5-cyclopropyl-2-(2-phenylpyrimidin-5-ylamino)benzoic acid | 1119084-96-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-cyclopropyl-2-(2-phenylpyrimidin-5-ylamino)benzoic acid
• 英文别名: 5-Cyclopropyl-2-[(2-phenylpyrimidin-5-yl)amino]benzoic acid
• CAS: 1119084-96-6
• 化学式: C₂₀H₁₇N₃O₂
• 分子量: 331.374
• InChiKey: MWKNDWLOLXYLPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  75.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 2-amino-5-cyclopropylbenzoate 在 copper(I) oxide 、 甲醇 、 sodium hydroxide 、 水 、 铜 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 15.0h， 生成 5-cyclopropyl-2-(2-phenylpyrimidin-5-ylamino)benzoic acid
  参考文献：
  名称：

  [EN] AZABIPHENYLAMINOBENZOIC ACID DERIVATIVES AS DHODH INHIBITORS
  [FR] DÉRIVÉS D'ACIDE AZABIPHÉNYLAMINOBENZOÏQUE COMME INHIBITEURS DE LA DHODH

  摘要：

  揭示了具有化学结构式(I)的新的阿扎比苯胺基苯甲酸衍生物；以及它们的制备过程、包含它们的药物组合物以及它们在治疗中作为脱氢乳酸脱氢酶（DHODH）抑制剂的用途。

  公开号：

  WO2009021696A1

文献信息

• Amino derivatives for the treatment of proliferative skin disorders
  申请人：Almirall, S.A.

  公开号：EP2444088A1

  公开（公告）日：2012-04-25

  Compositions comprising specific amino derivatives for their use in treating proliferative skin diseases or disorders and the use of specific amino derivatives in such a treatment is disclosed.

  本发明公开了包含特定氨基衍生物的组合物，用于治疗增生性皮肤疾病或疾病的用途，并公开了在此类治疗中使用特定氨基衍生物的方法。
• AZABIPHENYLAMINOBENZOIC ACID DERIVATIVES AS DHODH INHIBITORS
  申请人：Castro Palomino Laria Julio Cesar

  公开号：US20110212945A1

  公开（公告）日：2011-09-01

  The present disclosure relates to new azabiphenylaminobenzoic acid derivatives of formula (I); as well as processes for their preparation, pharmaceutical compositions comprising them, and their use in therapy as inhibitors of the dehydroorotate dihydrogenase (DHODH).

  本公开涉及新的式(I)的氮杂联苯氨基苯甲酸衍生物，以及它们的制备方法，包括它们的制药组合物，以及它们在治疗中作为脱氢鸟嘌呤二氢酶（DHODH）抑制剂的用途。
• Pyrimidyl- or pyridinylaminobenzoic acid derivatives
  申请人：Laboratorios Almirall, S.A.

  公开号：EP2100881A1

  公开（公告）日：2009-09-16

  New azabiphenylaminobenzoic acid derivatives having the chemcial structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of the dehydroorotate dihydrogenase (DHODH).

  本研究公开了具有式（I）化学结构的新型氮杂联苯氨基苯甲酸衍生物，以及它们的制备工艺、包含它们的药物组合物和它们在治疗中作为脱氢烟酸二氢酶（DHODH）抑制剂的用途。
• Combinations comprising methotrexate and DHODH inhibitors
  申请人：Almirall, S.A.

  公开号：EP2210615A1

  公开（公告）日：2010-07-28

  The present invention provides a combination which comprises (a) methotrexate and (b) a non-hepatotoxic DHODH inhibitor of formula (I): wherein: R1 is selected from the group consisting ofhydrogen atoms, halogen atoms, C1-4 alkyl, C3-4 cycloalkyl, -CF3 and -OCF3, R2 is selected from the group consisting of hydrogen atoms, halogen atoms and C1-4 alkyl groups, R3 is selected from the group consisting of -COOR5, -CONHR5, tetrazolyl, -SO2NHR5 and -CONHSO2R5 groups, wherein R5 is selected from the group consisting of a hydrogen atom and linear or branched C1-4 alkyl groups, R4 is selected from the group consisting of a hydrogen atom and a C1-4 alkyl group, R9 is selected from the group consisting of a hydrogen atom and a phenyl group, G1 represents a group selected from N and CR6 wherein R6 is selected from the group consisting ofhydrogen atoms, halogen atoms, C1-4 alkyl, C3-4 cycloalkyl, C1-4 alkoxy, - CF3, -OCF3, monocyclic N-containing C5-7 heteroaryl, monocyclic N-containing C3-7 heterocyclyl groups and C6-10 aryl groups which C6-10 aryl groups are optionally substituted with one or more substituents selected from halogen atoms and C1-4 alkyl groups, G2 represents a group selected from: • a hydrogen atom, a hydroxy group, a halogen atom, a C3-4 cycloalkyl group, a C1-4 alkoxy group and NRaRb, wherein Ra represents a C1-4 alkyl group and Rb is selected from a group consisting of C1-4 alkyl group and C1-4 alkoxy-C1-4 alkyl group, or Ra and Rb together with the nitrogen atom to which they are attached form a saturated 6 to 8 membered heterocyclic ring optionally containing one oxygen atom as an additional heteroatom, • a monocyclic or bicyclic 5 to 10 membered heteroaromatic ring containing one or more nitrogen atoms which is optionally substituted by one or more substituents selected from halogen atoms, C1-4 alkyl, C1-4 alkoxy, C3-4 cycloalkyl, C3-4 cycloalkoxy, -CF3, -OCF3, and -CONR7R8, wherein R7 and R8 are independently selected from hydrogen atom, linear or branched C1-4 alkyl groups, C3-7 cycloalkyl groups, or R7 and R8 together with the nitrogen atom to which they are attached form a group of formula wherein n is an integer from 0 to 3, and • a phenyl group which is optionally substituted by one or more substituents selected from halogen atoms, C1-4 alkyl, hydroxyl, C1-4 alkoxy, C3-4cycloalkyl, C3-4 cycloalkoxy, cyano, -CF3, -OCF3, -CONR7R8, oxadiazolyl, triazolyl, pyrazolyl and imidazolyl groups, which oxadiazolyl, triazolyl, pyrazolyl and imidazolyl groups are optionally substituted by C1-4 alkyl or C3-7 cycloalkyl groups and wherein R7 and R8 are independently selected from hydrogen atom, linear or branched C1-4 alkyl groups, C3-7 cycloalkyl groups, or R7 and R8 together with the nitrogen atom to which they are attached form a group of formula wherein n is an integer from 0 to 3 or, when G' represents CR6, G2 together with R6 forms a non-aromatic C5-10 carbocyclic group or a C6-10 aryl group, and the pharmaceutically acceptable salts and N-oxides thereof.

  本发明提供了一种组合物，它包括(a)甲氨蝶呤和(b)式(I)的非肝毒性 DHODH 抑制剂： 其中 R1 选自由氢原子、卤素原子、C1-4 烷基、C3-4 环烷基、-CF3 和 -OCF3 组成的组、 R2 选自氢原子、卤素原子和 C1-4 烷基组成的组、 R3 选自-COOR5、-CONHR5、四唑基、-SO2NHR5 和-CONHSO2R5 所组成的组，其中 R5 选自氢原子和直链或支链 C1-4 烷基所组成的组、 R4 选自氢原子和 C1-4 烷基组成的组、 R9 选自氢原子和苯基组成的组、 G1 代表选自 N 和 CR6 的基团，其中 R6 选自由氢原子、卤素原子、C1-4 烷基、C3-4 环烷基、C1-4 烷氧基、-CF3、-OCF3、含 N 的单环 C5-7 杂芳基、含 N 的单环 C3-7 杂环烯丙基和 C6-10 芳基组成的组，其中 C6-10 芳基任选被一个或多个选自卤素原子和 C1-4 烷基的取代基取代、 G2 代表选自以下的基团 - 氢原子、羟基、卤素原子、C3-4 环烷基、C1-4 烷氧基和 NRaRb，其中 Ra 代表 C1-4 烷基，Rb 选自 C1-4 烷基和 C1-4 烷氧基-C1-4 烷基组成的组，或 Ra 和 Rb 与它们所连接的氮原子一起形成一个饱和的 6 至 8 位杂环，该杂环可选地含有一个氧原子作为额外的杂原子、 - 含有一个或多个氮原子的单环或双环 5 至 10 个成员的杂芳香环，该环任选被一个或多个取代基取代，这些取代基选自卤素原子、C1-4 烷基、C1-4 烷氧基、C3-4 环烷基、C3-4 环烷氧基、-CF3、-OCF3 和 -CONR7R8，其中 R7 和 R8 独立地选自氢原子、直链或支链 C1-4 烷基、C3-7 环烷基，或 R7 和 R8 与它们所连接的氮原子一起形成一个式组 其中 n 为 0 至 3 的整数、 和 - 苯基，该基团可任选被一个或多个取代基取代，这些取代基选自卤素原子、C1-4 烷基、羟基、C1-4 烷氧基、C3-4 环烷基、C3-4 环烷氧基、氰基、-CF3、-OCF3、-CONR7R8、噁二唑基、三唑基、吡唑基和咪唑基，其中噁二唑基、三唑基、吡唑基和咪唑基可任选被一个或多个取代基取代，这些取代基选自卤素原子、C1-4 烷基、羟基、C1-4 烷氧基、C3-4 环烷基、C3-4 环烷氧基、氰基、-CF3、-OCF3、-CONR7R8、其中 R7 和 R8 独立地选自氢原子、直链或支链 C1-4 烷基、C3-7 环烷基，或 R7 和 R8 与它们所连接的氮原子一起形成式中的基团 其中 n 为 0 至 3 的整数 或者，当 G' 代表 CR6 时，G2 与 R6 一起形成非芳香的 C5-10 碳环基或 C6-10 芳基、 及其药学上可接受的盐类和 N-氧化物。
• Combinations comprising DHODH inhibitors and COX inhibitors
  申请人：Almirall, S.A.

  公开号：EP2444086A1

  公开（公告）日：2012-04-25

  Combinations comprising (a) DHODH inhibitors and (b) COX inhibitors and their use in treating skin diseases or disorders are disclosed.

  本研究公开了由(a) DHODH 抑制剂和(b) COX 抑制剂组成的组合物及其在治疗皮肤疾病或失调中的用途。