1. A compound of formula (I):
wherein
each of R1 and R2, independently, is H or C1-C8 alkyl; each of R3 and R4, independently, is H or -A-N(B)-D; at most one of R3 and R4 being H; and
each of R5, R6, R7, and R8, independently, is H, C1-C8 alkyl, or halogen;
in which A is C1-C12 alkyl optionally containing 1-6 heteroatoms; B is H or C1-C8 alkyl;
and D is C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, aryl, heteroaryl, \u2014C(O)Ra, \u2014SO2Ra, \u2014C(\u2550N\u2014CN)\u2014SRa, \u2014C(\u2550N\u2014CN)\u2014NRaRa\u2032, or \u2014C(\u2550N\u2014C(O)NH2)\u2014SRa; or B and D together are C5-C7 heterocycloalkyl or heteroaryl; each of Ra and Ra\u2032, independently, being H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, C3-C8 heterocycloalkyl, C5-C8 heterocycloalkenyl, aryl, or heteroaryl;
or a salt thereof.
2. The compound of claim 1, wherein A is C1-C12 alkylcarbonyl containing 1-6 heteroatoms and substituted with arylsulfonyl.
3. The compound of claim 2, wherein D is C1-C8 alkyl, heteroaryl, or aryl optionally substituted with C1-C8 alkyl, heteroaryl, \u2014NO2, \u2014ORb, \u2014N(Rb)\u2014C(O)Rb\u2032, \u2014NRbRb\u2032, \u2014CO2Rb, \u2014C(O)\u2014NRbRb\u2032, \u2014C(O)Rb, \u2014SO2\u2014NRbRb\u2032, or \u2014SO2Rb; or D and B together are C5-C7 heterocycloalkyl; each of Rb and Rb\u2032, independently, being H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, C3-C8 heterocycloalkyl, C5-C8 heterocycloalkenyl, aryl, or heteroaryl.
4. The compound of claim 3, wherein the compound is one of compounds 1-16, 19-38, 47-51, 53, 54, 56-65, and 67-90.
5. The compound of claim 1, wherein A is C1-C12 alkyl optionally containing 1-6 heteroatoms and optionally substituted with arylsulfonyl.
6. The compound of claim 5, wherein D is \u2014C(O)Ra, \u2014SO2Ra, \u2014C(\u2550N\u2014CN)\u2014SRa, \u2014C(\u2550N\u2014CN)\u2014NRaRa\u2032, or \u2014C(\u2550N\u2014C(O)NH2)\u2014SRa.
7. The compound of claim 6, wherein the compound is one of compounds 17, 18, 39-46, 52, and 55.
8. A compound of formula (I):
wherein
each of R1 and R2, independently, is H or C1-C8 alkyl; or R1 and R2 together are cycloalkyl;
each of R3 and R4, independently, is H or -A-N(B)-D; at most one of R3 and R4 being H; and
one of R5, R6, R7, and R8 is C1-C8 alkyl; the other of R5, R6, R7, and R8, independtly, is H, C1-C8 alkyl, or halogen;
in which A is C1-C12 alkyl optionally containing 1-6 heteroatoms; B is H or C1-C8 alkyl; and D is C1-C8 alkyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, aryl, heteroaryl, \u2014C(O)Ra, \u2014SO2Ra, \u2014C(\u2550N\u2014CN)\u2014SRa, \u2014C(\u2550N\u2014CN)\u2014NRaRa\u2032, or \u2014C(\u2550N\u2014C(O)NH2)\u2014SRa; or B and D together are C5-C7 heterocycloalkyl or heteroaryl; each of Ra and Ra\u2032, independently, being H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, C3-C8 heterocycloalkyl, C5-C8 heterocycloalkenyl, aryl, or heteroaryl;
or a salt thereof.
9. The compound of claim 8, wherein A is C1-C12 alkylcarbonyl containing 1-6 heteroatoms and substituted with arylsulfonyl.
10. The compound of claim 9, wherein D is aryl optionally substituted with \u2014ORb, or \u2014C(O)\u2014NRbRb\u2032; each of Rb and Rb\u2032, independently, being H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, C3-C8 heterocycloalkyl, C5-C8 heterocycloalkenyl, aryl, or heteroaryl.
11. The compound of claim 10, wherein the compound is compound 66.
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 method for measuring pulse wave velocity through an artery, comprising:
obtaining an image of the artery;
generating from the image a model of the artery;
selecting two reference points along the artery, such two reference points being separated a predetermined distance, D;
observing a change in the model at a first one of the two reference points and a corresponding change in the model at a second one of the two reference points along with a time difference T between the observed changes;
estimating the pulse wave velocity, PWV, in accordance with PWV=DT.
2. The method recited in claim 1 wherein the change is a sudden expansion of the artery along a path between the two reference points.
3. The method recited in claim 2 wherein the expansion is observed as an upslope in an artery diameter curve at each of the two reference points.
4. The method recited in claim 3 wherein the reference points are disposed along diameters of the artery.
5. The method recited in claim 4 wherein the reference points are disposed along centerlines of the artery.
6. The method recited in claim 5 wherein the onset of the radius increase in the artery is tracked using a quadratic sub-frame interpolation scheme.
7. The method recited in claim 1 wherein the distance is derived directly from the model by integrating the centerline length of the centerline of the artery between the two reference points.