1. A method for analyzing medical device data, said method comprising:
accessing data from a plurality of ventilators in operation;
analyzing an aggregate of said data; and
determining a ventilator operation trend of a ventilator of said plurality of said ventilators based on said analyzed aggregated data.
2. The method of claim 1, further comprising:
predicting ventilator operation of said ventilator based on said ventilator operation trend.
3. The method of claim 2, further comprising:
generating a notification of said predicted ventilator operation based on one or more of said ventilator operation trend and said aggregated data.
4. The method of claim 3, further comprising:
customizing said notification.
5. The method of claim 2, further comprising:
displaying said predicted ventilator operation.
6. The method of claim 1, wherein said data is selected from a group consisting of: modes of operation, vent settings, patient vital signs, breathing sounds, patient orientation.
7. The method of claim 1, wherein said predicted ventilator operation is associated with information selected from a group consisting of: neonatal oxygen delivery, lung protection strategy, sedation effects, weaning effects, suction effects and transpulmonary pressure.
8. The method of claim 1, wherein said accessing data from a plurality of ventilators in operation further comprises:
automatically accessing data from said plurality of ventilators in operation.
9. The method of claim 1, further comprising:
providing proactive treatment to a patient associated with said ventilator based on said ventilator operation trend.
10. A system for analyzing medical device data comprising:
a data accessor for accessing data from plurality of ventilators in operation;
a data analyzer for analyzing an aggregate of said data; and
ventilator operation trend determiner for determining a ventilator operation trend of a ventilator of said plurality of said ventilators based on said analyzed aggregated data.
11. The system of claim 10, further comprising:
a ventilator operation predictor for predicting ventilator operation of said ventilator based on said ventilator operation trend.
12. The system of claim 10, further comprising:
a notification generator for generating a notification of a predicted ventilator operation based on one or more of said ventilator operation trend and said aggregated data.
13. The system of claim 10, wherein said data is selected from a group consisting of: modes of operation, vent settings, patient vital signs, breathing sounds, patient orientation.
14. The system of claim 11, wherein said predicted ventilator operation is associated with information selected from a group consisting of: neonatal oxygen delivery, lung protection strategy, sedation effects, weaning effects, suction effects and transpulmonary pressure.
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. A compound of formula I or formula I\u2032:
or pharmaceutically acceptable salts, esters, hydrates, solvates, polymorphs, or prodrugs thereof,
wherein:
X is an optionally substituted carbocyclic, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
Z is O, S(O)m, NRx, OC(O), C(O), C(O)O, NRxC(O), or C(O)NRx;
each Rx is independently H or alkyl;
J is \u2014C(O)\u2014, \u2014O\u2014C(O)\u2014, \u2014C(O)O\u2014, \u2014N(R3)\u2014C(O)\u2014, \u2014C(S)\u2014, \u2014C(\u2550NR4)\u2014, \u2014N(R3)\u2014, \u2014S(O)\u2014, or \u2014S(O2)\u2014 or absent;
A is selected from the group consisting of the following:
(i) H, aryl; substituted aryl; heteroaryl; substituted heteroaryl;
(ii) heterocyclyl or substituted heterocyclyl; and
(iii) \u2014C1-C8 alkyl, \u2014C2-C8 alkenyl or \u2014C2-C8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms independently selected from O, S, and N; substituted \u2014C1-C8 alkyl, substituted \u2014C2-C8 alkenyl or substituted \u2014C2-C8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms independently selected from O, S and N; \u2014C3-C12 carbocyclic, substituted \u2014C3-C12 carbocyclic; \u2014C3-C12 cycloalkenyl, or substituted \u2014C3-C12 cycloalkenyl;
E is -G-R5;
wherein G is absent; optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
or \u2014O\u2014, \u2014S\u2014, N(R3)\u2014, \u2014N(R3)S(Op)\u2014, \u2014N(R3)C(O)\u2014, \u2014N(R3)C(O)S(Op)\u2014, \u2014OS(Op)\u2014, \u2014C(O)S(Op)\u2014, or \u2014C(O)N(R3)S(Op)\u2014;
each p is independently 0, 1, or 2;
R5 is H; optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; optionally substituted carbocyclic, optionally substituted heterocyclic, optionally substituted aryl, or optionally substituted heteroaryl;
denotes a carbon-carbon single or double bond (i.e.,
means
each of Ra, Rb, Rc, and Rd are each independently H or halo, wherein at least two of Ra, Rb, Rc, and Rd are halo; and Rb and Rd are absent if is a double bond each R3 and R4 is independently selected at each occurrence from the following: H, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted heterocyclic; and optionally substituted carbocyclic;
L is absent or a C2-05 saturated or unsaturated chain, optionally containing one to three heteroatoms independently selected from O, N and S(O)q, wherein L is optionally substituted with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, C1-C6alkyl, C2-C6alkenyl and C2-C6alkynyl, wherein each C1-C6alkyl, C2-C6alkenyl and C2-C6alkynyl, group is optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl and cyano;
j=independently 0, 1, 2, 3, or 4;
k=independently 0, 1, 2, or 3;
each m is independently 0, 1, or 2; and
q is independently 0, 1, or 2.
2. The compound of claim 1, wherein Z is O or OC(O); and
ring X is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl, 3.3.0bicyclooctanyl, 4.3.0bicyclononanyl, 4.4.0bicyclodecanyl, 2.2.2bicyclooctanyl, fluorenyl, phenyl, naphthyl, indanyl, tetrahydronaphthyl, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, NH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro 2,3-btetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isoindolinyl, isoindolenyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl;-1,2,5oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, or xanthenyl; each of which may be optionally substituted.
3. The compound of claim 2, wherein ring X is phenanthridinyl, quinoxalinyl, quinolinyl, or isoindolinyl.
4. The compound of claim 2, wherein ring X is
wherein
Y is N or \u2014C(R\u2033)\u2014;
wherein if Y is \u2014C(R\u2033)\u2014, then R\u2032 and R\u2033 taken together with the carbon atoms to which they are attached form a ring, which is optionally substituted;
R\u2032 is H, alkyl, alkenyl, alkynyl, carbocyclic, heterocyclyl, aryl, or heteroaryl, each of which may be optionally substituted;
each R1 is independently selected from halogen, hydroxy, amino, \u2014CN, \u2014CF3, \u2014N3, \u2014NO2, \u2014OR4, \u2014SR4, \u2014SOR4, \u2014SO2R4, \u2014N(R3)S(O)2R4, \u2014N(R3)(SO2)NR3R4, \u2014NR3R4, \u2014C(O)\u2014OR4, \u2014C(O)R4, \u2014C(O)NR3R4, \u2014N(R3)C(O)R4; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted heterocyclic; optionally substituted carbocyclic; optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted alkenyl, or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
each n is independently 0, 1, 2, 3, or 4;
each R3 and R4 are independently selected at each occurrence from the following:
optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted alkenyl or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted heterocyclic;
optionally substituted carbocyclic; or hydrogen; and
k is 0, 1, or 2.
5. The compound of claim 1, or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein:
Y is \u2014C(R\u2033)\u2014,
R\u2032 and R\u2033, taken together with the atoms to which each is attached, form a C5-C7 carbocycle or heterocycle which is optionally substituted with one or more R1;
m is 1, j is 2, k is 2, L is absent;
J is \u2014C(O)\u2014, \u2014O\u2014C(O)\u2014, \u2014N(R3)\u2014C(O)\u2014, \u2014S(O)\u2014, or \u2014S(O2)\u2014;
A is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted heteroaryl, optionally substituted aryl, optionally substituted heterocyclic, or optionally substituted carbocyclic;
each R1 is independently selected from H, halogen, hydroxy, amino, \u2014CN, \u2014CF3, \u2014N3, \u2014NO2, \u2014OR4, \u2014SR4, \u2014NR3R4, optionally substituted aryl; optionally substituted heteroaryl; optionally substituted heterocyclic; optionally substituted carbocyclic; optionally substituted haloalkyl, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl;
G is \u2014N(R3)S(O)p\u2014;
p is 0, 1, or 2;
each of R2a, R2b, R2c, and R2d are each independently H or F, wherein at least two of R2a, R2b, R2c, and R2d are F;
R5 is optionally substituted carbocyclic or heterocyclic;
each R3 and R4 is independently selected at each occurrence from the following: optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted alkenyl or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted heterocyclic; optionally substituted carbocyclic; or hydrogen; and
n is 0, 1, 2, 3, or 4.
6. The compound of claim 5 wherein J is \u2014C(O)\u2014, or \u2014O\u2014C(O)\u2014.
7. The compound of claim 5, wherein A is methyl, ethyl, propyl, iso-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, heptyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, triazinyl, furanyl, thiophenyl, pyrrolyl, isoxazolyl, or pyrazolyl; each of which may be optionally substituted.
8. The compound of claim 5, wherein G is \u2014N(R3)S(O)p\u2014 and R5 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, each of which is optionally substituted.
9. The compound of claim 5, wherein R2a and R2b are F.
10. The compound of claim 5, wherein R2c and R2d are F.
11. The compound of claim 1, of formula II:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein:
J is \u2014C(O)\u2014, \u2014O\u2014C(O)\u2014, \u2014N(R3)\u2014C(O)\u2014, \u2014S(O)\u2014, or \u2014S(O2)\u2014;
A is optionally substituted alkyl, or optionally substituted heteroaryl, optionally substituted aryl, optionally substituted heterocyclic, or optionally substituted carbocyclic;
R\u2032 is H, optionally substituted aryl; optionally substituted heteroaryl; or optionally substituted alkyl;
G is \u2014N(R3)S(O)p\u2014;
p is 0, 1, or 2;
each of R2a, R2b, R2c, and R2d are each independently H or F, wherein at least two of R2a, R2b, R2c, and R2d are F;
R5 is optionally substituted carbocyclic, optionally substituted heterocyclic, optionally substituted aryl, or optionally substituted heteroaryl; and
each R3 and R4 is independently selected at each occurrence from the following:
optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted alkenyl or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted heterocyclic; optionally substituted carbocyclic; or hydrogen.
12. The compound of claim 11, wherein R\u2032 is H, optionally substituted alkyl; optionally substituted aryl; or optionally substituted heteroaryl.
13. The compound of claim 11, wherein J is \u2014C(O)\u2014, or \u2014O\u2014C(O)\u2014.
14. The compound of claim 11, wherein A is methyl, ethyl, propyl, iso-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, heptyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, triazinyl, furanyl, thiophenyl, pyrrolyl, isoxazolyl, or pyrazolyl; each of which may be optionally substituted.
15. The compound of claim 11, wherein G is \u2014N(R3)S(O)p\u2014 and R5 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, each of which is optionally substituted.
16. The compound of claim 11, wherein R2a and R2b are F.
17. The compound of claim 11, wherein R2c and R2d are F.
18. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt, ester, or prodrug thereof, in combination with a pharmaceutically acceptable carrier or excipient.
19. A method of treating a viral infection in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt, ester or prodrug thereof.
20. A method of producing a compound of formula I, comprising the step of reacting a compound of formula I-a:
with a compound of formula I-b:
to arrive at a compound of formula I:
wherein:
X is an optionally substituted carbocyclic, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
Z is O, S(O)m, NRx, OC(O), C(O), C(O)O, NR\u2014C(O), or C(O)NRx;
each Rx is independently H or alkyl;
Nuc is a nucleophile;
LG is a leaving group;
J is \u2014C(O)\u2014, \u2014O\u2014C(O)\u2014, \u2014C(O)O\u2014, \u2014N(R3)\u2014C(O)\u2014, \u2014C(S)\u2014, \u2014C(\u2550NR4)\u2014, \u2014N(R3)\u2014, \u2014S(O)\u2014, or \u2014S(O2)- or absent;
A is selected from the group consisting of the following:
(i) H, aryl; substituted aryl; heteroaryl; substituted heteroaryl;
(ii) heterocyclyl or substituted heterocyclyl; and
(iii) \u2014C1-C8 alkyl, \u2014C2-C8 alkenyl or \u2014C2-C8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms independently selected from O, S, and N; substituted \u2014C1-C8 alkyl, substituted \u2014C2-C8 alkenyl or substituted \u2014C2-C8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms independently selected from O, S and N; \u2014C3-C12 carbocyclic, substituted \u2014C3-C12 carbocyclic; \u2014C3-C12 cycloalkenyl, or substituted \u2014C3-C12 cycloalkenyl;
E is -G-R5;
wherein G is absent; optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
or \u2014O\u2014, \u2014S\u2014, \u2014N(R3)\u2014, \u2014N(R3)S(Op)\u2014, \u2014N(R3)C(O)\u2014, \u2014N(R3)C(O)S(Op)\u2014, \u2014OS(Op)\u2014, \u2014C(O)S(Op)\u2014, or \u2014C(O)N(R3)S(Op)\u2014;
each p is independently 0, 1, or 2;
R5 is H; optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; optionally substituted carbocyclic, optionally substituted heterocyclic, optionally substituted aryl, or optionally substituted heteroaryl:
denotes a carbon-carbon single or double bond (i.e.,
means
each of Ra, Rb, Rc, and Rd are each independently H or halo, wherein at least two of Ra, Rb, Rc, and Rd are halo; and Rb and Rd are absent if is a double bond each R3 and R4 is independently selected at each occurrence from the following: H, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted heterocyclic; and optionally substituted carbocyclic;
L is absent or a C2-05 saturated or unsaturated chain, optionally containing one to three heteroatoms independently selected from O, N and S(O)q, wherein L is optionally substituted with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, C1-C6alkyl, C2-C6alkenyl and C2-C6alkynyl, wherein each C1-C6alkyl, C2-C6alkenyl and C2-C6alkynyl, group is optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl and cyano;
j=independently 0, 1, 2, 3, or 4;
k=independently 0, 1, 2, or 3;
each m is independently 0, 1, or 2; and
q is independently 0, 1, or 2.