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Kafe 바로가기국가/구분 | United States(US) Patent 등록 |
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국제특허분류(IPC7판) |
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출원번호 | US-0281015 (2002-10-26) |
발명자 / 주소 |
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출원인 / 주소 |
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대리인 / 주소 |
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인용정보 | 피인용 횟수 : 0 인용 특허 : 49 |
The present invention describes novel compounds of the formula: description="In-line Formulae" end="lead"(Q) d--Ln--Ch,description="In-line Formulae" end="tail" useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. Th
The present invention describes novel compounds of the formula: description="In-line Formulae" end="lead"(Q) d--Ln--Ch,description="In-line Formulae" end="tail" useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention further provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia, and myocardial reperfusion injury. The present invention still further provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.
What is claimed is described below: 1. An MRI contrast agent, comprising: a metal, wherein , the metal is a paramagnetic metal ion selected from the group: Gd(III), Dy(III), Fe(III), and Mn(II), a chelator capable of chelating the metal, and a targeting moiety, wherein the targeting moiety is bound
What is claimed is described below: 1. An MRI contrast agent, comprising: a metal, wherein , the metal is a paramagnetic metal ion selected from the group: Gd(III), Dy(III), Fe(III), and Mn(II), a chelator capable of chelating the metal, and a targeting moiety, wherein the targeting moiety is bound to the chelator, is a quinolone non-peptide and binds to a receptor that is upregulated during angiogenesis and the compound has 0-1 linking groups between the targeting moiety and chelator, the targeting moiety is a quinolone nonpeptide and the linking group is present between the targeting moiety and chelator. 2. A composition according to claim 1, wherein the linking group is present between the targeting moiety and chelator and the receptor is αvβ3 or αvβ 5. 3. A composition according to claim 2, wherein the metal ion is Gd(III). 4. A composition according to claim 3, wherein the contrast agent is 5. A compound, comprising: a targeting moiety and a surfactant, wherein the targeting moiety is bound to the surfactant, is a quinolone nonpeptide, and binds to a receptor that is upregulated during angiogenesis and the compound has 0-1 linking groups between the targeting moiety and surfactant. 6. A compound according to claim 5, wherein the linking group is present between the targeting moiety and surfactant. 7. A compound according to claim 6, wherein the receptor is the integrin αvβ3 or αvβ 5 and the compound is of the formula: description="In-line Formulae" end="lead"(Q) d--Ln--Sfdescription="In-line Formulae" end="tail" wherein, Q is a compound of Formula (II): including stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, or pharmaceutically acceptable salt or prodrug forms thereof wherein: R1e is selected from: Ae is--CH2--or--N(R10e)--; A1e and Be are independently--CH2--or--N(R10e)--; De is--N(R10e)--or--S--; Ee--Fe is--C(R2e)═C(R 3e)--or--C(R2e)2C(R3e)2--; Je is--C(R2e)--or--N--; Ke, Le and Me are independently--C(R2e)--or--C(R3e)--; R2e and R3e are independently selected from: H, C1-C4 alkoxy, NR11eR12e , halogen, NO2, CN, CF3, C1-C6 alkyl, C3-C6 alkenyl, C3-C7 cycloalkyl, C 3-C7 cycloalkyl(C1-C4 alkyl), aryl(C 1-C6 alkyl)-, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy)carbonyl, arylcarbonyl, and aryl substituted with 0-4 R7e, alternatively, when R2e and R3e are substituents on adjacent atoms, they can be taken together with the carbon atoms to which they are attached to form a 5-7 membered carbocyclic or 5-7 membered heterocyclic aromatic or nonaromatic ring system, said carbocyclic or heterocyclic ring being substituted with 0-2 groups selected from C1-C4 alkyl, C1-C4 alkoxy, halo, cyano, amino, CF3 and NO2; R2ae is selected from: H, C1-C10 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl), aryl, aryl(C1-C4 alkyl)-, (C2-C7 alkyl)carbonyl, arylcarbonyl, (C2-C10 alkoxy)carbonyl, C3-C7 cycloalkoxycarbonyl, C7-C11 bicycloalkoxycarbonyl, aryloxycarbonyl, aryl(C1-C10 alkoxy)carbonyl, C1-C6 alkylcarbonyloxy(C1-C4 alkoxy)carbonyl, arylcarbonyloxy(C1-C4 alkoxy) carbonyl, and C3-C7 cycloalkylcarbonyloxy(C1-C4 alkoxy)carbonyl; R7e is selected from: H, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, aryl, aryl(C1-C4 alkyl)-, (C1-C4 alkyl)carbonyl, CO2R18ae, SO2R 11e, SO2NR10eR11e, OR10e, and N(R11e)R12e; Ue is selected from: --(CH2)ne--,--(CH2) neO(CH2)me--,--(CH2) neN(R12)(CH2)me--,--NH(CH2)ne--,--(CH2)n eC(═O)(CH2)me--, --(CH2)neS(O)pe (CH2)me--,--(CH2)ne NHNH(CH2)me--, --N(R10e)C(═O)--,--NHC(═O)(CH2) ne--,--C(═O)N(R10e)--, and--N(R 10e)S(O)pe--; Ge is N or CR19e; We is--C(═O)--N(R10e)--(C1-C3 alkylene)-, in which the alkylene group is substituted by R8e and by R9e: R8e and R9e are independently selected from: H, CO2R18be, C(═O)R18be, CONR17R18be, C1-C10 alkyl substituted with 0-1 R 6e, C2-C10 alkenyl substituted with 0-1 R 6e, C2-C10 alkynyl substituted with 0-1 R 6e, C3-C8 cycloalkyl substituted with 0-1 R 6e, C5-C6 cycloalkenyl substituted with 0-1 R6e, (C1-C10 alkyl)carbonyl, C3-C10 cycloalkyl(C1-C4 alkyl)-, phenyl substituted with 0-3 R6e, naphthyl substituted with 0-3 R6e, a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R7e, C1-C10 alkoxy substituted with 0-2 R 7e, hydroxy, nitro,--N(R10e)R11e,--N(R 16e)R17e, aryl(C0-C6 alkyl)carbonyl, aryl(C3-C6 alkyl), heteroaryl(C1-C6 alkyl), CONR18aeR20e, SO2R18ae, and SO2NR18eaR20e, providing that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 1-2 R7e; R6e is selected from: H, C1-C10 alkyl, hydroxy, C1-C 10 alkoxy, nitro, C1-C10 alkylcarbonyl,--N(R 11e)R12e, cyano, halo, CF3, CHO, CO2R 18be, C(═O)R18be, CONR17eR18be, OC(═O)R10e, OR10e, OC(═O)NR10eR 11e, NR10eC(═O)R10e, NR10eC(═O) OR21e, NR10eC(═O)NR10eR11e, NR10eSO2NR10eR11e, NR10e SO2R21e, S(O)pR11e, SO2NR 10eR11e, aryl substituted with 0-3 groups selected from halogen, C 1-C6 alkoxy, C1-C6 alkyl, CF3, S(O)meMe, and--NMe2, aryl(C1-C4 alkyl)-, said aryl being substituted with 0-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, S(O)p eMe, and--NMe2, and a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R7e; R10e is selected from: H, CF3, C3-C6 alkenyl, C3-C11 cycloalkyl, aryl, (C3-C11 cycloalkyl) methyl, aryl(C1-C4 alkyl), and C1-C10 alkyl substituted with 0-2 R6e; R11e is selected from: H, hydroxy, C1-C8 alkyl, C3-C6 alkenyl, C3-C11 cycloalkyl, (C3-C11 cycloalkyl)methyl, C1-C6 alkoxy, benzyloxy, aryl, heteroaryl, heteroaryl(C1-C4 alkyl)-, aryl(C1-C4 alkyl), adamantylmethyl, and C1-C10 alkyl substituted with 0-2 R 4e; R4e is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, (C1-C10 alkyl)carbonyl, aryl, heteroaryl, aryl(C1-C6 alkyl)-, and heteroaryl(C1-C6 alkyl)-, wherein said aryl or heteroaryl groups are substituted with 0-2 substituents independently selected from the group consisting of C 1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2, alternatively, when R10e and R11e are both substituents on the same nitrogen atom (as in--NR10eR 11e) they may be taken together with the nitrogen atom to which they are attached to form a heterocycle selected from: 3-azabicyclononyl, 1,2, 3,4-tetrahydro-1-quinolinyl, 1,2,3,4-tetrahydro-2-isoquinolinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl, and 1-piperazinyl; said heterocycle being substituted with 0-3 groups selected from: C1-C6 alkyl, aryl, heteroaryl, aryl(C1-C4 alkyl)-, (C1-C6 alkyl)carbonyl, (C3-C7 cycloalkyl)carbonyl, (C1-C6 alkoxy) carbonyl, aryl(C1-C4 alkoxy)carbonyl, C1-C 6 alkylsulfonyl, and arylsulfonyl; R12e is selected from: H, C1-C6 alkyl, triphenylmethyl, methoxymethyl, methoxyphenyldiphenylmethyl, trimethylsilylethoxymethyl, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy) carbonyl, (C1-C6 alkyl)aminocarbonyl, C3-C 6 alkenyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, aryl, heteroaryl(C 1-C6 alkyl)carbonyl, heteroarylcarbonyl, aryl(C1-C6 alkyl)-, (C1-C6 alkyl)carbonyl, arylcarbonyl, C1-C6 alkylsulfonyl, arylsulfonyl, aryl(C1-C6 alkyl)sulfonyl, heteroarylsulfonyl, heteroaryl(C1-C6 alkyl)sulfonyl, aryloxycarbonyl, and aryl(C1-C6 alkoxy)carbonyl, wherein said aryl groups are substituted with 0-2 substituents selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halo, CF3, and nitro; R16e is selected from: --C(═O)OR18ae,--C(═O)R18be,--C(═O)N(R18be)2, --C(═O)NHSO2R18ae,--C(═O) NHC(═O)R18be, --C(═O)NHC(═O)OR18ae,--C(═O)NHSO 2NHR18be,--SO2R18ae, --SO2N(R18be)2, and--SO2 NHC(═O)OR18be; R17e is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, aryl, aryl(C1-C6 alkyl)-, and heteroaryl(C 1-C6 alkyl); R18ae is selected from: C1-C8 alkyl optionally substituted with a bond to Ln, C3-C11 cycloalkyl optionally substituted with a bond to Ln, aryl(C1-C6 alkyl)-optionally substituted with a bond to Ln, heteroaryl(C1-C6 alkyl)-optionally substituted with a bond to Ln, (C1-C6 alkyl)heteroaryl optionally substituted with a bond to Ln, biaryl(C1-C6 alkyl) optionally substituted with a bond to Ln, heteroaryl optionally substituted with a bond to Ln, phenyl substituted with 3-4 R19e and optionally substituted with a bond to L n, naphthyl substituted with 0-4 R19e and optionally substituted with a bond to Ln, and a bond to Ln, wherein said aryl or heteroaryl groups are optionally substituted with 0-4 R19e; R18be is H or R18ae; R19e is selected from: H, halogen, CF3, CO2H, CN, NO2,--NR11eR12e, OCF3, C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C 3-C11 cycloalkyl, C3-C7 cycloalkyl(C 1-C4 alkyl)-, aryl(C1-C6 alkyl)-, C 1-C6 alkoxy, C1-C4 alkoxycarbonyl, aryl, aryl-O--, aryl-SO2--, heteroaryl, and heteroaryl-SO2--, wherein said aryl and heteroaryl groups are substituted with 0-4 groups selected from hydrogen, halogen, CF3, C1-C3 alkyl, and C1-C3 alkoxy; R20e is selected from: hydroxy, C1-C10 alkyloxy, C3-C 11 cycloalkyloxy, aryloxy, aryl(C1-C4 alkyl)oxy, C2-C10 alkylcarbonyloxy(C1-C2 alkyl)oxy-, C2-C10 alkoxycarbonyloxy(C1-C2 alkyl)oxy-, C2-C10 alkoxycarbonyl(C1-C2 alkyl)oxy-, C3-C10 cycloalkylcarbonyloxy(C1-C2 alkyl)oxy-, C3-C10 cycloalkoxycarbonyloxy(C1-C2 alkyl)oxy-, C3-C10 cycloalkoxycarbonyl(C1-C 2 alkyl)oxy-, aryloxycarbonyl(C1-C2 alkyl)oxy-, aryloxycarbonyloxy(C1-C2 alkyl)oxy-, arylcarbonyloxy(C1-C2 alkyl)oxy-, C1-C5 alkoxy(C1-C5 alkyl) carbonyloxy(C1-C2 alkyl)oxy, (5-(C1-C5 alkyl)-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, and (R10e)(R11e)N--(C1-C10 alkoxy)-; R21e is selected from: C1-C8 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, (C3-C11 cycloalkyl) methyl, aryl, aryl(C1-C4 alkyl)-, and C 1-C10 alkyl substituted with 0-2 R7e; R22e is selected from: --C(═O)--R18be,--C(═O)N(R18be) 2,--C(═O)NHSO2R18ae,--C(═O) NHC(═O)R18be,--C(═O)NHC(═O)OR18ae, and--C(═O)NHSO2NHR18be; Ye is selected from: --COR20e,--SO3H,--PO3H,--CONHNHSO2CF3,--CONHSO2R18ae,--CONHSO2NHR18be,--NHCOCF3,--NHCONHSO2 R18ae,--NHSO2R18ae,--OPO3H2 ,--OSO3H,--PO3H2,--SO2NHCOR 18ae, --SO2NHCO2R18ae, me is 0-2; ne is 0-4; pe is 0-2; re is 0-2; with the following proviso: ne and meare chosen such that the number of atoms connecting R1e and Ye is in the range of 8-14; d is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Ln is a linking group having the formula: description="In-line Formulae" end="lead"((W) h--(CR6R7)g)x--(Z)k--((CR6aR7a)g'--(W)h')x';description="In-line Formulae" end="tail" W is independently selected at each occurrence from the group: O, S, NH, NHC(═O), C(═O)NH, NR8C(═O), C(═O)NR8, C(═O), C(═O)O, OC(═O), NHC(═S) NH, NHC(═O)NH, SO2, SO2NH, (OCH2CH 2)20-200, (CH2CH2O)20-200, (OCH2CH2CH2)20-200, (CH2 CH2CH2O)20-200, and (aa)t'; aa is independently at each occurrence an amino acid; Z is selected from the group: aryl substituted with 0-3 R 10, C3-10 cycloalkyl substituted with 0-3 R10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R 10; R6, R6a, R7, R7a, and R8 are independently selected at each occurrence from the group: H, ═O, COOH, SO3H, PO3H, C1-C5 alkyl substituted with 0-3 R10, aryl substituted with 0-3 R 10, benzyl substituted with 0-3 R10, and C1-C5 alkoxy substituted with 0-3 R10, NHC(═O)R11, C(═O)NHR11, NHC(═O)NHR11, NHR11, R11, and a bond to Sf; R10 is independently selected at each occurrence from the group: a bond to Sf, COOR11, C(═O)NHR 11, NHC(═O)R11, OH, NHR11, SO3H, PO3H,--OPO3H2,--OSO3H, aryl substituted with 0-3 R11, C1-5 alkyl substituted with 0-1 R12, C1-5 alkoxy substituted with 0-1 R12, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R 11; R11 is independently selected at each occurrence from the group: H, alkyl substituted with 0-1 R12, aryl substituted with 0-1 R12, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R12, C3-10 cycloalkyl substituted with 0-1 R12, polyalkylene glycol substituted with 0-1 R12, carbohydrate substituted with 0-1 R12, cyclodextrin substituted with 0-1 R12, amino acid substituted with 0-1 R12, polycarboxyalkyl substituted with 0-1 R12, polyazaalkyl substituted with 0-1 R12, peptide substituted with 0-1 R12, wherein the peptide is comprised of 2-10 amino acids, 3, 6-O-disulfo-B-D-galactopyranosyl, bis(phosphonomethyl)glycine, and a bond to Sf; R12 is a bond to Sf; k is selected from 0, 1, and 2; h is selected from 0, 1, and 2; h' is selected from 0, 1, and 2; g is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; g' is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; t' is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; x is selected from 0, 1, 2, 3, 4, and 5; x' is selected from 0, 1, 2, 3, 4, and 5; Sf is a surfactant which is a lipid or a compound of the formula: A9 is selected from the group: OH and OR27; A10 is OR27; R27 is C(═O)C1-20 alkyl; E1 is C1-10 alkylene substituted with 1-3 R28; R28 is independently selected at each occurrence from the group: R30,--PO3H--R30, ═O,--CO2R29,--C(═O)R29,--C(═O)N(R 29)2,--CH2OR29,--OR29,--N(R29)2, C1-C5 alkyl, and C2-C4 alkenyl; R29 is independently selected at each occurrence from the group: R30, H, C1-C6 alkyl, phenyl, benzyl, and trifluoromethyl; R30 is a bond to Ln; and a pharmaceutically acceptable salt thereof. 8. A compound according to claim 7, wherein the compound is of the formula: description="In-line Formulae" end="lead"Q--L n--Sfdescription="In-line Formulae" end="tail" wherein, Q is a compound of Formula (IV): including stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, or pharmaceutically acceptable salt or prodrug forms thereof wherein: R1e is selected from: R2e and R3e are independently selected from: H, C1-C4 alkoxy, NR11eR12e , halogen, NO2, CN, CF3, C1-C6 alkyl, C3-C6 alkenyl, C3-C7 cycloalkyl, C 3-C7 cycloalkyl(C1-C4 alkyl), aryl(C 1-C6 alkyl)-, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy)carbonyl, arylcarbonyl, and aryl substituted with 0-4 R7e, alternatively, when R2e and R3e are substituents on adjacent atoms, they can be taken together with the carbon atoms to which they are attached to form a 5-7 membered carbocyclic or 5-7 membered heterocyclic aromatic or nonaromatic ring system, said carbocyclic or heterocyclic ring being substituted with 0-2 groups selected from C1-C4 alkyl, C1-C4 alkoxy, halo, cyano, amino, CF3 and NO2; R2ae is selected from: H, C1-C10 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl), aryl, aryl(C1-C4 alkyl)-, (C2-C7 alkyl)carbonyl, arylcarbonyl, (C2-C10 alkoxy)carbonyl, C3-C7 cycloalkoxycarbonyl, C7-C11 bicycloalkoxycarbonyl, aryloxycarbonyl, aryl(C1-C10 alkoxy)carbonyl, p1 C1-C6 alkylcarbonyloxy(C1-C4 alkoxy) carbonyl, arylcarbonyloxy(C1-C4 alkoxy)carbonyl, and C3-C7 cycloalkylcarbonyloxy(C1-C4 alkoxy)carbonyl; R7e is selected from: H, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, aryl, aryl(C1-C4 alkyl)-, (C1-C4 alkyl)carbonyl, CO2R18ae, SO2R 11e, SO2NR10eR11e, OR10e, and N(R11e)R12e; Ue is selected from: --(CH2)ne--,--(CH2) neO(CH2)me--,--NH(CH2) ne--, --N(R10e)C(═O)--,--NHC(═O)(CH2) ne--, and--C(═O)N(R10e)--; Ge is N or CR19e; R8e is selected from: H, CO2R18be, C(═O)R18be, CONR17eR18be, C1-C10 alkyl substituted with 0-1 R 6e, C2-C10 alkenyl substituted with 0-1 R 6e, C2-C10 alkynyl substituted with 0-1 R 6e, C3-C8 cycloalkyl substituted with 0-1 R 6e, C5-C6 cycloalkenyl substituted with 0-1 R6e, (C1-C10 alkyl)carbonyl, C3-C10 cycloalkyl(C1-C4 alkyl)-, phenyl substituted with 0-3 R6e, naphthyl substituted with 0-3 R6e, a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R7e; R9e is selected from: C1-C10 alkyl substituted with 0-1 R 6e, C1-C10 alkoxy substituted with 0-2 R 7e, H, nitro, N(R11e)R12e, OC(═O)R 10e, OR10e, OC(═O)NR10eR11e, NR 10eC(═O)R10e, NR10eC(═O)OR21e, NR10eC(═O)NR10eR11e, NR10eSO 2NR10eR11e, NR10eSO2R21e , hydroxy, OR22e,--N(R10e)R11e,--N(R 16e)R17e, aryl(C0-C6 alkyl)carbonyl, aryl(C1-C6 alkyl), heteroaryl(C1-C6 alkyl), CONR18aeR20e, SO2R18ae, and SO2NR18aeR20e, providing that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 1-2 R7e; R6e is selected from: H, C1-C10 alkyl, hydroxy, C1-C 10 alkoxy, nitro, C1-C10 alkylcarbonyl,--N(R 11e)R12e, cyano, halo, CF3, CHO, CO2R 18be, C(═O)R18be, CONR17eR18be, OC(═O)R10e, OR10e, OC(═O)NR10eR 11e, NR10eC(═O)R10e, NR10eC(═O) OR21e, NR10eC(═O)NR10eR11e, NR10eSO2NR10eR11e, NR10e SO2R21e, S(O)peR11e, SO 2NR10eR11e, aryl substituted with 0-3 groups selected from halogen, C 1-C6 alkoxy, C1-C6 alkyl, CF3, S(O)meMe, and--NMe2, aryl(C1-C4 alkyl)-, said aryl being substituted with 0-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, S(O)p eMe, and--NMe2, and a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R7e; R10e is selected from: H, CF3, C3-C6 alkenyl, C3-C11 cycloalkyl, aryl, (C3-C11 cycloalkyl) methyl, aryl(C1-C4 alkyl), and C1-C10 alkyl substituted with 0-2 R6e; R11e is selected from: H, hydroxy, C1-C8 alkyl, C3-C6 alkenyl, C3-C11 cycloalkyl, (C3-C11 cycloalkyl)methyl, C1-C6 alkoxy, benzyloxy, aryl, heteroaryl, heteroaryl(C1-C4 alkyl)-, aryl(C1-C4 alkyl), adamantylmethyl, and C1-C10 alkyl substituted with 0-2 R 4e; R4e is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, aryl, heteroaryl, aryl(C1-C6 alkyl)-, and heteroaryl(C1-C6 alkyl)-, wherein said aryl or heteroaryl groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C 1-C4 alkoxy, F, Cl, Br, CF3, and NO2, R12e is selected from: H, C1-C6 alkyl, triphenylmethyl, methoxymethyl, methoxyphenyldiphenylmethyl, trimethylsilylethoxymethyl, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy) carbonyl, (C1-C6 alkyl)aminocarbonyl, C3-C 6 alkenyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, aryl, heteroaryl(C 1-C6 alkyl)carbonyl, heteroarylcarbonyl, aryl(C1-C6 alkyl)-, (C1-C6 alkyl)carbonyl, arylcarbonyl, C1-C6 alkylsulfonyl, arylsulfonyl, aryl(C1-C6 alkyl)sulfonyl, heteroarylsulfonyl, heteroaryl(C1-C6 alkyl)sulfonyl, aryloxycarbonyl, and aryl(C1-C6 alkoxy)carbonyl, wherein said aryl groups are substituted with 0-2 substituents selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halo, CF3, and nitro; R16e is selected from: --C(═O)OR18ae,--C(═O)R18be,--C(═O)N(R18be)2,--SO2R18ae, and--SO2N(R18be)2; R17e is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, aryl, aryl(C1-C6 alkyl)-, and heteroaryl(C 1-C6 alkyl); R18ae is selected from: C1-C8 alkyl optionally substituted with a bond to Ln, C3-C11 cycloalkyl optionally substituted with a bond to Ln, aryl(C1-C6 alkyl)-optionally substituted with a bond to Ln, heteroaryl(C1-C6 alkyl)-optionally substituted with a bond to Ln, (C1-C6 alkyl)heteroaryl optionally substituted with a bond to Ln, biaryl(C1-C6 alkyl) optionally substituted with a bond to Ln, heteroaryl optionally substituted with a bond to Ln, phenyl substituted with 3-4 R19e and optionally substituted with a bond to L n, naphthyl substituted with 0-4 R19e and optionally substituted with a bond to Ln, and a bond to Ln, wherein said aryl or heteroaryl groups are optionally substituted with 0-4 R19e; R18be is H or R18ae; R19e is selected from: H, halogen, CF3, CO2H, CN, NO2,--NR11eR12e, OCF3, C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C 3-C11 cycloalkyl, C3-C7 cycloalkyl(C 1-C4 alkyl)-, aryl(C1-C6 alkyl)-, C 1-C6 alkoxy, C1-C4 alkoxycarbonyl, aryl, aryl-O--, aryl-SO2--, heteroaryl, and heteroaryl-SO2--, wherein said aryl and heteroaryl groups are substituted with 0-4 groups selected from hydrogen, halogen, CF3, C1-C3 alkyl, and C1-C3 alkoxy; R20e is selected from: hydroxy, C1-C10 alkyloxy, C3-C 11 cycloalkyloxy, aryloxy, aryl(C1-C4 alkyl)oxy, C2-C10 alkylcarbonyloxy(C1-C2 alkyl)oxy-, C2-C10 alkoxycarbonyloxy(C1-C2 alkyl)oxy-, C2-C10 alkoxycarbonyl(C1-C2 alkyl)oxy-, C3-C10 cycloalkylcarbonyloxy(C1-C2 alkyl)oxy-, C3-C10 cycloalkoxycarbonyloxy(C1-C2 alkyl)oxy-, C3-C10 cycloalkoxycarbonyl(C1-C 2 alkyl)oxy-, aryloxycarbonyl(C1-C2 alkyl)oxy-, aryloxycarbonyloxy(C1-C2 alkyl)oxy-, arylcarbonyloxy(C1-C2 alkyl)oxy-, C1-C5 alkoxy(C1-C5 alkyl) carbonyloxy(C1-C2 alkyl)oxy, (5-(C1-C5 alkyl)-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, and (R10e)(R11e)N--(C1-C10 alkoxy)-; R21e is selected from: C1-C8 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, (C3-C11 cycloalkyl)methyl, aryl, aryl(C1-C4 alkyl)-, and C1-C10 alkyl substituted with 0-2 R 7e; R22e is selected from: --C(═O)--R18be,--C(═O)N(R18be) 2,--C(═O)NHSO2R18ae, --C(═O)NHC(═O)R18be,--C(═O)NHC(═ O)OR18ae, and --C(═O)NHSO2NHR18be; me is 0-2; ne is 0-4; and pe is 0-2; with the following proviso: ne and me are chosen such that the number of atoms connecting R1 and--COR 20e in Formula (IV) is in the range of 8-14; W is independently selected at each occurrence from the group: O, S, NH, NHC(═O), C(═O)NH, NR8C(═O), C(═O)NR8, C(═O), C(═O)O, OC(═O), NHC(═S) NH, NHC(═O)NH, SO2, SO2NH, (OCH2CH 2)20-200, (CH2CH2O)20-200, (OCH2CH2CH2)20-200, (CH2 CH2CH2O)20-200, and (aa)t'; aa is independently at each occurrence an amino acid; Z is selected from the group: aryl substituted with 0-1 R 10, C3-10 cycloalkyl substituted with 0-1 R10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R 10; R6, R6a, R7, R7a, and R8 are independently selected at each occurrence from the group: H, ═O, COOH, SO3H, C1-C5 alkyl substituted with 0-1 R10, aryl substituted with 0-1 R10, benzyl substituted with 0-1 R10, and C1-C5 alkoxy substituted with 0-1 R10, NHC(═O)R11, C(═O)NHR11, NHC(═O)NHR11, NHR11, R11, and a bond to Sf; k is 0 or 1; Sf is a surfactant which is a lipid or a compound of the formula: A9 is OR27; A10 is OR27; R27 is C(═O)C1-15 alkyl; E1 is C1-4 alkylene substituted with 1-3 R28; R28 is independently selected at each occurrence from the group: R30,--PO3H--R30, ═O,--CO2R29,--C(═O)R29,--CH2OR 29,--OR29, and C1-C5 alkyl; R29 is independently selected at each occurrence from the group: R30, H, C1-C6 alkyl, phenyl, and benzyl; R30 is a bond to Ln; and a pharmaceutically acceptable salt thereof. 9. An ultrasound contrast agent composition, comprising: (a) a compound of claim 7, comprising: an quinolone that binds to the integrin αvβ3, a surfactant and a linking group between the quinolone and the surfactant; (b) a parenterally acceptable carrier; and, (c) an echogenic gas. 10. An ultrasound contrast agent composition of claim 9, further comprising: 1,2-dipalmitoyl-sn-glycero-3-phosphotidic acid, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine, and N-(methoxypolyethylene glycol 5000 carbamoyl)-1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine. 11. An ultrasound contrast agent composition of claim 10, wherein the echogenic gas is a C2-5 perfluorocarbon. 12. A method of imaging cancer in a patient comprising: (1) administering, by injection or infusion, a ultrasound contrast agent composition of claim 9 to a patient; and (2) imaging the patient using sonography. 13. A method of imaging formation of new blood vessels in a patient comprising: (1) administering, by injection or infusion, a ultrasound contrast agent composition of claim 9 to a patient; (2) imaging the area of the patient wherein the desired formation of new blood vessels is located. 14. A method of imaging therapeutic angiogenesis in a patient comprising: (1) administering, by injection or infusion, an ultrasound contrast agent composition of claim 9 to a patient; (2) imaging the area of the patient wherein the desired formation of new blood vessels is located. 15. A method of imaging atherosclerosis in a patient comprising: (1) administering, by injection or infusion, an ultrasound contrast agent composition of claim 9 to a patient; (2) imaging the area of the patient wherein the atherosclerosis is located. 16. A method of imaging restenosis in a patient comprising: (1) administering, by injection or infusion, an ultrasound contrast agent composition of claim 9 to a patient; (2) imaging the area of the patient wherein the restenosis is located. 17. A method of imaging cardiac ischemia in a patient comprising: (1) administering, by injection or infusion, an ultrasound contrast agent composition of claim 9 to a patient; (2) imaging the area of the myocardium wherein the ischemic region is located. 18. A method of imaging myocardial reperfusion injury in a patient comprising: (1) administering, by injection or infusion, an ultrasound contrast agent composition of claim 9 to a patient; (2) imaging the area of myocardium wherein the reperfusion injury is located. 19. A kit for treating cancer, comprising a compound comprising a targeting moiety and a chelator, wherein the targeting moiety is bound to the chelator, is a quinolone nonpeptide, and binds to a receptor that is upregulated during angiogenesis and the compound has 0-1 linking groups between the targeting moiety and chelator, wherein the receptor is the integrin αvβ3 or α vβ3 and the compound is of the formula: description="In-line Formulae" end="lead"(Q) d--Ln--Ch or (Q)d--Ln--(C h)d'description="In-line Formulae" end="tail" wherein, Q is a compound of Formula (II): including stereoisomeric forms thereof or mixtures of stereoisomeric forms thereof, or pharmaceutically acceptable salt or prodrug forms thereof wherein: R1e is selected from: Ae is--CH2--or--N(R10e)--; A1e and Be are independently--CH2--or--N(R10e)--; De is--N(R10e)--or--S--; Ee--Fe is--C(R2e)═C(R 3e)--or--C(R2e)2C(R3e)2--; Je is--C(R2e)--or--N--; Ke, Le and Me are independently--C(R2e)--or--C(R3e)--; R2e and R3e are independently selected from: H, C1-C4 alkoxy, NR11eR12e , halogen, NO2, CN, CF3, C1-C6 alkyl, C3-C6 alkenyl, C3-C7 cycloalkyl, C 3-C7 cycloalkyl(C1-C4 alkyl), aryl(C 1-C6 alkyl)-, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy)carbonyl, arylcarbonyl, and aryl substituted with 0-4 R7e, alternatively, when R2e and R3e are substituents on adjacent atoms, they can be taken together with the carbon atoms to which they are attached to form a 5-7 membered carbocyclic or 5-7 membered heterocyclic aromatic or nonaromatic ring system, said carbocyclic or heterocyclic ring being substituted with 0-2 groups selected from C1-C4 alkyl, C1-C4 alkoxy, halo, cyano, amino, CF3 and NO2; R2ae is selected from: H, C1-C10 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl), aryl, aryl(C1-C4 alkyl)-, (C2-C7 alkyl)carbonyl, arylcarbonyl, (C2-C10 alkoxy)carbonyl, C3-C7 cycloalkoxycarbonyl, C7-C11 bicycloalkoxycarbonyl, aryloxycarbonyl, aryl(C1-C10 alkoxy)carbonyl, C1-C6 alkylcarbonyloxy(C1-C4 alkoxy)carbonyl, arylcarbonyloxy(C1-C4 alkoxy) carbonyl, and C3-C7 cycloalkylcarbonyloxy(C1-C4 alkoxy)carbonyl; R7e is selected from: H, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, aryl, aryl(C1-C4 alkyl)-, (C1-C4 alkyl)carbonyl, CO2R18ae, SO2R 11e, SO2NR10eR11e, OR10e, and N(R11e)R12e; Ue is selected from: --(CH2)ne--,--(CH2) neO(CH2)me--,--(CH2) neN(R12)(CH2)me--,--NH(CH2)ne--,--(CH2)n eC(═O)(CH2)me--, --(CH2)neS(O)pe (CH2)me--,--(CH2)ne NHNH(CH2)me--, --N(R10e)C(═O)--,--NHC(═O)(CH2) ne--,--C(═O)N(R10e)--, and--N(R 10e)S(O)pe--; Ge is N or CR19e; We is--C(═O)--N(R10e)--(C1-C3 alkylene)-, in which the alkylene group is substituted by R8e and by R9e: R8e and R9e are independently selected from: H, CO2R18be, C(═O)R18be, CONR17R18be, C1-C10 alkyl substituted with 0-1 R 6e, C2-C10 alkenyl substituted with 0-1 R 6e, C2-C10 alkynyl substituted with 0-1 R 6e, C3-C8 cycloalkyl substituted with 0-1 R 6e, C5-C6 cycloalkenyl substituted with 0-1 R6e, (C1-C10 alkyl)carbonyl, C3-C10 cycloalkyl(C1-C4 alkyl)-, phenyl substituted with 0-3 R6e, naphthyl substituted with 0-3 R6e, a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R7e, C1-C10 alkoxy substituted with 0-2 R 7e, hydroxy, nitro,--N(R10e)R11e,--N(R 16e)R17e, aryl(C0-C6 alkyl)carbonyl, aryl(C3-C6 alkyl), heteroaryl(C1-C6 alkyl), CONR18aeR20e, SO2R18ae, and SO2NR18aeR20e, providing that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 1-2 R7e; R6e is selected from: H, C1-C10 alkyl, hydroxy, C1-C 10 alkoxy, nitro, C1-C10 alkylcarbonyl,--N(R 11e)R12e, cyano, halo, CF3, CHO, CO2R 18be, C(═O)R18be, CONR17eR18be, OC(═O)R10e, OR10e, OC(═O)NR10eR 11e, NR10eC(═O)R10e, NR10eC(═O) OR21e, NR10eC(═O)NR10eR11e, NR10eSO2NR10eR11e, NR10e SO2R21e, S(O)pR11e, SO2NR 10eR11e, aryl substituted with 0-3 groups selected from halogen, C 1-C6 alkoxy, C1-C6 alkyl, CF3, S(O)meMe, and--NMe2, aryl(C1-C4 alkyl)-, said aryl being substituted with 0-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, S(O)p eMe, and--NMe2, and a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R7e; R10e is selected from: H, CF3, C3-C6 alkenyl, C3-C11 cycloalkyl, aryl, (C3-C11 cycloalkyl) methyl, aryl(C1-C4 alkyl), and C1-C10 alkyl substituted with 0-2 R6e; R11e is selected from: H, hydroxy, C1-C8 alkyl, C3-C6 alkenyl, C3-C11 cycloalkyl, (C3-C11 cycloalkyl)methyl, C1-C6 alkoxy, benzyloxy, aryl, heteroaryl, heteroaryl(C1-C4 alkyl)-, aryl(C1-C4 alkyl), adamantylmethyl, and C1-C10 alkyl substituted with 0-2 R 4e; R4e is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, (C1-C10 alkyl)carbonyl, aryl, heteroaryl, aryl(C1-C6 alkyl)-, and heteroaryl(C1-C6 alkyl)-, wherein said aryl or heteroaryl groups are substituted with 0-2 substituents independently selected from the group consisting of C 1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2, alternatively, when R10e and R11e are both substituents on the same nitrogen atom (as in--NR10eR 11e) they may be taken together with the nitrogen atom to which they are attached to form a heterocycle selected from: 3-azabicyclononyl, 1,2, 3,4-tetrahydro-1-quinolinyl, 1,2,3,4-tetrahydro-2-isoquinolinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl, and 1-piperazinyl; said heterocycle being substituted with 0-3 groups selected from: C1-C6 alkyl, aryl, heteroaryl, aryl(C1-C4 alkyl)-, (C1-C6 alkyl)carbonyl, (C3-C7 cycloalkyl)carbonyl, (C1-C6 alkoxy) carbonyl, aryl(C1-C4 alkoxy)carbonyl, C1-C 6 alkylsulfonyl, and arylsulfonyl; R12e is selected from: H, C1-C6 alkyl, triphenylmethyl, methoxymethyl, methoxyphenyldiphenylmethyl, trimethylsilylethoxymethyl, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy) carbonyl, (C1-C6 alkyl)aminocarbonyl, C3-C 6 alkenyl, C3-C7 cycloalkyl, C3 -C7 cycloalkyl(C1-C4 alkyl)-, aryl, heteroaryl(C 1-C6 alkyl)carbonyl, heteroarylcarbonyl, aryl(C1-C6 alkyl)-, (C1-C6 alkyl)carbonyl, arylcarbonyl, C1-C6 alkylsulfonyl, arylsulfonyl, aryl(C1-C6 alkyl)sulfonyl, heteroarylsulfonyl, heteroaryl(C1-C6 alkyl)sulfonyl, aryloxycarbonyl, and aryl(C1-C6 alkoxy)carbonyl, wherein said aryl groups are substituted with 0-2 substituents selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halo, CF3, and nitro; R16e is selected from: --C(═O)OR18ae,--C(═O)R18be,--C(═O)N(R18be)2, --C(═O)NHSO2R18ae,--C(═O) NHC(═O)R18be, --C(═O)NHC(═O)OR18ae,--C(═O)NHSO 2NHR18be,--SO2R18ae, --SO2N(R18be)2, and--SO2 NHC(═O)OR18be; R17e is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, aryl, aryl(C1-C6 alkyl)-, and heteroaryl(C 1-C6 alkyl); R18ae is selected from: C1-C8 alkyl optionally substituted with a bond to Ln, C3-C11 cycloalkyl optionally substituted with a bond to Ln, aryl(C1-C6 alkyl)-optionally substituted with a bond to Ln, heteroaryl(C1-C6 alkyl)-optionally substituted with a bond to Ln, (C1-C6 alkyl)heteroaryl optionally substituted with a bond to Ln, biaryl(C1-C6 alkyl) optionally substituted with a bond to Ln, heteroaryl optionally substituted with a bond to Ln, phenyl substituted with 3-4 R19e and optionally substituted with a bond to L n, naphthyl substituted with 0-4 R19e and optionally substituted with a bond to Ln, and a bond to Ln, wherein said aryl or heteroaryl groups are optionally substituted with 0-4 R19e; R18be is H or R18ae; R19e is selected from: H, halogen, CF3, CO2H, CN, NO2,--NR11eR12e, OCF3, C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C 3-C11 cycloalkyl, C3-C7 cycloalkyl(C 1-C4 alkyl)-, aryl(C1-C6 alkyl)-, C 1-C6 alkoxy, C1-C4 alkoxycarbonyl, aryl, aryl-O--, aryl-SO2--, heteroaryl, and heteroaryl-SO2--, wherein said aryl and heteroaryl groups are substituted with 0-4 groups selected from hydrogen, halogen, CF3, C1-C3 alkyl, and C1-C3 alkoxy; R20e is selected from: hydroxy, C1-C10 alkyloxy, C3-C 11 cycloalkyloxy, aryloxy, aryl(C1-C4 alkyl)oxy, C2-C10 alkylcarbonyloxy(C1-C2 alkyl)oxy-, C2-C10 alkoxycarbonyloxy(C1-C2 alkyl)oxy-, C2-C10 alkoxycarbonyl(C1-C2 alkyl)oxy-, C3-C10 cycloalkylcarbonyloxy(C1-C2 alkyl)oxy-, C3-C10 cycloalkoxycarbonyloxy(C1-C2 alkyl)oxy-, C3-C10 cycloalkoxycarbonyl(C1-C 2 alkyl)oxy-, aryloxycarbonyl(C1-C2 alkyl)oxy-, aryloxycarbonyloxy(C1-C2 alkyl)oxy-, arylcarbonyloxy(C1-C2 alkyl)oxy-, C1-C5 alkoxy(C1-C5 alkyl) carbonyloxy(C1-C2 alkyl)oxy, (5-(C1-C5 alkyl)-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, and (R10e)(R11e)N--(C1-C10 alkoxy)-; R21e is selected from: C1-C8 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, (C3-C11 cycloalkyl)methyl, aryl, aryl(C1-C4 alkyl)-, and C 1-C10 alkyl substituted with 0-2 R7e; R22e is selected from: --C(═O)--R18be,--C(═O)N(R18be) 2,--C(═O)NHSO2R18ae,--C(═O) NHC(═O)R18be,--C(═O)NHC(═O)OR18ae, and--C(═O)NHSO2NHR18be; Ye is selected from: --COR20e,--SO3H,--PO3H,--CONHNHSO2CF3,--CONHSO2R18ae,--CONHSO2NHR18be,--NHCOCF3,--NHCONHSO2 R18ae,--NHSO2R18ae,--OPO3H2 ,--OSO3H,--PO3H2,--SO2NHCOR 18ae, --SO2NHCO2R18ae, me is 0-2; ne is 0-4; pe is 0-2; re is 0-2; with the following proviso: ne and me are chosen such that the number of atoms connecting R1e and Ye is in the range of 8-14; d is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; d' is 1-100; Ln is a linking group having the formula: description="In-line Formulae" end="lead"((W) h--(CR6R7)g)x--(Z)k--((CR6aR7a)g'--(W)h')x';description="In-line Formulae" end="tail" W is independently selected at each occurrence from the group: O, S, NH, NHC(═O), C(═O)NH, NR8C(═O), C(═O)NR8, C(═O), C(═O)O, OC(═O), NHC(═S) NH, NHC(═O)NH, SO2, SO2NH, (OCH2CH 2)s, (CH2CH2O)s', (OCH2 CH2CH2)s", (CH2CH2CH 2O)t, and (aa)t'; aa is independently at each occurrence an amino acid; Z is selected from the group: aryl substituted with 0-3 R 10, C3-10 cycloalkyl substituted with 0-3 R10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R 10; R6, R6a, R7, R7a, and R8 are independently selected at each occurrence from the group: H, ═O, COOH, SO3H, PO3H, C1-C5 alkyl substituted with 0-3 R10, aryl substituted with 0-3 R 10, benzyl substituted with 0-3 R10, and C1-C5 alkoxy substituted with 0-3 R10, NHC(═O)R11, C(═O)NHR11, NHC(═O)NHR11, NHR11, R11, and a bond to Ch; R10 is independently selected at each occurrence from the group: a bond to Ch, COOR11, C(═O)NHR 11, NHC(═O)R11, OH, NHR11, SO3H, PO3H,--OPO3H2,--OSO3H, aryl substituted with 0-3 R11, C1-5 alkyl substituted with 0-1 R12, C1-5 alkoxy substituted with 0-1 R12, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R 11; R11 is independently selected at each occurrence from the group: H, alkyl substituted with 0-1 R12, aryl substituted with 0-1 R12, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R12, C3-10 cycloalkyl substituted with 0-1 R12, polyalkylene glycol substituted with 0-1 R12, carbohydrate substituted with 0-1 R12, cyclodextrin substituted with 0-1 R12, amino acid substituted with 0-1 R12, polycarboxyalkyl substituted with 0-1 R12, polyazaalkyl substituted with 0-1 R12, peptide substituted with 0-1 R12, wherein the peptide is comprised of 2-10 amino acids, 3, 6-O-disulfo-B-D-galactopyranosyl, bis(phosphonomethyl)glycine, and a bond to Ch; R12 is a bond to Ch; k is selected from 0, 1, and 2; h is selected from 0, 1, and 2; h' is selected from 0, 1, and 2; g is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; g' is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; s is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; s' is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; s" is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; t is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; t' is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; x is selected from 0, 1, 2, 3, 4, and 5; x' is selected from 0, 1, 2, 3, 4, and 5; Ch is a metal bonding unit having a formula selected from the group: A1, A2, A3, A4, A 5, A6, A7, and A8 are independently selected at each occurrence from the group: NR13, NR13 R14, S, SH, S(Pg), O, OH, PR13, PR13R 14, P(O)R15R16, and a bond to Ln; E is a bond, CH, or a spacer group independently selected at each occurrence from the group: C1-C10 alkyl substituted with 0-3 R17, aryl substituted with 0-3 R17, C3-10 cycloalkyl substituted with 0-3 R17, heterocyclo-C1-10 alkyl substituted with 0-3 R17, wherein the heterocyclo group is a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O, C6-10 aryl-C1-10 alkyl substituted with 0-3 R17, C1-10 alkyl-C6-10 aryl-substituted with 0-3 R17, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R 17; R13 and R14 are each independently selected from the group: a bond to Ln, hydrogen, C1-C10 alkyl substituted with 0-3 R17, aryl substituted with 0-3 R 17, C1-10 cycloalkyl substituted with 0-3 R17, heterocyclo-C1-10 alkyl substituted with 0-3 R17, wherein the heterocyclo group is a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O, C 6-10 aryl-C1-10 alkyl substituted with 0-3 R17, C1-10 alkyl-C6-10 aryl-substituted with 0-3 R17 , a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R 17, and an electron, provided that when one of R13 or R 14 is an electron, then the other is also an electron; alternatively, R13 and R14 combine to form ═C(R20)(R21); R15 and R16 are each independently selected from the group: a bond to Ln,--OH, C1-C10 alkyl substituted with 0-3 R17, C1-C10 alkyl substituted with 0-3 R17, aryl substituted with 0-3 R17, C3-10 cycloalkyl substituted with 0-3 R17, heterocyclo-C1-10 alkyl substituted with 0-3 R17, wherein the heterocyclo group is a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O , C6-10 aryl-C1-10 alkyl substituted with 0-3 R17, C1-10 alkyl-C6-10 aryl-substituted with 0-3 R17, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R 17; R17 is independently selected at each occurrence from the group: a bond to Ln, ═O, F, Cl, Br, I,--CF 3,--CN,--CO2R18,--C(═O)R18,--C(═O)N(R18)2,--CHO,--CH2OR18,--OC(═O)R18,--OC(═O)OR18a,--OR18,--OC(═O)N(R18)2,--NR19C(═O)R 18,--NR19C(═O)OR18a,--NR19C(═ O)N(R18)2,--NR19SO2N(R18) 2,--NR19SO2R18a,--SO3H,--SO2R18a,--SR18,--S(═O)R18a,--SO2N(R18)2,--N(R18)2,--NHC(═S)NHR18, ═NOR18, NO2,--C(═ O)NHOR18,--C(O)NHNR18R18a,--OCH2 CO2H, 2-(1-morpholino)ethoxy, C1-C5 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl, C 3-C6 cycloalkylmethyl, C2-C6 alkoxyalkyl, aryl substituted with 0-2 R18, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O; R18, R18a, and R19 are independently selected at each occurrence from the group: a bond to L n, H, C1-C6 alkyl, phenyl, benzyl, C1-C6 alkoxy, halide, nitro, cyano, and trifluoromethyl; Pg is a thiol protecting group; R20 and R21 are independently selected from the group: H, C1-C10 alkyl,--CN,--CO2R 25,--C(═O)R25,--C(═O)N(R25)2, C2-C10 1-alkene substituted with 0-3 R23, C 2-C10 1-alkyne substituted with 0-3 R23, aryl substituted with 0-3 R23, unsaturated 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R23, and unsaturated C3-10 carbocycle substituted with 0-3 R23; alternatively, R20 and R21, taken together with the divalent carbon radical to which they are attached form: R22 and R23 are independently selected from the group: H, R24, C1-C10 alkyl substituted with 0-3 R24, C2-C10 alkenyl substituted with 0-3 R24, C2-C10 alkynyl substituted with 0-3 R24, aryl substituted with 0-3 R24, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R24, and C 3-10 carbocycle substituted with 0-3 R24; alternatively, R22, R23 taken together form a fused aromatic or a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O; a and b indicate the positions of optional double bonds and n is 0 or 1; R24 is independently selected at each occurrence from the group: ═O, F, Cl, Br, I,--CF3,--CN,--CO 2R25,--C(═O)R25,--C(═O)N(R25) 2,--N(R25)3+,--CH2OR 25,--OC(═O)R25,--OC(═O)OR25a,--OR 25,--OC(═O)N(R25)2,--NR26C(═O) R25,--NR26C(═O)OR25a,--NR26 C(═O)N(R25)2,--NR26SO2N(R 25)2,--NR26SO2R25a,--SO 3H,--SO2R25a,--SR25,--S(═O)R 25a,--SO2N(R25)2,--N(R25) 2, ═NOR25,--C(═O)NHOR25,--OCH2 CO2H, and 2-(1-morpholino)ethoxy; and, R25, R25a, and R26 are each independently selected at each occurrence from the group: hydrogen and C1-C6 alkyl, or a pharmaceutically acceptable salt thereof, and at least one agent selected from the group consisting of a chemotherapeutic agent and a radiosensitizer agent, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 20. A kit according to claim 19 wherein said kit comprises a plurality of separate containers, wherein at least one of said containers contains a compound of claim 2, or a pharmaceutically acceptable salt thereof, and at least another of said containers contains one or more agents selected from the group consisting of a chemotherapeutic agent and a radiosensitizer agent, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 21. A kit according to claim 19, wherein the chemotherapeutic agent is selected from the group consisting of mitomycin, tretinoin, ribomustin, gemcitabine, vincristine, etoposide, cladribine, mitobronitol, methotrexate, doxorubicin, carboquone, pentostatin, nitracrine, zinostatin, cetrorelix, letrozole, raltitrexed, daunorubicin, fadrozole, fotemustine, thymalfasin, sobuzoxane, nedaplatin, cytarabine, bicalutamide, vinorelbine, vesnarinone, aminoglutethimide, amsacrine, proglumide, elliptinium acetate, ketanserin, doxifluridine, etretinate, isotretinoin, streptozocin, nimustine, vindesine, flutamide, drogenil, butocin, carmofur, razoxane, sizofilan, carboplatin, mitolactol, tegafur, ifosfamide, prednimustine, picibanil, levamisole, teniposide, improsulfan, enocitabine, lisuride, oxymetholone, tamoxifen, progesterone, mepitiostane, epitiostanol, formestane, interferon-alpha, interferon-2 alpha, interferon-beta, interferon-gamma, colony stimulating factor-1, colony stimulating factor-2, denileukin diftitox, interleukin-2, and leutinizing hormone releasing factor. 22. A kit according to claim 19, wherein the chemotherapeutic agent is selected from the group consisting of mitomycin, tretinoin, ribomustin, gemcitabine, vincristine, etoposide, cladribine, mitobronitol, methotrexate, doxorubicin, carboquone, pentostatin, nitracrine, zinostatin, cetrorelix, letrozole, raltitrexed, daunorubicin, fadrozole, fotemustine, thymalfasin, sobuzoxane, nedaplatin, cytarabine, bicalutamide, vinorelbine, vesnarinone, aminoglutethimide, amsacrine, proglumide, elliptinium acetate, ketanserin, doxifluridine, etretinate, isotretinoin, streptozocin, nimustine, vindesine, flutamide, drogenil, butocin, carmofur, razoxane, sizofilan, carboplatin, mitolactol, tegafur, ifosfamide, prednimustine, picibanil, levamisole, teniposide, improsulfan, enocitabine, and lisuride. 23. A kit according to claim 19 wherein the chemotherapeutic agent is selected from the group consisting of oxymetholone, tamoxifen, progesterone, mepitiostane, epitiostanol, and formestane. 24. A kit according to claim 19 wherein the chemotherapeutic agent is selected from the group consisting of interferon-alpha, interferon-2 alpha, interferon-beta, interferon-gamma, colony stimulating factor-1, colony stimulating factor-2, denileukin diftitox, interleukin-2, and leutinizing hormone releasing factor. 25. A kit according to claim 19, wherein radiosensitizer agent is selected from the group consisting of 2-(3-nitro-1,2,4-triazol-1-yl)-N-(2-methoxyethyl)acetamide, N-(3-nitro-4-quinolinyl)-4-morpholinecarboxamidine, 3-amino-1,2,4-benzotriazine-1,4-dioxide, N-(2-hydroxyethyl)-2-nitroimidazole-1-acetamide, 1-(2-nitroimidazol-1-yl)-3-(1-piperidinyl)-2-propanol, and 1-(2-nitro-1-imidazolyl)-3-(1-aziridino)-2-propanol. 26. A process for the preparation of diagnostic or therapeutic metallopharmaceutical composition, said process comprising generating a macrostructure from a plurality of molecular components wherein the plurality of components includes a targeting moiety and a chelator, wherein the targeting moiety is a quinolone nonpeptide, which is bound to the chelator, and binds to a receptor that is upregulated during angiogenesis and the compound has 0-1 linking groups between the targeting moiety and chelator.
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