WO1996040746B1 - Lysyloxidase inhibitors - Google Patents
Lysyloxidase inhibitorsInfo
- Publication number
- WO1996040746B1 WO1996040746B1 PCT/US1996/009102 US9609102W WO9640746B1 WO 1996040746 B1 WO1996040746 B1 WO 1996040746B1 US 9609102 W US9609102 W US 9609102W WO 9640746 B1 WO9640746 B1 WO 9640746B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- carbon atoms
- radical
- hydrogen
- unsaturated
- heterocyclic
- Prior art date
Links
- 102000004669 EC 1.4.3.13 Human genes 0.000 title 1
- 108010003894 EC 1.4.3.13 Proteins 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 230000002401 inhibitory effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 11
- 201000010099 disease Diseases 0.000 claims abstract 8
- KIWQWJKWBHZMDT-VKHMYHEASA-N L-homocysteine thiolactone Chemical compound N[C@H]1CCSC1=O KIWQWJKWBHZMDT-VKHMYHEASA-N 0.000 claims abstract 2
- 125000004432 carbon atoms Chemical group C* 0.000 claims 77
- -1 saturated aliphatic radical Chemical class 0.000 claims 36
- 229910052739 hydrogen Inorganic materials 0.000 claims 18
- 239000001257 hydrogen Substances 0.000 claims 18
- 125000004435 hydrogen atoms Chemical class [H]* 0.000 claims 18
- 125000003118 aryl group Chemical group 0.000 claims 14
- 125000003342 alkenyl group Chemical group 0.000 claims 12
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 125000000304 alkynyl group Chemical group 0.000 claims 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 12
- 125000000623 heterocyclic group Chemical group 0.000 claims 12
- FAYOCELKCDKZCA-UHFFFAOYSA-N 5-hydroxy-2,4-dimethylthiophen-3-one Chemical compound CC1SC(O)=C(C)C1=O FAYOCELKCDKZCA-UHFFFAOYSA-N 0.000 claims 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims 8
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 8
- 229910052717 sulfur Inorganic materials 0.000 claims 7
- 102000008186 Collagen Human genes 0.000 claims 6
- 108010035532 Collagen Proteins 0.000 claims 6
- 230000002159 abnormal effect Effects 0.000 claims 6
- 229960005188 collagen Drugs 0.000 claims 6
- 229920001436 collagen Polymers 0.000 claims 6
- 229910052760 oxygen Inorganic materials 0.000 claims 6
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 6
- 229910006069 SO3H Inorganic materials 0.000 claims 4
- 125000002252 acyl group Chemical group 0.000 claims 4
- 125000003545 alkoxy group Chemical group 0.000 claims 4
- 125000003368 amide group Chemical group 0.000 claims 4
- 125000000477 aza group Chemical group 0.000 claims 4
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 4
- 239000004202 carbamide Substances 0.000 claims 4
- 125000001651 cyanato group Chemical group [*]OC#N 0.000 claims 4
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims 4
- 125000001261 isocyanato group Chemical group *N=C=O 0.000 claims 4
- 125000002462 isocyano group Chemical group *[N+]#[C-] 0.000 claims 4
- 125000001810 isothiocyanato group Chemical group *N=C=S 0.000 claims 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 4
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 4
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- RVEZZJVBDQCTEF-UHFFFAOYSA-N sulfenic acid Chemical compound SO RVEZZJVBDQCTEF-UHFFFAOYSA-N 0.000 claims 4
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims 4
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims 4
- 150000003457 sulfones Chemical class 0.000 claims 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-N sulfonic acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 4
- 150000003462 sulfoxides Chemical class 0.000 claims 4
- 125000000858 thiocyanato group Chemical group *SC#N 0.000 claims 4
- 150000003568 thioethers Chemical class 0.000 claims 4
- 150000003573 thiols Chemical class 0.000 claims 4
- 229910052727 yttrium Inorganic materials 0.000 claims 4
- 206010059837 Adhesion Diseases 0.000 claims 3
- 206010060965 Arterial stenosis Diseases 0.000 claims 3
- 206010003210 Arteriosclerosis Diseases 0.000 claims 3
- 206010016654 Fibrosis Diseases 0.000 claims 3
- 210000004185 Liver Anatomy 0.000 claims 3
- 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 claims 3
- 208000005069 Pulmonary Fibrosis Diseases 0.000 claims 3
- 125000002723 alicyclic group Chemical group 0.000 claims 3
- 201000001320 atherosclerosis Diseases 0.000 claims 3
- 230000004761 fibrosis Effects 0.000 claims 3
- 200000000008 restenosis Diseases 0.000 claims 3
- YJQBUODOITVKCG-YFKPBYRVSA-N (2S)-2-(3-aminopropanoylamino)-4-sulfanylbutanoic acid Chemical compound NCCC(=O)N[C@H](C(O)=O)CCS YJQBUODOITVKCG-YFKPBYRVSA-N 0.000 claims 2
- DCNLDWGORPZUMT-LURJTMIESA-N (2S)-2-(4-aminobutanoylamino)-4-sulfanylbutanoic acid Chemical compound NCCCC(=O)N[C@H](C(O)=O)CCS DCNLDWGORPZUMT-LURJTMIESA-N 0.000 claims 2
- HOMBSCXWSACRAV-QMMMGPOBSA-N (2S)-2-(6-aminohexanoylamino)-4-sulfanylbutanoic acid Chemical compound NCCCCCC(=O)N[C@H](C(O)=O)CCS HOMBSCXWSACRAV-QMMMGPOBSA-N 0.000 claims 2
- YPKQGHMTSHYPOK-BYPYZUCNSA-N (2S)-2-[(2-aminoacetyl)amino]-4-sulfanylbutanoic acid Chemical compound NCC(=O)N[C@H](C(O)=O)CCS YPKQGHMTSHYPOK-BYPYZUCNSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 230000003510 anti-fibrotic Effects 0.000 abstract 1
- 230000003176 fibrotic Effects 0.000 abstract 1
- 230000001575 pathological Effects 0.000 abstract 1
Abstract
Compounds having anti-fibrotic effects are provided. Also provided is a method for treating disorders, diseases or conditions associated with pathological fibrotic states. The compounds useful in the present invention are homocysteine thiolactone and selected derivatives thereof.
Claims
1. A method of treating diseases and conditions associated with the abnormal deposition of collagen in a patient, which comprises administrating to the patient a therapeutically effective amount of a compound ofthe formula:
and salts thereof,
1 2 wherein R and R are the same or different, a hydrogen (-H), or an unsaturated or saturated aliphatic radical having from 1 to 50 carbon atoms, an unsaturated or saturated alicyclic radical having from 3 to 50 carbon atoms, or an aromatic radical having from
6 to 50 carbon atoms, wherein said carbons are substituted with a substituent selected from the group consisting of hydrogen (-H), chloro, fluoro, bromo, iodo, hydroxyl (-OH), alkoxyl (-OR'), acyl (-COR'), carboxyl (-CO2H), carboxyl esters (-CO2R'), amido (CONR/), amino (-NR"2), nitro (-NO2), nitroso (-NO), aza (-N=N-R'); diazonium (-N2 +) azido (-N3) hydrazino (-NR'-NR'2), cyano (-CN), isocyano (-NC), cyanato (NCO-), isocyanato (OCN-), thiocyanato (NCS-), isothiocyanato (SCN-), thioamido (-C(S)NR'2), thioether (-SR'), thiol (-SH), sulfoxide (-S(O)R'), sulfone (-S(O)2R'), sulfoximino (-S(O)(NR")R'), sulfonic acid (-SO3H), sulfonyl esters (-SO3R'), sulfmic acid (-SO2H), sulfinyl esters (-SO2R'), sulfenic acid (-SOH), sulfenyl esters (-SOR'), phospho (-OP(OXOR)2), phosphono (-P(O)(OR)2), urea (-NR'C(O)NR"2), and silyl (-SiR'3), and wherein R' a hydrogen (-H) or is an alkyl of 1 to 50 carbon atoms, an alkenyl or alkynyl of 2 to 50 carbon atoms, an aryl of 6 to 50 carbon atoms, or a heterocyclic of 0 to 50 carbon atoms, and R" is a hydrogen (-H) or an alkyl of 1 to 50 carbon atoms, an alkenyl or alkynyl of 2 to 50 carbon atoms, an aryl of 6 to 50 carbon atoms, or a heterocyclic of 0 to 50 carbon atoms, 3 5 4 wherein R may be a hydrogen (-H) or R -NH2, and wherein R may be a hydrogen (-H) or
R -NH , and wherein R and R are the same or different, an unsaturated or saturated aliphatic radical having two carbon atoms, an unsaturated or saturated branched or unbranched aliphatic radical having from 3 to 50 carbon atoms, an alicyclic or heterocyclic radical having from 0 to 50 carbon atoms, or an aromatic or heteroaromatic radical having from 1 to 50 carbon atoms, wherein said carbons are substituted with a substituent selected from the group consisting of hydrogen (-H), chloro, fluoro, bromo, iodo, hydroxyl (-OH), alkoxyl (-OR'), acyl (-COR'), carboxyl (-CO2H), carboxyl esters (-CO2R'), amido (CONR2"), amino (-N "^, nitro (-NO^, nitroso (-NO), aza (-N=N-R'), diazonium (-N2 +) azido (-N3) hydrazino (-NR'-NR'^, cyano (-CN), isocyano (-NC), cyanato (NCO-), isocyanato (OCN-), thiocyanato (NCS-), isothiocyanato (SCN-), thioamido (-C(S)NR'2), thioether (-SR'), thiol (-SH), sulfoxide (-S(O)R'), sulfone (-S(O)2R'), sulfoximino (-S(O)(NR")R'), sulfonic acid (-SO3H), sulfonyl esters (-SO3R'), sulfmic acid (-SO2H), sulfinyl esters (-SO2R'), sulfenic acid (-SOH), sulfenyl esters (-SOR'), phospho (-OP(O)(OR)2), phosphono (-P(O)(OR)2), urea (-NR'C(O)NR"2), and silyl (-SiR'3), and wherein R' is an alkyl of 1 to 50 carbon atoms, an alkenyl or alkynyl of 2 to 50 carbon atoms, an aryl of 6 to 50 carbon atoms, or a heterocyclic of 0 to 50 carbon atoms, and wherein R" is a hydrogen (-H) or an alkyl of 1 to 50 carbon atoms, an alkenyl or alkynyl of 2 to 50 carbon atoms, an aryl of 6 to 50 carbon atoms, or a heterocyclic of 0 to 50 carbon atoms, and wherein n is integer from 1 to 3, X is S or O, Y is S or O, with the provision that X or
Y must be S.
1 2 2. The method according to claim 1 wherein R or R is an an unsaturated or saturated aliphatic radical having from 1 to 25 carbon atoms, an unsaturated or saturated alicyclic radical having from 3 to 25 carbon atoms, or an aromatic radical having from 6 to 25 carbon atoms.
1 2
3. The method according to claim 1 wherein R or R is an an unsaturated or saturated aliphatic radical having from 1 to 15 carbon atoms, an unsaturated or saturated alicyclic radical having from 3 to 15 carbon atoms, or an aromatic radical having from 6 to 15 carbon atoms.
4. The method according to claim 1 wherein R' is an alkyl of 1 to 25 carbon atoms, an alkenyl or alkynyl of 2 to 25 carbon atoms, an aryl of 6 to 25 carbon atoms, or a heterocyclic of 0 to 25 carbon atoms.
5. The method according to claim 1 wherein R' is an alkyl of 1 to 15 carbon atoms, an alkenyl or alkynyl of 2 to 15 carbon atoms, an aryl of 6 to 15 carbon atoms, or a heterocyclic of 0 to 15 carbon atoms.
6. The method according to claim 1 wherein R" is an alkyl of 1 to 25 carbon atoms, an alkenyl or alkynyl of 2 to 25 carbon atoms, an aryl of 6 to 25 carbon atoms, or a heterocyclic of 0 to 25 carbon atoms.
7. The method according to claim 1 wherein R" is an alkyl of 1 to 15 carbon atoms, an alkenyl or alkynyl of 2 to 15 carbon atoms, an aryl of 6 to 15 carbon atoms, or a heterocyclic of 0 to 15 carbon atoms.
8. The method according to claim 1 wherein R and R are the same or different, an an unsaturated or saturated aliphatic radical having two carbon atoms, an unsaturated or saturated branched or unbranched aliphatic radical having from 3 to 25 carbon atoms, an alicyclic or heterocyclic radical having from 0 to 25 carbon atoms, or an aromatic having from 6 to 25 carbon atoms or heteroaromatic radical having from 1 to 25 carbon atoms.
9. The method according to claim 1 wherein R and R are the same or different, an an unsaturated or saturated aliphatic radical having two carbon atoms, an unsaturated or saturated branched or unbranched aliphatic radical having from 3 to 15 carbon atoms, an alicyclic or heterocyclic radical having from 0 to 15 carbon atoms, an aromatic radical having from 6 to 15 carbon atoms or heteroaromatic radical having from 1 to 15 carbon atoms.
10. The method according to claim 1 wherein the compound is selected from the group consisting of homocysteine thiolactone, glycylhomocysteine thiolactone, β-alanylhomocysteine thiolactone, γ-aminobutyrylhomocysteine thiolactone, lysylhomocysteine thiolactone, and ε-aminocaproylhomocysteine thiolactone, or mixtures thereof.
11. The method according to claim 1 wherein the disease or condition associated with the abnormal deposition of collagen is selected from the group consisting of atherosclerosis, arterial stenosis, restenosis, liver fibrosis, pulmonary fibrosis, surgical adhesions and burns.
12. A compound ofthe formula:
where m is an integer from 1 to 50, wherein R , R , R , R , R , and R are the same or different, a hydrogen (-H), or an unsaturated or saturated aliphatic radical having from 1 to 50 carbon atoms, an unsaturated or saturated alicyclic radical having from 3 to 50 carbon atoms, or an aromatic radical having from 6 to 50 carbon atoms, wherein said carbons are substituted with a substituent selected from the group consisting of hydrogen (-H), chloro, fluoro, bromo, iodo, hydroxyl (-OH), alkoxyl (-OR'), acyl (-COR'), carboxyl (-CO2H), carboxyl esters (-CO2R'), amido (CONR2"), amino (-NR"2), nitro (- NO ), nitroso (-NO), aza (-N=N-R'), diazonium (-N2 ) azido (-N3) hydrazino (-NR'-NR'2), cyano (-CN), isocyano (-NC), cyanato (NCO-), isocyanato (OCN-), thiocyanato (NCS-), isothiocyanato (SCN-), thioamido (-C(S)NR'2), thioether (-SR'), thiol (-SH), sulfoxide (-S(O)R'), sulfone (-S(O)2R'), sulfoximino (-S(O)(NR")R'), sulfonic acid (-SO3H), sulfonyl esters (-SO3R'), sulfinic acid (-SO2H), sulfinyl esters (-SO2R'), sulfenic acid (-SOH), sulfenyl esters (-SOR'), phospho (-OP(O)(OR)2), phosphono (-P(O)(OR)2), urea (-NR'C(O)NR"2), and silyl (-SiR'3), and wherein R' is hydrogen (-H) or an alkyl of 1 to 50 carbon atoms, an alkenyl or alkynyl of 2 to 50 carbon atoms, an aryl of 6 to 50 carbon atoms, or a heterocyclic of 0 to 50 carbon atoms, and R" is a hydrogen (-H) or an alkyl of 1 to 50 carbon atoms, an alkenyl or alkynyl of 2 to 50 carbon atoms, an aryl of 6 to 50 carbon atoms, or a heterocyclic of 0 to 50 carbon atoms, wherein n is integer from 1 to 3, X is S or O, Y is S or O, with the provision that X or Y must be S.
13. The compound according to claim 12 wherein m is an integer of from 1 to 25.
14. The compound according to claim 12 wherein m is an integer of from 1 to 5.
15. A method of treating diseases and conditions associated with the abnormal deposition of collagen in a patient, which comprises administering to the patient a therapeutically effective amount ofthe compound of claim 12.
16. The method according to claim 15 wherein the disease or condition associated with the abnormal deposition of collagen is selected from the group consisting of atherosclerosis, arterial stenosis, restenosis, liver fibrosis, pulmonary fibrosis, surgical adhesions and burns.
17. A compound of the formula."
wherein Z is hydrogen (-H), -(CH2)m NR'R",or -(CH2)m OR', wherein m is an integer from 0 to 50,
1 2 3 4 5 wherein R , R , R , R and R are the same or different, a hydrogen (-H) or an unsaturated or saturated aliphatic radical having from 1 to 50 carbon atoms, an unsaturated or saturated alicyclic radical having from 3 to 50 carbon atoms, or an aromatic radical having from 6 to 50 carbon atoms, wherein said carbons are substituted with a substituent selected from the group consisting of hydrogen (-H), chloro, fluoro, bromo, iodo, hydroxyl (-OH), alkoxyl (-OR'), acyl (-COR'), carboxyl (-CO2H), carboxyl esters (-CO2R'), amido (CONR2"), amino (-NR"2), nitro (-NO2), nitroso (-NO), aza (-N=N-R), diazonium (-N2 ) azido (-N3) hydrazino (-NR'-NR'2), cyano (-CN), isocyano (-NC), cyanato (NCO-), isocyanato (OCN-), thiocyanato (NCS-), isothiocyanato (SCN-), thioamido (-C(S)NR'2), thioether (-SR'), thiol (-SH), sulfoxide (-S(O)R'), sulfone (-S(O)2R'), sulfoximino (-S(O)(NR")R'), sulfonic acid (-SO3H), sulfonyl esters (-SO3R'), sulfinic acid (-SO2H), sulfinyl esters (-SO2R'), sulfenic acid (-SOH), sulfenyl esters (-SOR'), phospho (-OP(O)(OR)2), phosphono (-P(O)(OR)2), urea (-NR'C(O)NR"2), and silyl (-SiR'3), and wherein R' is hydrogen (-H) or an alkyl of 1 to 50 carbon atoms, an alkenyl or alkynyl of 2 to 50 carbon atoms, an aryl of 6 to 50 carbon atoms or a heterocyclic of 0 to 50 carbon atoms, and R" is a hydrogen (-H) or an alkyl of 1 to 50 carbon atoms, an alkenyl or alkynyl of 2 to 50 carbon atoms, an aryl of 6 to 50 carbon atoms or a heterocyclic of 0 to 50 carbon atoms, wherein n is an integer from 1 to 3, X is S or O, Y is S or O, with the provision that X or Y must be S, and with the further provision that when R , R , R , R and R are each hydrogen (-H), X is S and Y is O.
18. A method of treating diseases and conditions associated with the abnormal deposition of collagen in a patient, which comprises administering to the patient a therapeutically effective amount ofthe compound of claim 17.
19. The method according to claim 18 wherein the disease or condition associated with the abnormal deposition of collagen is selected from the group consisting of atherosclerosis, arterial stenosis, restenosis, liver fibrosis, pulmonary fibrosis, surgical adhesions and burns.
20. The method according to claim 18 wherein said compound is selected from the group consisting of glycylhomocysteine thiolactone, β-alanylhomocysteine thiolactone, γ-aminobutyrylhomocysteine thiolactone, lysylhomocysteine thiolactone, and ε-aminocaproylhomocysteine thiolactone, or mixtures thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU60497/96A AU6049796A (en) | 1995-06-07 | 1996-06-06 | Lysyloxidase inhibitors |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47306195A | 1995-06-07 | 1995-06-07 | |
| US08/473,061 | 1995-06-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1996040746A1 WO1996040746A1 (en) | 1996-12-19 |
| WO1996040746B1 true WO1996040746B1 (en) | 1997-03-06 |
Family
ID=23878032
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1996/009102 WO1996040746A1 (en) | 1995-06-07 | 1996-06-06 | Lysyloxidase inhibitors |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU6049796A (en) |
| WO (1) | WO1996040746A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9107935B2 (en) | 2009-01-06 | 2015-08-18 | Gilead Biologics, Inc. | Chemotherapeutic methods and compositions |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2782007B1 (en) * | 1998-08-05 | 2001-02-23 | Centre Nat Rech Scient | USE OF CALIX (N) ARENES FOR THE TREATMENT OF FIBROTIC DISEASES |
| GB9924195D0 (en) | 1999-10-13 | 1999-12-15 | Univ Nottingham | N-Acyl homoserine lactones for the treatment of cardiac tachyarrhythmias Ischaemic heart disease or congestive heart failure |
| US20030114410A1 (en) | 2000-08-08 | 2003-06-19 | Technion Research And Development Foundation Ltd. | Pharmaceutical compositions and methods useful for modulating angiogenesis and inhibiting metastasis and tumor fibrosis |
| GB0524991D0 (en) * | 2005-12-08 | 2006-01-18 | Ge Healthcare Ltd | Novel imaging agents for fibrosis |
| WO2009017833A2 (en) | 2007-08-02 | 2009-02-05 | Arresto Biosciences | Methods and compositions for treatment and diagnosis of fibrosis, tumor invasion, angiogenesis, and metastasis |
| KR20120063488A (en) | 2009-08-21 | 2012-06-15 | 길리아드 바이오로직스, 인크. | Catalytic domains from lysyl oxidase and loxl2 |
| WO2024002457A1 (en) * | 2022-06-27 | 2024-01-04 | Centre National De La Recherche Scientifique | Polyamides functionalized with chains containing thiol functions |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3037513C2 (en) * | 1980-10-03 | 1983-05-05 | Steffan, Wolfgang, 8425 Neustadt | Collagen wound dressing |
| IT1246766B (en) * | 1990-11-12 | 1994-11-26 | Medea Res Srl | - |
| US5326760A (en) * | 1992-06-29 | 1994-07-05 | Glaxo, Inc. | Aminobutanoic acid compounds having metalloprotease inhibiting properties |
| GB2276618A (en) * | 1993-03-29 | 1994-10-05 | Merck & Co Inc | Inhibitors of isoprenylated protein endoprotease |
-
1996
- 1996-06-06 WO PCT/US1996/009102 patent/WO1996040746A1/en active Application Filing
- 1996-06-06 AU AU60497/96A patent/AU6049796A/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9107935B2 (en) | 2009-01-06 | 2015-08-18 | Gilead Biologics, Inc. | Chemotherapeutic methods and compositions |
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