CN100453529C - 芳基磺酰胺及其类似物及其在治疗神经变性疾病中的用途 - Google Patents
芳基磺酰胺及其类似物及其在治疗神经变性疾病中的用途 Download PDFInfo
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- CN100453529C CN100453529C CNB988043815A CN98804381A CN100453529C CN 100453529 C CN100453529 C CN 100453529C CN B988043815 A CNB988043815 A CN B988043815A CN 98804381 A CN98804381 A CN 98804381A CN 100453529 C CN100453529 C CN 100453529C
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Classifications
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- C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
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Abstract
Description
实施例 | IC<sub>50</sub>(nmol/l) |
1 | 15 |
33 | 10 |
51 | 0.9 |
65 | 13 |
99 | 2.9 |
实施例 | K<sub>i</sub>(nmol/l) |
1 | 590 |
33 | 420 |
51 | 41 |
65 | 250 |
实施例 | ED<sub>-1℃</sub><sup>a)</sup>[mg/kg] |
1 | 1.0<sup>b)</sup> |
33 | 0.6<sup>b)</sup> |
51 | 0.1<sup>b)</sup> |
65 | 1.0<sup>b)</sup> |
99 | 0.6<sup>b)</sup> |
实施例 | 梗塞体积的减小% | 剂量 |
1 | 35 | 0.03mg/kg/h <sup>b)</sup> |
33 | 33 | 0.1mg/kg <sup>a)</sup> |
51 | 24 | 0.1mg/kg <sup>a)</sup> |
65 | 37(47) | 0.03mg/kg/h <sup>b)</sup>(0.01mg/kg/h) |
实施例 | 梗塞体积的减小% | 剂量 |
1 | 54(84) | 0.1mg/kg <sup>a)</sup>(1.0mg/kg <sup>a)</sup> |
33 | 42 | 0.1mg/kg <sup>a)</sup> |
51 | 54 | 0.01mg/kg/h <sup>b)</sup> |
65 | 53(65) | 0.1mg/kg <sup>a)</sup>(0.3mg/kg/h <sup>b)</sup>) |
实施例编号 | U | R<sup>49</sup> | R<sup>50</sup> | R<sup>51</sup> | 收率[%] |
152A | O | H | H | F | 91.5 |
153A | O | CF<sub>3</sub> | H | F | 94 |
154A | CH<sub>2</sub> | F | F | F | 93 |
155A | - | Cl | F | Cl | 55 |
实施例编号 | U | R<sup>49</sup> | R<sup>50</sup> | R<sup>51</sup> | NMR-数据(CDCl<sub>3</sub>)<sup>19</sup>F:CFCl<sub>3</sub>/<sup>1</sup>H:TMS:δ[ppm] | 收率[%] |
157A | O | H | H | F | -74.5(t,8Hz)/4.2(m,2H);3.95(m,4H) | 87 |
158A | O | CF<sub>3</sub> | H | F | -74.2/4.45(m,2H);4.2(m,1H);3.95(m,2H) | 75 |
159A | CH<sub>2</sub> | F | F | F | -74.2(CF<sub>3</sub>);-118(CF<sub>2</sub>)/3.8(m,2H);2.4(m,4H) | 91 |
160A | - | Cl | F | Cl | -68.5(2F);-120(1F) | 60 |
实施例编号 | R<sup>61</sup> | R<sup>62</sup> | 收率(%理论值) | M.p.(℃) | R<sub>f</sub> | MS m/e |
85 | CONH<sub>2</sub> | H | 32 | 206 | 0,45(XXII) | 416(M+NH<sub>4</sub>)(B) |
86 | H | CONHCH<sub>3</sub> | 82 | 204 | 0,11(XXII) | 430(M+NH<sub>4</sub>)(B) |
实施例编号 | 起始物实施例编号 | X | Y | 收率(%理论值) | M.P.(℃) | R<sub>f</sub> | MS m/e |
87 | 36 | NH<sub>2</sub> | H | 57 | 103,5 | 0,50(VII) | 405(M+H)(B) |
88 | 41 | H | NH<sub>2</sub> | 70 | 182 | - | 405(M+H)(C) |
实施例编号 | R<sup>63</sup> | R<sup>64</sup> | 收率(%理论值) | M.p.(℃) | R<sub>f</sub> | MS m/e |
92 | CH<sub>2</sub>OH | H | 51 | 200 | 0,06(IV) | 403(M+NH<sub>4</sub>)(B) |
93 | H | CH<sub>2</sub>OH | 91 | - | 0,13(VI) | 403(M+NH<sub>4</sub>)(B) |
实施例 | R<sup>2</sup> | 收率(%) | M.p.(℃) | R<sub>f</sub> | MS(m/e) |
206 | nBu | 81 | 0.45(XXVII) | 403(M+NH<sub>4</sub>)(B) | |
207 | Bzl | 82 | 油 | 0.45(XXX) | 437(M+NH<sub>4</sub>)(B) |
实施例 | R<sup>3</sup> | 收率(%理论值) | M.p.(℃) | R<sub>f</sub> | MS(m/e) |
250 | 乙基 | 22 | - | 0.48(XXXIII) | - |
251 | 异丙基 | 85 | 185 | 0.56(XXXIII) | 418(M+H)(E) |
252 | 正丁基 | 55 | 151 | 0.69(XXXIII) | 432(M+H)(E) |
实施例 | R<sup>66</sup> | 收率(%理论值) | M.p.(℃) | R<sub>f</sub> | MS(m/e) |
255 | 环丙基羰基 | 66 | 177 | 0.54(XLI) | 473(M+H)(E) |
256 | 苯甲酰基 | 46 | 197 | 0.56(XLI) | 509(M+H)(E) |
257 | 甲磺酰基 | 22 | 205 | 0.3(XLVI) | 483(M+H)(E) |
实施例 | R<sup>3</sup> | 收率(%理论值) | R<sub>f</sub> | MS |
300 | Me | 63 | 0.50(XXV) | 375(M+H),B |
301 | nPr | 50 | 0.58(XXV) | 403(M+H),B |
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DE19706902.9 | 1997-02-21 | ||
DE19706902 | 1997-02-21 | ||
DE19740785A DE19740785A1 (de) | 1997-02-21 | 1997-09-17 | Arylsulfonamide und Analoga |
DE19740785.4 | 1997-09-17 |
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CN2007101667578A Division CN101177385B (zh) | 1997-02-21 | 1998-02-10 | 芳基磺酰胺及其类似物及其在治疗神经变性疾病中的用途 |
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US4238626A (en) * | 1971-07-23 | 1980-12-09 | Hoechst Aktiengesellschaft | 4-Phenoxy-phenoxy-alkane-carboxylic acid derivatives and process for their manufacture |
US5093340A (en) * | 1986-09-24 | 1992-03-03 | Bayer Aktiengesellschaft | Substituted phenylsulphonamides |
US4931457A (en) * | 1989-06-28 | 1990-06-05 | Hoechst-Roussel Pharmaceuticals Inc. | Naphthylamino-and naphthyloxy-pyridinamine comounds useful as topical antiinflammatory agents for the treatment of skin disorders |
US4931457B1 (en) * | 1989-06-28 | 1993-11-16 | Hoechst-Roussel Pharmaceuticals Incorporated | Naphthylamino-and naphthyloxy-pyridineamin compounds useful as topical antiinflammatory agents for the treatment of skin disorders |
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