US 2008/0292548 A1Published application

Compounds and methods for 18f labeled agents

AssigneeBayer Pharma Aktiengesellschaft

InventorsLutz Lehmann, Ananth Srinivasan, Thomas Brumby, Detlef Suelzle, Timo Stellfeld, Keith Graham, Mylene Karramkam, Simon Ametamey

Life of this patent

Estimating the term…

Abstract

The present invention relates to novel compounds suitable for or already radiolabeled with 18F, methods of making such compounds and use of such compounds for diagnostic imaging. Such labeled compounds are characterized by Formula II, wherein the substituents G, Q, L, Y and U have the meaning as defined in the specification and claims.

Claims49

Dependent claims

A compound having general chemical Formula A

wherein
-G is selected from the group comprising —F, —Cl, —Br, —I, —NO, —NO2, —NR4COCF3, —NR4SO2CF3, —N(R4)SO2R5, —N(CF3)2, —NHCSNHR4, —N(SO2R5)2, —N(O)═NCONH2, —NR4CN, —NHCSR5, —N≡C, —N═C(CF3)2, —N═NCF3, —N═NCN, —NR4COR4, —NR4COOR5, —OSO2CF3, —OSO2C6H5, —OCOR5, —ONO2, —OSO2R5, —O—C═CH2, —OCF2CF3, —OCOCF3, —OCN, —OCF3, —C≡N, —C(NO2)3, —COOR4, —CONR4R5, —C(S)NH2, —CH═NOR4, —CH2SO2R4, —COCF3, —CF3, —CF2Cl—CBr3, —CClF2, —CCl3, —CF2CF3, —C≡CR4, —CH═NSO2CF3, —CH2CF3, —COR5, —CH═NOR5, —CH2CONH2, —CSNHR5, —CH═NNHCSNH2, —CH═NNHCONHNH2, —C≡C—CF3, —CF═CFCF3, —CF2—CF2—CF3, —CR4(CN)2, —COCF2CF2CF3, —C(CF3)3, —C(CN)3, —CR4═C(CN)2, -1-pyrryl, —C(CN)═C(CN)2, —C-pyridyl, —COC6H5, —COOC6H5, —SOCF3, —SO2CF3, —SCF3, —SO2CN, —SCOCF3, —SOR5, —S(OR5), —SC≡CR4, —SO2R5, —SSO2R5, —SR5, —SSR4, —SO2CF2CF3, —SCF2CF3, —S(CF3)═NSO2CF3, —SO2C6H5, —SO2N(R5)2, —SO2C(CF3)3, —SC(CF3)3, —SO(CF3)═NSO2CF3, —S(O)(═NH)CF3, —S(O)(═NH)R5, —S—C═CH2, —SCOR5, —SOC6H5, —P(O)C3F7, —PO(OR5)2, —PO(N(R5)2)2, —P(N(R5)2)2, —P(O)R52, and —PO(OR5)2 or another electron-drawing group wherein the respective substituent can be in ortho, para or meta position in respect of the K group,
-Q is hydrogen, unbranched or branched lower alkyl, aryl, heteroaryl, —O—(C1-C4 alkyl), —CN, -halogen, —SO2—R4, —NO2 or a condensed aryl or condensed heteroaryl wherein the respective substituent can be in ortho, para or meta position in respect of the K group,
wherein
R4 is hydrogen or unbranched or branched lower alkyl and
R5 is unbranched or branched lower alkyl,
-L- is a bond, —CO—, —SO2—, —(CH2)d—CO—, —SO—, —C≡C—CO—, —[CH2]m-E-[CH2]n—CO—, —[CH2]m-E-[CH2]n—SO2—, —C(═O)—O—, —NR10—, —O—, —(S)p—, —C(═O)NR12—, —C(═S)NR12—, —C(═S)O—, C1-C6 cycloalkyl, alkenyl, heterocycloalkyl, unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl, aralkyl, heteroaralkyl, alkyloxy, aryloxy, aralkyloxy, —SO2NR13—, —NR13SO2—, —NR13C(═O)O—, —NR13C(═O)NR12—, —NH—NH— and —NH—O—,
wherein
d is an integer of from 1 to 6,
m and n, independently, are any integer of from 0 to 5,
-E- is a bond, —S—, —O— or —NR9—,
wherein R9 is H, C1-C10 alkyl, aryl, heteroaryl or aralkyl,
p is any integer of from 1 to 3,
R10 and R12, independently, are selected from the group comprising H, C1-C10 alkyl, aryl, heteroaryl or aralkyl and
R13 is H, substituted or non substituted, linear or branched C1-C6 alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, aralkyl or heteroaralkyl,
Y is a bond or a spacer,
U is a targeting agent,
X− is CF3S(O)2O−, C4F9S(O)2O−, iodide anion, bromide anion, chloride anion, perchlorate anion (ClO4−), phosphate anion, trifluoroacetate anion (CF3—C(O)O−), or the anion of another salt of an inorganic or organic acid,
K is N+(R1)(R2)(R3)X− or W,
wherein
R1, R2 and R3 are independently from each other selected from the group comprising substituted or unsubstituted alkyl and aralkyl,
W is a fluororine isotope,
and a pharmaceutically acceptable salt of an inorganic or organic acid thereof, a hydrate, complex, ester, amide, solvate and prodrug thereof.

20 more elements

Peptide sequence selected from

SEQ ID NO:
1 Gln-Trp-Ala-Val-NMeGly-His-Sta-Leu-NH2
SEQ ID NO:
2 Gln-Trp-Ala-Val-Gly-His(Me)-Sta-Leu-NH2
SEQ ID NO:
3 Gln-Trp-Ala-Val-NMeGly-His(3Me)-Sta-Leu-NH2
SEQ ID NO:
4 Gln-Trp-Ala-Val-Gly-His(3Me)-Sta-Leu-NH2
SEQ ID NO:
7 Gln-Trp-Ala-Val-NMeGly-His(3Me)-Sta-Cpa-NH2
SEQ ID NO:
8 Gln-Trp-Ala-Val-Gly-His(3Me)-4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
12 Gln-Trp-Ala-Val-Gly-His(3Me)-4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
17 Gln-Trp-Ala-Val-Gly-His-4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
23 Gln-Trp-Ala-Val-NMeGly-His(3Me)-4-Am,5-MeHpA-Cpa-NH2
SEQ ID NO:
27 Gln-Trp-Ala-Val-NMeGly-His-FA02010-Cpa-NH2
SEQ ID NO:
28 Gln-Trp-Ala-Val-NMeGly-His-4-Am,5-MeHpA-tbuGly-NH2
SEQ ID NO:
30 Gln-Trp-Ala-Val-NMeGly-His(3Me)-Sta-tBuGly-NH2
SEQ ID NO:
32 Gln-Trp-Ala-Val-NMeGly-His(3Me)-4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
33 Gln-DTrp-Ala-Val-Gly-His-4-Am,5-MeHpA-tbuGly-NH2
SEQ ID NO:
34 Gln-DTrp-Ala-Val-Gly-His-4-Am-5-MeHxA-Cpa-NH2
SEQ ID NO:
35 Gln-Trp-Ala-Val-NMeGly-His(3Me)-Sta-Cpa-NH2
SEQ ID NO:
36 Gln-DTrp-Ala-Val-Gly-His-Sta-tbuAla-NH2
SEQ ID NO:
42 Gln-Trp-Ala-Val-Gly-His(3Me)-Sta-Cpa-NH2
SEQ ID NO:
43 Gln-Trp-Ala-Val-Gly-His(3Me)-Sta-tBuGly-NH2
SEQ ID NO:
46 Gln-Trp-Ala-Val-Gly-His(3Me)-4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
48 Gln-Trp-Ala-Val-Gly-His(3Me)-4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
49 Gln-Trp-Ala-Val-Gly-NMeHis-4-Am,5-MeHpA-Cpa-NH2
SEQ ID NO:
49 Gln-Trp-Ala-Val-Gly-NMeHis(3Me)-4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
50 Gln-Trp-Ala-Val-Gly-NMeHis-4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
51 Gln-Trp-Ala-Val-NMeGly-His-AHMHxA -Leu-NH2
SEQ ID NO:
52 Gln-Trp-Ala-Val-βAla-NMeHis-Tha-Cpa-NH2
SEQ ID NO:
53 Gln-Trp-Ala-Val-βAla-NMeHis-Phe-Cpa-NH2
SEQ ID NO:
54 Gln-Trp-Ala-Val-βAla-NMeHis-Phe-Leu-NH2
SEQ ID NO:
55 Gln-Trp-Ala-Val-βAla-DHis-Phe-Leu-NH2
SEQ ID NO:
56 Gln-Trp-Ala-Val-βAla-His-βhLeu-Leu-NH2
SEQ ID NO:
57 Gln-Trp-Ala-Val-βAla-His-βhIle-Leu-NH2
SEQ ID NO:
58 Gln-Trp-Ala-Val-βAla-His-βhLeu-tbuGly-NH2
SEQ ID NO:
59 Gln-Trp-Ala-Val-βAla-His(3Me)-Phe-Tha-NH2
SEQ ID NO:
60 Gln-Trp-Ala-Val-βAla-His(3Me)-Phe-Nle-NH2
SEQ ID NO:
61 Gln-Trp-Ala-Val-βAla-NMeHis-Phe-tbuGly-NH2
SEQ ID NO:
62 Gln-Trp-Ala-Val-βAla-NMeHis-Tha-tbuGly-NH2
SEQ ID NO:
63 Gln-Trp-Ala-Val-βAla-His(3Me)-Tha-tbuGly-NH2
SEQ ID NO:
64 Gln-Trp-Ala-Val-βAla-His(3Me)-Phe-Cpa-NH2
SEQ ID NO:
65 Gln-Trp-Ala-NMeVal-βAla-His-Phe-Leu-NH2
SEQ ID NO:
66 Gln-Trp-Ala-Val-βAla-His-NMePhe-Leu-NH2
SEQ ID NO:
67 Gln-DTrp-Ala-Val-βAla-His-Phe-Leu-NH2
SEQ ID NO:
68 Gln-Trp-DAla-Val-βAla-His-Phe-Leu-NH2
SEQ ID NO:
69 Gln-Trp-Ala-DVal-βAla-His-Phe-Leu-NH2
SEQ ID NO:
70 Gln-Trp-Ala-Val-βAla-His-DPhe-Leu-NH2
SEQ ID NO:
71 Gln-Trp-Ala-Val-βAla-His-βhIle-tbuGly-NH2
SEQ ID NO:
72 Gln-Trp-Ala-Val-NMeGly-His-4-Am,5-MeHpA-Cpa-NH2
SEQ ID NO:
73 Gln-Trp-Ala-Val-NMeGly-His-Sta-Cpa-NH2
SEQ ID NO:
74 Gln-Trp-Ala-Val-NMeGly-His-Sta-tbuAla-NH2
SEQ ID NO:
75 Gln-Trp-Ala-Val-NMeGly-His-4-Am,5-MeHpA-tbuAla-NH2
SEQ ID NO:
77 Gln-Trp-Ala-Val-His(Me)-Sta-Leu-NH2
SEQ ID NO:
82 Gln-Trp-Ala-Val-Gly-His(3Me)-FA4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
90 Gln-Trp-Ala-Val-Gly-His(3Me)-4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
91 Gln-Trp-Ala-Val-Gly-His-4-Am,5-MeHpA-Leu-NH2
SEQ ID NO:
101 Gln-Trp-Ala-Val-Gly-His(3Me)-4-Am-5-MeHpA-4-amino-5-methylheptanoic acid-Lue-NH2
SEQ ID NO:
102 Gln-Trp-Ala-Val-NMeGly-His(3Me)-4-Am-5-MeHpA-4-amino-5-methylheptanoic acid-Cpa-NH2.

107 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/851,910Filed 7 Sep 2007
Priority: EP 06090166.78 Sep 2006
Published: 27 Nov 2008
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07K 14/6555
Somatostatins: at least 1 amino acid in D-form
A61K 51/088
Peptides, e.g. proteins , carriers being peptides, polyamino acids, proteins: conjugates with carriers being peptides, polyamino acids or proteins
A61P 35/00
Antineoplastic agents
C07K 14/57545
Hormones: neuropeptide Y

Family

Application60/845,163Us provisional application · filed 18 Sep 2006
US 8,557,776 B2Related patent
US 2008/0292548 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound having general chemical Formula A

wherein
-G is selected from the group comprising —F, —Cl, —Br, —I, —NO, —NO2, —NR4COCF3, —NR4SO2CF3, —N(R4)SO2R5, —N(CF3)2, —NHCSNHR4, —N(SO2R5)2, —N(O)═NCONH2, —NR4CN, —NHCSR5, —N≡C, —N═C(CF3)2, —N═NCF3, —N═NCN, —NR4COR4, —NR4COOR5, —OSO2CF3, —OSO2C6H5, —OCOR5, —ONO2, —OSO2R5, —O—C═CH2, —OCF2CF3, —OCOCF3, —OCN, —OCF3, —C≡N, —C(NO2)3, —COOR4, —CONR4R5, —C(S)NH2, —CH═NOR4, —CH2SO2R4, —COCF3, —CF3, —CF2Cl—CBr3, —CClF2, —CCl3, —CF2CF3, —C≡CR4, —CH═NSO2CF3, —CH2CF3, —COR5, —CH═NOR5, —CH2CONH2, —CSNHR5, —CH═NNHCSNH2, —CH═NNHCONHNH2, —C≡C—CF3, —CF═CFCF3, —CF2—CF2—CF3, —CR4(CN)2, —COCF2CF2CF3, —C(CF3)3, —C(CN)3, —CR4═C(CN)2, -1-pyrryl, —C(CN)═C(CN)2, —C-pyridyl, —COC6H5, —COOC6H5, —SOCF3, —SO2CF3, —SCF3, —SO2CN, —SCOCF3, —SOR5, —S(OR5), —SC≡CR4, —SO2R5, —SSO2R5, —SR5, —SSR4, —SO2CF2CF3, —SCF2CF3, —S(CF3)═NSO2CF3, —SO2C6H5, —SO2N(R5)2, —SO2C(CF3)3, —SC(CF3)3, —SO(CF3)═NSO2CF3, —S(O)(═NH)CF3, —S(O)(═NH)R5, —S—C═CH2, —SCOR5, —SOC6H5, —P(O)C3F7, —PO(OR5)2, —PO(N(R5)2)2, —P(N(R5)2)2, —P(O)R52, and —PO(OR5)2 or another electron-drawing group wherein the respective substituent can be in ortho, para or meta position in respect of the K group,
-Q is hydrogen, unbranched or branched lower alkyl, aryl, heteroaryl, —O—(C1-C4 alkyl), —CN, -halogen, —SO2—R4, —NO2 or a condensed aryl or condensed heteroaryl wherein the respective substituent can be in ortho, para or meta position in respect of the K group,
wherein
R4 is hydrogen or unbranched or branched lower alkyl and
R5 is unbranched or branched lower alkyl,
-L- is a bond, —CO—, —SO2—, —(CH2)d—CO—, —SO—, —C≡C—CO—, —[CH2]m-E-[CH2]n—CO—, —[CH2]m-E-[CH2]n—SO2—, —C(═O)—O—, —NR10—, —O—, —(S)p—, —C(═O)NR12—, —C(═S)NR12—, —C(═S)O—, C1-C6 cycloalkyl, alkenyl, heterocycloalkyl, unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl, aralkyl, heteroaralkyl, alkyloxy, aryloxy, aralkyloxy, —SO2NR13—, —NR13SO2—, —NR13C(═O)O—, —NR13C(═O)NR12—, —NH—NH— and —NH—O—,
wherein
d is an integer of from 1 to 6,
m and n, independently, are any integer of from 0 to 5,
-E- is a bond, —S—, —O— or —NR9—,
wherein R9 is H, C1-C10 alkyl, aryl, heteroaryl or aralkyl,
p is any integer of from 1 to 3,
R10 and R12, independently, are selected from the group comprising H, C1-C10 alkyl, aryl, heteroaryl or aralkyl and
R13 is H, substituted or non substituted, linear or branched C1-C6 alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, aralkyl or heteroaralkyl,
Y is a bond or a spacer,
U is a targeting agent,
X− is CF3S(O)2O−, C4F9S(O)2O−, iodide anion, bromide anion, chloride anion, perchlorate anion (ClO4−), phosphate anion, trifluoroacetate anion (CF3—C(O)O−), or the anion of another salt of an inorganic or organic acid,
K is N+(R1)(R2)(R3)X− or W,
wherein
R1, R2 and R3 are independently from each other selected from the group comprising substituted or unsubstituted alkyl and aralkyl,
W is a fluororine isotope,
and a pharmaceutically acceptable salt of an inorganic or organic acid thereof, a hydrate, complex, ester, amide, solvate and prodrug thereof.

20 more elements

Facts

Application

11/851,910Filed 7 Sep 2007

Priority

EP 06090166.78 Sep 2006

Published

27 Nov 2008

Term ends

Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07K 14/6555
Somatostatins: at least 1 amino acid in D-form
A61K 51/088
Peptides, e.g. proteins , carriers being peptides, polyamino acids, proteins: conjugates with carriers being peptides, polyamino acids or proteins
A61P 35/00
Antineoplastic agents
C07K 14/57545
Hormones: neuropeptide Y