# US 7,612,106 B2 · Fused pyrazole derivatives and methods of treatment of metabolic-related disorders thereof

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- Number: US 7,612,106 B2
- Document ID: US7612106B2
- Status: Granted
- Kind: B2
- Application number: 11/601,184
- Filed: 2006-11-17
- Published: 2007-03-29
- Granted: 2009-11-03
- Earliest claimed: 2004-12-23
- Assignees: Arena Pharmaceuticals, Inc.
- Inventors: P. Douglas Boatman; Thomas O. Schrader; Graeme Semple; Philip J. Skinner; Jae-Kyu Jung
- Web page: https://patentgrep.com/patent/US7612106B2

## CPC

- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/50: for increasing or potentiating the activity of insulin
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 209/80: [b, c]- or [b, d]-condensed
- C07D 209/88: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
- C07D 231/54: condensed with carbocyclic rings or ring systems
- C07D 265/36: condensed with one six-membered ring
- C07D 471/04: Ortho-condensed systems
- C07D 471/14: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to certain fused pyrazole derivatives of Formula (Ia), and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists for the RUP25 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, insulin resistance, type 2 diabetes, Syndrome-X and the like. In addition, the present invention also provides for the use of the compounds of the invention in combination with other active agents such as those belonging to the class of α-glucosidase inhibitors, aldose reductase inhibitors, biguanides, HMG-CoA reductase inhibitors, squalene synthesis inhibitors, fibrates, LDL catabolism enhancers, angiotensin converting enzyme (ACE) inhibitors, insulin secretion enhancers, DP receptor antagonists, and the like.

## Claims

### Claim 1

A method of agonizing a RUP25 receptor comprising contacting said receptor with a compound of Formula (Ia):
wherein:
X is N and Z is CR7, or X is CR7 and Z is N;
R1 and R4 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, hydroxyl, nitro, sulfonamide and thiol;
R2 and R3 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, arylsulfinyl, arylsulfonyl, arylthio, carbamimidoyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, C1-6-dialkylamido, C1-6-dialkylthioamido, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C4-7 oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid and thiol; wherein said C1-6 alkyl is optionally substituted with substituents selected from the group consisting of C1-6 acyl, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 haloalkoxy, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, hydroxyl, nitro, phenoxy and phenyl; or
R2 and R3 together with the carbon to which they are both bonded form a C3-6 cycloalkyl;
R5 and R6 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, hydroxyl, nitro, sulfonamide and thiol; and R7 is carbo-C1-6-alkoxy, carboxy or tetrazol-5-yl.

### Claim 2 (depends on 1)

The method according to claim 1, wherein said compound is a partial agonist.

### Claim 3

A method of treating atherosclerosis in a human patient in need of such treatment comprising administering to said patient a compound of Formula (Ia):
or a pharmaceutically acceptable salt, hydrate or solvate thereof, in an amount that is effective to treat atherosclerosis; or a pharmaceutical composition comprising the compound of Formula (Ia), or the pharmaceutically acceptable salt, hydrate or solvate thereof, in an amount that is effective to treat atherosclerosis in combination with a pharmaceutically acceptable carrier;
wherein:
X is N and Z is CR7, or X is CR7 and Z is N;
R1 and R4 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, hydroxyl, nitro, sulfonamide and thiol;
R2 and R3 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, arylsulfinyl, arylsulfonyl, arylthio, carbamimidoyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, C1-6-dialkylamido, C1-6-dialkylthioamido, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C4-7 oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid and thiol; wherein said C1-6 alkyl is optionally substituted with substituents selected from the group consisting of C1-6 acyl, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 haloalkoxy, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, hydroxyl, nitro, phenoxy and phenyl; or
R2 and R3 together with the carbon to which they are both bonded form a C3-6 cycloalkyl;
R5 and R6 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, hydroxyl, nitro, sulfonamide and thiol; and R7 is carbo-C1-6-alkoxy, carboxy or tetrazol-5-yl.

### Claim 4

A method of treating dyslipidemia in a human patient in need of such treatment comprising administering to said patient a compound of Formula (Ia):
or a pharmaceutically acceptable salt, hydrate or solvate thereof, in an amount that is effective to treat dyslipidemia; or a pharmaceutical composition comprising the compound of Formula (Ia), or the pharmaceutically acceptable salt, hydrate or solvate thereof, in an amount that is effective to treat dyslipidemia in combination with a pharmaceutically acceptable carrier;
wherein:
X is N and Z is CR7, or X is CR7 and Z is N;
R1 and R4 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, hydroxyl, nitro, sulfonamide and thiol;
R2 and R3 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, arylsulfinyl, arylsulfonyl, arylthio, carbamimidoyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, C1-6-dialkylamido, C1-6-dialkylthioamido, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C4-7 oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid and thiol; wherein said C1-6 alkyl is optionally substituted with substituents selected from the group consisting of C1-6 acyl, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 haloalkoxy, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, hydroxyl, nitro, phenoxy and phenyl; or
R2 and R3 together with the carbon to which they are both bonded form a C3-6 cycloalkyl;
R5 and R6 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C3-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, hydroxyl, nitro, sulfonamide and thiol; and R7 is carbo-C1-6-alkoxy, carboxy or tetrazol-5-yl.

### Claim 5

A method of raising HDL in a human comprising administering to said human a therapeutically-effective amount of a compound of Formula (Ia):
or a pharmaceutically acceptable salt, hydrate or solvate thereof; or a pharmaceutical composition comprising a therapeutically-effective amount of the compound of Formula (Ia), or the pharmaceutically acceptable salt, hydrate or solvate thereof, in combination with a pharmaceutically acceptable carrier;
wherein:
X is N and Z is CR7, or X is CR7 and Z is N;
R1 and R4 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, hydroxyl, nitro, sulfonamide and thiol;
R2 and R3 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, arylsulfinyl, arylsulfonyl, arylthio, carbamimidoyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, C1-6-dialkylamido, C1-6-dialkylthioamido, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C4-7 oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid and thiol; wherein said C1-6 alkyl is optionally substituted with substituents selected from the group consisting of C1-6 acyl, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7cycloalkyloxy, C2-6 dialkylamino, C1-6 haloalkoxy, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, hydroxyl, nitro, phenoxy and phenyl; or
R2 and R3 together with the carbon to which they are both bonded form a C3-6 cycloalkyl;
R5 and R6 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, hydroxyl, nitro, sulfonamide and thiol; and R7 is carbo-C1-6-alkoxy, carboxy or tetrazol-5-yl.

### Claim 6 (depends on 3)

The method according to claim 3, wherein:
R2 and R3 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, arylsulfinyl, arylsulfonyl, arylthio, carbamimidoyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, C1-6-dialkylamido, C1-6-dialkylthioamido, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C4-7-oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid and thiol; wherein said C1-6 alkyl is optionally substituted with substituents selected from the group consisting of C1-6 acyl, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 haloalkoxy, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, hydroxyl, nitro, phenoxy and phenyl; and
provided that R1 and R4 are cis to each other.

### Claim 7 (depends on 4)

The method according to claim 4, wherein:
R2 and R3 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, arylsulfinyl, arylsulfonyl, arylthio, carbamimidoyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, C1-6-dialkylamido, C1-6-dialkylthioamido, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C4-7 oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid and thiol; wherein said C1-6 alkyl is optionally substituted with substituents selected from the group consisting of C1-6 acyl, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 haloalkoxy, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, hydroxyl, nitro, phenoxy and phenyl; and
provided that R1 and R4 are cis to each other.

### Claim 8 (depends on 5)

The method according to claim 5, wherein:
R2 and R3 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, arylsulfinyl, arylsulfonyl, arylthio, carbamimidoyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, C1-6-dialkylamido, C1-6-dialkylthioamido, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C4-7 oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid and thiol; wherein said C1-6 alkyl is optionally substituted with substituents selected from the group consisting of C1-6 acyl, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 haloalkoxy, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, hydroxyl, nitro, phenoxy and phenyl; and
provided that R1 and R4 are cis to each other.

### Claim 9

A method of producing a pharmaceutical composition comprising admixing a compound of Formula (Ia):
or a pharmaceutically acceptable salt, hydrate or solvate thereof,
wherein:
X is N and Z is CR7, or X is CR7 and Z is N;
R1 and R4 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide; C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, hydroxyl, nitro, sulfonamide and thiol;
R2 and R3 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, arylsulfinyl, arylsulfonyl, arylthio, carbamimidoyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, C1-6-dialkylamido, C1-6-dialkylthioamido, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C4-7 oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid and thiol; wherein said C1-6 alkyl is optionally substituted with substituents selected from the group consisting of C1-6 acyl, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 haloalkoxy, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, hydroxyl, nitro, phenoxy and phenyl; or
R2 and R3 together with the carbon to which they are both bonded form a C3-6 cycloalkyl;
R5 and R6 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, hydroxyl, nitro, sulfonamide and thiol; and R7is carbo-C1-6-alkoxy, carboxy or tetrazol-5-yl and a pharmaceutically acceptable carrier.

### Claim 10 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein:
R2 and R3 are each selected independently from the group consisting of H, C1-6 acyl, C1-6 acyloxy, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkyl, C1-6 alkylamino, C1-6 alkylcarboxamide, C1-6 alkylthiocarboxamide, C2-6 alkynyl, C1-6 alkylsulfonamide, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, C1-6 alkylthioureyl, C1-6 alkylureyl, amino, C1-6-alkylamido, amino-C1-6-alkylsulfonyl, C1-6-alkylthioamido, arylsulfinyl, arylsulfonyl, arylthio, carbamimidoyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 dialkylcarboxamide, C1-6 dialkylthiocarboxamide, C1-6-dialkylamido, C1-6-dialkylthioamido, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C4-7 oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid and thiol; wherein said C1-6 alkyl is optionally substituted with substituents selected from the group consisting of C1-6 acyl, C1-6 acyloxy, C1-6 alkoxy, C1-6 alkylamino, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C1-6 alkylthio, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C1-6 haloalkoxy, C1-6 haloalkylsulfinyl, C1-6 haloalkylsulfonyl, C1-6 haloalkylthio, hydroxyl, nitro, phenoxy and phenyl.

### Claim 11 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, provided that R1 and R4 are cis to each other.

### Claim 12 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 5, wherein X is N; Z is CR7; and R7 is carbo-C1-6-alkoxy or carboxy.

### Claim 13 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 8, wherein X is N; Z is CR7; and R7 is carboxy.

### Claim 14 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 8, wherein X is N; Z is CR7; and R7 is tetrazol-5-yl.

### Claim 15 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 8, wherein R1 and R4 are both H.

### Claim 16 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 8, wherein R5 and R6 are both H.

### Claim 17 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 8, wherein R1, R4, R5 and R6 are each H.

### Claim 18 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 8, wherein R2 is H or C1-6 alkyl; and R3 is H, C2-6 alkenyl, C1-6 alkyl, halogen or phenyl; wherein said C1-6 alkyl is optionally substituted with substituents selected from the group consisting of C1-6 alkoxy, hydroxyl, phenoxy and phenyl.

### Claim 19 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 8, wherein R2 is H or CH3; and R3 is H, CH3 or benzyl.

### Claim 20 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 8, wherein R2 is H or CH3; and R3 is H, methyl, ethyl, n-propyl, isopropyl, isobutyl, n-butyl, n-pentyl, vinyl, hydroxymethyl, methoxymethyl, benzyl, phenyl or phenoxymethyl.

### Claim 21 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 8, wherein:
X is N, Z is CR7, and R7 is carboxyl, —CO2Et or tetrazol-5-yl;
R1, R4, R5 and R6 are each H;
R2 is H or CH3; and
R3 is H, methyl, ethyl, n-propyl, isopropyl, isobutyl, n-butyl, n-pentyl, vinyl, hydroxymethyl, methoxymethyl, benzyl, phenyl or phenoxymethyl.

### Claim 22 (depends on 1, 6, 7)

The method according to any one of claims 1, 6, 7, and 8, wherein:
X is N, Z is CR7, and R7 is carboxyl; or
X is CR7, R7 is carboxyl or tetrazol-5-yl, and Z is N;
R1, R4, R5 and R6 are each H;
R2 is H or CH3; and
R3 is H, CH3 or benzyl.

### Claim 23 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, the compound having the structure:
or a pharmaceutically acceptable salt, solvate or hydrate thereof.

### Claim 24 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, the compound having the structure:
or a pharmaceutically acceptable salt, solvate or hydrate thereof.

### Claim 25 (depends on 1, 4, 5)

The method according to any one of claims 1, 4, 5, and 6, wherein the compound is selected from the group consisting of:
3b,4,4a,5-Tetrahydro-2H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole-3-carboxylic acid;
1a,3,5,5a-Tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid; and
4-(2H-Tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene; or
a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 26 (depends on 25)

The method according to claim 25, wherein the stereochemistry for the two carbons assigned as 3b and 4a, or 1a and 5a are both R.

### Claim 27 (depends on 1, 4, 5)

The method according to any one of claims 1, 4, 5, and 6, wherein the compound is selected from the group consisting of:
1-Benzyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1,1-Dimethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1,1-Dimethyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene; and
1-Benzyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene; or
a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 28 (depends on 1, 4, 5)

The method according to any one of claims 1, 4, 5, and 6, wherein the compound is selected from the group consisting of:
1-Methyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Isobutyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Butyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Pentyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Propyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Methoxymethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Ethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Benzyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Benzyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester;
1,1-Dimethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester;
1-Phenyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester;
1-Phenyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Ethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester;
1-Methyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester;
1-Pentyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester;
1-Isopropyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Vinyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester;
1-Vinyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Ethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester;
1-Methoxymethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester;
1-Hydroxymethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester; and
1-Hydroxymethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid; or
a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 29 (depends on 1, 4, 5)

The method according to any one of claims 1, 4, 5, and 6, wherein the compound is selected from the group consisting of:
1-Methylsulfanylmethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Ethoxymethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Cyclopropyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Spirocyclopropyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
(E)-1-Propenyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
(Z)-1-Propenyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
1-Phenoxymethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
Spiro[1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-1,1′-cyclopentan]-4-carboxylic acid;
Spiro[1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-1,1′-cyclohexan]-4-carboxylic acid;
1-Allyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid;
4-Methyl-3b,4,4a,5-tetrahydro-2H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole-3-carboxylic acid; and
1-Cyclopropylmethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid; or
a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 30 (depends on 1, 4, 5)

The method according to any one of claims 1, 4, 5, and 6, wherein the compound is selected from the group consisting of:
1-Methyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
1-Ethyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
1-Propyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
1-Isobutyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
1-Phenyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
1-Benzyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
1-Pentyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1 H-2,3-diaza-cyclopropa[a]pentalene;
1-Butyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
1-Isopropyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
1-Phenoxymethyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa [a]pentalene;
4-(2H-Tetrazol-5-yl)-1-vinyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
1-Methoxymethyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa [a]pentalene; and
[4-(2H-Tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-1-yl]-methanol; or
a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 31 (depends on 1, 4, 5)

The method according to any one of claims 1, 4, 5, and 6, wherein the compound is selected from the group consisting of:
1-Cyclopropyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
1-Spirocyclopropyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa [a]pentalene;
(E)-1-Propenyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
(Z)-1-Propenyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene;
5-(Spiro-[1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-1,1′-cyclopentan]-4-yl)-1H-tetrazole;
5-(Spiro-[1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-1,1′-cyclohexan]-4-yl)-1H-tetrazole; and
1-Allyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene; or
a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 32 (depends on 4)

The method according to claim 4, wherein the method further comprises administering to said human patient a DP receptor antagonist.

### Claim 33 (depends on 5)

The method according to claim 5, wherein the method further comprises administering to said human patient a DP receptor antagonist.

### Claim 34 (depends on 6)

The method according to claim 6, wherein the method further comprises administering to said human a DP receptor antagonist.

### Claim 35 (depends on 32, 33, 34)

The method according to any one of claims 32 to 34, wherein said DP receptor antagonist is selected from the group consisting of:
or a pharmaceutically acceptable salt, solvate or hydrate thereof.

### Claim 36 (depends on 35)

The method according to claim 35, wherein the compound is selected from:
or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 37 (depends on 32, 33, 34)

The method according to any one of claims 32 to 34, wherein the compound is selected from:
or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 38 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
1-cyclopropylmethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 39 (depends on 1, 3, 4)

The method according any one of claims 1, 3, 4, and 5, wherein the compound is:
endo-(1aR,5aS)-1-cyclopropylmethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa [a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 40 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
1-allyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 41 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
endo-(1aR,5aS)-1-allyl-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa [a] pentalene, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 42 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
1-allyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 43 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
endo-(1aR,5aS)-1-allyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 44 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
1-isobutyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 45 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
endo-(1aR,5aS)-1-isobutyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 46 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
1-ethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 47 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
endo-(1aR,5aS)-1-ethyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 48 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
1-methyl-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 49 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
endo-(1aR,5aS)-1-methyl-1a,3,5,5a-tetrahydro-1H-2,3 -diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 50 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
1a,3,5,5-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 51 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
(1aR,5aR)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 52 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 53 (depends on 1, 3, 4)

The method according to any one of claims 1, 3, 4, and 5, wherein the compound is:
(1aR,5aR)-4-(2H-tetrazol-5-yl)-1a,3,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

### Claim 54 (depends on 9)

The method according to claim 9, wherein the compound is selected from:
or a pharmaceutically acceptable salt, hydrate or solvate thereof.