Rho-kinase inhibitors

• US 20030125344A1
• Filed: 03/22/2002
• Published: 07/03/2003
• Est. Priority Date: 03/23/2001
• Status: Abandoned Application

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Bayer Corporation (Bayer AG)
• Inventors: Weber, Olaf, Hart, Barry, Khire, Uday, Boyer, Stephen, Wang, Chunguang, Lynch, Mark, Shao, Jianxing, Asgari, Davoud, Nagarathnam, Dhanaphalan, Liu, Xiao-Gao
• Application Number:
  US10/103,566
• Publication Number:
  US 20030125344A1
• Time in Patent Office: Days
• US Class Current: 514/266.2
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings

Abstract

Disclosed are compounds and derivatives thereof, their synthesis, and their use as Rho-kinase inhibitors. These compounds of the present invention are useful for inhibiting tumor growth, treating erectile dysfunction, and treating other indications mediated by Rho-kinase, e.g., coronary heart disease.

Claims

1. A compound of Formula I

2. A compound according to claim 1, wherein A is a 5-12 carbon-atom aromatic ring or ring system containing 1-3 rings, at least one of which is aromatic, in which 1-4 carbon atoms in one or more of the rings is optionally replaced by oxygen, nitrogen or sulfur atoms.

3. A compound according to claim 2, wherein each ring in A has 3-7 atoms.

4. A compound according to claim 1, wherein A is 2- or 3-furyl, 2- or 3-thienyl, 2- or 4-triazinyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolylyl, 2-, 4-, or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3-, 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, 1,2,3-triazol-1-, -4- or 5-yl, 1,2,4-triazol-1-, -3- or 5-yl, 1- or 5-tetrazolyl, 1,2,3-oxadiazol-4- or 5-yl, 1,2,4-oxadiazol-3- or 5-yl, 1,3,4-thiadiazol-2- or 5-yl, 1,2,4-oxadiazol-3- or 5-yl, 1,3,4-thiadiazol-2- or 5-yl, 1,3,4-thiadiazol-3- or 5-yl, 1,2,3-thiadiazol-4- or 5-yl, 2-, 3-, 4-, 5- or 6-2H-thiopyranyl, 2-, 3- or 4-4H-thiopyranyl, 3- or 4-pyridazinyl, pyrazinyl, 2-, 3-, 4-, 5-, 6- or 7-benzofuryl, 2-, 3-, 4-, 5-, 6- or 7-benzothienyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 1-, 2-, 4- or 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-benzopyrazolyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 3-, 4-, 5- 6- or 7-benzisoxazolyl, 1-, 3-, 4-, 5-, 6- or 7-benzothiazolyl, 2-, 4-, 5-, 6- or 7-benzisothiazolyl, 2-, 4-, 5-, 6- or 7-benz-1,3-oxadiazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolinyl, 1-, 3-, 4-, 5-, 6-, 7-, 8-isoquinolinyl, 1-, 2-, 3-, 4- or 9-carbazolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl, or 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 2- or 3-thienyl, 1,3,4-thiadiazolyl, 3-pyrryl, 3-pyrazolyl, 2-thiazolyl or 5-thiazolyl.

5. A compound according to claim 1, wherein A is cyclohexyl;

or C_5-12-aryl or C_5-12-heteroaryl each independently optionally substituted up to three times by (i) C₁-C₁₀-alkyl or C_2-10-alkenyl each optionally substituted with halogen up to perhalo;

(ii) C₃-C₁₀ cycloalkyl;

(iii) C_5-12-aryl optionally substituted by 1-3 halogen atoms;

(iv) C_5-12-heteroaryl;

(v) halogen;

(vi) —

CO—

OR₈;

(vii) —

CO—

R₈;

(viii) cyano;

(ix) —

OR₈;

(x) —

NR₈R₁₃;

(xi) nitro;

(xii) —

CO—

NR₈R₉;

(xiii) —

C_1-10-alkyl-NR₈R₉;

(xiv) —

NR₈—

CO—

R₁₂;

(xv) —

NR₈—

CO—

OR₉;

(xvi) —

NR₈—

SO₂—

R₉;

(xvii) —

SR₈;

(xviii) —

SO₂—

R₈;

(xix) —

SO₂13 NR₈R₉, or (xx) NR₈—

CO—

NHR₉.

6. A compound according to claim 1, wherein A is phenyl, pyridyl, pyrimidinyl, oxazolyl, furyl, thienyl, pyrrolyl, imidazolyl, isoxazolyl and pyrazinyl, each independently substituted up to three times by halogen, C_1-10-alkyl, C_1-10-alkoxyphenyl, naphthyl, —

OR₁₀,

7. A compound according to claim 1, wherein A is

8. A compound according to claim 1, wherein R⁵ in a, b or c is hydrogen or C_1-10-alkyl or C_2-10-alkyl optionally substituted by amino, N-lower alkylamino, N,N-dilower alkylamino, N-lower alkanoylamino, hydroxy, cyano, —

COOR₁₀, —

COR₁₄, —

OCOR₁₄, —

OR₁₀, C_5-10-heteroaryl, C_5-10-heteroaryloxy, or C_5-10-heteroaryl-C_1-10-alkoxy, halogen up to perhalo;

(iii) C₃-C₁₀ cycloalkyl, in which 1-3 carbon atoms are optionally independently replaced by O, N or S;

(iv) C_3-10-cycloalkenyl;

(v) partially unsaturated C_5-10-heterocyclyl;

(vi) aryl;

(vii) heteroaryl;

(viii) halogen;

(ix) —

CO—

OR₁₀;

(x) —

OCOR₁₀;

(xi) —

OCO₂R₁₀;

(xii) —

CHO;

(xiii) cyano;

(xiv) —

OR₁₆;

(xv) —

NR₁₀R₁₅;

(xvi) nitro;

(xvii) —

CO—

NR₁₀R₁₁;

(xviii) —

NR₁₀—

CO—

R₁₂;

(xix) —

NR₁₀—

CO—

OR₁₁;

(xx) —

NR₁₀—

SO₂—

R₁₂;

(xxi) —

SR₁₆;

(xxii) —

SOR₁₆;

(xxiii) —

SO₂—

R₁₆;

(xxiv) —

SO₂—

NR₁₀R₁₁;

(xxv) NR₁₀—

CO—

NHR₁₁;

(xxvi) amidino;

(xxvii) guanidino;

(xxviii) sulfo;

(xxix) —

B(OH)₂;

(xxx) —

OCON(R₁₀)₂;

or (xxxi) —

NR₁₀CON(R₁₀)₂.

9. A compound according to claim 1, wherein Y is N and R₁ is H.

10. A compound according to claim 9, wherein a is —

NR₆—

, R₆ is H, and c is —

N═

.

11. A compound according to claim 10, wherein p is 0 and R_1-4 are H.

12. A compound according to claim 11, wherein X is —

(CH₂)_x— and

x is 0.

13. A compound according to claim 12, wherein A is biphenyl optionally substituted by halogen.

14. A compound according to claim 1, of the formula:

2-(2,4-dichlorophenyl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 2-(4-chlorophenyl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 1-{4-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]phenyl}ethanone, N-(1H-indazol-5-yl)-2-[4-(trifluoromethyl)phenyl]-4-quinazolinamine, 2-(3-chloro-4-fluorophenyl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 2-(1,3-benzodioxol-5-yl)-N-(1H-indazol-5-yl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(4-methylphenyl)-4-quinazolinamine, 2-(3,4-dichlorophenyl)-N-(1H-indazol-5-yl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(1-naphthyl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(3,4,5-trimethoxyphenyl)-4-quinazolinamine, 2-(1-benzofuran-2-yl)-N-(1H-indazol-5-yl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(2-thienyl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(3-thienyl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(3-methoxyphenyl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(2-methoxyphenyl)-4-quinazolinamine, 2-(4-ethoxyphenyl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 2-(3,5-dimethyl-4-isoxazolyl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 2-(1,1′

-biphenyl-4-yl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 2-[4-(dimethylamino)phenyl]-N-(1H-indazol-5-yl)-4-quinazolinamine, 2-(1-benzothieN-2-yl)-N-(1H-indazol-5-yl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(4-methoxyphenyl)-4-quinazolinamine, 4-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]phenol, 2-dibenzo[b,d]furan-1-yl-N-(1H-indazol-5-yl)-4-quinazolinamine, 2-(2-fluoro-1,1′

-biphenyl-4-yl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 7-chloro-N-(1H-indazol-5-yl)-2-phenyl-4-quinazolinamine, N-(1H-indazol-5-yl)-6-nitro-2-phenyl-4-quinazolinamine, 2-(4-fluorophenyl)-N-(1H-indazol-5-yl)-6-nitro-4-quinazolinamine, 6-chloro-N-(1H-indazol-5-yl)-2-(4-methylphenyl)-4-quinazolinamine, 6-chloro-N-(1H-indazol-5-yl)-2-(4-methoxyphenyl)-4-quinazolinamine, 6-chloro-2-(4-fluorophenyl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 6-chloro-N-(1H-indazol-5-yl)-2-(3-methoxyphenyl)-4-quinazolinamine, 2-(4-bromophenyl)-6-chloro-N-(1H-indazol-5-yl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(2-quinoxalinyl)-4-quinazolinamine, 5-fluoro-N-(1H-indazol-5-yl)-2-(2-methylphenyl)-4-quinazolinamine, 5-fluoro-2-(4-fluorophenyl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 2-(3-chlorophenyl)-5-fluoro-N-(1H-indazol-5-yl)-4-quinazolinamine, 2-(4-bromophenyl)-5-fluoro-N-(1H-indazol-5-yl)-4-quinazolinamine, 5-fluoro-N-(1H-indazol-5-yl)-2-(3-methylphenyl)-4-quinazolinamine hydrochloride, 2-(3-bromophenyl)-5-fluoro-N-(1H-indazol-5-yl)-4-quinazolinamine hydrochloride, 2-(2-chlorophenyl)-5-fluoro-N-(1H-indazol-5-yl)-4-quinazolinamine, 5-fluoro-N-(1H-indazol-5-yl)-2-(3-methoxyphenyl)-4-quinazolinamine bis(trifluoroacetate), 5-fluoro-N-(1H-indazol-5-yl)-2-(2-quinoxalinyl)-4-quinazolinamine tris(trifluoroacetate), 5-fluoro-N-(1H-indazol-5-yl)-2-(1-naphthyl)-4-quinazolinamine bis(trifluoroacetate), 5-fluoro-N-(1H-indazol-5-yl)-2-(2-naphthyl)-4-quinazolinamine bis(trifluoroacetate), 5-fluoro-N-(1H-indazol-5-yl)-2-(4-pyridinyl)-4-quinazolinamine tris(trifluoroacetate), N-(1H-indazol-5-yl)-7-methyl-2-(2-quinoxalinyl)-4-quinazolinamine, 2-(3-chlorophenyl)-N-(1H-indazol-5-yl)-7-methyl-4-quinazolinamine, 2-(4-fluorophenyl)-N-(1H-indazol-5-yl)-7-methyl-4-quinazolinamine, N-(1H-indazol-5-yl)-7-methyl-2-(4-methylphenyl)-4-quinazolinamine″

, 2-(4-bromophenyl)-N-(1H-indazol-5-yl)-7-methyl-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(4-methoxyphenyl)-7-methyl-4-quinazolinamine, N-(1H-indazol-5-yl)-7-methyl-2-(2-methylphenyl)-4-quinazolinamine bis(trifluoroacetate), N-(1H-indazol-5-yl)-7-methyl-2-(3-methylphenyl)-4-quinazolinamine bis(trifluoroacetate), N-[2-(3-fluorophenyl)-7-methyl-4-quinazolinyl]-N-(1H-indazol-5-yl)amine bis(trifluoroacetate), 2-(3-bromophenyl)-N-(1H-indazol-5-yl)-7-methyl-4-quinazolinamine bis(trifluoroacetate), N-[2-(2-chlorophenyl)-7-methyl-4-quinazolinyl]-N-(1H-indazol-5-yl)amine bis(trifluoroacetate), N-(1H-indazol-5-yl)-2-(3-methoxyphenyl)-7-methyl-4-quinazolinamine bis(trifluoroacetate), 2-(3-furyl)-N-(1H-indazol-5-yl)-7-methyl-4-quinazolinamine bis(trifluoroacetate), N-(1H-indazol-5-yl)-7-methyl-2-(1-naphthyl)-4-quinazolinamine bis(trifluoroacetate), N-(1H-indazol-5-yl)-7-methyl-2-(2-naphthyl)-4-quinazolinamine bis(trifluoroacetate), N-(1H-indazol-5-yl)-7-methyl-2-(3-pyridinyl)-4-quinazolinamine tris(trifluoroacetate), N-(1H-indazol-5-yl)-7-methyl-2-(4-pyridinyl)-4-quinazolinamine tris(trifluoroacetate), 7-chloro-2-(3-chlorophenyl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 7-chloro-N-(1H-indazol-5-yl)-2-(4-methylphenyl)-4-quinazolinamine, 2-(4-bromophenyl)-7-chloro-N-(1H-indazol-5-yl)-4-quinazolinamine, 7-chloro-N-(1H-indazol-5-yl)-2-(3-methylphenyl)-4-quinazolinamine hydrochloride, 7-chloro-2-(3-fluorophenyl)-N-(1H-indazol-5-yl)-4-quinazolinamine bis(trifluoroacetate), 2-(3-bromophenyl)-7-chloro-N-(1H-indazol-5-yl)-4-quinazolinamine bis(trifluoroacetate), 7-chloro-N-(1H-indazol-5-yl)-2-(3-methoxyphenyl)-4-quinazolinamine bis(trifluoroacetate), N-[7-chloro-2-(2-furyl)-4-quinazolinyl]-N-(1H-indazol-5-yl)amine bis(trifluoroacetate), 7-chloro-N-(1H-indazol-5-yl)-2-(2-quinoxalinyl)-4-quinazolinamine tris(trifluoroacetate), 7-chloro-N-(1H-indazol-5-yl)-2-(1-naphthyl)-4-quinazolinamine bis(trifluoroacetate), 7-chloro-N-(1H -indazol-5-yl)-2-(2-naphthyl)-4-quinazolinamine bis(trifluoroacetate), 7-chloro-N-(1H-indazol-5-yl)-2-(3-pyridinyl)-4-quinazolinamine tris(trifluoroacetate), 2-(4-fluorophenyl)-N-(1H-indazol-5-yl)-6,7-dimethoxy-4-quinazolinamine, 2-(1,1′

-biphenyl-4-yl)-N-(1H-indazol-5-yl)-6,7-dimethoxy-4-quinazolinamine, N-(1H-indazol-5-yl)-6,7-dimethoxy-2-(3-methoxyphenyl)-4-quinazolinamine, N-(1H-indazol-5-yl)-6,7-dimethoxy-2-(4-vinylphenyl)-4-quinazolinamine, 2-(4-ethoxyphenyl)-N-(1H-indazol-5-yl)-6,7-dimethoxy-4-quinazolinamine, N-cyclopentyl-4-(1H-indazol-5-ylamino)-2-quinazolinecarboxamide, N-(3-fluorophenyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(2,4-difluorobenzyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(2-fluorobenzyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(4-bromophenyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(6,7-dimethoxy-2-{[4-(trifluoromethyl)phenyl]amino}-4-quinazolinyl)-N-(1H-indazol-5-yl)amine, N-(6,7-dimethoxy-2-{[4-(trifluoromethyl)benzyl]amino}-4-quinazolinyl)-N-(1H-indazol-5-yl)amine, N-[3-fluoro-5-(trifluoromethyl)benzyl]-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(3-fluorobenzyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(2,4-difluorobenzyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(4-fluorobenzyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(2,6-difluorobenzyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(3,5-difluorobenzyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(3-bromophenyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(2,6-difluorophenyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(2,5-difluorophenyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(2,4-difluorophenyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(2,3-difluorophenyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, N-(3,4-difluorophenyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl] amine, N-(3,5-difluorophenyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl] amine, N-{6,7-dimethoxy-2-[(2,3,4-trifluorophenyl)amino]-4-quinazolinyl}-N-(1H-indazol-5-yl)amine, N-{6,7-dimethoxy-2-[(2,4,5-trifluorophenyl)amino]-4-quinazolinyl}-N-(1H-indazol-5-yl)amine, N-{6,7-dimethoxy-2-[(2,4,6-trifluorophenyl)amino]-4-quinazolinyl}-N-(1H-indazol-5-yl)amine, N-{6,7-dimethoxy-2-[(2,3,6-trifluorophenyl)amino]-4-quinazolinyl}-N-(1H-indazol-5-yl)amine, N-(4-bromophenyl)-N-[4-(1H-indazol-5-ylamino)-6,7-dimethoxy-2-quinazolinyl]amine, 2-(3-aminophenyl)-N-(1H-indazol-5-yl)-4-quinazolinamine, N-{3-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]phenyl}isonicotinamide, N-{3-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]phenyl}acetamide, N-(4-chlorophenyl)-N-[4-1H-indazol-5-ylamino)-2-quinazolinyl]amine, N-(3-bromophenyl)-N-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]amine, N-(2-chlorophenyl)-N-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]amine, N-(3-fluorophenyl)-N-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]amine, N-(2-fluorophenyl)-N-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]amine, N-(1H-indazol-5-yl)-N-{2-[(2-methoxyphenyl)amino]-4-quinazolinyl}amine, N-(1H-indazol-5-yl)-N-{2-[(3-methoxyphenyl)amino]-4-quinazolinyl}amine, N-(3-chlorophenyl)-N-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]amine, N-(4-bromophenyl)-N-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]amine, N-(1H-indazol-5-yl)-N-(2-{[3-(trifluoromethyl)phenyl]amino}-4-quinazolinyl)amine, N-(1H-indazol-5-yl)-N-{2-[(4-phenoxyphenyl)amino]-4-quinazolinyl}amine, N-(1H-indazol-5-yl)-N-(2-{[4-(trifluoromethoxy)phenyl]amino}-4-quinazolinyl)amine, N-(1H-indazol-5-yl)-N-(2-{[3-(trifluoromethoxy)phenyl]amino}-4-quinazolinyl)amine, N-(4-fluorophenyl)-N-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]amine, N-(2-anilino-4-quinazolinyl)-N-(1H-indazol-5-yl)amine, 2-[4-(2-chlorophenyl)-1-piperazinyl]-N-(1H-indazol-5-yl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-[4-(2-pyrimidinyl)-1-piperazinyl]-4-quinazolinamine, N-(1H-indazol-5-yl)-2-[4-(2-methoxyphenyl)-1-piperazinyl]-4-quinazolinamine, 1-(4-{4-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]-1-piperazinyl}phenyl)ethanone, 4-(1H-indazol-5-ylamino)-2-quinazolinecarboxamide″

, 4-(1H-indazol-5-ylamino)-N-(4-pyridinyl)-2-quinazolinecarboxamide, 4-(1H-indazol-5-ylamino)-N-(4-methoxyphenyl)-2-quinazolinecarboxamide, N-cyclohexyl-4-(1H-indazol-5-ylamino)-2-quinazolinecarboxamide, N-cyclopentyl-4-(1H-indazol-5-ylamino)-2-quinazolinecarboxamide, 4-(1H-indazol-5-ylamino)-N-(2-pyridinyl)-2-quinazolinecarboxamide, 4-(1H-indazol-5-ylamino)-N-(3-quinolinyl)-2-quinazolinecarboxamide, 4-(1H-indazol-5-ylamino)-N-methyl-2-quinazolinecarboxamide, N-(1H-indazol-5-yl)-2-(4-morpholinylcarbonyl)-4-quinazolinamine, 2-(2,3-dihydro-1-benzofuran-5-yl)-N-(1H-indazol-5-yl)-4-quinazolinamine, 2-cyclopropyl-N-(1H-indazol-5-yl)-4-quinazolinamine, N-(1H-indazol-5-yl)-2-(trifluoromethyl)-4-quinazolinamine, N-(3-ethyl-1H-indazol-5-yl)-2-(4-methoxyphenyl)-4-quinazolinamine, 2-chloro-N-(3-ethyl-1H-indazol-5-yl)-4-quinazolinamine, 2-(2-fluoro-1,1′

-biphenyl-4-yl)-N-(1H-indazol-5-yl)-4-quinazolinamine dihydrochloride, 2-(2-fluoro-1,1′

-biphenyl-4-yl)-N-(1H-indazol-5-yl)-4-quinazolinamine dimethanesulfonate, 2-(2-fluoro-1,1′

-biphenyl-4-yl)-N-(1H-indazol-5-yl)-4-quinazolinamine benzenesulfonate, 2-(2-fluoro-1,1′

-biphenyl-4-yl)-N-(1H-indazol-5-yl)-4-quinazolinamine 4-methylbenzenesulfonate, or 2-dibenzo[b,d]furan-1-yl-N-(1H-indazol-5-yl)-4-quinazolinamine trifluoroacetate, 2-chloro-N-(1H-indazol-5-yl)-4-quinazolinamine.

15. A method of treating an indication mediated by Rho-kinase, comprising administering a compound of claim 1.

16. A method of treating an indication mediated by Rho-kinase, comprising administering a compound of claim 13.

17. A method of treating an indication mediated by Rho-kinase, comprising administering a compound of claim 14.

18. A method of treating hypertension, atherosclerosis, restenosis, cerebral ischemia, cerebral vasospasm, neuronal degeneration, spinal cord injury, cancer of the breast, colon, prostate, ovaries, brain or lung, thrombotic disorders, asthma, glaucoma, osteoporosis or erectile dysfunction, comprising administering to a host in need thereof a compound according to claim 1.

19. A method of treating hypertension, atherosclerosis, restenosis, cerebral ischemia, cerebral vasospasm, neuronal degeneration, spinal cord injury, cancer of the breast, colon, prostate, ovaries, brain or lung, thrombotic disorders, asthma, glaucoma, osteoporosis or erectile dysfunction, comprising administering to a host in need thereof a compound according to claim 13.

20. A method of treating hypertension, atherosclerosis, restenosis, cerebral ischemia, cerebral vasospasm, neuronal degeneration, spinal cord injury, cancer of the breast, colon, prostate, ovaries, brain or lung, thrombotic disorders, asthma, glaucoma and osteoporosis or erectile dysfunction, comprising administering to a host in need thereof a compound according to claim 14.

21. A process according to claim 15, wherein the host is a human.

22. A process according to claim 16, wherein the host is a human.

23. A process according to claim 17, wherein the host is a human.

24. A process according to claim 18, wherein the host is a human.

25. A process according to claim 19, wherein the host is a human.

26. A process according to claim 20, wherein the host is a human.

27. A process for the preparation of a compound of claim 1, comprising

(a) reacting a compound of formula II

with a compound of formula III

in the presence of a base, to produce a compound of formula IV

and optionally further reacting IV with arylboronic acid or A-NH₂, or

(b) reacting a substituted benzoyl chloride with dimethylamine to produce a compound of formula V

wherein R′

″

is (i) C₁-C₁₀ alkyl or C₂-C₁₀-alkenyl, each optionally substituted with halogen up to perhalo;

(ii) C₃-C₁₀ cycloalkyl;

(iii) aryl;

(iv) heteroaryl;

(v) halogen;

(vi) —

CO—

OR₈;

(vii) —

CO—

R₈;

(viii) cyano;

(ix) —

OR₈, (x) (x) —

NR₈R₁₃;

(xi) nitro;

(xii) —

CO—

NR₈R₉;

(xiii) —

C_1-10-alkyl-NR₈R₉;

(xiv) —

NR₈—

CO—

R₁₂;

(xv) —

NR₈—

CO—

OR₉;

(xvi) —

NR₈—

SO₂—

R₉;

(xvii) —

SR₈;

(xviii) —

SO₂—

R₈;

(xix) —

SO₂—

NR₈R₉;

or (xx) NR₈—

CO—

NHR₉,

reacting V with chloro-2-amino-benzonitrile to produce a compound of formula VI

and reacting VI with aminoindazole.