1. A compound of formula I
51
wherein
m is 1,2 or 3;
X is O or a direct bond;
R1 is H; C1-6alkyl optionally substituted by OH, acyl, halogen, cycloalkyl, phenyl or hydroxy-phenylene; C2-6alkenyl; C2-6alkynyl; or phenyl optionally substituted by OH;
R2 is
52
wherein R5 is H or C1-4alkyl optionally substituted by 1, 2 or 3 halogen atoms, and R6 is H or C1-4alkyl optionally substituted by halogen;
each of R3 and R4, independently, is H, C1-4alkyl optionally substituted by halogen, or acyl, and
R is C13-20alkyl which may optionally have in the chain an oxygen atom and which may optionally be substituted by nitro, halogen, amino, hydroxy or carboxy; or a residue of formula (a)
53
wherein R7 is H, C1-4alkyl or C1-4alkoxy, and R8 is substituted C1-20alkanoyl, phenylC1-14alkyl wherein the C1-14alkyl is optionally substituted by halogen or OH, cycloalkylC1-14alkoxy or phenylC1-14alkoxy wherein the cycloalkyl or phenyl ring is optionally substituted by halogen, C1-4alkyl andor C1-4alkoxy, phenylC1-4alkoxyC1-4alkyl, phenoxyC1-14alkoxy or phenoxyC1-4alkyl,
R being also a residue of formula (a) wherein R8 is C1-14alkoxy when R1 is C1-4alkyl, C2-6alkenyl or C2-6alkynyl,
in free form or in salt form.
2. A compound according to claim 1, wherein R is a residue of formula (a).
3. A compound of formula X
54
wherein
n is 2,3 or 4
R1x is H; C1-6alkyl optionally substituted by OH, acyl, halogen, cycloalkyl, phenyl or hydroxy-phenylene; C2-6alkenyl; C2-6alkynyl; or phenyl optionally substituted by OH;
R2x is H, C1-4alkyl or acyl each of R3x and R4x, independently, is H, C1-4alkyl optionally substituted by halogen or acyl,
R5x is H, C1-4alkyl or C1-4alkoxy, and
R6x is C1-20alkanoyl substituted by cycloalkyl; cycloalkylC1-14alkoxy wherein the cycloalkyl ring is optionally substituted by halogen, C1-4alkyl andor C1-4alkoxy; phenylC1-14alkoxy wherein the phenyl ring is optionally substituted by halogen, C1-4alkyl andor C1-4alkoxy, R6x being also C4-14alkoxy when R1x is C3-4alkyl substituted by OH or pentyloxy or hexyloxy when R1x is C1-4alkyl, provided that R6x is other than phenyl-butylenoxy when either R5x is H or R1x is methyl, in free form or in salt form.
4. A compound according to claim 3 wherein n is 2.
5. A compound according to claim 3 wherein R6x is alkanoyl substituted by cycloalkyl; cycloalkylC1-14alkoxy wherein the cycloalkyl ring is optionally substituted by halogen, C1-4alkyl andor C1-4alkoxy; phenylC1-4alkoxy wherein the phenyl ring is optionally substituted by halogen, C1-4alkyl andor C1-4alkoxy.
6. A compound according to claim 1 which is selected from phosphoric acid mono-2-amino-2-hydroxymethyl-4-4-(5-phenyl-pentanoyl)-phenyl-butyl ester, phosphoric acid mono-2-amino-4-4-(5-cyclohexyl-pentanoyl)-phenyl-2-hydroxymethyl-butyl ester, phosphoric acid mono-2-amino-2-hydroxymethyl-4-4-(7-phenyl-heptanoyl)-phenyl-butyl ester, phosphoric acid mono-(R)-2-amino-4-3-methoxy-4-(4-phenyl-butoxy)-phenyl-2-methyl-butyl ester, phosphoric acid mono-(R)-2-amino-2-methyl-4-4-(5-phenyl-pentyloxy)-phenyl-butyl) ester and phosphoric acid mono-(R)-2-amino-4-(4-hexyloxy-phenyl)-2-methyl-butyl ester, or a salt thereof.
7. A compound according to claim 3 which is selected from (R)-2-Amino-2-ethyl-4-3-methoxy-4-(4-phenyl-butoxy)-phenyl-butan-1-ol, (R)-2-Amino-2-ethyl-4-3-methoxy-4-(4-phenyl-butoxy)-phenyl-butan-1-ol, (R)-2-Amino-2-methyl-4-4-(5-phenyl-pentyloxy)-phenyl-butan-1-ol, (R)-2-Amino-2-methyl-4-4-(3-phenyl-propoxy)-phenyl-butan-1-ol, (R)-2-Amino-4-4-(3-cyclohexyl-propoxy)-phenyl-2-methyl-butan-1-ol and 1-4-(3-Amino-4-hydroxy-3-hydroxymethyl-butyl)-phenyl-5-cyclohexyl-pentan-1-one, or a salt thereof.
8. A compound according to claim 1 or 3, in free form or in a pharmaceutically acceptable salt form for use as a pharmaceutical.
9. A pharmaceutical composition comprising a compound according to claim 1 or 3 in free form or pharmaceutically acceptable salt form in association with a pharmaceutically acceptable diluent or carrier therefor.
10. A method for preventing or treating disorders or diseases mediated by T lymphocytes, in a subject in need of such treatment, which method comprises administering to said subject an effective amount of a compound according to claim 1 or 3 or a pharmaceutically acceptable salt thereof;
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. An electrosurgical device for tissue ablation, comprising:
a delivery cannula having a lumen and an open distal end in communication with the lumen; and
an electrode array deployable from, and retractable into, the cannula lumen through the open distal end, the electrode array comprising a plurality of tines, the tines having proximal ends secured to a mandrel carried in the cannula lumen, the mandrel movable axially relative to the cannula,
wherein the tines, when the electrode array is retracted into the cannula lumen, are nested in offset, circumferential layers about the mandrel.
2. The device of claim 1, the offset, circumferential layers including a first layer of tines and a second layer of tines overlaying the first layer, wherein the tines in the second layer are supported by respective edges of adjacent tines in the first layer.
3. The device of claim 1, comprising at least three offset, circumferential layers of tines.
4. The device of claim 1, wherein a pair of adjacent tines in a first layer have cross-sections comprising a base, first and second sides extending from opposing ends of and generally perpendicular to the base, and first and second shoulders extending at angles greater than 90\xb0 from respective ends of the first and second sides.
5. The device of claim 4, wherein the first and second shoulders meet, forming an angle of less than 180\xb0.
6. The device of claim 5, the first and second shoulders forming an angle of approximately 90\xb0.
7. The device of claim 5, the first and second shoulders forming an angle of less than 90\xb0.
8. The device of claim 4, wherein a tine in a second layer has first and second edges supported by respective shoulders of the adjacent tine pair.
9. The device of claim 8, the second layer tine having a cross-section substantially the same as the cross section of the adjacent first layer tines, but is nested in a reverse orientation.
10. The device of claim 4, wherein the first and second shoulders terminate at respective opposing ends of a top, the top being generally parallel to the base.
11. The device of claim 10, wherein a tine in a second layer has first and second edges supported by respective shoulders of the adjacent tine pair.
12. The device of claim 10, the second layer tine having a cross-section substantially the same as the cross section of the adjacent first layer tines, but is nested in a reverse orientation.
13. An electrosurgical device for tissue ablation, comprising:
a delivery cannula having a lumen and an open distal end in communication with the lumen; and
an electrode array deployable from, and retractable into, the cannula lumen through the open distal end, the electrode array comprising a plurality of tines, the tines having proximal ends secured to a mandrel carried in the cannula lumen, the mandrel movable axially relative to the cannula,
wherein the tines, when the electrode array is retracted into the cannula lumen, are nested in first and second circumferential layers about the mandrel, the first and second layers having a collective radial thickness less than twice a maximum radial thickness of any one tine.
14. The device of claim 13, wherein the tines in the first layer have cross-sections comprising a base, first and second sides extending from opposing ends of and generally perpendicular to the base, and first and second shoulders extending at angles greater than 90\xb0 from respective ends of the first and second sides.
15. The device of claim 14, wherein the tines in the second layer have first and second edges supported by respective shoulders of adjacent tines in the first layer.
16. The device of claim 14, wherein the tines in the second layer have cross-sections substantially the same as the first layer tines, but are nested in a reverse orientation.
17. The device of claim 14, wherein the first and second shoulders meet and form an angle of less than 180\xb0.
18. The device of claim 14, wherein the first and second shoulders meet and form an angle of approximately 90\xb0.
19. An electrosurgical device for tissue ablation, comprising:
a delivery cannula having a lumen and an open distal end in communication with the lumen; and
an electrode array deployable from, and retractable into, the cannula lumen through the open distal end, the electrode array comprising a plurality of tines, the tines having proximal ends secured to a mandrel carried in the cannula lumen, the mandrel movable axially relative to the cannula,
wherein the tines, when the electrode array is retracted into the cannula lumen, are nested in first and second circumferential layers about the mandrel, wherein the tines in the second layer are supported by respective edges of adjacent tines in the first layer, and wherein the first and second layers have a collective radial thickness less than twice a maximum radial thickness of any one tine.