Substituted sulfonamides useful as antiapoptotic Bcl inhibitors

• US 9,346,795 B2
• Filed: 05/23/2012
• Issued: 05/24/2016
• Est. Priority Date: 05/25/2011
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Borzilleri, Robert M., Cai, Zhen-Wei, Tebben, Andrew J., Perez, Heidi L., Zhang, Liping, Schroeder, Gretchen M., Wei, Donna D.
• Primary Examiner(s): Wilson, James O
• Assistant Examiner(s): Sackey, Ebenezer O
• Application Number:
  US14/122,173
• Publication Number:
  US 20140135318A1
• Time in Patent Office: 1,462 Days
• Field of Search: 514/221, 514/314, 514/235.2, 514/253.06, 514/230.5, 514/224.2, 540/567, 544/128, 544/47, 544/90, 544/363, 546/165
• US Class Current: 1/1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 401/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 403/10 linked by a carbon chain containing aromatic rings
• 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 413/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/10 linked by a carbon chain containing aromatic rings

Abstract

Disclosed are compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein: W and Q and G are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bcl-2 family antiapoptotic proteins for the treatment of cancer; and pharmaceutical compositions comprising such compounds.

Claims

1. A compound of Formula (I)

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein:

Q is;

(a) naphthalenyl substituted with zero to 3 substituents independently selected from —

OH, —

CN, Cl, Br, I, —

NO₂, —

N(CH₃)₂, —

C(O)OH, —

C(O)OCH₂CH₃, —

S(O)₂CH₂CH₃, C_1-3 alkoxy, —

OCH(CH₃)CH₂N(CH₃)₂, —

O(CH₂)₃N(CH₃)₂, —

OCH₂(phenyl), —

OCH₂(dichlorophenyl), —

OCH₂(benzoic acid), —

OCH₂(methyl benzoate), —

OCH₂(methylsulfonylphenyl), —

OCH₂(furanyl), —

OCH₂(N-methyl-1H-imidazolyl), —

O(CH₂)₂(N-methylpyrrolidinyl), —

O(CH₂)_2-3(morpholinyl), —

O(CH₂)₃(pyrrolidinyl), —

O(CH₂)₃(piperidinyl), O(CH₂)₃(N-methylpiperazinyl), —

O(CH₂)₃(pyridinyl), —

OCH₂CH₂OH, —

OCH₂CH₂O(C_1-2 alkyl), —

OCH₂CH₂O(phenyl), —

C(O)N(CH₃)₂, —

C(O)(N-methylpiperazinyl), —

C(O)(morpholinyl), and/or —

NHC(O)(dichlorophenyl);

(b) isoquinolinyl substituted with —

OCH₂CH₂(morpholinyl), —

SCH₂CH₂NH₂, or —

SCH₂C(O)OH;

(c)

3. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein W is:

4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein:

W is

5. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein:

W is

6. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein:

W is

7. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein:

W is

8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein:

W is

9. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein:

W is

10. A pharmaceutical composition, comprising;

a pharmaceutically acceptable carrier and a compound according to claim 1 or pharmaceutically acceptable salts thereof.

11. A method for treating cancer in a patient in need of such treatment, comprising administering to the patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein said cancer is selected from breast cancer, ovarian cancer, and prostate cancer.

12. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein said compound is selected from:

N,N-Dibutyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (1);

N,N-dibutyl-4-chloro-1-(4-(5-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (2);

N,N-dibutyl-4-chloro-1-(4-(6-(dimethylamino)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (3);

N,N-dibutyl-4-chloro-1-(4-(5-(dimethylamino)naphthalen-1-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (4);

N,N-dibutyl-4-chloro-1-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (5);

N,N-dibutyl-4-chloro-1-(4-(6-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (6);

N,N-dibutyl-4-chloro-1-(4-(8-iodonaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (7);

N,N-dibutyl-4-chloro-1-(4-(8-cyanonaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (8);

ethyl 7-(N-(4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl)-1-naphthoate (9);

N,N-dibutyl-4-chloro-1-(4-(7-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (10);

N,N-dibutyl-4-chloro-1-(4-(7-iodonaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (11);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(5-nitronaphthalen-1-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (12);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(4-(5-nitronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (13);

N,N-dibutyl-4-chloro-1-(4-(6-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (14);

N,N-dibutyl-4-chloro-1-(4-(7-cyanonaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (15);

ethyl 7-(N-(4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl)-2-naphthoate (16);

ethyl 7-(N-(4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl)-2-naphthoate (17);

1-(4-(7-(benzyloxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (18);

N,N-dibutyl-4-chloro-1-(4-(8-(3,4-dichlorobenzamido) naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (19);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(7-(4-(methylsulfonyl)benzyloxy)-naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (20);

N,N-dibutyl-4-chloro-1-(4-(8-(3,4-dichlorobenzyloxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (21);

N,N-dibutyl-4-chloro-1-(4-(7-(3,4-dichlorobenzyloxy) naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (22);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(7-((tetrahydrofuran-2-yl)methoxy) naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (23);

N,N-dibutyl-4-chloro-1-(4-(7-isopropoxynaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (24);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(7-(2-phenoxyethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (25);

methyl 4-((7-(N-(4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl)naphthalen-1-yloxy)methyl)benzoate (26);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (27);

N,N-dibutyl-4-chloro-1-(4-(7-(2-methoxyethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (28);

N,N-dibutyl-4-chloro-1-(4-(7-methoxynaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (29);

N,N-dibutyl-4-chloro-1-(4-(7-(2-ethoxyethoxy) naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (30);

1-(4-(8-bromo-5-(dimethylamino)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (31);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(8-(3-morpholinopropoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (32);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(7-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (33);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(7-(3-morpholinopropoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (34);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(7-(3-(4-methylpiperazin-1-yl)propoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (35);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(7-((1-methyl-1H-imidazol-2-yl)methoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (36);

N,N-dibutyl-4-chloro-1-(4-(7-(1-(dimethylamino)propan-2-yloxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (37);

N,N-dibutyl-4-chloro-5-methyl-1-(4-((7-(2-(1-methylpyrrolidin-2-yl)ethoxy)naphthalene-2-sulfonamido)methyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (38);

N,N-dibutyl-4-chloro-1-(4-(7-(3-(dimethylamino) propoxy)-naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (39);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(7-(3-(pyrrolidin-1-yl)propoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (40);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(7-(3-(piperidin-1-yl)propoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (41);

N,N-Dibutyl-4-chloro-5-methyl-1-(4-(7-(3-(pyridin-4-yl)propoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (42);

1-(4-(8-bromo-5-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (43);

N,N-dibutyl-4-chloro-1-(4-(5,8-dichloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (44);

7-(N-(4-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl)-1-naphthoic acid (45);

N,N-Dibutyl-4-chloro-5-methyl-1-(4-(7-(4-methylpiperazine-1-carbonyl)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (46);

N,N-Dibutyl-4-chloro-5-methyl-1-(4-(7-(morpholine-4-carbonyl)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (47);

N,N-Dibutyl-4-chloro-1-(4-(7-(dimethylcarbamoyl)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (48);

4-((7-(N-(4-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl)naphthalen-1-yloxy)methyl)benzoic acid (48);

N,N-Dibutyl-4-chloro-1-(4-(7-(2-hydroxyethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (50);

N,N-Dibutyl-4-chloro-1-(4-(7-hydroxynaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (51);

N,N-Dibutyl-4-chloro-1-(4-(indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (52);

N,N-dibutyl-4-chloro-1-(4-(1-ethylindolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (53);

1-(4-(1H-indol-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (54);

N,N-dibutyl-4-chloro-1-(4-(1-(cyclohexanecarbonyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (55);

N,N-dibutyl-4-chloro-1-(4-(1-ethyl-1H-indol-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (56);

N,N-dibutyl-4-chloro-1-(4-(1-(cyclohexylmethyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (57);

N,N-dibutyl-4-chloro-1-(4-(1-(3,4-dichlorobenzoyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (58);

N,N-dibutyl-4-chloro-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (59);

1-(4-(1-acetylindolin-6-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (60);

1-(4-(1-benzylindolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (61);

N,N-dibutyl-4-chloro-1-(4-(1-(3,4-difluorobenzyl) indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (62);

N,N-dibutyl-4-chloro-1-(4-(1-ethylindolin-6-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (63);

N,N-dibutyl-4-chloro-1-(4-(1-(2-(3,4-dichlorophenyl)acetyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (64);

N,N-dibutyl-4-chloro-1-(4-(1-(3,4-dichlorophenethyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (65);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(1-(2-(phenylthio)acetyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-1H-pyrazole-3-carboxamide (66);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(1-(2-(phenylthio) ethyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (67);

N,N-dibutyl-4-chloro-1-(4-(1-(3,4-dichlorobenzyl)-1H-indol-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (68);

N,N-dibutyl-4-chloro-1-(4-(1-((6-chloropyridin-2-yl)methyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (69);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(1-((1-methyl-1H-indol-6-yl)methyl) indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (70);

1-(4-(5-bromo-1-ethylindolin-6-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (71);

1-(4-(5-bromo-1-(3,4-dichlorobenzyl)indolin-6-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (72);

methyl 5-(N-(4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl)-1-(3,4-dichlorobenzyl)indoline-2-carboxylate (73);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(1-(morpholine-4-carbonyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (74);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(1-(2-morpholinoacetyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (75);

1-(4-(7-bromo-1-ethylindolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (76);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(1-(2-morpholinoethyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (77);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(1-((2-(2-morpholinoethoxy)pyridin-3-yl)methyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (78);

1-(4-(3-bromo-1H-indol-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (79);

1-(4-(3-bromo-1-ethyl-1H-indol-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (80);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(1-(3-morpholinopropanoyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (81);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(1-(3-morpholinopropyl)-1H-indol-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (82);

N,N-dibutyl-4-chloro-1-(4-(3-chloro-1-ethyl-1H-indol-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (83);

N,N-dibutyl-4-chloro-1-(4-(1-ethyl-3-iodo-1H-indol-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (84);

N,N-dibutyl-4-chloro-1-(4-(3,7-dibromo-1-ethyl-1H-indol-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (85);

N,N-Dibutyl-4-chloro-1-(4-(indolin-6-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (86);

(E)-1-(4-(5-(But-1-enyl)-1-ethylindolin-6-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (87);

N,N-Dibutyl-4-chloro-1-(4-(1-ethyl-5-morpholinoindolin-6-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (88);

(E)-N,N-Dibutyl-4-chloro-1-(4-(1-ethyl-5-(prop-1-enyl)indolin-6-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (89);

N,N-Dibutyl-4-chloro-1-(4-(1-(3,4-dichlorobenzyl)indolin-6-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (90);

N,N-Dibutyl-4-chloro-1-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (91);

1-(2-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (92);

(3R)-2-(2-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (93);

(3S)-2-(2-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (94);

N,N-Dibutyl-4-chloro-1-(2-((R)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (95);

N,N-Dibutyl-4-chloro-1-(2-(3,4-dihydro-2H-benzo[e][1,3]oxazine-3-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (96);

N,N-Dibutyl-4-chloro-5-methyl-1-(2-(1-methyl-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1H-pyrazole-3-carboxamide (97);

N,N-Dibutyl-4-chloro-1-(2-(4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (98);

1-(2-(7-Bromo-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (99);

2-(2-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid (100);

N,N-Dibutyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (101);

1-(2-(3-Bromo-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (102);

N,N-Dibutyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroquinazoline-3-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (103);

N,N-Dibutyl-4-chloro-1-(2-(1,1-dioxido-3,4-dihydro-2H-benzo[e][1,3]thiazine-3-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (104);

N,N-Dibutyl-4-chloro-1-(2-((S)-3-((3-methoxypropoxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (105);

N,N-Dibutyl-4-chloro-5-methyl-1-(2-((S)-3-((1-methylpiperidin-4-ylamino)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1H-pyrazole-3-carboxamide (106);

N,N-Dibutyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-((piperidin-4-ylamino)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (107);

N,N-dibutyl-4-chloro-1-(2-((S)-3-((dimethylamino) methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (108);

N,N-dibutyl-4-chloro-5-methyl-1-(2-((S)-3-(morpholinomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1H-pyrazole-3-carboxamide (109);

N,N-dibutyl-4-chloro-1-(2-((S)-3-((4-hydroxypiperidin-1-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (110);

N,N-dibutyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(pyrrolidin-1-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (111);

N,N-dibutyl-4-chloro-5-methyl-1-(2-((S)-3-((4-methylpiperazin-1-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1H-pyrazole-3-carboxamide (112);

N,N-dibutyl-4-chloro-1-(2-((S)-3-(((2-methoxyethyl)(methyl)amino)-methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (113);

N,N-dibutyl-4-chloro-1-(2-((S)-3-(((2-hydroxyethyl)(methyl)amino)-methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (114);

N,N-dibutyl-4-chloro-1-(2-((S)-3-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (115);

N,N-dibutyl-4-chloro-1-(2-((S)-3-((2-(dimethylamino) ethoxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (116);

1-(2-((S)-3-((2-(benzyloxy)ethoxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (117);

N,N-dibutyl-4-chloro-5-methyl-1-(2-(3-((4-methylpiperazin-1-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1H-pyrazole-3-carboxamide (118);

N,N-Dibutyl-4-chloro-1-(2-((S)-3-((2-hydroxyethoxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (119);

N,N-Dibutyl-4-chloro-1-(2-(3-(dimethylamino)-2,5-dihydro-1H-benzo[e][1,3]diazepine-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (120);

(Z)—

N,N-Dibutyl-4-chloro-1-(2-(3-((2-methoxyethyl)(methyl)amino)-2,5-dihydro-1H-benzo[e][1,3]diazepine-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (121);

3-(4-(N-Butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamido)phenyl)propanoic acid (122);

N-Butyl-4-chloro-N-(4-iodophenyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (123);

1-(3-(4-(N-Butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamido)phenyl)propanoyl)piperidine-4-carboxylic acid (124);

4-Chloro-N-(3,4-dichlorobenzyl)-N,5-dimethyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (125);

N-butyl-4-chloro-N-(3,4-dichlorobenzyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (126);

N-butyl-4-chloro-N-(3,4-dichlorophenethyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (127);

N-butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-N-(4,4,4-trifluorobutyl)-1H-pyrazole-3-carboxamide (128);

4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-bis(4,4,4-trifluorobutyl)-1H-pyrazole-3-carboxamide (129);

4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-bis(3,3,3-trifluoropropyl)-1H-pyrazole-3-carboxamide (130);

N-butyl-4-chloro-N-(3-isopropoxybenzyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-1H-pyrazole-3-carboxamide (131);

N-butyl-4-chloro-N-(3-(4-chlorophenoxy)benzyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-1H-pyrazole-3-carboxamide (132);

N-(4-butoxybenzyl)-N-butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (133);

N-butyl-4-chloro-N-(3,4-dichlorophenyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (134);

N-butyl-4-chloro-N-(3-chlorobenzyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (135);

N-butyl-4-chloro-N-(4-chlorobenzyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (136);

N-butyl-4-chloro-N-(4-(4-fluorophenoxy)phenyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (137);

N-butyl-4-chloro-N-(4-(4-chlorophenoxy)phenyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (138);

N-butyl-4-chloro-5-methyl-N-(1-methyl-1H-indol-2-yl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (139);

N-butyl-4-chloro-N-(3,4-dimethoxyphenyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (140);

N-butyl-4-chloro-N-(4-isopropoxyphenyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (141);

N-butyl-4-chloro-N-(3-chloro-4-methylphenyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (142);

N-(biphenyl-4-yl)-N-butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (143);

N-butyl-4-chloro-N-(4-methoxyphenyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (144);

N-butyl-4-chloro-N-(3-methoxyphenyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (145);

N-butyl-N-(3-tert-butylphenyl)-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (146);

N-(biphenyl-3-yl)-N-butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (147);

N-butyl-N-(4-tert-butylphenyl)-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (148);

N-butyl-4-chloro-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (149);

N-butyl-4-chloro-N-(3-isopropoxyphenyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (150);

N-butyl-4-chloro-5-methyl-N-(naphthalen-2-ylmethyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (151);

N-butyl-4-chloro-N-(3′

-chlorobiphenyl-3-yl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (152);

N-butyl-4-chloro-N-(4′

-chlorobiphenyl-3-yl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (153);

methyl 4-(N-butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamido)benzoate (154);

4-(N-butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamido)benzyl propionate (155);

N-Butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N-phenyl-1H-pyrazole-3-carboxamide (156);

N-Benzyl-N-butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (157);

N-Butyl-4-chloro-5-methyl-N-(3-(2-(4-methylpiperazin-1-yl)ethylamino)-3-oxopropyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-1H-pyrazole-3-carboxamide (158);

N-Butyl-4-chloro-N-(3-(1,3-dihydroxypropan-2-ylamino)-3-oxopropyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (159);

N-Butyl-4-chloro-N-(3-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-ylamino)-3-oxopropyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (160);

4-(N-Butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamido)benzoic acid (161);

2-(4-(N-Butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamido) phenyl)acetic acid (162);

4-Bromo-N,N-dibutyl-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (163);

N,N-Dibutyl-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (164);

N,N-Dibutyl-4-(hydroxymethyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (165);

3-(3-(Dibutylcarbamoyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazol-4-yl)propanoic acid (166);

N,N-Dibutyl-4-(3-(dimethylamino)propyl)-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (167);

N,N-Dibutyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (168);

N,N-Dibutyl-4-chloro-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (169);

N,N-Dibutyl-4-chloro-5-(2-hydroxyethyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (170);

2-(4-Chloro-3-(dibutylcarbamoyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazol-5-yl)acetic acid (171);

N,N-Dibutyl-4-chloro-5-(2-(cyclopropanesulfonamido)-2-oxoethyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (172);

2-(4-Chloro-3-(dibutylcarbamoyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazol-5-yl)ethyl carbamate (173);

2-(4-Chloro-3-(dibutylcarbamoyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazol-5-yl)ethyl 4-methylpiperazine-1-carboxylate (174);

2-(4-Chloro-3-(dibutylcarbamoyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazol-5-yl)ethyl 2-(4-methylpiperazin-1-yl)ethylcarbamate (175);

tent-Butyl 3-(N-butyl-4-chloro-1-(4-(7-iodonaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamido)propanoate (176);

N,N-Dibutyl-4-chloro-1-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (177);

N-Butyl-4-chloro-N-(3,4-dichlorobenzyl)-1-(4-(8-(ethylsulfonyl)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (178);

N-Butyl-4-chloro-N-(3,4-dichlorobenzyl)-1-(4-(7-iodonaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (179);

N-Butyl-4-chloro-N-(3,4-dichlorobenzyl)-5-methyl-1-(4-(7-(4-methylpiperazine-1-carbonyl)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (180);

N-Butyl-4-chloro-1-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N-(3,4-dichlorobenzyl)-5-methyl-1H-pyrazole-3-carboxamide (181);

N-Butyl-4-chloro-1-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(((2-hydroxyethyl)(methyl)amino)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N-(3,4-dichlorobenzyl)-5-methyl-1H-pyrazole-3-carboxamide (182);

N,N-Dibutyl-4-chloro-1-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl) phenyl)-5-methyl-1H-pyrazole-3-carboxamide (183);

N,N-Dibutyl-4-chloro-1-(2-((S)-3-((dimethylamino)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy) naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (184);

N,N-Dibutyl-4-chloro-5-methyl-1-(4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(morpholinomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (185);

N-Butyl-4-chloro-N-(3,4-dichlorobenzyl)-5-methyl-1-(4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(morpholinomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (186);

N-Butyl-4-chloro-N-(3,4-dichlorobenzyl)-1-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (187);

1-(2-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N-butyl-4-chloro-N-(3,4-dichlorobenzyl)-5-methyl-1H-pyrazole-3-carboxamide (188);

N,N-Dibutyl-4-chloro-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (189);

N,N-Dibutyl-4-chloro-1-(4-(1-ethylindolin-5-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (190);

4-(4-Chloro-3-(dibutylamino)-5-methyl-1H-pyrazol-1-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (191);

4-(4-Chloro-3-(dipropylamino)-5-methyl-1H-pyrazol-1-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-N-(naphthalen-2-ylsulfonyl)benzamide (192);

4-(4-Chloro-3-(dipropylamino)-5-methyl-1H-pyrazol-1-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (193);

3-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(4-chloro-3-(dipropylamino)-5-methyl-1H-pyrazol-1-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)benzamide (194);

4-(4-Chloro-3-(dipropylamino)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (195);

4-(4-Chloro-3-(dipropylamino)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (196);

3-(N-butyl-4-chloro-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamido) propanoic acid (197);

N,N-dibutyl-4-chloro-1-(4-(1-(3,4-dichlorobenzyl)-1H-indol-5-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (198);

1-(4-(3-bromo-1-(3,4-dichlorobenzyl)-1H-indol-5-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (199);

N-butyl-4-chloro-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-N-(3-(2-(4-methylpiperazin-1-yl)ethylamino)-3-oxopropyl)-1H-pyrazole-3-carboxamide (200);

1-(2-((S)-3-(aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(3-bromo-1-(3,4-dichlorobenzyl)-1H-indol-5-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (201);

N,N-dibutyl-4-chloro-1-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-((3-methoxypropoxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (202);

1-(2-((S)-3-(aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (203);

(Z)—

N-(8-bromo-5-chloronaphthalen-2-ylsulfonyl)-4-(4-chloro-3-(dipropylamino)-5-methyl-1H-pyrazol-1-yl)-3-(3-(dimethylamino)-2,5-dihydro-1H-benzo[e][1,3]diazepine-2-carbonyl)benzamide (204);

1-(4-(7-bromo-1-ethylindolin-5-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (205);

4-chloro-1-(4-(1-ethylindolin-5-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-N,N-dipropyl-1H-pyrazole-3-carboxamide (206);

N-(8-bromo-5-chloronaphthalen-2-ylsulfonyl)-4-(4-chloro-3-(dipropylamino)-5-methyl-1H-pyrazol-1-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (207);

1-(4-(7-bromo-1-ethyl-1H-indol-5-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (208);

1-(4-(7-bromo-1-ethylindolin-5-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-4-chloro-5-methyl-N,N-dipropyl-1H-pyrazole-3-carboxamide (209);

N,N-dibutyl-4-chloro-1-(4-(3,7-dibromo-1-ethyl-1H-indol-5-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (210);

1-(2-(6-bromo-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (211);

N,N-dibutyl-4-chloro-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (212);

2-(4′

-((N-butyl-4-chloro-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamido)methyl) biphenyl-4-yl)acetic acid (213);

2-(4′

-((4-chloro-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamido)methyl)biphenyl-4-yl)acetic acid (214);

4-(3-(dibutylcarbamoyl)-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-5-methyl-1H-pyrazol-4-yl)benzoic acid (215);

4-chloro-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-N,N-dipropyl-1H-pyrazole-3-carboxamide (216);

1-(4-(8-bromo-5-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N-butyl-4-chloro-N-(4′

-chlorobiphenyl-3-yl)-5-methyl-1H-pyrazole-3-carboxamide (217);

1-(4-(8-bromo-5-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N-butyl-4-chloro-N-(3′

-chlorobiphenyl-3-yl)-5-methyl-1H-pyrazole-3-carboxamide (218);

N-butyl-4-chloro-N-((4′

-chlorobiphenyl-4-yl)methyl)-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (219);

N-butyl-4-chloro-N-(4-(4-chlorophenoxy)phenyl)-1-(4-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (220);

N-butyl-4-chloro-N-(4′

-chlorobiphenyl-3-yl)-1-(4-(5,8-dichloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (221);

N-butyl-4-chloro-N-(3′

-chlorobiphenyl-3-yl)-1-(4-(5,8-dichloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide (222);

Ethyl 5-butyl-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl) phenyl)-1-phenyl-1H-pyrazole-3-carboxylate (223);

Ethyl 5-methyl-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-phenyl-1H-pyrazole-3-carboxylate (224);

Ethyl 5-butyl-1-(4-methoxyphenyl)-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (225);

Ethyl 5-butyl-1-(4-isopropylphenyl)-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (226);

Ethyl 5-butyl-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-(3-phenoxyphenyl)-1H-pyrazole-3-carboxylate (227);

Ethyl 5-butyl-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-(4-phenoxyphenyl)-1H-pyrazole-3-carboxylate (228);

Ethyl 5-butyl-1-(4-(4-chlorophenoxy)phenyl)-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (229);

Ethyl 5-butyl-1-(4-(3-chlorophenoxy)phenyl)-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (230);

Ethyl 1-(4-butoxyphenyl)-5-butyl-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (231);

Ethyl 5-butyl-1-(4-(2-hydroxyethyl)phenyl)-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (232);

Ethyl 1-(4-(allyloxy) phenyl)-5-butyl-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (233);

Ethyl 1-(biphenyl-4-yl)-5-butyl-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (234);

Ethyl 5-butyl-1-(3-(methoxycarbonyl)phenyl)-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (235);

4-(5-Butyl-3-(hydroxymethyl)-1-phenyl-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (236);

5-Butyl-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-phenyl-1H-pyrazole-3-carboxylic acid (237);

4-(5-Butyl-3-(hydroxymethyl)-1-(3-(hydroxymethyl)phenyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (238);

Ethyl 5-butyl-1-phenyl-4-(2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(2-(trimethylsilyl)ethylsulfonylcarbamoyl)phenyl)-1H-pyrazole-3-carboxylate (239);

4-(5-Butyl-3-(hydroxymethyl)-1-phenyl-1H-pyrazol-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-N-(2-(trimethylsilyl)ethylsulfonyl)benzamide (240);

4-(5-butyl-3-(hydroxymethyl)-1-(4-phenoxyphenyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (241);

4-(5-butyl-1-(4-(4-chlorophenoxy)phenyl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (242);

4-(5-butyl-1-(4-(3-chlorophenoxy)phenyl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (243);

4-(5-butyl-1-(4-butoxyphenyl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (244);

4-(5-butyl-1-(4-(2-hydroxyethyl)phenyl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (245);

4-(1-(4-(allyloxy)phenyl)-5-butyl-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (246);

4-(1-(biphenyl-4-yl)-5-butyl-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (247);

ethyl 5-butyl-4-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-(4-(3-chlorophenoxy)phenyl)-1H-pyrazole-3-carboxylate (248);

ethyl 5-butyl-1-(4-(3-chlorophenoxy)phenyl)-4-(4-(ethylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (249);

ethyl 5-butyl-1-(4-(3-chlorophenoxy)phenyl)-4-(4-(pentylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxylate (250);

ethyl 4-(4-(8-bromo-5-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-butyl-1-(4-(3-chlorophenoxy)phenyl)-1H-pyrazole-3-carboxylate (251);

4-(5-butyl-1-(4-(3-chlorophenoxy)phenyl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (252);

4-(5-butyl-1-(4-(3-chlorophenoxy)phenyl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(ethylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (253);

4-(5-butyl-1-(4-(3-chlorophenoxy)phenyl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(pentylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (254);

N-(8-bromo-5-chloronaphthalen-2-ylsulfonyl)-4-(5-butyl-1-(4-(3-chlorophenoxy)phenyl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (255);

4-(5-Butyl-3-(hydroxymethyl)-1-(4-hydroxyphenyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (256);

4-(5-Butyl-3-(hydroxymethyl)-1-(4-(3-hydroxypropoxy)phenyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (257);

(±

)-4-(5-Butyl-1-(4-(2,3-dihydroxypropoxy)phenyl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (258);

Ethyl 5-butyl-4-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1-phenyl-1H-pyrazole-3-carboxylate (259);

4-(5-Butyl-3-(hydroxymethyl)-1-phenyl-1H-pyrazol-4-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-N-(naphthalen-2-ylsulfonyl)benzamide (260);

Ethyl 4-(2-((S)-3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl) phenyl)-5-butyl-1-phenyl-1H-pyrazole-3-carboxylate (261);

Ethyl 4-(2-((S)-3-(aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-butyl-1-phenyl-1H-pyrazole-3-carboxylate (262);

3-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1H-pyrazol-4-yl)-N-(naphthalen-2-ylsulfonyl)benzamide (263);

N,N-Dibutyl-1-methyl-2-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-imidazole-4-carboxamide (264);

N,N-Dibutyl-1-(2-(methylamino)-2-oxoethyl)-2-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-imidazole-4-carboxamide (265);

N,N-Dibutyl-1-(3-hydroxypropyl)-2-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-imidazole-4-carboxamide (266);

N,N-Dibutyl-1-(3-(dimethylamino)propyl)-2-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-imidazole-4-carboxamide (267);

N,N-Dibutyl-2-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxamide (268);

2-(4-(Dibutylcarbamoyl)-2-(4-(naphthalen-1-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-imidazol-1-yl)acetic acid (269);

N,N-Dibutyl-2-(4-(8-iodonaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-methyl-1H-imidazole-4-carboxamide (270);

N,N-Dibutyl-2-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-phenethyl-1H-imidazole-4-carboxamide (271);

N,N-Dibutyl-2-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-(3-phenylpropyl)-1H-imidazole-4-carboxamide (272);

1-Benzyl-N,N-dibutyl-2-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-imidazole-4-carboxamide (273);

N,N-Dibutyl-1-(2-hydroxyethyl)-2-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1H-imidazole-4-carboxamide (274);

N,N-Dibutyl-2-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl) phenyl)-1-(2-methoxyethyl)-1H-imidazole-4-carboxamide (275);

N,N-Dibutyl-1-(2-(2-hydroxyethoxy)ethyl)-2-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1H-imidazole-4-carboxamide (276);

N,N-Dibutyl-2-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1-(2-morpholinoethyl)-1H-imidazole-4-carboxamide (277);

N,N-Dibutyl-2-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1-(3-morpholinopropyl)-1H-imidazole-4-carboxamide (278);

N,N-Dibutyl-2-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1-(3-(4-methylpiperazin-1-yl)propyl)-1H-imidazole-4-carboxamide (279);

N,N-Dibutyl-2-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-1-(2-(4-methylpiperazin-1-yl)ethyl)-1H-imidazole-4-carboxamide (280);

2-(2-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-1-methyl-1H-imidazole-4-carboxamide (281);

2-(2-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-iodonaphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-1-methyl-1H-imidazole-4-carboxamide (282);

N,N-Dibutyl-2-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-methyl-1H-imidazole-4-carboxamide (283);

N,N-Dibutyl-5-(4-(8-iodonaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-methyl-1H-imidazole-4-carboxamide (284);

N,N-Dibutyl-5-(4-(8-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-methyl-1H-imidazole-4-carboxamide (285);

N,N-Dibutyl-6-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)picolinamide (286);

4-(6-(Dibutylamino) pyridin-2-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (287);

4-(3-Bromo-6-(dibutylamino)pyridin-2-yl)-N-(7-chloronaphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (288);

4-(3-Bromo-6-(dibutylamino)pyridin-2-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (289);

4-(3-Bromo-6-(dibutylamino)pyridin-2-yl)-N-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (290);

4-(2-(Dibutylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (291);

N-(8-chloronaphthalen-2-ylsulfonyl)-4-(2-(dibutylamino)pyrimidin-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (292);

4-(2-(dibutylamino)pyrimidin-4-yl)-N-(7-iodonaphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (293);

4-(2-(dibutylamino)pyrimidin-4-yl)-N-(1-ethyl-1H-indol-5-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (294);

4-(2-(dibutylamino)pyrimidin-4-yl)-N-(1-(3,4-dichlorobenzyl)-1H-indol-5-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (295);

4-(2-(dipentylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (296);

N-(naphthalen-2-ylsulfonyl)-4-(2-(3-propylpyrrolidin-1-yl)pyrimidin-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (297);

4-(2-(butyl(3,4-dichlorobenzyl)amino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (298);

4-(2-(dipropylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (299);

4-(2-((cyclopropylmethyl)(propyl)amino) pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (300);

4-(2-(diethylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (301);

N-(naphthalen-2-ylsulfonyl)-4-(2-(3-phenethylpyrrolidin-1-yl)pyrimidin-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (302);

(S)-4-(2-(Dibutylamino)pyrimidin-4-yl)-3-(3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-N-(naphthalen-2-ylsulfonyl)benzamide (303);

(S)-3-(3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(2-(dibutylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)benzamide (304);

4-(2-(dibutylamino)pyrimidin-4-yl)-3-(isoindoline-2-carbonyl)-N-(naphthalen-2-ylsulfonyl)benzamide (305);

4-(2-(dibutylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (306);

4-(2-(dibutylamino)pyrimidin-4-yl)-N3,N3-dimethyl-N1-(naphthalen-2-ylsulfonyl) isophthalamide (307);

(S)—

N-(8-Chloronaphthalen-2-ylsulfonyl)-4-(2-(dibutylamino)pyrimidin-4-yl)-3-(3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (308);

(S)-4-(2-(Dibutylamino)pyrimidin-4-yl)-3-(3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-N-(7-iodonaphthalen-2-ylsulfonyl)benzamide (309);

(S)-4-(2-(Dibutylamino)pyrimidin-4-yl)-N-(1-ethylindolin-5-ylsulfonyl)-3-(3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (310);

4-(5-Chloro-2-(dibutylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (311);

4-(2-(Dibutylamino)-5-methylpyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (312);

4-(5-Chloro-2-(dibutylamino)pyrimidin-4-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (313);

N-(8-Chloronaphthalen-2-ylsulfonyl)-4-(2-(dibutylamino)-5-methylpyrimidin-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (314);

4-(5-Chloro-2-(dibutylamino)pyrimidin-4-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-N-(naphthalen-2-ylsulfonyl)benzamide (315);

4-(5-Bromo-2-(dibutylamino)pyrimidin-4-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-N-(naphthalen-2-ylsulfonyl)benzamide (316);

4-(5-Bromo-2-(dibutylamino)pyrimidin-4-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (317);

4-(5-Chloro-2-(dibutylamino)pyrimidin-4-yl)-N-(7-chloronaphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (318);

Ethyl 4-(4-(7-chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-2-(dibutylamino) pyrimidine-5-carboxylate (319);

4-(4-(7-Chloronaphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-2-(dibutylamino)pyrimidine-5-carboxylic acid (320);

4-(5-Chloro-2-(dibutylamino)pyrimidin-4-yl)-N-(1-(3,4-dichlorobenzyl)indolin-5-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (321);

4-(2-(Butyl(3,4-dichlorobenzyl)amino)-5-chloropyrimidin-4-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (322);

4-(5-Chloro-2-(dipropylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (323);

4-(5-Chloro-2-(dipropylamino)pyrimidin-4-yl)-3-(S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-N-(naphthalen-2-ylsulfonyl)benzamide (324);

4-(5-Bromo-2-(dipropylamino)pyrimidin-4-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-N-(naphthalen-2-ylsulfonyl)benzamide (325);

4-(5-Chloro-2-((cyclopropylmethyl)(propyl)amino)pyrimidin-4-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-N-(naphthalen-2-ylsulfonyl)benzamide (326);

3-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(5-chloro-2-(dipropylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)benzamide (327);

4-(5-Chloro-2-(dipropylamino)pyrimidin-4-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzamide (328);

3-((S)-3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(5-chloro-2-(dipropylamino)pyrimidin-4-yl)-N-(8-chloronaphthalen-2-ylsulfonyl)benzamide (329);

1-(4-(((1-((2-Aminoethyl)thio)isoquinolin-6-yl)sulfonyl)carbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (330); and

2-((6-(N-(4-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl) isoquinolin-1-yl)thio)acetic acid (331).