WO2006092032B1 - PHARMACEUTICAL COMPOSITIONS CONTAINING 1-METHYL-3,6,7,8-TETRAHYDROPIRAZOLO[3,4-b]PIRROLO[4,3-d]PYRIDINE-6,8-DIONE DERIVATIVES, USE, AND PROCESS FOR PREPARING THEM - Google Patents

PHARMACEUTICAL COMPOSITIONS CONTAINING 1-METHYL-3,6,7,8-TETRAHYDROPIRAZOLO[3,4-b]PIRROLO[4,3-d]PYRIDINE-6,8-DIONE DERIVATIVES, USE, AND PROCESS FOR PREPARING THEM

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Publication number
WO2006092032B1
WO2006092032B1 PCT/BR2006/000037 BR2006000037W WO2006092032B1 WO 2006092032 B1 WO2006092032 B1 WO 2006092032B1 BR 2006000037 W BR2006000037 W BR 2006000037W WO 2006092032 B1 WO2006092032 B1 WO 2006092032B1
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Prior art keywords
para
meta
ortho
alkyl
cycloalkyl
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Application number
PCT/BR2006/000037
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French (fr)
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WO2006092032A3 (en
WO2006092032A2 (en
Inventor
Lacerda Barreiro Eliezer De De
Fraga Carlos Alberto Manssour
Sudo Gisele Zapata
Sudo Roberto Takashi
Ricardo Menegatti
Original Assignee
Univ Rio De Janeiro
Lacerda Barreiro Eliezer De De
Fraga Carlos Alberto Manssour
Sudo Gisele Zapata
Sudo Roberto Takashi
Ricardo Menegatti
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Application filed by Univ Rio De Janeiro, Lacerda Barreiro Eliezer De De, Fraga Carlos Alberto Manssour, Sudo Gisele Zapata, Sudo Roberto Takashi, Ricardo Menegatti filed Critical Univ Rio De Janeiro
Publication of WO2006092032A2 publication Critical patent/WO2006092032A2/en
Publication of WO2006092032A3 publication Critical patent/WO2006092032A3/en
Publication of WO2006092032B1 publication Critical patent/WO2006092032B1/en

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    • 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
    • A61K31/437—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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/14—Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Neurosurgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Neurology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pain & Pain Management (AREA)
  • Epidemiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

The present invention is related to new derivatives of 1-methyl-3,6,7,8- tetrahydropirazolo[3,4-b]pirrolo[4,3-d]piridin-6,8-dione nucleus, preferably heterocyclic derivatives, acting as hypnotics and analgesic in the central nervous system, being useful in the treatment of anxiety and central hyperalgesia, including: anxiety relief, central hyperalgesia relief in mammals, preferably humans. It is also described pharmaceutical compositions containing said compounds and preparation processes.

Claims

AMENDED CLAIMS received by the International Bureau on 22 September 2006 (22.09.2006)PHARMACEUTICAL COMPOSITIONS CONTAINING 1-METHYL-3,6,7,8-TETRAHYDROPIRAZOLO[3,4-b]PIRROLO[4,3-d]PYRIDINE-6,8-DIONEDERIVATIVES, USE, AND PROCESS FOR PREPARING THEM.
1. Pharmaceutical composition characterized by comprising an active ingredient having the general formula (II):
Figure imgf000002_0001
wherein
R is, independently, hydrogen, alkyl, cycloalkyl;furyl, thiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl or isoquinolyl; or phenyl-W wherein W is, independently, hydrogen, ortho -alkyl, ortho-cycloalkyl, ortho -alkoxyl, ortho- cycloalkoxyl, ortho-thioxyl, ortho-aryoxyl, ortho -sulfones, ortho -sulphides, ortho- sulphoxides, ortho -sulfonates, ortho -sulfonamides, ortho -amine, ortho-amide, ortho -halides, ortho -carboalkoxyl, ortho-carbothioalkoxyl, ortho-trihaloalkene, ortho -ciano, ortho -nitro, meta-alkyl, meta-cycloalkyl, meta-alkoxyl, meta- cycloalkoxyl, meta-thioxyl, meta-aryoxyl, meta-sulfones, meta-sulphides, meta- sulphoxides, meta-sulfonates, meta-sulfonamides, meta-amine, meta-amide, meta-halides, meta-carboalkoxyl, meta-carbothioalkoxyl, meta-trihaloalkene, meta-ciano, meta-nitro, para-alkyl, para-cycloalkyl, para-alkoxyl, para- cycloalkoxyl, para-thioxyl, para-aryoxyl, para-sulfones, para-sulphides, para- sulphoxides, para-sulfonates, para-sulfonamides, para-amine, para-amide, para-halides, para-carboalkoxyl, para-carbothioalkoxyl, para-trihaloalkene, para-ciano or para-nitro; or its pharmaceutically acceptable salts, solvates and/or hydrates.
2. Pharmaceutical composition, according to claim 1 , characterized by the fact that it is 1-methyl-7-(4-nitrophenyl)-3-phenyl-3,6,7,8-tetrahydropyrazolo- [3,4-b]-pyrrolo-[3,4-d]-pyridine-6,8-dione or its pharmaceutically acceptable salts, solvates and/or hydrates.
3. Pharmaceutical composition, according to claim 1 , characterized by the fact that it is 1-methyl-7-(4-chlorophenyl)-3-phenyl-3,6,7,8- tetrahydropyrazolo-[3,4-b]-pyrrolo-[3,4-d]-pyridine-6,8-dione or its pharmaceutically acceptable salts, solvates and/or hydrates.
4. Process for the production of a compound having a general formula
(II):
Figure imgf000003_0001
wherein
R is, independently, hydrogen, alkyl, cycloalkyl; furyl, thiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl or isoquinolyl; or phenyl-W wherein W is, independently, hydrogen, ortho-alkyl, ortho-cycloalkyl, ortho -alkoxyl, ortho- cycloalkoxyl, ortho -thioxyl, ortho -aryoxyl, ortho -sulfones, ortho -sulphides, ortho- sulphoxides, ortho-sulfonates, ortho-sulfonamides, ortho-amine, ortho-amide, ortho -halides, ortho-carboalkoxyl, ortho -carbothioalkoxyl, ortho -trihaloalkene, ortho-c\ano, ortho-nitro, meta-alkyl, meta-cycloalkyl, meta-alkoxyl, meta- cycloalkoxyl, meta-thioxyl, meta-aryoxyl, meta-sulfones, meta-sulphides, meta- sulphoxides, meta-sulfonates, meta-sulfonamides, meta-amine, meta-amide, meta-halides, meta-carboalkoxyl, meta-carbothioalkoxyl, meta-trihaloalkene, meta-ciano, meta-nitro, para-alkyl, para-cycloalkyl, para-alkoxyl, para- cycloalkoxyl, para-thioxyl, para-aryoxyl, para-sulfones, para-sulphides, para- sulphoxides, para-sulfonates, para-sulfonamides, para-amine, para-amide, para-halides, para-carboalkoxyl, para-carbothioalkoxyl, para-trihaloalkene, para-ciano or para-nitro; or its pharmaceutically acceptable salts, solvates and/or hydrates; characterized by comprising the steps of: a) performing a sequential Michael's addition followed by 'in situ' cyclization by reacting β-iminobutyronitrile with a functional ized hydrazine in water and hydrochloridric acid; b) condensation of the compound formed in step a) with dimethylformamide dimethylacetal; and c) performing a hetero Diels-Alder, between the compound obtained in step b) with a nitrogen-functionalized pyrrole-2,5-dione derivative.
5. Use, of a compound of general formula (II):
Figure imgf000004_0001
wherein
R is, independently, hydrogen, alkyl, cycloalkyl; furyl, thiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl or isoquinolyl; or phenyl-W wherein W is, independently, hydrogen, ortho-alkyl, ortho- sycloalkyl, ortho-alkoxyl, ortho-cycloalkoxyl, ortho -thioxyl, orf/70-aryoxyl, orth o-sulfones, ortho -sulphides, ortho -sulphoxides, ortho -sulfonates, ortho-sulfonamides, ortho-amine ortho-amide, ortho -halides, ortho- carboalkoxyl, ortho-carbothioalkoxyl, ortho -trihaloalkene, ortho -ciano, ortho -nitro, meta-alkyl, meta-cycloalkyl, meta-alkoxyl, meta-cycloalkoxyl, meta-thioxyl, meta-aryoxyl, meta-sulfones, meta-sulphides, meta- sulphoxides, meta-sulfonatest meta-sulfonamides, meta-amine, meta- amide, meta-halides, meta-carboalkoxyl, meta-carbothioalkoxyl, meta- trihaloalkene, meta-ciano, meta-nitro, para-alkyl, para-cycloalkyl, para- alkoxyl, para-cycloalkoxyl, para-thioxyl, para-aryoxyl, para-sulfones, para-sulphides, para-sulphoxides, para-sulfonates, para-sulfonamides, para-amine, para-amide, para-halides, para-carboalkoxyl, para- carbothioalkoxyl, para-trihaloalkene, para-ciano or para-nitro; or its pharmaceutically acceptable salts, solvates and/or hydrates, in the preparation of medicines for the treatment of anxiety, sleep disturbances and/or pain-related symptoms.
PCT/BR2006/000037 2005-03-03 2006-03-03 PHARMACEUTICAL COMPOSITIONS CONTAINING 1-METHYL-3,6,7,8-TETRAHYDROPIRAZOLO[3,4-b]PIRROLO[4,3-d]PYRIDINE-6,8-DIONE DERIVATIVES, USE, AND PROCESS FOR PREPARING THEM WO2006092032A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
BRPI050.0727-5 2005-03-03
BRPI0500727-5A BRPI0500727A (en) 2005-03-03 2005-03-03 1-methyl-3,6,7,8-tetrahydropyrazolo [3,4, -b] pyrrolo [4,3-d] pyridine-6,8-dione derivatives, preparation process, pharmaceutical compositions containing same and related uses

Publications (3)

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WO2006092032A3 WO2006092032A3 (en) 2006-11-02
WO2006092032B1 true WO2006092032B1 (en) 2006-12-28

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TW201100423A (en) 2009-03-31 2011-01-01 Arqule Inc Substituted pyrazolo-pyrrolo-pyridine-dione compounds
CN110156775A (en) * 2018-02-12 2019-08-23 新发药业有限公司 A kind of pyrrole former times replaces the simple and convenient process for preparing of Buddhist nun
RU2771024C1 (en) * 2021-05-28 2022-04-25 Федеральное государственное автономное образовательное учреждение высшего образования "Белгородский государственный национальный исследовательский университет" (НИУ "БелГУ") Method and installation for the manufacture of diacetonitrile

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