BIS-OCTAHYDROPHENANTHRENE CARBOXAMIDES AND PROTEIN CONJUGATES THEREOF

1 . A compound of Formula I:

or a pharmaceutically acceptable salt, solvate, or stereoisomeric form thereof, wherein

each of Q 1 and Q 2 is independently —CH—, —C(O)—, —C(H)(OH)—, —C(OH) 2 —, —SO 2 —, —SO—, —PO(OR 11 )—, —PO(NR 11 NR 12 )—, —NR 11 —, or —N═;

W is —CH 2 —, —N(H)—, or —O—;

R 1 is independently —H, —OR 6 , —H, —NH 2 , alkyl, or —OP(O)(OR 6 ) 2 ;

R 2 is independently —H, —OH, —OR 11 , halide, —SO 2 NR 11 R 12 , —CONR 11 R 12 , —CH 2 NH 2 , R 3 , R 4 , R 5 , or —O—R 5 ;

wherein R 1 and R 2 are not simultaneously —H;

R 3 is —N(R 6 ) 2 ;

R 4 is —X—Y—Z;

X is selected from the group consisting of —O— and —N(H)—;

Y is selected from the group consisting of alkylene, substituted alkylene (will include oxo, i.e. ═O substitution), heteroalkylene, and substituted heteroalkylene;

Z is selected from the group consisting of —OH and —NH 2 ;

R 5 is alkyl, heterocycloalkyl, or substituted heterocycloalkyl, wherein each heterocycloalkyl or substituted heterocycloalkyl comprises one, two, or three heteroatoms selected from nitrogen and oxygen, and includes at least one —OH and —CH 2 OH, or at least one primary or secondary nitrogen;

each R 6 is, independently in each instance, —H, an amino acid residue, an N-alkyl amino acid residue, a peptide, a biodegradable moiety, or alkyl;

each R 7 is independently halo, C 1-6 alkyl, C 1-6 alkoxy, —CN, O-glucose, O-amino acid residue, and O-PEG n , wherein each n is an integer from 0-3; and

each R 11 and R 12 are independently —H, alkyl, and aryl.

2 . The compound of claim 1 according to Formula I:

or a pharmaceutically acceptable salt, solvate, or stereoisomeric form thereof, wherein

each of Q 1 and Q 2 is independently —CH 2 —, —C(O)—, —C(H)(OH)—, or —C(OH) 2 —;

W is —CH 2 —, —N(H)—, or —O—;

R 1 is independently —H, —OH, —NH 2 , alkyl, or —OP(O)(OR 6 ) 2 ;

R 2 is independently —H, —OH, —CH 2 NH 2 , R 3 , R 4 , R 5 , or —O—R 5 ;

wherein R 1 and R 2 are not simultaneously —H;

R 3 is —N(R 6 ) 2 ;

R 4 is —X—Y—Z;

X is selected from the group consisting of —O— and —N(H)—;

Y is selected from the group consisting of alkylene, substituted alkylene (will include oxo, i.e. ═O substitution), heteroalkylene, and substituted heteroalkylene;

Z is selected from the group consisting of —OH and —NH 2 ;

R 5 is alkyl, heterocycloalkyl, or substituted heterocycloalkyl, wherein each heterocycloalkyl or substituted heterocycloalkyl comprises one, two, or three heteroatoms selected from nitrogen and oxygen, and includes at least one —OH and —CH 2 OH, or at least one primary or secondary nitrogen;

each R 6 is, independently in each instance, —H, an amino acid residue, an N-alkyl amino acid residue, a peptide, or alkyl; and

each R 7 is independently halo, C 1-6 alkyl, C 1-6 alkoxy, —CN, O-glucose, O-amino acid residue, and O-PEG n , wherein each n is an integer from 0-3.

3 . The compound of claim 1 according to Formula Ia:

or a pharmaceutically acceptable salt, solvate, or stereoisomeric form thereof.

4 . The compound of claim 1 wherein Q 1 is —CH 2 — and Q 2 is —C(O)—.

5 . The compound of claim 1 wherein Q 1 is —C(H)(OH)— and Q 2 is —C(O)—.

6 . The compound of claim 1 wherein Q 1 is —C(O)— and Q 2 is —C(O)—.

7 . The compound of claim 1 wherein Q 1 is —C(O)— and Q 2 is —CH 2 —.

8 . The compound of claim 1 wherein Q 1 is —C(O)— and Q 2 is —C(H)(OH)—.

9 . The compound of claim 1 wherein W is —CH 2 —.

10 . The compound of claim 1 wherein W is —O—.

11 . The compound of claim 1 wherein W is —NH—.

12 . The compound of claim 1 wherein R 1 is —H and R 2 is R 3 , R 4 , R 5 , or —O—R 5 .

13 . The compound of claim 1 wherein R 1 is —OH and R 2 is R 3 , R 4 , R 5 , or —O—R 5 .

14 . The compound of claim 1 wherein R 1 is —OH or —OP(O)(OR 6 )(OH) and R 2 is —H.

15 . The compound of claim 1 according to Formula Ib:

or a pharmaceutically acceptable salt, solvate, or stereoisomeric form thereof.

16 . The compound of claim 1 wherein R 1 is —OH.

17 . The compound of claim 1 wherein R 2 is —O—(CH 2 ) n —Z and n is an integer from 1 to 4.

18 . The compound of claim 1 wherein R 2 is —N(H)C(O)—(CH 2 )) n —NH 2 and n is an integer from 1 to 4.

19 . The compound of claim 1 wherein R 2 is —N(H)C(O)—(CRR) n —NH 2 ; each R is —H—, —OH or —CH 2 OH; and n is an integer from 1 to 4.

20 . The compound of claim 1 wherein R 2 is N-piperazinyl.

21 . The compound of claim 1 wherein R 2 is —N(R 6 ) 2 .

22 . The compound of claim 1 wherein R 2 is N-serinyl.

23 . The compound of claim 1 wherein R 2 is O-glycosyl.

24 . The compound of claim 1 wherein R 1 is —OP(O)(OR 6 )(OH) and R 1 is —NH 2 .

25 . The compound of claim 1 selected from the group consisting of:

or a pharmaceutically acceptable salt, solvate or stereoisomeric form thereof.

26 . A linker-payload comprising the compound of claim 1 bonded to a linker.

27 . The linker-payload of claim 1 wherein the linker is bonded to an oxygen or a primary or secondary nitrogen of the compound of the preceding claims.

28 . The linker-payload of claim 26 , selected from the group consisting of

29 . An antibody-drug-conjugate comprising the compound of claim 1 bonded to an antibody, or an antigen binding fragment thereof.

30 . A compound of Formula A

or a pharmaceutically acceptable salt, or stereoisomeric form thereof, wherein

L is a linker;

BA is a binding agent;

k is an integer from 1 to 30;

each of Q 1 and Q 2 is independently —CH—, —C(O)—, —C(H)(OH)—, or —C(OH) 2 —;

W is —CH 2 —, —N(H)—, or —O—;

R is independently —H, —OH, or —OP(O)(OR 6 )(OH); and

each R 6 is, independently in each instance, —H, an amino acid residue, a peptide, or alkyl; and

each R 7 is independently halo, C 1-6 alkyl, C 1-6 alkoxy, —CN, O-glucose, O-amino acid residue, and O-PEG n , wherein each n is an integer from 0-3.

31 . A pharmaceutical composition comprising the compound, linker-payload, or antibody-drug-conjugate of claim 1 and a pharmaceutically acceptable excipient, carrier, or diluent.

32 . A method for the treatment of dyslipidemia, a metabolic disease, inflammation, or a neurodegenerative disease in a subject comprising the administration to the subject of an effective treatment amount of a compound of claim 1 .

33 . A method for the treatment of dyslipidemia in a subject comprising the administration to the subject of an effective treatment amount of a compound of claim 1 .

34 . A method for the treatment of a metabolic disease in a subject comprising the administration to the subject of an effective treatment amount of claim 1 .

35 . A method for the treatment of inflammation in a subject comprising the administration to the subject of an effective treatment amount of a compound of claim 1 .

36 . A method for the treatment of a neurodegenerative disease in a subject comprising the administration to the subject of an effective treatment amount of claim 1 .

37 - 53 . (canceled)