CN105384691B - A kind of preparation method and application of inhibitors of glutaminyl cyclase - Google Patents
A kind of preparation method and application of inhibitors of glutaminyl cyclase Download PDFInfo
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- CN105384691B CN105384691B CN201510701143.XA CN201510701143A CN105384691B CN 105384691 B CN105384691 B CN 105384691B CN 201510701143 A CN201510701143 A CN 201510701143A CN 105384691 B CN105384691 B CN 105384691B
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- 0 *c1ccccc1Br Chemical compound *c1ccccc1Br 0.000 description 2
- BWFVEKWOUBKUJV-UHFFFAOYSA-N C=CNc1ccccc1C1C=CC(F)=CC1 Chemical compound C=CNc1ccccc1C1C=CC(F)=CC1 BWFVEKWOUBKUJV-UHFFFAOYSA-N 0.000 description 1
- RAAMMSLPQGUIKS-UHFFFAOYSA-N Fc(cc1)ccc1-c1ccccc1NCCCBr Chemical compound Fc(cc1)ccc1-c1ccccc1NCCCBr RAAMMSLPQGUIKS-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N OB(c(cc1)ccc1F)O Chemical compound OB(c(cc1)ccc1F)O LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/61—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
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Abstract
The present invention discloses a kind of preparation method and application of inhibitors of glutaminyl cyclase.Wherein, preparation method includes step:(1) to carry boronate, amido and R1A unit raw materials and with bromine substituent and R2The starting of unit B raw material, through Suzuki coupling reactions, prepares A units and intermediate that unit B is coupled;(2) intermediate and dibromo alkyl chain being coupled using A units and unit B are reacted through SN2 as raw material and prepare the intermediate containing alkyl chain;(3) using the intermediate containing alkyl chain and imidazoles or imidazoles containing substituent group as raw material, inhibitors of glutaminyl cyclase is prepared through SN2 reactions.Preparation method in the present invention only needs Suzuki couplings, SN2 reactions etc. can be completed, and process route simple possible of the invention, high income is more suitable for preparing on a large scale;QC inhibitor can be widely applied to exploitation of the drugs of the QC specificity overexpression relevant diseases such as exploitation, AD of efficient QC inhibitor kind new medicine, original new drug and diagnostic kit etc..
Description
Technical field
The present invention relates to medicinal chemistry art more particularly to a kind of preparation methods of inhibitors of glutaminyl cyclase
And application.
Background technology
Glutaminyl cyclase (Glutaminylcyclase, QC, EC2.3.2.5) be one kind can with catalytic polypeptide,
The enzyme of the N-terminals glutamine residue such as albumen intramolecular cyclization reaction generation pyroglutamic acid (pGlu).1963, QC was for the first time in the torrid zone
It is found in plant papaya (Carica papaya) latex, rear research confirms, QC has point in plant, animal, microorganism
Cloth.Mammal QC has well-conserved, does not have any sequence homology between papaya QC, and has with bacterium aminopeptidase
There is significant sequence homology, therefore animal and plant QC has different evolutionary sources.In plant, the physiological function of QC is not
Very clearly, it may have certain effect during plant defense pathogenic microorganism.QC in animal body, which has, changes albumen
Important biomolecules function, the QC increased activities such as N-terminals chemical constitution, adjusting activity, enhancing stability is waited to be sent out in a variety of major diseases
Key effect in Anttdisease Mechanism is increasingly subject to the great attention of people.
Alzheimer disease (Alzheimer ' s disease, AD) is a kind of common neurodegenerative disease, is old
Dull-witted principal mode, AD patient are more than more than 65% old dementia patients sum.With the development of population in the world aging, AD
Incidence and patient numbers rapidly increase, and epidemiological survey is shown, AD, which has become, is only second to cardiovascular and cerebrovascular disease and tumour
The third-largest worldwide health problem.AD cardinal symptoms include progressive memory and cognition dysfunction etc., have irreversible, high
The features such as the death rate, current clinic there is no specific treatment medicine.
AD pathogenesis is complex, and people have proposed numerous it is assumed that including beta-amyloid protein (A from different perspectives
β) cascade theory, Tau albumen tangle precipitation theory, oxidative stress theory, biological metal ionic homeostasis is unbalance theory, mitochondria work(
Energy exhaustion theory etc..However, the definite pathomechanisms of AD remain unknown.Anti- AD Research progress of drugs based on above-mentioned academic hypothesis delays
Slowly.
Clinicopathological study is it has proven convenient that AD pathological characteristics are mainly A β precipitations and the neuron outside brain neuroblastoma member
Internal Hyperphosphorylationof Tau albumen entanglement etc..But it is in recent years, multinomial to be found in vivo with clinical research, with Elderly people human brain
Unlike portion's A β senile plaques precipitation, the main component of AD patient's brain senile plaque precipitation is not A β, but the A β to make a variation, especially
It is the pGlu-A β that N-terminal glutamine residue molecule inner ring condensation forms, especially pGlu-A β 42/pGlu-A β 40 etc., content is more than
50%.PGlu-A β have stronger neurotoxicity, faster aggregate and precipitate speed, stronger stability, and its generation is faced with AD
The generation of bed symptom is directly related, is marker than A β appearance earlier, more special with AD morbidities.
Correlative study further deeply shows that pGlu-A β are the products of QC enzyme catalysis, and selective depression QC lives
Property can significantly inhibit the generation of pGlu-A β and the formation of senile plaque precipitation, and be obviously improved the AD diseases such as cognition, impaired memory function
Shape.Meanwhile research finds that AD patient's brain QC specificity overexpressions are the significant lesions of AD morbidity early stages, early in generation
Before pGlu-A β, A β, the characteristic up-regulation of QC RNA is can detect in peripheral blood.As it can be seen that QC high expression be AD morbidity,
The crucial promoting factor of development, QC open new research direction, QC inhibitor for AD pathology and causal anti-AD drug researches
It is expected to become the strategic breakthrough mouth for innovating anti-AD drug developments.
In addition, QC is a variety of in rheumatic arthritis, non-alcoholic hepatitis, cutaneous melanoma, lupus erythematosus syndrome etc.
There is specificity overexpression in the morbidity of complex disease related to body inherent immunity functional disturbance.QC inhibitor also can be used for upper
State the treatment of a variety of diseases.
Currently, the correlative study of QC inhibitor is relatively fewer.EP1713780B1、EP2091948B1、US7304086B2、
US7371871B2、US7741354B2、US7892771B2、US8129160B2、US8188094B2、US8202897B2、
The patents such as US8227498B2, US20080214620A1, US200880286231A1, US20090269301A1 disclose one kind
Line style QC inhibitor molecules.Such QC inhibitor still has certain shortcoming, such as precursor structure in terms of structure and activity
Single, poorly water-soluble, cross-film poor performance, limited activity, synthesis step are cumbersome etc..Therefore, further expand QC inhibitor chemistry
Structure diversity, the design synthesis higher new QC inhibitor of druggability, and QC inhibitor is studied to AD, rheumatic arthritis, non-
The therapeutic effect of the diseases such as alcoholic hepatitis, cutaneous melanoma, lupus erythematosus syndrome and mechanism express related diseases to QC high
Managing mechanism study, causal new drug research, QC targeting early diagnosis and therapies etc. all has particularly important scientific meaning and answers
With value.
Invention content
In view of above-mentioned deficiencies of the prior art, the purpose of the present invention is to provide a kind of inhibition of glutaminyl cyclase
The preparation method and application of agent, it is intended to solve existing QC inhibitor its there are precursor structure is single, poorly water-soluble, cross-film performance
The problems such as difference, limited activity, cumbersome synthesis step.
Technical scheme is as follows:
A kind of preparation method of inhibitors of glutaminyl cyclase, the inhibitors of glutaminyl cyclase
General structure is as follows:
Wherein, A units are phenyl ring, six-membered Hetero-aromatic, five yuan of hetero-aromatic rings, seven yuan of aromatic rings, naphthalene, anthracene, naphthoquinones or more aromatic ring systems, R1
It is hydrogen, straight-chain alkyl, branched-chain alkyl, alkoxy, halogen, carboxyl, nitro, sulfonic group, amido, phosphate and its substituent
In one kind;
Unit B is phenyl ring, six-membered Hetero-aromatic, five yuan of hetero-aromatic rings, seven yuan of aromatic rings, naphthalene, anthracene, naphthoquinones or more aromatic ring systems, R2
It is hydrogen, straight-chain alkyl, branched-chain alkyl, alkoxy, halogen, carboxyl, nitro, sulfonic group, amido, phosphate and its substituent
In one kind;
In C cell, R on imidazole ring3It is hydrogen, straight-chain alkyl, branched-chain alkyl, alkoxy, halogen, amido and its substitution
One kind in object;
Wherein, preparation method includes step:
(1) to carry boronate, amido and R1A unit raw materials and with bromine substituent and R2Unit B raw material starting,
Through Suzuki coupling reactions, A units and the intermediate of unit B coupling are prepared;
(2) intermediate and dibromo alkyl chain being coupled using A units and unit B are prepared through SN2 reactions as raw material and contain alkyl
Middle-of-chain body;
(3) using the intermediate containing alkyl chain and imidazoles or imidazoles containing substituent group as raw material, paddy is prepared through SN2 reactions
Glutamine acyl group cyclase inhibitors.
A kind of application of inhibitors of glutaminyl cyclase, wherein:The glutaminyl cyclase is inhibited
Agent is applied to QC and targets in anti-AD lead drugs.
A kind of application of inhibitors of glutaminyl cyclase, wherein:The glutaminyl cyclase is inhibited
Agent is applied in the drug for the treatment of QC specificity overexpression diseases.
A kind of application of inhibitors of glutaminyl cyclase, wherein:The glutaminyl cyclase is inhibited
Agent is applied in QC diagnostic kits.
Advantageous effect:Preparation method in the present invention only needs Suzuki couplings, SN2 reactions etc. can be completed, compared to existing
There are technology, process route simple possible of the invention, high income is more suitable for preparing on a large scale;The QC inhibitor of the present invention can be wide
The drugs of the QC specificity overexpression relevant diseases such as general exploitation, AD applied to efficient QC inhibitor kind new medicine, original new drug and
Exploitation of diagnostic kit etc..
Description of the drawings
Fig. 1 is QC enzyme inhibition activity test philosophy schematic diagrames in the present invention.
Specific embodiment
The present invention provides a kind of preparation method and application of inhibitors of glutaminyl cyclase, to make the mesh of the present invention
, technical solution and effect it is clearer, clear and definite, the present invention is described in more detail below.It should be appreciated that described herein
Specific embodiment be only used to explain the present invention, be not intended to limit the present invention.
The inhibitors of glutaminyl cyclase (QC inhibitor) of the present invention, structural formula is as follows:
The QC inhibitor of the present invention, it includes three structural pharmacophore units:A, B and C, wherein, A units are phenyl ring, six
First hetero-aromatic ring (N, S, O), five yuan of hetero-aromatic rings (C, N, S, O), seven yuan of aromatic rings, naphthalene, anthracene, naphthoquinones or (miscellaneous) more aromatic ring systems, R1It is
Hydrogen, straight-chain alkyl, branched-chain alkyl, alkoxy, halogen, carboxyl, nitro, sulfonic group, amido, phosphate and its substituent
(such as hydrogen, the substitution of straight-chain alkyl, branched-chain alkyl, alkoxy, halogen, carboxyl, nitro, sulfonic group, amido or phosphate
Object) in one kind;R1It is monosubstituted or different location polysubstituted.
Unit B is phenyl ring, six-membered Hetero-aromatic (N, S, O), five yuan of hetero-aromatic rings (C, N, S, O), seven yuan of aromatic rings, naphthalene, anthracene, naphthoquinones
Or (miscellaneous) more aromatic ring systems, R2It is hydrogen, straight-chain alkyl, branched-chain alkyl, alkoxy, halogen, carboxyl, nitro, sulfonic group, amine
Base, phosphate and its substituent (such as hydrogen, straight-chain alkyl, branched-chain alkyl, alkoxy, halogen, carboxyl, nitro, sulfonic acid
The substituent of base, amido or phosphate) in one kind;R2It is monosubstituted or different location polysubstituted.
In C cell, R on imidazole ring3It is hydrogen, straight-chain alkyl, branched-chain alkyl, alkoxy, halogen, amido and its substitution
One kind in object.R3It is monosubstituted or different location polysubstituted.R3The position of substitution at 2,4 or 5 of imidazole ring.C cell
In, carbon atom n=1-4 in alkyl chain, such as n are 1,2,3 or 4.
Further, unit B and C cell are ortho position, meta or para position in the link position of A units.
Further, in same compound, A units are identical with the mother nucleus structure of unit B or differ, R1And R2Knot
Structure is identical or differs.
QC inhibitor in the present invention pharmaceutically acceptable salt, including lithium salts, sodium salt, sylvite, magnesium salts, calcium salt, iron
Salt, mantoquita, organic ammonium salt, hydrochloride, phosphate, acetate, propionate, oxalate, citrate etc..
The preparation method of the present invention includes step:
(1) to carry boronate, amido and R1A unit raw materials and with bromine substituent and R2Unit B raw material starting,
Through Suzuki coupling reactions, A units and the intermediate of unit B coupling are prepared;
(2) intermediate and dibromo alkyl chain being coupled using A units and unit B are prepared through SN2 reactions as raw material and contain alkyl
Middle-of-chain body;
(3) using the intermediate containing alkyl chain and imidazoles or imidazoles containing substituent group as raw material, paddy is prepared through SN2 reactions
Glutamine acyl group cyclase inhibitors.
Then can QC inhibitor obtained be subjected to Spectral Identification analysis after purification through silica gel column chromatography.
The present invention provides a kind of application of inhibitors of glutaminyl cyclase, wherein:By the glutaminyl
Cyclase inhibitors are applied to QC and target in anti-AD lead drugs.
Invention also provides a kind of another application of inhibitors of glutaminyl cyclase, wherein:By the glutamine
Acyl group cyclase inhibitors are applied to treatment QC specificity overexpressions disease (including rheumatic arthritis, non-alcoholic hepatitis, skin
Skin melanoma, lupus erythematosus syndrome etc.) drug in.
Invention also provides a kind of another application of inhibitors of glutaminyl cyclase, wherein:By the glutamine
Acyl group cyclase inhibitors are applied in QC diagnostic kits.
Embodiment 1:N- (3- (1H- imidazoles -1- bases) propyl) -3', 4'- dimethoxys-[1,1'- biphenyl] -2- amine (MQI-
1) synthesis, synthetic route are as follows:
A, 3', 4'- dimethoxy-[1,1'- biphenyl] -2- amine:By bromaniline (5.81mmol, 1 equivalent), 3,4- dimethoxies
Base phenyl boric acid (6.98mmol, 1.2 equivalents) and the complexing of [1,1 '-bis- (diphenylphosphine) ferrocene] palladium chloride (II) dichloromethane
Object (0.35mmol, 0.06 equivalent) is placed in 50ml round-bottomed flasks, is separately added into the dioxane of 10ml and the 2mol/L of 10ml
K2CO3Solution, 100 DEG C, flow back 3h.It adds in saturation NaCl solution and reaction is quenched, be cooled to room temperature, ethyl acetate extracts three times, closes
And rear saturation NaCl solution is washed once, anhydrous Na2SO4Dry, silica gel column chromatography collects product, yield 90%.
B, N- (3- bromopropyls) -3', 4'- dimethoxys-[1,1'- biphenyl] -2- amine:3', 4'- dimethoxy-[1,1'-
Biphenyl] -2- amine (872.32umol, 1 equivalent), 1,3- dibromopropanes (6.11mmol, 7 equivalents) be dissolved in 6ml anhydrous acetonitriles, it adds in
Anhydrous K2CO3(1.74mmol, 2 equivalents) solid is stirred at reflux overnight, and solvent is evaporated off, and ethyl acetate and water extraction three times, merge
Organic phase is simultaneously washed once, anhydrous Na with saturation NaCl solution2SO4Dry, silica gel column chromatography collects product, yield 48%.
C, N- (3- (1H- imidazoles -1- bases) propyl) -3', 4'- dimethoxys-[1,1'- biphenyl] -2- amine:Imidazoles
(285.51umol, 1 equivalent) is dissolved in 1ml anhydrous acetonitriles, adds in dry K2CO3(285.51umol, 1 equivalent), stirring at normal temperature
15min adds in gained N- (3- bromopropyls) -3', the anhydrous second of 1ml of 4'- dimethoxys-[1,1'- biphenyl] -2- amine in above-mentioned b
Nitrile solution, is refluxed overnight, and solvent is evaporated off, and ethyl acetate and water extraction three times, merge organic phase and wash one with saturation NaCl solution
It is secondary, anhydrous Na2SO4Dry, silica gel column chromatography collects product, yield 20%.
Embodiment 2:The fluoro- N- of 4'- (3- (4- methyl-1 H-imidazole-1-groups) propyl)-[1,1'- biphenyl] -2- amine (MQI-
31) synthesis, synthetic route are as follows:
A, fluoro- [1,1'- the biphenyl] -2- amine of 4'-:By bromaniline (5.81mmol, 1 equivalent), 4- fluorobenzoic boric acids
(6.98mmol, 1.2 equivalents) and [1,1 '-bis- (diphenylphosphine) ferrocene] palladium chloride (II) dichloromethane complex
(0.35mmol, 0.06 equivalent) is placed in 50ml round-bottomed flasks, and solvent is 10ml dioxane and 10ml 2mol/L K2CO3It is molten
Liquid, stirs 3h by 100 DEG C, adds in saturation NaCl solution and reaction is quenched, ethyl acetate extracts three times, saturation NaCl solution after merging
Wash primary, anhydrous Na2SO4Dry, silica gel column chromatography collects product, yield 94%.
B, N- (3- bromopropyls) -4'- fluorine [1,1'- biphenyl] -2- amine:Fluoro- [1,1'- the biphenyl] -2- amine of 4'-
(534.15umol, 1 equivalent) and 1,3- dibromopropane (3.74mmol, 7 equivalents) are dissolved in 4ml anhydrous acetonitriles, add in anhydrous K2CO3
(1.74mmol, 2 equivalents) solid is stirred at reflux overnight, and solvent is evaporated off, and ethyl acetate and water extraction three times, merge organic phase simultaneously
It is washed once with saturation NaCl solution, anhydrous Na2SO4Dry, silica gel column chromatography collects product, yield 45%.
C, the fluoro- N- of 4'- (3- (4- methyl-1 H-imidazole-1-groups) propyl)-[1,1'- biphenyl] -2- amine:4-methylimidazole
(324.48umol, 1 equivalent) is dissolved in 1ml anhydrous acetonitriles, adds in anhydrous K2CO3(285.51umol, 1 equivalent), stirring at normal temperature
15min;Add in the 1ml anhydrous acetonitriles of gained N- (3- bromopropyls) -4'- fluorine [1,1'- biphenyl] -2- amine in above-mentioned b, stirring
It is refluxed overnight, solvent is evaporated off, ethyl acetate and water extraction three times, merge organic phase and washed once with saturation NaCl solution, anhydrous
Na2SO4Dry, silica gel column chromatography collects product, yield 18%.
Embodiment 3:QC inhibitor tests QC enzyme inhibition activities
QC enzyme inhibition activity test philosophy schematic diagrames are as shown in Figure 1.Enzyme activity test carries out in 96 hole elisa Plates, uses
200ul pH8.0Tris buffer systems:The fresh preparation Gln-Gln of 0.3mM NADH, 2.0mM, 14mM α-ketoglutaric acids, 30U/ml
Glutamte dehydrogenase, 50mM Tris, pH8.0 buffer solutions, is eventually adding 0.28 μM of recombined human QC albumen and various concentration inhibitor
Mixed liquor, with NADH during 25 DEG C of microplate reader dynamic detection, absorption value changes in 15min at the 340nm wavelength after oscillation 30 seconds,
A data acquisition is carried out every 30s, according to test result, calculates IC of the inhibitor to QC enzyme activity inhibiting effect50Value, for not
Test result with QC inhibitor is as shown in table 1, and the structural formula of wherein QC inhibitor is:
Table 1
The anti-AD effects of embodiment 4QC inhibitor
With double transgenic AD mouse (B6C3-Tg (APPswe, PSEN1dE9) 85Dbo/MmJNju) for animal pattern, selection
Female 2 monthly age AD mouse, if medication group and control group, each 6, using MQI-1 as experimental drug, dosage 8.0mg/kg, abdominal cavity note
It penetrates, was administered once every two days, control group gives equivalent buffer solution, and continuous use carries out Behaviors survey after 6 weeks.Nest
Construction Behaviors surveys, are put into the test paper group of equivalent at random in each cage, and are uniformly distributed, and are being spaced 24 hours
Afterwards, the situation moved, crush and nested with test paper group that mouse rolls into a ball test paper is observed and recorded, the results showed that, medication group mouse is again
The behavior of building is obviously improved, and cognition, memory function significantly increase.AD associated pathologies are tested, and are put to death mouse, are taken brain tissue, sucrose
Serial dehydration carries out hat dress frozen section, then carries out Western Blot and ThS staining analysis, as a result table after OCT embeddings
Bright, the senile plaque precipitation of mouse brain significantly reduces after medication.Summary is tested, and MQI-1 is shown significantly in Mice Body
Anti- AD effect.
In conclusion the preparation method in the present invention, only needs Suzuki couplings, SN2 reactions etc. can be completed, compared to existing
There are technology, process route simple possible of the invention, high income is more suitable for preparing on a large scale;The QC inhibitor of the present invention is to QC
Inhibitory activity is notable, the IC of part of compounds50Reached 4.72 μM, as lead compound be worth further optimization design,
Synthesis, has the very high potential for being developed into novel, efficient QC.The QC inhibitor of the present invention can be used for AD, tumour, rheumatic to close
A variety of exploitation, pathogenesis and molecular mechanisms with QC specificity overexpression relevant disease causal treatment drugs such as section inflammation are ground
Study carefully, early diagnose and the exploitation of diagnostic kit etc..
It should be understood that the application of the present invention is not limited to the above, it for those of ordinary skills, can
To be improved or converted according to the above description, all these modifications and variations should all belong to the guarantor of appended claims of the present invention
Protect range.
Claims (4)
1. a kind of preparation method of inhibitors of glutaminyl cyclase, the knot of the inhibitors of glutaminyl cyclase
Structure general formula is as follows:
,
Wherein, A units are phenyl ring, R1It is hydrogen;
Unit B is phenyl ring, R2It is one kind in alkoxy or halogen;
In C cell, R on imidazole ring3It is one kind in hydrogen or straight-chain alkyl;
Carbon atom n=1-4 in alkyl chain;
It is characterized in that, preparation method includes step:
(1)To carry boronate, amido and R1A unit raw materials and with bromine substituent and R2Unit B raw material starting, warp
Suzuki coupling reactions prepare A units and the intermediate of unit B coupling;
(2)The intermediate and dibromo alkyl chain being coupled using A units and unit B are prepared through SN2 reactions as raw material and contain alkyl chain
Intermediate;
(3)Using the intermediate containing alkyl chain and imidazoles or imidazoles containing substituent group as raw material, glutamy is prepared through SN2 reactions
Amine acyl group cyclase inhibitors;
The unit B and C cell are ortho positions in the link position of A units.
2. a kind of application of inhibitors of glutaminyl cyclase as described in claim 1, it is characterised in that:By the paddy ammonia
Amide acyl group cyclase inhibitors are applied to prepare in the anti-AD lead drugs of QC targetings.
3. a kind of application of inhibitors of glutaminyl cyclase as described in claim 1, it is characterised in that:By the paddy ammonia
Amide acyl group cyclase inhibitors are applied in the drug for preparing treatment QC specificity overexpression diseases.
4. a kind of application of inhibitors of glutaminyl cyclase as described in claim 1, it is characterised in that:By the paddy ammonia
Amide acyl group cyclase inhibitors are applied to prepare the drug in QC diagnostic kits.
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