US 2006/0234923 A1 · Template-fixed peptidomimetics as medicaments against hiv and cancer

Abstract

Template-fixed β-hairpin peptidomimetics of the General Formula (I); wherein Z1 and Z2 are template-fixed chains of 4 and 6 or 5 and 7 α-amino acid residues which, depending on their positions in the chain are Gly, or Pro, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to prevent or to reduce HIV infections or to inhibit the growth of cancer cells or to inhibit inflammation. They can be used as medicaments to treat or prevent HIV infections and/or cancer or inflammatory disorders. These β-sheet peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Claims32

Dependent claims

1-39. (canceled)

Compounds of the general formula

is a group of one of the formulae
is a group of one of the formulae
-B-CO- is Asn;
Cys;
Gln;
His;
Met;
Phe;
Pro;
Ser;
Thr;
Trp;
Tyr;
Sar;
4AmPhe;
3AmPhe;
2AmPhe;
Phe(mC(NH2)═NH;
Phe(pC(NH2)═NH;
Phe(mNHC(NH2)═NH;
Phe(pNHC (NH2)═NH;
Phg;
Cha;
C4al;
C5al;
2-NaI;
1-NaI;
4Cl-Phe;
3Cl-Phe;
2Cl-Phe;
3,4Cl2Phe;
4F-Phe;
3F-Phe;
2F-Phe;
Tic;
Thi;
Tza;
Mso;
Y(Bzl);
Bip;
S(Bzl);
T(Bzl);
hCha;
hcys;
hSer;
hPhe;
Bpa;
Pip;
OctG;
MePhe;
MeNle;
MeAla;
MeIle;
MeVal;
or MeLeu;
or B is a group, having (L)-configuration, of formula
wherein R20 is H;
or lower alkyl;
and R64 is alkyl;
alkenyl;
aryl;
aryl-lower alkyl;
or heteroaryl-lower alkyl;
R1 is hydrogen or lower alkyl;
R2 is H;
lower alkyl;
lower alkenyl;
—(CH2)mOR55 (where R55 is lower alkyl;
or lower alkenyl);
—CH2)mSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)mNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mOCONR33R75 (where R33 is H;
lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64(where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
—(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R3 is H;
lower alkyl;
lower alkenyl;
—(CH2)mOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)mSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)mNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64 (where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy).
R4 is H;
lower alkyl;
lower alkenyl;
—(CH2)mOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)mSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)mNR33 R (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mN(R20)COR64(where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57:
is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy).
R5 is lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64(where:
R20 is H;
or lower alkyl;
R64 is alkyl;
alkenyl;
aryl;
aryl-lower alkyl;
or heteroaryl-lower alkyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy):
R6 is H;
lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R21)COR64 (where R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
—(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or
—(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R7 is lower alkyl;
lower alkenyl;
—(CH2)qOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)qSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)qNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)qOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)qNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)qN(R20)COR64(where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)rCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)qCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
—(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)rPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)rSO2R62 (where R is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6 —;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64 (where R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R9 is lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64(where R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
—(CH2)2NR57 (CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R10 is lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57:
H is or lower alkyl);
—(CH2)oNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64(where R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
—(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or
—(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R11 is H;
lower alkyl;
lower alkenyl;
—(CH2)mOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)mSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)mNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together ar —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mN(R20)COR64 (where R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R12 is H;
lower alkyl;
lower alkenyl;
—(CH2)mOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)mSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)mNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mNR20CONR33 R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mN(R20)COR64 (where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)rCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)rCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)rPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy):
R13 is lower alkyl;
lower alkenyl;
—(CH2)qOR55 (where R55 isis lower alkyl;
or lower alkenyl);
—(CH2)qSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)qNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)qOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)qNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(C H2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)qN(R20)COR64 (where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)rCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)qCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)rPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)rSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R14 is H;
lower alkyl;
lower alkenyl;
—(CH2)mOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)mSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)mNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl is R82:
H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mN(R20)COR64 (where:
R20 is H;
lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R15 is lower alkyl;
lower alkenyl;
—(CH2)0OR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64 (where R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—NR20COlower alkyl (R20=H;
or lower alkyl);
being particularly favoured;
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl, or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57 (CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or (CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R16 is lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33 R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64 (where R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
—(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
and R17 is lower alkyl;
lower alkenyl;
—(CH2)qOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)qSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)qNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)qOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)qNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)qN(R20)COR64(where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)rCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)qCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)rPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)rSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R20 is H;
or lower alkyl;
R18 is lower alkyl;
R19 is lower alkyl;
lower alkenyl;
—(CH2)pOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)pSR (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)pNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)pOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)pNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)pN(R20)COR64 (where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
(CH2)pCOOR57 (where R57:
lower alkyl;
or lower alkenyl);
(CH2)pCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
or lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)pSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or (CH2)oC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R21 is H;
lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)3NR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR 57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64 (where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl, or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
—(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R22 is lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33 R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64(where R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl, or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R23 is H;
lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33 R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64 (where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—NR COlower alkyl (R20═H;
or lower alkyl) being particularly favoured;
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl, or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R24 is lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64 (where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—NR20COlower alkyl (R20═H;
or lower alkyl) being particularly favoured;
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl, or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR6)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R25 is H;
lower alkyl;
lower alkenyl;
—(CH2)mOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)mNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
—(CH2)2NR57 (CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mN(R20)COR64 (where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R26 is H;
lower alkyl;
lower alkenyl;
—(CH2)mOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)mNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
—(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mNR20CONR33 R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)mN(R20)COR64 (where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl;
or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
or, alternatively, R25 and R26 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR34(CH2)2—;
R27 is H;
lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R21)COR64 (where R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl, or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
—(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
R28 is lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64(where R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—(CH2)oCOOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl, or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR6)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
and
R29 is lower alkyl;
lower alkenyl;
—(CH2)oOR55 (where R55 is lower alkyl;
or lower alkenyl);
—(CH2)oSR56 (where R56 is lower alkyl;
or lower alkenyl);
—(CH2)oNR33R34 (where R33 is lower alkyl;
or lower alkenyl;
R34 is H;
or lower alkyl;
or R33 and R34 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oOCONR33R75 (where R33 is H;
or lower alkyl;
or lower alkenyl;
R75 is lower alkyl;
or R33 and R75 taken together are
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oNR20CONR33R82 (where R20 is H;
or lower alkyl;
R33 is H;
or lower alkyl;
or lower alkenyl;
R82 is H;
or lower alkyl;
or R33 and R82 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oN(R20)COR64(where:
R20 is H;
or lower alkyl;
R64 is lower alkyl;
or lower alkenyl);
—NR20COlower-alkyl (R20═H;
or lower alkyl) being particularly favoured;
—(CH2)0COOR57 (where R57 is lower alkyl;
or lower alkenyl);
—(CH2)oCONR58R59 (where R58 is lower alkyl, or lower alkenyl;
and R59 is H;
lower alkyl;
or R58 and R59 taken together are —(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
where R57 is H;
or lower alkyl);
—(CH2)oPO(OR60)2 (where R60 is lower alkyl;
or lower alkenyl);
—(CH2)oSO2R62 (where R62 is lower alkyl;
or lower alkenyl);
or —(CH2)qC6H4R8 (where R8 is H;
F;
Cl;
CF3;
lower alkyl;
lower alkenyl;
or lower alkoxy);
Z and Z1 are chains of n and, respectively, n′ α-amino acid residues whereby either n is 4 and n′ is 6 or n is 5 and n′ is 7, the positions of said amino acid residues in said chain Z being counted starting from the N-terminal amino acid and the positions of said amino acid residues in said chain Z1 being counted starting from the C-terminal amino acid, whereby these amino acid residues are, depending on their position in the chains, Gly, or Pro, or of one of the types
C:
—NR20CH(R72)CO—;
D:
—NR2OCH(R73)CO—;
E:
—NR20CH(R74)CO—;
F:
—NR20CH(R84)CO—;
and
H:
—NR20—CH(CO—)—(CH2)4-7—CH(CO—)—NR20_;
—NR21—CH(CO—)—(CH2)pSS(CH2)p—CH(CO—)—NR20—;
—NR20—CH(CO—)—(—(CH2)pNR20CO(CH2)p—CH(CO—)—NR2—;
—NR20—CH(CO—)—(—(CH2)pNR20CONR20(CH2)p—CH(CO—)—NR20—;
and
I:
—NR86CH2CO—;
R71 is lower alkenyl;
—(CH2)p(C R61)sOR75;
—(CH2) (CHR61)sSR75;
—(CH2)p(CHR61)sOCONR33R75;
—(CH2)p(CHR61)sCOOR75;
—(CH2)pCONR58R59;
—(CH2)pPO(OR62)2;
—(CH2)pSO2R62;
or —(CH2)o—C6R67R68R69R70R76;
R72 is H, lower alkyl;
lower alkenyl;
—(CH2)p(CHR61)sOR85;
or —(CH2)p(CHR61)sSR85;
R73 is —(CH2)oR77;
—(CH2)rO(CH2)oR77;
—(CH2)rS(CH2)oR77;
or —(CH2)rNR20(CH2)oR77;
R74 is —(CH2)pNR78R79;
—(CH2)pNR77R80;
—(CH2)pC(═NR80)NR78R79;
—(CH2)pC(═NOR50)NR78R79;
—(CH2)pC(═NNR78R79)NR78R79;
—(CH2)pNR80C(═NR80)NR78R79;
—(CH2)pN═C(NR78R80)NR79R80;
—(CH2)pC6H4NR78R79;
—(CH2)pC6H4NR77R80;
—(CH2)pC6H4C(═NR80)NR78R79;
—(CH2)pC6H4C(═NOR50)NR78R79;
—(CH2)pC6H4C(═NNR78R79)NR78R79;
—(CH2)pC6H4NR80C(═NR80)NR78R79;
—(CH2)pC6H4N═C(NR78R80)NR79R80;
—(CH2)rO(CH2)mNR78R79;
—(CH2)rO(CH2)mNR77 R80;
—(CH2)rO(CH2)pC(═NR80)NR78R79;
—(CH2)rO(CH2)pC(═NOR50)NR78R79;
—(CH2)rO(CH2)pC(═NNR78R79)NR78R79;
—(CH2)rO(CH2)mNR80C(═NR80)NR78R79;
—(CH2)rO(CH2)mN═C(NR78R80)NR79R80;
—(CH2)rO(CH2)pC6H4CNR78R79;
—(CH2)rO(CH2)pC6H4C(═NR80)NR78R79;
—(CH2)rO(CH2)pC6H4C(═NOR50)NR78R79;
—(CH2)rO(CH2)pC6H4C(═NNR78R79)NR78R79;
—(CH2)rO(CH2)pC6H4NR80C(═NR80)NR78R79;
—(CH2)rS(CH2)mNR78R79;
—(CH2)rS(CH2)mNR77R80;
—(CH2)rS(CH2)pC(═NR80)NR78R79;
—(CH2)rS(CH2)pC(═NOR50)NR78R79;
—(CH2)rS(CH2)pC(═NNR78R79)NR75R79;
—(CH2)rS(CH2)mNR80C(═NR80)NR78R79;
—(CH2)rS(CH2)mN═C(NR78R8R)NR79R80;
—(CH2)rS(CH2)pC6H4CNR78R79;
—(CH2)rS(CH2)pC6H4C(═NR80)NR78R79;
—(CH2)rS(CH2)pC6H4C(═NOR50)NR78R79;
—(CH2)rS(CH2)pC6H4C(═NNR78R79)NR78R79;
—(CH2)rS(CH2)pC6 H4NR80C(═NR80)NR78R79;
—(CH2)pNR80COR64;
—(CH2)pNR80COR77;
—(CH2)pNR80CONR78R79;
or —(CH2)pC6H1NR80CONR78R79;
R75 is lower alkyl;
lower alkenyl;
or aryl-lower alkyl;
R33 and R75 taken together can form:
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or
(CH2)2NR57(CH2)2—;
R75 and R82 taken together can form:
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
R76 is H;
lower alkyl;
lower alkenyl;
aryl-lower alkyl;
—(CH2)oOR72;
—(CH2)oSR72;
—(CH2)oNR33R34;
—(CH2)oOCONR33R75;
—(CH2)oNR20CONR33R82;
—(CH2)oCOOR75;
—(CH2)oCONR58R59;
—(CH2)oPO(OR60)2;
—(CH2)pSO2R62;
or —(CH2)oCOR64;
R77 is —C6R67R68R69R70R76;
or a heteroaryl group of one of the formulae
R78 is H;
lower alkyl;
aryl;
or aryl-lower alkyl;
R78 and R82 taken together can form:
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
R79 is H;
lower alkyl;
aryl;
or aryl-lower alkyl;
or
R78 and R79, taken together, can be —(CH2)2-7—;
—(CH2)2O(CH2)2—;
or —(CH2)2NR57(CH2)2—;
R80 is H;
or lower alkyl;
R81 is H;
lower alkyl;
or aryl-lower alkyl;
R82 is H;
lower alkyl;
aryl;
heteroaryl;
or aryl-lower alkyl;
R33 and R82 taken together can form:
—(CH2)2-6—;
—(CH2)2O(CH2)2—;
—(CH2)2S(CH2)2—;
or —(CH2)2NR57(CH2)2—;
R83 is H;
lower alkyl;
aryl;
or —NR78R79;
R14 is —(CH2)pCONR78R79;
—(CH2)pNR80CONR78R79;
—(CH2)pC6H4CONR78R79;
or
—(CH2)pC6H4NR80CONR78R79;
R85 is lower alkyl;
or lower alkenyl;
R86 is R74;
—[(CH2)u—X]t—(CH2)vNR78R79;
—[(CH2)u—X]t—(CH2)v—C(═NR8)NR78R79;
X is —O—, NR20—, —S—, —OCOO—, u is 1-3, t is 1-6, v is 1-3;
with the proviso that in said chains Z and Z1 of n and, respectively, n′ α-amino acid residues
if n is 4 and n′ is 6, the amino acid residues in positions 1 to 4 of Z and in positions 1′ to 6′ of Z1 are:
P1:
of type C or of type D or of type E or of type F, or the residue is Pro;
P2:
of type E or of type F;
P3:
of type F, or the residue is Pro;
P4:
of type E;
P1′:
of type C or of type D or of type E or of type F, or the residue is Gly;
P2′:
of type D or of type C;
P3′:
of type F or the residue is Pro;
P4′:
of type D or of type C;
P5′:
of type E, or of type F or the residue is Pro;
and
P6′:
of type E or of type F, or the residue is Pro;
or
P3 and P3′, taken together, can form a group of type H;
and
if n is 5 and n′ is 7, the amino acid residues in positions 1 to 5 of Z and in positions 1′ to 7′ of Z1 are:
P1:
of type C or of type D or of type E or of type F, or the residue is Pro;
P2:
of type E or of type F;
P3:
of type F, or the residue is Pro;
P4:
of type F;
P5:
of type E
P1′:
of type C or of type D or of type E or of type F, or the residue is Pro;
P2′:
of type F;
P3′:
of type D or the residue is Pro;
P4′:
of type E or of type F;
P5′:
of type D, or the residue is Pro;
P6′:
of type E or of type F, or the residue is Pro;
and
P7′:
of type E or of type I, or the residue is Gly;
or
P2 and P2′ and/or P4 and P4′, taken together, can form a group of type H;
at P7′ also D-isomers being possible,
and pharmaceutically acceptable salts thereof.

2,058 more elements

Dependencies are inferred from the claim text.

Template-fixed peptidomimetics as medicaments against hiv and cancer

Life of this patent

Template-fixed peptidomimetics as medicaments against hiv and cancer

Life of this patent

Abstract

Claims32