CA2992796A1 - Pde4 inhibitor for the treatment of diabetic nephropathy - Google Patents
Pde4 inhibitor for the treatment of diabetic nephropathy Download PDFInfo
- Publication number
- CA2992796A1 CA2992796A1 CA2992796A CA2992796A CA2992796A1 CA 2992796 A1 CA2992796 A1 CA 2992796A1 CA 2992796 A CA2992796 A CA 2992796A CA 2992796 A CA2992796 A CA 2992796A CA 2992796 A1 CA2992796 A1 CA 2992796A1
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- compound
- inhibitor
- phosphodiesterase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 88
- 208000007342 Diabetic Nephropathies Diseases 0.000 title claims abstract description 87
- 208000033679 diabetic kidney disease Diseases 0.000 title claims abstract description 87
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title abstract description 13
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title abstract description 13
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims abstract description 54
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims abstract description 54
- 150000003839 salts Chemical class 0.000 claims description 290
- 229940126062 Compound A Drugs 0.000 claims description 285
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 284
- MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 claims description 196
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims description 196
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims description 196
- 239000005485 Azilsartan Substances 0.000 claims description 128
- 229960002731 azilsartan Drugs 0.000 claims description 128
- KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 claims description 127
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims description 126
- 229960002198 irbesartan Drugs 0.000 claims description 126
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 claims description 126
- 239000002083 C09CA01 - Losartan Substances 0.000 claims description 115
- 239000008194 pharmaceutical composition Substances 0.000 claims description 100
- 239000003112 inhibitor Substances 0.000 claims description 96
- 229960004773 losartan Drugs 0.000 claims description 86
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 claims description 86
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 claims description 70
- 102000015427 Angiotensins Human genes 0.000 claims description 52
- 108010064733 Angiotensins Proteins 0.000 claims description 52
- 239000002464 receptor antagonist Substances 0.000 claims description 52
- 229940044551 receptor antagonist Drugs 0.000 claims description 51
- 239000006186 oral dosage form Substances 0.000 claims description 49
- 241000124008 Mammalia Species 0.000 claims description 40
- 102000009027 Albumins Human genes 0.000 claims description 38
- 108010088751 Albumins Proteins 0.000 claims description 38
- 229940109239 creatinine Drugs 0.000 claims description 37
- 230000002485 urinary effect Effects 0.000 claims description 33
- 230000029142 excretion Effects 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 25
- 239000003937 drug carrier Substances 0.000 claims description 7
- JYJHFMXFMWXCSY-QGPMSJSTSA-N 5-[(2r,4ar,10br)-9-ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl]-1-methylpyridin-2-one Chemical group N([C@@H]1CC[C@@H](O)C[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C=1C=CC(=O)N(C)C=1 JYJHFMXFMWXCSY-QGPMSJSTSA-N 0.000 claims 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 abstract description 43
- 239000005541 ACE inhibitor Substances 0.000 abstract description 38
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 abstract description 35
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 abstract description 35
- 239000002552 dosage form Substances 0.000 description 80
- 229960000830 captopril Drugs 0.000 description 54
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 53
- 230000000875 corresponding effect Effects 0.000 description 42
- 230000000694 effects Effects 0.000 description 40
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 32
- 229960000519 losartan potassium Drugs 0.000 description 29
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 29
- 150000001875 compounds Chemical class 0.000 description 28
- 241000699670 Mus sp. Species 0.000 description 24
- 230000037396 body weight Effects 0.000 description 24
- 102000017011 Glycated Hemoglobin A Human genes 0.000 description 23
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 23
- 229910052700 potassium Inorganic materials 0.000 description 23
- 239000011591 potassium Substances 0.000 description 23
- 108010014663 Glycated Hemoglobin A Proteins 0.000 description 22
- 230000014509 gene expression Effects 0.000 description 20
- 238000012360 testing method Methods 0.000 description 19
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 16
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 16
- 206010020772 Hypertension Diseases 0.000 description 14
- 206010012601 diabetes mellitus Diseases 0.000 description 14
- 238000011260 co-administration Methods 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 239000003981 vehicle Substances 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 10
- 201000000083 maturity-onset diabetes of the young type 1 Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 102000015225 Connective Tissue Growth Factor Human genes 0.000 description 8
- 108010039419 Connective Tissue Growth Factor Proteins 0.000 description 8
- 102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 description 8
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 8
- 230000003834 intracellular effect Effects 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 210000002700 urine Anatomy 0.000 description 8
- 102000012422 Collagen Type I Human genes 0.000 description 7
- 108010022452 Collagen Type I Proteins 0.000 description 7
- 108010067306 Fibronectins Proteins 0.000 description 7
- 102000016359 Fibronectins Human genes 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 238000000692 Student's t-test Methods 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000036470 plasma concentration Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 102000001554 Hemoglobins Human genes 0.000 description 4
- 108010054147 Hemoglobins Proteins 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 208000020832 chronic kidney disease Diseases 0.000 description 4
- 238000002648 combination therapy Methods 0.000 description 4
- 201000000523 end stage renal failure Diseases 0.000 description 4
- 239000006207 intravenous dosage form Substances 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000009097 single-agent therapy Methods 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 241000725101 Clea Species 0.000 description 3
- 108020004635 Complementary DNA Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000036765 blood level Effects 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 208000017169 kidney disease Diseases 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 239000008177 pharmaceutical agent Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 230000002206 pro-fibrotic effect Effects 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 201000001474 proteinuria Diseases 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 239000007916 tablet composition Substances 0.000 description 3
- 229940086440 Angiotensin I converting enzyme inhibitor Drugs 0.000 description 2
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 102000030621 adenylate cyclase Human genes 0.000 description 2
- 108060000200 adenylate cyclase Proteins 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 230000003510 anti-fibrotic effect Effects 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 230000001593 cAMP accumulation Effects 0.000 description 2
- 238000011278 co-treatment Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000003205 diastolic effect Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 208000002173 dizziness Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- 229950008913 edisilate Drugs 0.000 description 2
- 229950007655 esilate Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- -1 funnarate Chemical compound 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 125000005490 tosylate group Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101000777550 Homo sapiens CCN family member 2 Proteins 0.000 description 1
- 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 1
- 101000609255 Homo sapiens Plasminogen activator inhibitor 1 Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 101100179469 Mus musculus Ighg2b gene Proteins 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 238000003016 alphascreen Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000003491 cAMP production Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007375 cmc medium Substances 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 108091005995 glycated hemoglobin Proteins 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000037219 healthy weight Effects 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 102000047612 human CCN2 Human genes 0.000 description 1
- 102000043283 human SERPINE1 Human genes 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 229940048153 losartan potassium 100 mg Drugs 0.000 description 1
- 229940048175 losartan potassium 50 mg Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000013227 male C57BL/6J mice Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 238000013059 nephrectomy Methods 0.000 description 1
- 238000013116 obese mouse model Methods 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000013105 post hoc analysis Methods 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000003087 receptor blocking agent Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000015598 salt intake Nutrition 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562198213P | 2015-07-29 | 2015-07-29 | |
| US62/198,213 | 2015-07-29 | ||
| PCT/EP2016/067968 WO2017017165A1 (en) | 2015-07-29 | 2016-07-28 | Pde4 inhibitor for the treatment of diabetic nephropathy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2992796A1 true CA2992796A1 (en) | 2017-02-02 |
Family
ID=56551407
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2992796A Abandoned CA2992796A1 (en) | 2015-07-29 | 2016-07-28 | Pde4 inhibitor for the treatment of diabetic nephropathy |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20200179369A1 (enExample) |
| EP (1) | EP3328381A1 (enExample) |
| JP (1) | JP2018521077A (enExample) |
| CN (1) | CN108135886A (enExample) |
| BR (1) | BR112018001116A2 (enExample) |
| CA (1) | CA2992796A1 (enExample) |
| EA (1) | EA201890346A1 (enExample) |
| MA (1) | MA42519A (enExample) |
| WO (1) | WO2017017165A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11179384B2 (en) | 2016-08-26 | 2021-11-23 | Takeda Gmbh | Treatment of nonalcoholic fatty liver disease |
| CN107157999A (zh) * | 2017-05-27 | 2017-09-15 | 青岛海蓝医药有限公司 | 川芎嗪硝酮衍生物在预防和治疗糖尿病并发症疾病中的应用 |
| CN114053281B (zh) * | 2020-08-10 | 2025-05-27 | 成都文鼎科技发展有限公司 | 治疗慢性肾病的方法和药物组合物 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7413751B2 (en) * | 2001-10-25 | 2008-08-19 | Depomed, Inc. | Methods of treatment using a gastric retained losartan dosage |
| US7157584B2 (en) * | 2004-02-25 | 2007-01-02 | Takeda Pharmaceutical Company Limited | Benzimidazole derivative and use thereof |
| EP2589599B1 (en) * | 2004-03-03 | 2014-06-25 | Takeda GmbH | Novel hydroxy-6-heteroarylphenanthridines and their use as PDE4 inhibitors |
| GB0504103D0 (en) * | 2005-02-28 | 2005-04-06 | Syngenta Ltd | Novel method |
-
2016
- 2016-07-28 US US15/746,560 patent/US20200179369A1/en not_active Abandoned
- 2016-07-28 JP JP2018503204A patent/JP2018521077A/ja active Pending
- 2016-07-28 MA MA042519A patent/MA42519A/fr unknown
- 2016-07-28 CA CA2992796A patent/CA2992796A1/en not_active Abandoned
- 2016-07-28 EP EP16744758.0A patent/EP3328381A1/en not_active Withdrawn
- 2016-07-28 BR BR112018001116-9A patent/BR112018001116A2/pt not_active Application Discontinuation
- 2016-07-28 CN CN201680056550.2A patent/CN108135886A/zh active Pending
- 2016-07-28 WO PCT/EP2016/067968 patent/WO2017017165A1/en not_active Ceased
- 2016-07-28 EA EA201890346A patent/EA201890346A1/ru unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2018521077A (ja) | 2018-08-02 |
| EP3328381A1 (en) | 2018-06-06 |
| WO2017017165A1 (en) | 2017-02-02 |
| BR112018001116A2 (pt) | 2018-09-11 |
| EA201890346A1 (ru) | 2018-08-31 |
| US20200179369A1 (en) | 2020-06-11 |
| CN108135886A (zh) | 2018-06-08 |
| MA42519A (fr) | 2018-06-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2579879B1 (en) | Triazine derivatives for delaying the onset of type 1 diabetes | |
| JP6337170B2 (ja) | ネコの全身性疾患の予防又は治療の為のアンジオテンシンｉｉ受容体アンタゴニスト | |
| EP2545920A1 (en) | Therapy for complications of diabetes | |
| JP7402907B2 (ja) | ネコの全身性疾患の予防又は治療用アンジオテンシンｉｉ受容体拮抗薬 | |
| CN119386017A (zh) | 用于治疗慢性肾病的齐泊腾坦和达格列净的组合 | |
| US20200179369A1 (en) | Treatment of diabetic nephropathy | |
| TW202038937A (zh) | 治療高血壓的方法 | |
| WO2009143403A1 (en) | Combination therapy for the management hypertension | |
| EA050364B1 (ru) | Комбинация зиботентана и дапаглифлозина для лечения хронического заболевания почек | |
| CN117396197A (zh) | 慢性肾脏病的猫的治疗方法 | |
| JP2009256209A (ja) | 降圧療法 | |
| Hongwei et al. | ASSA13-14-9 Efficacy and Safety of Olmesartan and Olmesartan Plus Hydrochlorothiazide Combined with Amlodipine in Chinese Patients with Mild to Moderate Essential Hypertension | |
| HK1180956A (en) | Therapy for complications of diabetes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20220301 |