Title:
UREA TYPE CINNAMIDE DERIVATIVE
Document Type and Number:
WIPO Patent Application WO/2007/135969
Kind Code:
A1
Abstract:
Disclosed is a compound represented by the formula (I) below or a pharmacologically acceptable salt thereof. Also disclosed is a use of the compound or salt as a pharmaceutical product. (I) (In the formula, Ar1 represents an imidazolyl group which may be substituted with a C1-6
alkyl group; Ar2 represents a phenyl group which may be substituted with a C1-6
alkoxy group; X1 represents a single bond; R1 and R2 respectively represent a C1-6
alkyl group or the like which may be substituted with a substituent such as a 5- to 14-membered aromatic heterocyclic group; and R3 represents a hydrogen atom or the like.)
More Like This:
Inventors:
KIMURA TEIJI (JP)
KAWANO KOKI (JP)
DOI ERIKO (JP)
KITAZAWA NORITAKA (JP)
MIYAGAWA TAKEHIKO (JP)
SATO NOBUAKI (JP)
KANEKO TOSHIHIKO (JP)
SHIN KOGYOKU (JP)
ITO KOICHI (JP)
TAKAISHI MAMORU (JP)
SASAKI TAKEO (JP)
HAGIWARA HIROAKI (JP)
KAWANO KOKI (JP)
DOI ERIKO (JP)
KITAZAWA NORITAKA (JP)
MIYAGAWA TAKEHIKO (JP)
SATO NOBUAKI (JP)
KANEKO TOSHIHIKO (JP)
SHIN KOGYOKU (JP)
ITO KOICHI (JP)
TAKAISHI MAMORU (JP)
SASAKI TAKEO (JP)
HAGIWARA HIROAKI (JP)
Application Number:
PCT/JP2007/060187
Publication Date:
November 29, 2007
Filing Date:
May 18, 2007
Export Citation:
Assignee:
EISAI R&D MAN CO LTD (JP)
KIMURA TEIJI (JP)
KAWANO KOKI (JP)
DOI ERIKO (JP)
KITAZAWA NORITAKA (JP)
MIYAGAWA TAKEHIKO (JP)
SATO NOBUAKI (JP)
KANEKO TOSHIHIKO (JP)
SHIN KOGYOKU (JP)
ITO KOICHI (JP)
TAKAISHI MAMORU (JP)
SASAKI TAKEO (JP)
HAGIWARA HIROAKI (JP)
KIMURA TEIJI (JP)
KAWANO KOKI (JP)
DOI ERIKO (JP)
KITAZAWA NORITAKA (JP)
MIYAGAWA TAKEHIKO (JP)
SATO NOBUAKI (JP)
KANEKO TOSHIHIKO (JP)
SHIN KOGYOKU (JP)
ITO KOICHI (JP)
TAKAISHI MAMORU (JP)
SASAKI TAKEO (JP)
HAGIWARA HIROAKI (JP)
International Classes:
C07D233/64; A61K31/4164; A61K31/4178; A61K31/454; A61K31/513; A61P25/28; C07D249/06; C07D249/08; C07D401/04; C07D401/12; C07D403/10; C07D405/12
Foreign References:
| JP2001508767A | 2001-07-03 | |||
| JP2005526807A | 2005-09-08 | |||
| JP2006502247A | 2006-01-19 | |||
| JPH10510512A | 1998-10-13 |
Other References:
VARNES J.G. ET AL.: "Discovery of N-propylurea 3-benzylpiperidines as selective CC chemokine receptor-3 (CCR3) antagonists", BIOORG. MED. CHEM. LETT., vol. 14, no. 7, 2004, pages 1645 - 1649, XP002332418
STARK H. ET AL.: "Search for novel leads for histamine H3-receptor antagonists: amine derivatives", PHARMAZIE, vol. 52, no. 6, 1997, pages 419 - 423, XP001246875
KAJBAF M. ET AL.: "Rapid and efficient purification of cimetropium bromide and mifentidine drug metabolite mixtures derived from microsomal incubates for analysis by mass spectrometry", J. CHROMATOGR. BIOMEDICAL APPLICATIONS, vol. 575, no. 1, 1992, pages 75 - 85, XP003019449
MARCUS S.L. ET AL.: "Stimulation of Rauscher leukemia virus DNA polymerase DNA-directed DNA synthesis by cationic trypanocides and polyamines", CANCER RES., vol. 45, no. 1, 1985, pages 112 - 115, XP008007340
YALE H.L. ET AL.: "Substituted s-triazoles and related compounds", J. MED. CHEM., vol. 9, no. 1, 1966, pages 42 - 46, XP003019450
PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 100, no. 18, 2 September 2003 (2003-09-02), pages 10417 - 10422
NITSCH RM: "Antibodies against 0-amyloid slow cognitive decline in Alzheimer's disease", NEURON, vol. 38, 22 May 2003 (2003-05-22), pages 547 - 554
JARRETT JT: "The carboxy terminus of the P amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimers' disease", BIOCHEMISTRY, vol. 32, no. 18, 1993, pages 4693 - 4697, XP002179077, DOI: doi:10.1021/bi00069a001
GLENNER GG: "Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 120, no. 3, 16 May 1984 (1984-05-16), pages 885 - 890, XP008024193, DOI: doi:10.1016/S0006-291X(84)80190-4
MASTERS CL: "Amyloid plaque core protein in Alzheimer disease and Down syndrome", PROCEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 2, no. 12, 8 June 1985 (1985-06-08), pages 4245 - 4249, XP009012931, DOI: doi:10.1073/pnas.82.12.4245
GOURAS GK: "Intraneuronal AP42 accumulation in human brain", AMERICAN JOURNAL OF PATHOLOGY, vol. 6, no. 1, 15 January 2000 (2000-01-15), pages 15 - 20, XP002258587
SCHEUNER D: "Secreted amyloid P-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease", NATURE MEDICINE, vol. 2, no. 8, August 1996 (1996-08-01), pages 864 - 870, XP002069156, DOI: doi:10.1038/nm0896-864
FORMAN MS: "Differential effects of the swedish mutant amyloid precursor protein on 0-amyloid accumulation and secretion in neurons and nonneuronal cells", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 51, 19 December 1997 (1997-12-19), pages 32247 - 32253
SHEARMAN MS: "L-685,458, an Aspartyl Protease Transition State Mimic, Is a Potent Inhibitor of Amyloid P-Protein Precursor y-Secretase Activity", BIOCHEMISTRY, vol. 39, no. 30, 1 August 2000 (2000-08-01), pages 8698 - 8704, XP002164178, DOI: doi:10.1021/bi0005456
SHEARMAN MS: "Catalytic Site-Directed y-Secretase Complex Inhibitors Do Not Discriminate Pharmacologically betweeen Notch S3 and P-APP Clevages", BIOCHEMISTRY, vol. 42, no. 24, 24 June 2003 (2003-06-24), pages 7580 - 7586
LANZ TA: "Studies of Ap pharmacodynamics in the brain, cerebrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the y-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-Nl-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY-411575", THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 9, no. 1, 30 April 2004 (2004-04-30), pages 49 - 55
WONG GT: "Chronic treatment with the y-secretase inhibitor LY-411,575 inhibits ß-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 279, no. 13, 26 March 2004 (2004-03-26), pages 12876 - 12882, XP002422797, DOI: doi:10.1074/jbc.M311652200
"Yuki Gosei (Organic Synthesis", vol. 14, August 2005, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 428 - 429
O. MITSUNOBU, SYNTHESIS, 1981, pages L
M.M.S. GIBSON ET AL., ANGEW. CHEM., vol. 80, 1968, pages 986
"Yuki Kagobutsu No Gosei To Hannou", vol. 14, February 1978, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 1333 - 1341
"Yuki Kagobutsu No Gosei To Hannou (Synthesis and Reaction of Organic Compounds", vol. 14, February 1978, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza (New Courses in Experimental Chemistry", pages: 1380 - 1384
PROCEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 100, no. 18, 2 September 2003 (2003-09-02), pages 10417 - 10422
NITSCH RM: "Antibodies against P-amyloid slow cognitive decline", ALZHEIMER'S DISEASE, NEURON, vol. 38, no. 4, 22 May 2003 (2003-05-22), pages 547 - 554
JARRETT JT: "The carboxy terminus of the P amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimers' disease", BIOCHEMISTRY, vol. 32, no. 18, 11 May 1993 (1993-05-11), pages 4693 - 4697, XP002179077, DOI: doi:10.1021/bi00069a001
GLENNER GG: "Alzheimer's disease; initial report of thepurification and characterization of a novel cerebrovascular amyloid protein", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 120, no. 3, 16 May 1984 (1984-05-16), pages 885 - 890, XP008024193, DOI: doi:10.1016/S0006-291X(84)80190-4
MASTERS CL: "Amyloid plaque core protein in Alzheimer disease and Down syndrome", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 2, no. 12, 8 June 1985 (1985-06-08), pages 4245 - 4249, XP009012931, DOI: doi:10.1073/pnas.82.12.4245
GOURAS GK: "Intraneuronal Ap42 accumulation in human brain", AMERICAN JOURNAL OF PATHOLOGY, vol. 6, no. 1, 15 January 2000 (2000-01-15), pages 15 - 20, XP002258587
SCHEUNER D: "Secreted amyloid protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease", NATURE MEDICINE, vol. 2, no. 8, August 1996 (1996-08-01), pages 864 - 870, XP002069156, DOI: doi:10.1038/nm0896-864
FORMAN MS: "Differential effects of the swedish mutant amyloid precursor protein on P-amyloid accumulation and secretion in neurons and nonneuronal cells", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 51, 19 December 1997 (1997-12-19), pages 32247 - 32253
BLASS JP: "Brain metabolism and brain disease: Is metabolic deficiency the proximate cause of Alzheimer dementia?", JOURNAL OF NEUROSCIENCE RESEARCH, vol. 66, no. 5, 1 December 2001 (2001-12-01), pages 851 - 856
EVIN G: "Alternative transcripts of presenilin-1 associated with frontotemporal dementia", NEUROREPORT, vol. 13, no. 5, 16 April 2002 (2002-04-16), pages 719 - 723
YASUHARA 0: "Accumulation of amyloid precursor protein in brain lesions of patients with Pick disease", NEUROSCIENCE LETTERS, vol. 171, no. 1-2, 25 April 1994 (1994-04-25), pages 63 - 66, XP024375434, DOI: doi:10.1016/0304-3940(94)90605-X
TELLER JK: "Presence of soluble amyloid ß-peptide precedes amyloid plaque formation in Down's syndrome", NATURE MEDICINE, vol. 2, no. 1, January 1996 (1996-01-01), pages 93 - 95
TOKUDA T: "Plasma levels of amyloid P proteins Apl-40 and Aß1-42(43) are elevated in Down's syndrome", ANNALS OF NEUROLOGY, vol. 41, no. 2, February 1997 (1997-02-01), pages 271 - 273, XP001002135, DOI: doi:10.1002/ana.410410220
HAYASHI Y: "Evidence for presenilin-1 involvement in amyloid angiopathy in the Alzheimer's disease-affected brain", BRAIN RESEARCH, vol. 789, no. 2, 13 April 1998 (1998-04-13), pages 307 - 314
"Alzheimer's disease and cerebral amyloid angiopathy cases", MOLECULAR MEDICINE, vol. 3, no. 10, October 1997 (1997-10-01), pages 695 - 707
CALHOUN ME: "Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 96, no. 24, 23 November 1999 (1999-11-23), pages 14088 - 14093
DERMAUT B: "Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer's Disease due to a novel presenilin-1 mutation", BRAIN, vol. 4, no. 12, 12 December 2001 (2001-12-12), pages 2383 - 2392
CRAS P: "Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala-->Gly mutation", ACTA NEUROPATHOLOGICA(BERL, vol. 96, no. 3, September 1998 (1998-09-01), pages 253 - 260
HERZIG MC: "Ap is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis", NATURE NEUROSCIENCE, vol. 7, no. 9, September 2004 (2004-09-01), pages 954 - 960
VAN DUINEN SG: "Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 84, no. 16, August 1987 (1987-08-01), pages 5991 - 5994, XP002685510, DOI: doi:10.1073/pnas.84.16.5991
LEVY E: "Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage", DUTCH TYPE, SCIENCE, vol. 248, no. 4959, 1 June 1990 (1990-06-01), pages 1124 - 1126, XP002067115, DOI: doi:10.1126/science.2111584
LAWS SM: "Association between the presenilin-1 mutation Glu318Gly and complaints of memory impairment", NEUROBIOLOGY OF AGING, vol. 23, no. 1, January 2002 (2002-01-01), pages 55 - 58
VAUCHER E: "Object recognition memory and cholinergic parameters in mice expressing human presenilin 1 transgenes", EXPERIMENTAL NEUROLOGY, vol. 175, no. 2, June 2002 (2002-06-01), pages 398 - 406
MORGAN D: "Ap peptide vaccination prevents memory loss in an animal model of Alzheimer's disease", NATURE, vol. 408, no. 6815, 21 December 2000 (2000-12-21), pages 982 - 985, XP002266055, DOI: doi:10.1038/35050116
MORAN PM: "Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human amyloid precursor protein", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 92, no. 12, 6 June 1995 (1995-06-06), pages 5341 - 5345
KOISTINAHO M: "P-amyloid precursor protein transgenic mice that harbor diffuse Ap deposits but do not form plaques show increased ischemic vulnerability: Role of inflammation", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 99, no. 3, 5 February 2002 (2002-02-05), pages 1610 - 1615
ZHANG F: "Increased susceptibility to ischemic brain damage in transgenic mice overexpressing the amyloid precursor protein", THE JOURNAL OF NEUROSCIENCE, vol. 17, no. 20, 15 October 1997 (1997-10-15), pages 7655 - 7661, XP000978981
SADOWSKI M: "Links between the pathology of Alzheimer's disease and vascular dementia", NEUROCHEMICAL RESEARCH, vol. 29, no. 6, June 2004 (2004-06-01), pages 1257 - 1266
O'RIORDAN S: "Presenilin-1 mutation(E280G), spastic paraparesis, and cranial MRI white-matter abnormalities", NEUROLOGY, vol. 59, no. 7, 8 October 2002 (2002-10-08), pages 1108 - 1110
GEHRMANN J: "Amyloid precursor protein (APP) expression in multiple sclerosis lesions", GLIA, vol. 15, no. 2, October 1995 (1995-10-01), pages 141 - 51
REYNOLDS WF: "Myeloperoxidase polymorphism is associated with gender specific risk for Alzheimer's disease", EXPERIMENTAL NEUROLOGY, vol. 5, no. 1, 15 January 1999 (1999-01-15), pages 31 - 41
SMITH DH: "Protein accumulation in traumatic brain injury", NEUROMOLECULAR MEDICINE, vol. 4, no. 1-2, 2003, pages 59 - 72, XP008097564, DOI: doi:10.1385/NMM:4:1-2:59
MATSUBARA-TSUTSUI M: "Molecular evidence of presenilin 1 mutation in familial early onset dementia", AMERICAN JOURNAL OF MEDICAL GENETICS, vol. 114, no. 3, 8 April 2002 (2002-04-08), pages 292 - 298
KIRKITADZE MD: "Paradigm shifts in Alzheimer's disease and other neurodegenerative disorders: the emerging role of oligomeric assemblies", JOURNAL OF NEUROSCIENCE RESEARCH, vol. 69, no. 5, 1 September 2002 (2002-09-01), pages 567 - 577
EVERT BO: "Inflammatory genes are upreglulated in expanded ataxin-3-expressing cell lines and spinocerebellar ataxia type 3 brains", THE JOURNAL OF NEUROSCIENCE, vol. 21, no. 15, 1 August 2001 (2001-08-01), pages 5389 - 5396
MANN DM: "Deposition of amyloid(A4) protein within the brains of persons with dementing disorders other than Alzheimer's disease and Down's syndrome", NEUROSCIENCE LETTERS, vol. 109, no. 1-2, 5 February 1990 (1990-02-05), pages 68 - 75, XP024361543, DOI: doi:10.1016/0304-3940(90)90539-L
PRIMAVERA J: "Brain accumulation of amyloid-O in Non-Alzheimer Neurodegeneration", JORNAL OF ALZHEIMER'S DISEASE, vol. 1, no. 3, October 1999 (1999-10-01), pages 183 - 193
GIASSON BI: "Interactions of amyloidogenic proteins", NEUROMOLECULAR MEDICINE, vol. 4, no. 1-2, 2003, pages 49 - 58
MASLIAH E: "P-amyloid peptides enhance a-synuclein accumulation and neuronal deficits in a trancgenic mouse model linking Alzheimer's disease and Parkinson's disease", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 98, no. 21, 9 October 2001 (2001-10-09), pages 12245 - 12250, XP002201752, DOI: doi:10.1073/pnas.211412398
BARRACHINA M: "Amyloid-P deposition in the cerebral cortex in Dementia with Lewy bodies is accompanied by a relative increase in AßPP mRNA isoforms containing the Kunitz protease inhibitor", NEUROCHEMISTRY INTERNATIONAL, vol. 46, no. 3, February 2005 (2005-02-01), pages 253 - 260
PRIMAVERA J: "Brain accumulation of amyloid-P in Non-Alzheimer Neurodegeneration", JORNAL OF ALZHEIMER'S DISEASE, vol. 1, no. 3, October 1999 (1999-10-01), pages 183 - 193
SCHMIDT ML: "Amyloid plaques in Guam amyotrophic lateral sclerosis/ parkinsonism-dementia complex contain species of Ap similar to those found in the amyloid plaques of Alzheimer's disease and pathological aging", ACTA NEUROPATHOLOGICA (BERL, vol. 95, no. 2, February 1998 (1998-02-01), pages 117 - 122
ITO H: "Demonstration of ß amyloid protein-containing neurofibrillary tangles in parkinsonism-dementia complex on Guam", NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, vol. 17, no. 5, October 1991 (1991-10-01), pages 365 - 373
ROSSO SM: "Coexistent tau andamyloid pathology in hereditary frontotemporal dementia with tau mutations", ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, vol. 920, 2000, pages 115 - 119
TOLNAY M: "Low amyloid(AP) plaque load and relative predominance of diffuse plaques distinguish argyrophilic grain disease from Alzheimer's disease", NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, vol. 25, no. 4, August 1999 (1999-08-01), pages 295 - 305
JIN LW: "Intracellular accumulation of amyloidogenic fragments of amyloid-P precursor protein in neurons with Niemann-Pick type C defects is associated with endosomal abnormalities", AMERICAN JOURNAL-OF PATHOLOGY, vol. 164, no. 3, March 2004 (2004-03-01), pages 975 - 985, XP055182583, DOI: doi:10.1016/S0002-9440(10)63185-9
SASAKI S: "Immunoreactivity of ß-amyloid precursor protein in amyotrophic lateral sclerosis", ACTA NEUROPATHOLOGICA(BERL, vol. 97, no. 5, May 1999 (1999-05-01), pages 463 - 468
TAMAOKA A: "Increased amyloid protein in the skin of patients with amyotrophic lateral sclerosis", JOURNAL OF NEUROLOGY, vol. 247, no. 8, August 2000 (2000-08-01), pages 633 - 635
HAMILTON RL: "Alzheimer disease pathology in amyotrophic lateral sclerosis", ACTA NEUROPATHOLOGICA, vol. 107, no. 6, June 2004 (2004-06-01), pages 515 - 522
TURNER BJ: "Brain P-amyloidaccumulation in transgenic mice expressing mutant superoxide dismutase 1", NEUROCHEMICAL RESEARCH, vol. 29, no. 12, December 2004 (2004-12-01), pages 2281 - 2286, XP019289706
WELLER RO: "Pathology of cerebrospinal fluid and interstitial fluid of the CNS: Significance for Alzheimer disease, prion disorders and multiple sclerosis", JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, vol. 57, no. 10, October 1998 (1998-10-01), pages 885 - 894
SILVERBERG GD: "Alzheimer's disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis", LANCET NEUROLOGY, vol. 2, no. 8, August 2003 (2003-08-01), pages 506 - 511, XP004810296, DOI: doi:10.1016/S1474-4422(03)00487-3
WELLER RO: "Cerebral amyloid angiopathy: Accumulation of Ap in interstitial fluid drainage pathways in Alzheimer's disease", ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, vol. 03, 9 April 2000 (2000-04-09), pages 110 - 117
YOW HY: "A role for cerebrovascular disease in determining the pattern of P-amyloid deposition in Alzheimer's disease", NEUROLOGY AND APPLIED NEUROBIOLOGY, vol. 28, 2002, pages 149
WELLER RO: "Cerebrovasculardisease is a major factor in the failure of elimination of A|] from the aging human brain", ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, vol. 977, November 2002 (2002-11-01), pages 162 - 168
SMITH MJ: "Variable phenotype of Alzheimer's disease with spastic paraparesis", ANNALS OF NEUROLOGY, vol. 49, no. 1, 2001, pages 125 - 129
CROOK R: "A variant of Alzheimer's disease with spastic pararesis and unusual plaques due to deletion of exon 9 of presenilin 1", NATURE MEDICINE, vol. 4, no. 4, 1998, pages 452 - 455
BARRACHINA M: "Amyloid-P deposition in the cerebral cortex in Dementia with Lewy bodies is accompanied by a relative increase in APPP mRNA isoforms containing the Kunitz protease inhibitor", NEUROCHEMISTRY INTERNATIONAL, vol. 46, no. 3, February 2005 (2005-02-01), pages 253 - 260
ATWOOD CS: "Cerebrovascular requirement for sealant, anti-coagulant and remodeling molecules that allow for the maintenance of vascular integrity and blood supply", BRAIN RESEARCH REVIEWS, vol. 43, no. 1, September 2003 (2003-09-01), pages 164 - 78
LOWENSON JD: "Protein aging: Extracellular amyloid formation and intracellular repair", TRENDS IN CARDIOVASCULAR MEDICINE, vol. 4, no. 1, 1994, pages 3 - 8, XP023117534, DOI: doi:10.1016/1050-1738(94)90019-1
SINGLETON AB: "Pathology of early-onset Alzheimer's disease cases bearing the Thrll3-114ins presenilin-1 mutation", BRAIN, vol. 123, December 2000 (2000-12-01), pages 2467 - 2474
GATTAZ WF: "Platelet phospholipase A2 activity in Alzheimer's disease and mild cognitive impairment", JOURNAL OF NEURAL TRANSMISSION, vol. 111, no. 5, May 2004 (2004-05-01), pages 591 - 601
ASSINI A: "Plasma levels of amyloid 0-protein 42 are increased in women with mild cognitive impariment", NEUROLOGY, vol. 63, no. 5, 14 September 2004 (2004-09-14), pages 828 - 831
DE MEYER GR: "Platelet phagocytosis and processing of P-amyloid precursor protein as a mechanism of macrophage activation in atherosclerosis", CIRCULATION RESEARCH, vol. 90, no. 11, 14 June 2002 (2002-06-14), pages 1197 - 1204
"Organic Synthesis", vol. 22, November 1992, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 1 - 5
"Yuki Gosei", vol. 19, June 1992, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 57 - 85
THAVONEKHAM, B. ET AL., SYNTHESIS, vol. 10, 1997, pages 1189 - 1194
RAJU, B. ET AL., BIOORG. MED. CHEM. LETT., vol. 8, pages 3043 - 3048
ATWAL, K.S. ET AL., J. MED. CHEM., vol. 39, 1996, pages 304 - 313
SANTILLI, A., J. ORG. CHEM., vol. 31, 1966, pages 4268
"Yuki Gosei", vol. 14, August 2005, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 1 - 49
"Yuki Gosei", vol. 14, August 2005, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 417 - 419
"Yuki Gosei", vol. 19, June 1992, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 438 - 446
"Yuki Gosei", vol. 14, August 2005, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 480 - 487
BAILEY, W., ORG. SYNTH., vol. 81, no. 204, pages 121
D.D. DAVEY ET AL., J. MED. CHEM., vol. 39, 1991, pages 2671 - 2677
S.S. CHANDRAN ET AL., BIOORG. MED. CHEM. LETT., vol. 11, 2001, pages 1493 - 1496
T. OKANO ET AL., BULL. CHEM. SOC. JPN., vol. 67, 1994, pages 2329 - 2332
"Yuki Gosei (Organic Synthesis) [III", February 1991, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza (New Courses in Experimental Chemistry", pages: 2 - 23
"Yuki Gosei (Organic Synthesis", vol. 21, February 1991, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza (New Courses in Experimental Chemistry", pages: 83 - 85
"Yuki Gosei", vol. 19, June 1992, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 363 - 482
S.L. BUCHWALD ET AL., TETRAHEDRON LETT., vol. 38, 1997, pages 6367 - 6370
J.F. HARTWIG ET AL., J. AM. CHEM. SOC., vol. 120, 1998, pages 827 - 828
T.W. GREEN: "Protective Groups in Organic Synthesis", 1981, JOHN WILEY & SONS, INC.
"Yuki Kagobutsu No Gosei To Hannou", vol. 14, November 1977, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 354 - 360
"Yuki Kagobutsu No Gosei To Hannou", vol. 14, February 1978, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 1261 - 1300
K. SAKAI ET AL., BULL. CHEM. SOC. JPN., vol. 59, 1986, pages 179 - 183
"Yuki Gosei", vol. 14, August 2005, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 537 - 542
K. NINOMIYA ET AL., TETRAHEDRON, vol. 30, 1974, pages 2151
HANESSIAN, S. ET AL., TETRAHEDRON LETTERS, vol. 41, 2000, pages 4999 - 5003
K. KURITA ET AL., ORG. SYNTH., vol. VI, 1988, pages 715
KNOELKER, H.-J. ET AL., SYNLETT, vol. 8, 1997, pages 925 - 928
"Yuki Gosei (Organic Synthesis", vol. 22, 1992, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza (New Courses in Experimental Chemistry", pages: 6 - 11
See also references of EP 2019093A4
STARK H. ET AL.: "Search for novel leads for histamine H3-receptor antagonists: amine derivatives", PHARMAZIE, vol. 52, no. 6, 1997, pages 419 - 423, XP001246875
KAJBAF M. ET AL.: "Rapid and efficient purification of cimetropium bromide and mifentidine drug metabolite mixtures derived from microsomal incubates for analysis by mass spectrometry", J. CHROMATOGR. BIOMEDICAL APPLICATIONS, vol. 575, no. 1, 1992, pages 75 - 85, XP003019449
MARCUS S.L. ET AL.: "Stimulation of Rauscher leukemia virus DNA polymerase DNA-directed DNA synthesis by cationic trypanocides and polyamines", CANCER RES., vol. 45, no. 1, 1985, pages 112 - 115, XP008007340
YALE H.L. ET AL.: "Substituted s-triazoles and related compounds", J. MED. CHEM., vol. 9, no. 1, 1966, pages 42 - 46, XP003019450
PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 100, no. 18, 2 September 2003 (2003-09-02), pages 10417 - 10422
NITSCH RM: "Antibodies against 0-amyloid slow cognitive decline in Alzheimer's disease", NEURON, vol. 38, 22 May 2003 (2003-05-22), pages 547 - 554
JARRETT JT: "The carboxy terminus of the P amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimers' disease", BIOCHEMISTRY, vol. 32, no. 18, 1993, pages 4693 - 4697, XP002179077, DOI: doi:10.1021/bi00069a001
GLENNER GG: "Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 120, no. 3, 16 May 1984 (1984-05-16), pages 885 - 890, XP008024193, DOI: doi:10.1016/S0006-291X(84)80190-4
MASTERS CL: "Amyloid plaque core protein in Alzheimer disease and Down syndrome", PROCEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 2, no. 12, 8 June 1985 (1985-06-08), pages 4245 - 4249, XP009012931, DOI: doi:10.1073/pnas.82.12.4245
GOURAS GK: "Intraneuronal AP42 accumulation in human brain", AMERICAN JOURNAL OF PATHOLOGY, vol. 6, no. 1, 15 January 2000 (2000-01-15), pages 15 - 20, XP002258587
SCHEUNER D: "Secreted amyloid P-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease", NATURE MEDICINE, vol. 2, no. 8, August 1996 (1996-08-01), pages 864 - 870, XP002069156, DOI: doi:10.1038/nm0896-864
FORMAN MS: "Differential effects of the swedish mutant amyloid precursor protein on 0-amyloid accumulation and secretion in neurons and nonneuronal cells", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 51, 19 December 1997 (1997-12-19), pages 32247 - 32253
SHEARMAN MS: "L-685,458, an Aspartyl Protease Transition State Mimic, Is a Potent Inhibitor of Amyloid P-Protein Precursor y-Secretase Activity", BIOCHEMISTRY, vol. 39, no. 30, 1 August 2000 (2000-08-01), pages 8698 - 8704, XP002164178, DOI: doi:10.1021/bi0005456
SHEARMAN MS: "Catalytic Site-Directed y-Secretase Complex Inhibitors Do Not Discriminate Pharmacologically betweeen Notch S3 and P-APP Clevages", BIOCHEMISTRY, vol. 42, no. 24, 24 June 2003 (2003-06-24), pages 7580 - 7586
LANZ TA: "Studies of Ap pharmacodynamics in the brain, cerebrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the y-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-Nl-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY-411575", THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 9, no. 1, 30 April 2004 (2004-04-30), pages 49 - 55
WONG GT: "Chronic treatment with the y-secretase inhibitor LY-411,575 inhibits ß-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 279, no. 13, 26 March 2004 (2004-03-26), pages 12876 - 12882, XP002422797, DOI: doi:10.1074/jbc.M311652200
"Yuki Gosei (Organic Synthesis", vol. 14, August 2005, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 428 - 429
O. MITSUNOBU, SYNTHESIS, 1981, pages L
M.M.S. GIBSON ET AL., ANGEW. CHEM., vol. 80, 1968, pages 986
"Yuki Kagobutsu No Gosei To Hannou", vol. 14, February 1978, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 1333 - 1341
"Yuki Kagobutsu No Gosei To Hannou (Synthesis and Reaction of Organic Compounds", vol. 14, February 1978, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza (New Courses in Experimental Chemistry", pages: 1380 - 1384
PROCEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 100, no. 18, 2 September 2003 (2003-09-02), pages 10417 - 10422
NITSCH RM: "Antibodies against P-amyloid slow cognitive decline", ALZHEIMER'S DISEASE, NEURON, vol. 38, no. 4, 22 May 2003 (2003-05-22), pages 547 - 554
JARRETT JT: "The carboxy terminus of the P amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimers' disease", BIOCHEMISTRY, vol. 32, no. 18, 11 May 1993 (1993-05-11), pages 4693 - 4697, XP002179077, DOI: doi:10.1021/bi00069a001
GLENNER GG: "Alzheimer's disease; initial report of thepurification and characterization of a novel cerebrovascular amyloid protein", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 120, no. 3, 16 May 1984 (1984-05-16), pages 885 - 890, XP008024193, DOI: doi:10.1016/S0006-291X(84)80190-4
MASTERS CL: "Amyloid plaque core protein in Alzheimer disease and Down syndrome", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 2, no. 12, 8 June 1985 (1985-06-08), pages 4245 - 4249, XP009012931, DOI: doi:10.1073/pnas.82.12.4245
GOURAS GK: "Intraneuronal Ap42 accumulation in human brain", AMERICAN JOURNAL OF PATHOLOGY, vol. 6, no. 1, 15 January 2000 (2000-01-15), pages 15 - 20, XP002258587
SCHEUNER D: "Secreted amyloid protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease", NATURE MEDICINE, vol. 2, no. 8, August 1996 (1996-08-01), pages 864 - 870, XP002069156, DOI: doi:10.1038/nm0896-864
FORMAN MS: "Differential effects of the swedish mutant amyloid precursor protein on P-amyloid accumulation and secretion in neurons and nonneuronal cells", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 51, 19 December 1997 (1997-12-19), pages 32247 - 32253
BLASS JP: "Brain metabolism and brain disease: Is metabolic deficiency the proximate cause of Alzheimer dementia?", JOURNAL OF NEUROSCIENCE RESEARCH, vol. 66, no. 5, 1 December 2001 (2001-12-01), pages 851 - 856
EVIN G: "Alternative transcripts of presenilin-1 associated with frontotemporal dementia", NEUROREPORT, vol. 13, no. 5, 16 April 2002 (2002-04-16), pages 719 - 723
YASUHARA 0: "Accumulation of amyloid precursor protein in brain lesions of patients with Pick disease", NEUROSCIENCE LETTERS, vol. 171, no. 1-2, 25 April 1994 (1994-04-25), pages 63 - 66, XP024375434, DOI: doi:10.1016/0304-3940(94)90605-X
TELLER JK: "Presence of soluble amyloid ß-peptide precedes amyloid plaque formation in Down's syndrome", NATURE MEDICINE, vol. 2, no. 1, January 1996 (1996-01-01), pages 93 - 95
TOKUDA T: "Plasma levels of amyloid P proteins Apl-40 and Aß1-42(43) are elevated in Down's syndrome", ANNALS OF NEUROLOGY, vol. 41, no. 2, February 1997 (1997-02-01), pages 271 - 273, XP001002135, DOI: doi:10.1002/ana.410410220
HAYASHI Y: "Evidence for presenilin-1 involvement in amyloid angiopathy in the Alzheimer's disease-affected brain", BRAIN RESEARCH, vol. 789, no. 2, 13 April 1998 (1998-04-13), pages 307 - 314
"Alzheimer's disease and cerebral amyloid angiopathy cases", MOLECULAR MEDICINE, vol. 3, no. 10, October 1997 (1997-10-01), pages 695 - 707
CALHOUN ME: "Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 96, no. 24, 23 November 1999 (1999-11-23), pages 14088 - 14093
DERMAUT B: "Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer's Disease due to a novel presenilin-1 mutation", BRAIN, vol. 4, no. 12, 12 December 2001 (2001-12-12), pages 2383 - 2392
CRAS P: "Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala-->Gly mutation", ACTA NEUROPATHOLOGICA(BERL, vol. 96, no. 3, September 1998 (1998-09-01), pages 253 - 260
HERZIG MC: "Ap is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis", NATURE NEUROSCIENCE, vol. 7, no. 9, September 2004 (2004-09-01), pages 954 - 960
VAN DUINEN SG: "Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 84, no. 16, August 1987 (1987-08-01), pages 5991 - 5994, XP002685510, DOI: doi:10.1073/pnas.84.16.5991
LEVY E: "Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage", DUTCH TYPE, SCIENCE, vol. 248, no. 4959, 1 June 1990 (1990-06-01), pages 1124 - 1126, XP002067115, DOI: doi:10.1126/science.2111584
LAWS SM: "Association between the presenilin-1 mutation Glu318Gly and complaints of memory impairment", NEUROBIOLOGY OF AGING, vol. 23, no. 1, January 2002 (2002-01-01), pages 55 - 58
VAUCHER E: "Object recognition memory and cholinergic parameters in mice expressing human presenilin 1 transgenes", EXPERIMENTAL NEUROLOGY, vol. 175, no. 2, June 2002 (2002-06-01), pages 398 - 406
MORGAN D: "Ap peptide vaccination prevents memory loss in an animal model of Alzheimer's disease", NATURE, vol. 408, no. 6815, 21 December 2000 (2000-12-21), pages 982 - 985, XP002266055, DOI: doi:10.1038/35050116
MORAN PM: "Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human amyloid precursor protein", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 92, no. 12, 6 June 1995 (1995-06-06), pages 5341 - 5345
KOISTINAHO M: "P-amyloid precursor protein transgenic mice that harbor diffuse Ap deposits but do not form plaques show increased ischemic vulnerability: Role of inflammation", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 99, no. 3, 5 February 2002 (2002-02-05), pages 1610 - 1615
ZHANG F: "Increased susceptibility to ischemic brain damage in transgenic mice overexpressing the amyloid precursor protein", THE JOURNAL OF NEUROSCIENCE, vol. 17, no. 20, 15 October 1997 (1997-10-15), pages 7655 - 7661, XP000978981
SADOWSKI M: "Links between the pathology of Alzheimer's disease and vascular dementia", NEUROCHEMICAL RESEARCH, vol. 29, no. 6, June 2004 (2004-06-01), pages 1257 - 1266
O'RIORDAN S: "Presenilin-1 mutation(E280G), spastic paraparesis, and cranial MRI white-matter abnormalities", NEUROLOGY, vol. 59, no. 7, 8 October 2002 (2002-10-08), pages 1108 - 1110
GEHRMANN J: "Amyloid precursor protein (APP) expression in multiple sclerosis lesions", GLIA, vol. 15, no. 2, October 1995 (1995-10-01), pages 141 - 51
REYNOLDS WF: "Myeloperoxidase polymorphism is associated with gender specific risk for Alzheimer's disease", EXPERIMENTAL NEUROLOGY, vol. 5, no. 1, 15 January 1999 (1999-01-15), pages 31 - 41
SMITH DH: "Protein accumulation in traumatic brain injury", NEUROMOLECULAR MEDICINE, vol. 4, no. 1-2, 2003, pages 59 - 72, XP008097564, DOI: doi:10.1385/NMM:4:1-2:59
MATSUBARA-TSUTSUI M: "Molecular evidence of presenilin 1 mutation in familial early onset dementia", AMERICAN JOURNAL OF MEDICAL GENETICS, vol. 114, no. 3, 8 April 2002 (2002-04-08), pages 292 - 298
KIRKITADZE MD: "Paradigm shifts in Alzheimer's disease and other neurodegenerative disorders: the emerging role of oligomeric assemblies", JOURNAL OF NEUROSCIENCE RESEARCH, vol. 69, no. 5, 1 September 2002 (2002-09-01), pages 567 - 577
EVERT BO: "Inflammatory genes are upreglulated in expanded ataxin-3-expressing cell lines and spinocerebellar ataxia type 3 brains", THE JOURNAL OF NEUROSCIENCE, vol. 21, no. 15, 1 August 2001 (2001-08-01), pages 5389 - 5396
MANN DM: "Deposition of amyloid(A4) protein within the brains of persons with dementing disorders other than Alzheimer's disease and Down's syndrome", NEUROSCIENCE LETTERS, vol. 109, no. 1-2, 5 February 1990 (1990-02-05), pages 68 - 75, XP024361543, DOI: doi:10.1016/0304-3940(90)90539-L
PRIMAVERA J: "Brain accumulation of amyloid-O in Non-Alzheimer Neurodegeneration", JORNAL OF ALZHEIMER'S DISEASE, vol. 1, no. 3, October 1999 (1999-10-01), pages 183 - 193
GIASSON BI: "Interactions of amyloidogenic proteins", NEUROMOLECULAR MEDICINE, vol. 4, no. 1-2, 2003, pages 49 - 58
MASLIAH E: "P-amyloid peptides enhance a-synuclein accumulation and neuronal deficits in a trancgenic mouse model linking Alzheimer's disease and Parkinson's disease", PROCEEDING NATIONAL ACADEMY OF SCIENCE USA, vol. 98, no. 21, 9 October 2001 (2001-10-09), pages 12245 - 12250, XP002201752, DOI: doi:10.1073/pnas.211412398
BARRACHINA M: "Amyloid-P deposition in the cerebral cortex in Dementia with Lewy bodies is accompanied by a relative increase in AßPP mRNA isoforms containing the Kunitz protease inhibitor", NEUROCHEMISTRY INTERNATIONAL, vol. 46, no. 3, February 2005 (2005-02-01), pages 253 - 260
PRIMAVERA J: "Brain accumulation of amyloid-P in Non-Alzheimer Neurodegeneration", JORNAL OF ALZHEIMER'S DISEASE, vol. 1, no. 3, October 1999 (1999-10-01), pages 183 - 193
SCHMIDT ML: "Amyloid plaques in Guam amyotrophic lateral sclerosis/ parkinsonism-dementia complex contain species of Ap similar to those found in the amyloid plaques of Alzheimer's disease and pathological aging", ACTA NEUROPATHOLOGICA (BERL, vol. 95, no. 2, February 1998 (1998-02-01), pages 117 - 122
ITO H: "Demonstration of ß amyloid protein-containing neurofibrillary tangles in parkinsonism-dementia complex on Guam", NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, vol. 17, no. 5, October 1991 (1991-10-01), pages 365 - 373
ROSSO SM: "Coexistent tau andamyloid pathology in hereditary frontotemporal dementia with tau mutations", ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, vol. 920, 2000, pages 115 - 119
TOLNAY M: "Low amyloid(AP) plaque load and relative predominance of diffuse plaques distinguish argyrophilic grain disease from Alzheimer's disease", NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, vol. 25, no. 4, August 1999 (1999-08-01), pages 295 - 305
JIN LW: "Intracellular accumulation of amyloidogenic fragments of amyloid-P precursor protein in neurons with Niemann-Pick type C defects is associated with endosomal abnormalities", AMERICAN JOURNAL-OF PATHOLOGY, vol. 164, no. 3, March 2004 (2004-03-01), pages 975 - 985, XP055182583, DOI: doi:10.1016/S0002-9440(10)63185-9
SASAKI S: "Immunoreactivity of ß-amyloid precursor protein in amyotrophic lateral sclerosis", ACTA NEUROPATHOLOGICA(BERL, vol. 97, no. 5, May 1999 (1999-05-01), pages 463 - 468
TAMAOKA A: "Increased amyloid protein in the skin of patients with amyotrophic lateral sclerosis", JOURNAL OF NEUROLOGY, vol. 247, no. 8, August 2000 (2000-08-01), pages 633 - 635
HAMILTON RL: "Alzheimer disease pathology in amyotrophic lateral sclerosis", ACTA NEUROPATHOLOGICA, vol. 107, no. 6, June 2004 (2004-06-01), pages 515 - 522
TURNER BJ: "Brain P-amyloidaccumulation in transgenic mice expressing mutant superoxide dismutase 1", NEUROCHEMICAL RESEARCH, vol. 29, no. 12, December 2004 (2004-12-01), pages 2281 - 2286, XP019289706
WELLER RO: "Pathology of cerebrospinal fluid and interstitial fluid of the CNS: Significance for Alzheimer disease, prion disorders and multiple sclerosis", JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, vol. 57, no. 10, October 1998 (1998-10-01), pages 885 - 894
SILVERBERG GD: "Alzheimer's disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis", LANCET NEUROLOGY, vol. 2, no. 8, August 2003 (2003-08-01), pages 506 - 511, XP004810296, DOI: doi:10.1016/S1474-4422(03)00487-3
WELLER RO: "Cerebral amyloid angiopathy: Accumulation of Ap in interstitial fluid drainage pathways in Alzheimer's disease", ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, vol. 03, 9 April 2000 (2000-04-09), pages 110 - 117
YOW HY: "A role for cerebrovascular disease in determining the pattern of P-amyloid deposition in Alzheimer's disease", NEUROLOGY AND APPLIED NEUROBIOLOGY, vol. 28, 2002, pages 149
WELLER RO: "Cerebrovasculardisease is a major factor in the failure of elimination of A|] from the aging human brain", ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, vol. 977, November 2002 (2002-11-01), pages 162 - 168
SMITH MJ: "Variable phenotype of Alzheimer's disease with spastic paraparesis", ANNALS OF NEUROLOGY, vol. 49, no. 1, 2001, pages 125 - 129
CROOK R: "A variant of Alzheimer's disease with spastic pararesis and unusual plaques due to deletion of exon 9 of presenilin 1", NATURE MEDICINE, vol. 4, no. 4, 1998, pages 452 - 455
BARRACHINA M: "Amyloid-P deposition in the cerebral cortex in Dementia with Lewy bodies is accompanied by a relative increase in APPP mRNA isoforms containing the Kunitz protease inhibitor", NEUROCHEMISTRY INTERNATIONAL, vol. 46, no. 3, February 2005 (2005-02-01), pages 253 - 260
ATWOOD CS: "Cerebrovascular requirement for sealant, anti-coagulant and remodeling molecules that allow for the maintenance of vascular integrity and blood supply", BRAIN RESEARCH REVIEWS, vol. 43, no. 1, September 2003 (2003-09-01), pages 164 - 78
LOWENSON JD: "Protein aging: Extracellular amyloid formation and intracellular repair", TRENDS IN CARDIOVASCULAR MEDICINE, vol. 4, no. 1, 1994, pages 3 - 8, XP023117534, DOI: doi:10.1016/1050-1738(94)90019-1
SINGLETON AB: "Pathology of early-onset Alzheimer's disease cases bearing the Thrll3-114ins presenilin-1 mutation", BRAIN, vol. 123, December 2000 (2000-12-01), pages 2467 - 2474
GATTAZ WF: "Platelet phospholipase A2 activity in Alzheimer's disease and mild cognitive impairment", JOURNAL OF NEURAL TRANSMISSION, vol. 111, no. 5, May 2004 (2004-05-01), pages 591 - 601
ASSINI A: "Plasma levels of amyloid 0-protein 42 are increased in women with mild cognitive impariment", NEUROLOGY, vol. 63, no. 5, 14 September 2004 (2004-09-14), pages 828 - 831
DE MEYER GR: "Platelet phagocytosis and processing of P-amyloid precursor protein as a mechanism of macrophage activation in atherosclerosis", CIRCULATION RESEARCH, vol. 90, no. 11, 14 June 2002 (2002-06-14), pages 1197 - 1204
"Organic Synthesis", vol. 22, November 1992, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 1 - 5
"Yuki Gosei", vol. 19, June 1992, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 57 - 85
THAVONEKHAM, B. ET AL., SYNTHESIS, vol. 10, 1997, pages 1189 - 1194
RAJU, B. ET AL., BIOORG. MED. CHEM. LETT., vol. 8, pages 3043 - 3048
ATWAL, K.S. ET AL., J. MED. CHEM., vol. 39, 1996, pages 304 - 313
SANTILLI, A., J. ORG. CHEM., vol. 31, 1966, pages 4268
"Yuki Gosei", vol. 14, August 2005, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 1 - 49
"Yuki Gosei", vol. 14, August 2005, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 417 - 419
"Yuki Gosei", vol. 19, June 1992, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 438 - 446
"Yuki Gosei", vol. 14, August 2005, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 480 - 487
BAILEY, W., ORG. SYNTH., vol. 81, no. 204, pages 121
D.D. DAVEY ET AL., J. MED. CHEM., vol. 39, 1991, pages 2671 - 2677
S.S. CHANDRAN ET AL., BIOORG. MED. CHEM. LETT., vol. 11, 2001, pages 1493 - 1496
T. OKANO ET AL., BULL. CHEM. SOC. JPN., vol. 67, 1994, pages 2329 - 2332
"Yuki Gosei (Organic Synthesis) [III", February 1991, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza (New Courses in Experimental Chemistry", pages: 2 - 23
"Yuki Gosei (Organic Synthesis", vol. 21, February 1991, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza (New Courses in Experimental Chemistry", pages: 83 - 85
"Yuki Gosei", vol. 19, June 1992, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 363 - 482
S.L. BUCHWALD ET AL., TETRAHEDRON LETT., vol. 38, 1997, pages 6367 - 6370
J.F. HARTWIG ET AL., J. AM. CHEM. SOC., vol. 120, 1998, pages 827 - 828
T.W. GREEN: "Protective Groups in Organic Synthesis", 1981, JOHN WILEY & SONS, INC.
"Yuki Kagobutsu No Gosei To Hannou", vol. 14, November 1977, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 354 - 360
"Yuki Kagobutsu No Gosei To Hannou", vol. 14, February 1978, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 1261 - 1300
K. SAKAI ET AL., BULL. CHEM. SOC. JPN., vol. 59, 1986, pages 179 - 183
"Yuki Gosei", vol. 14, August 2005, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza", pages: 537 - 542
K. NINOMIYA ET AL., TETRAHEDRON, vol. 30, 1974, pages 2151
HANESSIAN, S. ET AL., TETRAHEDRON LETTERS, vol. 41, 2000, pages 4999 - 5003
K. KURITA ET AL., ORG. SYNTH., vol. VI, 1988, pages 715
KNOELKER, H.-J. ET AL., SYNLETT, vol. 8, 1997, pages 925 - 928
"Yuki Gosei (Organic Synthesis", vol. 22, 1992, MARUZEN CO., LTD., article "Shin Jikken Kagaku Koza (New Courses in Experimental Chemistry", pages: 6 - 11
See also references of EP 2019093A4
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ASAMURA, Kiyoshi et al. (New Ohtemachi Bldg.2-1, Ohtemachi 2-chom, Chiyoda-ku Tokyo, JP)
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