WO1999044608A1 - New use - Google Patents
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- Publication number
- WO1999044608A1 WO1999044608A1 PCT/SE1999/000319 SE9900319W WO9944608A1 WO 1999044608 A1 WO1999044608 A1 WO 1999044608A1 SE 9900319 W SE9900319 W SE 9900319W WO 9944608 A1 WO9944608 A1 WO 9944608A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dione
- indole
- group
- phenyl
- compound
- Prior art date
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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
Definitions
- the present invention relates to the use of certain isatin and oxindole derivatives in the treatment of mycobacterial diseases, particularly those diseases caused by pathogenic mycobacteria such as Mycobacterium tuberculosis, M. bovis, M. avium and M. marinum.
- Tuberculosis is still a major public health problem affecting nearly all parts of the world. Based on skin test reactivity it has been estimated that about one-third of the world's population, i.e., 1.7 billion people, are infected with Mycobacterium tuberculosis. Despite the availability of effective chemotherapies, it is responsible for three million deaths and from eight to ten million new cases annually and thus remains the leading cause of death world-wide due to a single infectious agent: 26% of all preventable deaths, 7% of all deaths. According to the World Health Organisation, 450,000 deaths per year due to tuberculosis in developing countries occur in children under fifteen years of age, and the disease mostly affects the younger, more productive adults.
- the preferred mode of treatment for tuberculosis is the short course chemotherapy in which there are two phases.
- the first phase consists of a daily regimen for two months with isoniazid (300 mg), rifampicin (600 mg), pyrazinamide (3 g) and ethambutol (1.5 g).
- the second phase or the continuation phase consists of a daily regimen for the next four months with isoniazid and rifampicin.
- MDR-TB multi-drug resistant tuberculosis
- MDR-TB The number of cases of MDR-TB has doubled since 1984 and in many of them the tubercle bacilli are resistant to both isoniazid and rifampicin.
- MDR-TB is difficult to treat as such since most patients do not respond very well to the second-line drugs and the cost of alternate treatment procedures, including hospitalisation and possibly surgery, increases the cost to as much as ten times the cost of traditional treatment.
- WO 93/12085 and WO 94/29272 describe two classes of isatin and oxindole derivatives which function as acetylcholinesterase inhibitors and which have application as pharmaceuticals in the treatment of cognitive dysfunctions such as Alzheimer's disease, senile dementia, Parkinson's disease, Down's syndrome and Huntington's chorea.
- R represents a 3- to 7-membered (hetero)cycloalkyl group or
- R represents either a -C12 alkyl group optionally substituted by one or more halogen atoms, a group
- R represents a -C6 alkyl group
- R represents a cyclohexyl or phenyl group optionally substituted by one or more substituents selected from the group consisting of a halogen atom, -C 6 alkyl and
- n represents an integer from 2 to 4
- p and q independently represent an integer from 1 to 2
- Z represents N or CH
- R represents a cyclohexyl or phenyl group optionally substituted by one or more substituents selected from the group consisting of a halogen atom, Cj-Cg alkyl and -CO alkoxy group, or a pharmaceutically-acceptable salt or solvate thereof in the manufacture of a medicament for use in the treatment of a mycobacterial disease, in particular tuberculosis.
- R represents a 5- to 7-membered (hetero)cycloalkyl group (e.g. a cyclopentyl, cyclohexyl, cycloheptyl, pyrrolidinyl, imidazolinyl, pyrazolidinyl, piperidinyl, piperazinyl or morpholinyl group) or a phenyl group.
- R represents a cyclopentyl, cyclohexyl, cycloheptyl or 1 -piperidinyl group.
- R ⁇ represents either a C1 -C12, preferably C4-C12, alkyl group (e.g. a methyl, ethyl, propyl, butyl, 2-methylpropyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl or dodecyl group); a group (A) as defined above in which m represents an integer from 3 to 7,
- R represents a Cj-C ⁇ alkyl group (e.g. a methyl, propyl, butyl, pentyl,
- R represents a cyclohexyl or, preferably, phenyl group optionally substituted by one or more, e.g. one, two, three or four, substituents selected from the group consisting of a halogen atom (e.g. fluorine, chlorine or bromine), -Cg alkyl (e.g. methyl, ethyl or propyl) and Q-C ⁇ alkoxy (e.g.
- halogen atom e.g. fluorine, chlorine or bromine
- -Cg alkyl e.g. methyl, ethyl or propyl
- Q-C ⁇ alkoxy e.g.
- n represents an integer from 2 to 4, preferably 2, p and q independently represent an integer of 2 or preferably 1 , Z represents N or CH and R represents a cyclohexyl or, preferably, phenyl group optionally substituted by one or more, e.g. one, two, three or four, substituents selected from the group consisting of a halogen atom (e.g. fluorine, chlorine or bromine), C ⁇ -C ⁇ alkyl (e.g. methyl, ethyl or propyl) and -Cg alkoxy (e.g. methoxy, ethoxy or propoxy) group.
- a halogen atom e.g. fluorine, chlorine or bromine
- C ⁇ -C ⁇ alkyl e.g. methyl, ethyl or propyl
- -Cg alkoxy e.g. methoxy, ethoxy or propoxy
- the compounds of formula I may be prepared by processes known in the art or by processes analogous to those known in the art, for example, as described in WO 93/12085 and WO 94/29272.
- L represents a leaving group such as a halogen atom and R is as hereinbefore defined, and optionally thereafter forming a pharmaceutically-acceptable salt or solvate thereof.
- the process may conveniently be carried out in a solvent such as dimethylformamide or tetrahydrofuran and in the presence of a base such as triethylamine, anhydrous potassium carbonate or sodium hydride.
- a solvent such as dimethylformamide or tetrahydrofuran
- a base such as triethylamine, anhydrous potassium carbonate or sodium hydride.
- the process will suitably be carried out at a temperature in the range from 0 to 100 °C.
- the compounds of formula (I) or (I') may be converted to a pharmaceutically- acceptable salt or solvate thereof, preferably an acid addition salt such as a hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, tartrate, citrate, oxalate, methanesulphonate or/?-toluenesulphonate, or an alkali metal salt such as a sodium or potassium salt.
- an acid addition salt such as a hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, tartrate, citrate, oxalate, methanesulphonate or/?-toluenesulphonate, or an alkali metal salt such as a sodium or potassium salt.
- Certain compounds of formula (I) or (F) are capable of existing in stereoisomeric forms. It will be understood that the invention encompasses all geometric and optical isomers of the compounds of formula (I) or (F) and mixtures thereof including racemates. Tautomers and mixtures thereof also form an aspect of the present invention.
- the compounds according to the present invention are advantageous in that they possess bactericidal activity against mycobacteria, particularly pathogenic mycobacteria such as Mycobacterium tuberculosis, M. bovis, M. avium and M. marinum. Accordingly, in another aspect, the invention provides a method of treating a patient suffering from, or at risk of, a mycobacterial disease, which comprises administering to the patient a therapeutically effective amount of a compound of formula (I) or (F), or a pharmaceutically-acceptable salt or solvate thereof, as defined above.
- a compound of formula (I) or (F) or a pharmaceutically-acceptable salt or solvate thereof, as defined above.
- the compounds of formula (I) or (F) and pharmaceutically-acceptable salts and solvates thereof may be used on their own but will generally be administered in the form of a pharmaceutical composition in which the formula (I) or (F) compound/salt/solvate (active ingredient) is in association with a pharmaceutically-acceptable adjuvant, diluent or carrier.
- the pharmaceutical composition will preferably comprise from 0.05 to 99 %w (per cent by weight), more preferably from 0.10 to 70 %w, of active ingredient, and, from 1 to 99.95 %w, more preferably from 30 to 99.90 %w, of a pharmaceutically-acceptable adjuvant, diluent or carrier, all percentages by weight being based on total composition.
- the pharmaceutical composition may additionally contain another anti-tubercular agent and/or various other ingredients known in the art, for example, a lubricant, stabilising agent, buffering agent, emulsifying agent, viscosity- regulating agent, surfactant, preservative, flavouring or colorant.
- a pharmaceutical composition comprising a compound of formula (F), or a pharmaceutically-acceptable salt or solvate thereof, as hereinbefore defined in association with a pharmaceutically-acceptable adjuvant, diluent or carrier.
- the invention further provides a process for the preparation of a pharmaceutical composition of the invention which comprises mixing a compound of formula (F), or a pharmaceutically-acceptable salt or solvate thereof, as hereinbefore defined with a pharmaceutically-acceptable adjuvant, diluent or carrier.
- the daily dosage of formula (I) or (F) compound administered will, of course, vary with the compound employed, the mode of administration, the treatment desired and the mycobacterial disease indicated. However, in general, satisfactory results will be obtained when the compound of formula (I) or (F) is administered at a daily dosage not exceeding 1 g, e.g. in the range from 10 to 50 mg/kg body weight.
- the compounds according to the invention may be administered systemically, e.g. by oral administration in the form of tablets, capsules, syrups, powders or granules, or by parenteral administration in the form of solutions or suspensions.
- Example 2 7-Cvcloheptyl-l-r2-r4-(phenylmethyl)-l-piperazinvnethvn-lH-indole-2,3-dione
- the title compound was prepared in a manner similar to the process step described in the text from Page 7, line 34 to Page 8, line 5 of WO 94/29272 but using a haloalkane such as 1-bromononane together with 7-phenyl-lH-indole-2,3-dione.
- the title compound was prepared according to the process step described in the text from Page 7, line 34 to Page 8, line 5 of WO 94/29272 using 7-phenyl- lH-indole-2,3-dione and 1 ,4-dibromobutane.
- Each of the compounds of Examples 1 to 20 was assessed for bactericidal activity against M. tuberculosis by measuring its minimum inhibitory concentration (MIC) in the "BACTEC" (trade mark) system developed by Becton-Dickinson Diagnostic Instrument Systems, Sparks, U.S.A., which is based on a radiometric principle whereby carbon dioxide released by the catabolism of 14 C-palmitate is spectrophotometrically detected and quantitated in arbitrary units of measurement referred to as growth index (GI) units.
- MIC minimum inhibitory concentration
- BACTEC BACTEC vials were inoculated with 0.1 ml of M. tuberculosis (final bacterial concentration, 1 xlO 5 colony forming units per ml) and 0.1 ml of test compound in a range of concentrations. GI values were monitored until a value of > 30 was achieved for the 1: 100 dilution control.
- MIC is defined as the minimum concentration of test compound that effects a >95% inhibition of the culture in comparison to the undiluted control, when the control reaches a GI value of 999.
- Endpoint determination (>99% inhibition) is based on a conventional 1% resistance cut-off, wherein the organism is considered resistant to a particular concentration of test compound if growth of greater than 1 % of the bacterial population is observed.
- a comparison is made between growth of the organism in the presence of a pre-determined concentration of test compound and growth of the same organism diluted 1 : 100 in the absence of any test compound.
- the change in the GI values ( ⁇ GFj is used to determine the endpoint susceptibility of the organism to the test compound. If the ⁇ GI of the 1 : 100 control is greater than the ⁇ GI in the presence of the test compound, then the concentration of test compound used is considered to be bactericidal (>99% inhibition) for the organism.
- the MIC of the compounds of Examples 1 to 20 were determined for the following strains of M. tuberculosis:
- H37Ra 1 clinical isolate susceptible to isoniazid, rifampicin, ethambutol and streptomycin
- the compounds of Examples 1 to 20 demonstrate effective bactericidal activity against the above strains of M. tuberculosis which include single- and multiple-drug resistant strains.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Abstract
Description
Claims
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB998037249A CN100391455C (en) | 1998-03-06 | 1999-03-04 | New use |
DE69911380T DE69911380T2 (en) | 1998-03-06 | 1999-03-04 | USE OF ISATIN AND OXINDOL DERIVATIVES FOR THE PRODUCTION OF MEDICINAL PRODUCTS FOR THE TREATMENT OF MYCOBACTERIAL DISEASES |
EP99908059A EP1058548B1 (en) | 1998-03-06 | 1999-03-04 | The use of isatin and oxindole derivatives in the preparation of a medicament for use in the treatment of mycobacterial disease |
CA002320757A CA2320757A1 (en) | 1998-03-06 | 1999-03-04 | New use |
AT99908059T ATE249828T1 (en) | 1998-03-06 | 1999-03-04 | USE OF ISATIN AND OXINDOL DERIVATIVES FOR THE PRODUCTION OF MEDICINAL PRODUCTS FOR THE TREATMENT OF MYCOBACTERIAL DISEASES |
NZ506217A NZ506217A (en) | 1998-03-06 | 1999-03-04 | Compound for treatment of tuberculosis and other mycobacterial diseases |
BR9908510-0A BR9908510A (en) | 1998-03-06 | 1999-03-04 | Use of a compound, compound, process for preparing a compound, pharmaceutical composition, and process for treating a patient suffering from, or at risk for, a mycobacterial disease |
US09/284,516 US6906090B1 (en) | 1998-03-06 | 1999-03-04 | Compositions and methods for treating mycobacterial diseases |
KR1020007009824A KR20010041625A (en) | 1998-03-06 | 1999-03-04 | New Use |
AU27573/99A AU735381B2 (en) | 1998-03-06 | 1999-03-04 | New use |
JP2000534210A JP2002505286A (en) | 1998-03-06 | 1999-03-04 | New use |
NO20004419A NO20004419L (en) | 1998-03-06 | 2000-09-05 | New use |
HK01101845A HK1030885A1 (en) | 1998-03-06 | 2001-03-14 | The use of isatin and oxindole derivatives in the preparation of a medicament for use in the treatment of mycobacterial disease |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN464/MAS/98 | 1998-03-06 | ||
IN464MA1998 | 1998-03-06 | ||
SE9801370A SE9801370D0 (en) | 1998-04-20 | 1998-04-20 | New use |
SE9801370-9 | 1998-04-20 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1999044608A1 true WO1999044608A1 (en) | 1999-09-10 |
WO1999044608A8 WO1999044608A8 (en) | 2005-01-06 |
Family
ID=26324794
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE1999/000319 WO1999044608A1 (en) | 1998-03-06 | 1999-03-04 | New use |
Country Status (14)
Country | Link |
---|---|
US (1) | US6906090B1 (en) |
EP (1) | EP1058548B1 (en) |
JP (1) | JP2002505286A (en) |
KR (1) | KR20010041625A (en) |
CN (1) | CN100391455C (en) |
AT (1) | ATE249828T1 (en) |
AU (1) | AU735381B2 (en) |
BR (1) | BR9908510A (en) |
CA (1) | CA2320757A1 (en) |
DE (1) | DE69911380T2 (en) |
HK (1) | HK1030885A1 (en) |
NO (1) | NO20004419L (en) |
NZ (1) | NZ506217A (en) |
WO (1) | WO1999044608A1 (en) |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000066556A1 (en) * | 1999-05-04 | 2000-11-09 | American Home Products Corporation | Indoline derivatives as progesterone antagonists |
WO2001056974A2 (en) * | 2000-02-07 | 2001-08-09 | Genzyme Corporation | Inha inhibitors and their use as antibacterials |
US6306851B1 (en) | 1999-05-04 | 2001-10-23 | American Home Products Corporation | Cyclocarbamate and cyclic amide derivatives |
US6319912B1 (en) | 1999-05-04 | 2001-11-20 | American Home Products Corporation | Cyclic regimens using 2,1-benzisothiazoline 2,2-dioxides |
US6329416B1 (en) | 1999-05-04 | 2001-12-11 | American Home Products Corporation | Combination regimens using 3,3-substituted indoline derivatives |
US6339098B1 (en) | 1999-05-04 | 2002-01-15 | American Home Products Corporation | 2,1-benzisothiazoline 2,2-dioxides |
US6355648B1 (en) | 1999-05-04 | 2002-03-12 | American Home Products Corporation | Thio-oxindole derivatives |
US6358947B1 (en) | 1999-05-04 | 2002-03-19 | American Home Products Corporation | Tetracyclic progesterone receptor modulator compounds and methods |
US6358948B1 (en) | 1999-05-04 | 2002-03-19 | American Home Products Corporation | Quinazolinone and benzoxazine derivatives as progesterone receptor modulators |
US6369056B1 (en) | 1999-05-04 | 2002-04-09 | American Home Products Corporation | Cyclic urea and cyclic amide derivatives |
US6380235B1 (en) | 1999-05-04 | 2002-04-30 | American Home Products Corporation | Benzimidazolones and analogues |
US6380178B1 (en) | 1999-05-04 | 2002-04-30 | American Home Products Corporation | Cyclic regimens using cyclocarbamate and cyclic amide derivatives |
US6399593B1 (en) | 1999-05-04 | 2002-06-04 | Wyeth | Cyclic regimens using cyclic urea and cyclic amide derivatives |
US6407101B1 (en) | 1999-05-04 | 2002-06-18 | American Home Products Corporation | Cyanopyrroles |
US6417214B1 (en) | 1999-05-04 | 2002-07-09 | Wyeth | 3,3-substituted indoline derivatives |
US6423699B1 (en) | 1999-05-04 | 2002-07-23 | American Home Products Corporation | Combination therapies using benzimidazolones |
US6436929B1 (en) | 1999-05-04 | 2002-08-20 | Wyeth | Cyclothiocarbamate derivatives as progesterone receptor modulators |
US6462032B1 (en) | 1999-05-04 | 2002-10-08 | Wyeth | Cyclic regimens utilizing indoline derivatives |
US6498154B1 (en) | 1999-05-04 | 2002-12-24 | Wyeth | Cyclic regimens using quinazolinone and benzoxazine derivatives |
US6509334B1 (en) | 1999-05-04 | 2003-01-21 | American Home Products Corporation | Cyclocarbamate derivatives as progesterone receptor modulators |
US6759408B2 (en) | 1999-05-04 | 2004-07-06 | Wyeth | Combination regimens using progesterone receptor modulators |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101863823B (en) * | 2010-06-03 | 2012-02-08 | 山东大学 | 2-oxindole compounds, and ring-enlargement derivatives, preparation method and application thereof |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
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GR65270B (en) * | 1978-10-10 | 1980-07-31 | Fujisawa Pharmaceutical Co | Isatin derivatives and processes for the preparation thereof |
IE69677B1 (en) | 1989-12-11 | 1996-10-02 | Neurosearch As | Isatine derivatives their preparation and use |
US5164404A (en) | 1991-03-15 | 1992-11-17 | Neurosearch A/S | Hydrazone derivatives and their use |
SE9103752D0 (en) * | 1991-12-18 | 1991-12-18 | Astra Ab | NEW COMPOUNDS |
US5206366A (en) * | 1992-08-26 | 1993-04-27 | Pfizer Inc. | Process for preparing aryl piperazinyl-heterocyclic compounds |
US5270331A (en) * | 1993-01-26 | 1993-12-14 | Pfizer, Inc. | Prodrugs of antiinflammatory 3-acyl-2-oxindole-1-carboxamides |
SE9302080D0 (en) * | 1993-06-16 | 1993-06-16 | Ab Astra | NEW COMPOUNDS |
-
1999
- 1999-03-04 DE DE69911380T patent/DE69911380T2/en not_active Expired - Fee Related
- 1999-03-04 CN CNB998037249A patent/CN100391455C/en not_active Expired - Fee Related
- 1999-03-04 JP JP2000534210A patent/JP2002505286A/en active Pending
- 1999-03-04 BR BR9908510-0A patent/BR9908510A/en not_active Application Discontinuation
- 1999-03-04 US US09/284,516 patent/US6906090B1/en not_active Expired - Fee Related
- 1999-03-04 CA CA002320757A patent/CA2320757A1/en not_active Abandoned
- 1999-03-04 NZ NZ506217A patent/NZ506217A/en unknown
- 1999-03-04 AU AU27573/99A patent/AU735381B2/en not_active Ceased
- 1999-03-04 EP EP99908059A patent/EP1058548B1/en not_active Expired - Lifetime
- 1999-03-04 WO PCT/SE1999/000319 patent/WO1999044608A1/en not_active Application Discontinuation
- 1999-03-04 AT AT99908059T patent/ATE249828T1/en not_active IP Right Cessation
- 1999-03-04 KR KR1020007009824A patent/KR20010041625A/en not_active Application Discontinuation
-
2000
- 2000-09-05 NO NO20004419A patent/NO20004419L/en unknown
-
2001
- 2001-03-14 HK HK01101845A patent/HK1030885A1/en not_active IP Right Cessation
Non-Patent Citations (3)
Title |
---|
BOLL. SOC. IT. BIOL. SPER., Volume 62, No. 12, 1986, E. PISCOPO et al., "Studies on Heterocyclic Compounds: Indol-2,3-Dione Derivatives. VI. 3-Aryliminoindol-2(3H)-Ones and Their Mannich Bases with Antimicrobial Activity", pages 1449-1455. * |
INDIAN JOURNAL OF CHEMISTRY, Volume 21B, August 1982, RAJENDRA S. VERMA et al., "Synthesis of Alkyl 4-Ú{4'-(1,2-Dihydro-5-Chloro-2-Oxo-3H-Indol -3-Ylideneamino)-BenzoylüAmino¾Benzoates & Related Compounds", pages 775-777. * |
PHARMAZIE, Volume 34, No. 4, 1979, M. MOVRIN et al., "Biologisch Aktive Azomethine", pages 231-232. * |
Cited By (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6436929B1 (en) | 1999-05-04 | 2002-08-20 | Wyeth | Cyclothiocarbamate derivatives as progesterone receptor modulators |
US6319912B1 (en) | 1999-05-04 | 2001-11-20 | American Home Products Corporation | Cyclic regimens using 2,1-benzisothiazoline 2,2-dioxides |
US7081457B2 (en) | 1999-05-04 | 2006-07-25 | Wyeth | Cyclothiocarbamate derivatives as progesterone receptor modulators |
US6423699B1 (en) | 1999-05-04 | 2002-07-23 | American Home Products Corporation | Combination therapies using benzimidazolones |
US6329416B1 (en) | 1999-05-04 | 2001-12-11 | American Home Products Corporation | Combination regimens using 3,3-substituted indoline derivatives |
US6339098B1 (en) | 1999-05-04 | 2002-01-15 | American Home Products Corporation | 2,1-benzisothiazoline 2,2-dioxides |
US6355648B1 (en) | 1999-05-04 | 2002-03-12 | American Home Products Corporation | Thio-oxindole derivatives |
US6358947B1 (en) | 1999-05-04 | 2002-03-19 | American Home Products Corporation | Tetracyclic progesterone receptor modulator compounds and methods |
US6358948B1 (en) | 1999-05-04 | 2002-03-19 | American Home Products Corporation | Quinazolinone and benzoxazine derivatives as progesterone receptor modulators |
US6369056B1 (en) | 1999-05-04 | 2002-04-09 | American Home Products Corporation | Cyclic urea and cyclic amide derivatives |
US6380235B1 (en) | 1999-05-04 | 2002-04-30 | American Home Products Corporation | Benzimidazolones and analogues |
US6380178B1 (en) | 1999-05-04 | 2002-04-30 | American Home Products Corporation | Cyclic regimens using cyclocarbamate and cyclic amide derivatives |
US6391907B1 (en) | 1999-05-04 | 2002-05-21 | American Home Products Corporation | Indoline derivatives |
US6399593B1 (en) | 1999-05-04 | 2002-06-04 | Wyeth | Cyclic regimens using cyclic urea and cyclic amide derivatives |
US6407101B1 (en) | 1999-05-04 | 2002-06-18 | American Home Products Corporation | Cyanopyrroles |
US6417214B1 (en) | 1999-05-04 | 2002-07-09 | Wyeth | 3,3-substituted indoline derivatives |
US6306851B1 (en) | 1999-05-04 | 2001-10-23 | American Home Products Corporation | Cyclocarbamate and cyclic amide derivatives |
WO2000066556A1 (en) * | 1999-05-04 | 2000-11-09 | American Home Products Corporation | Indoline derivatives as progesterone antagonists |
US6946454B2 (en) | 1999-05-04 | 2005-09-20 | Wyeth | Thio-oxindole derivatives |
US6441019B2 (en) | 1999-05-04 | 2002-08-27 | Wyeth | Cyclocarbamate and cyclic amide derivatives |
US6462032B1 (en) | 1999-05-04 | 2002-10-08 | Wyeth | Cyclic regimens utilizing indoline derivatives |
US6498154B1 (en) | 1999-05-04 | 2002-12-24 | Wyeth | Cyclic regimens using quinazolinone and benzoxazine derivatives |
US6503939B2 (en) | 1999-05-04 | 2003-01-07 | Wyeth | Combination regimens using 3,3-substituted indoline derivatives |
US6509334B1 (en) | 1999-05-04 | 2003-01-21 | American Home Products Corporation | Cyclocarbamate derivatives as progesterone receptor modulators |
US6521657B2 (en) | 1999-05-04 | 2003-02-18 | Wyeth | Thio-oxindole derivatives |
US6544970B2 (en) | 1999-05-04 | 2003-04-08 | Wyeth | Cyclic regimens utilizing indoline derivatives |
US6562857B2 (en) | 1999-05-04 | 2003-05-13 | Wyeth | Cyanopyrroles |
US6566358B2 (en) | 1999-05-04 | 2003-05-20 | Wyeth | Cyclocarbamate derivatives as progesterone receptor modulators |
US6583145B1 (en) | 1999-05-04 | 2003-06-24 | Wyeth | Thio-oxindole derivatives |
US6608068B2 (en) | 1999-05-04 | 2003-08-19 | Wyeth | Indoline derivatives |
US6693103B2 (en) | 1999-05-04 | 2004-02-17 | Wyeth | 1,2,3,4-tetrahydro-2-thioxo-quinolinyl and 1,2,3,4-tetrahydro-2-oxo-quinolinyl derivatives as progesterone receptor modulators |
US6759408B2 (en) | 1999-05-04 | 2004-07-06 | Wyeth | Combination regimens using progesterone receptor modulators |
US6794373B2 (en) | 1999-05-04 | 2004-09-21 | Wyeth | Contraceptive methods using benzimidazolones |
US6835744B2 (en) | 1999-05-04 | 2004-12-28 | Wyeth | 3,3-substituted indoline derivatives |
WO2001056974A2 (en) * | 2000-02-07 | 2001-08-09 | Genzyme Corporation | Inha inhibitors and their use as antibacterials |
WO2001056974A3 (en) * | 2000-02-07 | 2002-07-18 | Genzyme Corp | Inha inhibitors and their use as antibacterials |
Also Published As
Publication number | Publication date |
---|---|
HK1030885A1 (en) | 2001-05-25 |
CN100391455C (en) | 2008-06-04 |
NO20004419L (en) | 2000-10-20 |
NZ506217A (en) | 2002-05-31 |
CA2320757A1 (en) | 1999-09-10 |
NO20004419D0 (en) | 2000-09-05 |
EP1058548B1 (en) | 2003-09-17 |
BR9908510A (en) | 2000-11-21 |
WO1999044608A8 (en) | 2005-01-06 |
ATE249828T1 (en) | 2003-10-15 |
KR20010041625A (en) | 2001-05-25 |
CN1292694A (en) | 2001-04-25 |
DE69911380T2 (en) | 2004-07-01 |
US6906090B1 (en) | 2005-06-14 |
AU2757399A (en) | 1999-09-20 |
EP1058548A1 (en) | 2000-12-13 |
DE69911380D1 (en) | 2003-10-23 |
JP2002505286A (en) | 2002-02-19 |
AU735381B2 (en) | 2001-07-05 |
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