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1. (WO1998049186) DIPEPTIDE SURROGATES CONTAINING ASPARAGINE-DERIVED TETRAHYDROPYRIMIDINONES
Latest bibliographic data on file with the International Bureau

Pub. No.: WO/1998/049186 International Application No.: PCT/US1998/008395
Publication Date: 05.11.1998 International Filing Date: 24.04.1998
Chapter 2 Demand Filed: 22.10.1998
IPC:
A61K 38/00 (2006.01) ,C07K 5/06 (2006.01) ,C07K 5/107 (2006.01)
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38
Medicinal preparations containing peptides
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
5
Peptides having up to four amino acids in a fully defined sequence; Derivatives thereof
04
containing only normal peptide links
06
Dipeptides
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
5
Peptides having up to four amino acids in a fully defined sequence; Derivatives thereof
04
containing only normal peptide links
10
Tetrapeptides
107
the side chain of the first amino acid containing carbocyclic rings, e.g. Phe, Tyr
Applicants:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA [US/US]; 1111 Franklin Street, Fifth Street Oakland, CA 94607-5200, US
Inventors:
KONOPELSKI, Joseph, P.; US
FILONOVA, Lubov, K.; US
Agent:
BERLINER, Robert; Fulbright & Jaworski L.L.P. 29th floor 865 S. Figueroa Street Los Angeles, CA 90017-2571, US
Priority Data:
09/065,29123.04.1998US
60/044,82825.04.1997US
Title (EN) DIPEPTIDE SURROGATES CONTAINING ASPARAGINE-DERIVED TETRAHYDROPYRIMIDINONES
(FR) SUBSTITUTS DE DIPEPTIDES CONTENANT DES TETRAHYDROPYRIMIDINONES DERIVES D'ASPARAGINE
Abstract:
(EN) Dipeptide surrogates Fmoc-Xxx-(cyclo)Asn-OBu are prepared from asparagine, aromatic aldehydes, and Fmoc-protected amino acid chlorides. The tetrahydropyrimidinone structure exist in a preferred ring conformation, as observed in a single crystal X-ray analysis of one of the derived carboxylic acids. As with other molecules with similar substitution patterns, the six-membered ring is held in a boat conformation. These dipeptide building blocks are deprotected at the C-terminal and/or N-terminal positions by known protocols. In addition, they function as ready participants for solid phase peptide synthesis. Finally, the constrained asparagine residue can be transformed to the native amino acid within a polypeptide framework, allowing for the direct interchange of a restricted system of known conformation and configuration to the native state under mild conditions. These peptide surrogates containing (cyclo)Asn are useful therapy of mammalian disease conditions, particularly in therapy of brain disorders.
(FR) La présente invention concerne des substituts de dipeptides Fmoc-Xxx-(cyclo)Asn-OBu obtenus à partir d'asparagine, d'aldéhydes aromatiques et de chlorures d'acides aminés protégés en Fmoc. La structure des tétrahydropyrimidinones existe avec une conformation préférée en cycle, tel qu'on l'observe par une analyse aux rayons X du monocristal de l'un des acides carboxyliques dérivés. Comme dans le cas des autres molécules à structure de substitution similaire, le cycle à 6 faces s'inscrit dans une conformation de bateau. Ces briques de base de dipeptides sont déprotégées en positions C terminales et/ou N terminales au moyen de protocoles connus. En outre, elles interviennent comme participants déjà prêts dans la synthèse de peptides en phase solide. Enfin, le radical asparagine soumis à des contraintes peut se transformer en acide aminé natif dans un réseau polypeptide, ce qui permet l'échange direct d'un système restreint de conformation et de configuration connues donnant l'état natif dans des conditions modérées. Ces substituts de peptides contenant du (cyclo)Asn conviennent particulièrement pour le traitement d'états pathologiques mammaliens, notamment le traitement de maladies neurodégénératives.
Designated States: AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GE, GH, GM, GW, HU, ID, IL, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, UZ, VN, YU, ZW
African Regional Intellectual Property Organization (ARIPO) (GH, GM, KE, LS, MW, SD, SZ, UG, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)
Also published as:
AU1998071626