1. A compound having the formula:
wherein:
X1 is \u2014CR6R7\u2014;
X2 is \u2550N\u2014;
p is 0 or 1;
y is 0 or 1;
z is 2;
each R1 is independently an optionally substituted group selected from C1-12 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur,
R2 is R;
R4 is R, \u2014C(O)R, \u2014CO2R, \u2014C(O)C(O)R, \u2014C(O)CH2C(O)R, \u2014C(O)N(R)2, \u2014S(O)R, \u2014S(O)2R, or \u2014S(O)2N(R)2;
R3 is R, halogen, \u2014CN, \u2014C(O)R, \u2014CO2R, \u2014C(O)C(O)R, \u2014C(O)CH2C(O)R, \u2014S(O)R, \u2014S(O)2R, \u2014C(O)N(R)2, or \u2014SO2N(R)2; or:
R3 and R4 are optionally taken together with their intervening atoms to form an optionally substituted ring selected from pyrrole, pyrazole, or 5-6 membered partially unsaturated monocyclic heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
R5 is hydrogen or \u2014NH2;
each of R6 and R7 is independently R;
Rx is hydrogen, or:
Rx and R2 are taken together to form an optionally substituted spirocyclic heterocyclic ring selected from a 5-6 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
Ring A1 is an optionally substituted ring selected from phenyl, a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-10 membered saturated or partially unsaturated bicyclic carbocyclic ring, a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered bicyclic aryl ring, a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
L is \u2014C(O)C(R)2NR\u2014; and
each R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic or 3-7 membered saturated carbocyclic, wherein a substituent on R is selected from \u2014CF3 or \u2014OH.
2. The compound of claim 1, wherein the compound is of formula IV-a:
3. The compound of claim 1, wherein L is:
4. The compound of claim 1, wherein p is 0.
5. The compound of claim 1, wherein R2 is hydrogen or optionally substituted C1-6 aliphatic.
6. The compound of claim 1, wherein Rx is hydrogen.
7. The compound of claim 1, wherein R5 is hydrogen.
8. The compound of claim 1, wherein R3 and R4 are taken together with their intervening atoms to form an optionally substituted ring selected from pyrrole or pyrazole.
9. The compound of claim 8, wherein the compound is of formula VII-a, or VIII-a:
10. The compound of claim 1, wherein R4 is hydrogen, \u2014C(O)R, or optionally substituted C1-6 aliphatic.
11. The compound of claim 1, wherein R3 is halogen, \u2014CN, or substituted or unsubstituted C1-6 alkyl.
12. The compound of claim 1, wherein Ring A1 is an optionally substituted ring selected from phenyl, an 8-10 membered bicyclic aryl ring, a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
13. The compound of claim 12, wherein Ring A1 is bicyclic.
14. The compound of claim 12, wherein Ring A1 is substituted phenyl.
15. The compound of claim 14, wherein substituents on Ring A1 are selected from halogen, \u2014CN, \u2014CF3, \u2014OH, \u2014NH2, \u2014N(R)2, \u2014COOH, \u2014SR, \u2014S(O)R, \u2014S(O)2R, \u2014S(O)N(R)2, \u2014S(O)2N(R)2, or C1-6 aliphatic.
16. A compound as shown in Table 1.
17. A pharmaceutical formulation comprising a compound of claim 1 and a pharmaceutically acceptable excipient.
18. A method of reducing the enzymatic activity of Bruton’s tyrosine kinase comprising contacting Bruton’s tyrosine kinase with an effective amount of a compound of claim 1 or a composition 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. A packet capture apparatus, comprising:
a packet capturing part receiving packets through a packet communication network;
a data extracting-storing part acquiring target packets including specific information from the received packets, extracting the target packets of each session, and storing the extracted target packets in a data storage part;
a capture on-off time estimating part estimating a capture cycle, a capture width, and a capture start time based on static information about the target packets to determine a start time and an end time of reception of the packets based on the capture cycle, the capture width, and the capture start time, the capture cycle being a time period during which the reception of the packets is performed, the capture width being a time period during which the reception of the packets is continued, the capture start time being a time when the reception of the packets is started;
a capture on-off time setting part setting the start time and the end time; and
a capture on-off controlling part using the start time and the end time being set to control intermittent packet reception by the packet capturing part, and
wherein the packet capturing part receives the packets during each capture width every capture cycle from the capture start time in accordance with the control by the capture on-off controlling part.
2. The packet capture apparatus according to claim 1, wherein the packet capturing part receives packets through the packet communication network during a predetermined estimated capture period, and
wherein the data extracting-storing part acquires the target packets from the packets received during the estimated capture period, extracts the target packets of each session, and stores the extracted target packets in the data storage part in according with the reception time of each target packet, and
the capture on-off time estimating part estimates the capture cycle, the capture width, and the capture start time based on dynamic information indicating a reception state of the packets received during the estimated capture period, instead of the static information about the target packets.
3. The packet capture apparatus according to claim 2, wherein the capture on-off time estimating part calculates a fluctuation, which represents a difference between a time when each target packet is actually received and a time when the target packet is to be received, from data about the target packets stored in the data storage part after the estimated capture period to use the calculated fluctuation as the dynamic information, and
the capture cycle is estimated based on a reception interval of at least two target packets having smaller fluctuations, estimates the capture width based on a maximum value in the fluctuations, and estimates the capture start time based on the time when the target packet having a minimum fluctuation is received.
4. The packet capture apparatus according to claim 1, wherein the static information includes a period of protocol data based on the specific information included in the target packets.
5. The packet capture apparatus according to claim 1, wherein the static information includes an arbitrary transmission interval of the target packets.
6. A packet capture method performed by a computer including packet capturing part for receiving packets from a packet communication network and data storage unit for storing the received packets, the packet capture method comprising:
receiving packets through a packet communication network;
acquiring target packets including specific information from the received packets, extracting the target packets of each session, and storing the extracted target packets in the data storage unit;
estimating a capture cycle, a capture width, and a capture start time based on static information about the target packets to determine a start time and an end time of the reception of the packets based on the capture cycle, the capture width, and the capture start time, the capture cycle being a time period during which the reception of the packets by the packet capturing part is performed, the capture width being a time period during which the reception of the packets is continued, the capture start time being a time when the reception of the packets is started;
setting the start time and the end time;
performing a control with the start time and the end time being set; and
receiving the packets during each capture width every capture cycle from the capture start time.
7. A computer-readable storage medium storing a packet capture program causing a computer to execute an operation, comprising:
receiving packets through a packet communication network;
acquiring target packets including specific information from the received packets, extracting the target packets of each session, and storing the extracted target packets in a data storage part;
estimating a capture cycle, a capture width, and a capture start time based on information about the target packets to determine a start time and an end time of the reception of the packets based on the capture cycle, the capture width, and the capture start time, the capture cycle being a time period during which the reception of the packets is performed, the capture width being a time period during which the reception of the packets is continued, the capture start time being a time when the reception of the packets is started;
setting the start time and the end time in control of the reception of the packets;
using the start time and the end time being set to control intermittent packet reception; and
receiving the packets during each capture width every capture cycle from the capture start time in accordance with the start time and the end time.
8. A computer implemented method, comprising:
selectively setting a parameter for capturing target packets among packets exchanged based on status information of the packets exchanged; and
controlling capturing of the target packets from each exchange session based on the parameter.