CN1376677A - [2-[5-(2-chloropyridineoxy)]methyl] azacyclobutane polypeptide derivative and its application - Google Patents
[2-[5-(2-chloropyridineoxy)]methyl] azacyclobutane polypeptide derivative and its application Download PDFInfo
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- CN1376677A CN1376677A CN 02113590 CN02113590A CN1376677A CN 1376677 A CN1376677 A CN 1376677A CN 02113590 CN02113590 CN 02113590 CN 02113590 A CN02113590 A CN 02113590A CN 1376677 A CN1376677 A CN 1376677A
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- methyl
- chloro
- oxygen base
- azacyclobutane
- pyridine oxygen
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- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 title claims abstract description 31
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 15
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 15
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 21
- 230000036592 analgesia Effects 0.000 claims description 7
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 229940024606 amino acid Drugs 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 2
- 229940124280 l-arginine Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 4
- 206010061218 Inflammation Diseases 0.000 abstract 1
- 230000000146 antalgic effect Effects 0.000 abstract 1
- 230000004054 inflammatory process Effects 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 15
- 230000036407 pain Effects 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- 238000005406 washing Methods 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 11
- 239000002904 solvent Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 6
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000000730 antalgic agent Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- 240000001307 Myosotis scorpioides Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 229920005654 Sephadex Polymers 0.000 description 3
- 239000012507 Sephadex™ Substances 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000001741 anti-phlogistic effect Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 238000010612 desalination reaction Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 229940127240 opiate Drugs 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 239000008896 Opium Substances 0.000 description 2
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical compound CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 229960001027 opium Drugs 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 102000003840 Opioid Receptors Human genes 0.000 description 1
- 108090000137 Opioid Receptors Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 150000001243 acetic acids Chemical class 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- PMPYSSMGWFNAAQ-UHFFFAOYSA-N dichloromethane;n,n-diethylethanamine Chemical compound ClCCl.CCN(CC)CC PMPYSSMGWFNAAQ-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000026781 habituation Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to [2-[5-(2-chloropyridineoxy)]methyl] azacyclobutane polypeptide derivative or pharmacologically receptible salt or its isomer, and its medical appication in preparing antalgic or inflammation relieving medicine.
Description
Affiliated technical field:
The present invention relates to a kind of [2-[5-(2-chloro-pyridine oxygen base)] methyl] isomer of azacyclobutane polypeptide derivative or pharmacy acceptable salt or this compound, with and in the application of medically making preparation analgesia or anti-inflammatory agent.
Technical background:
Seek stronger and more effective analgesic agent is medical community important research target always, a large amount of diseases and illness produce the pain as a disease or an illness part, removing this pain is the main aspect of improving or treating whole disease or illness, pain and possible alleviation thereof are also relevant with the mental status and the physical appearance of individual patient, and various analgesic agents are inequality to individuality or the patient's of colony action effect, need to seek new analgesic agent compound or medicine to satisfy different patients or crowd's demand.
Present stage, main analgesic agent had two classes, was divided into opiates and non-opium medicine, and opiates such as morphine act on opiate receptor in brain, thus the transmission of blocking-up pain signal in brain and spinal cord, and opiates such as morphine have easy abuse habituation.Non-opium such as NSAID (non-steroidal anti-inflammatory drug) are blocked the generation of prostaglandin(PG) usually to prevent the sensitization of nerve ending, and this kind sensitization helps pain signal to be passed in the brain, there are bigger side effect in prescription that great majority are commonly used or OTC (over-the-counter) NSAID (non-steroidal anti-inflammatory drug), and for example known NSAID (non-steroidal anti-inflammatory drug) such as acetylsalicylic acid cause stomach and duodenal stimulation and ulcer.
United States Patent (USP) (USP5629325) and Chinese patent (CN1245496A) have been described [2-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine and derivative thereof, these compounds have good analgesia and antiphlogistic effects.
Summary of the invention:
The invention provides [2-[5-(2-chloro-pyridine oxygen base)] methyl of a kind of being different from] the new compound of azetidine and derivative thereof, i.e. [2-[5-(2-chloro-pyridine oxygen base)] methyl] azacyclobutane polypeptide derivative or the medically acceptable salt or the isomer of this compound, with and in the application of medically making preparation analgesia or anti-inflammatory agent.
The invention is characterized in: a kind of new compound or its salt or its corresponding isomer with following structural (I) expression:
Wherein: X, Y can select in arbitrary amino acid,
Z can select in H, ethanoyl and arbitrary amino acid.
[2-[5-(2-chloro-pyridine oxygen base)] of the present invention methyl] isomer of azacyclobutane polypeptide derivative or medically acceptable salt and this compound is in the application of medically making preparation analgesia or anti-inflammatory agent.
[2-[5-(2-chloro-pyridine oxygen base)] of the present invention methyl] azetidine is configured as R.
X in the compound of the present invention is L-Arg.
Y in the compound of the present invention is Gly.
Z in the compound of the present invention is H or Gly or ethanoyl.
Compound of the present invention is an acetate at pharmacy acceptable salt.
Compound or its salt of the present invention or its corresponding isomer comprise at its compound that medically can represent:
A, glycyl-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine
B, ethanoyl-glycyl-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine
C, glycyl-glycyl-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine
The present invention is through proofs such as the scorching method tests in hot-plate analgesic test, mouse ear caused by dimethylbenzene xylene: the present invention medically can make analgesia, antiphlogistic use.
Embodiment:
Embodiment 1:
Glycyl-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine and synthetic
In reaction flask, add L-N successively
g-nitro-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine 4.15g (0.01 mole), N-tert-butoxy carbonyl-glycine 2.1g (0.012 mole), DIC 1.51g (0.012 mole), add methylene dichloride 50ml again, stirring reaction is 12 hours under the room temperature.Reaction solution with the washing of 1% hydrochloric acid soln, with the washing of 30ml saturated sodium carbonate solution, is used anhydrous sodium sulfate drying, the evaporated under reduced pressure solvent more again with the washing of 30ml saturated sodium carbonate solution.Residue dissolves with 10ml 50% trifluoracetic acid dichloromethane solution, and stirring reaction is 30 minutes under the room temperature, the evaporated under reduced pressure solvent.In residue, add 50ml vinyl acetic monomer and 1.5g palladium/carbon, fed hydrogen 12 hours under the stirring at room, add 50ml water after reaction is finished, stir after-filtration, the evaporated under reduced pressure solvent.Residue with sephadex G-25 desalination, is made elutriant with 5% acetum with the dissolving of 50ml5% acetum, collects component liquid, and lyophilize gets product 2.6g, yield 63.4%.Ultimate analysis: C:47.36%, H%:6.58, N%:18.41 (C
17H
26ClN
7O
3.2CH
3COOH calculated value: C:47.41%, H%:6.44, N%:18.43).Mass spectroscopy: m/e:412.9 (M+1), 434.9 (M+Na), [α]
D 20=+16.8 ° (c=1,1% aqueous acetic acid).
Embodiment 2:
Ethanoyl-glycyl-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine and synthetic
In reaction flask, add L-N successively
g-nitro-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine 4.15g (0.01 mole), N-tert-butoxy carbonyl-glycine 2.1g (0.012 mole), DIC 1.51g (0.012 mole), add methylene dichloride 50ml again, stirring reaction is 12 hours under the room temperature.Reaction solution with the washing of 1% hydrochloric acid soln, with the washing of 30ml saturated sodium carbonate solution, is used anhydrous sodium sulfate drying, the evaporated under reduced pressure solvent more again with the washing of 30ml saturated sodium carbonate solution.In residue, add 50ml vinyl acetic monomer and 1.5g palladium/carbon, fed hydrogen 12 hours under the stirring at room, add 50ml water after reaction is finished, stir after-filtration, the evaporated under reduced pressure solvent.Residue with sephadex G-25 desalination, is made elutriant with 5% acetum with the dissolving of 50ml 5% acetum, collects component liquid, and lyophilize gets product 2.9g, yield 63.9%.Ultimate analysis: C:49.12%, H%:6.45, N%:19.01 (C
19H
28ClN
7O
4.CH
3COOH calculated value: C:49.07%, H:6.28%, 19.07%).Mass spectroscopy: m/e:454.9 (M+1), 476.9 (M+Na), [α]
D 20=+17.00 (c=1,1% aqueous acetic acids).
Embodiment 3:
Glycyl-glycyl-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine and synthetic
In reaction flask, add L-N successively
g-nitro-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine 4.15g (0.01 mole), N-tert-butoxy carbonyl-glycine 2.1g (0.012 mole), DIC 1.51g (0.012 mole), add methylene dichloride 50ml again, stirring reaction is 12 hours under the room temperature.Reaction solution with the washing of 1% hydrochloric acid soln, with the washing of 30ml saturated sodium carbonate solution, is used anhydrous sodium sulfate drying, the evaporated under reduced pressure solvent more again with the washing of 30ml saturated sodium carbonate solution.Residue dissolves with 10ml 50% trifluoroacetic acid solution, and stirring reaction is 30 minutes under the room temperature, and the evaporated under reduced pressure solvent adds 10ml5% triethylamine dichloromethane solution in residue, and stirring reaction is 30 minutes under the room temperature, the evaporated under reduced pressure solvent.Add N-tert-butoxy carbonyl-glycine 2.1g (0.012 mole) in residue successively, DIC 1.51g (0.012 mole) adds methylene dichloride 50ml again, and stirring reaction is 12 hours under the room temperature.Reaction solution with the washing of 1% hydrochloric acid soln, with the washing of 30ml saturated sodium carbonate solution, is used anhydrous sodium sulfate drying, the evaporated under reduced pressure solvent more again with the washing of 30ml saturated sodium carbonate solution.In residue, add 50ml vinyl acetic monomer and 1.5g palladium/carbon, fed hydrogen 12 hours under the stirring at room, add 50ml water after reaction is finished, stir after-filtration, the evaporated under reduced pressure solvent.Residue with sephadex G-25 desalination, is made elutriant with 5% acetum with the dissolving of 50ml 5% acetum, collects component liquid, and lyophilize gets product 3.1g, yield 66.1%.Ultimate analysis: C:46.86%, H%:6.37, N%:18.95 (C
19H
29ClN
8O
4.2CH
3COOH calculated value: C:46.90, H:6.33, N:19.02).Mass spectroscopy: m/e:469.9 (M+1), 491.9 (M+Na), [α]
D 20=+14.5 ° (c=1,1% aqueous acetic acid).
Embodiment 4 hot-plate analgesic test
Choose body weight and be 40 of the female mices of 19-21 gram, be divided into 4 groups at random, 10 every group, adopt hot plate method to measure before the administration behind the threshold of pain, 1-3 group intravenous injection compd A, B and C, administration concentration is 1.0mg/ml, the administration volume is 0.5ml/20g; The 4th group with method injecting normal saline 0.5ml/20g.Respectively surveyed one time threshold of pain after the administration in 1.5 hours, 3 hours, 4.5 hours again.Calculate and respectively organize threshold of pain mean value, standard deviation and do the t check, relatively between each administration group and blank group there was no significant difference is arranged, the results are shown in following table:
Hot plate method is caused after the influence of pain and the two the comparing result group dosage animal drugs preceding threshold of pain administration threshold of pain (second) not other (mg/kg) several (second)
1.5 hours 3 hours 4.5 hours
(only) A 1.0 10 20.4 ± 2.7 46.8 ± 4.2
*48.2 ± 3.9
*46.9 ± 5.5
*B 1.0 10 20.7 ± 2.1 32.8 ± 3.9
*32.9 ± 4.3
*31.1 ± 3.1
*C 1.0 10 20.5 ± 2.8 35.4 ± 5.2
*36.6 ± 6.5
*36.0 ± 4.9
*Empty physiology salt
10 20.1 ± 2.4 21.1 ± 2.5 22.5 ± 2.7 21.7 ± 2.2 plain boiled waters are compared with the blank group
*P＜0.01
Test-results shows, compares with the blank group, and improve the threshold of pain of A, B, C group after the administration highly significant difference, and compd A, B, C all cause pain model to the mouse hot plate method obvious restraining effect.
The scorching method test of embodiment 5 mouse ear caused by dimethylbenzene xylene
Choose 40 of body weight 26-30g male mices, be divided into 4 groups at random, 10 every group.Dimethylbenzene is dripped in mouse right ear every mouse 30 μ l, left ear contrast.After causing scorching 1 hour, the 1st to the 3rd group of mouse difference abdominal injection compd A, B and C, administration concentration is 1.0mg/ml, the administration volume is 0.5ml/20g; The 4th group with method injecting normal saline 0.5ml/20g.
After the administration 2 hours, the dislocation of mouse cervical vertebra is caused death, cut two ears along the auricle baseline, be that the punch tool of 8mm is laid the garden auricle at the same position of left and right ear respectively with diameter, weigh, ask the poor of the left and right auricle weight of every mouse, as the swelling degree.The swelling degree is carried out statistical procedures, relatively between each administration group and blank group there was no significant difference is arranged, the results are shown in following table.
P-Xylol causes influence and the two comparing result group dosage number of animals swelling degree of mice ear
(mg/ml) (only) (ml) A 1.0 10 5.31 ± 0.925
*B 1.0 10 5.93 ± 0.813
*C 1.0 10 5.19 ± 0.848
*Blank physiological saline 10 8.72 ± 0.657 is compared with blank
*P＜0.01
Test-results shows, compares with the blank group, and A, B after the administration, C group all have significant differences, and the mice ear due to compd A, the equal p-Xylol of B, C presents tangible anti-inflammatory action.
The present invention is through proofs such as the scorching method tests in hot-plate analgesic test, mouse ear caused by dimethylbenzene xylene: the present invention has analgesia, antiphlogistic use.
Claims (8)
1, [2-[5-(2-chloro-pyridine oxygen base)] methyl] azacyclobutane polypeptide derivative and application thereof, it is characterized in that: a kind of new compound or its salt or its corresponding isomer with following structural (I) expression:
Wherein: X, Y can select in arbitrary amino acid,
Z can select in H, ethanoyl and arbitrary amino acid.
2, [2-[5-(2-chloro-pyridine oxygen base)] according to claim 1 methyl] azacyclobutane polypeptide derivative and application thereof, it is characterized in that: described [2-[5-(2-chloro-pyridine oxygen base)] methyl] isomer of azacyclobutane polypeptide derivative or medically acceptable salt and this compound does the application of preparation analgesia or anti-inflammatory agent in medical science.
3, [2-[5-(2-chloro-pyridine oxygen base)] according to claim 1 and 2 methyl] azacyclobutane polypeptide derivative and application thereof, it is characterized in that: [2-[5-(2-chloro-pyridine oxygen base)] of the present invention methyl] azetidine is configured as R.
4, [2-[5-(2-chloro-pyridine oxygen base)] according to claim 1 and 2 methyl] azacyclobutane polypeptide derivative and application thereof, it is characterized in that: the X in the described compound is L-Arg.
5, [2-[5-(2-chloro-pyridine oxygen base)] according to claim 1 and 2 methyl] azacyclobutane polypeptide derivative and application thereof, it is characterized in that: the Y in the described compound is Gly.
6, [2-[5-(2-chloro-pyridine oxygen base)] according to claim 1 and 2 methyl] azacyclobutane polypeptide derivative and application thereof, it is characterized in that: the Z in the described compound is H or Gly or ethanoyl.
7, [2-[5-(2-chloro-pyridine oxygen base)] according to claim 1 and 2 methyl] azacyclobutane polypeptide derivative and application thereof, it is characterized in that: compound of the present invention is an acetate at pharmacy acceptable salt.
8, [2-[5-(2-chloro-pyridine oxygen base)] according to claim 1 and 2 methyl] azacyclobutane polypeptide derivative and application thereof, it is characterized in that: described compound or its salt or its corresponding isomer comprise at its compound that medically can represent:
A, glycyl-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine
Or B, ethanoyl-glycyl-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine
Or C, glycyl-glycyl-o-dime thyl phosphoroamidothioate-[2R-[5-(2-chloro-pyridine oxygen base)] methyl] azetidine
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02113590 CN1208342C (en) | 2002-04-10 | 2002-04-10 | [2-[5-(2-chloropyridineoxy)]methyl] azacyclobutane polypeptide derivative and its application |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02113590 CN1208342C (en) | 2002-04-10 | 2002-04-10 | [2-[5-(2-chloropyridineoxy)]methyl] azacyclobutane polypeptide derivative and its application |
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| Publication Number | Publication Date |
|---|---|
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| CN1208342C CN1208342C (en) | 2005-06-29 |
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| Country | Link |
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