4(R)-benzyl-3-(2(R)-chlorosulfonylmethyl-3-methylbutyryl)oxazolidin-2-one | 424822-01-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 4(R)-benzyl-3-(2(R)-chlorosulfonylmethyl-3-methylbutyryl)oxazolidin-2-one
• 英文别名: 4-(R)-benzyl-3-(2-(R)-chlorosulfonylmethyl-3 methylbutyryl)oxazolidin-2-one；(2R)-2-[(4R)-4-benzyl-2-oxo-1,3-oxazolidine-3-carbonyl]-3-methylbutane-1-sulfonyl chloride
• CAS: 424822-01-5
• 化学式: C₁₆H₂₀ClNO₅S
• 分子量: 373.857
• InChiKey: HABVMTVKFOZXRX-ZIAGYGMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4(R)-benzyl-3-(2(R)-chlorosulfonylmethyl-3-methylbutyryl)oxazolidin-2-one 在 lithium hydroxide 、 草酰氯 、 双氧水 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 (2R)-2-[[2-(4-chlorophenoxy)ethyl-methylsulfamoyl]methyl]-N-hydroxy-3-methylbutanamide
  参考文献：
  名称：

  An enantioselective synthesis of sulphonamide hydroxamic acids as matrix metalloproteinase inhibitors

  摘要：

  A high yielding and enantioselective synthesis of alpha-substituted hydroxamic acids as inhibitors of matrix metalloproteinases is described. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(01)02151-7
• 作为产物：
  描述：

  4(R)-benzyl-3-(2(R)-acetylthiomethyl-3-methylbutyryl)oxazolidin-2-one 在 水 、 氯 作用下， 以 二氯甲烷 为溶剂， 生成 4(R)-benzyl-3-(2(R)-chlorosulfonylmethyl-3-methylbutyryl)oxazolidin-2-one
  参考文献：
  名称：

  [EN] HYDROXAMATE SULFONAMIDES AS CD23 SHEDDING INHIBITORS
  [FR] HYDROXAMATE SULFONAMIDES UTILISES EN TANT QU'INHIBITEURS DE L'ELIMINATION DE CD23

  摘要：

  一类哌啶和相关杂环衍生物，C位被取代的芳基或杂芳基基团取代，N位被乙磺酰基团取代，该基团在2位上被羟肟酸基团以及一系列替代取代基取代，作为CD23脱落的强效抑制剂，在治疗和/或预防过敏、炎症和肿瘤疾病方面是有用的。

  公开号：

  WO2004113298A1

文献信息

• [EN] HYDROXAMATE SULFONAMIDES AS CD23 SHEDDING INHIBITORS<br/>[FR] SULFONAMIDES D'HYDROXAMATE SERVANT D'INHIBITEURS D'ELIMINATION DU VIRUS CD23
  申请人：CELLTECH R&D LTD

  公开号：WO2004113312A1

  公开（公告）日：2004-12-29

  A class of piperazine and related heterocyclic derivatives, substituted at the 4-position by a substituted aryl or heteroaryl moiety, and at the 1-position by an ethylsulfonyl group which in turn is substituted at the 2-position by a hydroxamic acid moiety and also by a range of alternative substituents, being potent inhibitors of CD23 shedding, are useful in the treatment and/or prevention of allergic, inflammatory and neoplastic diseases.

  一类哌嗪和相关杂环衍生物，其在4位被取代芳基或杂环基取代，并在1位被乙磺酰基取代，乙磺酰基在2位被羟肟酸基取代，同时还被一系列替代基取代，这些化合物是CD23脱落的有效抑制剂，可用于治疗和/或预防过敏、炎症和肿瘤性疾病。
• Hydroxamic and carboxylic acid derivatives
  申请人：——

  公开号：US20020013333A1

  公开（公告）日：2002-01-31

  A pharmacologically active compound of formula (I) 1 wherein R 1 is OH or NHOH; R 2 is H, alklyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclo or heterocycloalkyl (any of which may be optionally substituted with one or more substituents selected from R 6 , W and WR 6 ); and R 3 is H or alkyl; or R 2 , R 3 and the carbon atom to which they are attached together represent a carbocyclic or heterocyclic ring (either of which may be substituted with one or more substituents selected from R 6 , W and WR 6 ), R 4 is alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR 10 , S(O) q R 10 where q is 0, 1 or 2, CONR 7 R 8 , CN or S(O) q NR 7 R 8 , two R 4 substituents may be attached to the same carbon atom to form C(R 4 ) 2 , where each R 4 is the same or different, or C(R 4 ) 2 may represent C═O; R 5 is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, CF 3 , OR 9 , COR 10 , S(O) q R 10 , CO 2 R 14 , CONR 7 R 8 , S(O) q NR 7 R 8 , halogen, NR 10 R 11 or CN, or two adjacent R 5 substituents may be combined to form a heterocyclic ring, R 6 is OR 9 , COR 10 , CO 2 R 15 , CONR 7 R 8 , NR 10 R 11 , S(O) q R 10 , S(O) q NR 7 R 5 , ═O, ═NOR 10 , succinimido or the group 2 R 7 and R 8 , which may be the same or different, are each H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylakyl, heterocycloalkyl or cycloalkylalkyl, or R 7 and R 8 and the nitrogen to which they are attached together represent a heterocyclic ring, R 9 is H, alkyl, CF 3 , CHF 2 , CH 2 F, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl; R 10 is H, alkyl, cycloalklyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl; and R 11 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, COR 12 , CONR 7 R 8 , S(O) q R 12 or S(O) q NR 7 R 8 ; or R 10 and R 11 and the nitrogen to which they are attached together represent a heterocyclic ring, R 12 is OR 9 or R 13 ; R 13 is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heterarylalkyl, heterocycloalkyl or cycloalkylalkyl; R 14 is H, alkyl or cycloalkyl; R 15 is Y, alkyl, cycloalkyl, arylalkyl or heteroarylalkyl; X is a bond (i.e. is absent), —O— 2 —C(O)—, —S(O) q —, —N(R 11 )—, —N(R 11 )C(R 16 ) 2 —, —S(O) q C(R 16 ) 2 —, —C(R 16 ) 2 N(R 11 )—, —C(R 16 ) 2 S(O) q —, —C(R 16 )═N—, —N═C(R 16 )—, —N(R 11 )SO 2 —, —SO 2 N(R 11 )—, —N(R 11 )CO— or —CON(R 11 )—; and the R 16 groups in C(R 16 ) 2 may be the same or different, Y is a bond (i.e. is absent), —O—, —C(O)—, —S(O) q —, —N(R 11 )—, —N(R 11 )C(R 16 ) 2 —, —S(O) q C(R 16 ) 2 —, —C(R 16 ) 2 N(R 11 )—, —C(R 16 ) 2 S(O) q —, —C(R 16 )—N—, —N═C(R 16 )—, —N(R 11 )SO 2 —, —SO 2 N(R 11 )—, —N(R 11 )CO— or —CON(R 11 )—; and the R 16 groups in C(R 16 ) 2 may be the same or different, R 16 is H, alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR 10 , S(O) q R 10 , CONR 7 R 8 , CN or S(O) q NR 7 R 8 ; R 17 is H or alkyl; W is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclo or heterocycloalkyl, represents a single or double bond, each k and m is independently 0, 1, 2 or 3, n is 0, 1 or 2; and p is 0, 1 or 2, provided that n+p does not exceed 3, or a salt, solvate, hydrate, N-oxide, protected amino, protected carboxy or protected hydroxamic acid derivative thereof

  一种化学式（I）的药理活性化合物，其中R1为OH或NHOH；R2为H，烷基，烯基，芳基，芳基烷基，杂芳基，杂芳基烷基，环烷基，环烷基烷基，杂环烷基或杂环烷基烷基（其中任何一个可以选择性地用R6，W和WR6中的一个或多个取代基取代）；R3为H或烷基；或者R2，R3和它们所连接的碳原子共同表示一个碳环或杂环（其中任何一个可以选择性地用R6，W和WR6中的一个或多个取代基取代），R4为烷基，环烷基，OR9，CO2R14，COR10，S（O）qR10（其中q为0，1或2），CONR7R8，CN或S（O）qNR7R8，两个R4取代基可以连接到同一个碳原子上形成C（R4）2，其中每个R4相同或不同，或C（R4）2可以表示C═O；R5为烷基，环烷基，芳基，杂芳基，杂环烷基，CF3，OR9，COR10，S（O）qR10，CO2R14，CONR7R8，S（O）qNR7R8，卤素，NR10R11或CN，或者相邻的两个R5取代基可以结合形成杂环；R6为OR9，COR10，CO2R15，CONR7R8，NR10R11，S（O）qR10，S（O）qNR7R5，═O，═NOR10，琥珀酰亚胺或2R7和R8的基团，它们可以相同或不同，分别为H，烷基，环烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基，杂环烷基烷基或环烷基烷基，或者R7和R8及它们所连接的氮共同表示一个杂环；R9为H，烷基， ，CHF2，CH2F，环烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基，杂环烷基烷基或环烷基烷基；R10为H，烷基，环烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基，杂环烷基烷基或环烷基烷基；R11为H，烷基，环烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基，杂环烷基烷基，环烷基烷基，COR12，CONR7R8，S（O）qR12或S（O）qNR7R8；或者R10和R11及它们所连接的氮共同表示一个杂环；R12为OR9或R13；R13为烷基，环烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基或杂环烷基烷基；R14为H，烷基或环烷基；R15为Y，烷基，环烷基，芳基烷基或杂芳基烷基；X为键（即不存在），—O—2—C（O）—，—S（O）q—，—N（R11）—，—N（R11）C（R16）2—，—S（O）qC（R16）2—，—C（R16）2N（R11）—，—C（R16）2S（O）q—，—C（R16）═N—，—N═C（R16）—，—N（R11）SO2—，—SO2N（R11）—，—N（R11）CO—或—CON（R11）—；C（R16）2中的R16取代基可以相同或不同；Y为键（即不存在），—O—，—C（O）—，—S（O）q—，—N（R11）—，—N（R11）C（R16）2—，—S（O）qC（R16）2—，—C（R16）2N（R11）—，—C（R16）2S（O）q—，—C（R16）—N—，—N═C（R16）—，—N（R11）SO2—，—SO2N（R11）—，—N（R11）CO—或—CON（R11）—；C（R16）2中的R16取代基可以相同或不同；R16为H，烷基，环烷基，OR9，CO2R14，COR10，S（O）qR10，CONR7R8，CN或S（O）qNR7R8；R17为H或烷基；W为烷基，环烷基，环烷基烷基，芳基，芳基烷基，杂芳基，杂芳基烷基，杂环烷基或杂环烷基烷基，表示单键或双键，每个k和m独立地为0，1，2或3，n为0，1或2；p为0，1或2，但n+p不得超过3；或其盐，溶剂化合物，水合物，N-氧化物，保护氨基，保护羧基或保护羟胺酸衍生物。
• Hydroxamic acid derivatives
  申请人：——

  公开号：US20030216404A1

  公开（公告）日：2003-11-20

  The invention encompasses novel compounds which are inhibitors of matrix metalloproteinase, ADAM or ADAM-TS enzymes, and which are useful for the treatment of diseases mediated by those enzymes, including degenerative diseases and certain cancers.

  本发明涵盖了一些新型的化合物，这些化合物是基质金属蛋白酶、ADAM或ADAM-TS酶的抑制剂，并且对于治疗由这些酶介导的疾病，包括退行性疾病和某些癌症，具有有益的作用。
• Hydroxamate sulfonamides as cd23 shedding inhibitors
  申请人：Owen Alan David

  公开号：US20060241118A1

  公开（公告）日：2006-10-26

  A class of piperazine and related heterocyclic derivatives, substituted at the 4-position by a substituted aryl or heteroaryl moiety, and at the 1-position by an ethylsulfonyl group which in turn is substituted at the 2-position by a hydroxamic acid moiety and also by a range of alternative substituents, being potent inhibitors of CD23 shedding, are useful in the treatment and/or prevention of allergic, inflammatory and neoplastic diseases.

  一类哌嗪和相关杂环衍生物，其在4-位被取代芳基或杂芳基取代，1-位被乙烷基磺酰基取代，该基团在2-位被羟肟酸基团和多种替代基团取代，是CD23脱落的有效抑制剂，可用于过敏、炎症和肿瘤疾病的治疗和/或预防。
• Approaches to a Scaleable Synthesis of CH8757:  A Potent Inhibitor of Matrix Metalloproteinases
  作者：Graham A. Frampton、Duncan R. Hannah、Neil Henderson、Ruth B. Katz、Ian H. Smith、Neil Tremayne、Robert J. Watson、Indrani Woollam

  DOI：10.1021/op049954q

  日期：2004.5.1

  The synthesis of the matrix metalloproteinase (MMP) inhibitor CH8757 is described. The discovery route has been modified to incorporate a three-stage one-pot sequence using alpha,alpha,alpha-trifluorotoluene as solvent. The formation of the hydroxamic acid using oxalyl chloride is catalysed by DBU, thus avoiding the use of DMF, which may form the highly toxic byproduct, dimethylcarbamoyl chloride.