WO2000001387A1 - Fungal growth inhibitors - Google Patents

Fungal growth inhibitors Download PDF

Info

Publication number
WO2000001387A1
WO2000001387A1 PCT/US1999/014835 US9914835W WO0001387A1 WO 2000001387 A1 WO2000001387 A1 WO 2000001387A1 US 9914835 W US9914835 W US 9914835W WO 0001387 A1 WO0001387 A1 WO 0001387A1
Authority
WO
WIPO (PCT)
Prior art keywords
pde
growth
inhibitors
fungal
plant
Prior art date
Application number
PCT/US1999/014835
Other languages
French (fr)
Inventor
Richard A. Nelson
Mohit B. Bhatia
Craig M. Lewis
Minghua Zhang
Original Assignee
Celgro, A Division Of Celgene Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Celgro, A Division Of Celgene Corporation filed Critical Celgro, A Division Of Celgene Corporation
Priority to AU48491/99A priority Critical patent/AU4849199A/en
Publication of WO2000001387A1 publication Critical patent/WO2000001387A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
    • A01N35/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical containing aliphatically bound aldehyde or keto groups, or thio analogues thereof; Derivatives thereof, e.g. acetals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
    • A01N37/38—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids having at least one oxygen or sulfur atom attached to an aromatic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A01N43/42—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N61/00—Biocides, pest repellants or attractants, or plant growth regulators containing substances of unknown or undetermined composition, e.g. substances characterised only by the mode of action
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/275—Nitriles; Isonitriles
    • A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine

Definitions

  • the invention relates to phosphodiesterase (PDE) inhibitors as antifiingal agents
  • Phosphodiesterases are a family of enzymes which control concentrations of cyclic nucleotides, particularly cyclic AMP (cAMP) and cyclic GMP (cGMP) in mammalian systems Beavo et al, ASPET Meeting Report, Molecular Pharmacology, vol 46, pp 399-405, (1994) cAMP and cGMP are both important molecules involved in cellular signal transduction, such that alteration in their cellular levels has profound effects on cellular physiology PDE's act to hydrolyze and therefore reduce the concentrations of cyclic nucleotides such as cAMP and cGMP Consequently, inhibitors of PDE activity have significant therapeutic potential in the pharmaceutical area and are being widely studied Murray et al, Biochemical Soc. Trans., vol 20 (1992), Palacios et al, II Farmaco, vol 50, No 12, 819-827 (1995), Current Pharmaceutical Design, vol l, No 2 (1995)
  • PDE's can be classified according to structure and specificity of action, and as many as seven different classes have been distinguished Beavo et al, ASPET Meeting Report, Molecular Pharmacology, vol 46, pp 399-405 (1994) PDE inhibitors similarly can be classified according to the classes of PDE's on which they are active, either as specific for one or more PDE's, or as non-selective. Nicholson et al, TIPS, vol.
  • anti-fungal refers to any agent capable of inhibiting
  • the present invention thus relates to PDE inhibitors, and their use as anti-fungal agents
  • PDE inhibitors either readily available, see Palacios et al , II Farmaco, vol 50, No 12, 819-827 (1995), Current Pharmaceutical Design, vol 1, No 2 (1995), or from
  • PDE inhibitors representing three mammalian classes and one nonspecific inhibitor, showed selective inhibition of fungal growth, with different inhibitors affecting different fungi within the ranges tested In contrast, no inhibition of early plant development was detected for any of the mammalian PDE inhibitors tested, suggesting that selective PDE inhibitors are capable of control fungal growth in plant and crop protection applications
  • the invention relates to an antifungal composition
  • an antifungal composition comprising at least one PDE inhibitor
  • the invention relates to a pesticidal composition
  • a pesticidal composition comprising at least one PDE inhibitor
  • the invention relates to a method for inhibiting fungal growth comprising administering an effective amount of at least one PDE inhibitor
  • the invention relates to a method of inhibiting fungal growth in a plant comprising administering to said plant an effective amount of a PDE inhibitor
  • Test compounds were dissolved in DMSO and subsequently diluted 1 100 into PDA at 55° C Four ml of PDA containing the test compounds was transferred to 2 1 cm ste ⁇ le tissue culture plates and allowed to cool at room temperature PDA wells with 1 0% DMSO and PDA wells without additions were used as controls for comparing the growth of the fungal test strains relative to the cultures exposed to the test compounds
  • PDE inhibitors were tested on a monocot (Pearl Millet) and either of two dicots (tomato or Pigweed) in a seedling gerrnination assay.
  • the assay consisted of placing
  • DMSO used to prepare the stock solutions of the PDE inhibitors also showed no effect on root or shoot growth at a final concentration of 0.05-0.1%, as used in these tests.

Abstract

Phosphodiesterase (PDE) inhibitors and their use as anti-fungal agents. The data suggesting these selective PDE inhibitors are capable of control fungal growth in plant and crop protection applications.

Description

FUNGAL GROWTH INHIBITORS
Field of the Invention The invention relates to phosphodiesterase (PDE) inhibitors as antifiingal agents
Background of the Invention
Phosphodiesterases (PDE's) are a family of enzymes which control concentrations of cyclic nucleotides, particularly cyclic AMP (cAMP) and cyclic GMP (cGMP) in mammalian systems Beavo et al, ASPET Meeting Report, Molecular Pharmacology, vol 46, pp 399-405, (1994) cAMP and cGMP are both important molecules involved in cellular signal transduction, such that alteration in their cellular levels has profound effects on cellular physiology PDE's act to hydrolyze and therefore reduce the concentrations of cyclic nucleotides such as cAMP and cGMP Consequently, inhibitors of PDE activity have significant therapeutic potential in the pharmaceutical area and are being widely studied Murray et al, Biochemical Soc. Trans., vol 20 (1992), Palacios et al, II Farmaco, vol 50, No 12, 819-827 (1995), Current Pharmaceutical Design, vol l, No 2 (1995)
PDE's can be classified according to structure and specificity of action, and as many as seven different classes have been distinguished Beavo et al, ASPET Meeting Report, Molecular Pharmacology, vol 46, pp 399-405 (1994) PDE inhibitors similarly can be classified according to the classes of PDE's on which they are active, either as specific for one or more PDE's, or as non-selective. Nicholson et al, TIPS, vol. 12 (1991) There is also evidence for cyclic nucleotides, particularly cAMP, and their role in signal transduction in both plants and fungi S Assmann, Plant Physwl, vol 108, pp 885-889 (1995),
Figure imgf000004_0001
et al , Genes & Development, vol 10, pp 2696-2700 (1996) For example, adenyl cyclase, responsible for the formation of cAMP has been cloned from _ tobacco plants Ichlkawa et al , Nature vol 390, (1997) and there is evidence for a cAMP-dependent signaling pathway in fungi Xu et al , Genes & Development, vol
10, pp 2696-2700 (1996) However, no PDE enzymes have been isolated from either plant or fungal sources, nor has the gene for any PDE been identified or cloned from these sources
Detailed Descπption of the Invention
As used herein the term "anti-fungal" refers to any agent capable of inhibiting
fungal growth, or killing fungal cells or spores
The present invention thus relates to PDE inhibitors, and their use as anti-fungal agents
In the present invention twelve chemical compounds known to be mammalian
PDE inhibitors, either readily available, see Palacios et al , II Farmaco, vol 50, No 12, 819-827 (1995), Current Pharmaceutical Design, vol 1, No 2 (1995), or from
studies at Celgene Corporation, were tested for their ability to inhibit fungal and plant growth Fungal inhibition was tested on myce al growth for a series of twelve fungi representing the different classes of mycology Plant growth inhibition was tested on
seed germination and early root and shoot development for a representative monocotyledon and a dicotyledon Surprisingly, PDE inhibitors representing three mammalian classes and one nonspecific inhibitor, showed selective inhibition of fungal growth, with different inhibitors affecting different fungi within the ranges tested In contrast, no inhibition of early plant development was detected for any of the mammalian PDE inhibitors tested, suggesting that selective PDE inhibitors are capable of control fungal growth in plant and crop protection applications
In a preferred embodiment, the invention relates to an antifungal composition comprising at least one PDE inhibitor
In another preferred embodiment, the invention relates to a pesticidal composition comprising at least one PDE inhibitor
In yet another preferred embodiment, the invention relates to a method for inhibiting fungal growth comprising administering an effective amount of at least one PDE inhibitor
In still another preferred embodiment, the invention relates to a method of inhibiting fungal growth in a plant comprising administering to said plant an effective amount of a PDE inhibitor
EXAMPLE 1
A seπes of PDE inhibitors was tested for potential to inhibit the growth of fungal test strains in vitro The results from that study are summarized in Table 1 below The assay was performed as follows
Fungal test strains were grown on potato dextrose agar (PDA) plates for a peπod of 1 to 5 days either at room temperature or 30° C depending on the growth characteπstics of the particular test strain After a period of growth, agar plugs (0 4 cm) were cut from the outside edge of the fungal colonies and transferred to the center of the tissue culture plates containing PDA or PDA plus the test compounds
Test compounds were dissolved in DMSO and subsequently diluted 1 100 into PDA at 55° C Four ml of PDA containing the test compounds was transferred to 2 1 cm steπle tissue culture plates and allowed to cool at room temperature PDA wells with 1 0% DMSO and PDA wells without additions were used as controls for comparing the growth of the fungal test strains relative to the cultures exposed to the test compounds
Inoculated plates were incubated at room temperature or 30° C The diameter of growth from the 0 4 cm inoculation plug was monitored over a time penod ranging from 17 hrs to 68 hrs Data reported in Table 1 are the diameters (cm) of growth for the control and treated strain at the same point in time Table 1
Antifύngal Test Results - PDE Inhibitors
c
DO (Λ
H
H C H m x m m
H c ι- m
M
Figure imgf000007_0001
Note 1 Starting from a 0 4 cm inoculation plug ; e , 0 4 cm colony diameter equals no growth
Key 1 - FUNGI ABBREVIATIONS
AF Aspergillus flavus MP Magnaporthe poae
PR Pythium rostratum CM Colletotrichum sp
BC Botrytis cinerea VA Verticillium albo-atrum
RZ Rhizoctonia sp. MR Mucor rouxii
SC Sclerotinia sp. NG No growth.
0) FO Fusarium oxysporum NA Not applicable c RS R izopus sttolonifer oo ω PC Phytophthora cinnamomi
H C Key 2 - COMPOUND NAME H m tn # Chemical Name x m 1 3,3-bis-(3-ethoxy-4 methoxyphenyl)propenonilrile m 2 2,2',2",2,"-[(4,6-Di-l-piperidinyl-pyrimido[5,4-d]pyrimidone-2,6-diyl)dinitrolo]tetrakisethanol
H 3 l-[(3,4-Dimethoxyphenyl)methyl]-6,-7-dimethoylsoquinoline
30 4 3a, 16a Eburnamenine 14 carboxylic acid ethyl ester
C r- 5 (E,Z)-3-(3-ethoxy-4-methoxyphenyl)-3-cyclohexylpropenonitrile m
N> 6 3,3-bis-(3,4-dimethoxyphenyl)propenonitrile σ> 7 (E,Z)-3 -(3 -cyclopentyloxy-4-methoxyphenyl)-3 -pheny lpropenonitrile
8 (E)-4-(3-cyclopentyloxy-4-methoxyphenyl)-buten-2-one
9 3,3-bis-(3,4-dimethoxyphenylpropenoic acid methyl ester
10 3-(4-pyridyl)-3-(3,4-dimethoxyphenyl)propenonitrile
11 (E,Z) 3-(3,4-dimethoxyphenyl)-3-(4-aminophenyl)propenonitrile
12 3-(3-ethoxy-4-methoxyphenyl)-3-(3,4-dimethoxyphenyl)propionitrile
13 Imazalil
Figure imgf000008_0001
EXAMPLE 2
PDE inhibitors were tested on a monocot (Pearl Millet) and either of two dicots (tomato or Pigweed) in a seedling gerrnination assay. The assay consisted of placing
sterile seeds on the surface of agarose medium (0.75% Type II agarose; Miracle-Gro
plant food; 12.5-25 μM of each individual PDE inhibitor in a 60mm Petri dish. Root and
shoot growth was compared to control cultures (no inhibitors) for seven days. No effect on either root or shoot growth was observed with compounds 1-11. The herbicide control
(20μM Pendimethalin) showed strong inhibition. The solvents acetone, methanol, and
DMSO used to prepare the stock solutions of the PDE inhibitors also showed no effect on root or shoot growth at a final concentration of 0.05-0.1%, as used in these tests.

Claims

oWhat is Claimed
1. An antifungal composition comprising at least one PDE inhibitor.
2. A pesticidal composition comprising at least one PDE inhibitor.
3. A method for inhibiting fungal growth comprising administering an effective amount of at least one PDE inhibitor.
4. A method of inhibiting fungal growth in a plant comprising administering to said plant en effective amount of a PDE inhibitor.
PCT/US1999/014835 1998-07-01 1999-06-30 Fungal growth inhibitors WO2000001387A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU48491/99A AU4849199A (en) 1998-07-01 1999-06-30 Fungal growth inhibitors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US9136798P 1998-07-01 1998-07-01
US60/091,367 1998-07-01

Publications (1)

Publication Number Publication Date
WO2000001387A1 true WO2000001387A1 (en) 2000-01-13

Family

ID=22227401

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/014835 WO2000001387A1 (en) 1998-07-01 1999-06-30 Fungal growth inhibitors

Country Status (2)

Country Link
AU (1) AU4849199A (en)
WO (1) WO2000001387A1 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002000919A2 (en) * 2000-06-23 2002-01-03 Millennium Pharmaceuticals, Inc. Screen for identifying inhibitors of glycosylphosphatidylnositol anchoring
WO2002004626A1 (en) * 2000-07-07 2002-01-17 Eisai Co., Ltd. Fungal cell wall synthesis gene
WO2003058233A1 (en) * 2001-12-28 2003-07-17 Eisai Co., Ltd. Method of screening compound having fungal cell wall synthesis inhibitory activity
EP1603864A2 (en) * 2003-03-05 2005-12-14 Celgene Corporation Diphenylethylene compounds and uses thereof
US7019030B2 (en) 1996-08-12 2006-03-28 Celgene Corporation Immunotherapeutic agents
US7468446B2 (en) 2004-09-03 2008-12-23 Celgene Corporation Substituted heterocyclic compounds and uses thereof
US7470723B2 (en) 2003-03-05 2008-12-30 Celgene Corporation Diphenylethylene compounds and uses thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5753666A (en) * 1995-08-02 1998-05-19 Chiroscience Limited Quinolones and their therapeutic use
US5801153A (en) * 1991-09-13 1998-09-01 Badaway; Mohammed A. Method of enhancing the antimicrobial properties of antibacterial antibiotics to massively control and prevent bacterial, fungal, and viral diseases in plants

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5801153A (en) * 1991-09-13 1998-09-01 Badaway; Mohammed A. Method of enhancing the antimicrobial properties of antibacterial antibiotics to massively control and prevent bacterial, fungal, and viral diseases in plants
US5753666A (en) * 1995-08-02 1998-05-19 Chiroscience Limited Quinolones and their therapeutic use

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7019030B2 (en) 1996-08-12 2006-03-28 Celgene Corporation Immunotherapeutic agents
WO2002000919A2 (en) * 2000-06-23 2002-01-03 Millennium Pharmaceuticals, Inc. Screen for identifying inhibitors of glycosylphosphatidylnositol anchoring
WO2002000919A3 (en) * 2000-06-23 2003-02-06 Millennium Pharm Inc Screen for identifying inhibitors of glycosylphosphatidylnositol anchoring
US7541332B2 (en) 2000-07-07 2009-06-02 Eisai R&D Management Co., Ltd. Fungal cell wall synthesis gene
US7375204B2 (en) 2000-07-07 2008-05-20 Eisai R&D Management Co., Ltd. Fungal cell wall synthesis gene
KR100888946B1 (en) 2000-07-07 2009-03-17 에자이 알앤드디 매니지먼트 가부시키가이샤 Fungal cell wall synthesis gene
WO2002004626A1 (en) * 2000-07-07 2002-01-17 Eisai Co., Ltd. Fungal cell wall synthesis gene
US7897387B2 (en) 2000-07-07 2011-03-01 Eisai R&D Management Co., Ltd. Fungal cell wall synthesis gene
US7928209B2 (en) 2000-07-07 2011-04-19 Eisai R & D Management Co. Ltd. Fungal cell wall synthesis gene
US7999090B2 (en) 2000-07-07 2011-08-16 Eisai Co., Ltd Fungal cell wall synthesis gene
WO2003058233A1 (en) * 2001-12-28 2003-07-17 Eisai Co., Ltd. Method of screening compound having fungal cell wall synthesis inhibitory activity
EP1603864A2 (en) * 2003-03-05 2005-12-14 Celgene Corporation Diphenylethylene compounds and uses thereof
EP1603864A4 (en) * 2003-03-05 2007-04-11 Celgene Corp Diphenylethylene compounds and uses thereof
US7312241B2 (en) 2003-03-05 2007-12-25 Celgene Corporation Diphenylethylene compounds and uses thereof
US7470723B2 (en) 2003-03-05 2008-12-30 Celgene Corporation Diphenylethylene compounds and uses thereof
US7468446B2 (en) 2004-09-03 2008-12-23 Celgene Corporation Substituted heterocyclic compounds and uses thereof

Also Published As

Publication number Publication date
AU4849199A (en) 2000-01-24

Similar Documents

Publication Publication Date Title
Moore et al. Selective inhibitors of neuronal nitric oxide synthase–is no NOS really good NOS for the nervous system?
Jeon et al. Attenuation of inducible nitric oxide synthase gene expression by delta 9-tetrahydrocannabinol is mediated through the inhibition of nuclear factor-kappa B/Rel activation.
Galle et al. Effects of the soluble guanylyl cyclase activator, YC‐1, on vascular tone, cyclic GMP levels and phosphodiesterase activity
Palmisano et al. Amino acid starvation induces reactivation of silenced transgenes and latent HIV-1 provirus via down-regulation of histone deacetylase 4 (HDAC4)
Marshall et al. Biological activities of pyridoacridines
Archer The chemotherapy of schistosomiasis
Sriram et al. 5-Nitro-2-furoic acid hydrazones: design, synthesis and in vitro antimycobacterial evaluation against log and starved phase cultures
North et al. Feline immunodeficiency virus, a model for reverse transcriptase-targeted chemotherapy for acquired immune deficiency syndrome
Buckner et al. Pharmacological characterization, structural studies, and in vivo activities of anti-Chagas disease lead compounds derived from tipifarnib
Tung et al. Japanese encephalitis virus induces matrix metalloproteinase‐9 in rat brain astrocytes via NF‐κB signalling dependent on MAPKs and reactive oxygen species
JP2010532385A (en) Methods, compositions and targets for complex cancer treatment
Victoriano et al. Transcriptional control of HIV replication by multiple modulators and their implication for a novel antiviral therapy
Zhu et al. Design, synthesis and biological activity of hydroxybenzoic acid ester conjugates of phenazine-1-carboxylic acid
Antypenko et al. Novel acyl thiourea derivatives: Synthesis, antifungal activity, gene toxicity, drug‐like and molecular docking screening
WO2000001387A1 (en) Fungal growth inhibitors
Han et al. Identification of resveratrol analogs as potent anti‐dengue agents using a cell‐based assay
Tazi et al. Selective inhibition of topoisomerase I and various steps of spliceosome assembly by diospyrin derivatives
Miljkovic et al. Leflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes
Tebbe et al. The effects of antirhino-and enteroviral vinylacetylene benzimidazoles on cytochrome P450 function and hepatic porphyrin levels in mice
Krishnasamy et al. Design, synthesis, and characterization of some hybridized pyrazolone pharmacophore analogs against Mycobacterium tuberculosis
Elhakeem et al. Synthesis and anti-mycobacterial evaluation of some new isonicotinylhydrazide analogues
Kholodniak et al. Novel N‐Cycloalkylcarbonyl‐N′‐arylthioureas: Synthesis, Design, Antifungal Activity and Gene Toxicity
Cai et al. Design, Synthesis, and Insecticidal Activity of Mesoionic Pyrido [1, 2-a] pyrimidinone Containing Isoxazole/Isoxazoline Moiety as a Potential Insecticide
Mizushina et al. Novel anti-inflammatory compounds from Myrsine seguinii, terpeno-benzoic acids, are inhibitors of mammalian DNA polymerases
Liu et al. Inhibition of inducible nitric oxide synthase by β‐lapachone in rat alveolar macrophages and aorta

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TR TT UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase