CN1491207A - 酰化的二氢化茚基胺及其作为药物的用途 - Google Patents
酰化的二氢化茚基胺及其作为药物的用途 Download PDFInfo
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- CN1491207A CN1491207A CNA028048369A CN02804836A CN1491207A CN 1491207 A CN1491207 A CN 1491207A CN A028048369 A CNA028048369 A CN A028048369A CN 02804836 A CN02804836 A CN 02804836A CN 1491207 A CN1491207 A CN 1491207A
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- phenyl
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P11/00—Drugs for disorders of the respiratory system
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- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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Abstract
Description
条件a条件b条件c条件d | Merck Porospher 55×2mm,5μ,梯度:95%H2O(0.05%TFA)至95%乙腈,4分钟,95%乙腈,1.5分钟,0.5ml/分钟)YMC J′Sphere ODS H80,33×2.1mm,3μ,梯度:90%H2O(0.05%TFA)至95%乙腈,2.5分钟,95%乙腈,0.8分钟,1ml/分钟)LiChroCart 55-2,PuroSpher STAR;RP18 e(MERCK),溶剂A:乙腈/水(90∶10)+0.5%甲酸;溶剂B:乙腈/水(10∶90)+0.5%甲酸;梯度:95%B 0.5分钟,在1.75分钟内从95%B至5%B,5%B 2.5分钟;1ml/分钟TLC,硅胶60,F254(Merck),溶剂:正庚烷∶乙酸乙酯=1∶1 |
化合物序号 | EC-50(μM) | TIR(max) |
1a | 6.0 | 2.80 |
1b | 0.2 | 3.00 |
4 | 3.0 | 2.95 |
5 | 30 | 2.50 |
6 | 1.2 | 2.55 |
7 | 0.1 | 2.57 |
8 | 8.0 | 2.20 |
21 | 0.8 | 4.10 |
22 | 7.0 | 2.10 |
23 | 5.0 | 2.20 |
24 | 2.5 | 2.88 |
25 | 12 | 2.70 |
化合物序号 | EC-50(μM) | TIR(max) |
26 | 0.9 | 3.80 |
27 | 0.2 | 3.60 |
28 | 2.5 | 4.40 |
29 | 0.8 | 3.80 |
30 | 3.0 | 2.94 |
31 | 6.0 | 3.05 |
32 | 1.7 | 4.00 |
33 | 4.0 | 3.30 |
34 | 1.7 | 3.40 |
41 | 0.18 | 2.4 |
61 | 0.7 | 2.60 |
66 | 0.14 | 2.7 |
69 | 0.4 | 4.20 |
73 | 0.7 | 4.00 |
185 | 27 | 2.4 |
187 | 4.4 | 2.5 |
189 | 10 | 2.2 |
203 | 16 | 2.7 |
216 | 0.7 | 2.8 |
230 | 0.820 | 4 |
233 | 13 | 2.5 |
236 | 22 | 2 |
237 | 7.7 | 2.5 |
243 | 0.110 | 2.8 |
246 | 0.670 | 2.5 |
248 | 7.8 | 2.8 |
249 | 15 | 2.5 |
250 | 58 | 2.5 |
251 | 13 | 2.6 |
253 | 13 | 2.2 |
化合物序号 | EC-50(μM) | TIR(max) |
256 | 11 | 2.5 |
257 | 4.3 | 2.7 |
262 | 5.8 | 2.8 |
263 | 13 | 2.5 |
264 | 0.580 | 2.9 |
265 | 0.183 | 2.7 |
266 | 22 | 2.5 |
267 | 2.8 | 2.5 |
268 | 0.485 | 3 |
272 | 1.6 | 2.9 |
273 | 2.6 | 2.8 |
274 | 21 | |
275 | 0.559 | 3 |
276 | 0.157 | 3 |
277 | 4.1 | 3 |
281 | 0.684 | 3 |
282 | 16 | 2.3 |
283 | 15 | 2.5 |
286 | 26 | 2.6 |
287 | 13 | 2.9 |
289 | 0.142 | 2.6 |
291 | 0.238 | 2.8 |
292 | 0.039 | 2.9 |
293 | 14 | 1.7 |
294 | 14 | 2.2 |
295 | 0.846 | 2.4 |
296 | 13 | 2.5 |
302 | 27 | 2.8 |
306 | 0.263 | 2.7 |
312 | 16 | 2.2 |
化合物序号 | EC-50(μM) | TIR(max) |
314 | 12 | 2.2 |
315 | 16 | 2.2 |
317 | 0.197 | 2.9 |
319 | 25 | 2.4 |
320 | 12 | 3 |
321 | 9.6 | 2.5 |
322 | 23 | 2.3 |
324 | 2.1 | 1.7 |
327 | 2.6 | 2.5 |
328 | 24 | 2.4 |
329 | 2.2 | 1.5 |
330 | 12 | 2.2 |
331 | 0.147 | 2.8 |
332 | 4.0 | 2 |
335 | 0.943 | 2.7 |
341 | 22 | 2.5 |
342 | 0.287 | 3 |
346 | 26 | 2.6 |
350 | 0.523 | 2.9 |
358 | 4.7 | 2.5 |
360 | 10 | 2.6 |
361 | 21 | 2.5 |
364 | 2.1 | 2.9 |
365 | 0.250 | 3 |
366 | 37 | 2.5 |
368 | 17 | 2.5 |
372 | 1.6 | 2.7 |
375 | 8.0 | 2.3 |
376 | 5.3 | 2.4 |
380 | 2.3 | 2.6 |
化合物序号 | EC-50(μM) | TIR(max) |
381 | 12 | 2.5 |
382 | 21 | 2.5 |
386A | 5.1 | 3.3 |
386B | 0.309 | 2.5 |
387 | 32 | 2.6 |
388 | 1.1 | 2.4 |
396A | 0.6 | 3.55 |
397 | 30 | 1.7 |
398B | 30 | 3.46 |
404 | 12 | 3.50 |
405 | 30 | 2.80 |
408 | 11 | 2.5 |
411 | 2.0 | 2.5 |
412 | 1.0 | 2.5 |
413 | 8.5 | 2.5 |
427 | 3.7 | 2.5 |
428 | 0.841 | 2.8 |
429 | 0.6 | 2.8 |
432 | 9.6 | 2.5 |
433 | 19 | 2.6 |
435 | 14 | 2.5 |
436 | 18 | 2.6 |
439 | 8.9 | 2.6 |
Claims (17)
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EP01102850.3 | 2001-02-13 |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN103018349A (zh) * | 2011-09-22 | 2013-04-03 | 北京美迪康信医药科技有限公司 | 一种二氢化茚酰胺化合物的检测分析方法 |
CN114206335A (zh) * | 2019-05-03 | 2022-03-18 | 普拉克西斯精密药物股份有限公司 | Kcnt1抑制剂和使用方法 |
WO2023098699A1 (en) * | 2021-12-01 | 2023-06-08 | Nanjing Immunophage Biotech Co., Ltd | Compounds and their uses as cd38 inhibitors |
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