methyl 2-(methylsulfonyl)-pyrimidine-4-carboxylate | 503072-46-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: methyl 2-(methylsulfonyl)-pyrimidine-4-carboxylate
• 英文别名: 2-methanesulfonyl-pyrimidin-4-carboxylic acid methyl ester；2-methanesulfonyl-pyrimidine-4-carboxylic acid methyl ester；methyl 2-methylsulfonylpyrimidine-4-carboxylate
• CAS: 503072-46-6
• 化学式: C₇H₈N₂O₄S
• 分子量: 216.218
• InChiKey: NWDADIBYIHDSHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  94.6
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  (+/-)-4-((5S,9R)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-9-yl)benzonitrile 、 methyl 2-(methylsulfonyl)-pyrimidine-4-carboxylate 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以28%的产率得到methyl 2-((5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)pyrimidine-4-carboxylate
  参考文献：
  名称：

  Small Molecule Antagonist of Leukocyte Function Associated Antigen-1 (LFA-1): Structure−Activity Relationships Leading to the Identification of 6-((5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)nicotinic Acid (BMS-688521)

  摘要：

  Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or alpha(L)beta(2), belongs to the beta(2) integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellular adhesion molecules 1, 2, and 3 (ICAM 1, 2, and 3). The interactions between LFA-1 and the ICAMs are critical for cell adhesion, and preclinical animal studies and clinical data from the humanized anti-LFA-1 antibody efalizumab have provided proof-of-concept for LFA-1 as an immunological target. This article will detail the structure activity relationships (SAR) leading to a novel second generation series of highly potent spirocyclic hydantoin antagonists of LFA-1. With significantly enhanced in vitro and ex vivo potency relative to our first clinical compound (1), as well as demonstrated in vivo activity and an acceptable pharmacokinetic and safety profile, 6-((5S,9R)-9-(4-cyanophenyl)-3-(3, 5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro-[4.4]nonan-7-yl)nicotinic acid (2e) was selected to advance into clinical trials.

  DOI：

  10.1021/jm100348u
• 作为产物：
  描述：

  2-甲硫基-4-嘧啶甲酸 在 氯化亚砜 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 methyl 2-(methylsulfonyl)-pyrimidine-4-carboxylate
  参考文献：
  名称：

  6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines

  摘要：

  本发明涉及能够防止炎性细胞因子的细胞外释放的化合物，该化合物包括所有对映异构体和二面角异构体形式和其药学上可接受的盐，其化学式为：其中R1为取代芳基；R4为取代或非取代芳基或杂环芳基。

  公开号：

  US06849627B2

文献信息

• 6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines
  申请人：The Procter & Gamble Company

  公开号：US20040038971A1

  公开（公告）日：2004-02-26

  The present invention relates to compounds which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: 1 wherein R 1 is substituted aryl; R 4 is substituted or unsubstituted aryl or heteroaryl.

  本发明涉及能够预防炎症细胞因子的细胞外释放的化合物，这些化合物包括所有对映异构体和二面体异构体形式以及其药学上可接受的盐，其化学式为：1其中R1为取代芳基；R4为取代或未取代的芳基或杂环芳基。
• 6,7-Dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which provide analgesia
  申请人：The Procter & Gamble Company

  公开号：US20040087639A1

  公开（公告）日：2004-05-06

  The present invention relates to compound which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: 1 wherein R comprises ethers or amines; R 1 is: a) substituted or unsubstituted aryl; or b) substituted or unsubstituted heteroaryl; each R 2 unit is independently selected from the group consisting of: a) hydrogen; b) —(CH 2 ) j O(CH 2 ) n R 8 ; c) —(CH 2 ) j NR 9a R 9b ; d) —(CH 2 ) j CO 2 R 10 ; e) —(CH 2 ) j OCO 2 R 10 f) —(CH 2 ) j CON(R 10 ) 2 ; g) —(CH 2 ) j OCON(R 10 ) 2 ; h) two R 2 units can be taken together to form a carbonyl unit; i) and mixtures thereof; R 8 , R 9a , R 9b , and R 10 are each independently hydrogen, C 1 -C 4 alkyl, and mixtures thereof; R 9a and R 9b can be taken together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; two R 10 units can be take together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; j is an index from 0 to 5, n is an index from 0 to 5; Z is O, S, NR 11 , or NOR 11 ; R 11 is hydrogen or C 1 -C 4 alkyl.

  本发明涉及一种化合物，其能够预防炎性细胞因子的细胞外释放。该化合物包括所有对映异构体和二对映异构体形式以及其药学上可接受的盐，其化学式如下：1其中R包括醚或胺；R1是：a）取代或未取代的芳基；或b）取代或未取代的杂环芳基；每个R2单元独立地选自以下组：a）氢；b）—（CH2）jO（CH2）nR8；c）—（CH2）jNR9aR9b；d）—（CH2）jCO2R10；e）—（CH2）jOCO2R10f）—（CH2）jCON（R10）2；g）—（CH2）jOCON（R10）2；h）两个R2单元可以结合成一个羰基单元；i）以及其混合物；R8、R9a、R9b和R10各自独立地是氢、C1-C4烷基或其混合物；R9a和R9b可以结合成由3到7个原子组成的环状或杂环状环；两个R10单元可以结合成由3到7个原子组成的环状或杂环状环；j是从0到5的指数，n是从0到5的指数；Z为O、S、NR11或NOR11；R11为氢或C1-C4烷基。
• Spirocyclic-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines
  申请人：The Procter & Gamble Co.

  公开号：US06566357B1

  公开（公告）日：2003-05-20

  The present invention relates to compound which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: wherein R comprises ethers or amines; R1 is: a) substituted or unsubstituted aryl; or b) substituted or unsubstituted heteroaryl; two R2 units on the same carbon atom are taken together to form a spirocyclic ring having from 4 to 7 atoms, the balance of the R2 units are independently selected from the group consisting of: a) hydrogen; b) —O(CH2)jR8; c) —(CH2)jNR9aR9b; d) —(CH2)jCO2R10; e) —(CH2)jOCO2R10 f) —CH2)jCON(R10)2; and g) two R2 units can be taken together to form a carbonyl unit; R8, R9a, R9b, and R10 are each independently hydrogen, C1-C4 alkyl, and mixtures thereof; R9a and R9b can be taken together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; two R10 units can be take together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; j is an index from 0 to 5; the index n is from 3 to 5.

  本发明涉及一种化合物，其能够防止炎症细胞因子的细胞外释放。该化合物包括所有对映异构体和立体异构体形式及其药学上可接受的盐，其化学式如下：其中，R包括醚或胺；R1为：a）取代或未取代的芳基；或b）取代或未取代的杂环芳基；在同一碳原子上的两个R2基团结合形成具有4至7个原子的螺环，其余的R2基团独立地选择自以下组：a）氢；b）—O(CH2)jR8；c）—(CH2)jNR9aR9b；d）—(CH2)jCO2R10；e）—(CH2)jOCO2R10；f）—CH2)jCON(R10)2；和g）两个R2基团可以结合形成一个羰基基团；R8、R9a、R9b和R10各自独立地为氢、C1-C4烷基和它们的混合物；R9a和R9b可以结合形成由3至7个原子组成的环；两个R10基团可以结合形成由3至7个原子组成的环；j为0至5的指数；指数n为3至5。
• [EN] 6,7-DIHYDRO-5H-PYRAZOLO[1,2-A]PYRAZOL-1-ONES WHICH CONTROL INFLAMMATORY CYTOKINES<br/>[FR] 6,7-DIHYDRO-5H-PYRAZOLO[1,2-A]PYRAZOL-1-ONES CONTROLANT LES CYTOKINES INFLAMMATOIRES
  申请人：PROCTER & GAMBLE

  公开号：WO2003024971A1

  公开（公告）日：2003-03-27

  The present invention relates to compound which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula (I): wherein R comprises ethers or amines; R1 is: a) substituted or unsubstituted aryl; or b) substituted or unsubstituted heteroaryl; each R2 unit is independently selected from the group consisting of: a) hydrogen; b) -(CH¿2?)jO(CH2)nR?8¿; c) -(CH¿2?)jNR?9aR9b¿; d) -(CH¿2?)jCO2R?10¿; e) -(CH¿2?)jOCO?2R10¿ f) -(CH¿2?)jCON(R?10)¿2 g) -(CH2)jOCON(R10)2; h) two R2 units can be taken together to form a carbonyl unit; i) and mixtures thereof; R?8, R9a, R9b, and R10¿ are each independently hydrogen, C¿1?-C4 alkyl, and mixtures thereof; R?9a and R9b¿ can be taken together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; two R10 units can be take together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; j is an index from 0 to 5, n is an index from 0 to 5;Z is O, S, NR11, or NOR11; R11 is hydrogen or C¿1?-C4 alkyl.

  本发明涉及一种能够防止炎性细胞因子的细胞外释放的化合物，该化合物包括所有对映异构体和立体异构体以及其药学上可接受的盐，其化学式为（I）：其中R包括醚或胺；R1是：a）取代或未取代的芳基；或b）取代或未取代的杂环基；每个R2基团独立地选择自以下群组：a）氢；b）-(CH2)jO(CH2)nR8；c）-(CH2)jNR9aR9b；d）-(CH2)jCO2R10；e）-(CH2)jOCO2R10；f）-(CH2)jCON（R10）2；g）-(CH2)jOCON（R10）2；h）两个R2基团可以结合形成一个羰基基团；i）及其混合物；R8、R9a、R9b和R10各自独立地是氢、C1-C4烷基和其混合物；R9a和R9b可以结合形成由3至7个原子组成的环烷基或杂环基；两个R10基团可以结合形成由3至7个原子组成的环烷基或杂环基；j是从0至5的指数，n是从0至5的指数；Z是O、S、NR11或NOR11；R11是氢或C1-C4烷基。
• 6,7-Dihydro-5H-pyrazolo[1,2a]pyrazol-1-ones whinch control inflammatory cytokines
  申请人：——

  公开号：US20040058944A1

  公开（公告）日：2004-03-25

  The present invention relates to 2-(4-fluorophenyl)-3-(2-phenoxy-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo-[1,2-a]pyrazol-1-one, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, having the formula: 1 and pharmaceutical compositions thereof, and methods for controlling the level of one or more inflammation inducing cytokines selected from the group consisting of, interleukin-1 (IL-1), Tumor Necrosis Factor-a (TNF-a), interleukin-6 (IL-6), and interleukin-8 (IL-8), thereby controlling, mediating, or abating disease states affected by the level of extracellular inflammatory cytokines in humans.

  本发明涉及2-(4-氟苯基)-3-(2-苯氧基嘧啶-4-基)-6,7-二氢-5H-吡唑并[1,2-a]吡唑-1-酮，包括其所有对映异构体和二对映异构体形式以及其药学上可接受的盐，其化学式为：1，以及其制药组合物和控制一种或多种炎症诱导细胞因子的水平的方法，所述细胞因子选自包括白细胞介素-1（IL-1）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）的群组，从而控制、调节或减轻受细胞外炎症细胞因子水平影响的人类疾病状态。