RU2009116678A

RU2009116678A - RADIOFLUORATION

Info

Publication number: RU2009116678A
Application number: RU2009116678/04A
Authority: RU
Inventors: Анант СРИНИВАСАН (DE); Анант Сринивасан; Лутц ЛЕМАНН (DE); Лутц Леманн; Ульрике РЁН (DE); Ульрике Рён; Тимо ШТЕЛЛЬФЕЛЬД (DE); Тимо Штелльфельд; Симон АМЕТАМЕЙ (CH); Симон АМЕТАМЕЙ; Ульрих КЛАР (DE); Ульрих Клар; Аилеен ХЁНЕ (CH); Аилеен ХЁНЕ; Линьцин МУ (CH); Линьцин МУ
Original assignee: Байер Шеринг Фарма Акциенгезельшафт (DE); Байер Шеринг Фарма Акциенгезельшафт
Priority date: 2006-10-02
Filing date: 2007-09-07
Publication date: 2010-11-10

Abstract

1. Соединение формулы I ! ! где X является группой пригодной для фторирования, которая отщепляется, и выбрана из группы, которая включает водород и OR3, ! где R3 является водородом, С1-С10алкилом, С2-С10алкенилом, С2-С10алкинилом, арилом, гетероарилом или аралкилом, ! R1 и R2, независимо, выбраны из группы, которая включает водород, линейный или разветвленный C1-С10алкил, арил, гетероарил и аралкил, ! В1 выбран из группы, которая включает -[СН2]m-D-[CH2ln-А-, ! где n и m независимо являются любыми целыми числами от 0 до 5, ! D являются связью, -S-, -О- или -NR4-, ! R4 является водородом, C1-С10алкилом, арилом, гетероарилом или аралкилом, ! А является алкилом, незамещенным или замещенным арилом или гетероарилом, ! E-Z1-Y1 является заместителем, выбранным из группы, которая включает ЕО-С(=O)-, ENR5-C(=O)-, EC(=O)-O-, EC(=O)-NR5-, ENR5-SO2-, ESO2-NR5-, E-O-, E-(S)p-, E-NR5-, ENR6C(=O)-NR7-, ENR6-C(=O)NR7-, ENR6C(=S)-NR7-, ENR6-C(=S)NR7-, EO-C(=O)O-, EOC(=O)-O-, EOC(=S)-O-, EO-C(=S)O-, ! где длинная одинарная связь, явным образом показанная в приведенной выше формуле, является связью между Z1 и Y1, и ! , , , , !, , , , ! , , , ! где стрелки, показанные в приведенной выше формуле, указывают связь между Z1 и Y1, ! R5, R6 и R7, независимо, являются водородом, линейным или разветвленным С1-С10алкилом, арилом, гетероарилом или аралкилом, ! p является любым целым числом от 1 до 3, и ! где E-Z1 является нацеливающим агент-радикалом и Е является биомолекулой, !или ! В2 является C1-С10алкилом-, незамещенным или замещенным -арилом- или незамещенным или замещенным -гетероарилом-, ! Y2 выбран из группы, которая включает связь, -С(=O)-, -SO2-, -С(=O)-(СН2)d-, -S(=O)-, -C(=O)-C≡C-, -C(=O)-[CH2]m-D-[CH2]n-, -SO2-[CH2]m-D-[CH2]n-, -O-C(=O)-, -NR10-, -О-, -(S)p-, -NR12-C(=O)-, -NR12-C(=S)-, -O-C(=S)-, -C1-С6-циклоалкил-, -алкенил-, -гетероциклоалкил-, незамещенный или замещен� 1. The compound of formula I! ! where X is a group suitable for fluorination, which is cleaved, and selected from the group that includes hydrogen and OR3,! where R3 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, aryl, heteroaryl or aralkyl,! R1 and R2 are independently selected from the group consisting of hydrogen, linear or branched C1-C10 alkyl, aryl, heteroaryl and aralkyl,! B1 is selected from the group which includes - [CH2] m-D- [CH2ln-A-,! where n and m are independently any integers from 0 to 5,! D are a bond, -S-, -O- or -NR4-,! R4 is hydrogen, C1-C10 alkyl, aryl, heteroaryl or aralkyl,! And is alkyl, unsubstituted or substituted by aryl or heteroaryl,! E-Z1-Y1 is a substituent selected from the group consisting of EO-C (= O) -, ENR5-C (= O) -, EC (= O) -O-, EC (= O) -NR5-, ENR5-SO2-, ESO2-NR5-, EO-, E- (S) p-, E-NR5-, ENR6C (= O) -NR7-, ENR6-C (= O) NR7-, ENR6C (= S) -NR7-, ENR6-C (= S) NR7-, EO-C (= O) O-, EOC (= O) -O-, EOC (= S) -O-, EO-C (= S) O -! where the long single bond explicitly shown in the above formula is the bond between Z1 and Y1, and! ,,,,!,,,,! ,,,! where the arrows shown in the above formula indicate the relationship between Z1 and Y1,! R5, R6 and R7, independently, are hydrogen, linear or branched C1-C10 alkyl, aryl, heteroaryl or aralkyl,! p is any integer from 1 to 3, and! where E-Z1 is a radical targeting agent and E is a biomolecule,! or! B2 is C1-C10 alkyl-, unsubstituted or substituted by -aryl- or unsubstituted or substituted by heteroaryl,! Y2 is selected from the group which includes a bond, -C (= O) -, -SO2-, -С (= O) - (СН2) d-, -S (= O) -, -C (= O) -C ≡C-, -C (= O) - [CH2] mD- [CH2] n-, -SO2- [CH2] mD- [CH2] n-, -OC (= O) -, -NR10-, -О -, - (S) p-, -NR12-C (= O) -, -NR12-C (= S) -, -OC (= S) -, -C1-C6-cycloalkyl-, -alkenyl-, - heterocycloalkyl, unsubstituted or substituted

Claims

1. The compound of formula I

where X is a group suitable for fluorination, which is cleaved, and selected from the group which includes hydrogen and OR ³ ,

where R ³ is hydrogen, C ₁ -C ₁₀ alkyl, C ₂ -C ₁₀ alkenyl, C ₂ -C ₁₀ alkynyl, aryl, heteroaryl or aralkyl,

R ¹ and R ² are independently selected from the group consisting of hydrogen, linear or branched C ₁ -C ₁₀ alkyl, aryl, heteroaryl and aralkyl,

B ^{1 is} selected from the group which includes - [CH ₂ ] _m -D- [CH ₂ l _n -A-,

where n and m are independently any integers from 0 to 5,

D are a bond, —S—, —O— or —NR ⁴ -,

R ⁴ is hydrogen, C ₁ -C ₁₀ alkyl, aryl, heteroaryl or aralkyl,

A is alkyl, unsubstituted or substituted by aryl or heteroaryl,

EZ ¹ -Y ¹ is a substituent selected from the group consisting of EO-C (= O) -, ENR ⁵ -C (= O) -, EC (= O) -O-, EC (= O) -NR ⁵ -, ENR ⁵ -SO ₂ -, ESO ₂ -NR ⁵ -, EO-, E- (S) _p -, E-NR ⁵ -, ENR ⁶ C (= O) -NR ⁷ -, ENR ⁶ -C ( = O) NR ⁷ -, ENR ⁶ C (= S) -NR ⁷ -, ENR ⁶ -C (= S) NR ⁷ -, EO-C (= O) O-, EOC (= O) -O-, EOC (= S) -O-, EO-C (= S) O-,

where the long single bond, explicitly shown in the above formula, is the bond between Z ¹ and Y ¹ , and

,

where the arrows shown in the above formula indicate the relationship between Z ¹ and Y ¹ ,

R ⁵ , R ⁶ and R ⁷ , independently, are hydrogen, linear or branched C ₁ -C ₁₀ alkyl, aryl, heteroaryl or aralkyl,

p is any integer from 1 to 3, and

where EZ ¹ is a targeting radical agent and E is a biomolecule,

or

B ² is C ₁ -C ₁₀ alkyl-, unsubstituted or substituted-aryl- or unsubstituted or substituted-heteroaryl-,

Y ^{2 is} selected from the group which includes a bond, -C (= O) -, -SO ₂ -, -C (= O) - (CH ₂ ) _d -, -S (= O) -, -C (= O ) -C≡C-, -C (= O) - [CH ₂ ] _m -D- [CH ₂ ] _n -, -SO ₂ - [CH ₂ ] _m -D- [CH ₂ ] _n -, -OC (= O) -, -NR ¹⁰ -, -О-, - (S) _p -, -NR ¹² -C (= O) -, -NR ¹² -C (= S) -, -OC (= S) -, -C ₁ -C ₆ cycloalkyl, alkenyl, heterocycloalkyl, unsubstituted or substituted aralkoxy, -NR ¹³ -SO ₂ -, -SO ₂ -NR ¹³ -, -OC (= O) -NR ¹³ -,

-NR ¹² -C (= O) -NR ¹³ -, -NH-NH- or -O-NH-,

where d is any integer from 1 to 6,

m and n, independently, are any integers from 0 to 5,

D is a bond, - S-, -O- or -NR ⁹ -,

where R ⁹ is hydrogen, C ₁ -C ₁₀ alkyl, aryl, heteroaryl or aralkyl,

p is any integer from 1 to 3,

R ¹⁰ and R ^{12 are} independently selected from the group consisting of hydrogen, unsubstituted or substituted linear or branched C ₁ -C ₁₀ alkyl, aryl, heteroaryl and aralkyl,

R ¹³ is hydrogen, unsubstituted or substituted, linear or branched C ₁ -C ₁₀ alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, aralkyl or heteroaralkyl,

EZ ² is a radical targeting agent, where E is a biomolecule and Z ² is a substituent selected from the group consisting of a bond and a spacer, where the spacer is a natural or non-natural amino acid sequence or non-amino acid group,

or a pharmaceutically acceptable salt thereof of an organic or inorganic acid, hydrate, complex, ester, amide, solvate or prodrug thereof.

2. The compound according to claim 1, where

represents

where X, R ¹ , R ² , A, n, m, D and E-Z ¹ -Y ¹ have the same meanings as in formula I according to claim 1, and

EZ ¹ is a radical targeting agent and E is a biomolecule.

3. The compound according to claim 1, where

represents

where X, E, Z ² , Y ² , A, n, m, and D have the same meanings as in formula I according to claim 1,

-L- is

,

where R ¹ and R ^{2 are} independently selected from the group consisting of hydrogen, linear or branched C ₁ -C ₁₀ alkyl, aryl, heteroaryl or aralkyl,

A is C ₁ -C ₁₀ alkyl, unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl, and

Y ² is a functional group or chain that contains a functional group and binds L to Z ² and which is selected from the group which includes a bond, —C (= O) -, —SO ₂ -, —C (= O) - (CH ₂ ) _d -, -SO-, -C (= O) -C≡C-, -C (= O) - [CH ₂ ] _m -D- [CH ₂ ] _n -, -SO ₂ - [CH ₂ ] _m -D- [CH ₂ ] _n -, -O-C (= O) -, -NR ¹⁰ -, -O-, - (S) _p -, -NR ¹² -C (= O) -, - NR ¹² -C (= S) -, -OC (= S) -, -C ₁ -C ₆ cycloalkyl-, -NR ¹³ SO ₂ -, -SO ₂ NR ¹³ -, OC (= O) -NR ¹³ - , -NR ¹² C (= O) NR ¹³ -, -NH-NH-, and -O-NH-,

where d is any integer from 1 to 6,

m and n are independently any integers from 0 to 5,

D is a bond, —S—, —O— or —NR ⁹ -,

R ⁹ is hydrogen, C ₁ -C ₁₀ alkyl, aryl, heteroaryl or aralkyl,

p is any integer from 1 to 3,

R ¹⁰ and R ^{12 are} independently selected from the group consisting of hydrogen, unsubstituted or substituted, linear or branched C ₁ -C ₁₀ alkyl, aryl, heteroaryl and aralkyl, and

R ¹³ is hydrogen, unsubstituted or substituted, linear or branched C ₁ -C ₆ alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, aralkyl or heteroaralkyl.

4. The compound according to claim 1, where the group X, which is cleaved, selected from the group which includes hydrogen or OR ³ , where R ³ is hydrogen, C ₁ -C ₁₀ alkyl, C ₁ -C ₁₀ alkenyl or C ₁ -C ₁₀ alkynyl.

5. The compound according to claim 4, where R ³ is hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkenyl or C ₁ -C ₆ alkynyl.

6. The compound according to claim 5, where R ³ is hydrogen or C ₁ -C ₆ alkyl.

7. The compound according to claim 1, where R ¹ and R ² independently are branched C ₂ -C ₅ alkyl.

8. The compound of claim 7, wherein R ¹ and R ² are selected from the group consisting of isopropyl, tert-butyl and isobutyl.

9. The compound according to claim 1, where Y ^{1,2 is} selected from the group which includes —C (═O) - and —SO ₂ -.

10. The compound according to claim 1, where Z ² is an amino acid sequence that contains from two (2) to twenty (20) amino acid residues.

11. The compound of claim 10, where Z ² is Arg-Ser, Arg-Ava, Lys (Me) 2-β-ala, Lys (Me) 2-ser, Arg-β-ala, Ser-Ser, Ser- Thr, Arg-Thr, S-alkylcysteine, cysteic acid, thioalkylcysteine (SS-alkyl) or

where k and l are any integers from 0 to 4.

12. The compound according to claim 11, where Z ² is a non-amino acid residue selected from the group which includes

-C (= O) - (CH ₂ ) _p -NH-, where p is any integer from 2 to 10, and

—C (= O) - (CH ₂ —CH ₂ —O) _q —CH ₂ —CH ₂ —NH—, where q is any integer from 0 to 5,

-NH-cycloalkyl-CO-, where the cycloalkyl is selected from C ₅ -C ₈ cycloalkyl, more preferably from C ₆ cycloalkyl, and

-NH-heterocycloalkyl- (CH ₂ ) _v -CO-, where the heterocycloalkyl is selected from C ₅ -C ₈ heterocycloalkyl, which contains carbon atoms and 1, 2, 3 or 4 heteroatoms of oxygen, nitrogen or sulfur, and v is any integer from 1 to 4.

13. The compound according to claim 1, where the biomolecule E is selected from the group which includes peptides, peptidomimetics, small molecules and oligonucleotides.

14. The compound according to claim 1, where the targeting agent radical Z ¹ -E is -NR'-peptide, -NR '- (CH ₂ ) _n- peptide, -NR'-small molecules, -NR' - (CH ₂ ) _n- small molecules, -NR'- oligonucleotide or -NR '- (CH ₂ ) _n- oligonucleotide,

where R 'is selected from the group which includes hydrogen and alkyl,

n is any integer from 1 to 6.

15. The compound according to item 13, where the biomolecule E is a peptide that contains from 4 to 100 amino acids.

16. The compound of claim 15, wherein the biomolecule E is selected from the group comprising somatostatin and its derivatives and related peptides, peptides specific for the somatostatin receptor, neuropeptide Y and its derivatives and related peptides, neuropeptide Y ₁ and its analogues, bombesin and its derivatives and related peptides, gastrin, gastrin releasing peptide and its derivatives and related peptides, epidermal growth factor (EGF of different origin), insulin growth factor (IGF) and IGF-1, integrins (α ₃ β ₁ , α _v β ₃ , α _v β ₃ , αIIb ₃ ), LHRH agonists and antagonists, growth factors that transforming, in particular TGF-α; angiotensin; cholecystokinin receptor peptides, cholecystokinin (CCK) and its analogues; neurotensin and its analogues, thyrotropin releasing hormone, mucus-forming adenylate cyclase activator peptide (PACAP) and their related peptides, chemokines, substrates and cell surface matrix metalloproteinase inhibitors, prolactin and its analogues, tumor necrosis factor, interleukins (IL-1, IL- 2, IL-4 or IL-6), interferons, vasoactive intestinal peptide (VIP) and their related peptides.

17. The compound according to clause 16, where the biomolecule E is bombesin, somatostatin or neuropeptide Y ₁ or their analogues.

18. The compound according to 17, where the biomolecule E contains analogues of bombesin that have a sequence of III or IV

AA ₁ -AA ₂ -AA ₃ -AA ₄ -AA ₅ -AA ₆ -AA ₇ -AA ₈ -NT ₁ T ₂ (type A) III, where

T ₁ = T ₂ = H, T ₁ = H, T ₂ = OH, T ₁ = CH ₃ , T ₂ = OH

AA ₁ = Gln, Asn, Phe (4-CO-NH ₂ )

AA ₂ = Trp, D-Trp

AA ₃ = Ala, Ser, Val

AA ₄ = Val, Ser, Thr

AA ₅ = Gly, (N-Me) Gly

AA ₆ = His, His (3-Me), (N-Me) His, (N-Me) His (3-Me)

AA ₇ = Sta, statin analogs and isomers, 4-Am, 5-MeHp, 4-Am, 5-MeHxA and γ-substituted amino acids

AA ₈ = Leu, Cpa, Cba, Cpn, Cha, t-buGly, tBuAla, Met, Nle, iso-Bu-Gly

AA ₁ -AA ₂ -AA ₃ -AA ₄ -AA ₅ -AA ₆ -AA ₇ -AA ₈ -NT ₁ T ₂ (type B) IV, where:

T ₁ = T ₂ = H, T ₁ = H, T ₂ = OH, T ₁ = CH ₃ , T ₂ = OH

AA ₁ = Gln, Asn, Phe (4-CO-NH ₂ )

AA ₂ = Trp, D-Trp

AA ₃ = Ala, Ser, Val

AA ₄ = Val, Ser, Thr

AA ₅ = βAla, β ² - and β3 amino acids as shown above

where SC is a side chain found in proteinogenic amino acids and homologues of proteinogenic amino acids,

AA ₆ = His, His (3-Me), (N-Me) His, (N-Me) His (3-Me)

AA ₇ = Phe, Tha, Nal,

AA ₈ = Leu, Cpa, Cba, Cpn, Cha, t-buGly, tBuAla, Met, Nle, iso-Bu-Gly.

19. The compound according to claim 1, selected from

20. The compound of General formula II

where In ^1,2 , Y ^1,2 , Z ^1,2 , E, R ¹ and R ² have the same meanings as in formula I,

F is a fluorine isotope, where F is selected from a radioactive or non-radioactive isotope, and a pharmaceutically acceptable salt thereof of an organic or inorganic acid, hydrate, complex, ester, amide, solvate or prodrug thereof.

21. The compound according to claim 20, where

there is

F is a fluorine isotope, where F is selected from a radioactive or non-radioactive isotope,

R ¹ , R ² , A, n, m, D and EZ ¹ -Y ¹ have the same meanings as in formula I above, and

EZ ¹ is a radical targeting agent, where E is a biomolecule.

22. The compound according to claim 20, where

has the following meaning

where F is a fluorine isotope, where F is selected from a radioactive or non-radioactive isotope,

L is

,

where R ¹ and R ² are independently selected from the group consisting of hydrogen, linear or branched C ₁ -C ₁₀ alkyl, aryl, heteroaryl and aralkyl, and

A is alkyl, unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl,

Y ² is a functional group or chain that contains a functional group and binds L to Z ² and which is selected from the group which includes a bond, —C (= O) -, —SO ₂ -, —C (= O) - (CH ₂ ) _d -, -SO-, -C (= O) -C≡C-, -C (= O) - [CH ₂ ] _m -D- [CH ₂ ] _n -, -SO ₂ - [CH ₂ ] _m -D- [CH ₂ ] _n -, -OC (= O) -, -NR ¹⁰ -, -O-, - (S) _p -, -NR ¹² -C (= O) -, -NR ¹² -C (= S) -, -OC (= S) -, -C ₁ -C ₆ cycloalkyl-, alkenyl-, heterocycloalkyl-, unsubstituted or substituted aryl-, unsubstituted or substituted -heteroaryl, -aralkyl-, - heteroaralkyl, -alkoxy-, aryloxy-, -aralkyloxy-, -aryl-, -NR ¹³ SO ₂ -, -SO ₂ NR ¹³ -, OC (= O) -NR ¹³ -, -NR ¹² C (= O) NR ¹³ -, -NH-NH-, and -O-NH-,

where d is any integer from 1 to 6,

m and n are independently any integers from 0 to 5,

D is a bond, —S—, —O— or —NR ⁹ -,

where R ⁹ is hydrogen, C ₁ -C ₁₀ alkyl, aryl, heteroaryl or aralkyl,

p is any integer from 1 to 3,

R ¹³ is hydrogen, substituted or unsubstituted, linear or branched C ₁ -C ₁₀ alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, aralkyl or heteroalkyl,

EZ ² is a radical targeting agent, where E is a targeting agent and Z ² is a moiety selected from the group consisting of a bond and a spacer, where the spacer is a natural or non-natural amino acid sequence or non-amino acid group, and

E is a biomolecule.

23. The compound according to claim 20, where F = ¹⁸ F.

24. The compound according to item 23, selected from

IIA-s-2: ¹⁸ F-Si (tBu) ₂ -C ₆ H ₄ -CH ₂ -CO-Ava - Gln-Trp-Ala-Val-NMeGly-His (3Me) -4-Am, 5-MeHpA -Cpa-NH ₂ ,

IIB-c-1: ¹⁹ F-Si (iPr) ₂ -C ₆ H ₄ -CH ₂ -CO-Ava - Gln-Trp-Ala-Val-Gly-His (3Me) -4-Am, 5-MeHpA -Leu-NH ₂ ,

IIB-c-2: ¹⁹ F-Si (tBu) ₂ -C ₆ H ₄ -CH ₂ -CO-Ava - Gln-Trp-Ala-Val-NMeGly-His (3Me) -4-Am, 5-MeHpA -Cpa-NH ₂ .

4- (fluorodiisopropylsilanylphenyl) -acetic acid

2-4- (fluorodiisopropylsilanylphenyl) ethanol

4-fluorodiisopropylsilanylbenzoic acid

4-fluorodiisopropylsilanylphenylmethanol

3- (4-fluorodiisopropylsilanylphenyl) propan-1-ol

3- (4-fluorodiisopropylsilanylphenyl) propionic acid

3- (3-fluorodiisopropylsilanylphenyl) propan-1-ol

3- (3-fluorodiisopropylsilanylphenyl) propionic acid

2-3- (fluorodiisopropylsilanylphenyl) ethanol

3- (fluorodiisopropylsilanylphenyl) -acetic acid

4- (fluorodiisobutylsilanylphenyl) acetic acid and

4-fluorodiisobutylsilanylbenzoic acid,

where fluorine means ¹⁸ F or ¹⁹ F.

25. The compound of General formula III

where FG ¹ is —OH, —Hal, —N ₃ , —CO ₂ R ⁸ , —NHR ⁵ , —N = C = O, —O = C = N, —S = C = N, —N = C = S, -O-SO ₂ -aryl, -O-SO ₂ -alkyl, -SO ₂ -Hal, -S ₃ H, -SH, -OC (= O) -Hal, -OC (= S) -Hal,

,

where Hal is a halogen atom, and

R ⁸ is hydrogen, C ₁ -C ₁₀ alkyl, C ₂ -C ₁₀ alkenyl, aralkyl or

and where X, R ¹ , R ² and B ^1,2 have the same meanings as in formula I.

26. Connection A.25, where

represents

where X, R ¹ , R ² , A, D, m and n have the same meanings as in formula IA and FG ¹ has the same meanings as in formula III.

27. A compound selected from the group consisting of

(ditretbutylhydroxysilanyl) -acetic acid

[4- (Hydroxydisiopropylsilanyl) phenyl] acetic acid

4- (diisopropylsilanylphenyl) -acetic acid

4- (diisopropylsilanylphenyl) -acetic acid 2,5-dioxopyrrolidin-1-yl ester

[4- (Hydroxyxyisopropylsilanyl) phenyl] acetic acid 2,5-dioxopyrrolidin-1-yl ester

4-diisopropylsilanylbenzoic acid

4- (hydroxydisopropylsilanyl) benzoic acid

4-diisopropylsilanylbenzoic acid 2,5-dioxopyrrolidin-1-yl ester

4- (Hydroxyxyisopropylsilanyl) benzoic acid 2,5-dioxopyrrolidin-1-yl ester

3- (4-diisopropylsilanylphenyl) propionic acid

3- (4-diisopropylsilanylphenyl) propionic acid 2,5-dioxopyrrolidin-1-yl ester

3- (3-diisopropylsilanylphenyl) propionic acid

3- (3-diisopropylsilanylphenyl) propionic acid 2,5-dioxopyrrolidin-1-yl ester

3- (diisopropylsilanylphenyl) -acetic acid

3- (diiisopropylsilanylphenyl) -acetic acid 2,5-dioxopyrrolidin-1-yl ester

4- (diiisobutylsilanylphenyl) -acetic acid

4- (diiisobutylsilanylphenyl) -acetic acid 2,5-dioxopyrrolidin-1-yl ester

[4- (Hydroxyxyisobutylsilanyl) phenyl] -acetic acid 2,5-dioxopyrrolidin-1-yl ester

[4- (Hydroxyxyisobutylsilanyl) phenyl] acetic acid

diisobutylsilanyl benzoic acid

4- (hydroxydisobutylsilanyl) benzoic acid

diisobutylsilanyl benzoic acid 2,5-dioxopyrrolidin-1-yl ester

4- (Hydroxyxyisobutylsilanyl) -benzoic acid 2,5-dioxopyrrolidin-1-yl ester

4- [3- (ethoxidiaisopropylsilanyl) -propylcarbamoyl] butyric acid

4- [3- (ethoxidiaisopropylsilanyl) propylcarbamoyl] butyric acid 2,5-dioxopyrrolidin-1-yl ester

5- [diiisobutyl- (4-phenylbutoxy) -silanyl] -valerianic acid 2,5-dioxopyrrolidin-1-yl ester

5 - [(4-polystyrene- (methoxybenzyloxy) -diisobutylsilanyl] -valerianic acid 2,5-dioxopyrrolidin-1-yl ester

5- (polystyrene-methoxydisobutylsilanyl) -valerianic acid 2,5-dioxopyrrolidin-1-yl ester

5- (polystyrene-ethoxydisobutylsilanyl) -valerianic acid 2,5-dioxopyrrolidin-1-yl ester.

28. The method of obtaining the compounds of formula 1 according to any one of claims 1 to 19, where the compound of formula III according to any one of claims 25 to 27 reacts with the compound of formula IV

where FG ² has the meaning as defined above for FG ¹ , and E has the same meaning as defined in any one of claims 1-19.

29. A process for preparing a compound of formula II as defined in any one of claims 20-24, wherein X is F, where F is a fluorine isotope, wherein said method comprises the step of reacting a compound of formula I with a fluorinating agent.

30. The method according to clause 29, where the reaction stage is carried out at a temperature of 80 ° C or lower.

31. The method according to clause 30, where the reaction temperature is 50 ° C or lower.

32. A compound selected from the group consisting of

4 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] acetic acid

2- [4 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] ethanol

4 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) benzoic acid

[4 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] methanol

3- [4 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] propan-1-ol

3- [4 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] propionic acid

3- [4 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] propan-1-ol

3- [3 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] propionic acid

2- [3 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] ethanol

[3 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] acetic acid

[4 - ([ ¹⁸ F] Fluorodiisobutylsilanyl) phenyl] acetic acid

4 - ([ ¹⁸ F] Fluorodiisobutylsilanyl) benzoic acid

N- (3 - ([ ¹⁸ F] Fluorodimethylsilyl) propyl) biphenyl-4-carboxamide

N- (3 - ([ ¹⁸ F] Fluorodiisopropylsilyl) propyl) biphenyl-4-carboxamide

[ ¹⁸ F] Fluorodiisopropyl- {4- [2- (tetrahydropyran-2-yloxy) ethyl] phenyl} silane

2- [4 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] acetyl-Val-βAIa-Phe-Gly-NH ₂ ;

3- [3 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] propanyl-Val-βAla-Phe-Gly-NH ₂ ;

2- [4 - ([ ¹⁸ F] Fluorodiisopropylsilanyl) phenyl] acetyl-Ala-Gln-Trp-Gly-His (3-Me) -FA1010-Leu-NH ₂

Benzyl 2- (ditretbutyl- [ ¹⁸ F] fluorosilyl) acetate

1- (Ditretbutylfluorosilyl) acetyl-Val-pAla-Phe-Gly-NH ₂

N-Benzyl-2- (4- (ditretbutyl [ ¹⁸ F] fluorosilyl) phenyl) acetamide

2- (4- (Ditretbutyl [ ¹⁸ F] fluorosilyl) phenyl) acetyl-Ala-Gln-Trp-Gly-His (3-Me) -FA1010-Leu-NH ₂ .

33. A composition that contains a compound of formula I or II, a pharmaceutically acceptable salt of an organic or inorganic acid, hydrate, complex, ester, amide, solvate or prodrug thereof.

34. The composition according to p, which further comprises a pharmaceutically acceptable carrier, diluent, adjuvant or excipient.

35. An imaging method that includes the step of administering to a patient a labeled compound of formula II according to any one of claims 20-24 or a pharmaceutically acceptable salt thereof of an organic or inorganic acid, hydrate, complex, ester, amide, solvate or prodrugs thereof in an amount that may be detected, and imaging the tissues of the specified patient.

36. A kit that includes a vial that contains a predetermined amount of a compound of formula I according to any one of claims 1-19, or a pharmaceutically acceptable salt thereof of an organic or inorganic acid, hydrate, complex, ester, amide, solvate or prodrug thereof.

37. The compound of formula I or II according to claim 1, or a pharmaceutically acceptable salt thereof of an organic or inorganic acid, hydrate, complex, ester, amide, solvate or prodrug thereof, for use as a medicament.

38. The compound of formula II according to claim 20, or a pharmaceutically acceptable salt thereof of an organic or inorganic acid, hydrate, complex, ester, amide, solvate or prodrug thereof, for use as a diagnostic imaging agent.

39. The compound of formula II according to claim 20, or a pharmaceutically acceptable salt thereof of an organic or inorganic acid, hydrate, complex, ester, amide, solvate or prodrug thereof, for use as a visualizing agent for positron emission tomography (PET).

40. The use of a compound of formula I or II according to any one of claims 1-24, or a pharmaceutically acceptable salt thereof of an organic or inorganic acid, hydrate, complex, ester, amide, solvate or prodrugs thereof, for the manufacture of a medicament.

41. The use of a compound of formula I or II according to any one of claims 1-24, or a pharmaceutically acceptable salt thereof of an organic or inorganic acid, hydrate, complex, ester, amide, solvate or prodrugs thereof, for the manufacture of a diagnostic imaging agent.

42. The application of paragraph 41, where the diagnostic imaging agent is intended for positron emission tomography.

43. The application of paragraph 41 for the manufacture of a diagnostic imaging agent for imaging tissue with target sites using an imaging agent.

44. The use of claim 41 for imaging tumors, imaging inflammatory and / or neurodegenerative diseases, such as multiple sclerosis or Alzheimer's disease, imaging diseases related to angiogenesis, such as solid tumor growth and rheumatoid arthritis.