CA2616196A1 - A pyridin quinolin substituted pyrrolo [1,2-b] pyrazole monohydrate as tgf-beta inhibitor - Google Patents

A pyridin quinolin substituted pyrrolo [1,2-b] pyrazole monohydrate as tgf-beta inhibitor Download PDF

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Publication number
CA2616196A1
CA2616196A1 CA002616196A CA2616196A CA2616196A1 CA 2616196 A1 CA2616196 A1 CA 2616196A1 CA 002616196 A CA002616196 A CA 002616196A CA 2616196 A CA2616196 A CA 2616196A CA 2616196 A1 CA2616196 A1 CA 2616196A1
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Canada
Prior art keywords
pyridin
quinolin
pyrrolo
dihydro
methyl
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Legal status (The legal status 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 status listed.)
Granted
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CA002616196A
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French (fr)
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CA2616196C (en
Inventor
Sreenivasa Reddy Mundla
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Eli Lilly and Co
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Eli Lilly And Company
Sreenivasa Reddy Mundla
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Publication of CA2616196A1 publication Critical patent/CA2616196A1/en
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Publication of CA2616196C publication Critical patent/CA2616196C/en
Expired - Fee Related legal-status Critical Current
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

The present invention provides crystalline 2-(6-methyl-pyridin-2-yl)-3-[6-amido- qumolin-4-yl)-5,6-dihydro-4H-pyrrolo[ l,2-b]pyrazole monohydrate.

Claims (10)

1. ~2-(6-Methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole monohydrate.
2. ~A crystalline 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole monohydrate of Claim 1 further characterized by the X-ray powder diffraction pattern (Cu radiation, .lambda. = 1.54056 .ANG.) comprising a peak at 9.05, and one or more peaks selected from the group comprising 11.02, 11.95, and 14.84 (2.THETA. +/- 0.1°).
3. ~A crystalline 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole monohydrate comprising 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole monohydrate of Claim 1 further characterized by the X-ray powder diffraction pattern (Cu radiation, .lambda. = 1.54056 .ANG.) comprising a peak at 9.05 (2.THETA. +/- 0.1°).
4. ~A crystalline 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole monohydrate of Claim 1 further characterized by the solid state 13C nuclear magnetic resonance having a chemical shift (ppm) of 108.8, 115.6, 122.6, and 171.0 (+/- 0.2) ppm.
5. ~A pharmaceutical composition comprising any of the compounds of Claims 1-4 and a pharmaceutically acceptable excipient, diluent, or carrier.
6. ~A method of inhibiting TGF-P signaling in a mammal comprising administering to a mammal in need of such treatment an effective amount of any of the compounds of Claims 1-5.
7. ~A method of treating conditions resulting from excessive TGF-.beta.
production in a mammal comprising administering to a mammal in need of such treatment a TGF-.beta.-signal suppressing amount of any of the compounds of Claims 1-5.
8. ~A process for making crystalline 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole monohydrate comprising the steps of crystallizing the anhydrous free base or re-crystallizing the monohydrate of (6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole from a ratio of about 0-90% organic solvent to water.
9. ~A process for making crystalline 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole monohydrate comprising the steps of reslurrying 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl-5,6-dihydro-pyrrolo[1,2-b]pyrazole in 0-90% organic solvent to water.
10. ~3-(6-cyano-quinolin-4-yl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole.
CA2616196A 2005-07-22 2006-06-29 A pyridin quinolin substituted pyrrolo [1,2-b] pyrazole monohydrate as tgf-beta inhibitor Expired - Fee Related CA2616196C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US70164105P 2005-07-22 2005-07-22
US60/701,641 2005-07-22
PCT/US2006/025377 WO2007018818A1 (en) 2005-07-22 2006-06-29 A pyridin quinolin substituted pyrrolo [1,2-b] pyrazole monohydrate as tgf-beta inhibitor

Publications (2)

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CA2616196A1 true CA2616196A1 (en) 2007-02-15
CA2616196C CA2616196C (en) 2012-08-21

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CA2616196A Expired - Fee Related CA2616196C (en) 2005-07-22 2006-06-29 A pyridin quinolin substituted pyrrolo [1,2-b] pyrazole monohydrate as tgf-beta inhibitor

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Country Link
US (1) US7872020B2 (en)
EP (1) EP1910370B1 (en)
JP (1) JP5242391B2 (en)
BR (1) BRPI0613639A2 (en)
CA (1) CA2616196C (en)
DK (1) DK1910370T3 (en)
ES (1) ES2542425T3 (en)
HR (1) HRP20150474T1 (en)
HU (1) HUE025209T2 (en)
IL (1) IL188181A (en)
MX (1) MX2008001020A (en)
PL (1) PL1910370T3 (en)
PT (1) PT1910370E (en)
RS (1) RS53999B1 (en)
SI (1) SI1910370T1 (en)
WO (1) WO2007018818A1 (en)

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WO2013009140A2 (en) * 2011-07-13 2013-01-17 Sk Chemicals Co., Ltd. 2-pyridyl substituted imidazoles as alk5 and/or alk4 inhibitors
US20150289795A1 (en) 2012-11-12 2015-10-15 Institució Catalana De Recerca I Estudis Avançats Methods and kits for the prognosis of colorectal cancer
HUE057521T2 (en) 2013-03-14 2022-05-28 Brigham & Womens Hospital Inc Compositions and methods for epithelial stem cell expansion and culture
AU2015311816B2 (en) 2014-09-03 2019-04-04 Massachusetts Institute Of Technology Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss
EP3277673B1 (en) 2015-04-01 2022-05-04 Rigel Pharmaceuticals, Inc. Tgf-beta inhibitors
WO2016210292A1 (en) 2015-06-25 2016-12-29 Children's Medical Center Corporation Methods and compositions relating to hematopoietic stem cell expansion, enrichment, and maintenance
JP6856648B2 (en) 2015-12-15 2021-04-07 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ CXCR4 receptor antagonist
CN108779437A (en) 2016-01-08 2018-11-09 麻省理工学院 The preparation of the enteroendocrine cell and insulin-producing cells of differentiation
US10213511B2 (en) 2016-03-02 2019-02-26 Frequency Therapeutics, Inc. Thermoreversible compositions for administration of therapeutic agents
US11260130B2 (en) 2016-03-02 2022-03-01 Frequency Therapeutics, Inc. Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor: IV
US10201540B2 (en) 2016-03-02 2019-02-12 Frequency Therapeutics, Inc. Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using GSK3 inhibitors: I
US20190119642A1 (en) 2016-03-15 2019-04-25 Children's Medical Center Corporation Methods and compositions relating to hematopoietic stem cell expansion
WO2018006870A1 (en) * 2016-07-07 2018-01-11 苏州科睿思制药有限公司 Galunisertib crystal form and preparation method therefor and use thereof
US10906905B2 (en) 2016-10-14 2021-02-02 Jiangsu Hengrui Medicine Co., Ltd. Five-membered heteroaryl ring bridged ring derivative, preparation method therefor and medical use thereof
MX2019007890A (en) 2016-12-30 2020-01-20 Frequency Therapeutics Inc 1h-pyrrole-2,5-dione compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells.
US11111248B2 (en) 2017-03-17 2021-09-07 Hangzhou Solipharma Co., Ltd. Crystal form of 2-(6-methyl-pyridin-2-yl)-3-yl-[6-amido-quinolin-4-yl]-5,6-dihydro-4H-pyrrolo[1,2-B]pyrazole, preparation method therefor and pharmaceutical composition thereof
CN110582279B (en) 2017-03-21 2023-07-14 杭州领业医药科技有限公司 Co-crystals of 2- (6-methyl-pyridin-2-yl) -3-yl- [ 6-amido-quinolin-4-yl ] -5, 6-dihydro-4H-pyrrolo [1,2-b ] pyrazole, methods for preparing the same and pharmaceutical compositions
WO2019042383A1 (en) * 2017-08-31 2019-03-07 苏州科睿思制药有限公司 Crystalline forms of galunisertib, preparation method therefor, and use thereof
WO2019105082A1 (en) * 2017-11-30 2019-06-06 苏州科睿思制药有限公司 Crystal form of galunisertib and preparation method therefor and use thereof
WO2019137027A1 (en) * 2018-01-12 2019-07-18 苏州科睿思制药有限公司 Crystal form of galunisertib and preparation method and use thereof
CA3093340A1 (en) 2018-03-20 2019-09-26 Icahn School Of Medicine At Mount Sinai Kinase inhibitor compounds and compositions and methods of use
US20210254006A1 (en) 2018-06-06 2021-08-19 Ideaya Biosciences, Inc. Methods of culturing and/or expanding stem cells and/or lineage committed progenitor cells using lactam compounds
US11617745B2 (en) 2018-08-17 2023-04-04 Frequency Therapeutics, Inc. Compositions and methods for generating hair cells by downregulating FOXO
CA3109647A1 (en) 2018-08-17 2020-02-20 Frequency Therapeutics, Inc. Compositions and methods for generating hair cells by upregulating jag-1
CN113508111A (en) 2018-12-31 2021-10-15 西奈山伊坎医学院 Kinase inhibitor compounds and compositions and methods of use
CN115282280A (en) * 2022-08-12 2022-11-04 中国科学技术大学 New use of TGF-beta 1 signal inhibitor

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UA80571C2 (en) 2002-11-22 2007-10-10 Lilly Co Eli Quinolinyl-pyrrolopyrazoles

Also Published As

Publication number Publication date
JP2009502780A (en) 2009-01-29
PT1910370E (en) 2015-06-30
IL188181A0 (en) 2008-03-20
SI1910370T1 (en) 2015-06-30
EP1910370A1 (en) 2008-04-16
JP5242391B2 (en) 2013-07-24
BRPI0613639A2 (en) 2012-02-22
MX2008001020A (en) 2008-03-25
ES2542425T3 (en) 2015-08-05
RS53999B1 (en) 2015-10-30
HRP20150474T1 (en) 2015-06-05
WO2007018818A1 (en) 2007-02-15
EP1910370B1 (en) 2015-04-22
IL188181A (en) 2014-05-28
HUE025209T2 (en) 2016-03-29
PL1910370T3 (en) 2015-09-30
CA2616196C (en) 2012-08-21
DK1910370T3 (en) 2015-06-08
US20100120854A1 (en) 2010-05-13
US7872020B2 (en) 2011-01-18

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