SK280292A3 - New derivatives of 5-amino-4-hydroxyhexane acid effecting as therapeutic agents - Google Patents

New derivatives of 5-amino-4-hydroxyhexane acid effecting as therapeutic agents Download PDF

Info

Publication number: SK280292A3
Authority: SK; Slovakia
Prior art keywords: phe; val; ylamide; morpholin; group
Prior art date: 1991-09-12

Application number

SK2802-92A

Other languages

English (en)

Slovak (sk)

Inventor

Marc Lang

Guido Bold

Alexander Fassler

Peter Schneider

Hoevest Peter Van

Original Assignee

Ciba Geigy Ag

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.)

1991-09-12

Filing date

1992-09-11

Publication date

1995-02-08

1992-09-11 Application filed by Ciba Geigy Ag filed Critical Ciba Geigy Ag

1995-02-08 Publication of SK280292A3 publication Critical patent/SK280292A3/sk

Links

239000002253 acid Substances 0.000 title claims description 96
239000003814 drug Substances 0.000 title claims description 3
TXRCHGMTTXKTPE-UHFFFAOYSA-N 2-aminohexan-3-ol Chemical class CCCC(O)C(C)N TXRCHGMTTXKTPE-UHFFFAOYSA-N 0.000 title 1
229940124597 therapeutic agent Drugs 0.000 title 1
125000000217 alkyl group Chemical group 0.000 claims abstract description 173
238000000034 method Methods 0.000 claims abstract description 103
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
238000004519 manufacturing process Methods 0.000 claims abstract description 10
-1 heterocycliccarbonyl Chemical group 0.000 claims description 410
150000001875 compounds Chemical class 0.000 claims description 357
229910052799 carbon Inorganic materials 0.000 claims description 153
229910052757 nitrogen Inorganic materials 0.000 claims description 143
150000001721 carbon Chemical group 0.000 claims description 129
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 105
150000003839 salts Chemical class 0.000 claims description 91
125000004433 nitrogen atom Chemical group N* 0.000 claims description 82
125000004093 cyano group Chemical group *C#N 0.000 claims description 77
125000003545 alkoxy group Chemical group 0.000 claims description 69
235000008206 alpha-amino acids Nutrition 0.000 claims description 69
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 62
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 55
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 52
150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 51
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 48
125000002252 acyl group Chemical group 0.000 claims description 46
238000011282 treatment Methods 0.000 claims description 41
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 39
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 39
230000008569 process Effects 0.000 claims description 39
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 38
230000002829 reductive effect Effects 0.000 claims description 38
125000003277 amino group Chemical group 0.000 claims description 37
229910052736 halogen Inorganic materials 0.000 claims description 37
150000002367 halogens Chemical class 0.000 claims description 36
239000001257 hydrogen Substances 0.000 claims description 36
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125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 36
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 35
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 34
239000004474 valine Substances 0.000 claims description 34
125000000623 heterocyclic group Chemical group 0.000 claims description 33
229940024606 amino acid Drugs 0.000 claims description 32
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235000001014 amino acid Nutrition 0.000 claims description 29
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 28
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108010016626 Dipeptides Proteins 0.000 claims description 26
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 25
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238000002360 preparation method Methods 0.000 claims description 24
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 23
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 23
229920006395 saturated elastomer Polymers 0.000 claims description 23
125000005505 thiomorpholino group Chemical group 0.000 claims description 21
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
239000011737 fluorine Substances 0.000 claims description 19
230000002209 hydrophobic effect Effects 0.000 claims description 19
125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 19
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125000004429 atom Chemical group 0.000 claims description 17
XWHHYOYVRVGJJY-UHFFFAOYSA-N 4-fluorophenylalanine Chemical compound OC(=O)C(N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-UHFFFAOYSA-N 0.000 claims description 16
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125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 claims description 14
150000001371 alpha-amino acids Chemical class 0.000 claims description 14
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201000010099 disease Diseases 0.000 claims description 13
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GEYBMYRBIABFTA-VIFPVBQESA-N O-methyl-L-tyrosine Chemical compound COC1=CC=C(C[C@H](N)C(O)=O)C=C1 GEYBMYRBIABFTA-VIFPVBQESA-N 0.000 claims description 12
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OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 11
125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 claims description 11
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
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OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 10
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QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
125000005493 quinolyl group Chemical group 0.000 claims description 9
CNBUSIJNWNXLQQ-NSHDSACASA-N (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CNBUSIJNWNXLQQ-NSHDSACASA-N 0.000 claims description 8
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 8
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 8
241001430294 unidentified retrovirus Species 0.000 claims description 8
241000725303 Human immunodeficiency virus Species 0.000 claims description 7
125000002883 imidazolyl group Chemical group 0.000 claims description 7
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125000000168 pyrrolyl group Chemical group 0.000 claims description 7
125000000335 thiazolyl group Chemical group 0.000 claims description 7
WMDZARSFSMZOQO-DRZSPHRISA-N Ile-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 WMDZARSFSMZOQO-DRZSPHRISA-N 0.000 claims description 6
GJNDXQBALKCYSZ-RYUDHWBXSA-N Val-Phe Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 GJNDXQBALKCYSZ-RYUDHWBXSA-N 0.000 claims description 6
KRNYOVHEKOBTEF-YUMQZZPRSA-N Val-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(O)=O KRNYOVHEKOBTEF-YUMQZZPRSA-N 0.000 claims description 6
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
125000001041 indolyl group Chemical group 0.000 claims description 6
125000005956 isoquinolyl group Chemical group 0.000 claims description 6
125000001544 thienyl group Chemical group 0.000 claims description 6
108010021889 valylvaline Proteins 0.000 claims description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 5
MKQLBNJQQZRQJU-UHFFFAOYSA-N morpholin-4-amine Chemical group NN1CCOCC1 MKQLBNJQQZRQJU-UHFFFAOYSA-N 0.000 claims description 5
VEYJKJORLPYVLO-RYUDHWBXSA-N Val-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 VEYJKJORLPYVLO-RYUDHWBXSA-N 0.000 claims description 4
LSYICPNAJSMBIC-UHFFFAOYSA-N hydroxymethyl hypofluorite Chemical compound OCOF LSYICPNAJSMBIC-UHFFFAOYSA-N 0.000 claims description 4
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125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
IAFSUZIBZMPMPK-UHFFFAOYSA-N thiomorpholin-4-amine Chemical group NN1CCSCC1 IAFSUZIBZMPMPK-UHFFFAOYSA-N 0.000 claims description 4
108010009962 valyltyrosine Proteins 0.000 claims description 4
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IOUPEELXVYPCPG-UHFFFAOYSA-N Valylglycine Chemical compound CC(C)C(N)C(=O)NCC(O)=O IOUPEELXVYPCPG-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
241001465754 Metazoa Species 0.000 claims description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
230000001225 therapeutic effect Effects 0.000 claims description 2
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125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
SOBXUYMZUBUAOG-UHFFFAOYSA-N 4-morpholin-4-ylsulfonylmorpholine Chemical class C1COCCN1S(=O)(=O)N1CCOCC1 SOBXUYMZUBUAOG-UHFFFAOYSA-N 0.000 claims 1
241000283073 Equus caballus Species 0.000 claims 1
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235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
ZJTYRNPLVNMVPQ-LBPRGKRZSA-N tert-butyl n-[(2s)-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](C=O)CC1=CC=CC=C1 ZJTYRNPLVNMVPQ-LBPRGKRZSA-N 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
150000003555 thioacetals Chemical class 0.000 description 1
238000007079 thiolysis reaction Methods 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
BJBUEDPLEOHJGE-IMJSIDKUSA-N trans-3-hydroxy-L-proline Chemical compound O[C@H]1CC[NH2+][C@@H]1C([O-])=O BJBUEDPLEOHJGE-IMJSIDKUSA-N 0.000 description 1
PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000005106 triarylsilyl group Chemical group 0.000 description 1
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
229940078499 tricalcium phosphate Drugs 0.000 description 1
235000019731 tricalcium phosphate Nutrition 0.000 description 1
229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
VTDQBKLDBJKTMS-UHFFFAOYSA-N trihydrate;hydrofluoride Chemical compound O.O.O.F VTDQBKLDBJKTMS-UHFFFAOYSA-N 0.000 description 1
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
108010020532 tyrosyl-proline Proteins 0.000 description 1
238000002604 ultrasonography Methods 0.000 description 1
125000003847 vaccenoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
238000010792 warming Methods 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0207—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)4-C(=0), e.g. 'isosters', replacing two amino acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Genetics & Genomics (AREA)
Virology (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Oncology (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Communicable Diseases (AREA)
Tropical Medicine & Parasitology (AREA)
AIDS & HIV (AREA)
Crystallography & Structural Chemistry (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

SK2802-92A 1991-09-12 1992-09-11 New derivatives of 5-amino-4-hydroxyhexane acid effecting as therapeutic agents SK280292A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
CH268991		1991-09-12
CH98092		1992-03-27
CH200792		1992-06-25

Publications (1)

Publication Number	Publication Date
SK280292A3 true SK280292A3 (en)	1995-02-08

Family

ID=27172572

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK2802-92A SK280292A3 (en)	1991-09-12	1992-09-11	New derivatives of 5-amino-4-hydroxyhexane acid effecting as therapeutic agents

Country Status (15)

Country	Link
EP (1)	EP0532466A3 (cs)
JP (1)	JPH05230095A (cs)
KR (1)	KR930006050A (cs)
AU (1)	AU661018B2 (cs)
CA (1)	CA2077948A1 (cs)
CZ (1)	CZ280292A3 (cs)
FI (1)	FI924035A7 (cs)
HU (1)	HUT63632A (cs)
IL (1)	IL103126A (cs)
MX (1)	MX9205208A (cs)
NO (1)	NO923533L (cs)
NZ (1)	NZ244288A (cs)
PL (1)	PL169969B1 (cs)
RU (1)	RU2067585C1 (cs)
SK (1)	SK280292A3 (cs)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5643878A (en) *	1991-09-12	1997-07-01	Ciba-Geigy Corporation	5-amino-4-hydroxyhexanoic acid derivatives
BR9306058A (pt) *	1992-03-11	1997-11-18	Narhex Ltd	Derivados de amina de hidrocarbonetos oxo- e hidroxi- substituidos
US6071895A (en)	1992-03-11	2000-06-06	Narhex Limited	Polar-substituted hydrocarbons
US5888992A (en) *	1992-03-11	1999-03-30	Narhex Limited	Polar substituted hydrocarbons
DE69333270T2 (de)	1992-03-11	2004-08-05	Narhex Ltd.	Aminderivate von oxo- und hydroxy- substituierten kohlenwasserstoffen
TW217410B (cs) *	1992-04-01	1993-12-11	Ciba Geigy
ES2093394T3 (es)	1992-12-23	1996-12-16	Ciba Geigy Ag	Derivados de hidrazina antiretrovirales.
EP0618222A3 (en) *	1993-03-11	1997-01-02	Ciba Geigy Ag	Dipeptid derivatives of 5-amino-4-hydroxy-hexanoic acid.
EP0626178A1 (de) *	1993-05-17	1994-11-30	Ciba-Geigy Ag	Verwendung von Hemmstoffen von HIV-Aspartatproteasen zur Bekämpfung von Tumorerkrankungen
IL110898A0 (en) *	1993-09-10	1994-11-28	Narhex Australia Pty Ltd	Polar-substituted hydrocarbons
IL110752A (en) *	1993-09-13	2000-07-26	Abbott Lab	Liquid semi-solid or solid pharmaceutical composition for an HIV protease inhibitor
US5559158A (en) *	1993-10-01	1996-09-24	Abbott Laboratories	Pharmaceutical composition
IL111991A (en) *	1994-01-28	2000-07-26	Abbott Lab	Liquid pharmaceutical composition of HIV protease inhibitors in organic solvent
AU4117396A (en) *	1994-11-29	1996-06-19	Novartis Ag	Morpholinoethylamide derivatives
US6037157A (en)	1995-06-29	2000-03-14	Abbott Laboratories	Method for improving pharmacokinetics
US5840835A (en) *	1995-10-30	1998-11-24	Merck & Co., Inc.	Inhibitors of peptide binding to MHC class II proteins
US5817757A (en) *	1995-10-30	1998-10-06	Merck & Co., Inc.	Inhibitors of peptide binding to MHO class II proteins
WO1997016188A1 (en) *	1995-10-30	1997-05-09	Merck & Co., Inc.	Novel inhibitors of peptide binding to mhc class ii proteins
US5914332A (en)	1995-12-13	1999-06-22	Abbott Laboratories	Retroviral protease inhibiting compounds
US6232333B1 (en)	1996-11-21	2001-05-15	Abbott Laboratories	Pharmaceutical composition
CA2359030A1 (en) *	1999-01-28	2000-08-03	Chugai Seiyaku Kabushiki Kaisha	Substituted phenethylamine derivatives
US6455734B1 (en) *	2000-08-09	2002-09-24	Magnesium Diagnostics, Inc.	Antagonists of the magnesium binding defect as therapeutic agents and methods for treatment of abnormal physiological states
KR100708221B1 (ko)	1999-08-31	2007-04-17	아지노모토 가부시키가이샤	에폭사이드 결정의 제조방법
ES2676151T3 (es)	2000-01-19	2018-07-17	Abbvie Inc.	Formulaciones farmacéuticas mejoradas
US6506786B2 (en)	2001-02-13	2003-01-14	Pharmacor Inc.	HIV protease inhibitors based on amino acid derivatives
US7265152B2 (en) *	2002-11-01	2007-09-04	Viropharma Incorporated	Benzofuran compounds, compositions and methods for treatment and prophylaxis of hepatitis C viral infections and associated diseases
US7388008B2 (en)	2004-08-02	2008-06-17	Ambrilia Biopharma Inc.	Lysine based compounds
WO2007062526A1 (en)	2005-11-30	2007-06-07	Ambrilia Biopharma Inc.	Lysine-based prodrugs of aspartyl protease inhibitors and processes for their preparation
CN102351791B (zh)	2006-01-27	2014-10-29	菲布罗根有限公司	使低氧诱导因子(hif)稳定的氰基异喹啉化合物
AU2007234408B2 (en)	2006-04-04	2011-05-19	Fibrogen, Inc.	Pyrrolo- and thiazolo-pyridine compounds as HIF modulators
ES2628730T3 (es)	2006-09-21	2017-08-03	Taimed Biologics, Inc.	Inhibidores de proteasa
WO2010056767A1 (en)	2008-11-14	2010-05-20	Fibrogen, Inc.	Thiochromene derivatives as hip hydroxylase inhibitors
SG10202009266PA (en)	2013-01-24	2020-10-29	Fibrogen Inc	Crystalline forms of {[1-cyano-5-(4-chlorophenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-acetic acid
CN115466316A (zh) *	2021-06-10	2022-12-13	首都医科大学	抑制迁移的1-咪唑-β-咔啉-3-甲酰-RGDF及制备,抗癌转移作用和应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5126326A (en) *	1989-06-06	1992-06-30	Bio-Mega, Inc.	Enzyme inhibiting peptide derivatives

1992
- 1992-09-03 EP EP19920810678 patent/EP0532466A3/de not_active Ceased
- 1992-09-07 JP JP4238424A patent/JPH05230095A/ja active Pending
- 1992-09-09 KR KR1019920016530A patent/KR930006050A/ko not_active Withdrawn
- 1992-09-09 FI FI924035A patent/FI924035A7/fi not_active Application Discontinuation
- 1992-09-10 IL IL103126A patent/IL103126A/xx not_active IP Right Cessation
- 1992-09-10 AU AU22889/92A patent/AU661018B2/en not_active Ceased
- 1992-09-10 CA CA002077948A patent/CA2077948A1/en not_active Abandoned
- 1992-09-10 NZ NZ244288A patent/NZ244288A/en unknown
- 1992-09-11 HU HU9202925A patent/HUT63632A/hu unknown
- 1992-09-11 CZ CS922802A patent/CZ280292A3/cs unknown
- 1992-09-11 SK SK2802-92A patent/SK280292A3/sk unknown
- 1992-09-11 NO NO92923533A patent/NO923533L/no unknown
- 1992-09-11 RU SU925052915A patent/RU2067585C1/ru active
- 1992-09-11 PL PL92295905A patent/PL169969B1/pl unknown
- 1992-09-11 MX MX9205208A patent/MX9205208A/es not_active IP Right Cessation

Also Published As

Publication number	Publication date
EP0532466A2 (de)	1993-03-17
MX9205208A (es)	1993-03-01
PL169969B1 (pl)	1996-09-30
HUT63632A (en)	1993-09-28
NO923533D0 (no)	1992-09-11
FI924035A7 (fi)	1993-03-13
NZ244288A (en)	1995-03-28
KR930006050A (ko)	1993-04-20
PL295905A1 (en)	1993-05-17
CZ280292A3 (en)	1994-01-19
AU2288992A (en)	1993-03-18
IL103126A0 (en)	1993-02-21
JPH05230095A (ja)	1993-09-07
IL103126A (en)	1997-09-30
HU9202925D0 (en)	1992-11-30
AU661018B2 (en)	1995-07-13
CA2077948A1 (en)	1993-03-13
EP0532466A3 (en)	1993-06-16
FI924035A0 (fi)	1992-09-09
NO923533L (no)	1993-03-15
RU2067585C1 (ru)	1996-10-10

Publication	Publication Date	Title
CZ280292A3 (en)	1994-01-19	Novel derivatives of 5-amino-4-hydroxyhexanoic acid which derivatives act as therapeutic agents
US5663200A (en)	1997-09-02	Antiviral ethers of aspartate protease substrate isosteres
CZ280651B6 (cs)	1996-03-13	Farmakologicky účinné hydrazinové deriváty a způsob jejich výroby
HUT74453A (en)	1996-12-30	2,9-diamino- and 2-amino-8-carbamoyl-4-hydroxy-alkane-carboxylic acid derivatives, process for preparing them, their intermediates, use and pharmaceutical compns. contg. the said compds.
US5643878A (en)	1997-07-01	5-amino-4-hydroxyhexanoic acid derivatives
JPH02300199A (ja)	1990-12-12	レトロウイルスプロテアーゼ阻害剤
CZ285793A3 (en)	1994-07-13	Anti-retroviral hydrazine derivatives
CZ223893A3 (en)	1994-05-18	Antiretroviral active acyl derivatives
US5409927A (en)	1995-04-25	Morpholin- and thiomorpholin-4-ylamides
CA2043603A1 (en)	1991-12-02	Hiv protease inhibitors and processes for their preparation
AU678202B2 (en)	1997-05-22	Acyloxyhexanoic acid derivatives
KR960000077B1 (ko)	1996-01-03	인간 면역 결핍 바이러스 프로테아제의 억제 화합물 및 그의 제조방법