Methods and compounds for treatment of lymphocyte-related diseases and conditions

1. A method for treatment of a cancer or an autoimmune disease or condition, the method comprising administering an effective amount of an oligomer to a patient in need thereof, wherein the oligomer comprises a backbone having a sequence of morpholino ring structures joined by intersubunit linkages, the intersubunit linkages joining a 3′-end of one morpholino ring structure to a 5′-end of an adjacent morpholino ring structure, wherein each morpholino ring structure is bound to a base-pairing moiety, such that the oligomer can bind in a sequence-specific manner to a target nucleic acid, wherein at least one of the intersubunit linkages has the following structure (I):

or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein:

R 1 is alkylaminyl;

L 1 is absent or present, and when present is selected from alkylene, aminoalkylene, oxyalkylene and thioalkylene;

X is, at each occurrence, independently S or O;

Y is, at each occurrence, independently —O— or —NH—; and

Z is an optionally substituted 5, 6 or 7-membered heterocyclic ring.

2. The method of claim 1 , wherein the morpholino ring structures have the following structure (i):

wherein B is, at each occurrence, independently a base-pairing moiety.

3. The method of claim 1 , wherein Z is pyrrolidinyl.

4. The method of claim 1 , wherein R 1 -L 1 -Z has the following structure:

5. The method of claim 1 , wherein alkylaminyl is —NHR″, where R″ is C 1 -C 6 alkyl.

6. The method of claim 1 , wherein L 1 is absent.

7. The method of claim 1 , wherein X is O.

8. The method of claim 1 , wherein Y is —O—.

9. The method of claim 1 , wherein at least one of the intersubunit linkages has the following structure (II):

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein:

R 2 and R 3 are each independently H or C 1 -C 6 alkyl,

X′ is S or O; and

Y′ is —O— or —NH—.

10. The method of claim 1 , wherein at least one of the intersubunit linkages has the following structure:

11. The method of claim 1 , wherein the cancer or autoimmune disease or condition is a T-cell-related disease or condition.

12. The method of claim 11 , wherein the T-cell is an activated T-cell, a CD4 cell, or a CD8 cell.

13. The method of claim 1 , wherein the disease or condition is cancer.

14. The method of claim 1 , wherein the disease or condition is an autoimmune disease or condition.

15. The method of claim 1 , wherein Z is piperidinyl.

16. The method of claim 1 , wherein Z is a piperidinyl ring, L 1 is absent, X is O, Y is —O—, and R 1 is alkylaminyl.

17. A method for treatment of cancer or an autoimmune disease or condition, the method comprising contacting activated T-cells with an oligomer comprising a backbone having a sequence of morpholino ring structures joined by intersubunit linkages, the intersubunit linkages joining a 3′-end of one morpholino ring structure to a 5′-end of an adjacent morpholino ring structure, wherein each morpholino ring structure is bound to a base-pairing moiety, such that the oligomer can bind in a sequence-specific manner to a target nucleic acid, wherein at least one of the intersubunit linkages has the following structure (I):

or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein:

R 1 is alkylaminyl;

L 1 is absent or present, and when present is selected from alkylene, aminoalkylene, oxyalkylene, oxoalkylene and thioalkylene;

X is, at each occurrence, independently S or O;

Y is, at each occurrence, independently —O— or —NH—; and

Z is an optionally substituted pyrrolidinyl, or piperidinyl ring.

18. The method of claim 17 , wherein Z is a piperidinyl ring, L 1 is absent, X is O, Y is —O—, and R 1 is alkylaminyl.