- Versatile Cp*Co(III)(LX) Catalyst System for Selective Intramolecular C-H Amidation Reactions
-
Herein, we report the development of a tailored cobalt catalyst system of Cp*Co(III)(LX) toward intramolecular C-H nitrene insertion of azidoformates to afford cyclic carbamates. The cobalt complexes were easy to prepare and bench-stable, thus offering a convenient reaction protocol. The catalytic reactivity was significantly improved by the electronic tuning of the bidentate LX ligands, and the observed regioselectivity was rationalized by the conformational analysis and DFT calculations of the transition states. The superior performance of the newly developed cobalt catalyst system could be broadly applied to both C(sp2)-H and C(sp3)-H carbamation reactions under mild conditions.
- Chang, Sukbok,Jung, Hoimin,Kim, Dongwook,Lee, Jeonghyo,Lee, Jia,Park, Juhyeon
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supporting information
p. 12324 - 12332
(2020/08/06)
-
- Synthesis and fungicidal activities of perfluoropropan-2-yl-based novel quinoline derivatives
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A series of novel perfluoropropan-2-yl-based quinoline derivatives was designed and synthesized utilizing tebufloquin as the lead compound. The structures of all the newly synthesized compounds were confirmed by spectroscopic data 1HNMR, MS and elemental analysis. The results of bioassay indicated that these compounds exhibited potent fungicidal activities against Erysiphe graminis. Especially, compound 8c displayed excellent activity with EC50 value at 1.48 mg / L, which was better than that of the commercialized fungicide-tebufloquin. The structure-activity relationship for these new compounds was also discussed.
- Zhang, Zai,Liu, Minhua,Liu, Weidong,Xiang, Jun,Li, Jianming,Li, Zhong,Liu, Xingping,Huang, Mingzhi,Liu, Aiping,Zheng, Xingliang
-
-
- Discovery of (3-Benzyl-5-hydroxyphenyl)carbamates as new antitubercular agents with potent in vitro and in vivo efficacy
-
A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625-6.25 μg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential.
- Cheng, Ya-Juan,Liu, Zhi-Yong,Liang, Hua-Ju,Fang, Cui-Ting,Zhang, Niu-Niu,Zhang, Tian-Yu,Yan, Ming
-
-
- PYRROLIDINE DERIVATIVES AS PPAR AGONISTS
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The present invention discloses a class of pyrrolidine derivatives as PPAR agonist, and their use for the treatment of some diseases of PPAR receptor-associated pathways (such as nonalcoholic steatohepatitis and concurrent fibrosis, insulin resistance, primary biliary cholgangitis, dyslipidenmia, hyperlipidemia, hypercholesterolemia, atherosclerosis, hypertriglyceridemia, cardiovascular disease, obesity or the like). In particular, the present invention discloses a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0842; 0843
(2019/08/02)
-
- Selective Activation of a Prodrug by Thioredoxin Reductase Providing a Strategy to Target Cancer Cells
-
Elevated reactive oxygen species and antioxidant defense systems have been recognized as one of the hallmarks of cancer cells. As a major regulator of the cellular redox homeostasis, the selenoprotein thioredoxin reductase (TrxR) is increasingly considered as a promising target for anticancer drug development. The current approach to inhibit TrxR predominantly relies on the modification of the selenocysteine residue in the C-terminal active site of the enzyme, in which it is hard to avoid the off-target effects. By conjugating the anticancer drug gemcitabine with a 1,2-dithiolane scaffold, an unprecedented prodrug strategy is disclosed that achieves a specific release of gemcitabine by TrxR in cells. As overexpression of TrxR is frequently found in different types of tumors, the TrxR-dependent prodrugs are promising for further development as cancer chemotherapeutic agents.
- Li, Xinming,Hou, Yanan,Meng, Xianke,Ge, Chunpo,Ma, Huilong,Li, Jin,Fang, Jianguo
-
supporting information
p. 6141 - 6145
(2018/04/30)
-
- Anticancer prodrug molecule and its preparation method and target compound
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The invention discloses an anticancer prodrug molecule and its preparation method and a target compound, and relates to the field of organic synthesis and molecular medicine. The target compound of the anticancer prodrug molecule can be selectively identified by protein which is excessively expressed in a cancer cell; the preparation method of the anticancer prodrug molecule includes steps of connecting the target compound to amino acid or hydroxyl of the anticancer active molecule; through the method, the target compound is connected with the anticancer active molecule, thus the anticancer prodrug molecule is prepared; after the target compound is identified by the protein specificity which is highly expressed in the cancer cell, the anticancer prodrug molecule is released and directly acted on the cancer cells, thereby reaching the purpose of targeted treatment.
- -
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Paragraph 0106
(2017/12/30)
-
- Preparation method of alicyclic and aromatic-aliphatic chloroformate
-
The invention belongs to the technical field of fine chemistry, and in particular relates to a preparation method of alicyclic and aromatic-aliphatic chloroformate. The preparation method is characterized in that alicyclic alcohol chloroformate or aromatic-aliphatic alcohol chloroformate is obtained by taking alicyclic alcohol or aromatic-aliphatic alcohol and bis(trichlormethyl)carbonate as raw materials, taking organic base as a catalyst and reacting in an organic solvent under certain reaction temperature and certain reaction time, wherein molar ratio among the alicyclic alcohol or the aromatic-aliphatic alcohol, the bis(trichlormethyl)carbonate and the organic base is 1 to (0.4 to 1) to (1.2 to 3); experiment time and experiment temperature are different in two stages, in the first stage, the reaction temperature is -10 to 0 DEG C, and the reaction time is 2 to 5 hours; in the second stage, the reaction temperature is 0 to 25 DEG C, and the reaction time is 7 to 13 hours; a mass ratio between the organic solvent and the alicyclic alcohol or the aromatic-aliphatic alcohol is (10 to 25) to 1; residue in a reaction system is effectively treated, and reaction waste is also recycled and utilized. The preparation method disclosed by the invention has the characteristics of stable reaction, high reaction yield and product purity, environment protection of a reaction process, low production cost, less emission of three wastes, simpleness in preparation technology and easiness in industrialization.
- -
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Paragraph 0044-0045
(2017/05/16)
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- NOVEL VINBLASTINE DERIVATIVES, THEIR PREPARATION, USE AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAID DERIVATIVES
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The invention provides vinblastine derivatives represented by the following formula 1 or their physiologically acceptable salts, their preparation, use and pharmaceutical compositions comprising the said derivatives. The said vinblastine derivatives show inhibiting activities against tumor cell lines and can be used as medicaments for treating malignant tumors.
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Page/Page column 42
(2009/12/05)
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- C(10) ETHYL ESTER AND C(10) CYCLOPROPYL ESTER SUBSTITUTED TAXANES
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Taxanes having an ethyl ester or cyclopropyl ester substituent at C(10), a keto substituent at C(9), a hydroxy substituent at C(7), a thienyl substituent at C(3') and a cyclobutyloxycarbamate or cyclopentyloxycarbamate substituent at C(3'), pharmaceutical compositions comprising such taxanes, methods of treatment and administration, and methods of preparation of medicaments comprising the taxanes.
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Page/Page column 46-47
(2009/12/27)
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- HCV PROTEASE INHIBITORS
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This invention relates to the compounds of formula (I) shown below. Each variable in formula (I) is defined in the specification. These compounds can be used to treat hepatitis C virus infection.
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Page/Page column 31
(2008/12/07)
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- NOVEL DITHIOLOPYRROLONES AND THEIR THERAPEUTICAL APPLICATIONS
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The present invention provides novel dithiolopyrrolone compounds and their salts, which promote production of white blood cells and are useful as prevention and treatments for microbial infections such as HIV infection and blood disorders such as neutropenia and other related diseases. The present invention also provides therapeutic compositions comprising particularly useful types of dithiolopyrrolones, the salts thereof, and methods and use in the manufacture of a medication for treatment of diseases.
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Page/Page column 38
(2008/06/13)
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- PHOSPHORUS-CONTAINING HEPATITIS C SERINE PROTEASE INHIBITORS
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The present invention relates to phosphorus-derived compounds of Formula I or Formula II, or a pharmaceutically acceptable salt, ester, or prodrug, thereof, which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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Page/Page column 59-60
(2008/06/13)
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- Acylaminoheteroaryl hepatitis C virus protease inhibitors
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The present invention discloses compounds of formulae I and II, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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Page/Page column 26
(2008/06/13)
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- AZA-PEPTIDE MACROCYCLIC HEPATITIS C SERINE PROTEASE INHIBITORS
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The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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Page/Page column 31
(2008/12/08)
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- N-FUNCTIONALIZED AMIDES AS HEPATITIS C SERINE PROTEASE INHIBITORS
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The present invention relates to functionalized amides of Formula I or Formula II, including pharmaceutically acceptable salts, esters, or prodrugs thereof which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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Page/Page column 39
(2008/12/04)
-
- HYDRAZIDE-CONTAINING HEPATITIS C SERINE PROTEASE INHIBITORS
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The present invention relates to novel hydrazide-containing compounds of Formula I or Formula II, including pharmaceutically acceptable salts, esters, or prodrugs thereof which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
- -
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Page/Page column 63
(2008/12/04)
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- AZA-TRIPEPTIDE HEPATITIS C SERINE PROTEASE INHIBITORS
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The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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Page/Page column 45
(2008/12/08)
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- MACROCYCLIC COMPOUNDS AS HCV NS3 PROTEASE INHIBITORS
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The present application describes macrocyclic compounds of formula (I) with NS3 protease inhibitory activity for treating hepatitis C virus infection.
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Page/Page column 225-226
(2008/12/08)
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- Quinoxalinyl Macrocyclic Hepatitis C Virus Serine Protease Inhibitors
-
The present invention relates to compounds, including compounds of Formula I, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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Page/Page column 47
(2008/06/13)
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- ANTIVIRAL COMPOUNDS
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The invention is related to phosphorus substituted anti-viral inhibitory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.
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Page/Page column 304; 306
(2008/06/13)
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- Macrocyclic hepatitis C serine protease inhibitors
-
The present invention relates to compounds of Formula I, II or Ill, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: wherein W is a substituted or unsubstituted heterocyclic ring system. The compounds inhibit serine protease activity, particularly the activity of hepatitis c virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis c virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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Page/Page column 127; 151; 167
(2008/06/13)
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- Macrocyclic compounds as inhibitors of viral replication
-
The embodiments provide compounds of the general formulas I-XIX, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating flaviviral infection, including hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
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-
-
- MACROCYCLIC CARBOXYLIC ACIDS AND ACYLSULFONAMIDES AS INHIBITORS OF HCV REPLICATION
-
The present invention provides compounds of the general formulas I-IX, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The present invention further provides treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
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Page/Page column 133-134
(2008/06/13)
-
- Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors
-
The present invention relates to compounds of Formula I or II, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
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Page/Page column 46
(2008/06/13)
-
- Substituted cycloalkyl P1' hepatitis C virus inhibitors
-
The present invention relates to tripeptide compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositions containing such analogs and methods for using these analogs in the treatment of HCV infection.
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Page/Page column 37
(2010/02/06)
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- Macrocyclic peptides active against the hepatitis C virus
-
The present invention covers macrocyclic compounds of formula I active in-vitro and in cellular assays against the NS3 protease of the hepatitis C virus. wherein W, R21, R22, R3, R4, D and A are as defined herein, or a pharmaceutically acceptable salts or ester thereof.
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-
-
- Macrocyclic peptides active against the hepatitis C virus
-
Compounds of formula I: wherein R1 is hydroxy or NHSO2R1A wherein R1A is (C1-8)alkyl, (C3-7)cycloalkyl or {(C1-6)alkyl-(C3-7)cycloalkyl}, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O(C1-6)alkyl, amido, amino or phenyl, or R1A is C6 or C10 aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C1-6)alkyl, O(C1-6)alkyl, amido, amino or phenyl; R2 is (C5-6)cycloalkyl and R3 is cyclopentyl; or a pharmaceutically acceptable salt thereof, useful as inhibitors of the HCV NS3 protease.
- -
-
-
- Macrocyclic peptides active against the hepatitis C virus
-
Compounds of formula I: wherein R1 is hydroxy or NHSO2R1A wherein R1A is (C1-8)alkyl, (C3-7)cycloalkyl or {(C1-6)alkyl-(C3-7)cycloalkyl}, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O(C1-6)alkyl, amido, amino or phenyl, or R1A is C6 or C10 aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C1-6)alkyl, O(C1-6)alkyl, amido, amino or phenyl; R2 is (C5-6)cycloalkyl and R3 is cyclopentyl; or a pharmaceutically acceptable salt thereof, useful as inhibitors of the HCV NS3 protease.
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- Thermal and induced decompositions of N′-alkoxycarbonyldihydropyridines: End product analysis and EPR spectra of azacyclohexadienyl radicals
-
Hydrogen abstraction from N-alkoxycarbonyldihydropyridines generated azacyclohexadienyl radicals (pyridinyl radicals) which are characterised by EPR spectroscopy. In the presence of peroxide initiators, N-alkoxycarbonyl-1,2-dihydropyridines decomposed with production of pyridine, the corresponding alkyl formate, alkyl benzoate and alkanol being formed as the major products. Absence of cyclised products in experiments with substrates containing hex-5-enyl, pent-4-enyloxy etc. units demonstrates that radical production must be minor and that N-alkoxycarbonylazacyclohexadienyl radicals do not readily undergo ss-scission of the exocyclic N-C bond. The most probable mechanism is a direct 1,2-elimination of formate. The alcohols which accompanied the other products are probably formed by hydrolysis of the formates and benzoates. Analogous chemistry is displayed by N-alkoxycarbonyl-1,4-dihydropyridines at higher temperatures where 1,4-elimination of formate is too rapid for homolytic radical production to compete.
- Baguley, Paul A.,Walton, John C.
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p. 1423 - 1429
(2007/10/03)
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- SUBSTITUTED OXOTREMORINE DERIVATIVES
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This disclosure describes novel substituted oxotremorine derivatives of formula I having nitrogen, oxygen or sulfur groups and the prodrug forms of these derivatives. The compounds have cholinergic activity. Also disclosed are methods for treating diseases of the central nervous system in mammals employing the compounds, pharmaceutical preparations containing the compounds and the processes for the production of the compounds. STR1
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-
-
- Rationally designed 'dipeptoid' analogues of cholecystokinin (CCK): N-terminal structure-affinity relationships of α-methyl-tryptophan derivatives
-
The structure-affinity relationships (SAR) between the N-terminii of a series of α-methyl-tryptophanylphenethylamide derivatives and the cholecystokinin (CCK) B receptor are discussed. A series of compounds with the general formula R-X-α-methyl-tryptophanylphenethylamide was prepared, where R is a cycloalkyl, a bicycloalkyl or a tricycloalkyl group and X is a urethane, thiourethane, amide, urea or a sulphinamide linking group. The CCK-B receptor binding affinities of these are discussed. The SAR form part of a systematic program for the rational design of 'dipeptoid' analogues of the neuropeptide CCK. Beginning with 1,1-dimethylpropyl (±)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2- [(2-phenylethyl)amino carbamate (IC50 = 4720 nM on CCK-B binding affinity) the N-terminal moiety was systematically changed for groups of varying size, shape and lipophilicity until the optimal N-terminal group was obtained and the favoured linking group chosen, resulting in the compound tricyclo[3.3.1.13,7)]dec-2-yl(R)-[(1H-indol-3-ylmethyl)-1-methyl- 2-oxo-2[(2-phenylethyl)amino]ethyl]carbamate with and IC50 = 32 nM on CCK-B receptor binding affinity.
- Eden,Higginbottom,Hill,Horwell,Hunter,Martin,Pritchard,Rahman,Richardson,Roberts
-
-
- SYNTHESES DE CARBONATES ET CARBAMATES BENZYLIQUES ET ALLYLIQUES
-
Different methods for the preparation of carbonates and carbamates derived from 1-phenylethyl, 2-cyclohexenyl and 1-methyl-2-propenyl are described.These conmpounds have been synthesized by the reactions of alcohols, phenols or amines with chloroformiates, imidazolocarbonates or corresponding mixed p-nitrophenylcarbonates. It is shown that these reactions can also be used for the introduction of 1-phenylethyloxycarbonyl - (I), 2-cyclohexenyloxycarbonyl - (II) and 1-methyl-2-propenyloxycarbonyl - (III) groups into alcohols, phenols and amines for the protection of hydroxyls and amino-groups.
- Kryczka, Boguslaw
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p. 147 - 158
(2007/10/02)
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- CYCLIZATIONS AND INTERMOLECULAR ADDITIONS OF ALKOXYCARBONYLOXY RADICALS FROM N-HYDROXYPYRIDINE-2-THIONE CARBONATES
-
Alkoxycarbonyloxy radicals from allyl and homoallyl alcohols cyclize in an exo fashion to give, respectively, 3-substituted 1,2-diol carbonates and 4-substituted 1,3-diol carbonates, whereas simple alkoxycarbonyloxy radicals add intermolecularly to ethyl vinyl ether to give, ultimately, carbonates of glycolaldehyde derivatives.
- Newcomb, Martin,Kumar, M. Udaya,Boivin, Jean,Crepon, Elisabeth,Zard, Samir Z.
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-
- 1-Aziridine carboxylic acid derivatives with immunostimulant activity
-
2-Substituted-1-aziridine-carboxylic acid esters exhibiting immuno-stimulant activity and of the formula STR1 wherein X is a carbamoyl or alkoxycarbonyl radical, and R1 is an aliphatic hydrocarbon radical optionally substituted by halogen, alkoxy, amino, carbamoyloxy, cycloalkyl, hydroxyl, an imido or heterocyclic radical, cycloalkyl; or aryl, aralkyl, aryloxyalkyl or arylthioalkyl wherein the aryl moiety is optionally substituted by halogen, alkyl, alkoxy, hydroxyl, amino, nitro, cyano, acyl, carbalkoxy, thioalkyl, alkylsulphonyl, phenyl or trifluoromethyl. Counterparts where X is --CN and R1 is as above, except for ethyl, are also new.
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