6-amino-N-(cyclohexylmethoxy)hexane-1-sulfonamide | 1170231-67-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: 6-amino-N-(cyclohexylmethoxy)hexane-1-sulfonamide
• CAS: 1170231-67-0
• 化学式: C₁₃H₂₈N₂O₃S
• 分子量: 292.443
• InChiKey: JQAMGGDAKUKZQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  89.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-amino-N-(cyclohexylmethoxy)hexane-1-sulfonamide 、 S-methyl-N-cyano-N'-4-pyridylisothiourea 在 吡啶 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以58%的产率得到6-(2-cyano-1-(pyridin-4-yl)guanidino)-N-(cyclohexylmethoxy)hexane-1-sulfonamide
  参考文献：
  名称：

  Nicotinamide Phosphoribosyltransferase Inhibitors, Design, Preparation, and Structure–Activity Relationship

  摘要：

  Existing pharmacological inhibitors for nicotinamide phosphoribosyltransferase (NAMPT) are promising therapeutics for treating cancer. By using medicinal and computational chemistry methods, the structure-activity relationship for novel classes of NAMPT inhibitors is described, and the compounds are optimized. Compounds are designed inspired by the NAMPT inhibitor APO866 and cyanoguanidine inhibitor scaffolds. In comparison with recently published derivatives, the new analogues exhibit an equally potent antiproliferative activity in vitro and comparable activity in vivo. The best performing compounds from these series showed subnanomolar antiproliferative activity toward a series of cancer cell lines (compound 15: IC50 0.025 and 0.33 nM, in A2780 (ovarian carcinoma) and MCF-7 (breast), respectively) and potent antitumor in vivo activity in well-tolerated doses in a xenograft model. In an A2780 xenograft mouse model with large tumors (500 mm(3)), compound 15 reduced the tumor volume to one-fifth of the starting volume at a dose of 3 mg/kg administered ip, bid, days 1-9. Thus, compounds found in this study compared favorably with compounds already in the clinic and warrant further investigation as promising lead molecules for the inhibition of NAMPT.

  DOI：

  10.1021/jm4009949
• 作为产物：
  描述：

  1,6-二溴己烷 在 五氯化磷 、 sodium sulfite 、 一水合肼 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 94.0h， 生成 6-amino-N-(cyclohexylmethoxy)hexane-1-sulfonamide
  参考文献：
  名称：

  Nicotinamide Phosphoribosyltransferase Inhibitors, Design, Preparation, and Structure–Activity Relationship

  摘要：

  Existing pharmacological inhibitors for nicotinamide phosphoribosyltransferase (NAMPT) are promising therapeutics for treating cancer. By using medicinal and computational chemistry methods, the structure-activity relationship for novel classes of NAMPT inhibitors is described, and the compounds are optimized. Compounds are designed inspired by the NAMPT inhibitor APO866 and cyanoguanidine inhibitor scaffolds. In comparison with recently published derivatives, the new analogues exhibit an equally potent antiproliferative activity in vitro and comparable activity in vivo. The best performing compounds from these series showed subnanomolar antiproliferative activity toward a series of cancer cell lines (compound 15: IC50 0.025 and 0.33 nM, in A2780 (ovarian carcinoma) and MCF-7 (breast), respectively) and potent antitumor in vivo activity in well-tolerated doses in a xenograft model. In an A2780 xenograft mouse model with large tumors (500 mm(3)), compound 15 reduced the tumor volume to one-fifth of the starting volume at a dose of 3 mg/kg administered ip, bid, days 1-9. Thus, compounds found in this study compared favorably with compounds already in the clinic and warrant further investigation as promising lead molecules for the inhibition of NAMPT.

  DOI：

  10.1021/jm4009949

文献信息

• [EN] NOVEL CYANOGUANIDINES<br/>[FR] NOUVELLES CYANOGUANIDINES
  申请人：TOPOTARGET AS

  公开号：WO2009086835A1

  公开（公告）日：2009-07-16

  This application discloses novel cyanoguanidines of the formula (I) wherein A is selected from -C(=O)-, -S(=O)2-, -C(=S)-, and -P(=O)(R5)-, wherein R5 is selected from C1-6-alkyl, C1-6-alkoxy, and hydroxy; B is selected from a single bond, -O-, -NR6- and -C(=O)-NR6-, wherein R6 is selected from hydrogen, optionally substituted C1-12-alkyl, optionally substituted C1-12-alkenyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl; and m is an integer of 0-12 and n is an integer of 0-12, wherein the sum m+n is 1-20; and R1 is selected from optionally substituted heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The compounds are usefuld for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT).

  该申请公开了一种新型氰胍啶化合物，其化学式为（I），其中A从-C（=O）-，-S（=O）2-，-C（=S）-和-P（=O）（R5）-中选择，其中R5选择自C1-6-烷基，C1-6-烷氧基和羟基；B从单键，-O-，-NR6-和-C（=O）-NR6-中选择，其中R6选择自氢，可选择地取代的C1-12-烷基，可选择地取代的C1-12-烯基，可选择地取代的芳基，可选择地取代的杂环烷基和可选择地取代的杂环芳基；m为0-12的整数，n为0-12的整数，其中m+n之和为1-20；R1选择自可选择地取代的杂环芳基；以及其药学上可接受的盐和前药。这些化合物可用作治疗由烟酰胺磷酸核糖转移酶（NAMPRT）水平升高引起的疾病或病况的药物。
• [EN] NOVEL UREA AND THIOUREA DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS D'URÉE ET DE THIOURÉE
  申请人：TOPOTARGET AS

  公开号：WO2010023307A1

  公开（公告）日：2010-03-04

  The present application discloses compounds of formula (I) wherein X is =O, =S, =NH, =NOH and =NO-Me; A is -C(=O)-, -S(=O)2 -, -C(=S)- and P(=O)(R5)-; B is, -O-, -(CH2) 3-6-, and O-(CH2)2-5-; D is, -O-, -CR7R8 -and -NR9; m is 0-12, n is 0-12, m+n is 1-20; p is 0-4; R1 is opt.sub. heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The application also discloses the compound for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT), e.g. inflammatory and tissue repair disorders; dermatosis; autoimmune diseases, Alzheimers disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, ataxia telengiectasia.

  本申请公开了以下式(I)的化合物，其中X为=O、=S、=NH、=NOH和=NO-Me；A为-C(=O)-、-S(=O)2-、-C(=S)-和P(=O)(R5)-；B为-O-、-(CH2)3-6-和O-(CH2)2-5-；D为-O-、-CR7R8-和-NR9；m为0-12，n为0-12，m+n为1-20；p为0-4；R1为opt.sub.杂环烷基；以及其药学上可接受的盐和前药。该申请还公开了该化合物用作治疗由尼克酰胺磷酸核糖转移酶(NAMPRT)水平升高引起的疾病或症状的药物，例如炎症和组织修复紊乱；皮肤病；自身免疫疾病，阿尔茨海默病，中风，动脉粥样硬化，再狭窄，糖尿病，肾小球肾炎，癌症，虚弱症，与感染相关的炎症和某些病毒感染，包括获得性免疫缺陷综合症（AIDS），成人呼吸窘迫综合征，遗传性共济失调。
• SQUARIC ACID DERIVATIVES AS INHIBITORS OF THE NICOTINAMIDE
  申请人：Christensen Mette Knak

  公开号：US20120225847A1

  公开（公告）日：2012-09-06

  The present application discloses novel squaric acid derivatives of the formula A: from —C(═O)—, —S(═O) 2 —, —C(═S)— and —P(═O)(R 5 )—; B: -, —O—, —NR 6 — and —C(═O)—NR 6 —; D: -, —O—, —CR 7 R 8 — and —NR 9 ; m=0-12; n=0-12; m+n=1-20; p=0-2; R 1 : heteroaryl, aryl; R 2 : H, C 1-12 -alkyl, C 3-12 -cycloalkyl, —[CH 2 CH 2 O] 1-10 —(C 1-6 -alkyl), C 1-12 -alkenyl, aryl, heterocyclyl, heteroaryl; R 3 : C 1-12 -alkyl, C 3-12 -cycloalkyl, —[CH 2 CH 2 O] 1-10 —(C 1-6 -alkyl), C 1-12 -alkenyl, aryl, heterocyclyl, heteroaryl; or R 2 and R 3 : N-containing heterocyclic/heteroaromatic ring; R 4 and R 4 *: H, C 1-12 -alkyl, C 1-12 -alkenyl; and pharmaceutically acceptable salts and prodrugs thereof, and their use in the treatment of diseases/conditions caused by an elevated level of NAMPRT (inflammatory and tissue repair disorders, particularly rheumatoid arthritis, inflammatory bowel disease, asthma and CPOD, osteoarthritis, osteoporosis and fibrotic diseases; dermatosis; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and viral infections, adult respiratory distress syndrome, ataxia telengiectasia).

  本申请公开了公式A的新型苯二甲酸衍生物：从—C（═O）—，—S（═O）2—，—C（═S）—和—P（═O）（R5）—；B：-，—O—，—NR6—和—C（═O）—NR6—；D：-，—O—，—CR7R8—和—NR9；m=0-12；n=0-12；m+n=1-20；p=0-2；R1：杂环芳基，芳基；R2：H，C1-12-烷基，C3-12-环烷基，—[CH2CH2O]1-10—（C1-6-烷基），C1-12-烯基，芳基，杂环烷基，杂环芳基；R3：C1-12-烷基，C3-12-环烷基，—[CH2CH2O]1-10—（C1-6-烷基），C1-12-烯基，芳基，杂环烷基，杂环芳基；或R2和R3：含氮杂环/杂芳基环；R4和R4*：H，C1-12-烷基，C1-12-烯基；以及其药学上可接受的盐和前药，以及它们在治疗由NAMPRT水平升高引起的疾病/状况中的用途（炎症和组织修复障碍，特别是类风湿性关节炎，炎症性肠病，哮喘和CPOD，骨关节炎，骨质疏松症和纤维性疾病；皮肤病；自身免疫性疾病，包括系统性红斑狼疮，多发性硬化症，银屑病性关节炎，强直性脊柱炎，组织和器官排斥，阿尔茨海默病，中风，动脉粥样硬化，再狭窄，糖尿病，肾小球肾炎，癌症，消瘦症，与感染和病毒感染相关的炎症，成人呼吸窘迫综合征，遗传性毛细血管扩张性共济失调）。
• NOVEL UREA AND THIOUREA DERIVATIVES
  申请人：Christensen Mette Knak

  公开号：US20120010172A1

  公开（公告）日：2012-01-12

  The present application discloses compounds of formula (I) wherein X is ═O, ═S, ═NH, ═NOH and ═NO-Me; A is —C(═O)—, —S(═O) 2 —, —C(═S)— and P(═O)(R 5 )—; B is, —O—, —(CH 2 ) 3-6 —, and O—(CH 2 ) 2-5 —; D is, —O—, —CR 7 R 8 — and —NR 9 ; m is 0-12, n is 0-12, m+n is 1-20; p is 0-4; R 1 is opt.sub. heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The application also discloses the compound for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT), e.g. inflammatory and tissue repair disorders; dermatosis; autoimmune diseases, Alzheimers disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, ataxia telengiectasia.
• NOVEL UREA AND THIOUREA DERIVATIVES
  申请人：TOPOTARGET A/S

  公开号：US20140357599A1

  公开（公告）日：2014-12-04

  The present application discloses compounds of formula (I) wherein X is ═O, ═S, ═NH, ═NOH and ═NO-Me; A is —C(═O)—, —S(═O) 2 —, —C(═S)— and P(═O)(R 5 )—; B is, —O—, —(CH 2 ) 3-6 —, and O—(CH 2 ) 2-5 —; D is, —O—, —CR 7 R 8 — and —NR 9 ; m is 0-12, n is 0-12, m+n is 1-20; p is 0-4; R 1 is opt.sub. heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The application also discloses the compound for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT), e.g. inflammatory and tissue repair disorders; dermatosis; autoimmune diseases, Alzheimers disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, ataxia telengiectasia.