JPWO2021035157A5 - - Google Patents

Description

Alternative combinations and variations of the provided examples will become apparent based on this disclosure. While it is not possible to provide specific examples for all of the many possible variations of the described embodiments, such combinations and variations may be the subject of the claims that ultimately arise.
Moreover, this application also includes the following aspects.
[Aspect 1]
A method of treating or preventing a kidney disorder, comprising administering to a subject in need of such treatment or prevention a pharmaceutically acceptable amount of a PDE1 inhibitor.
[Aspect 2]
A method according to aspect 1, wherein the renal disorder is selected from one or more of renal fibrosis, chronic renal disease, renal failure, glomerulosclerosis and nephritis.
[Aspect 3]
3. The method of aspect 1 or 2, wherein said condition is renal fibrosis.
[Aspect 4]
3. The method of aspect 1 or 2, wherein said condition is chronic kidney disease.
[Aspect 5]
3. The method of aspect 1 or 2, wherein said condition is renal failure.
[Aspect 6]
A method according to aspect 1 or 2, wherein said condition is glomerulosclerosis.
[Aspect 7]
3. The method of aspect 1 or 2, wherein said condition is nephritis.
[Aspect 8]
Kidney damage is diabetes, kidney damage, hypertension, cancer growth (e.g. polycystic kidney disease), or cardiovascular disease (e.g. angina pectoris, stroke, essential hypertension, pulmonary hypertension, secondary hypertension) , isolated systolic hypertension, diabetes-related hypertension, atherosclerosis-related hypertension, renovascular hypertension, congestive heart failure, myocardial, angina, and stroke, hypertension, inflammation 3. A method according to aspect 1 or 2, which results from sexual diseases or disorders, fibrosis, cardiac hypertrophy, vascular remodeling, and connective tissue diseases and disorders such as Marfan's syndrome.
[Aspect 9]
The method of any preceding aspect, wherein the renal impairment is a result of diabetes.
[Aspect 10]
The method of any preceding aspect, wherein the kidney damage results from damage to the kidneys.
[Aspect 11]
The method of any preceding aspect, wherein the renal impairment is a result of hypertension.
[Aspect 12]
The method of any preceding aspect, wherein the kidney damage results from cancer growth (eg, polycystic kidney disease).
[Aspect 13]
Renal damage is cardiovascular disease (e.g., angina pectoris, stroke, essential hypertension, pulmonary hypertension, secondary hypertension, isolated systolic hypertension, diabetes-related hypertension, atherosclerosis) hypertension, renovascular hypertension, congestive heart failure, myocardial, angina and stroke, hypertension, inflammatory diseases or disorders, fibrosis, cardiac hypertrophy, vascular remodeling, and connective tissue diseases and The method of any preceding aspect, resulting from a disorder such as Marfan's Syndrome.
[Aspect 14]
A PDE1 inhibitor is
(A) Formula I, in free, salt or prodrug form, including enantiomers, diastereoisomers and racemates:
[In the formula,
(i) R ₁ is H or C _1-4 alkyl (e.g. methyl);
(ii) R ₄ is H or C _1-4 alkyl and R ₂ and R ₃ are independently H or C _1-4 alkyl (e.g. R ₂ and R ₃ are both methyl or R ₂ is H and R ₃ is isopropyl), aryl, heteroaryl, (optionally hetero)arylalkoxy, or (optionally hetero)arylalkyl; or
R ₂ is H and R ₃ and R ₄ together form a dimethylene, trimethylene or tetramethylene bridge (preferably R ₃ and R ₄ together have a cis configuration , e.g., the carbons bearing R3 and R4 have the R and S configurations, _respectively ) _;
(iii) R5 _is substituted heteroarylalkyl, for example substituted with haloalkyl; or
R ₅ is attached to one of the nitrogens of the pyrazolo moiety of Formula I and is represented by Formula A:
(wherein X, Y and Z are independently N or C; R ₈ , R ₉ , R ₁₁ and R ₁₂ are independently H or halogen (e.g. Cl or F); , R ₁₀ is halogen, alkyl, cycloalkyl, haloalkyl (eg, trifluoromethyl), aryl (eg, phenyl), heteroaryl (eg, pyridyl optionally substituted with halogen (eg, pyrid-2-yl ), or thiadiazolyl (e.g. 1,2,3-thiadiazol-4-yl)), diazolyl, triazolyl, tetrazolyl, arylcarbonyl (e.g. benzoyl), alkylsulfonyl (e.g. methylsulfonyl), heteroarylcarbonyl, or alkoxy carbonyl; provided that when X, Y or Z is nitrogen, R ₈ , R ₉ or R ₁₀ are absent, respectively)
is a portion indicated by;
(iv) R ₆ is H, alkyl, aryl, heteroaryl, arylalkyl (eg benzyl), arylamino (eg phenylamino), heteroarylamino, N,N-dialkylamino, N,N-diarylamino , or N-aryl-N-(arylalkyl)amino (for example, N-phenyl-N-(1,1′-biphen-4-ylmethyl)amino);
(v) n is 0 or 1;
(vi) when n is 1, A is -C(R ₁₃ R ₁₄ )-, where R ₁₃ and R ₁₄ are independently H or C _1-4 alkyl, aryl, hetero aryl, (optionally hetero)arylalkoxy or (optionally hetero)arylalkyl];
(B) Formula Ia in free form, pharmaceutically acceptable salt form or prodrug form, including enantiomers, diastereoisomers and racemates:
[In the formula,
(i) R ₂ and R ₅ are independently H or hydroxy, and R ₃ and R ₄ together form a trimethylene or tetramethylene bridge [preferably R ₃ and R ₄ are supported have the R and S configurations, respectively]; or R ₂ and R ₃ are each methyl and R ₄ and R ₅ are each H; or R ₂ , R ₄ and R ₅ are H and R ₃ is isopropyl [preferably the carbon bearing R ₃ has the R configuration];
(ii) R ₆ is phenylamino (optionally halo- or hydroxy-substituted), benzylamino (optionally halo- or hydroxy-substituted), C 1-4 alkyl, _or C _1-4 alkylsulfide is; for example, phenylamino or 4-fluorophenylamino;
(iii) R ₁₀ is C _1-4 alkyl, methylcarbonyl, hydroxyethyl, carboxylic acid, sulfonamido, (optionally halo- or hydroxy-substituted) phenyl, (optionally halo- or hydroxy-substituted ) pyridyl (e.g. 6-fluoropyrid-2-yl), or thiadiazolyl (e.g. 1,2,3-thiadiazol-4-yl);
(iv) X and Y are independently C or N];
(C) Formula II in free, salt or prodrug form:
(i) X is C _1-6 alkylene (eg methylene, ethylene or prop-2-yn-1-ylene);
(ii) Y is a single bond, alkynylene (eg -C≡C-), arylene (eg phenylene) or heteroarylene (eg pyridylene);
(iii) Z is H, aryl (eg phenyl), heteroaryl (eg pyridyl, eg pyrid-2-yl), halo (eg F, Br, Cl), haloC 1-6 alkyl ₍ eg , trifluoromethyl), —C(O)—R ₁ , —N(R ₂ )(R ₃ ), or at least one atom selected from the group consisting of N or O C _3-7 cycloalkyl (for example, cyclopentyl, cyclohexyl, tetrahydro-2H-pyran-4-yl, or morpholinyl);
(iv) R ₁ is C _1-6 alkyl, haloC _1-6 alkyl, —OH or —OC _1-6 alkyl (eg —OCH ₃ );
(v) R ₂ and R ₃ are independently H or C _1-6 alkyl;
(vi) R ₄ and R ₅ are independently H, C _1-6 alkyl, or one or more of halo (eg fluorophenyl, eg 4-fluorophenyl), hydroxy (eg hydroxyphenyl, 4-hydroxyphenyl or 2-hydroxyphenyl) or aryl optionally substituted with C _1-6 alkoxy (eg phenyl);
(vii) wherein X, Y and Z are independently one or more of halo (e.g. F, Cl or Br), C _1-6 alkyl (e.g. methyl), haloC _1-6 alkyl ( trifluoromethyl), for example, Z is one or more halo (eg, 6-fluoropyrid-2-yl, 5-fluoropyrid-2-yl, 6-fluoropyrid-2-yl , 3-fluoropyrid-2-yl, 4-fluoropyrid-2-yl, 4,6-dichloropyrid-2-yl), haloC _1-6 alkyl (for example 5-trifluoromethylpyrid-2-yl) or heteroaryl, for example pyridyl, substituted with C 1-6 alkyl (for example 5-methylpyrid-2-yl) or Z is one or more halo (for example 4- fluorophenyl ₎ is aryl, for example phenyl, substituted with;
(D) Formula III, in free or salt form:
[In the formula,
(i) R ₁ is H or C _1-4 alkyl (e.g. methyl or ethyl);
(ii) R ₂ and R ₃ are independently H or C _1-6 alkyl (e.g. methyl or ethyl);
(iii) R ₄ is H or C _1-4 alkyl (eg methyl or ethyl);
(iv) R ₅ is independently -C(=O)-C _1-6 alkyl (eg -C(=O)-CH ₃ ) and C _1-6 hydroxyalkyl (eg 1-hydroxyethyl) aryl (e.g., phenyl) optionally substituted with one or more groups selected from;
(v) R ₆ and R ₇ are independently H or one or more independently selected from C _1-6 alkyl (e.g. methyl or ethyl) and halogen (e.g. F or Cl) aryl (e.g., phenyl) optionally substituted with groups, such as unsubstituted phenyl, or phenyl substituted with one or more halogens (e.g., F), or one or more C 1-6 alkyl _and one phenyl substituted with 1 or more halogens, or phenyl substituted with 1 C _1-6 alkyl and 1 halogen, for example 4-fluorophenyl or 3,4-difluorophenyl or 4-fluoro-3 - is methylphenyl;
(vi) n is 1, 2, 3 or 4];
(E) Formula IV in free or salt form
[(i) R ₁ is C _1-4 alkyl (eg, methyl or ethyl), or —NH(R ₂ ), where R ₂ is phenyl optionally substituted with halo (eg, fluoro) , for example 4-fluorophenyl;
(ii) X, Y and Z are independently N or C;
(iii) R ₃ , R ₄ and R ₅ are independently H or C _1-4 alkyl (e.g. methyl); or R ₃ is H and R ₄ and R ₅ together form a trimethylene bridge (preferably R ₄ and R ₅ together have a cis configuration, e.g. the carbons bearing R ₄ and R ₅ have the R and S configurations, respectively). are doing);
(iv) R6 _, R7 _and R8 _are independently
H.
C _1-4 alkyl (for example methyl),
pyrid-2-yl substituted with hydroxy, or
-S(O) _{2 -} NH2
is;
(v) with the proviso that when X, Y and/or Z are N, respectively, R ₆ , R ₇ and/or R ₈ are absent; and when X, Y and Z are all C, R ₆ , at least one of R ₇ or R ₈ is —S(O) ₂ —NH ₂ , or pyrid-2-yl substituted with hydroxy];
(F) formula V, in free or salt form;
[In the formula,
(iv) R ₁ is —NH(R ₄ ), wherein R ₄ is phenyl optionally substituted with halo (eg fluoro), such as 4-fluorophenyl;
(v) R ₂ is H or C _1-6 alkyl (e.g. methyl, isobutyl or neopentyl);
(vi) R ₃ is —SO ₂ NH ₂ or —COOH]; and
(G) Formula VI in free form or in pharmaceutically acceptable salt form
[In the formula,
(iv) R ₁ is —NH(R ₄ ), wherein R ₄ is phenyl optionally substituted with halo (eg fluoro), such as 4-fluorophenyl;
(v) R ₂ is H or C _1-6 alkyl (e.g. methyl or ethyl);
(vi) R ₃ is H, halogen (eg bromo), C _1-6 alkyl (eg methyl), aryl optionally substituted with halogen (eg 4-fluorophenyl), substituted with halogen heteroaryl (e.g. 6-fluoropyrid-2-yl or pyrid-2-yl), or acyl (e.g. acetyl)]
The method of any preceding aspect, wherein the compound is selected from
[Aspect 15]
PDE1 inhibitors are:
A method according to any preceding aspect, selected from any of
[Aspect 16]
A PDE1 inhibitor, in free form or in pharmaceutically acceptable salt form, of:
A method according to any preceding aspect, selected from any of
[Aspect 17]
wherein the PDE1 inhibitor is in free form or in pharmaceutically acceptable salt form,
The method of any of the preceding aspects, wherein
[Aspect 18]
wherein the PDE1 inhibitor is in free form or in pharmaceutically acceptable salt form,
The method according to any one of aspects 1 to 16, wherein
[Aspect 19]
A PDE1 inhibitor, in free or pharmaceutically acceptable form, of:
The method according to any one of aspects 1 to 14, wherein
[Aspect 20]
A PDE1 inhibitor, in free or pharmaceutically acceptable form, of:
The method according to any one of aspects 1 to 14, wherein
[Aspect 21]
Use of a PDE1 inhibitor in a method for treating or preventing kidney damage according to any of aspects 1-20.
[Aspect 22]
Use of a PDE1 inhibitor in the manufacture of a medicament for treating or preventing renal disorders according to any of aspects 1-20.

Claims (20)

A medicament for treating or preventing renal disorders , containing a PDE1 inhibitor . 2. A medicament according to claim 1, wherein the renal disorder is selected from one or more of renal fibrosis, chronic renal disease, renal failure, glomerulosclerosis and nephritis. 3. The medicament according to claim 1 or 2, wherein the renal disorder is renal fibrosis. 3. The medicament according to claim 1 or 2, wherein the renal disorder is chronic renal disease. 3. The medicament according to claim 1 or 2, wherein the renal disorder is renal failure. 3. The medicament according to claim 1 or 2, wherein the renal disorder is glomerulosclerosis. 3. The medicament according to claim 1 or 2, wherein the renal disorder is nephritis. Kidney damage is diabetes, kidney damage, hypertension, cancer growth (e.g. polycystic kidney disease), or cardiovascular disease (e.g. angina pectoris, stroke, essential hypertension, pulmonary hypertension, secondary hypertension) , isolated systolic hypertension, diabetes-related hypertension, atherosclerosis-related hypertension, renovascular hypertension, congestive heart failure, myocardial, angina, and stroke, hypertension, inflammation A medicament according to any one of claims 1 to 7 resulting from sexual diseases or disorders, fibrosis, cardiac hypertrophy, vascular remodeling, and connective tissue diseases and disorders such as Marfan's syndrome. . The medicament according to any one of claims 1 to 8, wherein the renal disorder is a result of diabetes. The medicament according to any one of claims 1 to 8, wherein the renal disorder is the result of damage to the kidneys. The medicament according to any one of claims 1 to 8, wherein the renal disorder is the result of hypertension. A medicament according to any one of claims 1 to 8, wherein the renal damage is the result of cancer growth (eg polycystic kidney disease). Renal damage is cardiovascular disease (e.g., angina pectoris, stroke, essential hypertension, pulmonary hypertension, secondary hypertension, isolated systolic hypertension, diabetes-related hypertension, atherosclerosis) hypertension, renovascular hypertension, congestive heart failure, myocardial, angina and stroke, hypertension, inflammatory diseases or disorders, fibrosis, cardiac hypertrophy, vascular remodeling, and connective tissue diseases and A medicament according to any one of claims 1 to 8, resulting from a disorder such as Marfan's syndrome). A PDE1 inhibitor is
(A) Formula I, in free, salt or prodrug form, including enantiomers, diastereoisomers and racemates:
[In the formula,
(i) R ₁ is H or C _1-4 alkyl (e.g. methyl);
(ii) R ₄ is H or C _1-4 alkyl and R ₂ and R ₃ are independently H or C _1-4 alkyl (e.g. R ₂ and R ₃ are both methyl or R ₂ is H and R ₃ is isopropyl), aryl, heteroaryl, (optionally hetero)arylalkoxy, or (optionally hetero)arylalkyl; or R ₂ is H and R ₃ and R ₄ together form a dimethylene, trimethylene or tetramethylene bridge (preferably R ₃ and R ₄ together have a cis configuration, for example R the carbons bearing ₃ and R ₄ have the R and S configurations, respectively);
(iii) _R5 is substituted heteroarylalkyl, for example substituted _with haloalkyl;
(wherein X, Y and Z are independently N or C; R ₈ , R ₉ , R ₁₁ and R ₁₂ are independently H or halogen (e.g. Cl or F); , R ₁₀ is halogen, alkyl, cycloalkyl, haloalkyl (eg, trifluoromethyl), aryl (eg, phenyl), heteroaryl (eg, pyridyl optionally substituted with halogen (eg, pyrid-2-yl ), or thiadiazolyl (e.g. 1,2,3-thiadiazol-4-yl)), diazolyl, triazolyl, tetrazolyl, arylcarbonyl (e.g. benzoyl), alkylsulfonyl (e.g. methylsulfonyl), heteroarylcarbonyl, or alkoxy carbonyl; provided that when X, Y or Z is nitrogen, R ₈ , R ₉ or R ₁₀ are absent, respectively)
is a portion indicated by;
(iv) R ₆ is H, alkyl, aryl, heteroaryl, arylalkyl (eg benzyl), arylamino (eg phenylamino), heteroarylamino, N,N-dialkylamino, N,N-diarylamino , or N-aryl-N-(arylalkyl)amino (for example, N-phenyl-N-(1,1′-biphen-4-ylmethyl)amino);
(v) n is 0 or 1;
(vi) when n is 1, A is -C(R ₁₃ R ₁₄ )-, where R ₁₃ and R ₁₄ are independently H or C _1-4 alkyl, aryl, hetero aryl, (optionally hetero)arylalkoxy or (optionally hetero)arylalkyl];
(B) Formula Ia in free form, pharmaceutically acceptable salt form or prodrug form, including enantiomers, diastereoisomers and racemates:
[In the formula,
(i) R ₂ and R ₅ are independently H or hydroxy, and R ₃ and R ₄ together form a trimethylene or tetramethylene bridge [preferably R ₃ and R ₄ are supported have the R and S configurations, respectively]; or R ₂ and R ₃ are each methyl and R ₄ and R ₅ are each H; or R ₂ , R ₄ and R ₅ are H and R ₃ is isopropyl [preferably the carbon bearing R ₃ has the R configuration];
(ii) R ₆ is phenylamino (optionally halo- or hydroxy-substituted), benzylamino (optionally halo- or hydroxy-substituted), C _1-4 alkyl, or C _1-4 alkylsulfide is; for example, phenylamino or 4-fluorophenylamino;
(iii) R ₁₀ is C _1-4 alkyl, methylcarbonyl, hydroxyethyl, carboxylic acid, sulfonamido, (optionally halo- or hydroxy-substituted) phenyl, (optionally halo- or hydroxy-substituted ) pyridyl (e.g. 6-fluoropyrid-2-yl), or thiadiazolyl (e.g. 1,2,3-thiadiazol-4-yl);
(iv) X and Y are independently C or N];
(C) Formula II in free, salt or prodrug form:
(i) X is C _1-6 alkylene (eg methylene, ethylene or prop-2-yn-1-ylene);
(ii) Y is a single bond, alkynylene (eg -C≡C-), arylene (eg phenylene) or heteroarylene (eg pyridylene);
(iii) Z is H, aryl (eg phenyl), heteroaryl (eg pyridyl, eg pyrid-2-yl), halo (eg F, Br, Cl), haloC _1-6 alkyl (eg , trifluoromethyl), —C(O)—R ¹ , —N(R ² )(R ³ ), or at least one atom selected from the group consisting of N or O C _3-7 cycloalkyl (for example, cyclopentyl, cyclohexyl, tetrahydro-2H-pyran-4-yl, or morpholinyl);
(iv) R ¹ is C _1-6 alkyl, haloC _1-6 alkyl, —OH or —OC _1-6 alkyl (eg —OCH ₃ );
(v) R ² and R ³ are independently H or C _1-6 alkyl;
(vi) R ⁴ and R ⁵ are independently H, C _1-6 alkyl, or one or more of halo (eg fluorophenyl, eg 4-fluorophenyl), hydroxy (eg hydroxyphenyl, 4-hydroxyphenyl or 2-hydroxyphenyl) or aryl optionally substituted with C _1-6 alkoxy (eg phenyl);
(vii) wherein X, Y and Z are independently one or more of halo (e.g. F, Cl or Br), C _1-6 alkyl (e.g. methyl), haloC _1-6 alkyl ( trifluoromethyl), for example, Z is one or more halo (eg, 6-fluoropyrid-2-yl, 5-fluoropyrid-2-yl, 6-fluoropyrid-2-yl , 3-fluoropyrid-2-yl, 4-fluoropyrid-2-yl, 4,6-dichloropyrid-2-yl), haloC _1-6 alkyl (for example 5-trifluoromethylpyrid-2-yl) or heteroaryl, for example pyridyl, substituted with C _1-6 alkyl (for example 5-methylpyrid-2-yl) or Z is one or more halo (for example 4-fluorophenyl) is aryl, for example phenyl, substituted with;
(D) Formula III, in free or salt form:
[In the formula,
(i) R ₁ is H or C _1-4 alkyl (e.g. methyl or ethyl);
(ii) R ₂ and R ₃ are independently H or C _1-6 alkyl (e.g. methyl or ethyl);
(iii) R ₄ is H or C _1-4 alkyl (eg methyl or ethyl);
(iv) R ₅ is independently -C(=O)-C _1-6 alkyl (eg -C(=O)-CH ₃ ) and C _1-6 hydroxyalkyl (eg 1-hydroxyethyl) aryl (e.g., phenyl) optionally substituted with one or more groups selected from;
(v) R ₆ and R ₇ are independently H or one or more independently selected from C _1-6 alkyl (e.g. methyl or ethyl) and halogen (e.g. F or Cl) aryl (e.g., phenyl) optionally substituted with groups, such as unsubstituted phenyl, or phenyl substituted with one or more halogens (e.g., F), or one or more C _1-6 alkyl and one phenyl substituted with 1 or more halogens, or phenyl substituted with 1 C _1-6 alkyl and 1 halogen, for example 4-fluorophenyl or 3,4-difluorophenyl or 4-fluoro-3 - is methylphenyl;
(vi) n is 1, 2, 3 or 4];
(E) Formula IV in free or salt form
[ In the formula,
(i) R ₁ is C _1-4 alkyl (eg, methyl or ethyl), or —NH(R ₂ ), where R ₂ is phenyl optionally substituted with halo (eg, fluoro); For example, 4-fluorophenyl;
(ii) X, Y and Z are independently N or C;
(iii) R ₃ , R ₄ and R ₅ are independently H or C _1-4 alkyl (e.g. methyl); or R ₃ is H and R ₄ and R ₅ together form a trimethylene bridge (preferably R ₄ and R ₅ together have a cis configuration, e.g. the carbons bearing R ₄ and R ₅ have the R and S configurations, respectively). are doing);
(iv) _R6 , _R7 and _R8 are independently
H.
C _1-4 alkyl (for example methyl),
pyrid-2-yl substituted with hydroxy, or -S(O) ₂ -NH ₂
is;
(v) with the proviso that when X, Y and/or Z are N, respectively, R ₆ , R ₇ and/or R ₈ are absent; and when X, Y and Z are all C, R ₆ , at least one of R ₇ or R ₈ is —S(O) ₂ —NH ₂ , or pyrid-2-yl substituted with hydroxy];
(F) formula V, in free or salt form;
[In the formula,
( i ) R ₁ is -NH(R ₄ ), wherein R ₄ is phenyl optionally substituted with halo (e.g. fluoro), e.g. 4-fluorophenyl;
( ii ) _R2 is H or _C1-6alkyl (e.g. methyl, isobutyl or neopentyl);
( iii ) R ₃ is —SO ₂ NH ₂ or —COOH]; and (G) Formula VI, in free form or in pharmaceutically acceptable salt form.
[In the formula,
( i ) R ₁ is -NH(R ₄ ), wherein R ₄ is phenyl optionally substituted with halo (e.g. fluoro), e.g. 4-fluorophenyl;
( ii ) _R2 is H or _C1-6alkyl (e.g. methyl or ethyl);
( iii ) R ₃ is H, halogen (eg bromo), C _1-6 alkyl (eg methyl), aryl optionally substituted with halogen (eg 4-fluorophenyl), substituted with halogen heteroaryl (e.g. 6-fluoropyrid-2-yl or pyrid-2-yl), or acyl (e.g. acetyl)]
The medicament according to any one of claims 1 to 13 , which is a compound selected from PDE1 inhibitors are:
The medicament according to any one of claims 1 to 14 , which is selected from any one of A PDE1 inhibitor, in free form or in pharmaceutically acceptable salt form, of:
The medicament according to any one of claims 1 to 15 , which is selected from any one of wherein the PDE1 inhibitor is in free form or in pharmaceutically acceptable salt form,
The medicament according to any one of claims 1 to 16 . wherein the PDE1 inhibitor is in free form or in pharmaceutically acceptable salt form,
The medicament according to any one of claims 1 to 16 . A PDE1 inhibitor, in free or pharmaceutically acceptable form, of:
The medicament according to any one of claims 1 to 15 . A PDE1 inhibitor, in free or pharmaceutically acceptable form, of:
The medicament according to any one of claims 1 to 15 .