II), X is selected from the group of 18F, 211At, 123I, 124I, 125I, 131I, 76Br, 77Br;
• and
• each R is independently selected from H, F, 2H, CH3, and cyclopentyl, and the R in formula (II) are the same as the R in formula (X).

A method of preparing a fibroblast activation protein inhibitor comprising:

• admixing a compound having a structure according to formula (XI) with a radiolabeled salt, MX, to form a compound having a structure according to formula (III):
• wherein
• Z has a structure selected from the group of:
• in formula (XI) and formula (III), Z and X are located at carbon 1′, 2′, or 3′, and the location of Z in formula (XI) and the location of X in formula (III) are the same;
• M is selected from the group of K, Li, Na, Rb, Cs, tetraethylammonium, and tetrabutylammonium;
• in the salt, MX, and in formula (III), X is selected from the group of 18F, 211At, 123I, 124I, 125I, 131I, 76Br, 77Br;
• and
• each R is independently selected from H, F, 2H, CH3, and cyclopentyl, and the R in formula (III) are the same as the R in formula (XI).