S 9788 | 140945-01-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: S 9788
• 英文别名: S9788；1-[4,6-bis(allylamino)-2-s-triazinyl]-4-[2,2-bis(p.fluorophenyl)ethylamino]piperidine；S-9788；6-(4-(2,2-di(4-Fluorophenyl)ethylamino)-1-piperidinyl)-N,N'-di-2-propenyl-1,3,5-triazine-2,4-diamine；6-[4-[2,2-bis(4-fluorophenyl)ethylamino]piperidin-1-yl]-2-N,4-N-bis(prop-2-enyl)-1,3,5-triazine-2,4-diamine
• CAS: 140945-01-3
• 化学式: C₂₈H₃₃F₂N₇
• 分子量: 505.614
• InChiKey: GERNFWKTMKWULM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  78
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(N-L-γ-谷氨酰基-S-亚硝基-L-半胱氨酰----甘氨酸 、 维拉帕米 、 cyclosporin A 、 S 9788 、 (+)-L-660,711 、 谷胱甘肽 、 、 、 、 、 、 Glycyl carboxylate 、 、 在 N-methyl 、 维拉帕米 作用下， 以 乙醇 为溶剂， 生成 壬酸
  参考文献：
  名称：

  MANIPULATING NITROSATIVE STRESS TO KILL PATHOLOGIC MICROBES, PATHOLOGIC HELMINTHS AND PATHOLOGICALLY PROLIFERATING CELLS OR TO UPREGULATE NITROSATIVE STRESS DEFENSES

  摘要：

  哺乳动物被用于治疗感染或与病理性增殖的哺乳动物细胞生长有关的疾病（例如某些癌症、再狭窄、良性前列腺肥大），通过给予一种硝化应激的调节剂，以选择性地杀死或减少引起感染的微生物或线虫或被微生物感染的宿主细胞或病理性增殖的哺乳动物细胞的生长。新型药剂包括α-烷基-S-烷基-同型半胱氨酸磺酰亚胺，其中α-烷基含有2至8个碳原子，S-烷基含有1至10个碳原子。在本发明的另一个方案中，需要增强硝化应激防御的哺乳动物被治疗，例如因为曾经有过短暂性缺血性发作而有中风风险的人类被治疗。增强硝化应激防御的治疗包括例如重复给予硝化应激调节剂的低剂量，以使受治疗的对象对硝化应激有增强的耐受性。在另一个发明中，哺乳动物通过系统给药L-丁硫氨酸-S-磺酰亚胺和增加硝化应激的药剂来治疗原虫感染。

  公开号：

  US20030096870A1
• 作为产物：
  描述：

  4,4-二乙氧基哌啶 在 盐酸 、 3 A molecular sieve 、 sodium cyanoborohydride 作用下， 以 甲醇 、 正丁醇 为溶剂， 反应 31.0h， 生成 S 9788
  参考文献：
  名称：

  New triazine derivatives as potent modulators of multidrug resistance

  摘要：

  A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5-mu-M in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the TIC by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.

  DOI：

  10.1021/jm00091a017

文献信息

• Manipulating nitrosative stress to kill pathologic microbes, pathologic helminths and pathologically proliferating cells or to upregulate nitrosative stress defenses
  申请人：——

  公开号：US20030207815A1

  公开（公告）日：2003-11-06

  Mammals are treated for infections or for conditions associated with pathologically proliferating mammalian cell growth (for example certain cancers, restenosis, benign prostatic hypertrophy) by administration of a manipulator of nitrosative stress to selectively kill or reduce the growth of the microbes or helminths causing the infection or of host cells infected with the microbes or of the pathologically proliferating mammalian cells. Novel agents include &agr;-alkyl-S-alkyl-homocysteine sulfoximines wherein the &agr;-alkyl contains 2 to 8 carbon atoms, and the S-alkyl-contains 1 to 10 carbon atoms. In another invention herein, mammals in need of increased nitrosative stress defenses are treated, e.g., humans at risk for a stroke because of having had a transient ischemic attack, are treated. Treatments to increase nitrosative stress defenses include, for example, repeated administrations of low doses of manipulators of nitrosative stress so that the subject treated has increased tolerance to nitrosative stress. In still another invention, mammals are treated for protozoal infections by systemic administration of L-buthionine-S-sulfoximine and agent that increases nitrosative stress.

  哺乳动物被治疗感染或与病理增殖哺乳动物细胞生长相关的情况（例如某些癌症，再狭窄，良性前列腺增生）通过给予一种硝化应激调节剂，以选择性地杀死或减少微生物或蠕虫引起的感染或受微生物感染的宿主细胞或病理增殖的哺乳动物细胞的生长。新型药剂包括α-烷基-S-烷基-同型半胱氨酸亚砜，其中α-烷基含2至8个碳原子，S-烷基含1至10个碳原子。在本发明的另一种方法中，需要增加硝化应激防御的哺乳动物被治疗，例如，由于患有短暂性缺血性发作而处于中风风险的人类被治疗。增加硝化应激防御的治疗包括例如反复给予低剂量的硝化应激调节剂，以使受治疗的对象对硝化应激具有增加的耐受性。在另一种发明中，哺乳动物通过系统给药L-丁硫氧嘧啶和增加硝化应激的药物来治疗原虫感染。
• Manipulating nitrosative stress to kill pathologic microbes, pathologic
  申请人：Duke University

  公开号：US06057367A1

  公开（公告）日：2000-05-02

  Mammals are treated for infections or for conditions associated with pathologically proliferating mammalian cell growth (for example, certain cancers, restenosis, benign prostatic hypertrophy) by administration of a manipulator of nitrosative stress to selectively kill or reduce the growth of the microbes or helminths causing the infection or of host cells infected with the microbes or of the pathologically proliferating mammalian cells. Novel agents include .alpha.-alkyl-S-alkyl-homocysteine sulfoximines wherein the .alpha.-alkyl contains 2 to 8 carbon atoms, and the S-alkyl-contains 1 to 10 carbon atoms. In another invention herein, mammals in need of increased nitrosative stress defenses are treated, e.g., humans at risk for a stroke because of having had a transient ischemic attack, are treated. Treatments to increase nitrosative stress defenses include, for example, repeated administrations of low doses of manipulators of nitrosative stress so that the subject treated has increased tolerance to nitrosative stress. In still another invention, mammals are treated for protozoal infections by systemic administration of L-buthionine-S-sulfoximine and agent that increases nitrosative stress.

  哺乳动物可以通过给予一种氮化应激的调节剂来治疗感染或与病理性增殖的哺乳动物细胞生长相关的疾病（例如某些癌症、再狭窄、良性前列腺增生），以选择性地杀死或减少导致感染的微生物或寄生虫或者感染微生物的宿主细胞或病理性增殖的哺乳动物细胞的生长。新型药物包括α-烷基-S-烷基-同型半胱氨酸亚磺酰胺，其中α-烷基含有2至8个碳原子，而S-烷基含有1至10个碳原子。在另一项发明中，需要增强氮化应激防御的哺乳动物得到了治疗，例如，因为曾经发生过短暂性缺血性发作而有中风风险的人类得到了治疗。增加氮化应激防御的治疗方法包括，例如，反复给予低剂量的氮化应激调节剂，以使接受治疗的受试者对氮化应激具有增加的耐受性。在另一项发明中，哺乳动物通过全身给药L-丁硫氨酸-S-亚磺酰胺和增加氮化应激的药物来治疗原虫感染。
• Manipulating nitrosative stress to upregulate nitrosative stress defenses
  申请人：Duke University

  公开号：US06359004B1

  公开（公告）日：2002-03-19

  Mammals are treated for infections or for conditions associated with pathologically proliferating mammalian cell growth (for example, certain cancers, restenosis, benign prostatic hypertrophy) by administration of a manipulator of nitrosative stress to selectively kill or reduce the growth of the microbes or helminths causing the infection or of host cells infected with the microbes or of the pathologically proliferating mammalian cells. Novel agents include &agr;-alkyl-S-alkyl-homocysteine sulfoximines wherein the &agr;-alkyl contains 2 to 8 carbon atoms, and the S-alkyl- contains 1 to 10 carbon atoms. In another invention herein, mammals in need of increased nitrosative stress defenses are treated, e.g., humans at risk for a stroke because of having had a transient ischemic attack, are treated. Treatments to increase nitrosative stress defenses include, for example, repeated administrations of low doses of manipulators of nitrosative stress so that the subject treated has increased tolerance to nitrosative stress. In still another invention, mammals are treated for protozoal infections by systemic administration of L-buthionine-S-sulfoximine and agent that increases nitrosative stress.

  哺乳动物因感染或与病理增殖的哺乳动物细胞生长相关的情况（例如某些癌症，再狭窄，良性前列腺增生）而接受处理，通过给予一种硝化应激的调节剂来选择性地杀死或减少引起感染的微生物或蠕虫，或感染微生物的宿主细胞或病理增殖的哺乳动物细胞的生长。新型药物包括α-烷基-S-烷基-同型半胱氨酸亚磺酰胺，其中α-烷基含2至8个碳原子，S-烷基含1至10个碳原子。在另一项发明中，需要增加硝化应激防御的哺乳动物得到治疗，例如因为出现短暂性缺血性发作而有中风风险的人类得到治疗。增加硝化应激防御的治疗包括，例如，重复给予低剂量的硝化应激调节剂，使接受治疗的对象对硝化应激具有增加的耐受性。在另一项发明中，哺乳动物因原虫感染而接受系统性的L-丁硫氨酸-S-亚磺酰胺和增加硝化应激的药物的治疗。
• Use of CNS penetrating anticancer compounds for the treatment of protozan diseases
  申请人：Dormeyer, Matthias

  公开号：EP1808173A1

  公开（公告）日：2007-07-18

  The present invention relates to the treatment of protozoal diseases by administering cytotoxic and/or cytostatic compounds, in particular those used in anticancer therapy, to patients. In particular, the invention relates to the use of anticancer agents that can penetrate into the CNS for treatment of late stage African sleeping sickness or cerebral malaria.

  本发明涉及通过向患者施用细胞毒性和/或细胞抑制化合物，特别是用于抗癌治疗的化合物来治疗原生动物疾病。特别是，本发明涉及使用可渗透到中枢神经系统的抗癌剂来治疗晚期非洲昏睡病或脑疟疾。
• Novel ABCA9 transporter and uses thereof
  申请人：Active Pass Pharmaceuticals, Inc.

  公开号：US20020123106A1

  公开（公告）日：2002-09-05

  The invention provides isolated nucleic acid molecules, designated ABCA9 transporter nucleic acid molecules, which encode novel ABC transporter family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing ABCA9 transporter nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which an ABCA9 transporter gene has been introduced or disrupted. The invention further provides isolated ABCA9 transporter proteins, fusion proteins, antigenic peptides, anti-ABCA9 transporter antibodies, and screening assays for ABCA9 transporter modulators. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

  本发明提供了编码新型 ABC 转运体家族成员的分离核酸分子，命名为 ABCA9 转运体核酸分子。本发明还提供了反义核酸分子、含有 ABCA9 转运体核酸分子的重组表达载体、导入表达载体的宿主细胞以及导入或破坏了 ABCA9 转运体基因的非人类转基因动物。本发明进一步提供了分离的 ABCA9 转运体蛋白、融合蛋白、抗原肽、抗 ABCA9 转运体抗体以及 ABCA9 转运体调节剂的筛选测定。还提供了利用本发明组合物的诊断和治疗方法。