Patent ID: 6342201
Filing Date: 2002-01-29
Classification: A61K,C07K

Abstract:
A compound of formula I(K)z-(L)y-(A1)aa-(A2)bb-(A3)cc-(A4)dd-(A5)ee-(A6)ff-(A7)gg-(A8)hh-(A9)jj-(A10)kk-(A11)ll-Ile-Ile-Trpâ€ƒâ€ƒ(I) in which aa, bb, cc, dd, ee, ff, gg, hh, jj, kk and ll are each, independent from one another, 0, 1 or 2, y and z are each, independent from one another, 0 or 1, K is a chelate-forming residual having the formula IIA or IIB in which T is a hydrogen atom or a bond at a metal atom or a sulfur protective group or wherein two T residuals form together with the attached S atoms inter- or intramolecular disulfide bridges, wherein R4 is of the formula IIC or IID wherein the *-marked carbon atoms are bound to the amino groups of the formula IIB, nâ€² is 1 or 2, i is from 2 to 6, and TT is an &agr;-amino acid group bonded by its amino group to form an amide group, or is: a chelate-forming residual having the formula IIE in which R6 represents a hydrogen or a C1-6-alkyl group, or K is chelate-forming residual having the formula IIF in which R7 to R18 each are independent from one another a hydrogen atom, a C1-10-alkyl chain or a bond on L; o; p and r each are 1 or 2; and T has the above meaning, or K is a chelate-forming residual having the formula IIG in which R19 to R24 are the same or different and are each, independent from one another, a hydrogen atom or a C1-4-alkyl group, and mâ€² is 2 or 3, or K is a chelate-forming residual having the formula IIH in which X1 is a bond, a methylene group or a CHY4-group, and one of the groups Y1, Y2, Y3 or Y4 is a bond to L and the remaining groups are independently a hydrogen or oxygen atom, T has the above given meaning, and A1, A2, A3 and A4 are equal or different and are each, independent from one another, hydrogen or a C1-6-alkyl group, or K is a chelate-forming residual having the formula IIJ in which R27 is a hydrogen atom or a C1-6-alkyl group substituted with one or two hydroxyl groups, R25 and R26 are each a hydrogen atom or together a carbonyl oxygen atom, A is a hydroxyl- or mercapto group, Y is a hydrogen atom, or a carboxy- or sulfonyl group and Z is a carbon atom or a nitrogen atom, or K is a chelate-forming residual having the formula IIK, (AA1)mm-(AA2)nn-(AA3)oo-(AA4)pp-(AA5)qq-(AA6)rrâ€ƒâ€ƒ(IIK) in which mm, nn, oo, pp, qq and rr are each, independent from one another, 0, 1 or 2, AA1 to AA6 are each, independent from one another, an &agr;-amino acid group bonded by its amino group to form an amide with the adjoining &agr;-amino acid, wherein optionally two available cysteine &agr;-amino acid groups are linked to one another to form one cysteine &agr;-amino acid group, or K is a chelating group having the formula IIL, in which Ra, Rb, Rc, Rd, Rf, Rg and Rh are the same or different and each is a hydrogen atom or a branched or non-branched C1-6-alkyl group, Re is a carboxy group or a non-branched, branched, cyclic or polycyclic C1-C60-alkyl-, alkenyl-, polyalkenyl-, alkinyl-, polyalkinyl-, aryl-, alkylaryl- or arylalkyl group, which is optionally substituted with hydroxy-, oxy-, oxo-, carboxy-, amninocarbonyl-, alkoxycarbonyl-, amino-, aldehyde- or alkoxy groups having up to 20 carbon atoms and/or optionally interrupted by one or more optionally substituted heteroatoms from O, N, S, P, As, and Se, T has the above meaning, L is a bond or a hydrogen atom or a non-branched, branched, cyclic or polycyclic C1-C60-alkyl, alkenyl-, polyalkenyl-, alkinyl-, polyalkenyl, aryl-, alkylaryl- or arylalkyl group, which is optionally substituted with one or more hydroxy-, mercapto-, alkylmercapto-, oxo-, oxy-, carboxy-, aminocarbonyl-, alkoxycarbonyl-, amino-, aldehyde- or alkoxy groups having up to 20 carbon atoms and/or optionally interrupted by one or more optionally substituted heteroatoms from O, N, S, P, As, Se, or L is a Z1â€”Râ€”Z2 group, in which R is a straight chain, branched, saturated or unsaturated C1-20 alkyl group which is optionally interrupted by one or more oxygen and/or sulfur atoms and/or carbonyl-, â€”NHCOâ€”, â€”N(C1-6-alkyl)COâ€”, â€”NHâ€” and â€”N(C1-6-alkyl)-groups and optionally substituted with hydroxy and/or epoxy groups, Z1 and Z2, independent from one another, each are an â€”Oâ€”, â€”Sâ€”, â€”(C&boxH;O)Oâ€”, â€”NH(C&boxH;S)NHâ€”, â€”(C&boxH;O)â€” or â€”NH(C&boxH;S)â€” group or a group having the formula &agr; in which s and t are each, independent from one another, 0, 1, 2 or 3, the ring B is a phenyl- or cyclohexyl residual and Z1 and Z2 have the above given meaning, A1 to A11 are each, independent from one another, a L-&agr;- or D-&agr;-amino acid group, â€”NHâ€”CH(Z)â€”COâ€” group, in which Z is Hâ€”, CH3â€”, (CH3)2CHâ€”, (CH3)2CHâ€”CH2â€”, CH3â€”CH2â€”CH(CH3)â€”, CH3â€”Sâ€”(CH2)2â€”, HOOCâ€”CH2â€”, HOOCâ€”(CH2)2â€”, H2Nâ€”(CH2)3â€”, H2Nâ€”C(&boxH;NH)â€”(CH2)3â€”, HOâ€”CH2â€”, CH3â€”CH(OH)â€”, HSâ€”CH2â€”, HSâ€”CH2â€”, HSâ€”(CH2)2â€”, H2Nâ€”COâ€”CH2â€”, H2Nâ€”COâ€”(CH2)2â€”, (HOOC)2CHâ€”CH2â€”, in which n is 0, 1 or 2, or Z is group or a taurine group, as well as complexes of these compounds with metal ions having atomic numbers 21-32, 37-39, 49-51 or 57-83 and their water-soluble salts.