CA1336738C - Produits intermediaires obtenus pendant la preparation de nouveaux analogues retro-inverses de la thymopentine - Google Patents

Produits intermediaires obtenus pendant la preparation de nouveaux analogues retro-inverses de la thymopentine

Info

Publication number: CA1336738C
Authority: CA; Canada
Prior art keywords: group; formula; tert; acid; mmol
Prior art date: 1987-03-19
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.): Expired - Fee Related

Application number

CA000616330A

Other languages

English (en)

Inventor

Alessandro Sisto

Antonio Silvio Verdini

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.)

Sclavo SpA

Eni Tecnologie SpA

Original Assignee

Sclavo SpA

Eniricerche SpA

Priority date (The priority date 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 date listed.)

1987-03-19

Filing date

1992-01-13

Publication date

1995-08-15

1987-03-19 Priority claimed from IT8719763A external-priority patent/IT1216908B/it

1992-01-13 Application filed by Sclavo SpA, Eniricerche SpA filed Critical Sclavo SpA

1992-01-13 Priority to CA000616330A priority Critical patent/CA1336738C/fr

1995-08-15 Application granted granted Critical

1995-08-15 Publication of CA1336738C publication Critical patent/CA1336738C/fr

2008-03-11 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

PSWFFKRAVBDQEG-YGQNSOCVSA-N thymopentin Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 PSWFFKRAVBDQEG-YGQNSOCVSA-N 0.000 title abstract description 40
229960004517 thymopentin Drugs 0.000 title abstract description 38
102400000160 Thymopentin Human genes 0.000 title abstract description 37
101800001703 Thymopentin Proteins 0.000 title abstract description 37
239000000543 intermediate Substances 0.000 title abstract description 9
238000002360 preparation method Methods 0.000 title abstract description 7
125000006239 protecting group Chemical group 0.000 claims abstract description 22
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 14
239000001257 hydrogen Substances 0.000 claims abstract description 13
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims abstract description 6
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims abstract description 4
-1 alkyl radical Chemical class 0.000 claims description 22
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
125000004432 carbon atom Chemical group C* 0.000 claims description 10
229910052799 carbon Inorganic materials 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000002877 alkyl aryl group Chemical group 0.000 claims description 2
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
150000001875 compounds Chemical class 0.000 description 62
239000000243 solution Substances 0.000 description 40
239000000047 product Substances 0.000 description 25
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
239000000203 mixture Substances 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
238000000034 method Methods 0.000 description 18
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
238000012360 testing method Methods 0.000 description 16
108090000765 processed proteins & peptides Proteins 0.000 description 15
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
150000003839 salts Chemical class 0.000 description 10
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
238000001727 in vivo Methods 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
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238000003756 stirring Methods 0.000 description 9
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 8
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 8
150000001408 amides Chemical class 0.000 description 8
238000011282 treatment Methods 0.000 description 8
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
210000001744 T-lymphocyte Anatomy 0.000 description 7
150000001413 amino acids Chemical class 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
230000008569 process Effects 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
239000007787 solid Substances 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
101710163560 Lamina-associated polypeptide 2, isoform alpha Proteins 0.000 description 6
101710189385 Lamina-associated polypeptide 2, isoforms beta/gamma Proteins 0.000 description 6
102400000159 Thymopoietin Human genes 0.000 description 6
239000000898 Thymopoietin Substances 0.000 description 6
229940024606 amino acid Drugs 0.000 description 6
235000001014 amino acid Nutrition 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
230000000694 effects Effects 0.000 description 6
235000019441 ethanol Nutrition 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
239000012634 fragment Substances 0.000 description 6
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
102000004196 processed proteins & peptides Human genes 0.000 description 6
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 5
238000005481 NMR spectroscopy Methods 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
235000011054 acetic acid Nutrition 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
230000004071 biological effect Effects 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
210000001541 thymus gland Anatomy 0.000 description 5
DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 4
102100025597 Caspase-4 Human genes 0.000 description 4
101100273284 Homo sapiens CASP4 gene Proteins 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
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125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
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QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
102000035195 Peptidases Human genes 0.000 description 3
108091005804 Peptidases Proteins 0.000 description 3
102000007079 Peptide Fragments Human genes 0.000 description 3
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HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
229960005261 aspartic acid Drugs 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
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BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 3
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ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
229960004441 tyrosine Drugs 0.000 description 3
XYXYXSKSTZAEJW-VIFPVBQESA-N (2s)-2-(phenylmethoxycarbonylamino)butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 XYXYXSKSTZAEJW-VIFPVBQESA-N 0.000 description 2
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
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208000023275 Autoimmune disease Diseases 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
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Classifications

- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA000616330A 1987-03-19 1992-01-13 Produits intermediaires obtenus pendant la preparation de nouveaux analogues retro-inverses de la thymopentine Expired - Fee Related CA1336738C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000616330A CA1336738C (fr)	1987-03-19	1992-01-13	Produits intermediaires obtenus pendant la preparation de nouveaux analogues retro-inverses de la thymopentine

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
IT19763A/87		1987-03-19
IT8719763A IT1216908B (it)	1987-03-19	1987-03-19	Analoghi retro-inversi della timopentina e dei suoi frammenti, il metodo per la loro sintesi ed il loro impiego per la preparazionedi composizioni farmaceutiche.
CA000561269A CA1315472C (fr)	1987-03-19	1988-03-11	Analogues retro-inverses de la thymopentine et leurs fragments, mode de preparation de ces nouveaux composes et de leurs intermediaires
CA000616330A CA1336738C (fr)	1987-03-19	1992-01-13	Produits intermediaires obtenus pendant la preparation de nouveaux analogues retro-inverses de la thymopentine

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000561269A Division CA1315472C (fr)	1987-03-19	1988-03-11	Analogues retro-inverses de la thymopentine et leurs fragments, mode de preparation de ces nouveaux composes et de leurs intermediaires

Publications (1)

Publication Number	Publication Date
CA1336738C true CA1336738C (fr)	1995-08-15

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Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000616330A Expired - Fee Related CA1336738C (fr)	1987-03-19	1992-01-13	Produits intermediaires obtenus pendant la preparation de nouveaux analogues retro-inverses de la thymopentine

Country Status (1)

Country	Link
CA (1)	CA1336738C (fr)

1992
- 1992-01-13 CA CA000616330A patent/CA1336738C/fr not_active Expired - Fee Related

Legal Events

Date	Code	Title	Description
1998-08-17	MKLA	Lapsed

Publication	Publication Date	Title
EP0282891B1 (fr)	1994-01-26	Thymopentine rétro-inverso analogues et leurs fragments, leur procédé de préparation et intermédiaires ainsi obtenus
EP0148133B1 (fr)	1989-03-22	Composés tripeptidiques contenant l'acide pyroglutamique et du tryptophane, leur procédé de préparation et applications thérapeutiques
EP0253190B1 (fr)	1992-12-30	Analogues de la tuftsine partiellement rétro-inversés, leur méthode de préparation et compositions pharmaceutiques les contenant
US4420424A (en)	1983-12-13	New peptides and a process for their preparation
Chorev et al.	1983	Synthesis of partially modified retro-inverso substance P analogs and their biological activity
EP0565148A2 (fr)	1993-10-13	Intermédiaires pour la préparation de H-Arg-X-Y-Z-Tyr-H
US5218089A (en)	1993-06-08	Retro-inverso analogues of thymopentin and the method for their synthesis
US6184345B1 (en)	2001-02-06	Branched building units for synthesizing cyclic peptides
CS235072B2 (en)	1985-04-16	Method of l-tyrosyl-d-alanyl-glycyl-l-phenylalanylamide's new derivatives production
US4018912A (en)	1977-04-19	Tripeptide derivatives with central nervous system activity and preparation thereof
US6057295A (en)	2000-05-02	Oligopeptides derived from C-reactive protein fragments
US4716149A (en)	1987-12-29	Partially modified, retro-inverso neurotensin analogs
US4491541A (en)	1985-01-01	Peptides
US4713367A (en)	1987-12-15	Retro-inverso analogs of the bradykinin potentiating peptide BPP5a
CA1336738C (fr)	1995-08-15	Produits intermediaires obtenus pendant la preparation de nouveaux analogues retro-inverses de la thymopentine
US5200506A (en)	1993-04-06	Process for preparing new thymopentin retro-inverso analogs and fragments thereof and the intermediates obtained therein
US4093713A (en)	1978-06-06	Dipeptide derivatives with central nervous system activity and preparation thereof
EP0375058B1 (fr)	1994-03-16	Analogues de la thrymopentine, leur procédé de préparation et leur emploi pour préparer des compositions pharmaceutiques
EP0406931B1 (fr)	1995-03-15	Analogues de la thymopentine avec toutes les liaisons rétro-inverties, leur méthode de préparation et leur utilisation pour la préparation de compositions pharmaceutiques
EP0393786B1 (fr)	1996-01-17	Rétro-inverso peptides, analogues de la thymopentine ayant une ou plusieurs liaisons, procédés pour les préparer et leur utilisation pour confectionner un médicament
USRE30496E (en)	1981-01-27	Tripeptide derivatives with central nervous system activity and preparation thereof
US6342481B1 (en)	2002-01-29	Oligopeptides derived from C-reactive protein fragments
JPS62501212A (ja)	1987-05-14	サブスタンスｐ及びそのフラグメントの誘導体
JPH07505640A (ja)	1995-06-22	Ｃ反応性タンパク断片の部分修飾及び逆転置テトラペプチド類似体
IE49262B1 (en)	1985-09-04	Psycho-pharmacological peptides,process for their preparation and therapeutical compositions containing them