- 英文名称
- Ramatroban
- 分子式
- C21H21FN2O4S
- 分子量
- 416.47
- 中文别名
- (R)-3-(3-(4-氟苯基磺酰胺基)-3,4-二氢-1H-咔唑-9(2H)-基)丙酸; 3R-(4-氟苯磺酰氨基)-1,2,3,4-四氢化-9H-咔唑-9-丙酸; 3R-[[(4-氟苯基)磺酰]氨基]-1,2,3,4-四氢-9H-咔唑-9-丙酸; 雷马曲斑; (R)-3-(3-(4-Fluorophenylsulfonamido)-3,4-dihydro-1H-carbazol-9(2H)-yl)propanoic acid; BAY U3405; BAY-U3405; CS-1350; 3R-[[(4-Fluorophenyl)sulfonyl]amino]-1,2,3,4-tetrahydro-9H-carbazole-9-propanoic acid; (3R)-3-[[(4-Fluorophenyl)sulfonyl]amino]-1,2,3,4-tetrahydro-9H-carbazole-9-propionic acid; 3-[(3R)-3-(4-Fluorophenylsulfonylamino)-1,2,3,4-tetrahydro-9H-carbazole-9-yl]propionic acid; 3-[(3R)-3-{[(4-Fluorophenyl)sulfonyl]amino}-1,2,3,4-tetrahydro-9H-carbazol-9-yl]propanoic acid; BAY u 3405; (+)-(3R)-3-(p-Fluorobenzenesulfonamido)-1,2,3,4-tetrahydrocarbazole-9-propionic acid; Baynas; 3-((3R)-3-(((4-Fluorophenyl)sulfonyl)amino)-1,2,3,4-tetrahydro-9H-carbazol-9-yl)propanoic Acid; BAY u-3405; 3-[(3R)-3-[(4-fluorophenyl)sulfonylamino]-1,2,3,4-tetrahydrocarbazol-9-yl]propanoic acid
- 用途
- - TP抑制剂
雷马曲班由德国拜耳公司研制，是作为抗心血管疾病药物开发的TP抑制剂，与日本新药株式会社合作在日本推广上市。仅在日本被批准为治疗哮喘和过敏性鼻炎的药物。
- 生物活性
Ramatroban 是一种选择性血栓素 A2 (TxA2，IC50=14 nM) 拮抗剂。Ramatroban 还通过抑制 PGD2 结合从而拮抗 CRTH2 (IC50=113 nM)。
- 靶点
Target
Value
TxA2 receptor
()
- 体外研究
Ramatroban is a potent human thromboxane receptor (hTP) antagonist with an IC
50
of 18 nM in a human TP binding assay. Ramatroban inhibits prostaglandin D
2
receptor DP2 (CRTH2) with an IC
50
of 113 nM in a human DP2 binding assay. Ramatroban also inhibits human CYP isoform CYP2C9 with an IC
50
of 15 μM. Ramatroban is a selective thromboxane-type prostanoid (TP) receptor antagonist. PGD
2
-stimulated human eosinophil migration is shown to be mediated exclusively through activation of CRTH2, and surprisingly, these effects are completely inhibited by Ramatroban. Ramatroban is an antagonist for CRTH2, and inhibits PGD
2
-induced migration of eosinophils via CRTH2 blockade.
3
H-labeled PGD
2
binds to a single site on CRTH2 transfectants with high affinity (K
D
=6.3 nM, B
max
=450 pM). Nonlabeled PGD
2
inhibits the binding of
3
H-labeled PGD
2
to CRTH2 transfectants in a concentration-dependent manner with an EC
50
value of 2.7 nM. Ramatroban shows significant inhibitory effects on the binding of
3
H-labeled PGD
2
to CRTH2, albeit with much lower potency (IC
50
=100 nM). Ramatroban also inhibits PGD
2
-induced Ca
2+
mobilization in CRTH2 transfectants to almost the same extent with an IC
50
value of 30 nM. Ramatroban completely inhibits the PGD
2
-induced migration of eosinophils in a concentration-dependent manner with an IC
50
value of 170 nM.
- 体内研究
Ramatroban is an orally bioavailable small molecule antagonist of CRTH2. Systemic administration of Ramatroban (30 mg/kg) in CRTH2
+/+
mice produces the same effects as seen in CRTH2 deficiency. Ramatroban completely blocks LPS-induced decreases in social and object exploratory behavior (p<0.01). In addition, tumor-impaired social interaction and object exploratory behavior in CRTH2
+/+
mice are completely reversed by a single injection of Ramatroban, even when the tumor is enlarged.
- 雷马曲班为高效的选择性TxA2/PGH2受体拮抗剂，可与平滑肌和血小板的TxA2受体特异性结合。雷马曲班的抗过敏反应基于抑制血管通透性和鼻粘膜高敏性及防止其它炎性反应发生。用于过敏性鼻炎。
