Peptide analogues and uses thereof
OwnerYihan Wang, Tomi K. Sawyer +1inventors
InventorsYihan Wang, Tomi K. Sawyer, David L. Berstein
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Abstract
This invention relates to compounds of the general formula: 1 in which RA, RB, RC, RD, RG and Z are as defined herein, and to their preparation and use.
Claims55
A compound having the structure (I):
- 52
- or a pharmaceutically acceptable derivative thereof,
- wherein RA and RB are each independently hydrogen, COOH, B(OH)2, a phosphorus-containing moiety, or an ester of any of the foregoing, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;
- Z and W are each independently a covalent bond or an aliphatic, heteroaliphatic, aryl, or heteroaryl linker of 1-10 carbon atoms;
- RC is an aliphatic, heteroaliphatic, aryl, heteroaryl, aliphatic(aryl), aliphatic(heteroaryl), heteroaliphatic(aryl), or heteroaliphatic(heteroaryl) moiety;
- RD is an aryl or heteroaryl moiety;
- RG is hydrogen or an alkyl group;
- wherein in each of the foregoing groups Z, W, RC, RD, and RG each alkyl, aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may independently be branched or unbranched, cyclic or acyclic or substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may independently be substituted or unsubstituted;
- and
- at least one of RA, RB, RC or RD comprises or is substituted with a phosphorus-containing moiety, with the proviso that:
- (i) if RA is the only phosphorus-containing moiety;
- if RD is a phenyl moiety substituted with a substituted or unsubstituted phenoxy or naphthyloxy moiety;
- and if -ZRB is a phenyl, benzyl or C1-6 alkyl moiety substituted with an amidino, guanidino, isothioureido or amino moiety, then RA is not —P(═O)(ORZ)(RX), where RZ is C1-6 perfluoroalkyl, phenyl or substituted phenyl and RX is C1-6 perfluoroalkoxy, phenoxy, halogen, C1-6 alkoxy or substituted phenoxy;
- and
- (ii) if RD is the only phosphorus-containing moiety and is a quinoline moiety substituted with —PO3H;
- then RC is not an alkyl, aryl, or aralkyl moiety substituted with nitro or amino.
A compound having the structure:
- 75
- wherein W is —(CH2)s wherein s is an integer from 0-6;
- V and U are each independently CR3 or N;
- RA is a phosphorus-containing moiety of Series I, Ia or Ib;
- wherein each occurrence of R3 is independently halogen;
- -GR1;
- -GCO(YR1);
- -GSO2(YR1);
- cyano, nitro or azido;
- each occurrence of Y is independently —O—, —S—, —NR1—, or a chemical bond linking R1 to P,
- each occurrence of R1 is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR1 moieties in which Y is a covalent bond, R1 may also be H;
- each occurrence of G is independently absent, or is —O—, —S—, —NR1— or (M)X;
- each occurrence of M is independently a substituted or unsubstituted methylene moiety, and any M-M′ moiety may be saturated or unsaturated;
- each occurrence of x is independently an integer from 0-6;
- and
- m is an integer from 0-3.
A compound having the structure:
- 78
- wherein V and U are each independently CR3 or N;
- RF is a phosphorus-containing moiety of Series I, Ia or Ib;
- wherein each occurrence of R3 is independently halogen;
- -GR1;
- -GCO(YR1);
- -GSO2(YR1);
- cyano, nitro or azido;
- each occurrence of Y is independently —O—, —S—, —NR1—, or a chemical bond linking R1 to P,
- each occurrence of R1 is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR1 moieties in which Y is a covalent bond, R1 may also be H;
- each occurrence of G is independently absent, or is —O—, —S—, —NR1— or (M)X;
- each occurrence of M is independently a substituted or unsubstituted methylene moiety, and any M-M′ moiety may be saturated or unsaturated;
- each occurrence of x is independently an integer from 0-6;
- p is 1 or 2;
- and
- m is an integer from 0-3.
A compound having the structure:
- 81
- wherein V and U are each independently CR3 or N;
- RE is a phosphorus-containing moiety of Series I, Ia or Ib;
- each occurrence of R3 is independently halogen;
- -GR1;
- -GCO(YR1);
- -GSO2(YR1);
- cyano, nitro or azido;
- each occurrence of Y is independently —O—, —S—, —NR1—, or a chemical bond linking R1 to P,
- each occurrence of R1 is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR1 moieties in which Y is a covalent bond, R1 may also be H;
- each occurrence of G is independently absent, or is —O—, —S—, —NR1— or (M)X;
- each occurrence of M is independently a substituted or unsubstituted methylene moiety, and any M-M′ moiety may be saturated or unsaturated;
- each occurrence of x is independently an integer from 0-6;
- n is 1 or 2;
- and
- m is an integer from 0-3.
A compound having the structure:
- 84
- wherein Z is —(CH2)s wherein s is an integer from 0-6;
- V and U are each independently CR3 or N;
- RB is a phosphorus-containing moiety of Series I, Ia or Ib;
- wherein each occurrence of R3 is independently halogen;
- -GR1;
- -GCO(YR1);
- -GSO2(YR1);
- cyano, nitro or azido;
- each occurrence of Y is independently —O—, —S—, —NR1—, or a chemical bond linking R1 to P,
- each occurrence of R1 is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR1 moieties in which Y is a covalent bond, R1 may also be H;
- each occurrence of G is independently absent, or is —O—, —S—, —NR1— or (M)X;
- each occurrence of M is independently a substituted or unsubstituted methylene moiety, and any M-M′ moiety may be saturated or unsaturated;
- each occurrence of x is independently an integer from 0-6;
- and
- m is an integer from 0-3.
A method for treating a bone-related disorder comprising administering a therapeutically effective amount of any one of compounds 1-7, or 39-46, or a pharmaceutically acceptable derivative thereof, to a subject in need thereof,
- and optionally further comprising administering an additional therapeutic agent.
A method for treating cancer comprising administering a therapeutically effective amount of any one of compounds 1-7, or 39-46, or a pharmaceutically acceptable derivative thereof, to a subject in need thereof,
- and optionally further comprising administering an additional therapeutic agent.
A method for inhibiting cell adhesion in a mammal comprising administering an effective amount of any one of compounds 1-7, or 39-46, or a pharmaceutically acceptable derivative thereof, to a subject in need thereof.
A method for inhibiting HIV infection comprising administering an effective amount of any one of compounds 1-7, or 39-46, or a pharmaceutically acceptable derivative thereof, to a subject in need thereof.
A method for inhibiting cyclic degradation in a cell comprising contacting a cell with an effective amount of any one of compounds 1-7, or 39-46, or a pharmaceutically acceptable derivative thereof.
A method for treating an inflammatory disorder comprising administering a therapeutically effective amount of any one of compounds 1-7, or 39-46, or a pharmaceutically acceptable derivative thereof, to a subject in need thereof,
- and optionally further comprising administering an additional therapeutic agent.
A method reducing the activity of NF-kB in a cell comprising contacting a cell with an effective amount of any one of compounds 1-7, or 39-46, or a pharmaceutically acceptable derivative thereof.
Dependencies are inferred from the claim text.