KR20220106123A - 피트 홉킨스 증후군 치료에 사용하기 위한 비시클릭 화합물 및 이의 사용방법 - Google Patents

피트 홉킨스 증후군 치료에 사용하기 위한 비시클릭 화합물 및 이의 사용방법 Download PDF

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KR20220106123A
KR20220106123A KR1020227017179A KR20227017179A KR20220106123A KR 20220106123 A KR20220106123 A KR 20220106123A KR 1020227017179 A KR1020227017179 A KR 1020227017179A KR 20227017179 A KR20227017179 A KR 20227017179A KR 20220106123 A KR20220106123 A KR 20220106123A
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파트리시아 코그램
조나단 필처
로렌스 어윈 글래스
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뉴렌 파마슈티컬즈 리미티드
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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
    • A61K31/495—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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/436—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 oxygen as a ring hetero atom, e.g. rapamycin
    • 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
    • A61K31/5365—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 ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—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 sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1825—Fibroblast growth factor [FGF]
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    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1841—Transforming growth factor [TGF]
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    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/185—Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
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    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
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    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Hospice & Palliative Care (AREA)
  • Molecular Biology (AREA)
  • Psychology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
KR1020227017179A 2019-10-22 2020-04-24 피트 홉킨스 증후군 치료에 사용하기 위한 비시클릭 화합물 및 이의 사용방법 Pending KR20220106123A (ko)

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US201962924452P 2019-10-22 2019-10-22
US62/924,452 2019-10-22
PCT/US2020/029739 WO2021080646A1 (en) 2019-10-22 2020-04-24 Bicyclic compounds and methods for their use in treating pitt hopkins syndrome

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KR20220106123A true KR20220106123A (ko) 2022-07-28

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US (2) US12472177B2 (enExample)
EP (1) EP4048264A4 (enExample)
JP (1) JP2022553060A (enExample)
KR (1) KR20220106123A (enExample)
CN (1) CN115243688A (enExample)
AU (1) AU2020369431B2 (enExample)
BR (1) BR112022007636A2 (enExample)
CA (1) CA3158406A1 (enExample)
CL (1) CL2022001023A1 (enExample)
CO (1) CO2022006718A2 (enExample)
IL (1) IL292408A (enExample)
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IL305132A (en) * 2021-02-12 2023-10-01 Neuren Pharmaceuticals Ltd Preparations for the treatment of the Prader-Willi phenomenon

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WO2008063311A2 (en) 2006-10-11 2008-05-29 Neuren Pharmaceuticals Limited Cyclic glycyl-2-allyl proline improves cognitive performance in impaired animals
SI1664050T1 (sl) 2003-09-03 2016-04-29 Neuren Pharmaceuticals Limited Nevroprotektične biciklične spojine in farmacevtski sestavki, vsebujoči le-te
WO2011037644A1 (en) * 2009-09-25 2011-03-31 Neuren Pharmaceuticals Limited Cyclic glycyl-2-allyl proline and its use in treatment of peripheral neuropathy
JP6574769B2 (ja) * 2013-07-25 2019-09-11 ニューレン ファーマシューティカルズ リミテッド 二環式化合物ならびに自閉症スペクトラム障害および神経発達障害の治療におけるそれらの使用方法

Non-Patent Citations (23)

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Title
Amiel J, Rio M, de Pontual L, 등 Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction. Am J Hum Genet. 2007;80(5):988-993.
Bertrand N, Castro DS, Guillemot F. Proneural genes and the specification of neural cell types. Nat Rev Neurosci. 2002;3(7):517-530.
Blake DJ, Forrest M, Chapman RM, 등 TCF4, schizophrenia, and Pitt-Hopkins Syndrome. Schizophr Bull. 2010;36(3):443-447. doi: https:// doi. org/10. 1093/ schbul/ sbq035.
Brockschmidt A, Todt U, Ryu S, 등 Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4. Hum Mol Genet. 2007;16(12):1488-1494.
Brzozka MM, Radyushkin K, Wichert SP, Ehrenreich H, Rossner MJ. Cognitive and Sensorimotor Gating Impairments in Transgenic Mice Overexpressing the Schizophrenia Susceptibility Gene Tcf4 in the Brain. Biol Psychiatry. 2010;68(1):33-40. https:// doi.org/10. 1016/j .biopsych. 2010. 03.015.
Crux S, Herms J, Dorostkar MM. Tcf4 regulates dendritic spine density and morphology in the adult brain. PLoS ONE. 2018;13(6):e0199359. https: //doi. org/ 10.1371/ journal. pone. 0199359.
de Pontual L, Mathieu Y, Golzio C, 등 Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins Syndrome. Hum Mutat. 2009;30(4):669-676.
Flora A, Garcia JJ, Thaller C, Zoghbi HY. The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors. Proc Nat Acad Sci U.S.A. 2007;104(39):15382-15387. DOI:10.1073/pnas.0707456104.
Forrest MP, Waite AJ, Martin-Rendon E, Blake DJ. Knockdown of human TCF4 affects multiple signaling pathways involved in cell survival, epithelial to mesenchymal transition and neuronal differentiation. PLoS One. 2013;8(8):e73169. https: //doi.org/ 10.1371/ journal.pone. 0073169.
Guan J, Gluckman P, Yang P 등 Cyclic glycine-proline regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1. Sci Rep. 2014;4:4388. DOI:10.1038/srep04388.
Guan J, Mathai S, Harris P, 등 Peripheral administration of a novel diketopiperazine, NNZ 2591, prevents brain injury and improves somatosensory-motor function following hypoxia-ischemia in adult rats. Neuropharmacology. 2007;53(6):749-762. https: //doi.org/ 10.1016/ j.neuropharm. 2007.08.010.
Guan J, Zhang R, Dale-Gandar L, Hodgkinson S, Vickers MH. NNZ-2591, a novel diketopiperazine, prevented scopolamine-induced acute memory impairment in the adult rat. Behav Brain Res. 2010;210(2):221-228. https: //doi.org /10.1016 /j.bbr.2010.02.039
Kennedy AJ 등 Tcf4 Regulates Synaptic Plasticity, DNA Methylation, and Memory Function. Cell Rep. 2016 Sep 6; 16(10): 2666-2685. 10.1016/ j.celrep.2016. 08.004.
Krishnamurthi RV, Mathai S, Kim AH, Zhang R, Guan J. A novel diketopiperazine improves functional recovery given after the onset of 6-OHDA-induced motor deficit in rats. Br J Pharmacol. 2009;156(4):662-672.
Navarrete K, Pedroso I, De Jong S, 등 TCF4 (e2-2; ITF2): A schizophrenia-associated gene with pleiotropic effects on human disease. Am J Med Genet B Neuropsychiatr Genet. 2013;162B(1):1-16. doi:https: //doi.org/ 10.1002/ ajmg.b. 32109.
Pscherer A, Dorflinger U, Kirfel J, 등 The helix-loop-helix transcription factor SEF-2 regulates the activity of a novel initiator element in the promoter of the human somatostatin receptor II gene. EMBO J. 1996;15(23):6680-6690. https: //doi.org/ 10.1002/j.1460-2075. 1996. tb01058.x
Rosenfeld JA, Leppig K, Ballif BC, 등 Genotype-phenotype analysis of TCF4 mutations causing Pitt-Hopkins syndrome shows increased seizure activity with missense mutations. Genet Med. 2009;11(11):797-805.
Sepp M, Kanike K, Eesmaa A, Urb M, Timmusk T. Functional diversity of human basic helix-loop-helix transcription factor TCF4 isoforms generated by alternative 5' exon usage and splicing. PLoS One. 2011;6(7):e22138. doi:10.1371/journal.pone.0022138.
Sweatt JD. Pitt-Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription. Exp Mol Med. 2013;45:e21. doi:10.1038/emm.2013.32.
Sweetser DA, Elsharkawi I, Yonker L, 등 Pitt-Hopkins Syndrome. 2012 Aug 30 [Updated 2018 Apr 12]. In: Adam MP, Ardinger HH, Pagon RA, 등, editors. Gene Reviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
Thaxton C, Kloth AD, Clark EP, Moy SS, Chitwood RA, Philpot BD. Common Pathophysiology in Multiple Mouse Models of Pitt-Hopkins Syndrome. J Neurosci. 2018;24;38(4):918-936. doi: 10.1523/JNEUROSCI.1305-17.2017. Epub 2017 Dec 8.
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ZA202204954B (en) 2025-10-29
US20220387426A1 (en) 2022-12-08
AU2020369431B2 (en) 2026-03-26
WO2021080646A1 (en) 2021-04-29
CA3158406A1 (en) 2021-04-29
IL292408A (en) 2022-06-01
EP4048264A1 (en) 2022-08-31
US12472177B2 (en) 2025-11-18
JP2022553060A (ja) 2022-12-21
EP4048264A4 (en) 2023-11-29
US20250367192A1 (en) 2025-12-04
CL2022001023A1 (es) 2023-03-10
CN115243688A (zh) 2022-10-25
US20230301994A9 (en) 2023-09-28
CO2022006718A2 (es) 2022-08-09
AU2020369431A1 (en) 2022-06-09

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