methyl 4-(acetylsulfanylmethyl)tetrahydropyran-4-carboxylate | 235753-82-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: methyl 4-(acetylsulfanylmethyl)tetrahydropyran-4-carboxylate
• 英文别名: 4-acetylsulfanylmethyl-tetrahydro-pyran-4-carboxylic acid methyl ester；Methyl 4-[(acetylsulfanyl)methyl]oxane-4-carboxylate；methyl 4-(acetylsulfanylmethyl)oxane-4-carboxylate
• CAS: 235753-82-9
• 化学式: C₁₀H₁₆O₄S
• 分子量: 232.301
• InChiKey: SBKWLRQWJCVHOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  77.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-(acetylsulfanylmethyl)tetrahydropyran-4-carboxylate 在 草酰氯 、 lithium hydroxide monohydrate 、 水 、 氯 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 3.75h， 生成 4-[4-((4-chlorophenyl)piperazin-1-yl)sulfonylmethyl]tetrahydropyran-4-carbonyl chloride
  参考文献：
  名称：

  Rapid Scale-Up of the Matrix Metalloproteinase Inhibitor CH5902:  Process Safety and Route Development Considerations

  摘要：

  The synthesis of the novel MMP inhibitor CH5902 is described. In this approach, the original discovery route has been streamlined and telescoped into a four-stage sequence, which has been demonstrated on a multikilogram scale. A number of issues arising from both process development and process safety concerns are discussed.

  DOI：

  10.1021/op0340762
• 作为产物：
  描述：

  四氢吡喃-4-羧酸甲酯 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.75h， 生成 methyl 4-(acetylsulfanylmethyl)tetrahydropyran-4-carboxylate
  参考文献：
  名称：

  Rapid Scale-Up of the Matrix Metalloproteinase Inhibitor CH5902:  Process Safety and Route Development Considerations

  摘要：

  The synthesis of the novel MMP inhibitor CH5902 is described. In this approach, the original discovery route has been streamlined and telescoped into a four-stage sequence, which has been demonstrated on a multikilogram scale. A number of issues arising from both process development and process safety concerns are discussed.

  DOI：

  10.1021/op0340762

文献信息

• HYDROXAMIC AND CARBOXYLIC ACID DERIVATIVES
  申请人：——

  公开号：US20030236416A1

  公开（公告）日：2003-12-25

  Compounds having therapeutic utility are of formula (I) B—X—(CH 2 ) n —CR 2 R 3 —CR 4 R 5 —COY  (I) wherein n = 0 - 1; X is S(O) 0-2 , Y is OR 1 or NHOH; R 2 and R 4 are independently H or a group (optionally substituted with R 10 ) selected from C 1-6 alkyl, C 2-6 alkenyl, aryl, C 1-6 alkyl-aryl, heteroaryl, C 1-6 alkyl-heteroaryl, heterocycloalkyl, C 1-6 alkyl-heterocycloalkyl, cycloalkyl and C 1-6 alkyl-cycloalkyl; and R 1 , R 3 and R 5 are independently H or C 1-6 alkyl; provided that not more than two of R 2 , R 3 , R 4 and R 5 are H; or any of CR 2 R 3 , CR 4 R 5 and CR 2 —CR 4 is a cycloalkyl or heterocycloalkyl ring optionally substituted with R 10 or a group (optionally substituted with R 10 ) selected from C 1-6 alkyl, aryl, C 1-6 alkyl-aryl, heteroaryl and C 1-6 alkyl-heteroaryl; B is heterocycloalkyl (optionally substituted by R 6 or R 7 ) bonded through carbon to X, or C 1-6 alkyl-heterocycloalkyl (optionally substituted with R 6 or R 7 ), or a group (substituted with R 6 ) selected from C 1-8 alkyl, C 2-6 alkenyl and C 2-6 alkynyl; R 6 is N(R 7 ) 2 , OR 7 , COR 7 , C(=NOR 9 )R 7 , NR 7 R 8 , S(O) 0-2 R 9 or SO 2 N(R 7 ) 2 ; R 7 is H or a group selected from C 1-6 alkyl, aryl, C 1-6 alkyl-aryl, heteroaryl, C 1-6 alkyl-heteroaryl, cycloalkyl, C 1-6 alkyl-cycloalkyl, heterocycloalkyl and C 1-6 alkyl-heterocycloalkyl, wherein said group is optionally substituted with R 9 , COR 9 , SO 0-2 R 9 , CO 2 R 9 , OR 9 , CONR 1 R 9 , NR 1 R 9 , halogen, CN, SO 2 NR 1 R 9 or NO 2 , and for each case of N(R 7 ) 2 the R 7 groups are the same or different or N(R 7 ) 2 is heterocycloalkyl optionally substituted with R 9 , COR 9 , SO 0-2 R 9 , CO 2 R 9 , OR 9 , CONR 1 R 9 , NR 1 R 9 , halogen, CN, SO 2 NR 1 R 9 or NO 2 ; R 8 is COR 7 , CON(R 7 ) 2 , CO 2 R 9 or SO 2 R 9 ; R 9 is C 1-6 alkyl, aryl, C 1-6 alkyl-aryl, heteroaryl or C 1-6 alkyl-heteroaryl; and R 10 is OR 7 , COR 7 , CO 2 R 1 , CON(R 7 ) 2 , NR 7 R 8 , S(O) 0-2 R 9 , SO 2 N(R 7 ) 2 , CN, halogen or cycloimidyl (optionally substituted with R 1 ); and the salts, solvates, hydrates, N-oxides, protected amino, protected carboxy and protected hydroxamic acid derivatives thereof.

  具有治疗效用的化合物的公式为(I)B—X—(CH2)n—CR2R3—CR4R5—COY  (I)，其中n为0-1；X为S(O)0-2，Y为OR1或NHOH；R2和R4独立地为H或从C1-6烷基、C2-6烯基、芳基、C1-6烷基芳基、杂芳基、C1-6烷基杂芳基、杂环烷基、C1-6烷基杂环烷基、环烷基和C1-6烷基环烷基中选择的（可选地用R10取代的）基团；R1、R3和R5独立地为H或C1-6烷基；但不得超过两个R2、R3、R4和R5为H；或CR2R3、CR4R5和CR2—CR4中的任何一个为杂环烷基或杂环烷基环，可选地用R10取代，或从C1-6烷基、芳基、C1-6烷基芳基、杂芳基和C1-6烷基杂芳基中选择的（可选地用R10取代的）基团；B为通过碳与X相连的杂环烷基（可选地用R6或R7取代），或C1-6烷基杂环烷基（可选地用R6或R7取代），或从C1-8烷基、C2-6烯基和C2-6炔基中选择的（用R6取代的）基团；R6为N(R7)2、OR7、COR7、C(=NOR9)R7、NR7R8、S(O)0-2R9或SO2N(R7)2；R7为H或从C1-6烷基、芳基、C1-6烷基芳基、杂芳基、C1-6烷基杂芳基、环烷基、C1-6烷基环烷基、杂环烷基和C1-6烷基杂环烷基中选择的基团，其中所述基团可选地用R9、COR9、SO0-2R9、CO2R9、OR9、CONR1R9、NR1R9、卤素、CN、SO2NR1R9或NO2取代，对于每种情况的N(R7)2，R7基团相同或不同，或N(R7)2为可选地用R9、COR9、SO0-2R9、CO2R9、OR9、CONR1R9、NR1R9、卤素、CN、SO2NR1R9或NO2取代的杂环烷基；R8为COR7、CON(R7)2、CO2R9或SO2R9；R9为C1-6烷基、芳基、C1-6烷基芳基、杂芳基或C1-6烷基杂芳基；R10为OR7、COR7、CO2R1、CON(R7)2、NR7R8、S(O)0-2R9、SO2N(R7)2、CN、卤素或环亚咪唑基（可选地用R1取代）；及其盐、溶剂化合物、水合物、N-氧化物、保护氨基、保护羧基和保护羟胺衍生物。
• 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，CF3，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。
• HYDROXAMIC ACID DERIVATIVES
  申请人：Darwin Discovery Limited

  公开号：EP1282614B1

  公开（公告）日：2003-11-12
• HYDROXAMIC AND CARBOXYLIC ACID DERIVATIVES HAVING MMP AND TNF INHIBITORY ACTIVITY
  申请人：Darwin Discovery Limited

  公开号：EP1286994A1

  公开（公告）日：2003-03-05