COMPOUNDS AND METHODS FOR THE TREATMENT OF ERB B2/NEU POSITIVE DISEASES

1 . A compound of Formula Ia:

or a salt thereof,

wherein

X is hydrogen or halo;

Y is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, and —C(═O)R 5 ;

R 1 is selected from the group consisting of hydrogen, —OH, —OC(═O)R 5 and —OR 5 ;

R 2 is hydrogen or C 1 -C 6 alkyl;

R 3 is methyl, —CH 2 OH, or —CH 2 C(═O)R 6 ;

R 4 is —OH or —SH;

R 5 is C 1 -C 6 alkyl or benzyl;

R 6 is C 1 -C 6 alkyl, phenyl or benzyl;

R 7 is hydrogen, C 1 -C 6 alkyl or an amino acid side chain;

R 8 is hydrogen or C 1-6 alkyl;

n is 0, 1, 2, 3, 4, 5, 6, 7 or 8;

p is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; and

Anti-HER2 is an anti-ERB B2/NEU (HER2) antibody.

2 . The compound of claim 1 , which is a compound of Formula Ib

or a pharmaceutically acceptable salt or solvate thereof.

3 . The compound of claim 1 , which is a compound of Formula Ic

or a pharmaceutically acceptable salt or solvate thereof,

wherein Anti-HER2 is an anti-ERB B2/NEU (HER2) antibody.

4 . The compound of claim 3 , wherein the compound connected to anti-ERB B2/NEU (HER2) antibody is N2′-deacetyl-N2′-(6-maleimido-1-oxo-hexyl)maytansine).

5 . The compound of claim 1 , wherein the anti-Erb B2/neu antibody is an antibody comprising trastuzumab or pertuzumab or an equivalent thereof.

6 . A pharmaceutical composition comprising a compound of claim 1 .

7 . A method of treating a proliferative, inflammatory or immunologic disease or condition in a patient in need thereof comprising administering an effective amount of a compound of claim 1 .

8 . A method of treating a proliferative, inflammatory or immunologic disease or condition characterized by Erb B2/neu positive cells in a patient in need thereof comprising administering an effective amount of a compound of Formula IVa:

or a salt thereof, wherein the compound of Formula IVa is generated as a result of a metabolic chemical reaction following administration of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to the patient, wherein AA is an amino acid or thiolated amino acid,

9 . A method of treating a proliferative, inflammatory or immunologic disease or condition characterized by Erb B2/neu positive cells in a patient in need thereof comprising administering an effective amount of a compound of Formula IVb:

or a salt thereof, wherein the compound of Formula IVb is generated as a result of a metabolic chemical reaction following administration of a compound of claim 2 , or a pharmaceutically acceptable salt thereof, to the patient, wherein AA is an amino acid or thiolated amino acid.

10 . A method of treating a proliferative, inflammatory or immunologic disease or condition characterized by Erb B2/neu positive cells in a patient in need thereof comprising administering an effective amount of a compound of Formula IVc:

or a salt thereof, wherein the compound of Formula IVc is generated as a result of a metabolic chemical reaction following administration of a compound of claim 3 , or a pharmaceutically acceptable salt thereof, to the patient, wherein AA is an amino acid or thiolated amino acid.

11 . The method of claim 8 , wherein AA is

wherein represents point of connection to the rest of the molecule.

12 . The compound of claim 1 , wherein:

X is halo;

Y is C 1 -C 6 alkyl;

R 1 is hydrogen;

R 2 is C 1 -C 6 alkyl;

R 3 is methyl;

R 4 is —OH;

R 7 is C 1 -C 6 alkyl; and

R 8 is C 1-6 alkyl.

13 . The compound of claim 1 , wherein:

X is Cl;

Y is C 1 -C 6 alkyl;

R 1 is hydrogen;

R 2 is C 1 -C 6 alkyl;

R 3 is methyl;

R 4 is —OH;

R 7 is C 1 -C 6 alkyl; and

R 8 is C 1-6 alkyl.

14 . A pharmaceutical composition comprising a compound of claim 13 .

15 . A method of treating a proliferative, inflammatory or immunologic disease or condition in a patient in need thereof comprising administering an effective amount of a compound of claim 13 .

16 . The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is suitable for injection or infusion.

17 . The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition is suitable for injection or infusion.