6-(4-((R)-2-(azetidine-1-carbonyl)-4-(3-chloro-1H-indole-6-sulfonyl)-6-oxopiperazin-1-ylmethyl)-piperidin-1-yl)-2-methyl-2H-pyridazin-3-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 6-(4-((R)-2-(azetidine-1-carbonyl)-4-(3-chloro-1H-indole-6-sulfonyl)-6-oxopiperazin-1-ylmethyl)-piperidin-1-yl)-2-methyl-2H-pyridazin-3-one
• 英文别名: 6-[4-[[(2R)-2-(azetidine-1-carbonyl)-4-[(3-chloro-1H-indol-6-yl)sulfonyl]-6-oxopiperazin-1-yl]methyl]piperidin-1-yl]-2-methylpyridazin-3-one
• 化学式: C₂₇H₃₂ClN₇O₅S
• 分子量: 602.114
• InChiKey: NGMQWKMPIUIGIV-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(3-chloro-1H-indole-6-sulfonyl)-1-(1-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-piperidin-4-ylmethyl)-6-oxopiperazine-2-carboxylic acid methyl ester 在 lithium hydroxide 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.08h， 生成 6-(4-((R)-2-(azetidine-1-carbonyl)-4-(3-chloro-1H-indole-6-sulfonyl)-6-oxopiperazin-1-ylmethyl)-piperidin-1-yl)-2-methyl-2H-pyridazin-3-one 、 6-(4-((S)-2-(azetidine-1-carbonyl)-4-(3-chloro-1H-indole-6-sulfonyl)-6-oxopiperazin-1-ylmethyl)-piperidin-1-yl)-2-methyl-2H-pyridazin-3-one
  参考文献：
  名称：

  WO2007/8142

  摘要：

  公开号：

文献信息

• Heterocyclic Sulfonamide Derivatives As Inhibitors Of Factor Xa
  申请人：Alstermark Christer

  公开号：US20080221063A1

  公开（公告）日：2008-09-11

  The invention relates to heterocyclic derivatives of formula (I), Chemical formula should be inserted here. Please see paper copy wherein R 1 is hydrogen or C 1-3 alkyl; R 2 is selected from hydroxy, C 1-5 alkyl, carboxy, cyano, tetrazolyl, N—C 1-5 alkyltetrazolyl, oxazolyl, C 1-5 oxazolyl, isoxazolyl, C 1-5 isoxazolyl, hydroxyC 1-5 alkyl, carboxy C 1-5 alkyl, C 1-5 alkoxyoxo C 1-5 alkyl, carbamoyl, C 1-5 alkylcarbamoyl, di(C 1-5 alkyl)carbamoyl, C 1-5 alkylcarbamoyl C 1-4 alkyl, hydroxy C 1-5 alkylcarbamoyl, C 1-5 alkoxy C 1-5 alkylcarbamoyl; —C 1-5 alkyl-Y 1 , —COOCHR 17 R 18 and —CONR 17 R 18 ; and R 3 is hydrogen or halogen; or a pharmaceutically acceptable salt thereof, said compounds possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the compounds, to their use, to pharmaceutical compositions comprising them, to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect, and to combinations comprising them.

  本发明涉及式（I）的杂环衍生物，化学式应在此处插入。请参阅纸质副本，其中R1是氢或C1-3烷基；R2选自羟基，C1-5烷基，羧基，氰基，四唑基，N- C1-5烷基四唑基，噁唑基，C1-5噁唑基，异噁唑基，C1-5异噁唑基，羟基C1-5烷基，羧基C1-5烷基，C1-5烷氧氧代C1-5烷基，氨基甲酰基，C1-5烷基氨基甲酰基，二（C1-5烷基）氨基甲酰基，C1-5烷基氨基甲酰基C1-4烷基，羟基C1-5烷基氨基甲酰基，C1-5烷氧基C1-5烷基氨基甲酰基；-C1-5烷基-Y1，-COOCHR17R18和CONR17R18；以及R3是氢或卤素；或其药学上可接受的盐，这些化合物具有抗血栓和抗凝血性质，因此在人类或动物的治疗方法中有用。本发明还涉及制备该化合物的方法，它们的用途，包括它们的制药组合物，用于制造用于产生抗血栓或抗凝血效应的药物的制剂以及包含它们的组合物。
• Heterocyclic Sulfonamide Derivatives as Inhibitors of Factor Xa
  申请人：Alstermark Christer

  公开号：US20080200431A1

  公开（公告）日：2008-08-21

  The invention relates to compounds of formula (I), Chemical formula should be inserted here. Please see paper copy wherein R 1 , R 2 , R 3 and R 4 are independently selected from carbon and nitrogen, and where is nitrogen; A 1 is a single bond or a double bond; n is 0, 1, 2 or 3; each R 5 is independently selected from hydrogen, halogen, C 1-3 alkyl, oxo, oxy, oxido and thioxo; R 6 is hydrogen or oxo; m is 0, 1, 2 or 3; A 2 is a single bond or a double bond; each R 7 is independently selected from hydrogen, hydroxy, oxo, C 1-5 alkyl, carboxy, cyano, tetrazolyl, N—C 1-5 alkyltetrazolyl, oxazolyl, C 1-5 oxazolyl, isoxazolyl, C 1-5 isoxazolyl, hydroxyC 1-5 alkyl, carboxy C 1-5 alkyl, C 1-5 alkoxyoxo C 1-5 alkyl, carbamoyl, C 1-5 alkylcarbamoyl, di(C 1-5 alkyl)carbamoyl, carbamoyl C 1-4 alkyl, C 1-5 alkylcarbamoyl C 1-4 alkyl, di(C 1-5 alkyl)carbamoyl C 1-4 alkyl, hydroxy C 1-5 alkylcarbamoyl, C 1-5 alkoxy C 1-5 alkylcarbamoyl, hydroxy C 1-5 alkylcarbamoyl C 1-4 alkyl, C 1-5 alkoxy C 1-5 alkylcarbamoyl C 1-4 alkyl, —CONR 8 (CH 2 ) x S(O) p R 9 , —CONH(CH 2 ) q NR 10 R 11 , —C 1-5 alkyl-Y 1 , —COOCHR 17 R 18 and —CONR 17 R 18 ; and R 30 is hydrogen, amino, methyl or halogen; or a pharmaceutically acceptable salt thereof, said compounds possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the compounds, to their use, to pharmaceutical compositions comprising them, to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect, and to combinations comprising them.

  本发明涉及公式（I）的化合物，化学式应在此处插入。请参阅纸质副本，其中R1、R2、R3和R4独立地选择为碳和氮，其中氮；A1是单键或双键；n为0、1、2或3；每个R5独立地选择为氢、卤素、C1-3烷基、氧、氧化物、氧化物和硫代氧；R6是氢或氧；m为0、1、2或3；A2是单键或双键；每个R7独立地选择为氢、羟基、氧、C1-5烷基、羧基、氰基、四唑基、N- C1-5烷基四唑基、噁唑基、C1-5噁唑基、异噁唑基、C1-5异噁唑基、羟基C1-5烷基、羧基C1-5烷基、C1-5烷氧氧化C1-5烷基、氨基甲酰基、C1-5烷基甲酰基、二（C1-5烷基）甲酰基、氨基甲酰基C1-4烷基、C1-5烷基甲酰基C1-4烷基、二（C1-5烷基）甲酰基C1-4烷基、羟基C1-5烷基甲酰基、C1-5烷氧基C1-5烷基甲酰基、羟基C1-5烷基甲酰基C1-4烷基、C1-5烷氧基C1-5烷基甲酰基C1-4烷基、-CONR8（CH2）xS（O）pR9，-CONH（CH2）qNR10R11，-C1-5烷基-Y1，-COOCHR17R18和-CONR17R18；R30是氢、氨基、甲基或卤素；或其药学上可接受的盐，该化合物具有抗血栓和抗凝作用，因此在人或动物的治疗方法中有用。本发明还涉及制备该化合物的方法，它们的用途，包含它们的制药组合物，用于制造用于产生抗血栓或抗凝作用的药物的制剂的用途，以及包含它们的组合物。
• WO2007/8146
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2007/8142
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] HETEROCYCLIC SULFONAMIDE DERIVATIVES AS INHIBITORS OF FACTOR XA<br/>[FR] DÉRIVÉS DE SULFONAMIDES HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DU FACTEUR XA
  申请人：ASTRAZENECA AB

  公开号：WO2007008142A1

  公开（公告）日：2007-01-18

  [EN] The invention relates to heterocyclic derivatives of formula (I), Chemical formula should be inserted here. Please see paper copy wherein R¹ is hydrogen or C_1-3alkyl; R² is selected from hydroxy, C_1-5alkyl, carboxy, cyano, tetrazolyl, N-C_1-5alkyltetrazolyl, oxazolyl, C_1-5oxazolyl, isoxazolyl, C_1-5isoxazolyl, hydroxyC_1-5alkyl, carboxy C_1-5alkyl, C_1-5alkoxyoxo C_1-5alkyl, carbamoyl, C_1-5alkylcarbamoyl, di(C_1-5alkyl)carbamoyl, C_1-5alkylcarbamoyl C_1-4alkyl, hydroxy C_1-5alkylcarbamoyl, C_1-5alkoxy C_1-5alkylcarbamoyl; -C_1-5alkyl-Y¹, -COOCHR¹⁷ R¹⁸ and -CON R¹⁷ R¹⁸; and R³ is hydrogen or halogen; or a pharmaceutically acceptable salt thereof, said compounds possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the compounds, to their use, to pharmaceutical compositions comprising them, to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect, and to combinations comprising them.
  [FR] L'invention concerne des dérivés hétérocycliques de formule (I) [Formule chimique à insérer ici. Voir copie papier] dans laquelle R¹ est un hydrogène ou un alkyle en C_1-3 ; R² est sélectionné entre un hydroxy, un alkyle en C_1-5, un carboxy, un cyano, un tétrazolyle, un N-(alkyl en C_1-5)tétrazolyle, un oxazolyle, un oxazolyle en C_1-5, un isoxazolyle, un isoxazolyle en C_1-5, un hydroxy(alkyle en C_1-5), un carboxy(alkyle en C_1-5), un (alcoxy en C_1-5)oxo(alkyle en C_1-5), un carbamoyle, un (alkyl en C_1-5)carbamoyle, un di(alkyl en C_1-5)carbamoyle, un (alkyl en C_1-5)carbamoyl(alkyle en C_1-4), un hydroxy(alkyl en C_1-5)carbamoyle, un (alcoxy en C_1-5)(alkyl en C_1-5)carbamoyle ; un groupe -(alkyl en C_1-5)-Y¹, -COOCHR¹⁷R¹⁸ et -CONR¹⁷R¹⁸ ; et R³ est un hydrogène ou un halogène ; ou un sel acceptable du point de vue pharmaceutique de ceux-ci, lesdits composés possédant des propriétés antithrombotiques et anticoagulantes et étant par conséquent utiles dans des procédés de traitement d'êtres humains ou d'animaux. L'invention concerne également des procédés pour la préparation des composés, leur utilisation, des compositions pharmaceutiques les comprenant, leur utilisation dans la fabrication de médicaments destinés à être utilisés dans la production d'un effet antithrombotique ou anticoagulant et des combinaisons les comprenant.