- Methyl 4-acetamido-2-butoxybenzoate derivatives as well as preparation method and application thereof
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The invention relates to methyl 4-acetamido-2-butoxybenzoate derivatives as well as a preparation method and application thereof, and belongs to the field of medicinal chemistry. The structural formula of the methyl 4-acetamido-2-butoxybenzoate derivatives is shown in the specification, wherein R1 is alkyl, substituted phenyl, heteroaromatic ring group or substituted styryl; and R2 is fatty aminoor benzylamino. The preparation method is simple and high in yield. Most compounds provided by the invention have good influenza virus neuraminidase inhibition activity.
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Paragraph 0007; 0022; 0023
(2020/08/03)
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- Preparation method of key intermediate 4-amino-5-halobenzofuran-7-carboxylic acid of 5-HT4 receptor stimulant
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The invention discloses a preparation method of a key intermediate 4-amino-5-halobenzofuran-7-carboxylic acid of a 1,5-HT4 receptor stimulant, belonging to the field of organic synthesis. According tothe preparation method, para-protected amino-o-hydroxybenzoic acid/hydroxybenzoate, a halogenating reagent and triethyl acetenyl silicon are used as main raw materials, and a three-step reaction is performed to obtain the 4-amino-5-halobenzofuran-7-carboxylic acid. The method has the advantages of simple process operation, short reaction steps, easy separation of the intermediate, total yield ofmore than 51%, usage cheap and easily available raw materials and greatly reduced production cost; and thus, the method has obvious competitive advantages.
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Paragraph 0076-0077; 0081-0082
(2020/03/02)
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- Preparation method of ethopabate
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The invention discloses a preparation method of ethopabate. Initially, para-aminosalicylic acid and p-toluene sulfonic acid are dissolved in methanol to form a mixed solution, the mixed solution is put in a reaction bottle, evenly stirred and heated, and a thermal insulation reaction is carried out; sodium acetate is added into a methyl p-aminosalicylate reaction liquid, the pH and temperature ofthe reaction liquid are controlled, acetylase is added, and a reaction is carried out to obtain methyl p-acetaminosalicylate; methyl p-acetaminosalicylate is added into acetone, heating is carried out, diethyl sulfate is added dropwisely, and after adding dropwisely is completed, a reaction is carried out to obtain ethopabate. The method has the advantages that industrial production can be achieved, resource conservation and environmental protection can be achieved, the cost can be better saved, the product quality is stable, the yield is high, and the method is suitable for large-scale industrial stable production.
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Paragraph 0022; 0024
(2018/04/01)
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- Synthetic method for prucalopride succinate intermediate 4-amino-5-chloro-2,3-dihydrobenzofuran-7-carboxylic acid
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The invention belongs to the technical field of medicines, and relates to a synthetic method for a prucalopride succinate intermediate 4-amino-5-chloro-2,3-dihydrobenzofuran-7-carboxylic acid. The final product 4-amino-5-chloro-2,3-dihydrobenzofuran-7-carboxylic acid is obtained by using p-aminosalicylic acid as a starting raw material, successively performing esterification, acylation, and twice halogenation to obtain 4-acetylamino-3-bromo-5-chloro-2-hydroxybenzoic acid methyl ester, then performing substitution reaction on 1,2-dibromoethane and the 4-acetylamino-3-bromo-5-chloro-2-hydroxybenzoic acid methyl ester to obtain 4-acetylamino-3-bromo-2-(2-bromoethoxy)-5-chlorobenzoic acid methyl ester, and successively performing cyclization and hydrolyzation. According to the invention, the raw materials are easy to get, the operation is simple and mild, the production period is short, the purity is high, the safety is good, the costs are low, and the synthetic method is suitable for industrialized production.
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Paragraph 0041; 0042
(2017/12/06)
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- Dual-Reactable Fluorescent Probes for Highly Selective and Sensitive Detection of Biological H2S
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Hydrogen sulfide (H2S) is an important endogenous signaling molecule with a variety of biological functions. Development of fluorescent probes for highly selective and sensitive detection of H2S is necessary. We show here that dual-reactable fluorescent H2S probes could react with higher selectivity than single-reactable probes. One of the dual-reactable probes gives more than 4000-fold turn-on response when reacting with H2S, the largest response among fluorescent H2S probes reported thus far. In addition, the probe could be used for high-throughput enzymatic assays and for the detection of Cys-induced H2S in cells and in zebrafish. These dual-reactable probes hold potential for highly selective and sensitive detection of H2S in biological systems. Two heads are better than one: Fluorescent probes with two types of reactive heads (R1 and R2) for H2S can lead to a higher selectivity than that of single-reactable probes (See Figure). The probe was used for highly selective and sensitive detection of biological H2S.
- Wei, Chao,Wang, Runyu,Zhang, Changyu,Xu, Guoce,Li, Yanyan,Zhang, Qiang-Zhe,Li, Lu-Yuan,Yi, Long,Xi, Zhen
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supporting information
p. 1376 - 1381
(2016/05/19)
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- AMIDE COMPOUNDS AS 5-HT4 RECEPTOR AGONISTS
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The present invention relates to compounds of formula (I), including their stereoisomers and pharmaceutically acceptable salts. This invention also relates to methods of making such compounds and pharmaceutical compositions comprising such compounds. The compounds of this invention are useful in the treatment of various disorders that are related to 5-hydroxytryptamine 4 (5-HT4) receptor.
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Page/Page column 25-26
(2016/09/22)
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- TYK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
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Paragraph 0955; 0956; 0957
(2016/09/26)
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- HETEROARYL COMPOUNDS AS 5-HT4 RECEPTOR LIGANDS
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The present invention relates to novel compounds of formula (I), and their pharmaceutically acceptable salts and compositions containing them. The present invention also relates to a process for the preparation of above said novel compounds, and their pharmaceutically acceptable salts. The compounds of formula (I) are useful in the treatment of various disorders that are related to 5-HT4 receptors.
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- HETEROARYL COMPOUNDS AS 5-HT4 RECEPTOR LIGANDS
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The present invention relates to novel compounds of formula (I), and their pharmaceutically acceptable salts and compositions containing them. The present invention also relates to a process for the preparation of above said novel compounds, and their pharmaceutically acceptable salts. The compounds of formula (I) are useful in the treatment of various disorders that are related to 5-HT4 receptors.
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Page/Page column 11
(2013/04/10)
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- 4,5-Diamino-3-Halo-2-Hydroxybenzoic Acid Derivatives and Preparations Thereof
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Disclosed are 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives and manufactures thereof. The 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives are presented by formula (I): wherein R1 group is H, CH3, or C2H5; R2 group is H, or Br; R3 group is CH3, or C3H7; and R4 group is H, or C(═NH)—NH2. 4,5-diamino-3-halo-2-hydroxybenzoic acid derivatives provided here were non-toxic to MDCK cells, particularly compounds 6a, 6b, 6c, 6e, 6f, 7a, 7b and 8 had better anti-H1N1 activity. In the future, these compounds can be used to focus on viral neuraminidases as targets to develop effective anti-influenza drugs.
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Page/Page column 9
(2012/05/04)
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- Synthesis and biological evaluation of berberine derivatives as IBS modulator
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Irritable bowel syndrome is the most common functional gastrointestinal disorder characterized by chronic abdominal pain or discomfort in association with a change in bowel habit. 5-HT receptor modulators have been developed as IBS therapeutic agents and proved to be effective in the treatment of the disease. In this letter, 12 berberine derivatives were designed and synthesized as 5-HT receptor modulators. Preliminary biological tests suggested that the new compounds exhibited promising activity for IBS therapy.
- Deng, Xin,Zhao, Xinxin,Han, Jing,Wang, Jingjie,Huang, Wenlong,Qian, Hai,Ge, Liang
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scheme or table
p. 489 - 493
(2012/08/29)
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- Investigation of Synthetic Routes to a Key Benzopyran Intermediate of a 5HT4 Agonist
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The supply route to GlaxoSmithKline's 5HT4 receptor agonist 1 centred on the construction of key benzopyran fragment 2. Our attempts to define the final manufacturing route for this component are described through a series of disconnections. The systematic approach undertaken towards the construction of the benzopyran skeleton focused on cycli- sation strategies from appropriate precursors and evaluation of the performance of the key steps.
- Rassias, Geracimos,Stevenson, Neil G.,Curtis, Neil R.,Northall, John M.,Gray, Matthew,Prodger, Jeremy C.,Walker, Andrew J.
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body text
p. 92 - 98
(2010/04/28)
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- Mild, efficient and rapid O-debenzylation of ortho-substituted phenols with trifluoroacetic acid
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The mild and efficient deblocking of aryl benzyl ethers with TFA is reported. Cleavage was fastest with ortho-electron-withdrawing groups on the phenolic ring, which we have attributed to a proton chelation effect, furnishing the deprotected phenols in excellent yields. The corresponding para-methoxybenzyl, allyl and iso-propyl ethers were also cleanly removed under these conditions. In addition, the selective aryl benzyl ether debenzylation in the presence of benzyl ester, Cbz carbamate and Boc carbamate functionalities was also observed. Crown Copyright
- Fletcher, Steven,Gunning, Patrick T.
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p. 4817 - 4819
(2008/09/21)
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- Design, synthesis, inhibitory activity, and SAR studies of hydrophobic p-aminosalicylic acid derivatives as neuraminidase inhibitors
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A series of hydrophobic p-aminosalicylic acid derivatives containing a lipophilic side chain at C-2 and an amino or guanidine at C-5 were synthesized and evaluated for their ability to inhibit neuraminidase (NA) of influenza A virus (H3N2). All compounds were synthesized in good yields starting from commercially available p-aminosalicylic acid (PAS) using a suitable synthetic strategy. These compounds showed potent inhibitory activity against influenza A NA. Within this series, six compounds, 11, 12, 13e, 16e, 17c, and 18e, have the good potency (IC50 = 0.032-0.049 μM), which are compared to Oseltamivir (IC50 = 0.021 μM) and could be used as lead compounds in the future.
- Zhang, Jie,Wang, Qiang,Fang, Hao,Xu, Wenfang,Liu, Ailin,Du, Guanhua
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p. 3839 - 3847
(2008/09/21)
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- A facile gold(I)-catalysed intramolecular alkyne hydroarylation approach to methyl 5-amino-2H-1-benzopyran-8-carboxylate derivatives
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A high yielding and selective method for producing methyl 5-amino-2H-1-benzopyran-8-carboxylate derivatives via gold(I)-catalysed intramolecular alkyne hydroarylation has been developed.
- Curtis, Neil R.,Prodger, Jeremy C.,Rassias, Geracimos,Walker, Andrew J.
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scheme or table
p. 6279 - 6281
(2009/04/06)
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- NOVEL COMPOUND
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The present invention relates to a novel benzofuran carboxamide derivative having pharmacological activity, to processes for its preparation, to compositions containing it and to its use in the treatment of diseases treatable by 5-HT4 agonism.
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Page/Page column 12; 27-28
(2008/06/13)
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- Halogenated antituberculosis agents
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Halogenated derivatives of two synthetic anti-tuberculosis agents, thioacetazone and p-aminosalicylic acid, have been synthesized. In general, the halogenated compound has the structure of Structure I: wherein X1is a halogen and X2is a second halogen or hydrogen, and Y is sulfur or oxygen; or, has the structure of Structure IV: wherein X1is a halogen and X2is a second halogen or hydrogen. Alternatively, the halogenated compounds may be pharmaceutically acceptable salts of these compounds. These halogenated derivatives possess anti-mycobacterial activity and are particularly useful for the treatment of Mycobacterium tuberculosis infections. In particular, fluorinated analogs of thioacetazone and p-amino-salicylic acid have been synthesized for use as anti-tuberculosis therapeutic agents either alone or in combination with other conventional anti-tuberculosis therapeutic agents.
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- Method of inhibiting neoplastic cells with indole derivatives
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A method for inhibiting neoplasia, particularly cancerous and precancerous lesions, by exposing the affected cells to indole derivatives.
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- Synthesis and radiolabeling of (S)-4-amino-5-iodo-2-methoxy-N (1- azabicyclo[2.2.2]oct-3-yl)benzamide, the Active enantiomer of [125i]iodozacopride, and re-evaluation of its 5-HT3 receptor affinity
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We report an improved synthesis of unlabeled (S)-iodozacopride, the radiolabeling of (S)-[125I]iodozacopride via deschloro-(S)-zacopride, and a re-evaluation of its affinity for the 5-HT3 receptor. Unlabeled (S)- iodozacopride was prepared in seven steps from 4-aminosalicylic acid via alkaline hydrolysis of its 4-acetamide derivative. Catalytic hydrogenation of (S)-iodozacopride gave deschloro-(S)-zacopride, identical to that obtained from (S)-3-amino-quinuclidine and 4-amino-2-metihoxybenzoic acid via its corresponding 1-imidazole derivative. Radioiodination to produce (S)- [125I]iodozacopride was accomplished by treatment of deschloro-(S)- zacopride with 5mCi sodium 125iodide and chloramine-T in hydrochloric acid. Purification of the reaction products using an HPLC system capable of detecting chlorinated side-products revealed a mixture of 2.1 mCi (1.3nmol) (S)-[125I]iodozacopride and (S)-zacopride (1.5 nmol). Saturation analysis of the binding of the purified (S)-[125I]iodozacopride to whole rat brain homogenates gave an estimated K(D) of 1.10±0.07 nM. As anticipated, this is approximately haft the K(D) reported for binding of racemic [125I]iodozacopride, and differs from the previously reported value by an order of magnitude. Analysis of the apparent binding affinity of a 1: 1 mixture of (S)-[125I]iodozacopride and (S)-zacopride suggests that the previous result may have been confounded by contamination of the product with unlabeled (S)-zacopride. Competition analysis of the displacement of (S)- [125I]iodozacopride binding by unlabeled (S)-iodozacopride and (S)- zacopride gave K(i) values of 0.95 and 0.21 nM, respectively.
- Hewlett, William A.,De Paulis, Tomas,Mason, N. Scott,Schmidt, Dennis E.,Trivedi, Bakula L.,Zhang, Zhang-Jin,Ebert, Michael H.
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p. 2079 - 2084
(2007/10/03)
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- (S)-4-amino-5-chloro-3-iodo-2-methoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)b enzamide (TRIZAC), a high-affinity ligand for the 5-HT-3 receptor
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TRIZAC is one of the most potent 5-HT-3 receptor antagonist reported to date, having 20-fold higher affinity than (S)-5-iodozacopride. This high affinity (K(i) 0.05 ± 0.01 nM) and a moderate apparent lipophilicity (log P(app) 2.12) makes TRIZAC a promising ligand for studying 5-HT-3 receptors.
- De Paulis, Tomas,Trivedi, Bakula L.,Zhang, Zhang-Jin,Schmidt, Dennis E.,Ebert, Michael H.,Hewlett, William A.
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p. 2657 - 2662
(2007/10/03)
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- Benzoic acid derivatives and use thereof
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A pharmaceutical composition for use in the treatment of psoriasis comprises 4-aminosalicylic acid (4-ASA) or 5-aminosalicylic acid (5-ASA) or a functional derivative thereof, said pharmaceutical composition being in a form suitable for topical administration. Furthermore, 4- or 5-ASA or a functional derivative thereof are used for the manufacture of pharmaceutical compositions for treating psoriasis, atopic dermatitis, allergic dermatitis, contact dermatitis, seborrhoic dermatitis, or acne diseases. The derivatives have the formulae: STR1 where W is COOX, wherein X is H, Li, Na, K, Mg0.5, Ca0.5, Zn0.5, Al0.33, Fe(II)0.5, Fe(III)0.33, NH4, NH3 R1, NH2 R12, NHR13, NR14, or R1, where R1 is substituted or unsubstituted C1-6 -alkyl, aryl-C1-4 -alkyl, or heteroaryl-C1-4 -alkyl; or COX, where X is NR1 R1', where R1' has the same meaning as R1 defined above and R1 and R1' may be identical or different; Y is H or R1 CO, where R1 is defined as above; Z1 and Z2, which may be identical or non-identical are H, R1 or R1 CO, where R1 is defined as above, or Z1 and Z2 represent R2, where R2 is substituted or unsubstituted C1-6 -alkylidene or aryl-C1-6 -alkylidene, or heteroaryl-C1-6 -alkylidene, or Z1, Z2 together with the nitrogen atom to which they are attached may represent a 3 to 7 membered saturated or unsaturated heterocyclic ring, or may represent a group of the formula --N=N--R3 where R3 is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.
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- Quinuclidyl benzoxepins as 5-HT3 antagonists
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Certain specific substituted 9-N-(1-azabicyclo-[2.2.2.]octan-3-yl)carboxamido-2,3,4,5-tetrahydro-1-benzoxepins and their valuable use as 5-HT3 antagonists having CNS and gastric prokinetic acticity and void of any significant D2 receptor binding properties are disclosed. Methods for their preparation also are described.
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- SYNTHESIS OF THE BACTERIAL COENZYME METHOXATIN
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A short total synthesis of the bacterial coenzyme methoxatin (1) (4,5-dihydro-4,5-dioxo-1H-pyrroloquinoline-2,7,9-tricarboxylic acid) is described.The route involves the two step conversion of 4-acetamido-2-benzyloxybenzaldehyde (5b) into methyl 6-acetamido-4-benzyloxyindole-2-carboxylate (7b) (74percent), followed by regioselective annulation of the third ring (55percent), and debenzylation and oxidation with benzoyl t-butyl nitroxide to give the tricyclic quinone triester (13) (methoxatin triester) (83percent).
- MacKenzie, A. Roderick,Moody, Christopher J.,Rees, Charles W.
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p. 3259 - 3268
(2007/10/02)
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