Patent ID: 6524553
Filing Date: 2003-02-25
Classification: A61K,C07D,C07K

Abstract:
A compound comprising:a) a targeting moiety; and b) a surfactant; â€ƒwherein the targeting moiety is bound to the surfactant by 0-1 linking groups; and wherein the targeting moiety is a nonpeptide which binds to a receptor that is upregulated during angiogenesis and the targeting moiety is a compound of Formula (I): â€ƒwherein: R1e is selected from: De is selected from: â€”N(R12e)â€”, or â€”Sâ€”; Je is selected from: â€”C(R2e)â€” or â€”Nâ€”; Ke, Le and Me are independently selected from: â€”C(R2e)â€” or â€”C(R3e)â€”; 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, C4-C11 cycloalkylalkyl, C6-C10 aryl substituted with 0-4 R7e, C7-C11 arylalkyl, C2-C7 alkylcarbonyl, C1-C4 alkoxycarbonyl, or C7-C11 arylcarbonyl; 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 optionally substituted with 0-2 groups selected from C1-C4 alkyl, C1-C4 alkoxy, halo, cyano, amino, CF3 or NO2; Ue is selected from: â€”(CH2)neâ€”, â€”(CH2)neO(CH2)meâ€”, â€”(CH2)neN(R12e)(CH2)meâ€”, â€”(CH2)neC(&boxH;O)(CH2)meâ€”, â€”(CH2)neS(O)pe(CH2)meâ€”, â€”(CH2)neNHNH(CH2)meâ€”, â€”N(R10e)C(&boxH;O)â€”, â€”C(&boxH;O)N(R10e)â€”, or â€”N(R10e)S(O)peâ€”; We is â€”C(&boxH;O)â€”N(R10e)â€”(C1-C3 alkylene)-, in which the alkylene group is optionally substituted by: CO2R18ae, C(&boxH;O)R18ae, CONR17eR18ae, C1-C10 alkyl, substituted with 0-1 R6e, C5-C10 alkenyl, substituted with 0-1 R6e C5-C10 alkynyl, substituted with 0-1 R6e, C3-C8 cycloalkyl, substituted with 0-1 R6e, C5-C6 cycloalkenyl, substituted with 0-1 R6e, C1-C10 alkylcarbonyl, C3-C10 cycloalkylalkyl, phenyl substituted with 1-3 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 is saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R7e, hydroxy, C5-C10 alkoxy, nitro, N(R10e)R11e, â€”N(R16e)R17e, C5-C10 alkyl substituted with 0-3 R7e, aryl(C0-C6 alkyl)carbonyl, aryl(C3-C6 alkyl), heteroaryl(C1-C6 alkyl), CONR18aeR20e, SO2R18ae, or SO2NR18aeR20e and providing that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups is unsubstituted or substituted independently with 1-2 R7e; R6e is selected from: H, C1-C10 alkyl, hydroxy, C1-C10 alkoxy, nitro, C1-C10 alkylcarbonyl, â€”N(R11e)R12e, cyano, halo, CF3, CHO, CO2R18be, C(&boxH;O)R18be, CONR17eR18be, OC(&boxH;O)R10e, OR10e, OC(&boxH;O)NR10eR11e, NR10eC(&boxH;O)R10e, NR10eC(&boxH;O)OR21e, NR10eC(&boxH;O)NR10eR11e, NR10eSO2NR10eR11e, NR10eSO2R21e, S(O)peR11e, SO2NR10eR11e, C6-C10 aryl substituted with 0-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, S(O)meMe, or â€”NMe2; C7-C11 arylalkyl, said aryl being optionally substituted with 1-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, S(O)peMe, or â€”NMe2, or a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring is saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R7e; R7e is selected from: H, C1-C4 alkyl, hydroxy, C1-C4 alkoxy, C6-C10 aryl, C7-C11 arylalkyl, (C1-4 alkyl)carbonyl, CO2R18ae, SO2R11e, SO2NR10eR11e, OR10e, or N(R11e)R12e; Ye is selected from: â€”COR20e, â€”SO3H, â€”PO3H, â€”CONHNHSO2CF3, â€”CONHSO2R18ae, â€”CONHSO2NHR18be, â€”NHCOCF3, â€”NHCONHSO2R18ae, â€”NHSO2R18ae, â€”OPO3H2, â€”OSO3H, â€”PO3H2, â€”SO3H, â€”SO2NHCOR18ae, â€”SO2NHCO2R18ae, or R10e is selected from: H, C3-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylmethyl, aryl, aryl(C1-C4 alkyl), or C1-C10 alkyl substituted with 0-2 R4e; R11e is selected from: H, hydroxy, C1-C8 alkyl, C3-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylmethyl, C1-C6 alkoxy, benzyloxy, C6-C10 aryl, heteroaryl, heteroarylalkyl, aryl(C1-4 alkyl), adamantylmethyl, or C1-C10 alkyl substituted with 0-2 R4e; alternatively, when R10e and R11e are both substituents on the same nitrogen atom they are 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 or 1-piperazinyl; said heterocycle being optionally substituted with 0-3 groups selected from: C1-C6 alkyl, C6-C10 aryl, heteroaryl, C7-C11 arylalkyl, C1-C6 alkylcarbonyl, C3-C7 cycloalkylcarbonyl, C1-C6 alkoxycarbonyl, C7-C11 arylalkoxycarbonyl, C1-C6 alkylsulfonyl or C6-C10 arylsulfonyl; R4e is selected from: H, C1-C10 alkyl, C1-C10 alkylcarbonyl, aryl, arylalkyl, cycloalkyl, or cycloalkylalkyl; R12e is selected from: H, C1-C6 alkyl, triphenylmethyl, methoxymethyl (MOM), methoxyphenyldiphenylmethyl, trimethylsilylethoxymethyl (SEM), (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy)carbonyl; (C1-C6 alkyl)aminocarbonyl, C3-C6 alkenyl, C3-C7 cycloalkyl, C4-C11 cycloalkylalkyl, aryl, heteroaryl(C1-C6 alkyl)carbonyl, heteroarylcarbonyl, aryl C1-C6 alkyl, (C1-C6 alkyl)carbonyl, or arylcarbonyl, C1-C6 alkylsulfonyl, arylsulfonyl, aryl(C1-C6 alkyl)sulfonyl, heteroarylsulfonyl, heteroaryl(C1-C6 alkyl)sulfonyl, aryloxycarbonyl, or aryl(C1-6 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; R14e is selected from: H, C1-C4 alkyl, phenyl(C1-C4 alkyl), or a bond to the linking group; R16e is selected from: â€”C(&boxH;O)OR18ae, â€”C(&boxH;O)R18be, â€”C(&boxH;O)N(R18be)2, â€”C(&boxH;O)NHSO2R18ae, â€”C(&boxH;O)NHC(&boxH;O)R18be, â€”C(&boxH;O)NHC(&boxH;O)OR18ae, â€”C(&boxH;O)NHSO2NHR18be, â€”SO2R18ae, â€”SO2N(R18be)2 or, â€”SO2NHC(&boxH;O)OR18be; R17e is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C4-C11 cycloalkylalkyl, aryl, aryl(C1-C6 alkyl)-, or heteroaryl(C1-6 alkyl); R18ae is selected from: C1-C8 alkyl optionally substituted with a bond to the linking group, C3-C11 cycloalkyl optionally substituted with a bond to the linking group, aryl(C1-C6 alkyl)- optionally substituted with a bond to the linking group, heteroaryl(C1-C6 alkyl)- optionally substituted with a bond to the linking group, (C1-C6 alkyl)heteroaryl optionally substituted with a bond to the linking group, biaryl(C1-C6 alkyl) optionally substituted with a bond to the linking group, heteroaryl optionally substituted with a bond to the linking group, phenyl substituted with 3-4 R19e and optionally substituted with a bond to the linking group, naphthyl substituted with 0-4 R19e and optionally substituted with a bond to the linking group, and a bond to the linking group, wherein said aryl or heteroaryl groups are optionally substituted with 0-4 R19e; R18be is selected from: R18ae or H; R19e is selected from: H, halogen, CF3, CO2H, CN, NO2, NR11eR12e, C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C11 cycloalkyl, C4-C11 cycloalkylalkyl, aryl(C1-6 alkyl)-, C1-C6 alkoxy, OCF3, or C1-4 alkoxycarbonyl, aryl, â€”Oâ€”aryl, â€”SO2â€”aryl, heteroaryl, or â€”SO2-heteroaryl, wherein said aryl and heteroaryl groups are each substituted with 0-4 groups selected from hydrogen, halogen, CF3, C1-C3 alkyl, or C1-C3 alkoxy; R20e is selected from: hydroxy, C1-C10 alkyloxy, C3-C11 cycloalkyloxy, C6-C10 aryloxy, C7-C11 aralkyloxy, C3-C10 alkylcarbonyloxyalkyloxy, C3-C10 alkoxycarbonyloxyalkyloxy, C2-C10 alkoxycarbonylalkyloxy, C5-C10 cycloalkylcarbonyloxyalkyloxy, C5-C10 cycloalkoxycarbonyloxyalkyloxy, C5-C10 cycloalkoxycarbonylalkyloxy, C7-C11 aryloxycarbonylalkyloxy, C8-C12 aryloxycarbonyloxyalkyloxy, C8-C12 arylcarbonyloxyalkyloxy, C5-C10 alkoxyalkylcarbonyloxyalkyloxy, C5-C10 (5-alkyl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, C10-C14 (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, or (R11e)(R12e)Nâ€”(C1-C10 alkoxy)-; R21e is selected from: C1-C8 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylmethyl, C6-C10 aryl, C7-C11 arylalkyl, or C1-C10 alkyl substituted with 0-2 R7e; me is 0-2; ne is 0-4; pe is 0-2; with the following provisos: (1) ne and me are selected such that the number of atoms connecting R1e and Ye is in the range of 8-14; (2) in the definition of We, the substituent on the alkylene group is not an unsubstituted pyridyl radical.