- Synthesis and anti-Pneumocystis carinii activity of conformationally restricted analogues of pentamidine
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A series of conformationally restricted analogues of pentamidine in which the flexible central bridge has been replaced by trans-cyclopropyl, phenyl, pyridinyl, piperazinyl or homopiperazinyl groups as conformationally restricted linkers have been synthesized. The anti-Pneumocystis carinii activity of these compounds was evaluated in a cell culture model and the DNA binding affinity was determined by thermal denaturation measurements. At 1 μM, compounds 2, 3, 5, 7, 9 and pentamidine were highly effective and caused total inhibition of P. carinii growth in culture. At 0.1 μM, compounds 2, 5, 7 and 10 were more active than pentamidine with N, N'- bis(4amidinophenyl)piperazine 7 being approximately 15-fold more effective than pentamidine. The most active compounds, 7 and 10, showed strong binding affinities for calf thymus DNA and poly(dA-dT); however, a clear correlation between DNA binding affinity and the in vitro anti-P, carinii activity of these compounds was not observed. The results suggest that the nature of the central linker influences the biological actions of these compounds.
- Tao, Bin,Huang, Tien L,Zhang, Qian,Jackson, Latasha,Queener, Sherry F.,Donkor, Isaac O.
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- Development of an SNAr Reaction: A Practical and Scalable Strategy to Sequester and Remove HF
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A simple and operationally practical method to sequester and remove fluoride generated through the SNAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubbe
- Blacker, A. John,Moran-Malagon, Gabriel,Powell, Lyn,Reynolds, William,Stones, Rebecca,Chapman, Michael R.
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- Development of an SNAr Reaction: A Practical and Scalable Strategy to Sequester and Remove HF
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A simple and operationally practical method to sequester and remove fluoride generated through the SNAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubbe
- Blacker, A. John,Moran-Malagon, Gabriel,Powell, Lyn,Reynolds, William,Stones, Rebecca,Chapman, Michael R.
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p. 1086 - 1091
(2018/09/29)
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- Anti-Inflammation Compounds
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The present invention refers to: a compound having the general formula (I), wherein n is 0, 1, 2 or; m is 0, 1, 2 or 3; o is 0, 1, 2 or 3; W, X, Y and Z are independently selected from CH, N or N-oxide; A is NR4, C═O, C═S, OP(O)(O), P═O, CH2, or a heteroarly selected from the group consisting of (a), (b), (c), (d), (e), (f), (g); V is C═O, O, S, CH2, or NR5; as well as its use in treating inflammatory diseases such as asthma, COPD, inflammation post infection, arthritis, atherosclerosis, pain and dermatitis.
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Paragraph 0132; 0134
(2014/06/23)
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- 1,4-Diarylpiperazines and analogs as anti-tubercular agents: Synthesis and biological evaluation
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Despite progress in modern chemotherapy to combat tuberculosis, the causative pathogen Mycobacterium tuberculosis (M.tb.) is far from eradicated. Bacillary resistance to anti-mycobacterial agents, bacillary persistence and human immunodeficiency virus (HIV) co-infection hamper current drug treatment to completely cure the infection, generating a constant demand for novel drug candidates to tackle these problems. A small library of novel heterocyclic compounds was screened in a rapid luminometric in vitro assay against the laboratory M.tb. strain H37Rv. A group of amidines was found to have the highest potency and was further evaluated for acute toxicity against C3A hepatocytes. Next, the most promising compounds were evaluated for activity against a multi-drug resistant clinical isolate. The group of amidines was also tested for their ability to kill intracellular M.tb. residing in mouse J774A.1 macrophages. Finally, we report on a correlation between the structural differences of the compounds and their anti-mycobacterial activity.
- Forge,Cappoen,Laurent,Stanicki,Mayence,Huang,Verschaeve,Huygen,Vanden Eynde
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scheme or table
p. 95 - 101
(2012/04/10)
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- ANTI-INFECTIVE COMPOUNDS
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The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.
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Page/Page column 21
(2011/10/10)
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- Bisbenzamidine derivatives for use as antioxidant
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The invention is directed to the use of bisbenzamidine compounds of Formula (I) as antioxidant and as neuroprotective agents, wherein R1, R2, R3, R4 and L have the meaning defined in the claims.
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- Antitumor and anti-Pneumocystis carinii activities of novel bisbenzamidines
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Among a library of 17 bisbenzamidines connected with various linkers, compounds with a flexible pentanediamide (10) or hexanediamide (12) linker were the most potent derivatives against rat Pneumocystis carinii (IC50 values of 3 and 2 nM, respe
- Vanden Eynde, Jean Jacques,Mayence, Annie,Johnson, Melissa T.,Huang, Tien L.,Collins, Margaret S.,Rebholz, Sandra,Walzer, Peter D.,Cushion, Melanie T.,Donkor, Isaac O.
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p. 143 - 157
(2007/10/03)
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- Piperazine-linked bisbenzamidines: A novel class of antileishmanial agents
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A series of 13 1,4-diarylpiperazines has been prepared, evaluated for antileishmanial activity and their binding affinity to DNA was measured. Among these compounds, 1,4-bis[4-(1H-benzimidazol-2-yl)phenyl]piperazine (14) emerged as the most active compoun
- Mayence, Annie,Vanden Eynde, Jean Jacques,LeCour Jr., Louis,Walker, Larry A.,Tekwani, Babu L.,Huang, Tien L.
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p. 547 - 553
(2007/10/03)
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- Parallel Solution-Phase Synthesis of Conformationally Restricted Congeners of Pentamidine and Evaluation of Their Antiplasmodial Activities
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Conformationally restricted bisbenzamidines and related congeners have been synthesized and evaluated for activity against two Plasmodium falciparum strains. The most active compounds, bisbenzamidines linked by a 1,4-piperazinediyl core, had IC50/su
- Mayence, Annie,Vanden Eynde, Jean Jacques,Krogstad, Fran M.,Krogstad, Donald J.,Cushion, Melanie T.,Huang, Tien L.
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p. 2700 - 2705
(2007/10/03)
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- Trypanocidal activity of conformationally restricted pentamidine congeners
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A series of conformationally restricted congeners of pentamidine in which the flexible pentyl bridge of pentamidine was replaced by trans-1,2-bismethylenecyclopropyl, phenyl, pyridinyl, piperazinyl, homopiperazinyl, and piperidinyl groups were synthesized
- Donkor, Isaac O.,Huang, Tien L.,Tao, Bin,Rattendi, Donna,Lane, Schennella,Vargas, Marc,Goldberg, Burt,Bacchi, Cyrus
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p. 1041 - 1048
(2007/10/03)
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- Synthesis, antituberculosis activity, and DNA binding affinity of a highly diverse library of 1,4-diarylpiperazines
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A library of eighteen 1,4-diarylpiperazines has been synthesized and evaluated for antituberculosis activity and DNA binding affinity. Among them, 4,4′-(1,4-piperazinediyl)bis(N-alkylbenzenecarboximidamides) emerged as attractive leads for further drug development.
- Vanden Eynde, Jean Jacques,Mayence, Annie,Lecour Jr., Louis,Huang, Tien L.
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p. 401 - 414
(2007/10/03)
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