CN112341389B - Nitrogen-containing aromatic heterocycle substituted quinoline formamide derivative and application thereof - Google Patents
Nitrogen-containing aromatic heterocycle substituted quinoline formamide derivative and application thereof Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/50—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 4
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- C07D401/00—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
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
Abstract
The invention discloses a nitrogen-containing aromatic heterocycle substituted quinoline formamide derivative and application thereof, wherein the structural formula of the nitrogen-containing aromatic heterocycle substituted quinoline formamide derivative is shown as a formula (4):
wherein R is 1 Selected from H, C1-C3 alkyl or C3-C5 cycloalkyl; r is 2 Selected from C1-C3 alkyl, C3-C5 cycloalkoxy or halogen; r 3 Is a nitrogen-containing aromatic heterocyclic group selected from one of the following groups:
and
Description
Technical Field
The invention relates to a nitrogen-containing aromatic heterocycle substituted quinoline formamide derivative and application thereof.
Background
Isocitrate dehydrogenase 1 (IDH 1) is a key rate-limiting enzyme in the tricarboxylic acid cycle (TCA). Mainly exists in cytoplasm and peroxisome, can utilize Nicotinamide Adenine Dinucleotide Phosphate (NADP) as an electron acceptor to oxidize and decarboxylate isocitrate into alpha-ketoglutarate (alpha-ketoglutarate, alpha-KG) and produce reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH), and both products are involved in energy metabolism, amino acid and vitamin synthesis and the like, so that the activity regulation of the enzyme can directly influence different biological pathways of IDH1 or IDH1 substrates involved in regulation and play different biological functions. Recent studies have found that IDH1 has higher mutation in various malignant tumors including glioma, acute myelogenous leukemia, chondrosarcoma, cholangiocarcinoma and acute lymphatic leukemia, including IDH1/R132H, IDH1/R132L and IDH1/R132C, and the like, and the mutation of IDH1/R132H is the main mutation. After IDH1 is mutated, the capability of catalyzing oxidative decarboxylation of isocitrate to generate a-KG is greatly reduced, and meanwhile, the mutated IDH1 also has a new function of catalyzing NADPH-dependent reduction reaction enhancement to reduce a-KG into 2-hydroxyglutaric acid (2-HG), so that 2-HG and alpha-KG compete due to the similarity of the structures of 2-HG and alpha-KG. Both of these causes reduce the activity of some dioxygenases, including Proline Hydroxylase (PHD), the Tet family of DNA hydroxylases, and histone lysine demethylases (KDMs), which are α -KG dependent, ultimately leading to tumorigenesis. In view of the important role of IDH1/132H in tumorigenesis and progression, IDH1/132H has become an attractive anti-tumor target. Therefore, the development of a highly effective IDH1/R132H inhibitor having a novel structure for the development of a novel highly effective and low toxic antitumor agent has become an urgent necessity.
Disclosure of Invention
The invention aims to provide nitrogen-containing heterocyclic aromatic substituted quinoline carboxamide derivatives which can be used as isocitrate dehydrogenase 1 mutant (IDH1/R132H) inhibitors and used for treating IDH1/R132H mediated related diseases.
A nitrogen-containing aromatic heterocycle substituted quinoline formamide derivative or pharmaceutically acceptable salt thereof with a structural formula shown as a formula (4):
wherein R is 1 Selected from H, C1-C3 alkyl or C3-C5 cycloalkyl; r 2 Selected from C1-C3 alkyl, C3-C5 cycloalkoxy or halogen;
R 3 is a nitrogen-containing aromatic heterocyclic group selected from one of the following groups:
the preparation method of the quinoline formamide derivative comprises the following steps: taking a 2-chloroquinoline-4-carboxylic acid derivative shown in a formula (1) as a raw material, carrying out a condensation reaction with a benzylamine derivative shown in a formula (2) under the action of CDI to obtain an intermediate (3) shown in a formula (3), and then carrying out a condensation reaction with a nitrogen-containing aromatic heterocyclic compound to obtain a quinoline carboxamide derivative target product shown in a formula (4), wherein the reaction formula is as follows:
wherein the nitrogen-containing aromatic heterocyclic compound is imidazole, piperazine, morpholine, 4-hydroxypiperidine, 4-piperidone acetal hydrochloride or 1,2, 4-triazole;
R 1 selected from H, C1-C3 alkyl or C3-C5 cycloalkyl; r 2 Selected from C1-C3 alkyl, C3-C5 cycloalkoxy or halogen;
R 3 is a nitrogen-containing aromatic heterocyclic group selected from one of the following groups:
the structural formula is shown as formula (4), and the nitrogen-containing aromatic heterocycle substituted quinoline formamide derivatives or pharmaceutically acceptable salts thereof are used as IDH1/R132H inhibitors.
The structural formula is shown as formula (4), and the application of the nitrogen-containing aromatic heterocycle substituted quinoline formamide derivative or pharmaceutically acceptable salt thereof in preparing IDH1/R132H mediated disease treatment medicines.
By adopting the technology, compared with the prior art, the invention has the following beneficial effects:
the nitrogen-containing aromatic heterocycle substituted quinoline formamide derivatives designed and synthesized by the invention are novel isocitrate dehydrogenase 1 mutant (IDH1/R132H) inhibitors, are suitable for drug development with the isocitrate dehydrogenase 1 mutant (IDH1/R132H) as a target spot, and the obtained drugs can be used for treating malignant tumors such as glioma, acute myelogenous leukemia and the like.
Detailed Description
The present invention is further illustrated by the following examples, which should not be construed as limiting the scope of the invention.
Example 1: 2-chloro-N- (4-methylbenzyl) quinoline-4-carboxamide 3a
162mg (0.78mmol) of 2-chloroquinoline-4-carboxylic acid, 140mg (0.86mmol) of N' N-Carbonyldiimidazole (CDI) and 20ml of methylene chloride were charged in a reaction flask, and stirred at 35 ℃ for 20 minutes, 106mg (0.88mmol) of 4-methylbenzylamine was further added thereto and reacted at room temperature for 18 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to give 183mg of 3a as a white solid in a yield of 75.5% and a melting point of 192 ℃ and 194 ℃. 1 H NMR(500MHz,CDCl 3 )δ8.27-8.21(m,1H),8.10-8.03(m,1H),7.84-7.76(m,1H),7.68-7.60(m,1H),7.46(s,1H),7.30(d,J＝8.0Hz,2H),7.22(d,J＝7.8Hz,2H),6.32-6.27(m,1H),4.70(d,J＝5.7Hz,2H),2.38(s,3H).
Example 2: n- (4-bromobenzyl) -2-chloroquinoline-4-carboxamide 3b
The synthesis of example 2 was carried out as in example 1, except that 4-methylbenzylamine was replaced with an equimolar amount of 4-bromobenzylamine, and the procedure was as in example 1. The final reaction gave the target compound 3b as a white solid in a yield of 67.7%, melting point 221-. 1 H NMR(500MHz,CDCl 3 )δ8.19(dd,J＝8.6,1.7Hz,1H),8.05(d,J＝8.5Hz,1H),7.84-7.76(m,1H),7.67-7.59(m,1H),7.57-7.50(m,2H),7.45(s,1H),7.33-7.26(m,2H),6.45(s,1H),4.69(d,J＝5.9Hz,2H).
Example 3: n- (4-chlorobenzyl) -2-chloroquinoline-4-carboxamide 3c
The synthesis of example 3 was performed as in example 1, except that 4-methylbenzylamine was replaced with an equimolar amount of 4-chlorobenzylamine, and the procedure was otherwise the same as in example 1. Finally, the white solid target compound 3c is obtained through the reaction, the yield is 60.1 percent, and the melting point is 147-149 ℃. 1 H NMR(500MHz,CDCl 3 )δ8.20(dd,J＝8.3,1.4Hz,1H),8.05(d,J＝8.5Hz,1H),7.83-7.75(m,1H),7.67-7.59(m,1H),7.46(s,1H),7.40-7.34(m,4H),6.88(s,1H),4.71(d,J＝5.9Hz,2H).
Example 4- (1H-imidazol-1-yl) -N- (4-methylbenzyl) quinoline-4-carboxamide 4a
50mg (0.16mmol) of the compound 3a, 13mg (0.19mmol) of imidazole, 187mg (0.57mmol) of cesium carbonate and 8mL of anhydrous DMF were charged in a reaction flask and reacted at 80 ℃ for 90 minutes. After completion of the reaction, the reaction mixture was cooled, poured into 30mL of water, extracted with ethyl acetate (20 mL. times.3), the organic phases were combined, washed with saturated brine (50 mL. times.3), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (DCM: MeOH. RTM. 30:1, v/v) to give 36mg of a pale yellow solid as a mesh The target compound 4a was obtained in a yield of 65.5%, melting point: 225-. 1 H NMR(500MHz,CDCl 3 )δ8.44(s,1H),8.26-8.15(m,1H),8.08-8.04(m,1H),7.84-7.75(m,2H),7.63-7.58(m,1H),7.55(s,1H),7.36-7.31(m,2H),7.25-7.18(m,3H),6.59-6.54(m,1H),4.74(d,J＝5.6Hz,2H),2.38(s,3H).
Example 5: n- (4-bromobenzyl) -2- (1H-imidazol-1-yl) quinoline-4-carboxamide 4b
The synthesis of example 5 was performed as in example 4, except that the compound 3a was replaced by an equimolar amount of the compound 3b, and the procedure was as in example 4. The final reaction gave the target compound 4b as a white solid in a yield of 63.9%, melting point 213-215 ℃. 1 H NMR(500MHz,CDCl 3 )δ8.46(s,1H),8.20-8.14(m,1H),8.10-8.05(m,1H),7.86-7.78(m,2H),7.66-7.58(m,1H),7.56-7.52(m,3H),7.37-7.26(m,2H),7.22-7.18(m,1H),6.77-6.73(m,1H),4.74(d,J＝5.9Hz,2H).
Example 6: n- (4-chlorobenzyl) -2- (1H-imidazol-1-yl) quinoline-4-carboxamide 4c
Example 6 was synthesized as in example 4, except that the starting material 3a was replaced with an equimolar amount of the 3c compound, and the procedure was otherwise the same as in example 4. Finally, the reaction is carried out to obtain the target compound 4c as a white solid, the yield is 69.3 percent, and the melting point is 209-211 ℃. 1 H NMR(500MHz,CDCl 3 )δ8.37(s,1H),8.17(dd,J＝8.4,1.4Hz,1H),8.08-8.01(m,1H),7.84-7.77(m,1H),7.76(s,1H),7.64-7.56(m,1H),7.51(s,1H),7.45-7.34(m,4H),7.15-7.11(m,2H),4.74(d,J＝5.9Hz,2H).
Example 7: 2- (piperazin-1-yl) -N- (4-methylbenzyl) quinoline-4-carboxamide 4d
50mg (0.16mmol) of the 3a compound, 138mg (1.60mmol) of piperazine, 45mg (0.32mmol) of potassium carbonate and 10mL of anhydrous DMF were added to a reaction flask, and the mixture was heated to 90 ℃ to react for 10 hours. After the reaction, the reaction mixture was cooled to room temperature and poured into 30mL of water, extracted with ethyl acetate (3X 20mL), the organic phases were combined, washed with saturated brine (3X 50mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (DCM: MeOH ═ 30:1, v/v) to give 41mg of the objective compound 4d as a yellow solid in a yield of 72.0% and a melting point of 199-. 1 H NMR(500MHz,CDCl 3 )δ7.95–7.91(m,1H),7.72(d,J＝8.6Hz,1H),7.62–7.53(m,1H),7.34–7.24(m,3H),7.21(d,J＝7.8Hz,2H),7.06(s,1H),6.25(s,1H),4.69(d,J＝5.6Hz,2H),3.72(t,J＝5.1Hz,4H),3.05–2.99(m,4H),2.37(s,3H).
Example 8: 2- (morpholin-1-yl) -N- (4-methylbenzyl) quinoline-4-carboxamide 4e
The synthesis of example 8 was performed as in example 7, except that piperazine was replaced by morpholine in equimolar amount and the procedure was as in example 7. Finally, the reaction is carried out to obtain the target compound 4e as yellow solid, the yield is 45 percent, and the melting point is 143-145 ℃. 1 H NMR(500MHz,CDCl 3 )δ7.93(dd,J＝8.4,1.3Hz,1H),7.71(dd,J＝8.5,1.2Hz,1H),7.62–7.54(m,1H),7.34–7.25(m,3H),7.22(s,1H),7.20(s,1H),7.00(s,1H),6.37(s,1H),4.69(d,J＝5.7Hz,2H),3.86(t,J＝5.0Hz,4H),3.68(t,J＝5.0Hz,4H),2.38(s,3H).
Example 9: 2- (4-hydroxypiperidin-1-yl) -N- (4-methylbenzyl) quinoline-4-carboxamide 4f
Example 9 the synthesis is as in example 7, except that piperazine is replaced by an equimolar amount of 4-hydroxypiperidine and the remainder isThe procedure was as in example 7. The final reaction gave the target compound 4f as a yellow solid in 15% yield, mp 171-173 ℃. 1 H NMR(500MHz,CDCl 3 )δ7.91(dd,J＝8.2,1.5Hz,1H),7.73(d,J＝7.9Hz,1H),7.59–7.51(m,1H),7.34–7.18(m,6H),7.08(s,1H),6.35(s,1H),4.69(d,J＝5.6Hz,2H),4.03–3.93(m,1H),3.72–3.60(m,2H),3.39–3.21(m,2H),2.15–1.97(m,2H),1.84–1.67(m,2H)，2.37(s,3H).
Example 10: n- (4-methylbenzyl) -2- (4-oxopiperidin-1-yl) -quinoline-4-carboxamide 4g
50mg (0.16mmol) of the compound 3a, 32mg (0.18mmol) of 4-piperidone ethylene glycol hydrochloride, 67mg (0.49mmol) of potassium carbonate and 2mL of DMSO were placed in a reaction flask, and the temperature was raised to 120 ℃ to react for 8 hours. After the reaction was completed, the reaction solution was cooled to room temperature and poured into 30mL of water, extracted with ethyl acetate (3X 20mL), and the organic phases were combined, washed with saturated brine (3X 50mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain 50mg of a key intermediate (which was directly used in the next reaction). The intermediate is dissolved in 1.5mL of THF, and then 1.5mL of dilute sulfuric acid is added to react for 2h at room temperature. After the reaction, the reaction solution was poured into 30mL of water and saturated NaHCO was used 3 The solution was adjusted to pH 7-8, extracted with ethyl acetate (3X 20mL), the organic phases were combined, washed with saturated brine (3X 50mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (DCM: EA: 10:1, v/v) to give 15mg of a pale yellow solid with a yield of 25% and a melting point of 196 ℃ 198 ℃. 1 H NMR(500MHz,DMSO-d 6 )δ7.89(dd,J＝8.4,1.4Hz,1H),7.68–7.62(m,1H),7.62–7.54(m,1H),7.38(s,1H),7.32–7.23(m,3H),7.19(s,1H),7.18(s,1H),4.51(d,J＝6.0Hz,2H),4.08(t,J＝6.1Hz,4H),2.48(t,J＝6.1Hz,4H),2.30(s,3H).
Example 11: 2- (1,2, 4-triazole-1-yl) -N- (4-methylbenzyl) quinoline-4-formamide 4h
Dissolving 14mg (0.19mmol) of 1,2, 4-triazole in 3mL of anhydrous DMF, cooling to 0-5 ℃, adding 8.5mg (0.21mmol) of 60% sodium hydride, keeping the temperature, stirring for 0.5h, adding 20mg (0.16mmol) of 3a, and heating to 90 ℃ for reaction for 8 h. After the reaction, the reaction mixture was cooled to room temperature and poured into 15mL of water, extracted with ethyl acetate (5X 50mL), the organic phases were combined, washed with saturated brine (3X 200mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (PE: EA ═ 1:1, v/v) to give 7mg of a white solid for 4 hours, yield 32%, melting point: 235-. 1 H NMR(500MHz,CDCl 3 )δ9.37(s,1H),8.32(dd,J＝8.5,1.3Hz,1H),8.15(d,J＝4.9Hz,2H),8.11–8.06(m,1H),7.82(ddd,J＝8.5,6.9,1.4Hz,1H),7.68–7.60(m,1H),7.32(s,1H),7.30(s,1H),7.21(s,1H),7.20(s,1H),6.42(s,1H),4.72(d,J＝5.6Hz,2H),2.37(s,3H).
Example 12: n- (4-methylbenzyl) -2- (pyridin-4-yl) quinoline-4-carboxamide 4i
97.5mg (0.39mmol) of 2- (pyridin-4-yl) quinoline-4-carboxylic acid, 70mg (0.43mmol) of N' N-Carbonyldiimidazole (CDI) and 10ml of methylene chloride were charged in a reaction flask, and the mixture was stirred at 35 ℃ for 20 minutes. Then, 53mg (0.44mmol) of 4-methylbenzylamine was added thereto, and the reaction was carried out at room temperature for 18 hours. After the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to give the objective compound 4i as a pale yellow solid with a yield of 37.9% and a melting point of 163-. 1 H NMR(500MHz,CDCl 3 )δ8.82-8.76(m,2H),8.30-8.21(m,2H),8.09-8.03(m,2H),7.97(s,1H),7.87-7.79(m,1H),7.70-7.63(m,1H),7.34(d,J＝8.0Hz,2H),7.23(d,J＝7.8Hz,2H),6.42(s,1H),4.75(d,J＝5.7Hz,2H),2.38(s,3H)。
EXAMPLE 13 determination of IDH1/R132H inhibitory Activity
The activity measuring method of IDH1-R312H utilizes a fluorescence detection technology. The reaction of this method was carried out in a 384-well deep well plate, the total volume of the reaction being 50 ul. A mixture of protein, inhibitor, NADPH and alpha-KG comprising: Tris-HCl 25mM (pH7.0), 25mM NaCl, BSA 0.025%, 8mM MnCl2 to form the reaction system IDH 1-R132H. The reaction utilizes the decrease in NADPH to determine enzyme activity. Wherein the inhibitor is one of the compounds 4a-4 i.
NADPH can emit a detectable fluorescence signal with the wavelength of 460nm after excitation of excitation light at 340nm, so as to observe the activity change of the enzyme and the inhibition of the compound. Multiple background wells without enzyme and full enzyme active wells without compounds 4a-4i were set up in the reaction. The value of IC50 is given by the formula: y100/(1 +10^ ((LogIC50-X) × HillSlope)). In IDH1-R132H reaction system, NADPH concentration is 12. mu.M, enzyme concentration is 27nM, and the results of the test of partial compounds are shown in Table 1:
TABLE 1 inhibitory Activity of object Compounds on IDH1/R132H
Wherein in Table 1,% inhibition (20 μm) means that the inhibitory activity of the target compound was first tested at a concentration of 20 μm.
The statements in this specification merely set forth a list of implementations of the inventive concept and the scope of the present invention should not be construed as limited to the particular forms set forth in the examples.
Claims (1)
1. The application of the nitrogen-containing aromatic heterocycle substituted quinoline formamide derivative with the structural formula shown as a formula (4) or pharmaceutically acceptable salt thereof in preparing IDH1/R132H mediated disease treatment medicines is characterized in that the structural formula of the formula (4) is as follows:
wherein R is 1 Selected from H, R 2 Selected from C1-C3 alkyl or halogen;
R 3 is a nitrogen-containing aromatic heterocyclic group selected from one of the following groups:
。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105777751A (en) * | 2016-04-26 | 2016-07-20 | 浙江工业大学 | Double-aryl maleimide compound, pharmaceutically acceptable salt thereof, method for preparing double-aryl maleimide compound and pharmaceutically acceptable salt and application of double-aryl maleimide compound and pharmaceutically acceptable salt |
| CN107001328A (en) * | 2014-09-19 | 2017-08-01 | 福马治疗股份有限公司 | It is used as pyridine 2 (1H) ketone qualone derivative of saltant type isocitric dehydrogenase inhibitor |
| CN112321571A (en) * | 2020-10-27 | 2021-02-05 | 浙江工业大学 | 2-furan-quinoline-4-formamide compound and application thereof |
-
2020
- 2020-10-27 CN CN202011162649.5A patent/CN112341389B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107001328A (en) * | 2014-09-19 | 2017-08-01 | 福马治疗股份有限公司 | It is used as pyridine 2 (1H) ketone qualone derivative of saltant type isocitric dehydrogenase inhibitor |
| CN105777751A (en) * | 2016-04-26 | 2016-07-20 | 浙江工业大学 | Double-aryl maleimide compound, pharmaceutically acceptable salt thereof, method for preparing double-aryl maleimide compound and pharmaceutically acceptable salt and application of double-aryl maleimide compound and pharmaceutically acceptable salt |
| CN112321571A (en) * | 2020-10-27 | 2021-02-05 | 浙江工业大学 | 2-furan-quinoline-4-formamide compound and application thereof |
Non-Patent Citations (17)
| Title |
|---|
| RN 1097463-17-6;STN;《CA-REGISTRY》;20090129;全文 * |
| RN 1180219-54-8;STN;《CA-REGISTRY》;20090904;全文 * |
| RN 1223021-80-4;STN;《CA-REGISTRY》;20100513;全文 * |
| RN 1223190-46-2;STN;《CA-REGISTRY》;20100514;全文 * |
| RN 1296719-03-3;STN;《CA-REGISTRY》;20110518;全文 * |
| RN 521282-87-1;STN;《CA-REGISTRY》;20030528;全文 * |
| RN 689269-05-4;STN;《CA-REGISTRY》;20040604;全文 * |
| RN 713120-11-7;STN;《CA-REGISTRY》;20040820;全文 * |
| RN 713121-83-6;STN;《CA-REGISTRY》;20040820;全文 * |
| RN 750610-37-8;STN;《CA-REGISTRY》;20040924;全文 * |
| RN 823832-27-5;STN;《CA-REGISTRY》;20050201;全文 * |
| RN 897768-00-2;STN;《CA-REGISTRY》;20060801;全文 * |
| RN 900346-44-3;STN;《CA-REGISTRY》;20060810;全文 * |
| RN 903672-49-1;STN;《CA-REGISTRY》;20060823;全文 * |
| RN 923530-27-2;STN;《CA-REGISTRY》;20070227;全文 * |
| RN 923546-90-1;STN;《CA-REGISTRY》;20070227;全文 * |
| RN 924487-80-9;STN;《CA-REGISTRY》;20070302;全文 * |
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