# US 9,040,516 B2 · Uracil derivative and use thereof for medical purposes

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- Number: US 9,040,516 B2
- Document ID: US9040516B2
- Status: Granted
- Kind: B2
- Application number: 14/236,571
- Filed: 2012-07-31
- Published: 2014-06-26
- Granted: 2015-05-26
- Earliest claimed: 2011-08-01
- Assignees: Sumitomo Dainippon Pharma Co., Ltd.
- Applicants: Tomoya Shiro; Masanori Tobe; Katsumi Kubota; Yosuke Takanashi; Tomoaki Nakamura; Toshihiko Sone
- Inventors: Tomoya Shiro; Masanori Tobe; Katsumi Kubota; Yosuke Takanashi; Tomoaki Nakamura; Toshihiko Sone
- Web page: https://patentgrep.com/patent/US9040516B2

## CPC

- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 9/08: Vasodilators for multiple indications
- 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 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 11/08: Bronchodilators
- A61P 13/12: of the kidneys
- A61P 15/06: Antiabortive agents; Labour repressants
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/14: containing three or more hetero rings
- C07D 403/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D 409/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- C07F 7/1804: {Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896)}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The present invention provides: an uracil derivative represented by general formula (I) or a physiologically acceptable salt thereof (in the formula, R1 represents a hydrogen atom, a C1-10 alkyl group, a C2-6 alkene group or a 3- to 6-membered saturated or 4- to 6-membered unsaturated aliphatic ring group which may contain 1 to 2 hetero atoms independently selected from the group consisting of N, O and S; R2 represents a hydrogen atom, a halogen atom, a cyano group, —NRcRd, —N═CHN(CH3)2, or an C1-3 alkyl group; Ar1 and Ar2 independently represent a 5- to 6-membered aromatic ring group which may contain 1 to 3 hetero atoms independently selected from the group consisting of N, O and S; and L represents a 6-membered aromatic ring group which may contain 1 to 4 nitrogen atoms, a pyrazole group, a triazole group, or an imidazole group); and a therapeutic agent or prophylactic agent for various inflammatory diseases associated with elastase, comprises the compound or the like as an active ingredient.

## Claims

### Claim 1

A compound represented by formula (I) or physiologically acceptable salts thereof:
wherein
R1 represents a hydrogen atom, a C1-10alkyl group, a C2-6 alkene group or a three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S,
said alkyl group and said alkene group for R1 is optionally substituted at substitutable positions with one or multiple substituents selected from the group consisting of
Substituent List 1:
(1) hydroxy group,
(2) halogen atom,
(3) cyano group,
(4) C1-6 alkoxy group wherein said alkoxy group is optionally substituted at substitutable positions with
hydroxy group,
halogen atom,
cyano group,
—C(═O)ORb,
—C(═O)NRcRd,
five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaC(═O)NRcRd group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or —NRcRd group or
three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group each optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaC(═O)NRcRd group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group,
(5) C1-6 alkylthio group wherein said alkylthio group is optionally substituted at substitutable positions with
hydroxy group,
halogen atom,
cyano group,
—C(═O)ORb,
—C(═O)NRcRd,
five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaC(═O)NRcRd group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or —NRcRd group or
three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group each optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaC(═O)NRcRd group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group,
(6) five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is optionally substituted at substitutable positions with
C1-3 alkyl group optionally substituted with hydroxy or halogen,
C1-3 alkoxy group optionally substituted with hydroxy or halogen,
hydroxy group,
halogen atom,
cyano group,
—NRaC(═O)Rb,
—NRaC(═O)NRcRd,
—NRaS(═O)mRb,
—C(═O)ORb,
—C(═O)NRcRd,
—S(═O)mNRcRd,
—S(═O)mRb or
—NRcRd,
(7) three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group each optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with
C1-3 alkyl group wherein said alkyl group is optionally substituted with hydroxy, halogen, cyano, —NRaC(═O)Rb, —NRaC(═O)NRcRd, —NRaS(═O)mRb, —C(═O)ORb, —C(═O)NRcRd or —NRcRd,
C1-3 alkoxy group optionally substituted with hydroxy or halogen,
hydroxy group,
halogen atom,
cyano group,
—NRaC(═O)Rb,
—NRaC(═O)NRcRd,
—NRaS(═O)mRb,
—C(═O)ORb,
—C(═O)NRcRd,
—C(O)Rb,
—S(═O)mNRcRd,
—S(═O)mRb,
—NRcRd or
oxo group,
(8) —NRaRc group,
(9) —OC(═O)NRcRd group,
(10) —C(═O)Rf group,
(11) —S(═O)mRg group,
(12) thiol group,
(13) nitro group and
(14) —ORe group,
said three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group for R1 is optionally substituted at substitutable positions with one or multiple substituents selected from the group consisting of
Substituent List 2:
(1) hydroxy group,
(2) halogen atom,
(3) cyano group,
(4) C1-6 alkyl group wherein said alkyl group is optionally substituted at substitutable positions with
hydroxy group,
halogen atom,
cyano group,
five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or —NRcRd group or
three- to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group,
(5) C1-6 alkoxy group wherein said alkoxy group is optionally substituted at substitutable positions with
hydroxy group,
halogen atom,
cyano group,
five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or a —NRcRd group or
three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group,
(6) C1-6 alkylthio group wherein said alkylthio group is optionally substituted at substitutable positions with
hydroxy group,
halogen atom,
cyano group,
five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or —NRcRd group or
three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group,
(7) five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is optionally substituted at substitutable positions with
C1-3 alkyl group optionally substituted with hydroxy or halogen,
C1-3 alkoxy group optionally substituted with hydroxy or halogen,
hydroxy group,
halogen atom,
cyano group,
—NRaC(═O)Rb,
—NRaS(═O)mRb,
—C(═O)ORb,
—C(═O)NRcRd,
—S(═O)mNRcRd,
—S(═O)mRb or
—NRcRd,
(8) three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with
C1-3 alkyl group optionally substituted with hydroxy or halogen,
C1-3 alkoxy group optionally substituted with hydroxy or halogen,
hydroxy group,
halogen atom,
cyano group,
—NRaC(═O)Rb,
—NRaS(═O)mRb,
—C(═O)ORb,
—C(═O)NRcRd,
—NRcRd or
oxo group,
(9) —NRaRe group,
(10) —OC(═O)NRcRd group,
(11) —C(═O)Rf group,
(12) —S(═O)mR8 group,
(13) thiol group,
(14) oxo group,
(15) nitro group,
(16) —NRaC(═O)Rb group,
(17) —NRaC(═O)NRcRd group,
(18) —NRaS(═O)mRb group,
(19) —C(═O)ORb group and
(20) —C(═O)NRcRd group,
R2 represents a hydrogen atom, a halogen atom, a cyano group, a —NRcRd group, a —N—CHN(CH3)2 group or a C1-3 alkyl group wherein said alkyl group is optionally substituted with hydroxy, halogen, —NRcRd, —ORa or —OC(═O)Ra,
Ar1 represents a five to six-membered aromatic ring group optionally containing one to three heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is substituted at substitutable positions with C1-6 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, nitro group, phenyl group, —NRaC(═O)Rh group, —NRaS(═O)mRh group, —NRaC(═O)NRcRd group, —C(═O)NRcRd group, —C(═O)ORa group, —C(═O)Ra group, —S(═O)mNRcRd group, —S(═O)nRh group or —NRcRd group,
L represents a six membered unsubstituted aromatic ring group optionally containing 1 to 2 nitrogen atoms, a Pyr-1 group of the following formula or a Tri-1 group of the following formula:
wherein the bond 1 represents a binding to uracil ring, the bond 2 represents a binding to Ar2, and the Z1 and Z2 represent independently of each other a cyano group, a halogen atom, a —C(═O)NRcRd group, a —C(═O)ORb2 group, a —CHO group, a nitro group, a hydroxy group, a —NRcRd group, a —NRaC(═O)Rh group, a hydrogen atom, a —S(═O)mNRc2Rd2 group, a —S(═O)mNRaC(═O)Rb3 group, a —S(═O)mNRaC(═O)ORb4 group, a —S(═O)mNRaC(═O)NRaRb3 group, a —S(═O)mRg2 group, a —S—Rg3 group, a three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said saturated aliphatic ring group is optionally substituted with hydroxy, halogen, C1-6 alkyl, C1-3 alkoxy, —C(═O)ORa, —C(═O)Ra or —NRaRb, a C1-6 alkyl group or an C2-6 alkene group wherein said alkyl group and said alkene group are independently of each other optionally substituted with halogen, hydroxy, —NRcRd, —C(═O)NRcRd, —NRaS(═O)mRh, —C(═O)NRcRd or —C(═O)ORa,
Ar2 represents a five to six-membered aromatic ring group optionally containing one to three heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is substituted at one or more substitutable positions with C1-6 alkyl group optionally substituted with hydroxy, cyano or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, nitro group, —NRaC(═O)Rh group, —NRaS(═O)mRh group, —NRaC(═O)NRcRd group, —C(═O)NRcRd group, —C(═O)ORa group, —C(═O)Ra group, —S(═O)mNRcRd group, —S(═O)nRh group or —NRcRd group,
Ra represents a hydrogen atom or a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy or halogen,
Rb represents a hydrogen atom, a C1-6 alkyl group optionally substituted with hydroxy or halogen, a benzyl group optionally substituted with methoxy or nitro, or a C3-6 cycloalkyl group optionally substituted with hydroxy or halogen,
Rb2 represents a hydrogen atom, a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy, —NRaRb or halogen, a benzyl group wherein said benzyl group is optionally substituted with methoxy or nitro or a C3-6 cycloalkyl group wherein said cycloalkyl group is optionally substituted with hydroxy or halogen,
Rb3 represents a hydrogen atom, a phenyl group wherein said phenyl group is optionally substituted with halogen, a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy or halogen or a C3-6 cycloalkyl group wherein said cycloalkyl group is optionally substituted with hydroxy or halogen,
Rb4 represents a hydrogen atom, a phenyl group wherein said phenyl group is optionally substituted with halogen, a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy or halogen, a C3-6 cycloalkyl group wherein said cycloalkyl group is optionally substituted with hydroxy or halogen or an 2-isopropyl-5-methylcyclohexyl,
Rc and Rd represent independently of each other a hydrogen atom or a C1-3 alkyl group optionally substituted with C1-3 alkoxy, cyano, hydroxy or halogen, or alternatively may combine each other together with N to which they are attached and optionally together with further one to two heteroatoms independently selected from the group consisting of N, O and S to represent a four to six-membered saturated or unsaturated aliphatic ring group wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-6 alkyl group (said alkyl group is optionally substituted with hydroxy, —NRaRb, —NRaC(═O)ORh or —NRaC(═O)Rh), C1-3 alkoxy group, —NRaRb group, —NRaC(═O)ORh group, —NRaC(═O)Rh group, —C(═O)ORa group, hydroxy group, halogen atom or oxo group,
Rc2 and Rd2 represent independently of each other a hydrogen atom or a C1-3 alkyl group wherein said alkyl group is optionally substituted with phenyl group optionally substituted with methoxy, —NRaRb group, —NRa(C═O)ORh group, —NRaC(═O)Rh group, C1-3 alkoxy group, cyano group, hydroxy group or halogen atom, or alternatively may combine each other together with N to which they are attached and optionally together with further one to two heteroatoms independently selected from the group consisting of N, O and S to represent a four to six-membered saturated or unsaturated aliphatic ring group wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-6 alkyl group, C1-3 alkoxy group, —NRaRb group, —NRaC(═O)ORh group, —NRaC(═O)Rh group, —C(═O)ORa group, hydroxy group, halogen atom or oxo group,
Rc represents
a hydrogen atom,
a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy or —NRcRd,
an -A group,
a —C(═O)-A group,
a C1-6 alkylcarbonyl group wherein the alkyl moiety of said alkylcarbonyl is optionally substituted with hydroxy, halogen, cyano, C1-3 alkoxy or —NRcRd,
a C1-6 alkoxycarbonyl group wherein the alkyl moiety of said alkoxycarbonyl group is optionally substituted with hydroxy or halogen,
a —C(═O)NRcRd group or
a —S(═O)mRb group,
Rf represents
a hydrogen atom,
a hydroxy group,
a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy or —NRcRd,
a C1-3 alkoxy group wherein said alkoxy group is optionally substituted with phenyl group optionally substituted with methoxy or nitro, hydroxy group, cyano group, halogen atom, C1-3 alkoxy group or —NRcRd group,
an -A group or
a —NRaRi group,
Rg represents
a hydroxy group,
a chlorine atom,
a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy or —NRcRd,
an -A group or
a —NRaRi group,
Rg2 represents
a hydroxy group,
a chlorine atom,
a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy or —NRcRd or
an -A group,
Rg3 represents
a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy or —NRcRd or
an -A group,
Rh represents a C1-6 alkyl optionally substituted with hydroxy or halogen,
Ri represents
a hydrogen atom,
a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy, C3-6 cycloalkyl or —NRcRd,
an -A group,
a —C(═O)Rh group,
a —C(═O)A group or
a C1-6 alkylcarbonyl group wherein the alkyl moiety of said alkylcarbonyl group is optionally substituted with hydroxy, halogen, cyano, C1-3 alkoxy or —NRcRd,
A represents
a five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —C(═O)OH group or —NRcRd group,
a three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group each optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —C(═O)OH group, —NRcRd group or oxo group,
m represents an integer of 1 or 2 and
n represents an integer of 0 to 2.

### Claim 2 (depends on 1)

The compound according to claim 1 or physiologically acceptable salts thereof, wherein
Z1 and Z2 represent independently of each other a cyano group, a halogen atom, a —C(═O)NRcRd group, a —C(═O)ORb2 group, a —CHO group, a nitro group, a —NRaC(═O)Rb group, a hydrogen atom, a —S(═O)mNRc2Rd2 group, a —S(═O)mNRaC(O)Rb3 group, a —S(═O)mNRaC(═O)ORb4 group, a —S(═O)mNRaC(═O)NRaRb3 group, a —S(═O)mRg2 group, a three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said saturated aliphatic ring group is optionally substituted with halogen, C1-6 alkyl, —C(O)ORa or —C(═O)Ra or a C1-6 alkyl group wherein said alkyl group is optionally substituted with halogen, —C(═O)NRcRd, —NRaS(═O)mRh, —C(═O)NRcRd or —C(═O)ORa.

### Claim 3 (depends on 1, 2)

The compound according to claim 1 or 2 or physiologically acceptable salts thereof wherein
Ar1 represents a benzene ring or a pyridine ring wherein said benzene ring and said pyridine ring are independently of each other substituted at one to three substitutable positions with C1-6 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, nitro group, phenyl group, —C(═O)NRcRd group, —C(═O)ORa group, —C(═O)Ra group, —S(═O)nRh group or —NRcRd group, and
Ar2 represent a benzene ring or a pyridine ring wherein said benzene ring and said pyridine ring are substituted independently of each other at one to three substitutable positions with C1-6 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, nitro group, —C(═O)NRcRd group, —C(═O)ORa group, —C(═O)Ra group, —S(═O)nRh group or —NRcRd group.

### Claim 4 (depends on 1)

The compound according to claim 1 or physiologically acceptable salts thereof wherein
Ar1 represents the following formula of Ar1-1:
wherein K1, K2, K3 and K4 represent all carbon atoms for benzene ring, or only one nitrogen atom and the remaining carbon atoms for pyridine ring, and X represents a C1-6 alkyl group optionally substituted with hydroxy or halogen, a C1-3 alkoxy group optionally substituted with hydroxy or halogen, a hydroxy group, a halogen atom, a cyano group, a nitro group, a phenyl group, a —C(═O)NRcRd group, a —C(═O)ORa group, a —C(═O)Ra group, a —S(═O)nRh group or a —NRcRd group,
said benzene ring and said pyridine ring are optionally substituted at one to two substitutable positions of K1 to K4 with further C1-6 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, nitro group, —C(═O)NRcRd group, —C(═O)ORa group, —C(═O)Ra group, —S(═O)nRh group or —NRcRd group,
Ar2 represents the following formula Ar2-1:
wherein L1, L2, L3 and L4 represent all carbon atoms for benzene ring, or only one nitrogen atom and the remaining carbon atoms for pyridine ring, and Y represents a C1-6 alkyl group optionally substituted with hydroxy or halogen, a C1-3 alkoxy group optionally substituted with hydroxy or halogen, a hydroxy group, a halogen atom, a cyano group, a nitro group, a —C(═O)NRcRd group, a —C(═O)ORa group, a —C(═O)Ra group, a —S(═O)nRh group or a —NRcRd group,
said benzene ring and said pyridine ring are optionally substituted at one to two substitutable positions of L1 to L4 with further C1-6 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, nitro group, —C(═O)NRcRd group, —C(═O)ORa group, —C(═O)Ra group, —S(═O)nRh group or —NRcRd group.

### Claim 5 (depends on 1)

The compound according to claim 1 or physiologically acceptable salts thereof wherein R2 represents a —NRcRd group, a —N═CHN(CH3)2 group or a C1-3 alkyl group wherein said alkyl group is optionally substituted with hydroxy, halogen, —NRcRd, —ORa or —OC(═O)Ra.

### Claim 6 (depends on 1)

The compound according to claim 1 or physiologically acceptable salts thereof, wherein
Ra represents a hydrogen atom or a C1-6 alkyl group optionally substituted with hydroxy or halogen,
Rb represents a C1-6 alkyl group optionally substituted with hydroxy or halogen,
Rb2 represents a hydrogen atom, a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy, —NRaRb or fluorine or a C3-6 cycloalkyl group wherein said cycloalkyl group is optionally substituted with hydroxy or fluorine,
Rb3 represents a hydrogen atom, a phenyl group wherein said phenyl group is optionally substituted with fluorine or chlorine, a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy or fluorine or a C3-6 cycloalkyl group wherein said cycloalkyl group is optionally substituted with hydroxy or fluorine,
Rb4 represents a hydrogen atom, a phenyl group wherein said phenyl group is optionally substituted with fluorine or chlorine, a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy or fluorine, a C3-6 cycloalkyl group wherein said cycloalkyl group is optionally substituted with hydroxy or fluorine or an 2-isopropyl-5-methylcyclohexyl,
Rc and Rd represent independently of each other a hydrogen atom or a C1-3 alkyl group wherein said alkyl group is optionally substituted with C1-3 alkoxy, cyano, hydroxy or fluorine, or alternatively may combine each other together with N to which they are attached and optionally together with further one to two heteroatoms independently selected from the group consisting of N, O and S to represent a four to six-membered saturated aliphatic ring group wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy, —NRaRb, —NRaC(═O)ORh or —NRaC(═O)Rh, C1-3 alkoxy group, —NRaRb group, —NRaC(═O)ORa group, —NRaC(═O)Ra group, —C(═O)ORa group, hydroxy group, fluorine atom or oxo group,
Rc2 an Rd2 represent independently of each other a hydrogen atom or a C1-3 alkyl group wherein said alkyl group is optionally substituted with phenyl group optionally substituted with methoxy, —NRaRb group, —NRa(C═O)ORh group, —NRaC(═O)Rh group, C1-3 alkoxy group, cyano group, hydroxy group or fluorine atom, or alternatively combine each other together with N to which they are attached and optionally together with further one to two heteroatoms independently selected from the group consisting of N, O and S to represent a four to six-membered saturated aliphatic ring group wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-6 alkyl, C1-3 alkoxy, —NRaRb, —NRaC(═O)ORh, —NRaC(═O)Rh, —C(═O)ORa, hydroxy, fluorine or oxo,
Re represents a C1-6 alkyl group wherein said alkyl group is optionally substituted with hydroxy or fluorine, an -A group, an C1-6 alkylcarbonyl group wherein the alkyl moiety of said alkylcarbonyl group is optionally substituted with hydroxy or fluorine or a —S(═O)2Rb group,
Rf represents a hydroxy group, an -A group or an —NRaRi group,
Rg represents a hydroxy group, a C1-3 alkyl group wherein said alkyl group is optionally substituted with hydroxy, fluorine or —NRcRd, a chlorine atom, an -A group or a —NRaRi group,
Rg2 represents a hydroxy group, a C1-3 alkyl group wherein said alkyl group is optionally substituted with hydroxy or fluorine, a chlorine atom or an -A group,
Rg3 represents a C1-6 alkyl group wherein aid alkyl group is optionally substituted with hydroxy, fluorine or —NRcRd,
Rh represents a C1-3 alkyl group optionally substituted with hydroxy or fluorine,
Ri represents a C1-3 alkyl group wherein said alkyl group is optionally substituted with hydroxy, C1-3 alkoxy or fluorine or an -A group,
A represents
an aromatic ring group selected from the group consisting of phenyl, pyridyl and tetrazolyl wherein said aromatic ring group is optionally substituted at substitutable positions with hydroxy or fluorine or
an aliphatic ring group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-3 alkyl, C1-3 alkoxy, hydroxy, fluorine, —NRcRd or oxo, and
m represents an integer of 1 or 2.

### Claim 7 (depends on 1)

The compound according to claim 1 or physiologically acceptable salts thereof wherein
R1 represents a C1-10 alkyl group wherein said alkyl group is optionally substituted at substitutable positions with one to three substituents selected from the group consisting of
Substituent List 8:
(1) hydroxy group,
(2) halogen atom,
(3) cyano group,
(7) three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with
C1-3 alkyl group optionally substituted with hydroxy or halogen,
C1-3 alkoxy group optionally substituted with hydroxy or halogen,
hydroxy group,
halogen atom,
cyano group,
—NRaC(═O)Rb,
—NRaS(═O)mRb,
—C(═O)ORb,
—C(═O)NRcRd,
—C(═O)Rb,
—NRcRd or
oxo group;
(8) —NRaRe group,
(10) —C(═O)Rf group,
(11) —S(═O)mRg group, and
(12) thiol group,
or
a three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with one or multiple substituents selected from the group consisting of
Substituent List 9:
(1) hydroxy group,
(2) halogen atom,
(3) cyano group,
(4) C1-6 alkyl group wherein said alkyl group is optionally substituted at substitutable positions with
hydroxy group,
halogen atom,
cyano group,
five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(O)mRb group or —NRcRd group or
three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group,
(5) C1-6 alkoxy group wherein said alkoxy group is optionally substituted at substitutable positions with
hydroxy group,
halogen atom,
cyano group,
five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S wherein said aromatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or a —NRcRd group or
three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group,
(11) —C(═O)Rf group,
(12) —S(═O)mRg group, and
(14) oxo group.

### Claim 8 (depends on 1)

The compound according to claim 1 or physiologically acceptable salts thereof wherein
R1 represents
a C1-10 alkyl group wherein said alkyl group is optionally substituted at substitutable positions with one to three substituents selected from the group consisting of
Substituent List 10:
(1) hydroxy group,
(2) halogen atom,
(7) three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S wherein said aliphatic ring group is optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy, halogen, —C(═O)ORb, —C(═O)NRcRd, —C(═O)Rb or oxo group,
(8) —NRaRe group, and
(11) —S(═O)2Rg group
or
a three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N and O wherein said aliphatic ring group is optionally substituted at substitutable positions with one or multiple substituents selected from the group consisting of
Substituent List 11:
(1) hydroxy group,
(2) halogen atom,
(4) C1-6 alkyl group wherein said alkyl group is optionally substituted at substitutable positions with hydroxy or halogen,
(9) —NRaRe group,
(11) —C(═O)Rf group and
(14) oxo group.

### Claim 9 (depends on 1)

The compound according to claim 1 or physiologically acceptable salts thereof wherein L represents a Pyr-1 group.

### Claim 10 (depends on 1)

The compound according to claim 1 or physiologically acceptable salts thereof wherein
the formula (I) represents the following formula (I′″):
wherein Z1 represents a cyano group, a halogen atom, a —C(═O)NRcRd group, a —C(═O)ORb2 group, a hydrogen atom, a —S(═O)2NRc2Rd2 group, a —S(O)2NRaC(═O)Rb3 group, a —S(═O)2NRaC(═O)ORb4 group, a —S(═O)2NRaC(═O)NRaRb3 group or a S(═O)2Rg group,
X represents a C1-3 alkyl group optionally substituted one or multiple fluorine atoms or a nitro group, and
Y represents a cyano group, a chlorine atom or a nitro group.

### Claim 11 (depends on 10)

The compound according to claim 10 or physiologically acceptable salts thereof wherein
Z1 represents a —C(═O)NRcRd group, a —C(═O)ORb2 group, a —S(═O)2NRc2Rd2 group, a —S(═O)2NRa2C(═O)Rb3 group, a —S(═O)2NRaC(═O)ORb4 group, a —S(═O)—NRaC(═O)NRaRb3 group, a S(═O)2Rg group, an iodine atom, a bromine atom or a chlorine atom, and
R2 represents a C1-3 alkyl group optionally substituted with hydroxy.

### Claim 12 (depends on 1)

The compound according to claim 1 selected from the following Group or physiologically acceptable salts thereof,
Group:
4-[5-[3,6-Dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-1H-pyrazol-1-yl]benzonitrile,
4-[5-[6-Methyl-2,4-dioxo-3-propyl-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]-1H-pyrazol-1-yl]benzonitrile,
4-(5-(3-Ethyl-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile,
4-[5-[1-(3-Chlorophenyl)-3,6-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl]-1H-pyrazol-1-yl]benzonitrile,
4-(5-(3,6-Dimethyl-2,4-dioxo-1-m-tolyl-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile,
4-(5-(3-Isopropyl-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile,
4-(5-(6-Ethyl-3-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile,
(R)-4-(5-(3-(1-Hydroxypropan-2-yl)-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile,
4-(4-(3-Isopropyl-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4H-1,2,4-triazol-3-yl)benzonitrile,
(S)-4-(5-(2,4-Dioxo-3-(5-oxopyrrolidin-3-yl)1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile,
1-(4-Cyanophenyl)-5-(3-isopropyl-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxamide,
4-(Dimethylamino)butyl 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxylate,
(±)-1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonic acid,
(+)-1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonaic acid,
(−)-1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonaic acid,
(±)-1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphienyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide,
(−)-1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide,
(+)-1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide,
(+)-1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide.0.5 IPA solvates,
(±)-1-(4-Cyanophenyl)-5-(3-ethyl-6-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide,
(+)-1-(4-Cyanophenyl)-5-(3-ethyl-6-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide,
N-(1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyridin-5-yl)-1H-pyrazole-4-ylsulfonyl)pivalamine,
Butyl 1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-ylsulfonylcarbamate,
N-(1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-ylsulfonyl)benzamide,
1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-N-(ethylcarbonyl)-1H-pyrazole-4-sulfonamide,
(±)-4-(5-(3,6-Dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl-4-(methylsulfonyl)-1H-pyrazol-1-yl)benzonitrile,
(+)-4-(5-(3,6-Dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl-4-(methylsulfonyl)-1H-pyrazol-1-yl)benzonitrile,
(±)-4-(5-(3-Isopropyl-6-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl-4-(methylsulfonyl)-1H-pyrazol-1-yl)benzonitrile,
4-(5-(3-Ethyl-6-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)-1H-pyrazol-1-yl)benzonitrile,
(R)-4-(5-(6-Methyl-2,4-dioxo-3-(pyrolidin-3-yl)-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile,
4-(5-(3,6-Dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4-fluoro-1H-pyrazol-1-yl)benzonitrile,
4-(4-Chloro-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile,
1-(4-Cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carbonitrile,
(R)-4-(5-(6-Methyl-3-(methanesulfonyl)propan-2-yl)-2,4-dioxo-3-(1-oxopropane-2-yl)-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile,
(R)-2-(5-(1-(4-Cyanophenyl)-1H-pyrazol-5-yl)-4-methyl-2,6-dioxo-3-(3-trifluoromethylphenyl)-2,3-dihydropyrimidin-1(6H)-yl)propane-1-sulfonamide and
5-(4-Cyanophenyl)-4-(3-ethyl-6-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4H-1,2,4-triazole-3-carboxamide.

### Claim 13 (depends on 1)

A method of treating inflammatory diseases or cancers, comprising the step of:
administering the compound according to claim 1 or physiologically acceptable salts thereof to a patient in need thereof.

### Claim 14 (depends on 1)

A pharmaceutical composition for use in treatment or prophylaxis of inflammatory diseases or cancers comprising the compound according to claim 1 or physiologically acceptable salts thereof as active ingredient.

### Claim 15 (depends on 1)

The compound according to claim 1, wherein the compound is 4-(5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile or physiologically acceptable salts thereof.

### Claim 16 (depends on 1)

The compound according to claim 1, wherein the compound is 1-(4-cyanophenyl)-5-(3-isopropyl-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-carboxamide or physiologically acceptable salts thereof.

### Claim 17 (depends on 1)

The compound according to claim 1, wherein the compound is (+)-1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide or physiologically acceptable salts thereof.

### Claim 18 (depends on 1)

The compound according to claim 1, wherein the compound is (±)-1-(4-cyanophenyl)-5-(3-ethyl-6-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide or physiologically acceptable salts thereof.

### Claim 19 (depends on 1)

The compound according to claim 1, wherein the compound is (+)-4-(5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl-4-(methylsulfonyl)-1H-pyrazol-1-yl)benzonitrile or physiologically acceptable salts thereof.

### Claim 20 (depends on 1)

The compound according to claim 1, wherein the compound is (±)-4-(5-(3-Isopropyl-6-methyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl-4-(methylsulfonyl)-1H-pyrazol-1-yl)benzonitrile or physiologically acceptable salt thereof.