We claim:
1. A compound of the formula I
4
wherein R1 is selected from
a (C3-C10) linear or branched aklyl group which is unsubstituted, monosubstituted, disubstituted, or trisubstituted with a group selected from
OR3 where R3 is selected from hydrogen and a (C1-C4)-alkyl;
NR4R5 where R4 and R5 are independently selected from hydrogen and a (C1-C4)-alkyl;
a halogen;
O; and
COOH;; and
a (C3-C10) linear or branched alkenyl group which is unsubstituted, monosubstituted, disubstituted, or trisubstituted with a group selected from
OR3 where R3 is selected from hydrogen and a (C1-C4)-alkyl;
NR4R5 where R4 and R5 are independently selected from hydrogen and a (C1-C4)-alkyl;
a halogen;
O; and
COOH;;
R2 is selected from
a (C3-C10) linear or branched aklyl group which is unsubstituted, monosubstituted, disubstituted, or trisubstituted with a group selected from
OR3 where R3 is selected from hydrogen and a (C1-C4)-alkyl;
NR4R5, where R4 and R5 are independently selected from hydrogen and a (C1-C4)-alkyl;
a halogen;
O; and
COOH; and
a (C3-C10) linear or branched alkenyl group which is unsubstituted or monosubstituted, disubstituted, or trisubstituted with a group selected from
OR3 where R3 is selected from hydrogen and a (C1-C4)-alkyl;
NR4R5, where R4 and R5 are independently selected from hydrogen and a (C1-C4)-alkyl;
a halogen;
O; and
COOH; and
Z is a hexose which is in pyranoid form via a C-glycosidic bond, or a stereoiosmer or physiologically tolerable salt thereof.
2. A compound of the formula I as claimed in claim 1, wherein
R1 is nonadienyl,
R2 is nonadienyl and
Z is selected from D()-glucose, D()-mannose, D()-galactose, and D()-talose.
3. The compound stromemycin having the following structure
5
4. A process for a preparing a compound of claim 3 comprising
a) culturing a microorganism selected from DSM12038, mutants of DSM12038, and variants of DSM12038 in an aqueous nutrient medium; and
b) isolating stromemycin.
5. A process according to claim 4 further comprising purifying stromemycin.
6. A process for preparing a compound of formula I of claim 1 comprising reductively hydrogenating the compound of claim 3 under sufficient conditions wherein R1 and R2 of formula I are together C9-alkyls to form a compound of formula I.
7. A process for preparing a compound of formula I of claim 2 comprising ozonolysis of the compound of claim 3 under sufficient conditions wherein R1 and R2 are together selected from CH2CH2CH2OH, CH2CH2CHO, and CH2CH2COOH to form a compound of formula I.
8. A process for preparing a compound of formula I of claim 1 comprising ozonolysis of the compound of claim 3 under sufficient conditions wherein R1 and R2 are together selected from CH2CH2CH2OH, CH2CH2CHO, and CH2CH2COOH to form a compound of formula I.
9. A process for preparing a compound of formula I of claim 2 comprising ozonolysis of the compound of claim 3 under sufficient conditions wherein R1 and R2 are together selected from CH2CH2CH2OH, CH2CH2CHO, and CH2CH2COOH to form a compound of formula I.
10. A process according to claim 8 further comprising treating the compound of formula I with at least one alkylidenephosphorane under sufficient conditions to extend R1 and R2 by 1, 2, 3, 4, 5, 6, or 7 methylene groups wherein the methylene groups are bonded to least one functional group selected from hydroxyl, ether, fluorine, chlorine, bromine, iodine, an amino group, and methyl.
11. A process according to claim 9 further comprising treating the compound of formula I with at least one alkylidenephosphorane under sufficient conditions to extend R1 and R2 by 1, 2, 3, 4, 5, 6, or 7 methylene groups wherein the methylene groups are bonded to least one functional group selected from hydroxyl, ether, fluorine, chlorine, bromine, iodine, an amino group, and methyl.
12. A process according to claim 8 further comprising separating the compound of formula I into component enantiomers by treating with at least one reagent selected from enantiomerically pure acids and enantiomerically pure bases.
13. A process according to claim 8 further comprising separating the compound of formula I into component enantiomers by chromatography on chiral stationary phases.
14. A process according to claim 8 further comprising derivatizing the compound of formula I with chiral entantiomerically pure compounds selected from at least one amino acid to form diastereomers with chiral auxiliary groups; separating the diaestereomers under sufficient conditions; and removing the chiral auxiliary groups under sufficient conditions.
15. A process according to claim 5 further comprising treating stromemycin with an acid or base to form a physiologically acceptable salt.
16. A process according to claims 6, 7, 8, 9, 10, 11, 12, 13, or 14 further comprising treating the compound of formula I with an acid or base to form a physiologically acceptable salt.
17. A pharmaceutical composition according to claim 1 comprising a compound of formula I and at least one excipient.
18. A pharmaceutical composition according to claim 2 comprising a compound of formula I and at least one excipient.
19. A pharmaceutical composition comprising a compound of claim 3 and at least one excipient.
20. A pharmaceutical composition according to claim 17 further comprising an active ingredient other than a compound of formula I, and a pharmaceutically suitable and physiologically tolerable vehicle.
21. A method of treatment or prophylaxis of conditions involving increased activity of matrix-degrading metalloproteinases comprising administering a pharmaceutically effective amount of a compound of formula I to an animal or human host in need thereof.
22. A method of treatment or prophylaxis of conditions involving increased activity of matrix-degrading metalloproteinases comprising administering a pharmaceutically effective amount of stromemycin to an animal or human host in need thereof.
23. A method for treating tissue disorders selected from osteoarthrosis, spondylosis, chondrolysis after joint trauma or relatively long joint immobilization after meniscus or patella injuries or tearing of the ligaments, collagenoses, periodontal conditions, wound healing disorders, chronic conditions of the locomotory apparatus, inflammatorily, immunologically or metabolically caused acute and chronic arthritis, arthropathy, myalgia, disorders of the bone metabolism, ulceration, atherosclerosis, stenoses, inflammation, carcinomatous disorders, formation of tumor metasases, cachexia, anorexia, and septic shock comprising administering a pharmaceutically acceptable amount of a compound of formula I to an animal or human host in need thereof.
24. A method for treating tissue disorders selected from osteoarthrosis, spondylosis, chondrolysis after joint trauma or relatively long joint immobilization after meniscus or patella injuries or tearing of the ligaments, collagenoses, periodontal conditions, wound healing disorders, chronic conditions of the locomotory apparatus, inflammatorily, immunologically or metabolically caused acute and chronic arthritis, arthropathy, myalgia, disorders of the bone metabolism, ulceration, atherosclerosis, stenoses, inflammation, carcinomatous disorders, formation of tumor metasases, cachexia, anorexia, and septic shock comprising administering a pharmaceutically acceptable amount of stromemycin to an animal or human host in need thereof.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for operating a magnetic resonance system, comprising the steps of:
prior to acquiring diagnostic magnetic resonance data from an examination volume of a subject with a data acquisition pulse sequence including a plurality of RF pulses emitted from an RF antenna, individually radiating said plurality of RF pulses into the examination volume and determining an effective volume within said examination volume for each of said RF pulses, and, for each of said RF pulses, measuring a B1 field distribution produced in the effective volume for that RF pulse; and
acquiring said diagnostic magnetic resonance data by applying said data acquisition pulse sequence to said subject and, in said data acquisition pulse sequence, optimizing each of said RF pulses by electronic shimming to homogenize the B1 field distribution produced thereby in the effective volume of each shimmed RF pulse; and
reconstructing an image of the subject from the acquired magnetic resonance diagnostic data.
2. A method as claimed in claim 1 wherein measuring said B1 field distribution has measurement parameters associated therewith, and wherein applying said pulse sequence to said subject has control parameters associated therewith for emitting the respective RF pulses in said pulse sequence, and wherein the step of determining said effective volume comprises automatically determining said effective volume for each of said RF pulses dependent on at least one of said measurement parameters and the respective control parameters for that RF pulse.
3. A method as claimed in claim 1 wherein at least one of said RF pulses is a slice-selective RF pulse, and comprising, for said slice-selective RF pulse, determining said effective volume to substantially correspond to the selected slice produced by said slice-selective RF pulse.
4. A method as claimed in claim 1 wherein said pulse sequence is designed to obtain said magnetic resonance data from a plurality of slices in said examination volume, and includes a preparation RF pulse, and comprising determining the effective volume for said preparation RF pulse based on a set union of said plurality of slices.
5. A method as claimed in claim 1 wherein said pulse sequence includes a regional preparation RF pulse effective in a region of the examination subject, and comprising determining said effective volume as being substantially equal to said region.
6. A method as claimed in claim 1 comprising, for each of said RF pulses, determining one optimization volume within the effective volume for that RF pulse, dependent on a predetermined region of interest, and optimizing each of said RF pulses to homogenize said B, field within said optimization volume thereof.
7. A method as claimed in claim 1 wherein said radio frequency antenna comprises a plurality of antenna elements, and comprising emitting each of said RF pulses from said antenna elements by activating the respective antenna elements with a respective phase and a respective amplitude, and comprising optimizing said RF pulses by selectively adjusting the respective phase and the respective amplitude used to emit the respective RF pulse, to optimize said B1 field in said effective volume.
8. A method as claimed in claim 7 wherein the step of determining said B1 field distribution comprises separately determining a B1 field distribution for each of said antenna elements.
9. A method as claimed in claim 1 comprising, upon optimization of each of said RF pulses, storing optimized control parameters associated with the emission of said RF pulses that produce the optimization of the respective RF pulses, and operating said RF antenna with the stored control parameters, when applying said pulse sequence to said subject, to emit said optimized RF pulses.
10. A magnetic resonance system comprising:
a magnetic resonance scanner configured to interact with an examination subject, said magnetic resonance scanner being operable to acquire diagnostic magnetic resonance data from the subject with a data acquisition pulse sequence that includes a plurality of RF pulses, said magnetic resonance scanner including an RF antenna that emits said RF pulses in an examination volume of the subject, and a field distribution measuring unit;
a control unit connected to said magnetic resonance scanner that operates said RF antenna, prior to acquiring said diagnostic magnetic resonance data, to individually radiate said plurality of RF pulses into said examination volume and that operates said measuring unit in order to measure a respective B1 field distribution produced in the examination volume by each of said RF pulses, said control unit determining an effective volume within said examination volume for each of said RF pulses, and that operates said magnetic resonance scanner with said data acquisition pulse sequence in order to acquire said diagnostic magnetic resonance data from said examination volume of the subject, said control unit, in said data acquisition pulse sequence, optimizing each of said RF pulses by electronic shimming in order to homogenize the B1 field distribution produced thereby in the effective volume of each shimmed RF pulse; and
a computer supplied with the acquired diagnostic magnetic resonance data that reconstructs an image of the subject from said diagnostic magnetic resonance data.
11. A magnetic resonance system as claimed in claim 10 comprising a user interface allowing a user to enter a designation of a region of interest within said examination volume, and wherein said control device, for each of said RF pulses, determines an optimization volume for that RF pulse within said effective volume thereof, dependent on said region of interest, and optimizes said RF pulses to homogenize said B1 field distribution within said optimization volume.
12. A magnetic resonance system as claimed in claim 10 wherein said radio frequency antenna comprises a plurality of antenna elements, and wherein said control unit operates the respective antenna elements with respective phases and respective amplitudes for each of said RF pulses to optimize said RF pulses to homogenize said B1 field distribution in the respective effective volumes thereof.
13. A computer-readable medium encoded with a data structure and being loadable into a programmable control device of a magnetic resonance system, said magnetic resonance system having an RF antenna that emits RF pulses each having a B1 field distribution associated therewith, said computer program causing said control unit to operate said magnetic resonance scanner to:
prior to acquiring diagnostic magnetic resonance data from an examination volume of a subject with a data acquisition pulse sequence including a plurality of said RF pulses, individually radiate said plurality of RF pulses into the examination volume, and determine an effective volume within said examination volume for each of said RF pulses, and, for each of said RF pulses, measure the B1 field distribution produced in the effective volume for that RF pulse; and
apply said data acquisition pulse sequence to said subject in order to acquire said diagnostic magnetic resonance data from said examination volume and, in said data acquisition pulse sequence, optimize each of said RF pulses by electronic shimming in order to homogenize the B1 field distribution produced thereby in the effective volume of each shimmed RF pulse, and to store the acquired diagnostic magnetic resonance data in order to allow an image of the subject to be reconstructed therefrom.