Compounds that release hydrogen sulfide and uses thereof 机翻标题: 暂无翻译,请尝试点击翻译按钮。

源语言标题
(JP2017186362) 硫化​水素​を​放出​する​化合​物​及び​その​使用
公开号/公开日
JP2017186362 A 2017-10-12 [JP2017186362] / 2017-10-12
申请号/申请日
2017JP-0116884 / 2017-06-14
发明人
WOOD MARK;MATTHEW WHITEMAN;ALEXIS PERRY;
申请人
UNIVERSITY OF EXETER;
主分类号
IPC分类号
A01N-057/34A01P-013/00A01P-021/00A61K-031/66A61K-031/67A61P-001/04A61P-001/16A61P-003/00A61P-003/04A61P-003/06A61P-003/10A61P-007/08A61P-009/00A61P-009/10A61P-009/12A61P-011/00A61P-011/06A61P-013/12A61P-019/02A61P-019/10A61P-021/02A61P-025/00A61P-025/14A61P-025/16A61P-025/28A61P-027/02A61P-029/00A61P-031/04A61P-035/00A61P-039/02C07F-009/54C07F-009/6553
摘要
(JP2017186362) PROBLEM TO BE SOLVED: To provide uses of compounds comprising a mitochondrial targeting group linked to a group that releases hydrogen sulfide or a pharmaceutically acceptable salt thereof in surgical or therapeutic treatment of humans or animals, and uses of the compounds in the treatment of plants as well as certain forms of the compounds.SOLUTION: According to the invention, a compound comprising a mitochondrial targeting group linked to a group that releases in vivo hydrogen sulfide can selectively and slowly release HS to or around the mitochondria in a cell.  The compound can be used to provide excellent bioavailability of hydrogen sulfide in cells.SELECTED DRAWING: Figure 1
机翻摘要
暂无翻译结果,您可以尝试点击头部的翻译按钮。
地址
代理人
代理机构
;
优先权号
2011GB-0017095 2011-09-30
主权利要求
(JP2017186362) 1. Linked to a hydrogen sulfide release group and a compound containing a mitochondrial targeting (mitochondrial targeting group) group, or a pharmaceutically acceptable salt thereof, surgical or therapeutic use in the treatment of the human or animal. 2. Wherein the mitochondria-targeting group, phosphonium, arsonium cation, ammonium cation, furupurichin, MKT-077, pyridinium ceramide, quinolium, liposomal cation, sorbitol guanidine, cyclic guanidine and a lipophilic cation is selected from a rhodamine, a compound according to claim 1. 3. Wherein said hydrogen sulfide release group, thiocarbamoyl group, thioxo group or a 5 - - dithiol -3 - - 5H-1, 2, -4 - - dithiol - 5 - - yl - 5H-1, 2 thioxo group, an oxo group or a 5 - - dithiol -3 - - 5H-1, 2, -4 - - dithiol - 5 - - oxo - 5H-1, 2-yl group, -3 - - dithiol - 5 - - yl-hydroxyimino - 5H-1, 2 group, hydroxyimino group or a 5 - - dithiol -4 - - 5H-1, 2, phosphino dithioates hosufinojichio acid group or, wherein any of the claims 1 or 2 compound 1.  4. Wherein said compound is represented by the following formula: MTG-L-S [in the formula, the S,  (xLxWx, X S is, or O N FixedDocument_add OH represents; R1 、R2 R and3 may each independently be a hydrogen, C1-12 alkyl, C1-12 C alkoxy or6-10 represents aryl, each C1-12 alkyl, C1-12 C alkoxy or6-10 aryl group, a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -1 alkoxy substituted with one or more substituents selected from the radical group substituted, or may be substituted) to release hydrogen sulfide selected from a group; L can, or a direct bond or a linker, the linker, and a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -one or more substituent selected from an alkoxy group substituted by a 1, or a substituted C1-20 alkylene and, in this case, the alkylene chain of 1-10 carbon atoms or 0, C6-10 arylene, -0 -, -S -, - NR4 -、-C (0) NR4 -、-NR4 C (0) -、-C(O) -、-OC(O) -、-C (0) 0-spacer moiety is selected from a portion of which is substituted by, the R4 C hydrogen or1-12 alkyl, the C6-10 arylene moieties, and a halogen atom, hydroxy, C1-12 C alkyl and1-12 1, 2, 3 alkoxy group selected from a substituted group substituted by 4 or, that is not replaced with or; MTG is overdub, mitochondria-targeting group] a compound represented by the, or a pharmaceutically acceptable salt, of any one of claims 1-3 compound.  5. L is wherein, according to the following expression: -L ' -Y FixedDocument_add Z- [in the formula, L'is, a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -alkoxy groups selected from among groups 1 one or more substituent groups has been substituted, or is not substituted with a branched or straight chain C1-20 alkylene group; Y may, - and a direct bond, - OC (O) - or -C (0) 0 - represent; Z has, directly bonded, or a halogen atom, hydroxy, C1-12 alkyl and C1-12 alkoxy groups selected from among groups 1, 2, 3 or 4 three substituents on the substituted, not substituted or is a phenylene group] is a linker represented by, the use of a compound according to claim 4.  6. L'is, represented by the following formula - (CH2)n -[wherein n is 1-19 integer] represented by straight-chain alkylene group, -Y FixedDocument_add Z- moiety, represented by the following formula  represented, S is,  selected from, the group Ph GPIIbffla mitochondria and MTG3 Pin, the use of a compound according to claim 5. 7. By the in vivo release of hydrogen sulfide is expected to be reduced in the treatment or prevention of a disease or disorder is used, the use of any one of claims 1-6 compound. 8. Wherein the disease or disorder is: an inflammatory joint disease (i), rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, ulcerative colitis, inflammatory bowel disease, including atherosclerosis or hepatitis, a chronic inflammatory disease or disorder; (ii) endotoxic shock, septic shock, or hemorrhagic shock comprising, an acute inflammatory disease or disorder; (iii) osteoarthritis, and osteoporosis, or type II I or diseases or disorders associated with diabetes; (iv) vascular complication of obesity, diabetes, metabolic syndrome, aging of the natural, high blood pressure, myocardial infarction, ischemia, ischemic heart disease, reperfusion injury, hypoxia, ischemia-reperfusion injury, hypoxia-reperfusion injury, retinopathy or neuropathy, a disease or disorder is related to the magnitude of the vasculopathy; (v) Alzheimer's disease, amyotrophic lateral sclerosis, motor neuron disease, Parkinson's disease, hanchindon Trombiculiasis, tauopathies (tauopathy), extrapyramidal and movement disorders, or, ataxia telangiectasia, corticobasal degeneration or neuronal disorder including progressive supranuclear, astrocyte or a glial cell killing Remarkably neuronal disease, a neurodegenerative disease; Trombiculiasis (vi) the magnitude of the blood vessel, or vascular dementia comprising, age-related disease or disorder; (vii) renal or hepatic disease or disorder associated with organ failure comprising; (viii) ischemia-reperfusion injury, cardiovascular disease including hyperlipidemia and hypercholesterolemia, chronic and/or acute kidney injury associated with a disease or disorder; (ix) the cancer or a cell containing the disease or disorder associated with abnormal proliferation; in, a compound according to claim 7. 9. Claims 7 or 8 Viroloay suffering from a disease or disorder, or a method of treating a patient is likely to be, in a compound of any one of claims 1-6 comprising administering to a patient, the method. 10. For promoting the growth of the plants in the treatment of the plants, a herbicidally in the processing of the plant, or plant pore closure to prevent or reduce, or cause an opening of the pores, to release hydrogen sulfide mitochondrial targeting group linked group-containing compound, or a pharmaceutically acceptable salt thereof. 11. Wherein the mitochondria-targeting group, phosphonium, arsonium cation, ammonium cation, furupurichin, MKT-077, pyridinium ceramide, quinolium, liposomal cation, sorbitol guanidine, cyclic guanidine is selected from a rhodamine and a lipophilic cation, for use according to claim 10. 12. Wherein the release group is hydrogen sulfide, chichi oh carbamoyl group, a dithiol group or 5 - - thioxo -3 - - 5H-1, 2, thioxo group or a 5 - - dithiol -4 - - 5H-1, 2, -3 - - dithiol - 5 - - oxo - 5H-1, 2-yl group, -4 - - dithiol - 5 - - oxo - 5H-1, 2-yl group, -3 - - dithiol - 5 - - yl-hydroxyimino - 5H-1, 2 group, hydroxyimino group or a 5 - - dithiol -4 - - 5H-1, 2, phosphino dithioates hosufinojichio containing an acid group or, wherein the use of any of claims 10 or 11 1.  13. The compound of, MTG-L-S [in the formula, the S,  (xLxWx, X S is, or O N FixedDocument_add OH represents; R1 、R2 R and3 may each independently be hydrogen, C1-12 alkyl, C1-12 C alkoxy or6-10 represents aryl, each C1-12 alkyl, C1-12 C alkoxy or6-10 aryl group, a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -alkoxy substituted one or more substituent groups selected from among groups substituted with 1, or may be substituted) to release hydrogen sulfide selected from the group; L can, or a direct bond or a linker, the linker, and a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -one or more substituent selected from an alkoxy group substituted by a 1, or a substituted C1-20 alkylene and, wherein, in the alkylene chain is 0 or 1-10 carbon atoms, C6-10 arylene, -0 -, -S -, - NR4 -、-C (0) NR4 -、-NR4 C (0) -、-C(O) -、-OC(O) -、-C (0) 0-spacer moiety selected from substituted, the R4 C hydrogen or1-12 alkyl, the C6-10 arylene moieties, and a halogen atom, hydroxy, C1-12 C alkyl and1-12 1, 2, 3 selected from an alkoxy group substituted with substituted with 4 or, that is not replaced with or; MTG is overdub, mitochondria-targeting group] a compound represented by the, or a pharmaceutically acceptable salt, of any one of claims 10-12 used.  14. L is wherein, according to the following expression: -L ' -Y FixedDocument_add Z- [in the formula, L'is, a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -alkoxy groups selected from among groups 1 one or more substituent groups has been substituted, or is not substituted with a branched or straight chain C1-20 alkylene group; Y may, - and a direct bond, - OC (O) - or -C (0) 0 - represent; Z has, directly bonded, or a halogen atom, hydroxy, C1-12 alkyl and C1-12 alkoxy groups selected from among groups 1, 2, 3 or 4 three substituents on the substituted, not substituted or is a phenylene group] is a linker represented by the formula, according to claim 13 used.  15. L'is, represented by the following formula - (CH2)n -[wherein n is 1-19 integer] represented by straight-chain alkylene group, -Y FixedDocument_add Z- moiety, represented by the following formula  represented, S is,  selected from, the group Ph GPIIbffla mitochondria and MTG3 Pin, for use according to claim 14.  16. Of the formula: MTG-L-S [in the formula, the S,  (xLxWx, X S is, or O N FixedDocument_add OH represents; R1 、R2 R and3 may each independently be hydrogen, C1-12 alkyl, C1-12 C alkoxy or6-10 represents aryl, each C1-12 alkyl, C1-12 C alkoxy or6-10 aryl group, a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -1 alkoxy substituted with one or more substituents selected from the radical group substituted, or may be substituted) to release the hydrogen sulfide is selected from the group; L is, according to the following expression: -L ' -Y FixedDocument_add Z- (in the formula, L'is, represented by the following formula - (CH2)n -(1-19 n is an integer of formula) is represented by a linear alkylene group; Y can, or a direct bond, - OC (O) - or -C (0) represent 0 -; Z has, directly bonded, or a halogen atom, hydroxy, C1-12 C alkyl and1-12 1, 2, 3 alkoxy or 4 groups selected from among groups substituted with a substituent group, or a phenylene group not substituted with the alkyl) represented by the linker; MTG is and, in the mitochondria-targeting group] a compound represented by, or a pharmaceutically acceptable salt. 17. Wherein the mitochondria-targeting group, phosphonium, arsonium cation, ammonium cation, furupurichin, MKT-077, pyridinium ceramide, quinolium, liposomal cation, sorbitol guanidine, cyclic guanidine and a lipophilic cation is selected from a rhodamine, a compound according to claim 16.  18. Wherein the partially -Y FixedDocument_add Z -, represented by the following formula  represented by the formula, 1 wherein any of the claims 16 or 17 compound.  19. S is said, represented by the following formula  is selected from a, compound of any one of claims 16-18.  20. Wherein said mitochondrial targeting group Ph is MTG3 P+ in the, compound of any one of claims 16-19.  21. Represented by the following formula  comprising a cation selected from the group consisting, of a compound of any one of claims 16-20. Claims amended 20170713 1. Surgery or treatment for treating a human or animal, to release hydrogen sulfide group in conjunction with a compound containing (mitochondrial targeting group) mitochondrial targeting group, or a pharmaceutically acceptable salt thereof or a pharmaceutical composition containing, themitochondrial targeting group, phosphonium cations, arsonium cation, ammonium cation, furupurichin, MKT-077, pyridinium ceramide, quinolium, liposomal cation, sorbitol guanidine, cyclic guanidine and rhodamine selected from lipophilic cation、or mitochondrial targeting peptide, a pharmaceutical composition. 2. To release hydrogen sulfide group, thiocarbamoyl group, a dithiol group or a -3 - - thioxo - 5 - - 5H-1, 2, a dithiol group or a -4 - - thioxo - 5 - - 5H-1, 2, a dithiol group or a -3 - - oxo 5 - - 5H-1, 2, a dithiol group or a -4-5 - - oxo - 5H-1, 2, a dithiol group or a -3-5 - - hydroxyimino - 5H-1, 2, a dithiol group or a -4-5 - - hydroxyimino - 5H-1, 2, or phosphino dithioates hosufinojichio acid group,according to claim 1 compound, or a pharmaceutically acceptable salt thereof and a pharmaceutical composition containing. 3. The following equation:MTG-L-S[in the formula, S is,  (in the formula, X is S, O or N-OH represents; R1 、R2 and R3 is each independently represent a hydrogen, C1-12 alkyl, C1-12 alkoxy or C6-10 represents aryl, each C1-12 alkyl, C1-12 alkoxy or C6-10 is an aryl group, a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -alkoxy substituents substituted with one or more selected from substituted 1, substituted or not) to release hydrogen sulfide selected from the group; L is, and a direct bond or linker, the linker, a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -1 alkoxy substituted with one or more selected from the groupsubstituted, or substituted notC1-20 alkylene and, here, in the alkylene chain of 1-10 carbon atoms or 0, C6-10 arylene, -O -, -S -, - NR4 -、-C(O) NR4 -、-NR4 C(O) -、-C(O) -、-OC(O) -、-C(O) O-moiety substituted with a spacer portion, the R4 is hydrogen or C1-12 alkyl, the C6-10 arylene moieties, a halogen atom, hydroxy, C1-12 alkyl and C1-12 1, 2, 3 selected from an alkoxy group which is substituted with 4 or substituted, or not substituted with; is then MTG,according to claim 1mitochondrial targeting group] represented by、claims 1 or 2 according to any of the compound, or a pharmaceutically acceptable salt, pharmaceutical composition. 4. Wherein L is, the following equation: -L ' - Y-Z - [in the formula, L'is,- and a direct bond, ora halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -1 selected from an alkoxy group substituted with one or more substituents, or substituted notlinearC1-20 alkylene group; Y is, - and a direct bond, - OC (O) - or -C (O) represents O -; Z is, or a direct bond, or a halogen atom, hydroxy, C1-12 alkyl and C1-12 1, 2, 3 4 is selected from an alkoxy group or substituted with one substituent, or a phenylene group substituted by at leastrepresenting]linker represented by,compound according to claim 3, or a pharmaceutically acceptable salt, the pharmaceutical composition. 5. L'is, the following formula - (CH2) n -[wherein n is 1-19 integer] represented by the straight-chain alkylene group, - Y-Z - portion, the following equation  represented by, S is,  selected from, mitochondria and targeting group MTG is Ph3 P+ in,according to claim 4 compound or its pharmaceutically acceptable salt, pharmaceutical composition. 6. In vivo release of hydrogen sulfide is expected to be reduced by the treatment or prevention of a disease or disordercompound according to any one of claims 1-5 for, or a pharmaceutically acceptable salt, pharmaceutical composition, thedisease or disorder is: (i) inflammatory joint disease, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, ulcerative colitis, inflammatory bowel disease, including hepatitis or atherosclerosis, chronic inflammatory disease or disorder; (ii) endotoxic shock, sepsis, hemorrhagic shock or including, acute inflammatory disease or disorder; (iii) osteoarthritis, osteoporosis, or diabetes type II or type Iincluding, mitochondrial dysfunctionassociated with the disease or disorder; (iv) vasculature complications of obesity, diabetes, metabolic syndrome, natural aging, hypertension, myocardial infarction, ischemia, ischemic heart disease, reperfusion injury, hypoxia, ischemia-reperfusion injury, hypoxia-reperfusion injury, retinopathy or neuropathy, a disease or disorder associated with the magnitude of the vasculopathy; (v) Alzheimer's disease, amyotrophic lateral sclerosis, motor neuron disease, parkinsonism, hanchindon disease, tauopathies (tauopathy), extrapyramidal movement disorders and, or, ataxia telangiectasia, corticobasal degeneration or progressive supranuclear disorder including neurons, an astrocyte or a glial cell killing significant nerve disease, a neurodegenerative disease; vasculopathy (vi) the magnitude of, or including vascular dementia, age-related disease or disorder; (vii) through the kidneys or liverorgan insufficiency,diseases or disorders associated with organ dysfunctions; (viii) ischemia-reperfusion injury, cardiovascular disease including hypercholesterolemia and hyperlipidemia, chronic and/or a disease or disorder associated with acute kidney injury; or (ix) cancer diseases or disorders associated with abnormal cell proliferation; in,pharmaceutical composition. 7. For promoting growth of the plants in the treatment of the plants, the herbicidal processing in the plant, or plant pore closure for prevents or reduces, or for trigger opening of the pores, to release hydrogen sulfide group linked to a mitochondrial targeting group-containing compound, or a pharmaceutically acceptable saltin, themitochondrial targeting group, phosphonium cations, arsonium cation, ammonium cation, furupurichin, MKT-077, pyridinium ceramide, quinolium, liposomal cation, sorbitol guanidine, cyclic guanidine and rhodamine selected from lipophilic cation、or mitochondrial targeting peptide, used. 8. To release hydrogen sulfide group, chichi oh carbamoyl group, a dithiol group or a -3 - - thioxo - 5 - - 5H-1, 2, a dithiol group or a -4 - - thioxo - 5 - - 5H-1, 2, a dithiol group or a -3 - - oxo 5 - - 5H-1, 2, a dithiol group or a -4-5 - - oxo - 5H-1, 2, a dithiol group or a -3-5 - - hydroxyimino - 5H-1, 2, a dithiol group or a -4-5 - - hydroxyimino - 5H-1, 2, or phosphino dithioates hosufinojichio acid group,used according to claim 7. 9. Wherein said compound is an, MTG-L-S [in the formula, S is,  (in the formula, X is S, O or N-OH represents; R1 、R2 and R3 is each independently represent a hydrogen, C1-12 alkyl, C1-12 alkoxy or C6-10 represents aryl, each C1-12 alkyl, C1-12 alkoxy or C6-10 is an aryl group, a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -alkoxy substituents substituted with one or more selected from the group substituted by 1, or may be substituted) to release hydrogen sulfide selected from the group; L is, a direct connection or linker, the linker, a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -1 alkoxy substituted with one or more selected from substitutedwas, or a substituted notC1-20 alkylene and, in this case, the alkylene chain of 1-10 carbon atoms or 0, C6-10 arylene, -O -, -S -, - NR4 -、-C(O) NR4 -、-NR4 C(O) -、-C(O) -、-OC(O) -、-C(O) O-moiety substituted with a spacer portion, the R4 is hydrogen or C1-12 alkyl, the C6-10 arylene moieties, a halogen atom, hydroxy, C1-12 alkyl and C1-12 1, 2, 3 4 is selected from an alkoxy group which is substituted with substituted or, or not substituted with; is then MTG,according to claim 7mitochondrial targeting group] a compound represented by the, or a pharmaceutically acceptable salt,use according to any one of claims 7 or 8. 10. Wherein L is, according to the following formula: -L ' - Y-Z - [in the formula, L'is,is a direct bond, ora halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -alkoxy group selected from 1 substituted with one or more substituted, or substituted notlinearC1-20 alkylene group; Y is, a direct bond, - OC (O) - or -C (O) O- represents; Z is, or a direct bond, or a halogen atom, hydroxy, C1-12 alkyl and C1-12 alkoxy group selected from 1, 2, 3 or 4 in which one substituent of substituted, or not substituted with a phenylene grouprepresenting]linker represented by,claim 9use. 11. L'is, the following formula - (CH2) n -[wherein n is 1-19 integer] represented by the straight-chain alkylene group, - Y-Z - portion, the following equation  represented by, S is,  selected from, mitochondria and the targeting group is Ph MTG3 P+ in,claim 10use. 12. The following equation: MTG-L-S [in the formula, S is,  (in the formula, X is S, O or N-OH represents; R1 、R2 and R3 is each independently represent a hydrogen, C1-12 alkyl, C1-12 alkoxy or C6-10 represents aryl, each C1-12 alkyl, C1-12 alkoxy or C6-10 is an aryl group, a halogen atom, hydroxy, C1-12 alkoxy, C1-12 alkyl, hydroxy -C1-12 -alkyl, halo -C1-12 -alkyl and halo -C1-12 -alkoxy substituents substituted with one or more selected from the group substituted by 1, or may be substituted) to release hydrogen sulfide selected from the group; L is, the following equation: -L ' - Y-Z - (in the formula, L'is, by the following formula - (CH2) n -(is n in the formula2-19an integer) and is a linear alkylene group represented by; Y is, a direct bond, - OC (O) - or -C (O) represents O -; Z is, or a direct bond, or a halogen atom, hydroxy, C1-12 alkyl and C1-12 1, 2, 3 4 is selected from an alkoxy group or substituted with one substituent, or a phenylene group substituted by at leastrepresenting) represented by linker; MTG is and, mitochondrial targeting grouprepresents, the mitochondrial targeting groups, phosphonium cations, arsonium cation, ammonium cation, furupurichin, MKT-077, pyridinium ceramide, quinolium, liposomal cation, sorbitol guanidine, and rhodamine lipophilic cation selected from cyclic guanidine, or mitochondrial targeting group]compound represented by the, or a pharmaceutically acceptable salt. 13. Wherein S is, the following equation  selected from,claim 12compound. 14. Said mitochondrial targeting group is Ph MTG3 P+ in,any one of claims 12 or 13compound. 15. Cationfollowing equation  selected fromin, any one of claims 12-14 compound or a pharmaceutically acceptable salt.
法律状态
(JP2017186362) LEGAL DETAILS FOR JP2017186362  Actual or expected expiration date=2032-10-01    Legal state=ALIVE    Status=PENDING     Event publication date=2017-06-14  Event code=JP/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=JP JP2017116884  Application date=2017-06-14  Standardized application number=2017JP-0116884     Event publication date=2017-07-13  Event code=JP/A521  Event type=Restitution or restoration  Written amendment  Effective date of the event=2017-07-13  JAPANESE INTERMEDIATE CODE: A523     Event publication date=2017-07-13  Event code=JP/A621  Event indicator=Pos  Event type=Examination events  Written request for application examination  Effective date of the event=2017-07-13  JAPANESE INTERMEDIATE CODE: A621     Event publication date=2017-09-04  Event code=JP/A871  Event type=ACL  Event type=Examination events  Explanation of circumstances concerning accelerated examination  Effective date of the event=2017-09-04  JAPANESE INTERMEDIATE CODE: A871     Event publication date=2017-09-12  Event code=JP/A975  Event type=ACL  Event type=Examination events  Report on accelerated examination  Effective date of the event=2017-09-12  JAPANESE INTERMEDIATE CODE: A971005     Event publication date=2017-09-19  Event code=JP/A131  Event indicator=Neg  Event type=Examination events  Notification of reasons for refusal  Effective date of the event=2017-09-19  JAPANESE INTERMEDIATE CODE: A131     Event publication date=2017-10-12  Event code=JP/A  Event type=Examination events  Published application  Publication country=JP  Publication number=JP2017186362  Publication stage Code=A  Publication date=2017-10-12  Standardized publication number=JP2017186362     Event publication date=2017-12-15  Event code=JP/A601  Event type=Examination events  Written request for extension of term  Effective date of the event=2017-12-15  JAPANESE INTERMEDIATE CODE: A601     Event publication date=2018-03-19  Event code=JP/A521  Event type=Restitution or restoration  Written amendment  Effective date of the event=2018-03-19  JAPANESE INTERMEDIATE CODE: A523     Event publication date=2018-04-03  Event code=JP/A131  Event indicator=Neg  Event type=Examination events  Notification of reasons for refusal  Effective date of the event=2018-04-03  JAPANESE INTERMEDIATE CODE: A132
专利类型码
A
国别省市代码
若您需要申请原文,请登录。

最新评论

暂无评论。

登录后可以发表评论

意见反馈
返回顶部