What is claimed is:
1. A coupling assembly comprising:
a female coupling member, having a receiving end and a distal end, and including a cavity opening onto the receiving end, the cavity having an annular groove, the annular groove having a receiving-side edge and a distal-side edge;
a male coupling member, having a leading end and a trailing end, and including an annular rib, the rib having a tapered leading edge, a trailing edge and a maximum diameter between the leading and trailing edges, the male coupling member being sized for insertion into the cavity of the female coupling member so that the trailing edge of the annular rib is able to pass the receiving-side edge of the annular groove in the female coupling member;
a diametrically expandable locking ring carried in the annular groove of the female coupling member, the locking ring having an un-expanded inner diameter that is less than the maximum diameter of the annular rib on the male coupling member, and the locking ring being diametrically expandable to have an inner diameter that is at least slightly larger than the maximum diameter of the annular rib on the male coupling member;
at least one mechanical actuator, carried on the male coupling member, on a trailing end side of the annular rib, adjacent to the trailing edge of the annular rib, and operable to project radially outwardly to a radial height at least equal to a radial height of the annular rib at the maximum diameter of the annular rib;
the mechanical actuator capable of being actuated by one of actuation by hand and actuation with the assistance of a tool;
whereby upon insertion of the male coupling member into the cavity of the female coupling member, the tapered leading edge of the annular rib on the male coupling member contacts an inner surface of the locking ring, causing the locking ring to diametrically expand as the locking ring advances towards the trailing edge of the annular rib, and upon passing the trailing edge of the annular rib, the locking ring contracts again and is maintained in a locking position between the trailing edge of the annular rib and the receiving side edge of the annular groove; and
whereby the male coupling member may be removed again from the female coupling member by actuating the mechanical actuator to project radially outwardly and contact the inner surface of the locking ring causing the locking ring to diametrically expand again so that the annular rib of the male coupling member may pass again by the locking ring.
2. The coupling assembly of claim 1, wherein the mechanical actuator includes at least one lever operable to splay radially outwardly.
3. The coupling assembly of claim 2, wherein the lever includes:
a carrier mounted for rotation on the male coupling member on a trailing end side of the annular rib and axially spaced from the annular rib;
an outer cam surface of the male coupling member positioned axially between the trailing edge of the annular rib and the carrier, and extending in a circumferential direction from a minimum diameter that is substantially radially recessed with respect to the annular rib to an end diameter that approximates the maximum diameter of the annular rib;
a pin extending axially from a substantially fixed radial point on the carrier, approximate the minimum diameter, and extending over at least a portion of the outer cam surface;
whereby rotation of the carrier causes the pin to slide in a circumferential direction along the outer cam surface such that pin splays radially outwardly as the pin approaches the end diameter of the outer cam surface.
4. The coupling assembly of claim 3, wherein the outer cam surface is a substantially flat surface on a plane parallel to a tangent of a rotational axis of the carrier.
5. The coupling assembly of claim 3, wherein the pin is pivotally received within the carrier, allowing the pin to pivot radially with respect to the carrier.
6. The coupling assembly of claim 5, comprising a plurality of the pins, uniformly distributed about a circumference of the male coupling member.
7. The coupling assembly of claim 6, comprising four of the pins, uniformly distributed about the circumference of the male coupling member.
8. The coupling assembly of claim 6, wherein the locking ring is a split ring of resilient material.
9. The coupling assembly of claim 8, wherein the resilient material is spring steel.
10. The coupling assembly of claim 6, wherein the carrier is a rotatable dial.
11. The coupling assembly of claim 1O, wherein the dial includes a textured circumferential surface to improve gripping by a user.
12. The coupling assembly of claim 6, wherein the carrier is adapted for engagement by a tool.
13. The coupling assembly of claim 12, wherein the carrier includes a plurality of flats circuferentially distributed thereabout for engagement by a wrench.
14. The coupling assembly of claim 12, wherein the carrier includes a female coupling mechanism on a circumferential side of the carrier adapted for engagement by a male coupling mechanism on the tool.
15. The coupling assembly of claim 14, further comprising a freely rotatable ring, concentric with and substantially encapsulating at least an axial portion of the carrier, the encapsulating ring including a hole extending radially therethrough and axially aligned with the female coupling mechanism of the carrier, whereby the male coupling mechanism may pass through the radial hole in the encapsulating ring to engage with the female coupling mechanism of the carrier.
16. The coupling assembly of claim 6, further comprising a ring, concentric with and substantially encapsulating at least an axial portion of the carrier, the ring being freely rotatable with respect to the carrier in a locked state and linked for concurrent rotation with the carrier in an unlocked state.
17. The coupling assembly of claim 16, wherein:
the carrier includes a female coupling mechanism on a circumferential side of the carrier adapted for engagement by a male coupling mechanism of a tool; and
the encapsulating ring includes a hole extending radially therethrough and axially aligned with the female coupling mechanism of the carrier, whereby the male coupling mechanism may pass through the radial hole in the encapsulating ring to engage with the female coupling mechanism of the carrier, thereby providing the unlocked state of the carrier and encapsulating ring.
18. The coupling assembly of claim 6, further comprising an o-ring seal abutting a leading-end side of the carrier and circumscribing the plurality of pins used for the corresponding plurality of levers.
19. The coupling assembly of claim 18, wherein:
the carrier is rotatably mounted upon a cylindrical, trailing-end segment of the male coupling member; and
the coupling assembly further comprises an o-ring seal abutting a trailing-end side of the carrier and circumscribing the trailing-end segment of the male coupling member.
20. The coupling assembly of claim 1, wherein:
the male coupling member includes an axial bore extending into the leading end to provide for the transport of fluids or gasses therein;
the female coupling member includes an axial bore extending into a distal end of the cavity, providing fluid communication with the axial bore extending into the leading end of the male coupling member when the male and female coupling members are coupled together; and
the cavity of the female coupling member includes a inner circumferential surface that substantially matches an outer circumferential surface of the male coupling member, at least from a leading end of the male coupling member to the maximum diameter of the annular rib.
21. The coupling assembly of claim 20, wherein the male coupling member includes at least one circumferential seal carried between the leading end of the male coupling member and the tapered leading edge of the annular rib, for providing a seal between the male coupling member and the female coupling member.
22. The coupling assembly of claim 21, wherein the male coupling member includes a chamferred annular leading edge.
23. The coupling assembly of claim 1, wherein the mechanical actuator includes:
a carrier mounted for rotation on the male coupling member on a trailing end side of the annular rib and axially spaced from the annular rib;
a cylindrical segment of the male coupling member positioned axially between the trailing edge of the annular rib and the carrier, the cylindrical segment having an outer diameter approximate the maximum diameter of the annular rib, the cylindrical segment of the male coupling member including a plurality of substantially flat, outer cam surfaces cut or formed therein and uniformly distributed about a circumference cylindrical segment, each outer cam surface extending tangentially from a minimum diameter that is substantially radially recessed with respect to the annular rib to the outer diameter of the cylindrical segment;
a plurality of pins corresponding to the plurality of outer cam surfaces, each pin extending axially from a respective, substantially fixed radial point on the carrier, approximate the minimum diameter, and extending over at least a portion of the respective outer cam surface, and the pin being radially pivotable or flexible with respect to the radial point on the carrier;
whereby rotation of the carrier causes the pins to slide in a circumferential direction along their respective outer cam surfaces such that pins splay radially outwardly as they approach the outer diameter cylindrical segment, where such radially outward splaying of the pins applies pressure to the inner surface of the locking ring, causing the locking ring to diametrically expand.
24. The coupling assembly of claim 23, wherein the carrier is a manually rotatable dial.
25. The coupling assembly of claim 23, wherein the carrier is adapted for engagement by a tool.
26. The coupling assembly of claim 25, wherein the carrier includes a plurality of flats circuferentially distributed thereabout for engagement by a wrench.
27. The coupling assembly of claim 25, wherein the carrier includes a female coupling mechanism on a circumferential side of the carrier adapted for engagement by a male coupling mechanism on the tool.
28. The coupling assembly of claim 27, further comprising a freely rotatable ring, concentric with and substantially encapsulating at least an axial portion of the carrier, the encapsulating ring including a hole extending radially therethrough and axially aligned with the female coupling mechanism of the carrier, whereby the male coupling mechanism may pass through the radial hole in the encapsulating ring to engage with the female coupling mechanism of the carrier.
29. The coupling assembly of claim 23, further comprising a ring, concentric with and substantially encapsulating at least an axial portion of the carrier, the ring being freely rotatable with respect to the carrier in a locked state and linked for concurrent rotation with the carrier in an unlocked state.
30. The coupling assembly of claim 29, wherein:
the carrier includes a female coupling mechanism on a circumferential side of the carrier adapted for engagement by a male coupling mechanism of a tool; and
the encapsulating ring includes a hole extending radially therethrough and axially aligned with the female coupling mechanism of the carrier, whereby the male coupling mechanism may pass through the radial hole in the encapsulating ring to engage with the female coupling mechanism of the carrier, thereby providing the unlocked state of the carrier and encapsulating ring.
31. The coupling assembly of claim 1, wherein the trailing edge of the annular rib is substantially normal to a circumferential outer surface of the annular rib at the maximum diameter of the annular rib.
32. A coupling assembly comprising:
a female coupling member, having a receiving end and a distal end, and including a cavity opening onto the receiving end, the cavity having an annular groove, the annular groove having a receiving-side edge and a distal-side edge;
a male coupling member, having a leading end and a trailing end, and including an annular rib, the rib having a tapered leading edge, a trailing edge and a maximum diameter between the leading and trailing edges, the male coupling member being sized for insertion into the cavity of the female coupling member so that the trailing edge of the annular rib is able to pass the receiving-side edge of the annular groove in the female coupling member;
a diametrically expandible locking ring carried in the annular groove of the female coupling member, the locking ring having an un-expanded inner diameter that is less than the maximum diameter of the annular rib on the male coupling member, and the locking ring being diametrically expandible to have an inner diameter that is at least slightly larger than the maximum diameter of the annular rib on the male coupling member;
a dial carried for manual rotation on the male coupling member; and
a mechanical actuator carried on the male coupling member operatively coupled to the dial wherein the mechanical actuator extends radially outwardly with respect to the male coupling member upon rotation of the dial in a first direction to a radial height at least approximately equal to a radial height of the annular rib at the maximum diameter of the annular rib, and retracts radially inwardly with respect to the male coupling member upon rotation of the dial in an opposite direction;
whereby upon insertion of the male coupling member into the cavity of the female coupling member, the tapered leading edge of the annular rib on the male coupling member contacts an inner surface of the locking ring, causing the locking ring to diametrically expand as the locking ring advances towards the trailing edge of the annular rib, and upon passing the trailing edge of the annular rib, the locking ring contracts again and is maintained in a locking position between the trailing edge of the annular rib and the receiving side edge of the annular groove; and
whereby the male coupling member may be removed again from the female coupling member by rotating the dial in the first direction so that the mechanical actuator projects radially outwardly and contacts the inner surface of the locking ring causing the locking ring to diametrically expand again so that the annular rib of the male coupling member may pass again by the locking ring.
33. The coupling assembly of claim 32, wherein the dial is adapted for manual rotation without the assistance of tools.
34. The coupling assembly of claim 32, wherein the dial is adapted for engagement by a tool for assisting in the manual rotation of the dial.
35. The coupling assembly of claim 34, wherein the dial includes a plurality of flats circuferentially distributed thereabout for engagement by a wrench.
36. The coupling assembly of claim 34, wherein the dial includes a female coupling mechanism on a circumferential side of the dial adapted for engagement by a male coupling mechanism on the tool.
37. The coupling assembly of claim 36, further comprising a freely rotatable ring, concentric with and substantially encapsulating at least an axial portion of the dial, the encapsulating ring including a hole extending radially therethrough and axially aligned with the female coupling mechanism of the dial, whereby the male coupling mechanism may pass through the radial hole in the encapsulating ring to engage with the female coupling mechanism of the dial.
38. The coupling assembly of claim 32, further comprising a ring, concentric with and substantially encapsulating at least an axial portion of the dial, the ring being freely rotatable with respect to the dial in a locked state and linked for concurrent rotation with the dial in an unlocked state.
39. The coupling assembly of claim 38, wherein:
the dial includes a female coupling mechanism on a circumferential side of the dial adapted for engagement by a male coupling mechanism of a tool; and
the encapsulating ring includes a hole extending radially therethrough and axially aligned with the female coupling mechanism of the dial, whereby the male coupling mechanism may pass through the radial hole in the encapsulating ring to engage with the female coupling mechanism of the dial, thereby providing the unlocked state of the dial and encapsulating ring.
40. The coupling assembly of claim 32, wherein the mechanical actuator includes a pin operable, upon rotation of the dial in a first direction, to splay radially outwardly.
41. The coupling assembly of claim 40, wherein:
the mechanical actuator includes a cam surface axially positioned between the annular rib and the dial, the cam surface extending in a circumferential direction from a first diameter that is substantially radially recessed with respect to the annular rib to a second diameter that approximates the maximum diameter of the annular rib;
the dial rotates about a central axis of the male coupling member; and
the pin extends axially from a radial point on the dial approximate the first diameter, and extends over at least a portion of the cam surface;
whereby rotation of the carrier causes the pin to slide in the circumferential direction along the cam surface from the first diameter towards the second diameter, which in turn causes the pin to splay radially outwardly as the pin approaches the second diameter.
42. The coupling assembly of claim 41, wherein the mechanical actuator includes a plurality of the pins and a corresponding plurality of the cam surfaces, respectively uniformly spaced about a circumference of the male coupling member.
43. A fluid-line coupling assembly comprising:
a female coupling member including a channel extending axially therethrough and a cavity opening onto a receiving end of the female coupling member, the cavity communicating with the channel;
a male coupling member including a channel extending axially therethrough;
a releasable retaining assembly carried on the female and male coupling members, adapted to retain the male coupling member within the cavity of the female coupling member when the male coupling member is inserted within the cavity of the female coupling member;
a rotatable actuator carried on one of the male and female coupling members, operatively connected with at least one component of the releasable fastening assembly and adapted to release the releasable retaining assembly upon rotation of the actuator so that the male coupling member may be removed from the female coupling member; and
a ring, concentric with and substantially encapsulating at least an axial portion of the rotatable actuator, the ring being freely rotatable with respect to the rotatable in a locked state and linked for concurrent rotation with the rotatable in an unlocked state.
44. The fluid-line coupling assembly of claim 43, wherein:
the rotatable actuator includes a female coupling mechanism on a circumferential side of the rotatable actuator adapted for engagement by a male coupling mechanism of a tool; and
the encapsulating ring includes a hole extending radially therethrough and axially aligned with the female coupling mechanism of the rotatable actuator, whereby the male coupling mechanism may pass through the radial hole in the encapsulating ring to engage with the female coupling mechanism of the rotatable actuator, thereby providing the unlocked state of the rotatable actuator and encapsulating ring.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A method for treating cancer comprising administering to a subject having cancer a sufficient amount of a compound having the formula:
24
a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer to provide a Cmax of about 20 to 4000 ngmL of the compound in the subject’s plasma or a Cmax of about 40 to 8000 ngmL of the compound in the subject’s blood.
2. The method of claim 1, wherein the amount of the compound is sufficient to provide a Cmax of about 50 to 500 ngmL of the compound in the subject’s plasma or a Cmax of about 100 to 1000 ngmL of the compound in the subject’s blood.
3. The method of claim 1, wherein the amount of the compound is sufficient to provide a Cmax of about 50 to 250 ngmL of the compound in the subject’s plasma or a Cmax of about 100 to 500 ngmL of the compound in the subject’s blood.
4. The method of claim 1, wherein the amount of the compound is sufficient to provide a Cmax of about 75 to 150 ngmL of the compound in the subject’s plasma or a Cmax of about 150 to 300 ngmL of the compound in the subject’s blood.
5. The method of claim 1, wherein the amount of the compound is sufficient to provide a Cmax of about 100 to 2000 ngmL of the compound in the subject’s plasma or a Cmax of about 200 to 4000 ngmL of the compound in the subject’s blood.
6. The method of claim 1, wherein the amount of the compound is sufficient to provide a Cmax of 100 to 1000 ngmL of the compound in the subject’s plasma or a Cmax of about 200 to 2000 ngmL of the compound in the subject’s blood.
7. The method of claim 1, wherein the lactate salt of the compound is administered to the subject and the subject is a human.
8. The method of claim 7, wherein the lactate salt is in an aqueous solution and is administered orally to the human subject.
9. A method for treating cancer comprising administering to a subject having cancer a sufficient amount of a compound having the formula:
25
a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer to provide about 10 to 2,000 ngmL of the compound in the subject’s plasma 24 hours after administration or about 20 to 4,000 ngmL of the compound in the subject’s blood 24 hours after administration.
10. The method of claim 9, wherein the amount of the compound administered is sufficient to provide about 20 to 1,000 ngmL of the compound in the subject’s plasma 24 hours after administration or about 40 to 2,000 ngmL of the compound in the subject’s blood 24 hours after administration.
11. The method of claim 9, wherein the amount of the compound administered is sufficient to provide about 40 to 500 ngmL of the compound in the subject’s plasma 24 hours after administration or about 80 to 1,000 ngmL of the compound in the subject’s blood 24 hours after administration.
12. The method of claim 9, wherein the amount of the compound administered is sufficient to provide about 40 to 250 ngmL of the compound in the subject’s plasma 24 hours after administration or about 80 to 500 ngmL of the compound in the subject’s blood 24 hours after administration.
13. The method of claim 9, wherein the subject is a human.
14. The method of claim 13, wherein the lactate salt of the compound is administered to the subject.
15. The method of claim 14, wherein the lactate salt is in a pill, capsule, tablet, gelcap, caplet, suspension, or aqueous solution and is administered orally to a human subject.
16. The method of claim 9, wherein the compound is administered as a pharmaceutical composition comprising fructose.
17. The method of claim 16, wherein the pharmaceutical composition further comprises a flavoring agent.
18. The method of claim 17, wherein the flavoring agent comprises tetrarome mandarine flavor.
19. The method of claim 18, wherein the pharmaceutical composition further comprises water.
20. The method of claim 9, further comprising mixing the solid compound with water to form an aqueous mixture before administering the compound to the subject.
21. The method of claim 9, wherein the compound is administered as a pharmaceutical composition selected from granules, powders, suspensions, tablets, pills, capsules, gelcaps, caplets, emulsions, syrups, elixirs, slurries, sprays, aerosols, or solutions.
22. The method of claim 21, wherein the pharmaceutical composition is selected from tablets, pills, capsules, gelcaps, or caplets.
23. The method of claim 9, wherein the compound is administered by injection as a short bolus, slow infusion, or long-term infusion.
24. The method of claim 23, wherein the injection is administered once, twice, three times, or four times daily.
25. The method of claim 9, wherein the amount of the compound administered to the subject ranges from 0.25 to 30 mgkg body weight of the subject.
26. The method of claim 9, wherein the amount of the compound administered to the subject ranges from about 25 to 1500 mgday.
27. The method of claim 9, wherein the amount of the compound administered to the subject ranges from about 200 to 500 mgday.
28. The method of claim 9, wherein the cancer to be treated is a solid tumor.
29. The method of claim 9, wherein the cancer to be treated is a leukemia.
30. The method of claim 9, wherein the cancer to be treated is selected from prostate, colorectal, breast, multiple myeloma, pancreatic, small cell carcinoma, acute myelogenous leukemia, chronic myelogenous leukemia, myelo-proliferative disease, nonsmall cell lung, small cell lung, chronic lymphoid leukemia, sarcoma, melanoma, lymphoma, thyroid, neuroendocrine, renal cell, gastric, gastrointestinal stromal, glioma, brain, or bladder.
31. The method of claim 9, further comprising administering the compound as part of a treatment cycle, wherein the treatment cycle comprises administering the amount of the compound daily for 7, 14, 21, or 28 days, followed by 7 or 14 days without administration of the compound.
32. The method of claim 31, wherein the treatment cycle comprises administering the amount of the compound daily for 7 days, followed by 7 days without administration of the compound.
33. The method of claim 31, wherein the treatment cycle is repeated one or more times.
34. The method of claim 31, further comprising administering the amount of the compound once, twice, three times, or four times daily during the administration phase of the treatment cycle.
35. The method of claim 9, further comprising administering the amount of the compound once, twice, three times, or four times daily or every other day during a course of treatment.
36. A method for treating cancer comprising administering to a subject having cancer a sufficient amount of a compound having the formula:
26
a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer to provide an AUC of about 500 to 60,000 ng*hmL of the compound in the subject’s plasma or about 750 to 120,000 ng*hmL of the compound in the subject’s blood.
37. The method of claim 36, wherein the AUC is about 1,000 to 30,000 ng*hmL of the compound in the subject’s plasma or about 1,500 to 60,000 ng*hmL of the compound in the subject’s blood.
38. The method of claim 36, wherein the AUC is about 2,000 to 15,000 ng*hmL of the compound in the subject’s plasma or about 3,000 to 30,000 ng*hmL of the compound in the subject’s blood.
39. A method for determining a metabolic profile for a compound having the formula:
27
a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer, in a subject, the method comprising measuring the amount of at least one metabolite of the compound in one or more samples of urine, blood, or tissue taken from the subject.
40. The method of claim 39, wherein the at least one metabolite is an N-oxide compound having the formula:
28
41. The method of claim 39, wherein the at least one metabolite is an N-desmethyl compound having the formula:
29
42. The method of claim 41, wherein the at least one metabolite further includes a second metabolite that is an N-oxide compound having the formula:
30
43. The method of claim 41, wherein the metabolite is measured by ultraviolet spectroscopy or liquid chromatography-mass spectroscopy.
44. A method of determining the amount of a compound having the formula:
31
a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer in a subject, the method comprising measuring the amount of the compound in a sample of urine, blood, or tissue taken from the subject after the compound has been administered to the subject.
45. The method of claim 44, further comprising measuring the amount of a metabolite of the compound in the sample.
46. The method of claim 45, wherein the metabolite is an N-oxide compound having the formula:
32
47. The method of claim 46, wherein the metabolite is an N-desmethyl compound having the formula:
33
48. The method of claim 44, further comprising withdrawing two or more samples from the subject at different times after the compound has been administered to the subject.
49. A method for treating cancer comprising administering to a subject having cancer a compound having the formula:
34
a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer, wherein the amount of compound administered to the subject in a first treatment cycle is 25 mg per day, and the amount of compound administered is increased with each subsequent treatment cycle until either 1500 mg of compound is administered to the subject per day or dose-limiting toxicity is observed in the subject.
50. The method of claim 49 wherein the amount of compound administered is doubled with each subsequent treatment cycle after the first.
51. The method of claim 50 wherein the treatment cycle comprises administering the same amount of the compound daily for 7 days followed by 7 days without administration of the compound.
52. A method of treating cancer, comprising administering to a subject having cancer, a sufficient amount of a compound having the formula I
35
a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer, and exposing the subject to one or both compounds of formula II and formula III selected from:
36
whereby one or both of the compounds of formula II and formula III are produced by metabolism of the compound of formula I by the subject, to provide a combined Cmax for one or more of the compounds of formula I, formula II, and formula III ranging from about 20 to about 4000 ngmL in the subject’s plasma or a combined Cmax for one or more of the compounds of formula I, formula II, and formula III ranging from about 40 to about 8000 ngmL in the subject’s blood.
53. A method for treating cancer comprising exposing a subject having cancer to an amount of one or more compounds having a formula selected from:
37
an active metabolite thereof, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer, sufficient to provide a combined Cmax of about 20 to 4000 ngmL of the one or more compounds in the subject’s plasma or a combined Cmax of about 40 to 8000 ngmL of the one or more compound in the subject’s blood.
54. The method of claim 53, wherein the amount of the one or more compounds provides a Cmax for one of the compounds of about 35 to 2600 ngmL in the subject’s plasma or a Cmax for one of the compounds of about 35 to 6000 ngmL in the subject’s blood.
55. The method of claim 53, wherein the amount of the one or more compounds provides a Cmax for one of the compounds of about 35 to 1200 ngmL in the subject’s plasma or a Cmax for one of the compounds of about 50 to 2400 ngmL in the subject’s blood.
56. The method of claim 53, wherein the compound of formula:
38
the pharmaceutically acceptable salt thereof, the tautomer thereof, or the pharmaceutically acceptable salt of the tautomer is administered to the subject.
57. The method of claim 53, wherein the compound of formula:
39
the pharmaceutically acceptable salt thereof, the tautomer thereof, or the pharmaceutically acceptable salt of the tautomer is administered to the subject.
58. The method of claim 53, wherein the compound of formula:
40
the pharmaceutically acceptable salt thereof, the tautomer thereof, or the pharmaceutically acceptable salt of the tautomer is administered to the subject.