- A new synthesis of carmethizole and related nitrogen analogues
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A new efficient six-step synthesis of carmethizole, a novel big- carbamate alkylating agent, and syntheses of related nitrogen analogues are described, using a key 4,5-disubstituted imidazole intermediate 8.
- Hay, Michael P.,Denny, William A.
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- Intramolecular hydrogen bond strength and pKa determination of N,N′-disubstituted imidazole-4,5-dicarboxamides
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(Chemical Equation Presented) N,N′-Disubstituted imidazole-4,5- dicarboxamides (I45DCs) form an intramolecular hydrogen bond worth an estimated 14 ± 1 kcal/mol, as measured with a model structure in DMSO-d6 at 3 mM, thereby predisposing the molecular conformation to a folded rather than extended form. The I45DCs also show evidence of aggregation in both CDCl3 (>1 mM) and DMSO-d6 (>10 mM) solutions. These compounds are uncharacteristically weak bases in comparison with imidazoles bearing similar electron-withdrawing groups.
- Rush, Jeremy R.,Sandstrom, Stacey L.,Yang, Jianqing,Davis, Rebecca,Prakash, Om,Baures, Paul W.
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- Synthesis of [1,3, NH2-15N3] (5′S)-8,5′-cyclo-2′-deoxyguanosine
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To facilitate NMR studies and low-level detection in biological samples by mass spectrometry, [1,3, NH2-15N3] (5′S)-8,5′-cyclo-2′-deoxyguanosine was synthesized from imidazole-4,5-dicarboxylic acid in 21 steps. The three
- Malik, Chanchal K.,Das, Rajat S.,Basu, Ashis K.
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p. 376 - 381
(2013/08/23)
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- METHOD FOR PRODUCING 1-BIPHENYLMETHYLIMIDAZOLE COMPOUND
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The present invention provides a method for producing a 1-biphenylmethylimidazole compound having superior angiotensin II receptor antagonistic activity, or an intermediate thereof. The present invention provides a method for producing a compound having the formula (5) (R1 , Ra : H, an alkyl group) by oxidizing a compound having the formula (1) (R a : H, an alkyl group) using an oxidizing agent in the presence of a radical initiation reagent, and then reacting with an ammonia-generating reagent and a compound having the formula R 1 CHO (R 1 : H, an alkyl group) or a compound having the formula R1C(ORb)3 (R1: H,an alkyl group; Rb : an alkyl group).
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Page/Page column 27-28
(2011/04/18)
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- Monocyclic L-nucleosides, analogs and uses thereof
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Novel monocyclic L- nucleoside compounds have general formula (I). Embodiments of these compounds are contemplated to be useful in treating a wide variety of diseases including infections, infestations, neoplasms, and autoimmune diseases. Viewed in terms of mechanism, embodiments of the novel compounds show immunomodulatory activity, and are expected to be useful in modulating the cytokine pattern, including modulation of Th 1 and Th 2 response.
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- Design, synthesis and evaluation of imidazolylmethyl carbamate prodrugs of alkylating agents
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Two approaches to prodrugs of alkylating agents based on an imidazolylmethyl carbamate nucleus were explored. A 2-azido analogue (3) of the bis-carbamate carmethizole (1) displayed similar aerobic cytotoxicity to 1 in a panel of human and murine cell lines. Approaches to the 2-amino and 2- carbamoyl analogues are described. In the second approach an imidazolylmethanol was used as a 'trigger' linked via a carbamate to the alkylating agent N,N-bis(2-chlorethyl)amine (BCEA). Nitroimidazole and methylsulphinylimidazole carbamate prodrugs 6-8 were 5-20-fold less toxic than BCEA. Despite this deactivation in the prodrug form, little increase in cytotoxicity was observed under hypoxia. The data suggest that BCEA released on bioreduction is not sufficiently potent to contribute significant additional cytotoxicity. (C) 2000 Elsevier Science Ltd.
- Hay, Michael P.,Wilson, William R.,Denny, William A.
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p. 645 - 657
(2007/10/03)
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- Monocyclic L-Nucleosides, analogs and uses thereof
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Novel monocyclic L-Nucleoside compounds have the general formula STR1 Embodiments of these compounds are contemplated to be useful in treating a wide variety of diseases including infections, infestations, neoplasms, and autoimmune diseases. Viewed in terms of mechanism, embodiments of the novel compounds show immunomodulatory activity, and are expected to be useful in modulating the cytokine pattern, including modulation of Th1 and Th2 response.
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- 15N-Multilabeled Adenine and Guanine Nucleosides. Syntheses of [1,3,NH2-15N3]- and [2-13C-1,3,NH2-15N3]-Labeled Adenosine, Guanosine, 2′-Deoxyadenosine, and 2′-Deoxyguanosine
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We report a high-yield route to the following specifically 15N- and 13C-multilabeled nucleosides: [1,3,NH2-15N3]- and [2-13C-1,3,NH2-15N3]-adenosine; [1,3,NH2-15N3]- and [2-13C-1,3,NH2-15N3]-guanosine; [1,3,NH2-15N3]- and [2-13C-1,3,NH2-15N 3]-2′-deoxyadenosine; [1,3,NH2-15N3]- and [2-13C-1,3,-NH2-15N 3]-2′-deoxyguanosine. In each set, the 13C2 atom functions as a "tag" that allows the 15N1 and 15N3 atoms to be unambiguously differentiated from the untagged versions in 15N NMR of RNA or DNA fragments. The key intermediate of this synthetic strategy for both the adenine and guanine nucleosides is [NH2,CONH2-15N 2]-5-amino-4-iimdazolecarboxamide. The [2-13C]-label is added through a ring closure using [13C]-sodium ethyl xanthate (NaS13CSOEt). Enzymatic transglycosylation of either multilabeled 6-chloropurine or multilabeled 2-mercaptohypoxanthine and a final reaction with 15NH3 give the adenine and guanine nucleosides. This is the first report of a [3-15N]-labeled guanine nucleoside.
- Abad, Jose-Luis,Gaffney, Barbara L.,Jones, Roger A.
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p. 6575 - 6582
(2007/10/03)
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- 2-SUBSTITUTED INDANE-2-CARBOXYALKYL DERIVATIVES USEFUL AS INHIBITORS OF ENKEPHALINASE AND ACE
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The present invention relates to novel 2-substituted indane-2-carboxyalkyl derivatives useful as inhibitors of enkephalinase and ACE.
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- 2-substituted indane-2-mercaptoacetylamide tricyclic derivatives useful as inhibitors of enkephalinase
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The present invention relates to novel 2-substitited indane-2-mercaptoacetylamide tricyclic derivatives which are useful as inhibitors of Enkephalise.
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- Hexitol derivatives having vasodilative activity
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Disclosed is a hexitol derivative represented by the formula (I): STR1 wherein Q represents a formula selected from the group consisting of STR2 wherein a represents NH, O or S; each of b, c and d independently represents CH or N; each of R1, R2, R3 and R4 independently represents hydrogen, lower alkyl, trifluoromethyl, aryl, lower alkanoyloxy, amino, lower alkylamino, lower alkanoylamino, lower alkanoyl, aroyl, halogen, nitro, (CH2)m OR 7, (CH2)m SR7, (CH2)m CO2 R7 where R7 represents hydrogen or lower alkyl and m represents an integer of 0 to 3; each of R5 and R6 independently represents hydrogen or lower alkyl; U represents >N-- or STR3 W represents a single bond, --O-- or --S--; X represents STR4 wherein each of Y1 and Y2 independently represents hydrogen, lower alkyl, hydroxyl, lower alkanoyloxy, nitrile or phenyl; or Y1 and Y2 are combined together to form oxygen; each of Y3 and Y4 independently represents hydrogen or lower alkyl; and l is an integer of 0 to 6, and where l is an integer of 2 to 6, each STR5 may be the same or different; Z represents hydrogen or nitro; and, n is 2 or 3 or a pharmaceutically acceptable salt thereof. The compounds show prominent coronary vasodilative activities, and are useful in treating angina pectoris and myocardial infarction.
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