US4537859A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for preparing 3-hydroxy-ML-236B derivatives known as M-4 and M-4'
Assignee: Sankyo Co Ltd
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Filing: 1982-11-18
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Granted: 1985-08-27
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Expires: 2002-11-18
Abstract
Abstract Compounds of formula (I): ##STR1## (wherein OH represents OH or OH), that is to say M-4 carboxylic acid and M-4' carboxylic acid, as well as pharmaceutically acceptable salts and esters thereof and the corresponding ring-closed lactones may be prepared by contacting an ML-236B compound with a microorganism of the genus Nocardia or a cell-free, enzyme-containing extract thereof and then, if necessary, subjecting the resulting product to one or more of the following reactions: hydrolysis, salification, esterification and lactonisation. The resulting M-4 and M-4' derivatives have the ability to inhibit the biosynthesis of cholesterol and are therefore of value in the therapy and/or prophylaxis of hyperlipaemia and arteriosclerosis.
Inventors
- 👤 Akira Terahara
- 👤 Minoru Tanaka
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:15
CPC Classifications
C; C12; C12P; C12P7/00; C12P7/40; C12P7/42; A; A61; A61P; A61P9/00; A61P9/10; C12N; C12N1/00; C12N1/20; C12N1/205; C12P17/00; C12P17/02; C12P17/06; C12P7/62; C12R; C12R2001/00; C12R2001/01; C12R2001/365; Y; Y10; Y10S; Y10S435/00; Y10S435/8215; Y10S435/822; Y10S435/872
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
74 words
A process for preparing a compound of formula (I): ##STR7## wherein OH represents OH or OH, pharmaceutically acceptable salts and esters thereof and the corresponding ring-closed lactones, which process comprises contacting an ML-236B compound selected from the group consisting of ML-236B carboxyic acid, salts and esters thereof and the corresponding ML-236B lactone with a hydroxylation enzyme produced by a microorganism of the genus Nocardia to produce the hydroxylated ML-236B compound of the formula (I).
Claim 2
Dependent Claim
74 words
A process for preparing a compound of formula (I): ##STR7## wherein OH represents OH or OH, pharmaceutically acceptable salts and esters thereof and the corresponding ring-closed lactones, which process comprises contacting an ML-236B compound selected from the group consisting of ML-236B carboxyic acid, salts and esters thereof and the corresponding ML-236B lactone with a hydroxylation enzyme produced by a microorganism of the genus Nocardia to produce the hydroxylated ML-236B compound of the formula (I).
Claim 3
Dependent Claim
31 words
A process as claimed in claim 1, wherein said ML-236B compound is contacted with said enzyme by cultivating a microorganism of the genus Nocardia in a medium containing said ML-236B compound.
Claim 4
Dependent Claim
28 words
A process as claimed in claim 2, wherein said microorganism is a species selected from the group consisting of Nocardia autotrophica, Nocardia asteroides, Nocardia farcinica and Nocardia coeliaca.
Claim 5
Dependent Claim
50 words
A process as claimed in claim 2, wherein said microorganism is selected from the group consisting of: Nocardia autotrophica FERM P-6181 Nocardia autotrophica subsp. canberrica FERM P-6182 Nocardia autotrophica subsp. amethystina FERM P-6183 Nocardia autotrophica IFO 12743 Nocardia asteroides IFO 3424 Nocardia farcinica ATCC 3318 and Nocardia coeliaca ATCC 17040.
Claim 6
Dependent Claim
41 words
A process as claimed in claim 2, wherein said microorganism is selected from the group consisting of: Nocardia autotrophica FERM P-6181 Nocardia autotrophica subsp. canberrica FERM P-6182 Nocardia autotrophica subsp. amethystina FERM P-6183 Nocardia autotrophica IFO 12743 Nocardia asteroides IFO 3424.
Claim 7
Dependent Claim
34 words
A process as claimed in claim 2, wherein said microorganism is selected from the group consisting of: Nocardia autotrophica FERM P-6181 Nocardia autotrophica subsp. canberrica FERM P-6182 and Nocardia autotrophica subsp. amethystina FERM P-6183.
Claim 8
Dependent Claim
31 words
A process as claimed in claim 1, wherein said ML-236B compound is contacted with said enzyme by contacting whole cells of a microorganism of the genus Nocardia with said ML-236B compound.
Claim 9
Dependent Claim
28 words
A process as claimed in claim 7, wherein said microorganism is a species selected from the group consisting of Nocardia autotrophica, Nocardia asteroides, Nocardia farcinica and Nocardia coeliaca.
Claim 10
Dependent Claim
50 words
A process as claimed in claim 7, wherein said microorganism is selected from the group consisting of: Nocardia autotrophica FERM P-6181 Nocardia autotropica subsp. canberrica FERM P-6182 Nocardia autotrophica subsp. amethystina FERM P-6183 Nocardia autotrophica IFO 12743 Nocardia asteroides IFO 3424 Nocardia farcinica ATCC 3318 and Nocardia coeliaca ATCC 17040.
Claim 11
Dependent Claim
41 words
A process as claimed in claim 7, wherein said microorganism is selected from the group consisting of: Nocardia autotrophica FERM P-6181 Nocardia autotrophica subsp. canberrica FERM P-6182 Nocardia autotrophica subsp. amethystina FERM P-6183 Nocardia autotrophica IFO 12743 Nocardia asteroides IFO 3424.
Claim 12
Dependent Claim
34 words
A process as claimed in claim 7, wherein said microorganism is selected from the group consisting of: Nocardia autotrophica FERM P-6181 Nocardia autotrophica subsp. canberrica FERM P-6182 and Nocardia autotrophica subsp. amethystina FERM P-6183.
Claim 13
Dependent Claim
32 words
A process as claimed in claim 1, wherein said ML-236B compound is contacted with said enzyme by contacting said compound with a cell-free, enzyme-containing extract of a microorganism of the genus Nocardia.
Claim 14
Dependent Claim
28 words
A process as claimed in claim 12, wherein said microorganism is a species selected from the group consisting of Nocardia autotrophica, Nocardia asteroides, Nocardia farcinica and Nocardia coeliaca.
Claim 15
Dependent Claim
50 words
A process as claimed in claim 12, wherein said microorganism is selected from the group consisting of: Nocardia autotrophica FERM P-6181 Nocardia autotrophica subsp. canberrica FERM P-6182 Nocardia autotrophica subsp. amethystina FERM P-6183 Nocardia autotrophica IFO 12743 Nocardia asteroides IFO 3424 Nocardia farcinica ATCC 3318 and Nocardia coeliaca ATCC 17040.
Claim 16
Dependent Claim
41 words
A process as claimed in claim 12, wherein said microorganism is selected from the group consisting of: Nocardia autotrophica FERM P-6181 Nocardia autotrophica subsp. canberrica FERM P-6182 Nocardia autotrophica subsp. amethystina FERM P-6183 Nocardia autotrophica IFO 12743 Nocardia asteroides IFO 3424.
Claim 17
Dependent Claim
34 words
A process as claimed in claim 12, wherein said microorganism is selected from the group consisting of: Nocardia autotrophica FERM P-6181 Nocardia autotrophica subsp. canberrica FERM P-6182 and Nocardia autotrophica subsp. amethystina FERM P-6183.
Claim 18
Dependent Claim
34 words
A process as claimed in claim 1, wherein said microorganism is selected from the group consisting of Nocardia autotrophica FERM P-6181, Nocardia autotrophica subsp. canberrica FERM P-6182 and Nocardia autotrophica subsp. amethystina FERM P-6183.
Claim 19
Dependent Claim
19 words
A process as claimed in claim 1, wherein there is produced an M-4 compound in which OH represents OH.
Claim 20
Dependent Claim
19 words
A process as claimed in claim 17, wherein there is produced an M-4 compound in which OH represents OH.
Claim 21
Dependent Claim
19 words
A process as claimed in claim 1, wherein there is produced an M-4' compound in which OH represents OH.
Claim 22
Dependent Claim
19 words
A process as claimed in claim 17, wherein there is produced an M-4' compound in which OH represents OH.
Claim 23
Dependent Claim
20 words
A process as claimed in claim 1, wherein there is produced the sodium salt of said compound of formula (I).
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-08-26 | 1989-02-25 | 1989-08-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-08-26 | 1993-02-25 | 1993-08-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-08-26 | 1997-02-25 | 1997-08-27 | $7700.00 | Window Closed / Lapsed |