JP2015524419A5 - - Google Patents
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- JP2015524419A5 JP2015524419A5 JP2015523532A JP2015523532A JP2015524419A5 JP 2015524419 A5 JP2015524419 A5 JP 2015524419A5 JP 2015523532 A JP2015523532 A JP 2015523532A JP 2015523532 A JP2015523532 A JP 2015523532A JP 2015524419 A5 JP2015524419 A5 JP 2015524419A5
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- Prior art keywords
- aib
- seq
- hypoglycemia
- glu
- ser
- Prior art date
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- 206010020993 Hypoglycaemia Diseases 0.000 claims 40
- 230000002218 hypoglycaemic Effects 0.000 claims 40
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 31
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 23
- MTCFGRXMJLQNBG-REOHCLBHSA-N L-serine Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 21
- 150000001875 compounds Chemical class 0.000 claims 17
- 150000003839 salts Chemical class 0.000 claims 15
- 239000011780 sodium chloride Substances 0.000 claims 15
- 239000012453 solvate Substances 0.000 claims 15
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims 10
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims 10
- 241000024188 Andala Species 0.000 claims 9
- 125000003275 alpha amino acid group Chemical group 0.000 claims 9
- 206010012601 Diabetes mellitus Diseases 0.000 claims 6
- 230000001154 acute Effects 0.000 claims 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 claims 5
- 238000006467 substitution reaction Methods 0.000 claims 5
- 125000000030 D-alanine group Chemical group [H]N([H])[C@](C([H])([H])[H])(C(=O)[*])[H] 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims 3
- 208000004981 Coronary Disease Diseases 0.000 claims 3
- 206010058108 Dyslipidaemia Diseases 0.000 claims 3
- 208000002705 Glucose Intolerance Diseases 0.000 claims 3
- 206010018464 Glycogen storage disease type I Diseases 0.000 claims 3
- 206010020772 Hypertension Diseases 0.000 claims 3
- 102000004877 Insulin Human genes 0.000 claims 3
- 108090001061 Insulin Proteins 0.000 claims 3
- 206010022498 Insulinoma Diseases 0.000 claims 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 3
- 206010061227 Lipid metabolism disease Diseases 0.000 claims 3
- 208000008589 Obesity Diseases 0.000 claims 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 3
- 208000001072 Type 2 Diabetes Mellitus Diseases 0.000 claims 3
- 201000001320 atherosclerosis Diseases 0.000 claims 3
- 239000002876 beta blocker Substances 0.000 claims 3
- 230000001684 chronic Effects 0.000 claims 3
- 201000008739 coronary artery disease Diseases 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 229940079593 drugs Drugs 0.000 claims 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 3
- 235000020828 fasting Nutrition 0.000 claims 3
- 230000002496 gastric Effects 0.000 claims 3
- 201000004541 glycogen storage disease I Diseases 0.000 claims 3
- 150000007523 nucleic acids Chemical class 0.000 claims 3
- 108020004707 nucleic acids Proteins 0.000 claims 3
- 235000020824 obesity Nutrition 0.000 claims 3
- 230000035935 pregnancy Effects 0.000 claims 3
- BVQVLAIMHVDZEL-UHFFFAOYSA-N 1-phenyl-1,2-propanedione Chemical group CC(=O)C(=O)C1=CC=CC=C1 BVQVLAIMHVDZEL-UHFFFAOYSA-N 0.000 claims 2
- 125000000660 D-proline group Chemical group [H]N1[C@](C(=O)[*])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 125000002574 D-valine group Chemical group [H]N([H])[C@@]([H])(C(=O)[*])C(C([H])([H])[H])(C([H])([H])[H])[H] 0.000 claims 2
- 208000004930 Fatty Liver Diseases 0.000 claims 2
- 108060003199 Glucagon Proteins 0.000 claims 2
- 229960004666 Glucagon Drugs 0.000 claims 2
- MASNOZXLGMXCHN-ZLPAWPGGSA-N Glucagonum Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims 2
- 206010019708 Hepatic steatosis Diseases 0.000 claims 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 2
- 239000000556 agonist Substances 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 2
- 101500013968 human Glucagon Proteins 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 125000004435 hydrogen atoms Chemical class [H]* 0.000 claims 2
- 230000000607 poisoning Effects 0.000 claims 2
- 231100000572 poisoning Toxicity 0.000 claims 2
- 231100000240 steatosis hepatitis Toxicity 0.000 claims 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims 2
- 206010012335 Dependence Diseases 0.000 claims 1
- 210000004185 Liver Anatomy 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
Claims (21)
- 式(I):
R1‐Z‐R2 (I)
{式中、
R1が、水素、C1‐4アルキル、アセチル、ホルミル、ベンゾイル又はトリフルオロアセチルであり;
R2が、OH又はNH2であり;そして
Zが、式(Ia):
His‐Ser‐Gln‐Gly‐Thr‐Phe‐Thr‐Ser‐Asp‐Tyr‐Ser‐Lys‐Tyr‐Leu‐Asp‐Ser‐Arg‐Arg‐Ala‐Gln‐Asp‐Phe‐Val‐Gln‐Trp‐Leu‐Glu‐Asn‐Thr (Ia)
の配列に由来し、且つ、以下の:
X2が、Aib及びAlaから選択され;
X3が、His、Pro、Dab(Ac)、Dap(Ac)及びGln(Me)から選択され;
X4が、DAlaであり;
X9が、Gluであり;
X10が、Val、Leu、N‐Me‐Tyr及びN‐Me‐DTyrから選択され;
X15が、Gluであり;
X16が、Aib、Lys、Glu、Leu、Val、DVal、Phe、His、Arg、Pro、DPro、N‐Me‐Ser及びN‐Me‐DSerから選択され;
X17が、Ala及びSerから選択され;
X20が、Glu及びLysから選択され;
X21が、Glu、Lys及びSerから選択され;
X24が、Lys、Ser、Glu及びAlaから選択され;
X28が、Ser、Lys及びGluから選択されるか、又は存在せず;
X29が、Ser及びAlaから選択されるか、又は存在しない、
のように2、3、4、9、10、15、16、17、20、21、24、28及び29から選択される配列位置にのみ存在する少なくとも4個のアミノ酸置換又は欠失をさらに含むアミノ酸配列であって、
但し、Zが、以下の:
HSQGTFTSDYSKYLDSARAEDFVKWLEST;及び
HSQGTFTSDYSKYLESRRAKEFVEWLEST、
から選択されない。}を有する化合物、又は医薬的に許容されるその塩若しくは溶媒和物であって、
前記化合物は、グルカゴンアゴニスト活性、ならびに、天然ヒトグルカゴンと比較して、改善された溶解性及び/又は安定性を有することを特徴とする、化合物、又は医薬的に許容されるその塩若しくは溶媒和物。 - 式(I):
R1‐Z‐R2 (I)
{式中、
R1が、水素、C1‐4アルキル、アセチル、ホルミル、ベンゾイル又はトリフルオロアセチルであり;
R2が、OH又はNH2であり;そして
Zが、式(Ia):
His‐Ser‐Gln‐Gly‐Thr‐Phe‐Thr‐Ser‐Asp‐Tyr‐Ser‐Lys‐Tyr‐Leu‐Asp‐Ser‐Arg‐Arg‐Ala‐Gln‐Asp‐Phe‐Val‐Gln‐Trp‐Leu‐Glu‐Asn‐Thr (Ia)
の配列に由来し、且つ、以下の:
X2が、Aib及びAlaから選択され;
X3が、His及びProから選択され;
X9が、Gluであり;
X10が、N‐Me‐Tyr及びN‐Me‐DTyrから選択され;
X15が、Gluであり;
X16が、Aib、Lys、Glu、Leu、Val、DVal、Phe、His、Arg、Pro、DPro、N‐Me‐Ser及びN‐Me‐DSerから選択され;
X17が、Ala及びSerから選択され;
X20が、Glu及びLysから選択され;
X21が、Glu、Lys及びSerから選択され;
X24が、Lys、Ser、Glu及びAlaから選択され;
X28が、Ser及びLysから選択されるか、又は存在せず;
X29が、Ser及びAlaから選択されるか、又は存在しない、
のように2、3、9、10、15、16、17、20、21、24、28及び29から選択される(Xで示された)配列位置にのみ存在する少なくとも4個のアミノ酸置換又は欠失をさらに含むアミノ酸配列であって、
但し、Zが、以下の:
HSQGTFTSDYSKYLDSARAEDFVKWLEST;及び
HSQGTFTSDYSKYLESRRAKEFVEWLEST、
から選択されない。}を有する化合物、医薬的に許容されるその塩若しくは溶媒和物であって、
前記化合物は、グルカゴンアゴニスト活性、ならびに、天然ヒトグルカゴンと比較して、改善された溶解性及び/又は安定性を有することを特徴とする、化合物、又は医薬的に許容されるその塩若しくは溶媒和物。 - 前記式(I)の化合物の2、3、4、9、10、15、16、17、20、21、24、28及び29から選択される(Xで示された)アミノ酸配列位置の少なくとも4個のアミノ酸置換又は欠失が、以下の:
X2が、Aib及びAlaから選択され;
X3が、His及びProから選択され;
X4が、DAlaであり;
X9が、Gluであり;
X10が、N‐Me‐Tyr及びN‐Me‐DTyrから選択され;
X15が、Gluであり;
X16が、Aib、Lys、Glu、Leu、Val、Phe、His及びArgから選択され;
X17が、Ala及びSerから選択され;
X20が、Glu及びLysから選択され;
X21が、Glu、Lys及びSerから選択され;
X24が、Lys、Ser、Glu及びAlaから選択され;
X28が、Ser、Glu及びLysから選択されるか、又は存在せず;
X29が、Ser及びAlaから選択されるか、又は存在しない、
である、請求項1に記載の化合物、又は医薬的に許容されるその塩若しくは溶媒和物。 - 前記少なくとも4個のアミノ酸置換又は欠失が、式(I)の化合物の2、3、4、10、15、16、17、20、21、24、28及び29から選択される(Xで示された)アミノ酸配列位置に存在し、以下の:
X2が、Alaであり;
X3が、Dab(Ac)、Dap(Ac)及びGln(Me)であり;
X4が、DAlaであり;
X10が、Leu及びValから選択され;
X15が、Gluであり;
X16が、Aib、Lys、Glu、Leu及びValから選択され;
X17が、Alaであり;
X20が、Glu及びLysから選択され;
X21が、Glu及びSerから選択され;
X24が、Lys、Ser及びGluから選択され;
X28が、Ser、Glu及びLysから選択され;
X29が、Alaであるか、又は存在しない、
である、請求項1に記載の化合物、又は医薬的に許容されるその塩若しくは溶媒和物。 - 前記少なくとも4個のアミノ酸置換又は欠失が、式(I)の化合物の2、3、4、16、17、20、21、24、28及び29から選択される(Xで示された)アミノ酸配列位置に存在し、以下の:
X2が、Alaであり;
X3が、Dab(Ac)、Dap(Ac)、Gln(Me)又はHisであり;
X4が、DAlaであり;
X16が、Aib、Lys、Gluから選択され;
X17が、Alaであり;
X20が、Glu及びLysから選択され;
X21が、Glu及びSerから選択され;
X24が、Lys、Ser及びGluから選択され;
X28が、Ser、Glu及びLysから選択され;
X29が、Alaであるか、又は存在しない、
である、請求項1に記載の化合物、又は医薬的に許容されるその塩若しくは溶媒和物。 - 前記X17が、Alaである、請求項1〜5のいずれか1項に記載の化合物。
- 前記Zが、以下の:
HSQGTFTSDYSKYLDSARAESFVKWLEST(配列番号2)
HSQGTFTSDYSKYLDSARAEDFVKWLEET(配列番号3)
HSQGTFTSDYSKYLDKARAEDFVKWLEST(配列番号4)
HSQGTFTSDYSKYLDSARAEDFVAWLEST(配列番号5)
HSQGTFTSDYSKYLDEARAKDFVEWLEKT(配列番号6)
HSQGTFTSDYSKYLDSARAEDFVEWLEST(配列番号7)
HSQGTFTSDYSKYLESARAEDFVKWLEST(配列番号9)
HSQGTFTSDYSKYLDSARAEEFVKWLEST(配列番号10)
HSQGTFTSDYSKYLDSARAEDFVSWLEST(配列番号11)
HSQGTFTSDLSKYLDSARAEDFVKWLEST(配列番号12)
HSQGTFTSDYSKYLD‐Aib‐ARAEDFVKWLEST(配列番号13)
HSQGTFTSDYSKYLDSARAEDFVKWLES(配列番号14)
HSQGTFTSDYSKYLDEARAEDFVKWLEST(配列番号15)
HSQGTFTSDYSKYLD‐Aib‐ARAESFVKWLEST(配列番号16)
HSQGTFTSDYSKYLESARAESFVKWLEST(配列番号17)
HSQGTFTSDYSKYLDLARAEDFVKWLEST(配列番号18)
HSQGTFTSDYSKYLDKRRAEDFVSWLEST(配列番号19)
HSQGTFTSDYSKYLDVARAESFVKWLEST(配列番号20)
HAQGTFTSDYSKYLD‐Aib‐ARAESFVKWLEST(配列番号21)
HSQGTFTSDYSKYLD‐Aib‐ARAEEFVKWLEST(配列番号22)
HSQ‐DAla‐TFTSDYSKYLD‐Aib‐ARAESFVKWLEST(配列番号23)
HSQGTFTSDVSKYLD‐Aib‐ARAESFVKWLEST(配列番号24)
HS‐[Dab(Ac)]‐GTFTSDYSKYLD‐Aib‐ARAESFVKWLEST(配列番号25)
HSQGTFTSDYSKYLD‐Aib‐RRAESFVKWLEST(配列番号26)
HS‐[Gln(Me)]‐GTFTSDYSKYLD‐Aib‐ARAESFVKWLEST(配列番号27)
HSQGTFTSDYSKYLDEARAKSFVEWLEKT(配列番号28)
HSQGTFTSDYSKYLDEARAKSFVEWLEST(配列番号29)
HSQGTFTSDYSKYLD‐Aib‐ARAKSFVEWLEKT(配列番号30)
HSQGTFTSDYSKYLD‐Aib‐ARAESFVKWLESA(配列番号31)
HSQGTFTSDYSKYLD‐Aib‐ARAESFVKWLEST(配列番号32)
HS‐[Dab(Ac)]‐GTFTSDYSKYLD‐Aib‐ARAESFVKWLEST(配列番号33)
HSQGTFTSDYSKYLD‐Aib‐ARAEEFVSWLEKT(配列番号34)
HSQGTFTSDYSKYLD‐Aib‐ARAEKFVEWLEST(配列番号35)
HSQGTFTSDYSKYLD‐Aib‐ARAEEFVAWLEST(配列番号36)
HSQGTFTSDYSKYLD‐Aib‐ARAEEFVKWLEET(配列番号37)
HSQGTFTSDYSKYLE‐Aib‐ARAEEFVKWLEST(配列番号38)
HSHGTFTSDYSKYLD‐Aib‐ARAEEFVKWLEST(配列番号39)
HS‐[Dab(Ac)]‐GTFTSDYSKYLD‐Aib‐ARAEEFVKWLEST(配列番号40)及び
HS‐[Dap(Ac]‐GTFTSDYSKYLD‐Aib‐ARAEEFVKWLEST(配列番号41)、
から成る群から選択される、請求項1〜5のいずれか1項に記載の化合物、又は医薬的に許容されるその塩若しくは溶媒和物。 - 以下の:
Hy‐HSQGTFTSDYSKYLDSARAESFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLDSARAEDFVKWLEET‐OH、
Hy‐HSQGTFTSDYSKYLDKARAEDFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLDSARAEDFVAWLEST‐OH、
Hy‐HSQGTFTSDYSKYLDEARAKDFVEWLEKT‐OH、
Hy‐HSQGTFTSDYSKYLDSARAEDFVEWLEST‐OH、
Hy‐HSQGTFTSDYSKYLESARAEDFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLDSARAEEFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLDSARAEDFVSWLEST‐OH、
Hy‐HSQGTFTSDLSKYLDSARAEDFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLD‐Aib‐ARAEDFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLDSARAEDFVKWLES‐OH、
Hy‐HSQGTFTSDYSKYLDEARAEDFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLD‐Aib‐ARAESFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLESARAESFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLDLARAEDFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLDKRRAEDFVSWLEST‐OH、
Hy‐HSQGTFTSDYSKYLDVARAESFVKWLEST‐OH、
Hy‐HAQGTFTSDYSKYLD‐Aib‐ARAESFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLD‐Aib‐ARAEEFVKWLEST‐OH、
Hy‐HSQ‐DAla‐TFTSDYSKYLD‐Aib‐ARAESFVKWLEST‐OH、
Hy‐HSQGTFTSDVSKYLD‐Aib‐ARAESFVKWLEST‐OH、
Hy‐HS‐[Dab(Ac)]‐GTFTSDYSKYLD‐Aib‐ARAESFVKWLEST‐NH2、
Hy‐HSQGTFTSDYSKYLD‐Aib‐RRAESFVKWLEST‐OH、
Hy‐HS‐[Gln(Me)]‐GTFTSDYSKYLD‐Aib‐ARAESFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLDEARAKSFVEWLEKT‐OH、
Hy‐HSQGTFTSDYSKYLDEARAKSFVEWLEST‐OH、
Hy‐HSQGTFTSDYSKYLD‐Aib‐ARAKSFVEWLEKT‐OH、
Hy‐HSQGTFTSDYSKYLD‐Aib‐ARAESFVKWLESA‐OH、
Hy‐HSQGTFTSDYSKYLD‐Aib‐ARAESFVKWLEST‐NH2、
Hy‐HS‐[Dab(Ac)]‐GTFTSDYSKYLD‐Aib‐ARAESFVKWLEST‐OH、
Hy‐HSQGTFTSDYSKYLD‐Aib‐ARAEEFVSWLEKT‐OH、
Hy‐HSQGTFTSDYSKYLD‐Aib‐ARAEKFVEWLEST‐OH、
Hy‐HSQGTFTSDYSKYLD‐Aib‐ARAEEFVAWLEST‐OH、
Hy‐HSQGTFTSDYSKYLD‐Aib‐ARAEEFVKWLEET‐OH、
Hy‐HSQGTFTSDYSKYLE‐Aib‐ARAEEFVKWLEST‐OH、
Hy‐HSHGTFTSDYSKYLD‐Aib‐ARAEEFVKWLEST‐NH2、
Hy‐HS‐[Dab(Ac)]‐GTFTSDYSKYLD‐Aib‐ARAEEFVKWLEST‐OH、
Hy‐HS‐[Dab(Ac)]‐GTFTSDYSKYLD‐Aib‐ARAEEFVKWLEST‐NH2、
Hy‐HS‐[Dap(Ac)]‐GTFTSDYSKYLD‐Aib‐ARAEEFVKWLEST‐NH2、
又は医薬的に許容されるその塩若しくは溶媒和物から成る群から選択される、請求項1〜5のいずれか1項に記載の化合物。 - 請求項1〜7のいずれか1項に記載のペプチドZをコードする核酸構築物であって、前記ペプチドが、完全に天然に存在するアミノ酸から成ることを特徴とする、核酸構築物。
- 請求項9に記載の核酸構築物を含む発現ベクター。
- 請求項9に記載の核酸構築物又は請求項10に記載の発現ベクターを含む宿主細胞。
- 請求項1〜8のいずれか1項に記載の化合物、又は医薬的に許容されるその塩若しくは溶媒和物、及び医薬的に許容し得る担体を含む医薬組成物。
- 処置を必要としている対象の疾患又は病態を処置するための医薬組成物であって、治療的に有効な量の、請求項1〜8のいずれか1項に記載の化合物、又は医薬的に許容されるその塩若しくは溶媒和物を含む前記医薬組成物。
- 前記疾患が、以下の:低血糖、急性低血糖、慢性低血糖、2型糖尿病、耐糖能異常、1型糖尿病、肥満、冠動脈性心疾患、アテローム性動脈硬化症、高血圧、脂質異常症、脂肪肝、β‐ブロッカー中毒、インスリノーマ及びVon Gierkes病から成る群から選択される、請求項13に記載の医薬組成物。
- 前記疾患又は病態が、低血糖である、請求項14に記載の医薬組成物。
- 前記低血糖が、以下の:糖尿病性低血糖、急性インスリン誘発性低血糖、非糖尿病性低血糖、反応性低血糖、空腹時低血糖、薬物誘発性低血糖、アルコール誘発性低血糖、胃バイパス誘発性低血糖及び妊娠中に生じる低血糖から成る群から選択される、請求項15に記載の医薬組成物。
- 医療処置方法における使用のための、請求項1〜8のいずれか1項に記載の化合物、又は医薬的に許容されるその塩若しくは溶媒和物。
- 低血糖、急性低血糖、慢性低血糖、2型糖尿病、耐糖能異常、1型糖尿病、肥満、冠動脈性心疾患、アテローム性動脈硬化症、高血圧、脂質異常症、脂肪肝、β‐ブロッカー中毒、インスリノーマ及びVon Gierkes病の処置のための、請求項1〜8のいずれか1項に記載の化合物、又は医薬的に許容されるその塩若しくは溶媒和物。
- 前記低血糖が、以下の:糖尿病性低血糖、急性インスリン誘発性低血糖、非糖尿病性低血糖、反応性低血糖、空腹時低血糖、薬物誘発性低血糖、アルコール誘発性低血糖、胃バイパス誘発性低血糖及び妊娠中に生じる低血糖から成る群から選択される、請求項18に記載の使用のための化合物、又は医薬的に許容されるその塩若しくは溶媒和物。
- 低血糖、急性低血糖、慢性低血糖、2型糖尿病、耐糖能異常、1型糖尿病、肥満、冠動脈性心疾患、アテローム性動脈硬化症、高血圧、脂質異常症、脂肪肝、β‐ブロッカー中毒、インスリノーマ及びVon Gierkes病の処置のための薬剤の調製における、請求項の1〜8のいずれか1項に記載の化合物、又は医薬的に許容されるその塩若しくは溶媒和物の使用。
- 前記低血糖が、以下の:糖尿病性低血糖、急性インスリン誘発性低血糖、非糖尿病性低血糖、反応性低血糖、空腹時低血糖、薬物誘発性低血糖、アルコール誘発性低血糖、胃バイパス誘発性低血糖及び妊娠中に生じる低血糖から成る群から選択される、請求項20に記載の使用。
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