IS-741 | 141283-87-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: IS-741
• 英文别名: N-(2-ethylsulfonylamino-5-trifluoromethyl-pyridin-3-yl)cyclohexanecarboxamide；N-(2-ethylsulfonylamino-5-trifluoromethyl-3-pyridyl)cyclohexanecarboxamide；N-(2-ethylsulfonylamino-5-trifluoromethyl-3-pyridyl)cylohexanecarboxamide；Fuzapladib；N-[2-(ethylsulfonylamino)-5-(trifluoromethyl)pyridin-3-yl]cyclohexanecarboxamide
• CAS: 141283-87-6
• 化学式: C₁₅H₂₀F₃N₃O₃S
• 分子量: 379.403
• InChiKey: TUWCZRFHNIOVTC-UHFFFAOYSA-N

物化性质

• 密度：
  1.411±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  96.5
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氯-5-三氟甲基吡啶 在 硝酸 、 铁粉 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 溶剂黄146 、 二甲基亚砜 为溶剂， 反应 14.0h， 生成 IS-741
  参考文献：
  名称：

  新型N-（2-磺酰基氨基-5-三氟甲基-3-吡啶基）羧酰胺衍生物作为磷脂酶A2抑制剂的合成及其抗胰腺炎活性。

  摘要：

  已经制备了新的N-（2-磺酰基氨基-5-三氟甲基-3-吡啶基）羧酰胺衍生物，并将其评估为磷脂酶A2（PLA2）抑制剂。在这些化合物中，将IS-741（1j的钠盐）对大鼠通过闭合十二指肠环法诱发的急性出血性胰腺炎显示出最高和最稳定的治疗效果，作为进一步开发的候选药物。

  DOI：

  10.1248/cpb.43.1696

文献信息

• [EN] PHARMACEUTICAL COMPOSITIONS WITH IMPROVED DISSOLUTION<br/>[FR] COMPOSITIONS PHARMACEUTIQUES A DISSOLUTION AMELIOREE
  申请人：TRANSFORM PHARMACEUTICALS INC

  公开号：WO2004000284A1

  公开（公告）日：2003-12-31

  The invention relates to methods of screening mixtures containing a pharmaceutical compound an excipient to identify properties of the pharmaceutical compound/excipient combination that retard solid-state nucleation. The invention further relates to increasing the solubility, dissolution and bioavailability of a drug with low solubility in gastric fluids conditions by combining the drug with a recrystallization/precipitation retardant and an optional enhancer.

  本发明涉及筛选包含药物化合物和赋形剂的混合物的方法，以识别延缓固态成核的药物化合物/赋形剂组合的特性。该发明还涉及通过将药物与再结晶/沉淀抑制剂和可选增效剂结合，来增加低溶解度药物在胃液条件下的溶解度、溶出性和生物利用度。
• Pharmaceutical compositions with improved dissolution
  申请人：Tawa Mark

  公开号：US20060134198A1

  公开（公告）日：2006-06-22

  The invention relates to methods of screening mixtures containing a pharmaceutical compound and an excipient to identify properties of the pharmaceutical compound/excipient combination that retard solid-state nucleation. The invention further relates to increasing the solubility, dissolution and bioavailability of a drug with low solubility in gastric fluids conditions by combining the drug with a precipitation retardant and an optional enhancer.

  本发明涉及筛选混合物的方法，该混合物含有药物化合物和赋形剂，以识别药物化合物/赋形剂组合的性质，以延缓固态成核。本发明还涉及通过将药物与沉淀抑制剂和可选增效剂结合，在胃液条件下增加低溶解度药物的溶解度、溶出度和生物利用度的方法。
• Diaminotrifluoromethylpyridine derivatives and phospholipase A.sub.2
  申请人：Ishihara Sangyo Kaisha Ltd.

  公开号：US05229403A1

  公开（公告）日：1993-07-20

  A diaminotrifluoromethylpyridine derivative of the formula (I) or its salt: ##STR1## wherein X is --CW.sup.1 R.sup.1, --COCOR.sup.2, --CW.sup.1 NHCOR.sup.2, --C(.dbd.W.sup.1 (W.sup.2 W.sup.3 or --CW.sup.1 N(R.sup.4)R.sup.5, and Y is alkyl, --CW.sup.3 R.sup.6, --COCOR.sup.7, --NHCOR.sup.7, --C(.dbd.W.sup.3)W.sup.4 R.sup.8, --(NH).sub.m SO.sub.2 R.sup.9, --(NH).sub.m SO.sub.2 OR.sup.10 or --(NH).sub.m SO.sub.2 N R.sup.11)R.sup.12, wherein each of R.sup.1, R.sup.6 and R.sup.9, which are independent from one another, is a chain hydrocarbon group which may be substituted, a monocyclic hydrocarbon group which may be substituted, a polycyclic hydrocarbon group which may be substituted, a monocyclic heterocycle group which may be substituted or a polycyclic heterocycle group which may be substituted, each of R.sup.2 and R.sup.7, which are independent from each other, is alkyl which may be substituted, alkoxy which may be substituted, phenyl which may be substituted or phenoxy which may be substituted, each of R.sup.3, R.sup.8 and R.sup.10, which are independent from one another, is alkyl which may be substituted, alkenyl which may be substituted, alkynyl which may be substituted, cycloalkyl which may be substituted, phenyl which may be substituted or benzyl which may be substituted, each of R.sup.4, R.sup.5, R.sup.11 and R.sup.12, which are independent from one another, is alkyl which may be substituted, each of W.sup.1, W.sup.2, W.sup.3 and W.sup.4, which are independent from one another, is an oxygen atom or a sulfur atom, and m is 0 or 1, provided that a combination wherein one of X and Y is --COCF.sub.2 X.sup.1 wherein X.sup.1 is a hydrogen atom, a halogen atom, alkyl or haloalkyl, and the other is --COCF.sub.2 X.sup.2 wherein X.sub.2 is a hydrogen atom, a halogen atom, alkyl, haloalkyl or alkylcarbonyl, or --COOX.sup.3 wherein X.sup.3 is alkyl which may be substituted or phenyl which may be substituted, is excluded.

  化合物的名称为一种二氟甲基吡啶二胺衍生物的盐，其化学式为（I）：##STR1## 其中X为--CW.sup.1 R.sup.1，--COCOR.sup.2，--CW.sup.1 NHCOR.sup.2，--C(.dbd.W.sup.1(W.sup.2W.sup.3或--CW.sup.1 N(R.sup.4)R.sup.5，Y为烷基，--CW.sup.3 R.sup.6，--COCOR.sup.7，--NHCOR.sup.7，--C(.dbd.W.sup.3)W.sup.4 R.sup.8，--(NH).sub.m SO.sub.2 R.sup.9，--(NH).sub.m SO.sub.2 OR.sup.10或--(NH).sub.m SO.sub.2 NR.sup.11)R.sup.12，其中每个独立的R.sup.1，R.sup.6和R.sup.9是链烃基，可以被取代的单环烃基，可以被取代的多环烃基，可以被取代的单环杂环基或可以被取代的多环杂环基，每个独立的R.sup.2和R.sup.7是可以被取代的烷基，可以被取代的烷氧基，可以被取代的苯基或可以被取代的苯氧基，每个独立的R.sup.3，R.sup.8和R.sup.10是可以被取代的烷基，可以被取代的烯基，可以被取代的炔基，可以被取代的环烷基，可以被取代的苯基或可以被取代的苄基，每个独立的R.sup.4，R.sup.5，R.sup.11和R.sup.12是可以被取代的烷基，每个独立的W.sup.1，W.sup.2，W.sup.3和W.sup.4是氧原子或硫原子，m为0或1，但其中X和Y之一为--COCF.sub.2X.sup.1，其中X.sup.1为氢原子，卤原子，烷基或卤代烷基，另一个为--COCF.sub.2X.sup.2，其中X.sub.2为氢原子，卤原子，烷基，卤代烷基或烷基羰基，或--COOX.sup.3，其中X.sup.3是可以被取代的烷基或可以被取代的苯基。
• Diaminotrifluoromethylpyridine derivatives, process for their production
  申请人：Ishihara Sangyo Kaisha Ltd.

  公开号：US05492908A1

  公开（公告）日：1996-02-20

  A method of treating rheumatoid arthritis using a diaminotrifluoromethylpyridine derivative of the formula (I) or its salt: ##STR1## wherein X is --CW.sup.1 R.sup.1, --COCOR.sup.2, --CW.sup.1 NHCOR.sup.2, --C(.dbd.W.sup.1)W.sup.2 R.sup.3 or --CW.sup.1 N(R.sup.4)R.sup.5, and Y is alkyl, --CW.sup.3 R.sup.6, --COCOR.sup.7, --NHCOR.sup.7, --C(.dbd.W.sup.3)W.sup.4 R.sup.8, --(NH).sub.m SO.sub.2 R.sup.9, --(NH).sub.m SO.sub.2 OR.sup.10 or --(NH).sub.m SO.sub.2 N(R.sup.11)R.sup.12, wherein each of R.sup.1, R.sup.6 and R.sup.9, which are independent from one another, is a chain hydrocarbon group which may be substituted, a monocyclic hydrocarbon group which may be substituted, a polycyclic hydrocarbon group which may be substituted, a monocyclic heterocycle group which may be substituted or a polycyclic heterocycle group which may be substituted as further defined herein.

  使用公式（I）或其盐的二氨基三氟甲基吡啶衍生物治疗类风湿性关节炎的方法： 其中X为--CW1R1，--COCOR2，--CW1NHCOR2，--C(.dbd.W1)W2R3或--CW1N(R4)R5，Y为烷基，--CW3R6，--COCOR7，--NHCOR7，--C(.dbd.W3)W4R8，--(NH)mSO2R9，--(NH)mSO2OR10或--(NH)mSO2N(R11)R12，其中R1，R6和R9分别是独立的链烃基，可以被取代的单环烃基，可以被取代的多环烃基，可以被取代的单环杂环基或可以被取代的多环杂环基，如此处进一步定义。
• Diaminotrifluoromethylpyridine compounds and phospholipase A.sub.2
  申请人：Ishihara Sangyo Kaisha Ltd.

  公开号：US05260320A1

  公开（公告）日：1993-11-09

  A diaminotrifluoromethylpyridine derivative of the formula (I) or its salt: ##STR1## wherein X is --CW.sup.1 R.sup.1, --COCOR.sup.2, --CW.sup.1 NHCOR.sup.2, --C(.dbd.W.sup.1)W.sup.2 R.sup.3 or --CW.sup.1 N(R.sup.4)R.sup.5, and Y is alkyl, --CW.sup.3 R.sup.6, --COCOR.sup.7, --NHCOR.sup.7, --C(.dbd.W.sup.3)W.sup.4 R.sup.8, --(NH).sub.m SO.sub.2 R.sup.9, --(NH).sub.m SO.sub.2 OR.sup.10 or --(NH).sub.m SO.sub.2 N(R.sup.11)R.sup.12, wherein each of R.sup.1, R.sup.6 and R.sup.9, which are independent from one another, is a chain hydrocarbon group which may be substituted, a monocyclic hydrocarbon group which may be substituted, a polycyclic hydrocarbon group which may be substituted, a monocyclic heterocycle group which may be substituted or a polycyclic heterocycle group which may be substituted, each of R.sup.2 and R.sup.7, which are independent from each other, is alkyl which may be substituted, alkoxy which may be substituted, phenyl which may be substituted or phenoxy which may be substituted, each of R.sup.3, R.sup.8 and R.sup.10, which are independent from one another, is alkyl which may be substituted, alkenyl which may be substituted, alkynyl which may be substituted, cycloalkyl which may be substituted, phenyl which may be substituted or benzyl which may be substituted, each of R.sup.4, R.sup.5, R.sup.11 and R.sup.12, which are independent from one another, is alkyl which may be substituted, each of W.sup.1, W.sup.2, W.sup.3 and W.sup.4, which are independent from one another, is an oxygen atom or a sulfur atom, and m is 0 or 1, provided that a combination wherein one of X and Y is --COCF.sub.2 X.sup.1 wherein X.sup.1 is a hydrogen atom, a halogen atom, alkyl or haloalkyl, and the other is --COCF.sub.2 X.sup.2 wherein X.sup.2 is a hydrogen atom, a halogen atom, alkyl, haloalkyl or alkylcarbonyl, or --COOX.sup.3 wherein X.sup.3 is alkyl which may be substituted or phenyl which may be substituted, is excluded.

  一种公式（I）或其盐的二氨基三氟甲基吡啶衍生物：##STR1## 其中X是--CW.sup.1 R.sup.1，--COCOR.sup.2，--CW.sup.1 NHCOR.sup.2，--C（.dbd.W.sup.1）W.sup.2 R.sup.3或--CW.sup.1 N（R.sup.4）R.sup.5，而Y是烷基，--CW.sup.3 R.sup.6，--COCOR.sup.7，--NHCOR.sup.7，--C（.dbd.W.sup.3）W.sup.4 R.sup.8，--（NH）.sub.m SO.sub.2 R.sup.9，--（NH）.sub.m SO.sub.2 OR.sup.10或--（NH）.sub.m SO.sub.2 N（R.sup.11）R.sup.12，其中R.sup.1，R.sup.6和R.sup.9互相独立，分别是链烃基，可取代的单环烃基，可取代的多环烃基，可取代的单环杂环基或可取代的多环杂环基，R.sup.2和R.sup.7互相独立，分别是可取代的烷基，可取代的烷氧基，可取代的苯基或可取代的苯氧基，R.sup.3，R.sup.8和R.sup.10互相独立，分别是可取代的烷基，可取代的烯基，可取代的炔基，可取代的环烷基，可取代的苯基或可取代的苄基，R.sup.4，R.sup.5，R.sup.11和R.sup.12互相独立，分别是可取代的烷基，W.sup.1，W.sup.2，W.sup.3和W.sup.4互相独立，分别是氧原子或硫原子，m为0或1，但排除其中一个X和Y是--COCF.sub.2X.sup.1，其中X.sup.1是氢原子，卤素原子，烷基或卤代烷基，另一个是--COCF.sub.2X.sup.2，其中X.sup.2是氢原子，卤素原子，烷基，卤代烷基或烷基羰基，或--COOX.sup.3，其中X.sup.3是可取代的烷基或可取代的苯基的组合。