3-chloro-4-cyanobenzylamine | 202522-15-4

• 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: 3-chloro-4-cyanobenzylamine
• 英文别名: 4-aminomethyl-2-chloro-benzonitrile；4-(Aminomethyl)-2-chlorobenzonitrile
• CAS: 202522-15-4
• 化学式: C₈H₇ClN₂
• mdl: MFCD18392455
• 分子量: 166.61
• InChiKey: MIYUHKALQKBPEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chloro-4-cyanobenzylamine 、 3-乙氧基-4-[(2-甲基-2-丁烷基)氨基]-3-环丁烯-1,2-二酮 以 乙醇 为溶剂， 反应 8.0h， 以32%的产率得到2-Chloro-4-[[[2-(2-methylbutan-2-ylamino)-3,4-dioxocyclobuten-1-yl]amino]methyl]benzonitrile
  参考文献：
  名称：

  Design and SAR of Novel Potassium Channel Openers Targeted for Urge Urinary Incontinence. 2. Selective and Potent Benzylamino Cyclobutenediones

  摘要：

  A novel series of benzylamine, potassium channel openers (KCOs) is presented as part of our program toward designing new, bladder-selective compounds for the treatment of urge urinary incontinence (UUI). We have found that the in vitro potency of (R)-4-[3,4-dioxo-2-(1,2,2-trimethyl-propylamino)-cyclobut-1-enylamino]3-ethyl-benzonitrile 1 in the relaxation of precontracted rat detrusor strips can also be obtained with cyanobenzylamine derivative 4 (IC50 = 0.29 mu M) (Figure 3). Addition of a 2-Cl substituted benzylamine moiety and changing the alkylamino substituent of 4 to a t-Bu amine gives 31 (IC50 = 0.14 mu M)-a compound with similar in vitro potency as 4 as well as relaxant activity on bladder smooth muscle in vivo when administered orally (31, ED50 = 3 mg/kg) in a rodent model of bladder instability. Further modifications, particularly the replacement of the t-Bu amino substituent with a tert-amylamine, gave a similarly active compound 60 (IC50 = 0.10 mu M) which shows excellent in vivo efficacy (ED50 = 0.6 mg/kg). Moreover, 60, 3-(2,4-dichloro-6-methyl-benzylamino)-4- 1,1-dimethylpropylamino)-cyclobut-3-ene-1,2-dione (WAY-151616), shows excellent tissue selectivity for bladder K channels over arterial tissue (60, MAP ED20 = 100 mg/kg; selectivity: MAP ED20/ bladder ED50 = 166). Other manipulations of the benzylamino cyclobutenediones, acylation of the benzylamine, conversion of the benzylamine substituent to a benzamide, homologation of the benzylamine to a phenethylamine, and incorporation of a methyl group at the benzyl carbon, all led to substantial loss of in vitro activity, although some in vivo activity was maintained in the acylated analogues. Compound 60 represents an attractive candidate for development in the treatment of UUI.

  DOI：

  10.1021/jm9905108

文献信息

• Heterocyclyl substituted 1-alkoxy acetic acid amides
  申请人：Gobbi Claudio Luca

  公开号：US20050137168A1

  公开（公告）日：2005-06-23

  The invention is concerned with novel heterocyclyl substituted 1-alkoxy acetic acid derivatives of formula (I) wherein R 1 to R 6 and A are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit the formation of coagulation factors Xa, IXa and thrombin induced by factor VIIa and tissue factor and can be used as medicaments.

  这项发明涉及一种新颖的杂环烷基取代的1-烷氧基乙酸衍生物，其化学式为（I），其中R1至R6和A的定义如描述和索赔中所述，以及其生理上可接受的盐。这些化合物抑制由VIIa因子和组织因子诱导的凝血因子Xa、IXa和凝血酶的形成，并可用作药物。
• Novel thrombin inhibitors
  申请人：——

  公开号：US20020169318A1

  公开（公告）日：2002-11-14

  The invention relates to a compound of the formula I 1 or a salt thereof with a physiologically tolerated acid, or stereoisomers thereof, wherein R 1 , R 2 , A, B, C and D have the meanings described in the specification.

  本发明涉及一种公式I1的化合物或其生理上耐受的酸盐，或其立体异构体，其中R1，R2，A，B，C和D的含义如说明书中所述。
• Novel mandelic acid derivatives
  申请人：——

  公开号：US20040122057A1

  公开（公告）日：2004-06-24

  The invention is concerned with novel mandelic acid derivatives of formula (I) 1 wherein R 1 to R 10 , X and Y are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds inhibit the formation of coagulation factors Xa, IXa and thrombin induced by factor VIIa and tissue factor.

  本发明涉及公式（I）1的新型苯甲酸衍生物，其中R1至R10，X和Y如说明书和权利要求中所定义，并且其药学上可接受的盐。这些化合物抑制由因子VIIa和组织因子诱导的凝血因子Xa，IXa和凝血酶的形成。
• Mandelic acid derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US07129238B2

  公开（公告）日：2006-10-31

  The invention is concerned with novel mandelic acid derivatives of formula (I) wherein R1 to R10, X and Y are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds inhibit the formation of coagulation factors Xa, IXa and thrombin induced by factor VIIa and tissue factor.

  本发明涉及一种新型的苯乙酸衍生物，其化学式为(I)，其中R1到R10、X和Y的定义如说明书和权利要求中所述，以及其药学上可接受的盐。这些化合物可以抑制因子VIIa和组织因子诱导的凝血因子Xa、IXa和凝血酶的形成。
• Substituted N-arylmethylamino derivatives of cyclobutene-3, 4-diones
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP1151990A1

  公开（公告）日：2001-11-07

  The compounds of the formula: wherein R1, R2, R3 and A are as defined herein are useful, via potassium channel modulation, in the treatment of disorders associated with smooth muscle contraction. Such disorders include, but are not limited to, urinary incontinence, hypertension, asthma, premature labor, irritable bowel syndrome, congestive heart failure, angina and cerebral vascular disease.

  式中的化合物 其中 R1、R2、R3 和 A 如本文所定义，通过调节钾通道，可用于治疗与平滑肌收缩有关的疾病。这些疾病包括但不限于尿失禁、高血压、哮喘、早产、肠易激综合征、充血性心力衰竭、心绞痛和脑血管疾病。