WO2019215075A1 - 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors - Google Patents

1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors Download PDF

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Publication number
WO2019215075A1
WO2019215075A1 PCT/EP2019/061532 EP2019061532W WO2019215075A1 WO 2019215075 A1 WO2019215075 A1 WO 2019215075A1 EP 2019061532 W EP2019061532 W EP 2019061532W WO 2019215075 A1 WO2019215075 A1 WO 2019215075A1
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Prior art keywords
group
alkyl
indazole
alkoxy
mmol
Prior art date
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Ceased
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PCT/EP2019/061532
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English (en)
French (fr)
Inventor
Guido Furlotti
Claudia CAVARISCHIA
Rosa BUONFIGLIO
Rosella Ombrato
Tommaso Iacoangeli
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Angelini Acraf SpA
Original Assignee
Aziende Chimiche Riunite Angelini Francesco ACRAF SpA
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Publication date
Application filed by Aziende Chimiche Riunite Angelini Francesco ACRAF SpA filed Critical Aziende Chimiche Riunite Angelini Francesco ACRAF SpA
Priority to LTEPPCT/EP2019/061532T priority Critical patent/LT3790873T/lt
Priority to US17/051,352 priority patent/US11472795B2/en
Priority to DK19721295.4T priority patent/DK3790873T3/da
Priority to AU2019265606A priority patent/AU2019265606B2/en
Priority to CA3094896A priority patent/CA3094896A1/en
Priority to EP19721295.4A priority patent/EP3790873B1/en
Priority to MDE20210228T priority patent/MD3790873T2/ro
Priority to IL278330A priority patent/IL278330B2/en
Priority to MX2020011882A priority patent/MX2020011882A/es
Priority to SM20220227T priority patent/SMT202200227T1/it
Priority to UAA202006085A priority patent/UA128089C2/uk
Priority to SG11202009230WA priority patent/SG11202009230WA/en
Priority to SI201930227T priority patent/SI3790873T1/sl
Priority to ES19721295T priority patent/ES2913975T3/es
Priority to JP2020562568A priority patent/JP7411574B2/ja
Priority to RS20220482A priority patent/RS63255B1/sr
Priority to KR1020207030163A priority patent/KR102778690B1/ko
Priority to HRP20220664TT priority patent/HRP20220664T1/hr
Priority to CN201980029405.9A priority patent/CN112135821B/zh
Priority to BR112020021922-3A priority patent/BR112020021922A2/pt
Priority to EA202092422A priority patent/EA202092422A1/ru
Priority to PL19721295T priority patent/PL3790873T3/pl
Publication of WO2019215075A1 publication Critical patent/WO2019215075A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • GSK-3 Human GSK-3 are encoded by two different and independent genes, which leads to GSK-3a and GSK-3 proteins, with molecular weights of about 51 and 47 kDa, respectively.
  • the two isoforms share nearly identical sequences in their kinase domains, while outside of the kinase domain, their sequences differ substantially ( Benedetti et at., Neuroscience Letters, 2004, 368, 123-126).
  • GSK-3a is a multifunctional protein serine kinase
  • GSK- 3b is a serine-threonine kinase.
  • GSK-3 the role of GSK-3 in cancer is a well-accepted phenomenon.
  • the compounds according to this invention are useful for the treatment of the pathological conditions arising from the uncontrolled activation and/or over- expression of GSK-3 , selected from the group comprising (i) insulin-resistance disorders, such as type-2 diabetes, syndrome X, obesity and polycystic ovary syndrome; (ii) neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease and Huntington’s disease; (iii) mood disorders, such as bipolar disorders and depressive disorders; (iv) schizophrenic disorders; (v) cancerous disorders, such as prostate, pancreatic, ovarian, and colon-rectal cancer and MLL-associated leukaemia; (vi) inflammation, (vii) osteoporosis, (viii) cardiac hypertrophy, (ix) epilepsies and (x) neuropathic pain.
  • insulin-resistance disorders such as type-2 diabetes, syndrome X, obesity and polycystic ovary syndrome
  • neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s
  • the present invention relates to the use of 1 H-indazole-3-carboxamide compounds having the following general formula (I):
  • the term“C 1 -C6 alkyl amino” has the meaning of a“C 1 -C6 alkyl” group wherein one or more hydrogen atoms are substituted by an amino group having the formula -NR 1 R 2 , wherein R 1 and R 2 are independently a hydrogen atom, a Ci-C 4 alkyl group, a C 2 -C 4 alkenyl group, a C 2 -C 4 alkynyl group, and a phenyl group, or R 1 and R 2 together with the nitrogen atom form an aliphatic heterocyclic ring having 5 to 6 members, optionally comprising at least one additional heteroatom selected from N, S and O.
  • the pharmaceutically acceptable organic bases are selected from the group consisting of tromethamine, lysine, arginine, glycine, alanine and ethanolamine.
  • the present invention also includes the prodrugs, stereoisomers, and enantiomers of the compounds of formula (I) described above.
  • prodrug refers to an agent, which is converted into the parent drug in vivo by some physiological chemical process (e.g., a prodrug on being brought to the physiological pH is converted to the desired drug form).
  • Prodrugs are often useful because, in some situations, they may be easier to administer than the parent drug. They may, for instance, be bioavailable by oral administration whereas the parent drug is not.
  • the prodrug may also have improved solubility in pharmacological compositions over the parent drug.
  • Ester prodrugs of the compounds disclosed herein are specifically contemplated.
  • An ester may be formed from a hydroxyl functional group linked to a compound of formula (I) above by reaction with a carboxylic acid or an aminoacid. While not intending to be limiting, an ester may be an alkyl ester, an aryl ester, or a heteroaryl ester.
  • alkyl has the meaning generally understood by those skilled in the art and refers to linear, branched, or cyclic alkyl moieties.
  • the dosage forms of the pharmaceutical composition of the present invention can be prepared by techniques that are familiar to a pharmaceutical chemist, and comprise mixing, granulation, compression, dissolution, sterilization and the like.
  • the title compound was obtained according to general procedure D, step 3 using 5-(2,3-difluorophenyl)-1 /-/-indazole-3-carboxylic acid (XVa, 0.07 g, 0.25 mmol), (tetrahydro-2/-/-pyran-3-yl)methanamine (lllh, 0.04g, 0.37 mmol), EtsN (0.04 g, 0.05 ml_, 0.37 mmol) and PyBOP (0.13 g, 0.25 mmol).
  • the crude was purified by flash chromatography (S1O2, CHC /MeOH, then C18, H 2 O/ACN/0.01 % TFA) to give 0.02 g of the title product.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
PCT/EP2019/061532 2018-05-07 2019-05-06 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors Ceased WO2019215075A1 (en)

Priority Applications (22)

Application Number Priority Date Filing Date Title
LTEPPCT/EP2019/061532T LT3790873T (lt) 2018-05-07 2019-05-06 1h-indazol-3-karboksamido junginiai kaip glikogeno sintazės kinazės 3 beta inhibitoriai
US17/051,352 US11472795B2 (en) 2018-05-07 2019-05-06 1H-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
DK19721295.4T DK3790873T3 (da) 2018-05-07 2019-05-06 1h-indazol-3-carboxamidforbindelser som glycogensynthase-kinase-3-beta-inhibitorer
AU2019265606A AU2019265606B2 (en) 2018-05-07 2019-05-06 1H-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
CA3094896A CA3094896A1 (en) 2018-05-07 2019-05-06 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
EP19721295.4A EP3790873B1 (en) 2018-05-07 2019-05-06 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
MDE20210228T MD3790873T2 (ro) 2018-05-07 2019-05-06 Compuși 1H-indazol-3-carboxamidici în calitate de inhibitori ai glicogensintazkinazei 3-beta
IL278330A IL278330B2 (en) 2018-05-07 2019-05-06 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
MX2020011882A MX2020011882A (es) 2018-05-07 2019-05-06 Compuestos de 1h-indazole-3-carboxamida como inhibidores de glucogeno sintasa cinasa 3 beta.
SM20220227T SMT202200227T1 (it) 2018-05-07 2019-05-06 Composti di 1h-indazol-3-carbossammide come inibitori della glicogeno sintasi chinasi 3 beta
UAA202006085A UA128089C2 (uk) 2018-05-07 2019-05-06 1h-індазол-3-карбоксамідні сполуки як інгібітори кінази-3 бета глікогенсинтази
SG11202009230WA SG11202009230WA (en) 2018-05-07 2019-05-06 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
SI201930227T SI3790873T1 (sl) 2018-05-07 2019-05-06 1H-indazol-3-karboksamidne spojine kot inhibitorji kinaze glikogen sintaze 3 beta
ES19721295T ES2913975T3 (es) 2018-05-07 2019-05-06 Compuestos de 1H-indazol-3-carboxamida como inhibidores de la glucógeno sintasa cinasa-3 beta
JP2020562568A JP7411574B2 (ja) 2018-05-07 2019-05-06 グリコーゲンシンターゼキナーゼ３ベータ阻害剤としての１ｈ－インダゾール－３－カルボキサミド化合物
RS20220482A RS63255B1 (sr) 2018-05-07 2019-05-06 1h-indazol-3-karboksamid jedinjenja kao inhibitori glikogen sintaza kinaze 3 beta
KR1020207030163A KR102778690B1 (ko) 2018-05-07 2019-05-06 글리코겐 합성효소 키나아제 3 베타 억제제로서 1h-인다졸-3-카복사마이드 화합물
HRP20220664TT HRP20220664T1 (hr) 2018-05-07 2019-05-06 1h-indazol-3-karboksamid spojevi kao inhibitori glikogen sintaza kinaze 3 beta
CN201980029405.9A CN112135821B (zh) 2018-05-07 2019-05-06 作为糖原合酶激酶3β抑制剂的1H-吲唑-3-甲酰胺化合物
BR112020021922-3A BR112020021922A2 (pt) 2018-05-07 2019-05-06 composto de 1h-indazol-3-carboxamida, uso de compostos de 1h-indazol-3-carboxamida, método de tratamento de um estado patológico surgindo da ativação descontrolada e/ou super-expressão de gsk-3b, e, composição farmacêutica
EA202092422A EA202092422A1 (ru) 2018-05-07 2019-05-06 1h-индазол-3-карбоксамидные соединения в качестве ингибиторов киназы гликогенсинтазы 3-бета
PL19721295T PL3790873T3 (pl) 2018-05-07 2019-05-06 Związki 1h-indazolo-3-karboksyamidowe jako inhibitory kinazy syntazy glikogenu 3 beta

Applications Claiming Priority (2)

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EP18171084 2018-05-07
EP18171084.9 2018-05-07

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WO2019215075A1 true WO2019215075A1 (en) 2019-11-14

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PCT/EP2019/061532 Ceased WO2019215075A1 (en) 2018-05-07 2019-05-06 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors

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US (1) US11472795B2 (https=)
EP (1) EP3790873B1 (https=)
JP (1) JP7411574B2 (https=)
KR (1) KR102778690B1 (https=)
CN (1) CN112135821B (https=)
AU (1) AU2019265606B2 (https=)
BR (1) BR112020021922A2 (https=)
CA (1) CA3094896A1 (https=)
CY (1) CY1125293T1 (https=)
DK (1) DK3790873T3 (https=)
EA (1) EA202092422A1 (https=)
ES (1) ES2913975T3 (https=)
GE (2) GEP20227437B (https=)
HR (1) HRP20220664T1 (https=)
HU (1) HUE058894T2 (https=)
IL (1) IL278330B2 (https=)
LT (1) LT3790873T (https=)
MA (1) MA52557A (https=)
MD (1) MD3790873T2 (https=)
MX (1) MX2020011882A (https=)
PL (1) PL3790873T3 (https=)
PT (1) PT3790873T (https=)
RS (1) RS63255B1 (https=)
SG (1) SG11202009230WA (https=)
SI (1) SI3790873T1 (https=)
SM (1) SMT202200227T1 (https=)
UA (1) UA128089C2 (https=)
WO (1) WO2019215075A1 (https=)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022052861A1 (zh) * 2020-09-09 2022-03-17 成都奥睿药业有限公司 5-取代吲哚3-酰胺衍生物及其制备方法和用途
EP4079732A4 (en) * 2019-12-16 2023-10-18 Korea Research Institute of Chemical Technology NEW INDAZOLE DERIVATIVE AND ITS USE
JP2023553426A (ja) * 2020-12-08 2023-12-21 ディスアーム セラピューティクス， インコーポレイテッド Ｓａｒｍ１のベンゾピラゾール阻害剤

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994010174A1 (en) 1992-11-05 1994-05-11 Smithkline Beecham Plc Piperidine derivatives as 5-ht4 receptor antagonists
WO2004014864A1 (en) 2002-08-10 2004-02-19 Astex Technology Limited 1h-indazole-3-carboxamide compounds as cyclin dependent kinases (cdk) inhibitors
WO2004074275A1 (en) 2003-02-18 2004-09-02 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Indazolamides with analgesic activity
WO2004101548A1 (en) 2003-05-15 2004-11-25 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Indazole having analgesic activity ,
WO2010109005A1 (en) 2009-03-27 2010-09-30 Abbott Gmbh & Co. Kg Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors
WO2013124169A1 (en) 2012-02-21 2013-08-29 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Use of 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
WO2013124158A1 (en) 2012-02-21 2013-08-29 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
WO2015143380A1 (en) 2014-03-20 2015-09-24 Samumed, Llc 5-substituted indazole-3-carboxamides and preparation and use thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101061599B1 (ko) * 2008-12-05 2011-09-02 한국과학기술연구원 비정상 세포 성장 질환의 치료를 위한 단백질 키나아제 저해제인 신규 인다졸 유도체, 이의 약학적으로 허용가능한염 및 이를 유효성분으로 함유하는 약학적 조성물
EP3473099A1 (en) * 2011-09-14 2019-04-24 Samumed, LLC Indazole-3-carboxamides and their use as wnt/b-catenin signaling pathway inhibitors
AU2019224075A1 (en) * 2018-02-23 2020-09-10 Samumed, Llc 5-heteroaryl substituted indazole-3-carboxamides and preparation and use thereof

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994010174A1 (en) 1992-11-05 1994-05-11 Smithkline Beecham Plc Piperidine derivatives as 5-ht4 receptor antagonists
WO2004014864A1 (en) 2002-08-10 2004-02-19 Astex Technology Limited 1h-indazole-3-carboxamide compounds as cyclin dependent kinases (cdk) inhibitors
WO2004074275A1 (en) 2003-02-18 2004-09-02 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Indazolamides with analgesic activity
WO2004101548A1 (en) 2003-05-15 2004-11-25 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Indazole having analgesic activity ,
WO2010109005A1 (en) 2009-03-27 2010-09-30 Abbott Gmbh & Co. Kg Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors
WO2013124169A1 (en) 2012-02-21 2013-08-29 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Use of 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
WO2013124158A1 (en) 2012-02-21 2013-08-29 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors
WO2015143380A1 (en) 2014-03-20 2015-09-24 Samumed, Llc 5-substituted indazole-3-carboxamides and preparation and use thereof
US9745271B2 (en) 2014-03-20 2017-08-29 Samumed, Llc 5-substituted indazole-3-carboxamides and preparation and use thereof

Non-Patent Citations (35)

* Cited by examiner, † Cited by third party
Title
BENEDETTI ET AL., NEUROSCIENCE LETTERS, vol. 368, 2004, pages 123 - 126
BIRCH ET AL., CANCER CELL, vol. 17, 2010, pages 529 - 531
CEDAZO-MINGUEZ ET AL., JOURNAL OF NEUROCHEMISTRY, vol. 87, 2003, pages 1152 - 1164
CHEN ET AL., J. NEUROCHEM., vol. 72, 1999, pages 1327 - 1330
COHEN ET AL., FEBS LETT., vol. 410, 1997, pages 3 - 10
DOKKEN ET AL., AM J. PHYSIOL. ENDOCRINOL. METAB., vol. 288, 2005, pages E1188 - E1194
DUKA T. ET AL., THE FASEB JOURNAL, vol. 23, 2009, pages 2820 - 2830
DURAN J. ET AL.: "GSK-3{3/NFA T Signaling Is Involved in Testosterone-Induced Cardiac Myocyte Hypertrophy", PLOS ONE, vol. 11, no. 12, 15 December 2016 (2016-12-15)
E. BEUREL ET AL.: "Glycogen synthase kinase-3 (GSK-3): Regulation, actions, and diseases", PHARMACOLOGY & THERAPEUTICS, vol. 148, 2015, pages 114 - 131, XP029199331, DOI: doi:10.1016/j.pharmthera.2014.11.016
EMAMIAN ET AL., NAT GENET, vol. 36, 2004, pages 131 - 137
EMBI ET AL., EUR J BIOCHEM, vol. 107, 1980, pages 519 - 527
G. KLAMERET, CURRENT MEDICINAL CHEMISTRY, vol. 17, no. 26, 2010, pages 2873 - 2281
GARCEA ET AL., CURRENT CANCER DRUG TARGETS, vol. 7, 2007, pages 209 - 215
GEETHA ET AL., BRITISH JOURNAL PHARMACOLOGY, vol. 156, 2009, pages 885 - 898
GHOSH ET AL., CLIN CANCER RES, vol. 11, 2005, pages 4580 - 4588
GOULD, EXPERT. OPIN. THER. TARGETS, vol. 10, 2006, pages 377 - 392
GRIMES; JOPE, PROGRESS IN NEUROBIOLOGY, vol. 65, 2001, pages 391 - 426
HANGER ET AL., NEUROSCI. LETT., vol. 147, 1992, pages 58 - 62
HERNANDEZ; AVILA, FEBS LETTERS, vol. 582, 2008, pages 3848 - 3854
HONG; LEE, J. BIOL. CHEM., vol. 272, 1997, pages 19547 - 19553
J. FENG ET AL.: "Photoactivation of TAZ via Akt/GSK-3(3 signaling pathway promotes osteogenic differentiation", INT J BIOCHEM CELL BIOL., vol. 66, September 2015 (2015-09-01), pages 59 - 68
JIA LUO, CANCER LETTERS, vol. 273, 2009, pages 194 - 200
JOPE; ROH, CURR. DRUG TARGETS, vol. 7, 2006, pages 1421 - 1434
KLEIN; MELTON, PROC. NATL. ACAD. SCI. USA, vol. 93, 1996, pages 8455 - 8459
M. RAHMATI ET AL.: "Decreased Activity in Neuropathic Pain Form and Gene Expression of Cyclin-Dependent Kinase5 and Glycogen Synthase Kinase-3 Beta in Soleus Muscle of Wistar Male Rats", IRAN RED CRESCENT MED J., vol. 17, no. 6, June 2015 (2015-06-01)
MATHES, C., EXPERT OPIN. THER. TARGETS, vol. 10, no. 2, 2006, pages 230 - 241
MAZANETZ; FISCHER, NAT REV DRUG DISCOV., vol. 6, 2007, pages 464 - 479
MEIJER ET AL., CHEM. BIOL., vol. 10, 2003, pages 1255 - 1266
MEIJER L. ET AL., TRENDS PHARM SCI, vol. 25, 2004, pages 471 - 480
QI CAO ET AL., CELL RESEARCH, vol. 16, 2006, pages 671 - 677
RING DB ET AL., DIABETES, vol. 52, 2003, pages 588 - 595
RINNAB ET AL., NEOPLASIA, vol. 10, 2008, pages 624 - 633
S. PHUKAN ET AL.: "GSK-3β: role in therapeutic landscape and development of modulators", BRITISH JOURNAL OF PHARMACOLOGY, vol. 160, 2010, pages 1 - 19
WANG ET AL., CYTOKINE, vol. 53, 2010, pages 130 - 140
Z. LI ET AL.: "Valproate Attenuates Endoplasmic Reticulum Stress-Induced Apoptosis in SH-SY5Y Cells via the AKT/GSK-3(3 Signaling Pathway", INT J MOL SCI., vol. 18, no. 2, 8 February 2017 (2017-02-08)

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