A Concise One‐Pot Synthesis of 3,4‐Diaryl‐1H‐pyrazoles from Natural Isoflavones and Hydrazine Hydrate

An efficient protocol has been developed for the preparation of a series of new 3,4-diaryl-1H-pyrazoles, potential pharmacological and agricultural targets, by the reaction of hydrazine hydrate with different natural isoflavones or their derivatives. The target compounds were obtained in good-to-excellent yields (80–95%; Table 2) under fairly mild reaction conditions (80°) tolerating various functional groups. The new compounds were fully characterized, and the single-crystal X-ray structures of 3,5-diethoxy-2-[4-(4-ethoxyphenyl)-1H-pyrazol-3-yl]phenol (26) and of the peracetylated compound 2-{1-acetyl-4-[4-acetoxy-3-(diacetylamino)phenyl]-1H-pyrazol-3-yl}-5-acetoxyphenyl acetate (35) were solved (Figure).

[1]  Youhong Hu,et al.  Three-component, one-pot reaction for the combinatorial synthesis of 1,3,4-substituted pyrazoles. , 2006, Journal of combinatorial chemistry.

[2]  Qiu-ya Wang,et al.  Hydrogen Bonding and Aromatic π–π Stacking in the Crystal Structures of Water-Soluble Daidzein Derivatives , 2005 .

[3]  Qiu-ya Wang,et al.  Synthesis and Crystal Structure of [Co(H2O)6](C19H17O4SO3)2⋅8H2O , 2005 .

[4]  Qiu-ya Wang,et al.  Syntheses and Crystal Structures of Diethylated Daidzein Sulfonates , 2005 .

[5]  Xavier Barril,et al.  Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design. , 2005, Journal of medicinal chemistry.

[6]  Koji Tsuboi,et al.  In vivo radioprotection of mice by 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone; Radicut), a clinical drug. , 2004, Journal of radiation research.

[7]  V. Khilya,et al.  Synthetic and modified isoflavonoids XV. Interaction of synthetic analogs of isoflavones with hydrazine hydrate and its derivatives , 1994, Chemistry of Natural Compounds.

[8]  V. Nesterov,et al.  Synthesis of 6-amino-4-aryl-5-cyano-3-(3-cyanopyridin-2-ylthiomethyl)-2,4-dihydropyrano[2,3-c]pyrazoles and their hydrogenated analogs. Molecular structure of 6-amino-5-cyano-3-(3-cyano-4,6-dimethylpyridin-2-ylthiomethyl)-4-(2-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole , 2003 .

[9]  Paul Workman,et al.  Overview: translating Hsp90 biology into Hsp90 drugs. , 2003, Current cancer drug targets.

[10]  Dennis H. Evans,et al.  One-step synthesis of substituted 6-amino-5-cyanospiro-4-(piperidine-4')- 2H,4H-dihydropyrazolo[3,4-b]pyrans. , 2002, Organic letters.

[11]  P. Workman,et al.  HSP90 as a new therapeutic target for cancer therapy: the story unfolds , 2002, Expert opinion on biological therapy.

[12]  N. Igidov,et al.  1,3,4,6-Tetracarbonyl Compounds: IV. Reaction of 3,4-Dihydroxy-2,4-hexadiene-1,6-diones with Hydrazine and Arylhydrazines , 2001 .

[13]  R. Morimoto,et al.  Role of the heat shock response and molecular chaperones in oncogenesis and cell death. , 2000, Journal of the National Cancer Institute.

[14]  K. Erol,et al.  Synthesis and preliminary evaluation of new 5-pyrazolinone derivatives as analgesic agents. , 2000, European journal of medicinal chemistry.

[15]  S. Lin-Shiau,et al.  Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells. , 1999, European journal of cancer.

[16]  J. J. Parlow.  SYNTHESIS OF PYRAZOLECARBONYLAMINOPYRIDINECARBOXAMIDES AS HERBICIDES , 1998 .

[17]  D. Nauduri,et al.  Antibacterials and antimycotics: Part 1: Synthesis and activity of 2-pyrazoline derivatives. , 1998, Chemical & pharmaceutical bulletin.

[18]  G. Perra,et al.  Antimicrobial and antineoplastic activities of new 4-diazopyrazole derivatives , 1998 .

[19]  E. A. Badawey,et al.  Nonsteroidal antiinflammatory agents - Part 1: Antiinflammatory, analgesic and antipyretic activity of some new 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-ones , 1998 .

[20]  Shuko Okui,et al.  Synthesis and Insecticidal Activity ofN-(4-Aryloxybenzyl)-pyrazolecarboxamide Derivatives , 1998 .

[21]  S. Ojala,et al.  Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[22]  C. Strock,et al.  Synthesis and Insecticidal Activity of Novel Pyrazole Methanesulfonates , 1997 .

[23]  K. Nakamura,et al.  Studies on anti-inflammatory agents. IV. Synthesis and pharmacological properties of 1,5-diarylpyrazoles and related derivatives. , 1997, Chemical & pharmaceutical bulletin.

[24]  S. Manenti,et al.  Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: a comparison with tyrosine kinase and protein kinase C inhibition. , 1997, Biochemical pharmacology.

[25]  P. C. Ruenitz.  Drugs for Osteoporosis Prevention: Mechanisms of Bone Maintenance , 1995, Current Medicinal Chemistry.

[26]  I. Dreosti,et al.  The antioxidant activity of genistein in vitro , 1995 .

[27]  J. Reginster.  Ipriflavone: pharmacological properties and usefulness in postmenopausal osteoporosis. , 1993, Bone and mineral.

[28]  S. Kadota,et al.  2'-Hydroxymatteucinol, a new C-methyl flavanone derivative from Matteccia orientalis; potent hypoglycemic activity in streptozotocin (STZ)-induced diabetic rat. , 1993, Chemical & pharmaceutical bulletin.

[29]  E. Taylor,et al.  Synthesis of pyrazolo 3,4-pyrimidine analogues of the potent agent N-4-2-2-amino-4 3-oxo-7-pyrrolo 2,3-pyrimidin-5-yl ethylbenzoyl-L-glutamic acid (LY231514) , 1992 .

[30]  D. Dexter,et al.  Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization. , 1990, Journal of medicinal chemistry.

[31]  T. Heffner,et al.  1,3-Dialkyl-4-(iminoarylmethyl)-1H-pyrazol-5-ols. A series of novel potential antipsychotic agents. , 1987, Journal of medicinal chemistry.

[32]  P. Hilgard,et al.  Anticoagulants in the treatment of cancer. , 1976, European journal of cancer.