CN107849073A - 具有增加的生物利用度的阿伏西地前药 - Google Patents
具有增加的生物利用度的阿伏西地前药 Download PDFInfo
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- CN107849073A CN107849073A CN201680028628.XA CN201680028628A CN107849073A CN 107849073 A CN107849073 A CN 107849073A CN 201680028628 A CN201680028628 A CN 201680028628A CN 107849073 A CN107849073 A CN 107849073A
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/453—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
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- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
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- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
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- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
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Abstract
Description
参数 | 数值 | SD |
C0(ng/mL) | 270.3 | 48.6 |
AUCin(hr·ng/mL) | 135.6 | 21.1 |
AUC0-t(hr·ng/mL) | 129.9 | 22.8 |
AUCin/AUC0-t(%) | 104.6 | 2.3 |
Vd(L/kg) | 17.50 | 1.93 |
CLp(L/hr/kg) | 7.5 | 1.1 |
Vdss(L/kg) | 17.71 | 10.08 |
MRTin(hr) | 2.5 | 1.8 |
t1/2(hr) | 1.6 | 0.4 |
参数 | 数值 | SD |
Cmax(ng/mL) | 178.6 | 47 |
Tmax(hr) | 2.92 | 4.4 |
AUCin(hr·ng/mL) | 1280.5 | 194 |
AUC0-t(h·ng/mL) | 1241.2 | 185 |
AUCin/AUC0-t(%) | 103.2 | 0.8 |
生物利用度(%) | 99.03 | 30.2 |
t1/2(hr) | 4.40 | 0.5 |
时间(hr) | IV(ng/mL) | SD | PO(ng/mL) | SD |
0.083 | 429.6 | 144.0 | # | # |
0.25 | 82.0 | 6.6 | 30.0 | 9.7 |
0.50 | 24.6 | 4.2 | 20.4 | 6.6 |
1.00 | 9.3 | 2.8 | 9.3 | 0.4 |
2.00 | BQL | - | BQL | - |
4.00 | BQL | - | BQL | - |
6.00 | BQL | - | BQL | - |
8.00 | BQL | - | BQL | - |
24.00 | BQL | - | BQL | - |
化合物IB′的剂量 | 肿瘤生长抑制(%) |
媒介物(即不含化合物IB′) | 0 |
7.5mg/kg | 69 |
2..5mg/kg | 12 |
7.5mg/kg,q7dx3 | 74 |
化合物IB′的剂量 | MCL-1表达的减少(%) |
媒介物(即不含化合物IB′) | 0.0 |
2.5mg/kg | 54 |
0.5mg/kg | 61 |
0.1mg/kg | 46 |
0.02mg/kg | 0.0 |
Claims (23)
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CN113490499A (zh) * | 2018-12-04 | 2021-10-08 | 大日本住友制药肿瘤公司 | 用作治疗癌症的活性剂的cdk9抑制剂及其多晶型物 |
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