DNA-directed alkylating agents: synthesis, antitumor activity and DNA affinity of bis-N,N′-trisubstituted 1,2,4-triazolo-piperazines

Vacca, 1994, An orally bioavailable human-immunodeficiency-virus type-1 protease inhibitor, Proc. Natl. Acad. Sci. USA, 91, 4096, 10.1073/pnas.91.9.4096 B.D. Dorsey, R.B. Levin, S.L.McDaniel, J.P. Vacca, J.P. Guare, P.L. Darke, et al., L-735,524: the design of a potent and orally bioavailable HIV protease inhibitor, J. Med. Chem. 37 (1994) 3443–3451; D.L. Romero, R.A. Morge, M.J. Genin, C. Biles, M. Busso, L. Resnick, et al., Bis(heteroaryl)piperazine (DHAP) RT inhibitors: structure-activity relationship of novel indole analogues and the indentification of monomethanesulfonate (U-901525), J. Med. Chem. 36 (1993) 1505–1508 Romero, 1994, Discovery, synthesis, and bioactivity of bis(Heteroaryl)piperazines. A novel class of nonnucleosides HIV-1 reverse-transcriptase inhibitors, J. Med. Chem., 37, 999, 10.1021/jm00033a018 Romero, 1991, Nonnucleosides reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type-1 replication, Proc. Natl. Acad. Sci. USA, 88, 8806, 10.1073/pnas.88.19.8806 Mao, 1998, Structure-based design of N-[2-(1-piperidinylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea and N-[2-(1-piperazinylethyl)]-N''-[2-(5-bromopyridyl)]-thiourea as potent non-nucleoside inhibitors of HIV-1 reverse transcriptase, Bioorg. Med. Chem., 6, 1789 Tuker, 1998, Piperazinyl oxazolidinone antibacterial agents containing a pyridine, diazene, or triazene heteroaromatic ring, J. Med. Chem., 41, 3727, 10.1021/jm980274l Malinka, 2002, Synthesis of some pyrrolo[3,4-d]pyridazinones and their preliminary anticancer, antimycobacterial and CNS screening, Pharmazie, 56, 384 Malinka, 2000, Synthesis and preliminary screening of derivatives of 2-(4-arylpiperazin-1-ylalkyl)-3-oxoisothiazolo[5,4-b]pyridines as CNS and antimycobacterial agents, Pharmazie, 55, 416 Winkelmann, 1974, Protozoacidal 1-methyl-5-nitro-2-(1-piperazinylmethyl)-imidazoles (Farbwerke Hoechst A.-G), Ger. Offen. J. Da Settimo, 1986, Synthesis of pyrido[1,2-a]pyrimidin-4-ones. Potential antihypertensive agents, Farmaco, 41, 926 Archibald, 1974, 1,4-Bis(2-indol-3-ylethyl)piperazines, J. Med. Chem., 17, 745, 10.1021/jm00253a018 Beyerle, 1966, Piperazinocoumarine coronary dilators, (Cassella Farbwerke Mainkur A.-G.) 1,135,907 (Cl C 07d) 1968, Ger. Appl., 21 1969, Chem. Abstr., 71, 49978e Tanaka, 1994, Antiplatelet agents based on cycloxygenase inhibition without ulcergenosis. Evaluation and synthesis of 4,5-bis(4-methoxyphenyl)-2-substituted-thiazoles, J. Med. Chem., 37, 1189, 10.1021/jm00034a017 Mahajan, 1975, Inhibtion of 17,20(17-hydroxyprogesterone)-lyase by progesterone, Steriods, 25, 217, 10.1016/S0039-128X(75)90118-X Santen, 1983, Site of action of low dose ketoconazole on androgen biosynthesis in men, J. Clin. Endocrind. Metab., 57, 732, 10.1210/jcem-57-4-732 Hammar, 1974, Pharmaceutical 8-(4-methyl-1-piperazinylcarbonyl)-dibenzol[3,4:6,7]bicyclo[3,2.1]octa-3,6-diene, Ger. Offen. J., 11 1975, Chem. Abstr., 82, 4308x Bruno, 2001, Bis-naphthylureas and related compounds: synthesis, chemical properties, DNA affinity and antineoplastic activity, Pharmazie, 56, 361 Renhowe, 2001, Growth factor kinases in cancer, vol. 35, 109 Tiwari, 1979, Search for new antihelmintica, Part I Synthesis of piperazine derivatives, Indian J. Chem., 188, 379 Raghupathi, 1991, Analogues of the 5-HT1A serotonin antagonist 1(-2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine with reduced a1-adrenergic affinity, J. Med. Chem., 34, 2633, 10.1021/jm00112a043 van Steen, 1998, Functional characteristic of a series of N4-substituted 1-(2,3-dihydro-1,4-benzodioxan-5-yl)piperazines as 5-HT1A receptor ligands, Bioorg. Med. Chem. Lett., 8, 2457, 10.1016/S0960-894X(98)00406-5 Terán, 1998, Phenylpiperazine derivatives with strong affinity for 5HT1A, D2A and D3 receptors, Bioorg. Med. Chem. Lett., 8, 3567, 10.1016/S0960-894X(98)00646-5 Löber, 1999, Azaindole derivatives with high affinity for the dopamine D4 receptor: synthesis, ligand binding studies and comparison of molecular electrostatic potential maps, Bioorg. Med. Chem. Lett., 9, 97, 10.1016/S0960-894X(98)00692-1 Van Tol, 1991, Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine, Nature, 350, 610, 10.1038/350610a0 Walczynski, 1999, Non-imidazole histamine H3 ligands, Part 2 New 2-substituted benzothiazoles as histamine H3 antagonists, Arch. Pharm. Pharm. Med. Chem., 332, 389, 10.1002/(SICI)1521-4184(199911)332:11<389::AID-ARDP389>3.0.CO;2-U Tsukuda, 1998, Modeling, synthesis and biological activity of novel antifungal agents (1), Bioorg. Med. Chem. Lett., 8, 1819, 10.1016/S0960-894X(98)00316-3 Al-Soud, 1998, Reaction of 1-(chloroalkyl)-1-aza-2-azoniaallene salts with alkenes: preparation of cyclic azo, (azoalkyl)azonium, and formazanium compounds, Synthesis, 721, 10.1055/s-1998-2059 Benzig, 1960, Über Neue, a,a'-disubstitutierte azoalkane, Leibigs Ann. Chem., 631, 1, 10.1002/jlac.19606310102 Benzig, 1960, Mechanismus der Zersetzung von aa'-Dichlo-Azoalkanen in Wässerigem Aceton, Leibgis Ann. Chem., 631, 10, 10.1002/jlac.19606310103 Al-Masoudi, 1998, Synthesis of C- and N-nucleosides from 1-aza-2-azoniaellene and 1,3-diaza-2-azoniaallene salts, J. Chem. Soc. Perkin Trans., 1, 947, 10.1039/a707079i Al-Soud, 1999, Synthesis and antiviral activity of some 1,2,4-triazole C-nucleosides from 1-(chloroalkyl)-1-aza-2-azo-niaallene salts, Nucleos. Nucleot., 18, 1985, 10.1080/07328319908044859 Al-Masoudi, 1999, Synthesis and spectroscopic analysis of some acyclic C-nucleosides and the homo-C-analogues from 1-(chloroalkyl)-1-aza-2-azoniaallene salts, Tetrahedron, 15, 751, 10.1016/S0040-4020(98)01080-1 Al-Soud, 1999, Synthesis and antiviral activity of some 1-(1,5-dialkyl-1H-1,2,4-triazole-3-yl)thymines, Arch. Pharm. Pharm. Med. Chem., 332, 143, 10.1002/(SICI)1521-4184(19994)332:4<143::AID-ARDP143>3.0.CO;2-C Al-Soud, 2001, Synthesis and antitumor activity of some new phthalimide analogues, Pharmazie, 56, 372 Al-Masoudi, 1999, Synthesis and reactions of 1,5- and 1,3-dialkyl derivatives of (D-manno-pentitol-1-yl)-1H-1,2,4-triazole nucleosides derived from 1-(chloroalkyl)-1-aza-2-azoniaallene salts, Carbohydr. Res., 318, 67, 10.1016/S0008-6215(99)00084-1 Al-Soud, 2002, Synthesis of 1-[4-(1,5-disubstituted-1H-1,2,4-triazol-3-yl)benzyl]-1H-indols and 5,6-dihaloquinolones as potential antitumor agents, Org. Prep. Proc. Int. (OPPI), 49, 658, 10.1080/00304940209355790 Al-Soud, 2003, New potential antitumor agents: 1,2,4-triazoles bearing benzotriazol, acetoxyhydrazides, 5-mercapto-1,2,4-triazole and sugar hydrazone analogues, Bioorg. Med. Chem., 11, 1701, 10.1016/S0968-0896(03)00043-9 Al-Soud, 2003, Synthesis of 3'-1,2,4-triazolo- and 3'-1,3,4-thiadiazol-iminothymidines, Heteroatom Chem., 14, 298, 10.1002/hc.10146 Adelson, 1935, Derivatives of piperazine, Part IV Reactions with derivatives of monochloroacetic acid, J. Am. Chem. Soc., 57, 1280, 10.1021/ja01310a031 Luten, 1937, The preparation of aminonitriles and their quarternary ammonium derivatives, J. Org. Chem., 3, 588, 10.1021/jo01223a007 Wang, 1992, 1,2,4-triazolium salts from the reaction of 1-aza-2-azoniaallene salts with nitriles, Synthesis, 710, 10.1055/s-1992-26206 Wang, 1994, On the reaction of 1-aza-2-azoniaallene salts with acetylenes, Chem. Ber., 127, 541, 10.1002/cber.19941270313 Willker, 1993, Gradient selection in inverse heteronuclear correlation spectroscopy, Mag. Reson. Chem., 31, 287, 10.1002/mrc.1260310315 Monks, 1991, Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines, J. Natl. Cancer Inst., 83, 757, 10.1093/jnci/83.11.757 Seshadri, 1983, Adriamycin analogues. Preparation and biological evaluation of some novel 14-thiaadriamycins, J. Med. Chem., 26, 11, 10.1021/jm00355a003 Trent, 1996, Targeting the minor groove of DNA: crystal structures of two complexes between furan derivatives of berenil and the DNA dodecamer d(CGCGAATTCGCG)2, J. Med. Chem., 39, 4554, 10.1021/jm9604484