ZA200104672B - Procollagen C-porteinase inhibitors. - Google Patents

Procollagen C-porteinase inhibitors. Download PDF

Info

Publication number: ZA200104672B
Authority: ZA; South Africa
Prior art keywords: compound; alkyl; aralkyl; heteroaralkyl; resin
Prior art date: 1998-12-10

Application number

ZA200104672A

Other languages

English (en)

Inventor

Sharon Marie Dankwardt

Keith Adrian Murray Walker

Harold Edgar Van Wart

Original Assignee

Hoffmann La Roche

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.)

1998-12-10

Filing date

2001-06-07

Publication date

2002-09-09

2001-06-07 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2002-09-09 Publication of ZA200104672B publication Critical patent/ZA200104672B/en

Links

239000003112 inhibitor Substances 0.000 title claims description 4
108010050808 Procollagen Proteins 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims description 200
-1 aralkenyl Chemical group 0.000 claims description 143
125000000217 alkyl group Chemical group 0.000 claims description 103
229910052739 hydrogen Inorganic materials 0.000 claims description 76
239000001257 hydrogen Substances 0.000 claims description 75
125000004475 heteroaralkyl group Chemical group 0.000 claims description 65
125000003710 aryl alkyl group Chemical group 0.000 claims description 57
125000003118 aryl group Chemical group 0.000 claims description 57
125000000753 cycloalkyl group Chemical group 0.000 claims description 57
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 55
125000001072 heteroaryl group Chemical group 0.000 claims description 53
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102100028728 Bone morphogenetic protein 1 Human genes 0.000 claims description 39
125000002947 alkylene group Chemical group 0.000 claims description 31
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
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125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 21
238000000034 method Methods 0.000 claims description 21
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125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
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235000012424 soybean oil Nutrition 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
230000000153 supplemental effect Effects 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical compound OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 1
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
238000001890 transfection Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
238000013519 translation Methods 0.000 description 1
230000014621 translational initiation Effects 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
238000000108 ultra-filtration Methods 0.000 description 1
210000004325 uterine smooth muscle cell Anatomy 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
JPZXHKDZASGCLU-LBPRGKRZSA-N β-(2-naphthyl)-alanine Chemical compound C1=CC=CC2=CC(C[C@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-LBPRGKRZSA-N 0.000 description 1
ORQXBVXKBGUSBA-QMMMGPOBSA-N β-cyclohexyl-alanine Chemical compound OC(=O)[C@@H](N)CC1CCCCC1 ORQXBVXKBGUSBA-QMMMGPOBSA-N 0.000 description 1

Classifications

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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
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- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06147—Dipeptides with the first amino acid being heterocyclic and His-amino acid; Derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06156—Dipeptides with the first amino acid being heterocyclic and Trp-amino acid; Derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

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Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
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Pharmacology & Pharmacy (AREA)
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Peptides Or Proteins (AREA)

ZA200104672A 1998-12-10 2001-06-07 Procollagen C-porteinase inhibitors. ZA200104672B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US11166198P	1998-12-10	1998-12-10

Publications (1)

Publication Number	Publication Date
ZA200104672B true ZA200104672B (en)	2002-09-09

Family

ID=22339762

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200104672A ZA200104672B (en)	1998-12-10	2001-06-07	Procollagen C-porteinase inhibitors.

Country Status (12)

Country	Link
US (2)	US6426402B1 (tr)
EP (1)	EP1137661A1 (tr)
JP (1)	JP2002531576A (tr)
KR (1)	KR20010080709A (tr)
CN (1)	CN1330661A (tr)
AR (1)	AR021596A1 (tr)
AU (1)	AU772575B2 (tr)
BR (1)	BR9916004A (tr)
CA (1)	CA2352740A1 (tr)
TR (1)	TR200101663T2 (tr)
WO (1)	WO2000034313A1 (tr)
ZA (1)	ZA200104672B (tr)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6777217B1 (en)	1996-03-26	2004-08-17	President And Fellows Of Harvard College	Histone deacetylases, and uses related thereto
US20030129724A1 (en)	2000-03-03	2003-07-10	Grozinger Christina M.	Class II human histone deacetylases, and uses related thereto
US7244853B2 (en)	2001-05-09	2007-07-17	President And Fellows Of Harvard College	Dioxanes and uses thereof
CN1638790A (zh)	2002-01-29	2005-07-13	Wyeth公司	用于调节连接蛋白半通道的组合物和方法
FR2840897B1 (fr)	2002-06-14	2004-09-10	Fournier Lab Sa	Nouveaux derives d'arylsulfonamides et leur utilisation en therapeutique
AU2004215624B2 (en) *	2003-02-25	2011-06-02	Topotarget Uk Limited	Hydroxamic acid compounds comprising a bicyclic heteroaryl group as HDAC inhibitors
US20070160655A1 (en) *	2003-04-23	2007-07-12	Sefton Michael V	Hydroxyamate-containing materials for the inhibition of matrix metalloproteinases
US20040213758A1 (en) *	2003-04-23	2004-10-28	Rimon Therapeutics Ltd.	Hydroxyamate-containing materials for the inhibition of matrix metalloproteinases
US7317019B2 (en)	2003-08-21	2008-01-08	Bristol Myers Squibb Co.	N-alkylated diaminopropane derivatives as modulators of chemokine receptor activity
KR100629712B1 (ko) *	2003-08-26	2006-09-29	(주)아모레퍼시픽	항노화 효과를 나타내는 히드록삼산 유도체 및 이의제조방법
JP5744376B2 (ja)	2005-03-22	2015-07-08	プレジデントアンドフェローズオブハーバードカレッジ	タンパク質分解障害の治療
PL2010168T3 (pl) *	2006-02-14	2014-09-30	The President And Fellows Of Harvard College	Inhibitory deacetylazy histonowej
US8222423B2 (en)	2006-02-14	2012-07-17	Dana-Farber Cancer Institute, Inc.	Bifunctional histone deacetylase inhibitors
CN101484156B (zh)	2006-05-03	2015-11-25	哈佛大学校长及研究员协会	组蛋白脱乙酰基酶和微管蛋白脱乙酰基酶抑制剂
WO2009097893A1 (en) *	2008-02-04	2009-08-13	Proyecto De Biomedicina Cima, S.L.	Methods for the treatment of cardiac disease associated to myocardial fibrosis using an inhibitor of pcp
CA2716347C (en) *	2008-02-21	2017-06-20	Sequoia Pharmaceuticals, Inc.	Amino acid inhibitors of cytochrome p450
CN102164888B (zh)	2008-07-23	2015-06-03	哈佛大学校长及研究员协会	脱乙酰酶抑制剂和其用途
AU2009276343A1 (en)	2008-08-01	2010-02-04	Bioxiness Pharmaceuticals, Inc.	Methionine analogs and methods of using same
US8716344B2 (en)	2009-08-11	2014-05-06	President And Fellows Of Harvard College	Class- and isoform-specific HDAC inhibitors and uses thereof
EP3092233A1 (en) *	2014-01-10	2016-11-16	Glaxosmithkline Intellectual Property (No. 2) Limited	Hydroxy formamide derivatives and their use
WO2017006296A1 (en) *	2015-07-09	2017-01-12	Glaxosmithkline Intellectual Property (No.2) Limited	N-hydroxyformamide compounds and compositions comprising them for use as bmp1, tll1 and/or tll2 inhibitors
US9813673B2 (en)	2016-01-20	2017-11-07	Gerard Dirk Smits	Holographic video capture and telepresence system
CN115197102B (zh) *	2021-04-12	2023-10-20	山东大学	类肽异羟肟酸类恶性疟原虫氨肽酶抑制剂及其制备方法和应用

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IE54551B1 (en)	1982-01-22	1989-11-22	Ici Plc	Amide derivatives
JPH01146896A (ja) *	1987-12-04	1989-06-08	Fuji Yakuhin Kogyo Kk	新規なペプチジルヒドロキサム酸誘導体
WO1992022523A2 (en) *	1991-06-14	1992-12-23	Research Corporation Technologies, Inc.	Peptide derivatives of collagenase inhibitor
WO1995012612A1 (en) *	1993-11-05	1995-05-11	Warner-Lambert Company	Substituted di- and tripeptide inhibitors of protein:farnesyl transferase
JPH0925293A (ja) *	1995-02-14	1997-01-28	Teijin Ltd	ヒスチジル−ヒドロキサム酸誘導体
US5703092A (en) *	1995-04-18	1997-12-30	The Dupont Merck Pharmaceutical Company	Hydroxamic acid compounds as metalloprotease and TNF inhibitors
JPH08311096A (ja)	1995-05-18	1996-11-26	Teijin Ltd	Ｍｍｐ阻害作用を有する新規なヒスチジル−ヒドロキサム酸誘導体
EP0845987A4 (en)	1995-08-08	2000-05-24	Fibrogen Inc	C-PROTEINASE INHIBITORS FOR THE TREATMENT OF CONDITIONS RELATED TO COLLAGEN OVERPRODUCTION
IT1283637B1 (it)	1996-05-14	1998-04-23	Italfarmaco Spa	Composti ad attivita' antinfiammatoria ed immunosoppressiva
EP0994104A4 (en)	1996-06-27	2001-09-12	Ono Pharmaceutical Co	ARYL SULFIDE, SULFOXIDE AND SULPHONE DERIVATIVES AND MEDICINAL PRODUCTS CONTAINING THEM AS AN ACTIVE INGREDIENT
WO1998015525A1 (fr)	1996-10-07	1998-04-16	Sumitomo Pharmaceuticals Co., Ltd.	Acides hydroxamiques
AR016751A1 (es)	1996-11-22	2001-08-01	Athena Neurosciences Inc	Metodo para inhibir la liberacion del peptido beta-amiloide en una celula, composicion farmaceutica y compuestos utiles en dicho metodo
FR2762315B1 (fr)	1997-04-22	1999-05-28	Logeais Labor Jacques	Derives d'amino-acides inhibiteurs des metalloproteases de la matrice extracellulaire et de la liberation du tnf alpha
AUPO721997A0 (en) *	1997-06-06	1997-07-03	Queensland Institute Of Medical Research, The	Anticancer compounds
AU7751598A (en) *	1997-06-11	1998-12-30	Carlton And United Breweries Limited	A container for separately storing flowable materials but allowing mixing of materials when required

1999
- 1999-12-06 CA CA002352740A patent/CA2352740A1/en not_active Abandoned
- 1999-12-06 AU AU25375/00A patent/AU772575B2/en not_active Ceased
- 1999-12-06 JP JP2000586755A patent/JP2002531576A/ja active Pending
- 1999-12-06 KR KR1020017007101A patent/KR20010080709A/ko not_active Application Discontinuation
- 1999-12-06 WO PCT/EP1999/009519 patent/WO2000034313A1/en not_active Application Discontinuation
- 1999-12-06 CN CN99814311A patent/CN1330661A/zh active Pending
- 1999-12-06 EP EP99968338A patent/EP1137661A1/en not_active Withdrawn
- 1999-12-06 TR TR2001/01663T patent/TR200101663T2/tr unknown
- 1999-12-06 BR BR9916004-8A patent/BR9916004A/pt not_active IP Right Cessation
- 1999-12-09 AR ARP990106263A patent/AR021596A1/es unknown
- 1999-12-10 US US09/459,201 patent/US6426402B1/en not_active Expired - Fee Related
2001
- 2001-06-07 ZA ZA200104672A patent/ZA200104672B/en unknown
2002
- 2002-02-07 US US10/072,730 patent/US6951918B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US6951918B2 (en)	2005-10-04
CA2352740A1 (en)	2000-06-15
US6426402B1 (en)	2002-07-30
EP1137661A1 (en)	2001-10-04
JP2002531576A (ja)	2002-09-24
AU2537500A (en)	2000-06-26
TR200101663T2 (tr)	2001-11-21
WO2000034313A1 (en)	2000-06-15
BR9916004A (pt)	2001-10-02
KR20010080709A (ko)	2001-08-22
AR021596A1 (es)	2002-07-31
AU772575B2 (en)	2004-04-29
US20020169133A1 (en)	2002-11-14
CN1330661A (zh)	2002-01-09

Publication	Publication Date	Title
ZA200104672B (en)	2002-09-09	Procollagen C-porteinase inhibitors.
US6034056A (en)	2000-03-07	Fibronectin adhesion inhibitors
EP0529568B1 (en)	1997-01-15	Novel orally-active elastase inhibitors
US5053392A (en)	1991-10-01	Novel arginine, glycine, aspartic acid derivatives as platelet-aggregation inhibitors
EP0460679A2 (en)	1991-12-11	Endothelin antagonistic peptide derivatives
KR20000022075A (ko)	2000-04-25	세포 접착 억제 화합물
US5430025A (en)	1995-07-04	Elastase-inhibiting peptides bearing a C-terminal trifluoromethylketone moiety
JP2002512625A (ja)	2002-04-23	細胞接着阻害薬としての複素環アミド化合物
NZ224452A (en)	1991-06-25	Heterocyclically-substituted tripeptide human leukocytic elastase inhibitors
WO2000015657A1 (en)	2000-03-23	Piperizine-4-phenyl derivatives as inhibitors of the interaction between mdm2 and 53
KR20010083140A (ko)	2001-08-31	유로키나제 및 혈관 형성의 억제제
AU769319B2 (en)	2004-01-22	Sulfonamide hydroxamates
US4703034A (en)	1987-10-27	Novel cyclic tetrapeptide
US4320051A (en)	1982-03-16	Analgesic tripeptide amides
CN113583088A (zh)	2021-11-02	用于治疗胃癌的环肽及其药物组合物
FI75175B (fi)	1988-01-29	Process foer framstaellning av n-karboxialkylprolin innehaollande tripeptider.
FR2540867A1 (fr)	1984-08-17	Halo-aminocetones utilisables comme intermediaires pour la preparation de peptides substitues
MXPA01005750A (es)	2002-02-26	Inhibidores de la procolageno c-proteinasa
US6492394B1 (en)	2002-12-10	Sulfonamide hydroxamates
US7964701B2 (en)	2011-06-21	Alpha-fetoprotein peptides
US20080039403A1 (en)	2008-02-14	Alpha-fetoprotein peptides and uses thereof
US4247543A (en)	1981-01-27	Organic compounds
Suli-Vargha et al.	1987	Synthesis and antitumor activity of N-terminal proline-containing peptide-(chloroethyl) nitrosoureas
CA1291482C (en)	1991-10-29	Intermediates useful in the preparation of aminothiol substituted dipeptides
JPH06503315A (ja)	1994-04-14	シクロヘキシルスタチン型のレニン−抑制性ペプチド類、それらの製造方法および薬品中におけるそれらの使用