5-amino-2-[(E)-2-(4-amino-2-(aminosulfonyl)phenyl)ethenyl]benzene sulfonamide | 299183-42-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 5-amino-2-[(E)-2-(4-amino-2-(aminosulfonyl)phenyl)ethenyl]benzene sulfonamide
• 英文别名: 5-Amino-2-[(E)-2-(4-amino-2-(aminosulfonyl)phenyl)ethenyl]benzenesulfonamide；5-amino-2-[(E)-2-(4-amino-2-sulfamoylphenyl)ethenyl]benzenesulfonamide
• CAS: 299183-42-9
• 化学式: C₁₄H₁₆N₄O₄S₂
• 分子量: 368.437
• InChiKey: ODIOYCSHSLNKFV-OWOJBTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  189
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  、 5-amino-2-[(E)-2-(4-amino-2-(aminosulfonyl)phenyl)ethenyl]benzene sulfonamide 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 以37%的产率得到
  参考文献：
  名称：

  Synthesis of (bis)Sulfonic acid, (bis)Benzamides as follicle-Stimulating hormone (FSH) antagonists

  摘要：

  Screening efforts identified (bis)sulfonic acid. (bis)benzamides (1-3) as compounds that interact with the follicle stimulating-hormone receptor (FSHR) and inhibit FSH-stimulated CAMP accumulation with IC50 values in the low micromolar range. Structure-activity relationship studies using novel analogues of 1-3 revealed that two phenylsulfonic acid moieties were necessary for activity and that the carbon-carbon double bond of the stilbene sub-series was the optimum spacer connecting these groups. Selected analogues (2, 14, and 50) were also able to block FSHR-dependent estradiol production in rat primary ovarian granulosa cells and progesterone secretion in a clonal mouse adrenal Y1 cell line. IC50 values for these compounds in these assays were in the low micromolar range. Optimization of the benzoic acid side chains of 1-3 led to gains in selectivity versus activity at the thyroid stimulating hormone (TSH) receptor (TSHR). For instance, while stilbene (bis)sulfonic acid congener 2 was only 10-fold selective for FSHR over TSHR, analogue 50 with an IC50 value of 0.9 muM in the FSHR-cAMP assay was essentially inactive at 30muM in the TSHR-cAMP assay. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00324-8
• 作为产物：
  描述：

  2-甲基-5-硝基苯磺酰氯 在 ammonium hydroxide 、 air 、 tin chloride dihydrate 、 potassium tert-butylate 作用下， 以 乙醚 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 5-amino-2-[(E)-2-(4-amino-2-(aminosulfonyl)phenyl)ethenyl]benzene sulfonamide
  参考文献：
  名称：

  Synthesis of (bis)Sulfonic acid, (bis)Benzamides as follicle-Stimulating hormone (FSH) antagonists

  摘要：

  Screening efforts identified (bis)sulfonic acid. (bis)benzamides (1-3) as compounds that interact with the follicle stimulating-hormone receptor (FSHR) and inhibit FSH-stimulated CAMP accumulation with IC50 values in the low micromolar range. Structure-activity relationship studies using novel analogues of 1-3 revealed that two phenylsulfonic acid moieties were necessary for activity and that the carbon-carbon double bond of the stilbene sub-series was the optimum spacer connecting these groups. Selected analogues (2, 14, and 50) were also able to block FSHR-dependent estradiol production in rat primary ovarian granulosa cells and progesterone secretion in a clonal mouse adrenal Y1 cell line. IC50 values for these compounds in these assays were in the low micromolar range. Optimization of the benzoic acid side chains of 1-3 led to gains in selectivity versus activity at the thyroid stimulating hormone (TSH) receptor (TSHR). For instance, while stilbene (bis)sulfonic acid congener 2 was only 10-fold selective for FSHR over TSHR, analogue 50 with an IC50 value of 0.9 muM in the FSHR-cAMP assay was essentially inactive at 30muM in the TSHR-cAMP assay. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00324-8

文献信息

• [EN] ARYL SULFONIC ACIDS AND DERIVATIVES AS FSH ANTAGONISTS<br/>[FR] ACIDES SULFONIQUES ARYLES ET DERIVES TELS QUE LES ANTAGONISTES FSH
  申请人：AMERICAN HOME PROD

  公开号：WO2000058277A1

  公开（公告）日：2000-10-05

  This invention provides compounds of formula (I) having the structure wherein Q is hydrogen or -SO2R1; X is a bond, O, S(O)¿n?, -CH=CH-, -CH2CH2-, -C C-, or -CH2S(O)nCH2-; R?1¿ is OH, NH¿2?, C1 to C6 alkoxy, C1 to C3 perfluoroalkoxy; Ar is (a) or (b); Ar' is (c) or (d); R?2 and R4¿ are each, independently, hydrogen, OR6, -S(O)¿m?R?6, -NHR6, -N(R6)¿2, or -CH2SO2CH3; R?3 and R5¿ are each, independently, hydrogen, -NO¿2?, -NH2, -SO2R?9¿, or -CH¿2R?9; R6 is hydrogen, C¿1? to C6 alkyl, C3 to C6 alkenyl, -CH2CH2Z, -CH2COR?7, -CH¿2CH=CHCOR7, (e), (f) or (g); Y¿1? and Y?3¿ are each, independently, N, or CH; Y?2 and Y4¿ are each independently, O, S, or NR?13; R7 is -OR8, -NHR8, -N(R8)¿2, or -NHCH2CH2OR8; Z is -OR¿8?, -OCH2CH2OR?8, -N(R8)¿2, or (h); R8 is hydrogen or C1 to C3 alkyl; R9 is C1 to C6 alkyl, C3 to C6 alkenyl, OH, NHR?10, N(R10)¿2, CH2COR11, -CH2CH=CHCOR11, or (i); R10 is C1 to C3 alkyl, C3 to C4 alkenyl, phenyl, -CH2CH2OCH3, or -(j); R?11 is -OR12, -NHR12, -N(R12)¿2, or -NHCH2CH2OR12; R12 is hydrogen, or C¿1? to C3 alkyl; R?13¿ is hydrogen, or C¿1? to C3 alkyl; W is a bond, CH2, CH2CH2, O, S(O)q, NCHO, NCOCH3, or NR?12¿; m is 0 - 2; n is 0 - 2; q is 0 - 2, with the proviso that R?2 and R3¿ are not both hydrogen; or pharmaceutically acceptable salt thereof, which are useful as contraceptive agents.

  本发明提供了具有结构式(I)的化合物，其中Q为氢或-SO2R1; X为键，O，S(O)n，-CH=CH-，-CH2CH2-，-CC-或-CH2S(O)nCH2-; R1为OH，NH2，C1到C6烷氧基，C1到C3全氟烷氧基; Ar为(a)或(b); Ar'为(c)或(d); R2和R4分别独立地为氢，OR6，-S(O)mR6，-NHR6，-N(R6)2或-CH2SO2CH3; R3和R5独立地为氢，-NO2，-NH2，-SO2R9或-CH2R9; R6为氢，C1到C6烷基，C3到C6烯基，-CH2CH2Z，-CH2COR7，-CH2CH=CHCOR7，(e)，(f)或(g); Y1和Y3独立地为N或CH; Y2和Y4独立地为O，S或NR13; R7为-OR8，-NHR8，-N(R8)2或-NHCH2CH2OR8; Z为-OR8，-OCH2CH2OR8，-N(R8)2或(h); R8为氢或C1到C3烷基; R9为C1到C6烷基，C3到C6烯基，OH，NHR10，N(R10)2，CH2COR11，-CH2CH=CHCOR11或(i); R10为C1到C3烷基，C3到C4烯基，苯基，-CH2CH2OCH3或-(j); R11为-OR12，-NHR12，-N(R12)2或-NHCH2CH2OR12; R12为氢或C1到C3烷基; R13为氢或C1到C3烷基; W为键，CH2，CH2CH2，O，S(O)q，NCHO，NCOCH3或NR12; m为0-2; n为0-2; q为0-2，但R2和R3不能同时为氢; 或其药学上可接受的盐，其作为避孕剂有用。
• Aryl sulfonic acids and derivatives as FSH antagonists
  申请人：American Home Products Corporation

  公开号：US20020111369A1

  公开（公告）日：2002-08-15

  This invention provides compounds of formula I having the structure 1 wherein Q is hydrogen or —SO 2 R 1 ; X is a bond, O, S(O) n , —CH═CH—, —CH 2 CH 2 —, —C≡C—, or —CH 2 S(O) n CH 2 —; R 1 is OH, NH 2 , C 1 to C 6 alkoxy, C 1 to C 3 perfluoroalkoxy; 2 R 2 and R 4 are each, independently, hydrogen, OR 6 , —S(O) m R 6 , —NHR 6 , —N(R 6 ) 2 , or —CH 2 SO 2 CH 3 ; R 3 and R 5 are each, independently, hydrogen, —NO 2 , —NH 2 , —SO 2 R 9 , or —CH 2 R 9 ; R 6 is hydrogen, C 1 to C 6 alkyl, C 3 to C 6 alkenyl, —CH 2 CH 2 Z, —CH 2 COR 7 , —CH 2 CH═CHCOR 7 3 Y 1 and Y 3 are each, independently, N, or CH; Y 2 and Y 4 are each independently, O, S, or NR 13 ; R 7 is —OR 8 , —NHR 8 , —N(R 8 ) 2 , or —NHCH 2 CH 2 OR 8 ; Z is —OR 8 , —OCH 2 CH 2 OR 8 , —N(R 8 ) 2 , or 4 R 8 is hydrogen, or C 1 to C 3 alkyl; R 9 is C 1 to C 6 alkyl, C 3 to C 6 alkenyl, OH, NHR 10 , N(R 10 ) 2 , CH 2 COR 11 , —CH 2 CH═CHCOR 11 , or 5 R 10 is C 1 to C 3 alkyl, C 3 to C 4 alkenyl, phenyl, —CH 2 CH 2 OCH 3 , or 6 R 11 is —OR 12 , NHR 12 , —N(R 12 ) 2 , or —NHCH 2 CH 2 OR 12 ; R 12 is hydrogen, or C 1 to C 3 alkyl; R 13 is hydrogen, or C 1 to C 3 alkyl; W is a bond, CH 2 , CH 2 CH 2 , O, S(O) q , NCHO, NCOCH 3 , or NR 12 ; m is 0-2; n is 0-2; q is 0-2, with the proviso that R 2 and R 3 are not both hydrogen; or pharmaceutically acceptable salt thereof, which are useful as contraceptive agents.

  本发明提供了式I的化合物，其具有结构1， 其中， Q为氢或—SO2R1； X为键合，O，S(O)n，—CH═CH—，—CH2CH2—，—C≡C—或—CH2S(O)nCH2—； R1为OH，NH2，C1到C6烷氧基，C1到C3全氟烷氧基； R2和R4各自独立地为氢，OR6，—S(O)mR6，—NHR6，—N(R6)2或—CH2SO2CH3； R3和R5各自独立地为氢，—NO2，—NH2，—SO2R9或—CH2R9； R6为氢，C1到C6烷基，C3到C6烯基，—CH2CH2Z，—CH2COR7，—CH2CH═CHCOR73； Y1和Y3各自独立地为N或CH； Y2和Y4各自独立地为O，S或NR13； R7为—OR8，—NHR8，—N(R8)2或—NHCH2CH2OR8； Z为—OR8，—OCH2CH2OR8，—N(R8)2或 4 R8为氢或C1到C3烷基； R9为C1到C6烷基，C3到C6烯基，OH，NHR10，N(R10)2，CH2COR11，—CH2CH═CHCOR11或 5 R10为C1到C3烷基，C3到C4烯基，苯基，—CH2CH2OCH3或 6 R11为—OR12，NHR12，—N(R12)2或—NHCH2CH2OR12； R12为氢或C1到C3烷基； R13为氢或C1到C3烷基； W为键合，CH2，CH2CH2，O，S(O)q，NCHO，NCOCH3或NR12； m为0-2； n为0-2； q为0-2； 但R2和R3不能同时为氢； 或其药学上可接受的盐，其作为避孕剂具有用途。
• JPH0249078A
  申请人：——

  公开号：JPH0249078A

  公开（公告）日：1990-02-19
• US6355633B1
  申请人：——

  公开号：US6355633B1

  公开（公告）日：2002-03-12
• Synthesis of (bis)Sulfonic acid, (bis)Benzamides as follicle-Stimulating hormone (FSH) antagonists
  作者：Jay Wrobel、Daniel Green、James Jetter、Wenling Kao、John Rogers、M Claudia Pérez、Jill Hardenburg、Darlene C Deecher、Francisco J López、Brian J Arey、Emily S Shen

  DOI：10.1016/s0968-0896(01)00324-8

  日期：2002.3

  Screening efforts identified (bis)sulfonic acid. (bis)benzamides (1-3) as compounds that interact with the follicle stimulating-hormone receptor (FSHR) and inhibit FSH-stimulated CAMP accumulation with IC50 values in the low micromolar range. Structure-activity relationship studies using novel analogues of 1-3 revealed that two phenylsulfonic acid moieties were necessary for activity and that the carbon-carbon double bond of the stilbene sub-series was the optimum spacer connecting these groups. Selected analogues (2, 14, and 50) were also able to block FSHR-dependent estradiol production in rat primary ovarian granulosa cells and progesterone secretion in a clonal mouse adrenal Y1 cell line. IC50 values for these compounds in these assays were in the low micromolar range. Optimization of the benzoic acid side chains of 1-3 led to gains in selectivity versus activity at the thyroid stimulating hormone (TSH) receptor (TSHR). For instance, while stilbene (bis)sulfonic acid congener 2 was only 10-fold selective for FSHR over TSHR, analogue 50 with an IC50 value of 0.9 muM in the FSHR-cAMP assay was essentially inactive at 30muM in the TSHR-cAMP assay. (C) 2002 Elsevier Science Ltd. All rights reserved.