JP2003509411A - Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production - Google Patents

Abstract

(57) Summary The present invention relates to novel lactams having formula (I), pharmaceutical compositions thereof, and methods of using the same. The novel lactams of the present invention inhibit the processing of amyloid precursor protein. More specifically, it acts to inhibit the production of Aβ peptide, thereby preventing the formation of neurological deposits of amyloid protein. More specifically, the present invention relates to treating neurological disorders associated with production of β-amyloid, such as Alzheimer's disease and Down's syndrome. Embedded image

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention relates to novel lactams having drug properties and bioeffects, pharmaceutical compositions and uses thereof. The novel compounds of the present invention inhibit the processing of amyloid precursor protein. More specifically, the novel compounds of the present invention are Aβ
It acts to inhibit the production of peptides and thereby prevent the formation of neurological deposits of amyloid proteins. More particularly, the present invention relates to the treatment of neurological disorders associated with β-amyloid production, such as Alzheimer's disease and Down's syndrome.

BACKGROUND OF THE INVENTION Alzheimer's disease (AD) is clinically characterized by a progressive loss of memory, temporal and positional orientation, cognition, reasoning, judgment and emotional stability. It is a degenerative brain disorder. AD is a common cause of progressive dementia in humans and one of the leading causes of death in the United States. AD is recognized in all races and ethnic groups around the world and is a major health problem now and in the future. No treatment is currently available to effectively prevent AD or reverse its clinical symptoms and underlying pathophysiology (for a review, see D
ennis J. Selkoe; Cell Biology of Amyloid (β) Protein Precursors and Mechanisms of Alzheimer's Disease, Annu Rev Cell Biol, 1
994, 10: 373-403).

Histopathological examination of brain tissue obtained at necropsy or of brain tissue from a neurosurgical specimen of an affected individual reveals the appearance of amyloid plaques and neurofibrillary tangles in the cerebral cortex of such patients. I was killed. Similar changes occur in trisomy 21 (
(Down syndrome) and in patients with hereditary cerebral hemorrhage with Dutch amyloidosis. Neurofibrillary tangles are abnormal proteinaceous filament bundles that are not membrane bound, and biochemical and immunological studies indicate that their major protein subunits are altered phosphorylated forms of tau protein. The conclusion was reached (Se
(Reviewed by lkoe (1994)).

Biochemical and immunological studies have shown that the characteristic proteinaceous component of amyloid plaques is a protein of about 4.2 kilodaltons (kD) consisting of about 39 to 43 amino acids. It was revealed. This protein, referred to as Aβ, β-amyloid peptide, and sometimes β / A4, is referred to herein as Aβ. In addition to its deposition in amyloid plaques, Aβ
It is also found in the walls of meningeal and parenchymal arterioles, arterioles, capillaries, and sometimes venules. In 1984, Aβ was first purified and a partial amino acid was reported (Glenner and Wong, Biochem. Biop.
hys. Res. Commun. 120: 885-890). Isolation and sequence data for the first 28 amino acids is described in US Pat. No. 4,666,829.

Consistent evidence accumulated over the last decade reveals that Aβ is an integral polypeptide derived from a type 1 integral membrane protein termed β-amyloid precursor protein (APP). It was βAPP is normally produced by many cells both in vivo and in cultured cells of various animal and human origin. Aβ is derived from the cleavage of βAPP by an as yet unknown enzyme (protease) system called secretase.

The existence of at least four proteolytic activities has been claimed. To them
Produces a β-secretase that produces the N-terminus of Aβ, an α-secretase that cleaves near the 16/17 peptide bond in Aβ, and a C-terminal Aβ fragment ending at positions 38, 39, 40, 42 and 43. Alternatively, or later, a gamma-secretase is included that results in a C-terminal extended precursor that is truncated to the above polypeptides.

Several lines of evidence suggest that aberrant accumulation of Aβ plays a major role in the pathology of AD. First, Aβ is the major protein found in amyloid plaques. Second, Aβ is neurotoxic and may be associated with the neuronal death found in AD patients. Third,
A missense DNA mutation at position 717 in the 770 isoform of βAPP is not found in a few families of unaffected individuals with a genetically determined (familial) form of AD, whereas it is found in affected individuals. Can be issued. In addition, some other βAP
P mutations have been shown in familial AD. Fourth, similar neuropathological changes have been observed in transgenic animals overexpressing a mutant form of human βAPP. Fifth, individuals with Down syndrome have increased gene dosage of βA.
Have PP and develop early-onset AD. Taken together, these reports strongly suggest that Aβ accumulation may have a causal relationship with AD.

Inhibiting Aβ production suppresses amyloid plaque formation, reduces neurotoxicity, and generally prevents neurological degeneration by affecting the pathologies associated with Aβ production, And the hypothesis of reducing it is being advocated. Therefore,
One method of treatment is based on drugs that inhibit the formation of Aβ in vivo.

The method of treatment can target the formation of Aβ via enzymes involved in the proteolytic processing of β-amyloid precursor protein. A compound that inhibits the activity of β-secretase or γ-secretase, either directly or indirectly, can suppress the production of Aβ. Conveniently, compounds that specifically target γ-secretase can suppress the production of Aβ. Such inhibition of β-secretase or γ-secretase can thereby reduce the production of Aβ and thereby reduce or prevent neurological disorders associated with Aβ protein.

SUMMARY OF THE INVENTION One object of the present invention is to provide a novel compound useful as an Aβ protein production inhibitor, or a pharmaceutically acceptable salt or prodrug thereof.

It is an object of the invention to provide a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one compound of the invention or a pharmaceutically acceptable salt or prodrug form thereof. Is another purpose of.

A method of treating a degenerative neurological disorder, wherein a host in need of such treatment is treated with a therapeutically effective amount of at least one compound of the invention or a pharmaceutically acceptable salt form thereof. Alternatively, it is another object of the invention to provide a method which comprises administering a prodrug form.

These and other objects will be apparent from the detailed description below, which are compounds of formula (I):

[0014]

[Chemical 17]

[0015] Alternatively, its pharmaceutically acceptable salt form or prodrug form (wherein Q, R ² , R³, R^Five, R^5a, R⁶, B, W, X, Y and Z are defined below)
It was achieved by the present inventors' discovery that it is an effective production inhibitor of.

Detailed Description of the Preferred Embodiments Accordingly, in a first embodiment, the present invention provides a novel compound of formula (I) as defined below:

[0017]

[Chemical 18]

Alternatively, it provides a pharmaceutically acceptable salt form or prodrug thereof, wherein Q is Q ¹ , (C ₁ -C ₃ alkyl) -O-Q ¹ , (C ₁ -C ₃ alkyl) ^{) -S-Q 1, (C} 1 ~C 3 ^{alkyl) -S (= O) -Q 1} , (C 1 ~C 3 _{alkyl) -S (= O) 2 -Q} 1 , or, (C ₁ -C ₃ alkyl) -N (R ²⁰ ) -Q ¹ ;

[0019] Q ¹ is, 0-3 C ₁ -C ₈ alkyl substituted with R ^1a, C ₂ ~C ₈ alkenyl substituted with 0-3 R ^1a, to three zero C ₂ -C ₈ alkynyl which is substituted with R ^1a, C ₃ ~C ₁₀ cycloalkyl substituted with 0-3 R ^1b, C ₃ -C substituted with 0-3 R ^1b ₁₀ carbocyclic ring, containing 0-3 C ₆ -C ₁₀ aryl substituted by R ^1b or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0 to 3 A 5- to 10-membered heterocycle substituted with R ^1b ;

R ^1a is, in each occurrence, H, C ₁ -C ₆ alkyl, OR ¹⁴ , Cl, F
^{, Br, I, NR 15 R} 16, CF 3, 0 to 3 amino C ₃ -C ₁₀ carbocycle substituted with R ^1b, ~C C ₆ is substituted with 0-3 R ^1b ₁₀ Independently selected from aryl and 5 to 10 membered heterocycles containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. Done;

R ^1b represents H, OH, Cl, F, Br, I, CN, N in each occurrence.
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, C ₁ -C ₄ haloalkyl -S-, and (C ₁ -C ₆ alkyl) -O-C (= O) - independently selected from;

R ² is H, methyl, ethyl, propyl or butyl; R ³ is H, C ₁ -C ₆ alkyl, —C (═O) (C ₁ -C ₆ alkyl), —C (
═S) (C ₁ -C ₆ alkyl), or —C (═O) NR ²¹ R ²² ; or R ² and OR ^{3 taken} together form C═O or C═N—OH. Do;

[0023] R ⁵ is, H, OR ^14, 0 to 3 amino C ₁ -C ₆ alkyl substituted with R ^5b, C ₁ ~C ₆ alkoxy substituted with 0-3 R ^5b, C ₂ -C ₆ alkenyl substituted with 0-3 R ^5b, C ₂ ~C ₆ alkynyl substituted with 0-3 R ^5b, is substituted with 0-3 R ^5c C ₃ -C ₁₀ cycloalkyl, 0-3 C ₃ -C ₁₀ carbocycle substituted with R ^5c, 0-3 C ₆ -C ₁₀ aryl substituted by R ^5c or nitrogen, 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from oxygen and sulfur and substituted with 0 to 3 R ^5c ;

R ^5a is H, C ₁ -C ₄ alkyl, or C ₂ -C ₄ alkenyl; or, R ⁵ and R ^{5a taken} together are substituted with 0 to 3 R ^5c. 3
Membered to 7-membered cycloalkyl ring can be formed, and if desired, the cycloalkyl ring formed by combining R ⁵ and R ^5a can be benzofused, and the benzofused ring can be It ^may be substituted with 0 to 3 R ^5c ; R ^5b is in each occurrence H, C ₁ -C ₆ alkyl, CF ₃ , OR ¹⁴ ,
Cl, F, Br, I, ═O, CN, NO ₂ , NR ¹⁵ R ¹⁶ , acetyl, SCH ₃ , S
_{(= O) CH 3, S} (= O) 2 CH 3, C 2 ~C 6 alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ halo Alkoxy, C ₁
-C ₄ haloalkyl -S-, 0-3 C ₃ -C ₁₀ cycloalkyl substituted with R ^5c, C ₃ ~C ₁₀ carbocycle substituted with 0-3 R ^5c, 0 To C ₆ -C ₁₀ aryl substituted with 3 to 5 R ^5c , and 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^5c Independently selected from a 5- to 10-membered heterocycle represented by: R ^5c in each ^occurrence H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, and C ₁ -C ₄ are independently selected from haloalkyl -S-;

R ⁶ is H or C ₁ -C ₆ alkyl; W is — (CR ⁸ R ^8a ) _p −; p is 0, 1, 2, 3 or 4;

R ⁸ and R ^8a , in each ^occurrence , are independent of H, F, C ₁ -C ₄ alkyl, C ₂ -C ₄ alkenyl, C ₂ -C ₄ alkynyl, and C ₃ -C ₈ cycloalkyl. It is selected; X is a bond, 0-3 C ₆ -C ₁₀ aryl which is substituted with R ^Xb, C ₃ ~C ₁₀ cycloalkyl substituted with 0-3 R ^Xb, 0 C ₃ -C ₁₀ carbocycle substituted with 1 to 3 R ^Xb , or 5 to 10 membered heterocycle substituted with 0 to 2 R ^Xb ; R ^Xb is the respective occurrences. At, H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, and C ₁ -C ₄ are independently selected from haloalkyl -S-; Y is a bond or _{^{- (CR 9 R 9a) t}} -V- (CR 9 R 9a) u - a and; t Is 0, 1, 2 or 3; u is 0, 1, 2 or 3;

R ⁹ and R ^9a in each ^occurrence are independently selected from H, F, C ₁ -C ₆ alkyl, or C ₃ -C ₈ cycloalkyl; V is a bond, —C (= O)-, -O-, -S-, -S (= O)-, -S (= O
_{) 2 -, - N (R} 19) -, - C (= O) NR 19b -, - NR 19b C (= O) -, -
NR ^19b S (= O) _2- , -S (= O) ₂ NR ^19b- , -C (= O) O-, or-
OC (= O) - and is; Z is, H, 0-2 C ₁ -C ₈ alkyl substituted with R ^12, C ₂ -C ₄ substituted with 0-2 R ¹² alkenyl, substituted with 0-2 C ₂ -C ₄ alkynyl substituted with R ^12, C ₆ ~C ₁₀ aryl substituted with 0-4 R ^12b, 0-4 R ^12b C ₃ -C ₁₀ carbocycle is or nitrogen, containing 1 to 4 heteroatoms selected from oxygen and sulfur, and 5-membered to 10-membered substituted with 0-3 R ^12b, Ring B is saturated, partially saturated, or unsaturated, and each additional lactam carbon is substituted with 0-2 R ¹¹ and is optionally In that case, -N =, -NH-, -N (R < ¹⁰ >)-, -O-, -S-, -S (
6 members containing a heteroatom selected from ═O)-and —S (═O) ₂ —, 7
Member or an 8-membered lactam; and further, two R ¹¹ substituents present on adjacent atoms are taken together to form a C ₃ -C ₆ carbocyclic condensed group, a benzo-condensed group, or a 5-membered to 6-membered A heteroaryl fused group may be formed, in which case the 5- to 6-membered heteroaryl fused group comprises 1 to 2 heteroatoms selected from N, O and S, and a benzofused group. Or a 5-6 membered heteroaryl fused group is substituted with 0-3 R ¹³ .

R ¹⁰ is H, C (═O) R ¹⁷ , C (═O) OR ¹⁷ , C (═O) NR ¹⁸ R ¹⁹ , S
(= O) ₂ NR ¹⁸ R ¹⁹ , S (= O) ₂ CR ¹⁷ , C ₁ -C ₆ alkyl substituted with 0 to 2 R ^10a , substituted with 0 to 4 R ^10b C ₆ -C ₁₀ aryl, contain 0-3 C ₃ -C ₁₀ carbocycle substituted with R ^10b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and A 5- to 10-membered heterocycle optionally substituted with 0 to 3 R ^10b ;

R ^10a is, in each occurrence, H, C ₁ -C ₆ alkyl, OR ¹⁴ , Cl,
F, Br, I, = O , CN, NO 2, NR 15 R 16, CF 3, 0 to four aryl substituted with R ^10b, C ₃ substituted with 0-3 R ^10b To C ₁₀ carbocycle or 5 to 10 members containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and optionally substituted with 0 to 3 R ^10b. Independently selected from the heterocycles of

R ^10b is, in each ^occurrence , H, OH, C ₁ -C ₆ alkyl, C ₁ -C ₄
Alkoxy, Cl, F, Br, I , CN, NO 2, NR 15 R 16, CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2 CH 3, C 1 ~C 6 Independently selected from alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ haloalkoxy, and C ₁ -C ₄ haloalkyl-S-;

[0031]   R¹¹Is H, C in each occurrence₁~ C_FourAlkoxy, Cl, F, Br
, I, = O, CN, NO₂, NR¹⁸R¹⁹, C (= O) R¹⁷, C (= O) OR¹⁷,
C (= O) NR¹⁸R¹⁹, S (= O)₂NR¹⁸R¹⁹, CF₃, 0 to 1 R^11aC replaced by₁~ C₆Alkyl, 0 to 3 R^11bC replaced by₆~ C_TenAryl, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl,
F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, CF₃, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;

[0032]   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;

R ¹³ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, C ₁ -C ₄ alkoxy, Cl, F, Br, I, CN, NO ₂ , NR ¹⁵ R ¹⁶ , and CF. Independently selected from ₃ ;

R ¹⁴ is independently selected from H, phenyl, benzyl, C ₁ -C ₆ alkyl, and C ₂ -C ₆ alkoxyalkyl in each ^occurrence ; R ^14a is H, phenyl, benzyl or C ₁ -C ₆ alkyl;

R ¹⁵ is, in each occurrence, H, C ₁ -C ₆ alkyl, phenyl, benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (═O) —, (C ₁ -C ₆ alkyl). )
-O-C (= O) - , and (C ₁ -C ₆ alkyl) -S (= O) ₂ - independently selected from;

R ¹⁶ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, phenyl,
Benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (= O) -, (C 1 ~C 6 alkyl) -O-C (= O) -, and (C ₁ -C ₆ alkyl) -S ( ═O) ₂ — independently; —NR ¹⁵ R ¹⁶ is a heterocyclic ring selected from the group of piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinyl. May;

R ¹⁷ is H, C ₁ -C ₆ alkyl, or C ₂ -C ₆ alkoxyalkyl, aryl substituted with ^0-4 R ^17a , or aryl-CH ₂ — (wherein Aryl is substituted with ^0-4 R ^17a ); R ^17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, —OH, F, Cl, Br, I. , CF ₃ , OCF ₃ , SCH _{3
, S (= O) CH 3} , S (= O) 2 CH 3, -NH 2, -N (CH 3) 2 or C _1,
~ C ₄ haloalkyl;

R ¹⁸ is, in each occurrence, H, C ₁ -C ₆ alkyl, phenyl, benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (═O) —, and (C ₁ -C _6). alkyl) -S (= O) ₂ - independently selected from; or, -NR ¹⁷ R ¹⁸ is selected piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, from the group of piperazinyl and N- methylpiperidinyl May be a heterocyclic ring;

R ¹⁹ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, phenyl,
Benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (= O) -, and (C ₁ ~
C ₆ alkyl) -S (= O) ₂ - independently selected from; R ^19b, at each occurrence, is independently selected from H and C ₁ -C ₆ alkyl;

R ²⁰ is H, OH, C ₁ -C ₄ alkyl, phenyl, benzyl or phenethyl;

R ²¹ is independently selected in each occurrence from H, C ₁ -C ₆ alkyl, phenyl, benzyl and phenethyl; and

R ²² in each occurrence is independently selected from H, C ₁ -C ₆ alkyl, phenyl, benzyl and phenethyl.

[2] In a preferred embodiment, the present invention provides a compound of formula (I) as defined below.
Provides compound: Q is selected from the group _{^{consisting, Q 1, (C 1 ~C}} 3 ^{alkyl) -O-Q 1, (C} 1 ~C 3 ^{alkyl) -S-Q 1, (C} 1 ~C 3 alkyl) -S (= O) -Q ^1, be a (C ₁ -C _{3 alkyl) -S (= O) 2 -Q} 1 , or, (C ₁ ~C ₃ ^{alkyl) -N (R 20) -Q 1} ;

[0044] Q ¹ is, 0-3 C ₁ -C ₆ alkyl substituted with R ^1a, C ₂ ~C ₆ alkenyl substituted with 0-3 R ^1a, to three zero C ₂ -C ₆ alkynyl which is substituted with R ^1a, C ₃ ~C ₁₀ cycloalkyl substituted with 0-3 R ^1b, C ₃ -C substituted with 0-3 R ^1b ₁₀ carbocyclic ring, containing 0-3 C ₆ -C ₁₀ aryl substituted by R ^1b or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0 to 3 A 5- to 10-membered heterocycle substituted with R ^1b ;

R ^1a is, in each occurrence, H, C ₁ -C ₆ alkyl, OR ¹⁴ , Cl, F
^{, Br, I, NR 15 R} 16, CF 3, 0 to 3 amino C ₃ -C ₁₀ carbocycle substituted with R ^1b, ~C C ₆ is substituted with 0-3 R ^1b ₁₀ Independently selected from aryl and 5 to 10 membered heterocycles containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. R ^1b is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, C ₁ -C ₄ haloalkyl -S-, and (C ₁ -C ₆ alkyl) -O-C (= O) - independently selected from;

R ² is H, methyl, ethyl, propyl or butyl;

R ³ is H, C ₁ -C ₄ alkyl, —C (═O) (C ₁ -C ₄ alkyl), —C (
═S) (C ₁ -C ₄ alkyl), or —C (═O) NR ²¹ R ²² ;

[0048] R ⁵ is, H, OR ^14, 0 to 3 amino C ₁ -C ₆ alkyl substituted with R ^5b, C ₁ ~C ₆ alkoxy substituted with 0-3 R ^5b, C ₂ -C ₆ alkenyl substituted with 0-3 R ^5b, C ₂ ~C ₆ alkynyl substituted with 0-3 R ^5b, is substituted with 0-3 R ^5c C ₃ -C ₁₀ cycloalkyl, 0-3 C ₃ -C ₁₀ carbocycle substituted with R ^5c, 0-3 C ₆ -C ₁₀ aryl substituted by R ^5c or nitrogen, 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from oxygen and sulfur and substituted with 0 to 3 R ^5c ; R ^5a is H, C ₁ -C ₄ alkyl, or a C ₂ -C ₄ alkenyl; or, R ⁵ and R ^5a together, 3 to be substituted with 0-3 R ^5c
A 5 to 7-membered cycloalkyl ring can be formed; R ^5b in each occurrence is H, C ₁ -C ₆ alkyl, CF ₃ , OR ¹⁴ ,
Cl, F, Br, I, ═O, CN, NO ₂ , NR ¹⁵ R ¹⁶ , acetyl, SCH ₃ , S
_{(= O) CH 3, S} (= O) 2 CH 3, C 2 ~C 6 alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ halo Alkoxy, C ₁
-C ₄ haloalkyl -S-, 0-3 C ₃ -C ₁₀ cycloalkyl substituted with R ^5c, C ₃ ~C ₁₀ carbocycle substituted with 0-3 R ^5c, 0 To C ₆ -C ₁₀ aryl substituted with 3 to 5 R ^5c , and 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^5c Independently selected from a 5- to 10-membered heterocycle represented by: R ^5c in each ^occurrence H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, and C ₁ -C ₄ are independently selected from haloalkyl -S-;

R ⁶ is H, methyl or ethyl; W is — (CR ⁸ R ^8a ) _p −; p is 0, 1 or 2;

R ⁸ and R ^8a in each occurrence are independently selected from H, F, methyl and ethyl; X is a bond, phenyl substituted with 0 to 3 R ^Xb , 0 C ₃ -C ₆ cycloalkyl substituted with 3 to 3 R ^Xb , or a 5 to 6 membered heterocycle substituted with 0 to 2 R ^Xb ; R ^Xb is in each occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, and C ₁ -C ₄ are independently selected from haloalkyl -S-; Y is a bond or _{^{- (CR 9 R 9a) t}} -V- (CR 9 R 9a) u - a and; t Is 0, 1 or 2; u is 0, 1 or 2;

R ⁹ and R ^9a in each ^occurrence are independently selected from H, F, methyl and ethyl; V is a bond, —C (═O) —, —O—, —S—, -S (= O)-, -S (= O
) _2- , -N (R < ¹⁹ >)-, -C (= O) NH-, -NHC (= O)-, -NHS.
(═O) ₂ — or —S (═O) ₂ NH—; Z is H, halo, C ₁ -C ₄ alkyl substituted with 0 to 2 R ¹² , 0 to 2 C ₂ -C ₄ alkenyl substituted with pieces of R ^12, 0 to 2 amino C ₂ -C ₄ alkynyl substituted with R ^12, C ₆ ~C substituted with 0-4 R ^12b ₁₀ aryl, contain 0-4 C ₃ -C ₆ carbocycle substituted with R ^12b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0 to 3 5 to 6 membered heterocyclic ring substituted with R ^12b ; Ring B is saturated, partially saturated or unsaturated, and each additional lactam carbon is 0. 1 to 2 R < ¹¹ >, and if desired, -N =, -NH-, -N (R < ¹⁰ >)-, -O-, -S-, -S (
= O) - and -S (= O) ₂ - Yes 7-membered lactam having a hetero atom selected from; In addition, two R ¹¹ substituents present adjacent atoms, taken together, C ₃ To C ₆ carbocyclic fused group, benzo fused group, or 5-membered to 6-membered heteroaryl fused group, wherein 5-membered to 6-membered heteroaryl fused group can be It contains one to two heteroatoms selected from, and benzo fused group or a 5- to 6-membered heteroaryl fused groups is substituted with 0-3 R ^13;

R ¹⁰ is H, C (═O) R ¹⁷ , C (═O) OR ¹⁷ , C (═O) NR ¹⁸ R ¹⁹ , S
(= O) ₂ NR ¹⁸ R ¹⁹ , S (= O) ₂ R ¹⁷ , C ₁ -C ₆ alkyl substituted with 0 to 2 R ^10a , substituted with 0 to 4 R ^10b C ₆ -C ₁₀ aryl, contain 0-3 C ₃ -C ₁₀ carbocycle substituted with R ^10b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and A 5- to 10-membered heterocycle optionally substituted with 0 to 3 R ^10b ; R ^10a in each occurrence is H, C ₁ -C ₆ alkyl, OR ¹⁴ , Cl,
F, Br, I, = O , CN, NO 2, NR 15 R 16, CF 3, or 0-4 aryl substituted with R ^10b, are independently selected from; R ^10b are each In the presence of H, OH, C ₁ -C ₆ alkyl, C ₁ -C ₄
Alkoxy, Cl, F, Br, I , CN, NO 2, NR 15 R 16, CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2 CH 3, C 1 ~C 6 Independently selected from alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ haloalkoxy, and C ₁ -C ₄ haloalkyl-S-;

[0053]   R¹¹Is H, C in each occurrence₁~ C_FourAlkoxy, Cl, F, Br
, I, = O, CN, NO₂, NR¹⁸R¹⁹, C (= O) R¹⁷, C (= O) OR¹⁷,
C (= O) OR¹⁸R¹⁹, S (= O)₂NR¹⁸R¹⁹, CF₃, 0 to 1 R^11aC replaced by₁~ C₆Alkyl, 0 to 3 R^11bC replaced by₆~ C_TenAryl, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl,
F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, CF₃, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;

[0054]   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;

R ¹³ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, C ₁ -C ₄ alkoxy, Cl, F, Br, I, CN, NO ₂ , NR ¹⁵ R ¹⁶ , and CF. Independently selected from ₃ ;

R ¹⁴ in each occurrence is independently selected from H, phenyl, benzyl, C ₁ -C ₆ alkyl, and C ₂ -C ₆ alkoxyalkyl;

R ¹⁵ is, in each occurrence, H, C ₁ -C ₆ alkyl, phenyl, benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (═O) —, (C ₁ -C ₆ alkyl). )
-O-C (= O) - , and (C ₁ -C ₆ alkyl) -S (= O) ₂ - independently selected from;

R ¹⁶ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, phenyl,
Benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (= O) -, (C 1 ~C 6 alkyl) -O-C (= O) -, and (C ₁ -C ₆ alkyl) -S ( ═O) ₂ — independently; —NR ¹⁵ R ¹⁶ is a heterocyclic ring selected from the group of piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinyl. May;

R ¹⁷ is H, aryl, aryl-CH ₂ —, C ₁ -C ₆ alkyl, or C ₂ —
C ₆ alkoxyalkyl;

R ¹⁸ is, in each occurrence, H, C ₁ -C ₆ alkyl, phenyl, benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (═O) —, and (C ₁ -C _6). Independently selected from alkyl) -S (= O) _2- ;

R ¹⁹ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, phenyl,
Benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (= O) -, and (C ₁ ~
C ₆ alkyl) -S (= O) ₂ - independently from selected; or, -NR ¹⁷ R ¹⁸ is selected piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, from the group of piperazinyl and N- methylpiperidinyl May be a heterocyclic ring represented by

R ²⁰ is H, OH, C ₁ -C ₄ alkyl, phenyl, benzyl or phenethyl;

R ²¹ is, in each occurrence, independently selected from H, C ₁ -C ₆ alkyl, phenyl, benzyl and phenethyl;

R ²² in each occurrence is independently selected from H, C ₁ -C ₆ alkyl, phenyl, benzyl and phenethyl.

[0065]   [2] In a preferred embodiment, the invention provides that ring B is selected from:

[0066]

[Chemical 19]

And a compound of formula (I) in which each benzofused group is substituted with 0 to 3 R ¹³ .

[4] In a preferred embodiment, the present invention provides the compound of formula (I
Compound of a):

[0069]

[Chemical 20]

Alternatively, a pharmaceutically acceptable salt form or prodrug thereof is provided, wherein Q is Q ¹ , (C ₁ -C ₃ alkyl) -O—Q ¹ , (C ₁ -C ₃ alkyl) ^{) -S-Q 1, (C} 1 ~C 3 ^{alkyl) -S (= O) -Q 1} , (C 1 ~C 3 _{alkyl) -S (= O) 2 -Q} 1 , or, (C ₁ -C ₃ alkyl) -N (R ²⁰ ) -Q ¹ ;

[0071] Q ¹ is, 0-3 C ₁ -C ₆ alkyl substituted with R ^1a, C ₂ ~C ₆ alkenyl substituted with 0-3 R ^1a, to three zero C ₂ -C ₆ alkynyl which is substituted with R ^1a, C ₃ ~C ₁₀ cycloalkyl substituted with 0-3 R ^1b, C ₃ -C substituted with 0-3 R ^1b ₁₀ carbocyclic ring, containing 0-3 C ₆ -C ₁₀ aryl substituted by R ^1b or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0 to 3 A 5- to 10-membered heterocycle substituted with R ^1b ;

R ^1a is, in each occurrence, H, C ₁ -C ₆ alkyl, OR ¹⁴ , Cl, F
^{, Br, I, NR 15 R} 16, CF 3, 0 to 3 amino C ₃ -C ₁₀ carbocycle substituted with R ^1b, ~C C ₆ is substituted with 0-3 R ^1b ₁₀ Independently selected from aryl and 5 to 10 membered heterocycles containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. R ^1b is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, C ₁ -C ₄ haloalkyl -S-, and (C ₁ -C ₆ alkyl) -O-C (= O) - independently selected from;

R ² is H, methyl or ethyl;

[0074] R ⁵ is, H, OR ^14, 0 to 3 amino C ₁ -C ₆ alkyl substituted with R ^5b, C ₁ ~C ₆ alkoxy substituted with 0-3 R ^5b, C ₂ -C ₆ alkenyl substituted with 0-3 R ^5b, C ₂ ~C ₆ alkynyl substituted with 0-3 R ^5b, is substituted with 0-3 R ^5c C ₃ -C ₁₀ cycloalkyl, 0-3 C ₃ -C ₁₀ carbocycle substituted with R ^5c, 0-3 C ₆ -C ₁₀ aryl substituted by R ^5c or nitrogen, 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from oxygen and sulfur and substituted with 0 to 3 R ^5c ; R ^5a is H, C ₁ -C ₄ alkyl, or a C ₂ -C ₄ alkenyl; or, R ⁵ and R ^5a together, 3 to be substituted with 0-3 R ^5c
A 5 to 7-membered cycloalkyl ring can be formed; R ^5b in each occurrence is H, C ₁ -C ₆ alkyl, CF ₃ , OR ¹⁴ ,
Cl, F, Br, I, ═O, CN, NO ₂ , NR ¹⁵ R ¹⁶ , acetyl, SCH ₃ , S
_{(= O) CH 3, S} (= O) 2 CH 3, C 2 ~C 6 alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ halo alkoxy, and C ₁ -C ₄ haloalkyl -S-, 0-3 C ₃ -C ₁₀ cycloalkyl substituted with R ^5c, C ₃ -C ₁₀ substituted with 0-3 R ^5c Carbocycle, 0 to 3 C ₆ -C ₁₀ aryl substituted with R ^5c , and 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 to 3 is a independently selected from heterocyclic 5-membered to 10-membered substituted with R ^5c; R ^5c, at each occurrence, H, OH, Cl, F , Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, and C ₁ -C ₄ are independently selected from haloalkyl -S-; W is _{^{- (CR 8 R 8a) p}} - a and; p is 0, 1 or 2;

R ⁸ and R ^8a in each occurrence are independently selected from H, F, methyl and ethyl; X is a bond, phenyl substituted with 0 to 3 R ^Xb , 0 C ₃ -C ₆ cycloalkyl substituted with 3 to 3 R ^xb , or 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 to 2 R ^xb A substituted 5- to 6-membered heterocycle; R ^Xb , in each ^occurrence, is H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, and C ₁ -C ₄ are independently selected from haloalkyl -S-; Y is a bond or _{^{- (CR 9 R 9a) t}} -V- (CR 9 R 9a) u - a and; t Is 0, 1 or 2; u is 0, 1 or 2;

R ⁹ and R ^9a in each ^occurrence are independently selected from H, F, methyl and ethyl; V is a bond, —C (═O) —, —O—, —S—, -S (= O)-, -S (= O
) _2- , -N (R ¹⁹ )-, -C (= O) NH-, or -NHC (= O)-; Z is H, halo, substituted with 0 to 2 R ^12. that C ₁ -C ₄ alkyl, 0-2 C ₂ -C ₄ alkenyl substituted with R ^12, C ₂ ~C ₄ alkynyl substituted with 0-2 R ^12, 0 to 4 C ₆ -C ₁₀ aryl which is substituted by number of R ^12b, C ₃ ~C ₆ carbocycle is substituted with 0-4 R ^12b, or nitrogen, 1 to 4 substituents selected from oxygen and sulfur, A 5-membered to 6-membered heterocycle containing a heteroatom of and substituted with 0 to 3 R ^12b ;

[0077]

[Chemical 21]

[0078] Selected from;   R¹¹Is H, C in each occurrence₁~ C_FourAlkoxy, Cl, F, Br
, I, = O, CN, NO₂, NR¹⁸R¹⁹, C (= O) R¹⁷, C (= O) OR¹⁷,
C (= O) NR¹⁸R¹⁹, S (= O)₂NR¹⁸R¹⁹, CF₃, 0 to 1 R^11aC replaced by₁~ C₆Alkyl, 0 to 3 R^11bC replaced by₆~ C_TenAryl, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl,
F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, CF₃, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;

[0079]   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;

R ¹³ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, C ₁ -C ₄ alkoxy, Cl, F, Br, I, CN, NO ₂ , NR ¹⁵ R ¹⁶ , and CF. Independently selected from ₃ ;

R ¹⁴ in each occurrence is independently selected from H, phenyl, benzyl, C ₁ -C ₆ alkyl, and C ₂ -C ₆ alkoxyalkyl;

R ¹⁵ is, in each occurrence, H, C ₁ -C ₆ alkyl, phenyl, benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (═O) —, (C ₁ -C ₆ alkyl). )
-O-C (= O) - , and (C ₁ -C ₆ alkyl) -S (= O) ₂ - independently selected from;

R ¹⁶ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, phenyl,
Benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (= O) -, (C 1 ~C 6 alkyl) -O-C (= O) -, and (C ₁ -C ₆ alkyl) -S ( ═O) ₂ — independently; —NR ¹⁵ R ¹⁶ is a heterocyclic ring selected from the group of piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinyl. May;

R ¹⁷ is H, aryl, aryl-CH ₂ —, C ₁ -C ₆ alkyl, or C ₂ —
C ₆ alkoxyalkyl;

R ¹⁸ is, in each occurrence, H, C ₁ -C ₆ alkyl, phenyl, benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (═O) —, and (C ₁ -C _6). Independently selected from alkyl) -S (= O) _2- ;

R ¹⁹ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, phenyl,
Benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (= O) -, and (C ₁ ~
C ₆ alkyl) -S (= O) ₂ - independently selected from; or, -NR ¹⁸ R ¹⁹ is selected piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, from the group of piperazinyl and N- methylpiperidinyl May be a heterocyclic ring

R ²⁰ is H, OH, C ₁ -C ₄ alkyl, phenyl, benzyl or phenethyl.

[5] In a preferred embodiment, the present invention provides the compound of formula (I
Compound of a):

[0089]

[Chemical formula 22]

[0090] Provide In the formula,   Ring B is

[0091]

[Chemical formula 23]

Q is Q ¹ or (C ₁ -C ₃ alkyl) -O-Q ¹ ; Q ¹ is C ₁ -C ₆ substituted with 0-3 R ^1a alkyl, substituted with 0-3 C ₂ -C ₆ alkenyl substituted with R ^1a, C ₂ ~C ₆ alkynyl substituted with 0-3 R ^1a, 0-3 R ^1b C ₃ -C ₁₀ cycloalkyl which is, 0-3 C ₃ -C ₁₀ carbocycle substituted with R ^1b, 0-3 C ₆ -C ₁₀ aryl substituted by R ^1b or, 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b ;

R ^1a is, in each occurrence, H, C ₁ -C ₆ alkyl, OR ¹⁴ , Cl, F
^{, Br, I, NR 15 R} 16, CF 3, 0 to 3 amino C ₃ -C ₁₀ carbocycle substituted with R ^1b, ~C C ₆ is substituted with 0-3 R ^1b ₁₀ Aryl, and independently from a 5- to 10-membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. R ^1b is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, C ₁ -C ₄ haloalkyl -S-, and (C ₁ -C ₆ alkyl) -O-C (= O) - independently selected from;

R ² is H, methyl or ethyl;

[0095] R ⁵ is, H, OR ^14, 0 to 3 amino C ₁ -C ₆ alkyl substituted with R ^5b, C ₂ ~C ₆ alkenyl substituted with 0-3 R ^5b, 0-3 C ₂ -C ₆ alkynyl substituted with R ^5b, C ₃ ~C ₆ cycloalkyl substituted with 0-3 R ^5c, is substituted with 0-3 R ^5c A C ₃ -C ₆ carbocycle, 0 to 3 phenyl substituted with R ^5c , or 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 to 3 Is a 5-7 membered heterocycle substituted with R ^5c ; R ^5a is H, C ₁ -C ₄ alkyl, or C ₂ -C ₄ alkenyl; or, R ⁵ and R ^5a are together, C ₄ -C ₇ can form a cycloalkyl ring; R ^5b, at each occurrence, H, C ₁ -C ₆ alkyl, CF ₃ OR ^14,
Cl, F, Br, I, ═O, CN, NO ₂ , NR ¹⁵ R ¹⁶ , acetyl, SCH ₃ , S
_{(= O) CH 3, S} (= O) 2 CH 3, C 2 ~C 6 alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ halo Alkoxy, C ₁
-C ₄ haloalkyl -S-, 0-3 C ₃ -C ₁₀ cycloalkyl substituted with R ^5c, C ₃ ~C ₁₀ carbocycle substituted with 0-3 R ^5c, 0 To C ₆ -C ₁₀ aryl substituted with 3 to 5 R ^5c , and 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^5c Independently selected from a 5- to 10-membered heterocycle represented by: R ^5c in each ^occurrence H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, and C ₁ -C ₄ are independently selected from haloalkyl -S-; W is _{^{- (CR 8 R 8a) p}} - a and; p is 0, 1 or 2;

R ⁸ and R ^8a in each occurrence are independently selected from H, methyl and ethyl; X is a bond, phenyl substituted with 0 to 3 R ^Xb , 0 to 3 C ₃ -C ₆ cycloalkyl substituted with 1 R ^Xb , or containing 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 2 R ^Xb R ^xb is H, OH, Cl, F, Br, I, CN, N in each occurrence.
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, and C ₁ -C ₄ are independently selected from haloalkyl -S-; Y is a bond or _{^{- (CR 9 R 9a) t}} -V- (CR 9 R 9a) u - a and; t Is 0, 1 or 2; u is 0, 1 or 2;

R ⁹ and R ^9a in each ^occurrence are independently selected from H, F, methyl and ethyl; V is a bond, —C (═O) —, —O—, —S—, -S (= O)-, -S (= O
) _2- , -N (R < ¹⁹ >)-, -NHC (= O)-, or -C (= O) NH-; Z is H, F, Cl, Br, 0 to 2 R C ₁ -C ₄ alkyl substituted with ^12, 0-2 C ₂ -C ₄ alkenyl substituted with R ^12, C ₂ -C ₄ alkynyl substituted with 0-2 R ^12, 0-4 C ₆ -C ₁₀ aryl which is substituted with R ^12b, C ₃ ~C ₁₀ carbocycle substituted with 0-4 R ^12b, or nitrogen, 1 selected from oxygen and sulfur, A 5- to 6-membered heterocycle containing 1 to 4 heteroatoms and substituted with 0 to 3 R ^12b ;

[0098]   R¹¹Is, in each occurrence, H, ═O, NR¹⁸R¹⁹, C (= O) R¹⁷,
C (= O) OR¹⁷, C (= O) NR¹⁸R¹⁹, S (= O)₂NR¹⁸R¹⁹, CF₃, 0 to 1 R^11aC replaced by₁~ C₆Alkyl, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 7-membered heterocycle substituted with Independently selected from;   R^11aIs H, C in each occurrence₁~ C_FourAlkyl, OR¹⁴, Cl,
F, Br, = O, CN, NO₂, NR¹⁵R¹⁶, CF₃, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 7-membered heterocycle substituted with Independently selected from;   R^11bIs H, OH, Cl, F, Br, CN, NO in each presence.₂ , NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂CH ₃ , C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~ C_Four
Haloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-;

[0099]   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;

R ¹³ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, C ₁ -C ₄ alkoxy, Cl, F, Br, I, CN, NO ₂ , NR ¹⁵ R ¹⁶ , and CF. Independently selected from ₃ ;

R ¹⁴ in each occurrence is independently selected from H, phenyl, benzyl, C ₁ -C ₆ alkyl, and C ₂ -C ₆ alkoxyalkyl;

R ¹⁵ is, in each occurrence, H, C ₁ -C ₆ alkyl, phenyl, benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (═O) —, (C ₁ -C ₆ alkyl). )
-O-C (= O) - , and (C ₁ -C ₆ alkyl) -S (= O) ₂ - independently selected from;

R ¹⁶ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, phenyl,
Benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (= O) -, (C 1 ~C 6 alkyl) -O-C (= O) -, and (C ₁ -C ₆ alkyl) -S ( ═O) ₂ — independently; —NR ¹⁵ R ¹⁶ is a heterocyclic ring selected from the group of piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinyl. And R ¹⁷ is H, aryl, aryl-CH ₂ —, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkoxyalkyl;

R ¹⁸ is, in each occurrence, H, C ₁ -C ₆ alkyl, phenyl, benzyl, phenethyl, (C ₁ -C ₆ alkyl) -C (═O) —, and (C ₁ -C _6). alkyl) -S (= O) ₂ - independently selected from; or, -NR ¹⁸ R ¹⁹ is selected piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, from the group of piperazinyl and N- methylpiperidinyl May be a heterocyclic ring; and

R ¹⁹ in each occurrence is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and phenethyl.

[5] In a preferred embodiment, the present invention provides the formula (I) as defined below.
provides a compound of a): wherein, Q is located at Q ^1; Q ¹ is C ₁ -C ₆ alkyl substituted with 0-3 R ^1a, 0-3 R ^1a in C ₂ -C ₆ alkenyl substituted, 0-3 C ₂ -C ₆ alkynyl substituted with R ^1a, C ₃ ~C ₁₀ cycloalkyl substituted with 0-3 R ^1b, 0-3 C ₃ -C ₁₀ carbocycle substituted with R ^1b, is selected from 0-3 C ₆ -C ₁₀ aryl substituted by R ^1b or nitrogen, oxygen and sulfur 1 A 5- to 10-membered heterocycle containing 1 to 4 heteroatoms and substituted with 0 to 3 R ^1b ;

R ^1a is, in each occurrence, H, C ₁ -C ₆ alkyl, OR ¹⁴ , Cl, F
^{, Br, I, NR 15 R} 16, CF 3, 0 to 3 amino C ₃ -C ₁₀ carbocycle substituted with R ^1b, ~C C ₆ is substituted with 0-3 R ^1b ₁₀ Independently selected from aryl and 5 to 10 membered heterocycles containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. R ^1b is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, C ₁ -C ₄ haloalkyl -S-, and (C ₁ -C ₆ alkyl) -O-C (= O) - independently selected from;

R ² is H, methyl or ethyl;

[0109] R ⁵ is, H, OR ^14, 0 to 3 amino C ₁ -C ₆ alkyl substituted with R ^5b, C ₂ ~C ₆ alkenyl substituted with 0-3 R ^5b, or be a 0-3 C ₂ -C ₆ alkynyl substituted with R ^5b: R ^5a is, H, there methyl, ethyl, propyl, butyl or C ₂ -C ₄ alkenyl; or, R ⁵ And R ^5a can be taken together to form a C ₄ -C ₇ cycloalkyl ring; R ^5b in each occurrence is H, methyl, ethyl, propyl, butyl,
^{_{CF 3, OR 14, Cl,}} F, Br, I, = O, C 3 ~C 7 cycloalkyl substituted with NR ¹⁵ R ^16, 0 to 3 amino R ^5c, 0 to 3 amino R ^5c A C ₃ -C ₇ carbocycle substituted with phenyl, 0 to 3 phenyl substituted with R ^5c , and 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 are independently selected from 5- to 7-membered heterocyclic ring is substituted with number to three R ^5c; R ^5c, at each occurrence, H, OH, Cl, F , Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ -C ₄ alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₂ haloalkyl, and C ₁ independently of -C ₂ haloalkoxy selected; W is - (CHR ⁸⁾ _p - a is P is 0 or 1;

[0110] R ⁸ is H, methyl or ethyl; X is a bond, phenyl substituted with 0-2 R ^Xb, C ₅ -C substituted with 0-3 R ^Xb _6- cycloalkyl or a 5-6 membered heterocycle containing 1-3 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0-2 R ^Xb ; R ^Xb is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, and C ₁ -C ₄ are independently selected from haloalkyl -S-; Y is a _{bond, -V -, - CH 2 -V} -, - V-CH 2 -, or -CH ₂ - V-
CH _2- ; V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O.
) _2- , or -N (R ¹⁹ )-; Z is H, F, Cl, Br, C ₁ -C ₄ alkyl substituted with 0 to 2 R ¹² , 0 to 2 C ₂ is substituted with R ¹² in -C ₄ alkenyl, 0-2 C ₂ -C ₄ alkynyl substituted with R ^12, C ₆ -C ₁₀ substituted with 0-4 R ^12b aryl, contain 0-4 C ₃ -C ₆ carbocycle substituted with R ^12b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 A 5- to 6-membered heterocycle substituted with R ^12b of

R ¹¹ is, in each occurrence, H, ═O, NR ¹⁸ R ¹⁹ , C (═O) R ¹⁷ ,
C (= O) OR ¹⁷ , C (= O) NR ¹⁸ R ¹⁹ , S (= O) ₂ NR ¹⁸ R ¹⁹ , CF ₃ , C ₁ -C ₆ alkyl substituted with 0 to 1 R ^11a. , phenyl substituted with 0-3 R ^11b, 0-3 C ₃ -C ₆ carbocycle substituted with R ^11b, or nitrogen, 1 to 4 substituents selected from oxygen and sulfur, Containing 0 to 3 heteroatoms and substituted with 0 to 3 R ^11b and being pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and tetrazolyl. is independently selected from heterocyclic ring of 5 to 7 ring members selected from; R ^11a, at each occurrence, H, methyl, ethyl, propyl, butyl, methoxy, ethoxy , Propoxy, Cl, F, = O, NR 15 R 16, CF 3, 0 to 3 amino phenyl substituted with R ^11b, 0 to 3 amino C ₃ -C ₆ carbons substituted with R ^11b A ring or containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^11b and pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and are independently selected from heterocyclic ring of 5 to 7 ring members selected from tetrazolyl; R ^11b, at each occurrence, H, OH, Cl , F, NR ¹⁵ R ¹⁶ , CF ₃ , acetyl, SCH ₃ , S (═O) CH ₃ , S (═O) ₂ CH ₃ , methyl, ethyl,
Propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl,
And independently selected from C ₁ -C ₂ haloalkoxy;

[0112]   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;

R ¹³ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, C ₁ -C ₄ alkoxy, Cl, F, Br, I, CN, NO ₂ , NR ¹⁵ R ¹⁶ , and CF. Independently selected from ₃ ;

R ¹⁴ in each occurrence is independently selected from H, phenyl, benzyl, C ₁ -C ₄ alkyl, and C ₂ -C ₄ alkoxyalkyl;

R ¹⁵ is, in each occurrence, H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl;

R ¹⁶ is, in each occurrence, H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl, CH ₃ CH ₂ C (═O) —, CH ₃ C (
_{= O) -, CH 3 CH} 2 OC (= O) -, CH 3 OC (= O) -, CH 3 CH 2 S (
═O) ₂ — and CH ₃ S (═O) ₂ — independently; R ¹⁷ is H, phenyl, benzyl, C ₁ -C ₄ alkyl, or C ₂ -C ₄ alkoxyalkyl. ;

R ¹⁸ is, in each occurrence, H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl; and

R ¹⁹ in each occurrence is independently selected from H, OH, methyl, ethyl, propyl and butyl.

[7] In a preferred embodiment, the present invention provides the compound of formula (I
provides a compound of a): wherein, Q is located at Q ^1; Q ¹ is C ₁ -C ₆ alkyl substituted with 0-3 R ^1a, 0-3 R ^1a in C ₂ -C ₆ alkenyl substituted, 0-3 C ₂ -C ₆ alkynyl substituted with R ^1a, C ₃ ~C ₆ cycloalkyl substituted with 0-3 R ^1b, Phenyl substituted with 0 to 3 R ^1b or containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b 5 A 6-membered heterocycle;

R ^1a is, in each occurrence, H, methyl, ethyl, propyl, butyl,
^{OR 14, Cl, F, Br} , I, C 3 ~C 6 carbocycle substituted with _{^{NR 15 R 16, CF 3,}} 0 to 3 amino R ^1b, is substituted with 0-3 R ^1b Phenyl, and independently from a 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. R ^1b is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, C ₁ -C ₂ haloalkoxy, (methyl) OC (= O) -
, (Ethyl) OC (= O)-, (propyl) OC (= O)-, and (butyl)
Independently selected from OC (= O)-;

R ² is H or methyl;

[0122] R ⁵ is, H, OR ^14, 0 or to 1 amino C ₁ -C ₄ alkyl substituted with R ^5b, C ₂ ~C ₄ alkenyl which is substituted with 0 to 1 amino R ^5b, Or C ₂ -C ₄ alkynyl substituted with 0 to 1 R ^5b ; R ^5a is H, methyl, ethyl, propyl or butyl; or R ⁵ and R ^5a are taken together , A cyclobutyl ring, a cyclopentyl ring, a cyclohexyl ring or a cycloheptyl ring; R ^5b in each occurrence is H, methyl, ethyl, propyl, butyl,
^{_{CF 3, OR 14, Cl,}} F, = O, C 3 ~C 7 cycloalkyl substituted with NR ¹⁵ R ^16, 0-3 R ^5c, is substituted with 0-3 R ^5c C ₃ -C ₇ carbocyclic ring contains zero or phenyl substituted with to three R ^5c, and nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 Substituted with R ^5c and is pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,
Independently selected from a 5- to 7-membered heterocycle selected from homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and tetrazolyl; R ^5c in each ^occurrence is H, OH, Cl, F, NR ¹⁵ R ¹⁶ , CF ₃
, Acetyl, SCH ₃ , S (═O) CH ₃ , S (═O) ₂ CH ₃ , methyl, ethyl,
Propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl,
And C ₁ -C ₂ are independently selected from haloalkoxy; W is a bond, -CH ₂ -, or -CH (CH ₃₎ - a and; X is a bond, with 0 to 1 amino R ^Xb Substituted phenyl, 0 to 1 C ₅ -C ₆ cycloalkyl substituted with R ^xb , or containing 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 Substituted with 1 R ^Xb and is pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,
A 5- to 6-membered heterocycle selected from pyrazolyl, imidazolyl, oxazolyl and isoxazolyl; R ^Xb , in each ^occurrence, is H, OH, Cl, F, Br, NR ¹⁵ R ¹⁶ ,
CF _{3, acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2 CH 3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ ~ It is independently selected from C ₂ haloalkoxy; Y is a bond, -V -, - V-CH 2 -, or a -CH ₂ V-; V is a bond, -C (= O) -, - O-, -S-, -S (= O)-, -S (= O
) _2- , or -N (R ¹⁹ )-; Z is H, F, Cl, Br, C ₁ -C ₄ alkyl substituted with 0 to 2 R ¹² , 0 to 2 C ₂ is substituted with R ¹² in -C ₄ alkenyl, 0-2 C ₂ -C ₄ alkynyl substituted with R ^12, C ₆ -C ₁₀ substituted with 0-4 R ^12b aryl, contain 0-4 C ₃ -C ₆ carbocycle substituted with R ^12b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 A 5- to 6-membered heterocycle substituted with R ^12b of

R ¹¹ is in each occurrence H, NR ¹⁸ R ¹⁹ , CF ₃ , C ₁ -C ₄ alkyl substituted with 0 to 1 R ^11a , 0 to 3 R ^11b . substituted phenyl, contain 0-3 C ₃ -C ₆ carbocycle substituted with R ^11b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0 5 to 7 membered substituted with 3 to ¹¹ R ^11b and selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and tetrazolyl. Independently selected from a heterocycle; R ^11a is, in each ^occurrence , H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, Propoxy, Cl, F, = O, NR 15 R 16, CF 3, 0 or phenyl substituted with to three R ^11b, C ₃ ~C ₆ carbocycle substituted with 0-3 R ^11b , Or 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^11b and pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl , Piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and tetrazolyl independently selected from a 5- to 7-membered heterocycle; R ^11b in each ^occurrence is H, OH, Cl, F, NR ¹⁵ R ¹⁶ , CF ₃ , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁
˜C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy independently selected;

R ¹² is, in each occurrence, H, OH, Cl, F, Br, NR ¹⁵ R ¹⁶ ,
^{-C (= O) NR 15 R} 16, CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (
═O) ₂ CH ₃ , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy, phenyl substituted with ^0-4 R ^12b. , A C _{3 to} C ₆ carbocycle substituted with 0 to 4 R ^12b , or 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 to 3 is independently selected from heterocyclic ring 5-6 membered substituted with R ^12b; R ^12b, at each occurrence, H, OH, Cl, F , Br, NR 15 R 16
, CF ₃ , acetyl, SCH ₃ , S (═O) CH ₃ , S (═O) ₂ CH ₃ , methyl,
Independently selected from ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy;

R ¹³ is, in each occurrence, H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, Br, CN, NR ¹⁵ R ¹⁶ ,
It is independently selected from and CF _3;

R ¹⁴ is, in each occurrence, independently selected from H, phenyl, benzyl, methyl, ethyl, propyl and butyl;

R ¹⁵ in each occurrence is independently selected from H, methyl, ethyl, propyl or butyl;

R ¹⁶ in each occurrence is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and phenethyl;

R ¹⁸ is, in each occurrence, H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl; and

R ¹⁹ in each occurrence is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and phenethyl.

[0131]   [8] In a preferred embodiment, the present invention provides a compound of formula (I
Providing a compound of a): In the formula,   Q is -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH₂CH₂CH₂CH₃ , -CH₂CH₂CH₂CH₂CH₃, -CH₂CH₂CH₂CH₂CH₂CH₃, -CH
(CH₃)₂, -CH (CH₃) CH₂CH₃, -CH₂CH (CH₃)₂, -CH₂C
(CH₃)₃, -CF₃, -CH₂CF₃, -CH₂CH₂CF₃, -CH₂CH₂CH₂CF₃, -CH = CH₂, -CH₂CH = CH₂, -CH₂C (CH₃) = CH₂, -CH₂C
H = C (CH₃)₂, -CH₂CH₂CH = CH₂, -CH₂CH₂C (CH₃) = CH ₂ , -CH₂CH₂CH = C (CH₃)₂, Cis-CH₂CH = CH (CH₃), C
is-CH₂CH₂CH = CH (CH₃), Trans-CH₂CH = CH (CH₃
), Trans-CH₂CH₂CH = CH (CH₃), -C≡CH, -CH₂C≡CH, -CH₂C≡C (CH₃), Cyclopropyl-, cyclobutyl-, cyclopentyl-, cyclohexyl-, cyclo
Clopropyl-CH₂-, Cyclobutyl-CH₂-, Cyclopentyl-CH₂-,
Cyclohexyl-CH₂-, Cyclopropyl-CH₂CH₂-, Cyclobutyl-C
H₂CH₂-, Cyclopentyl-CH₂CH₂-, Cyclohexyl-CH₂CH₂-,
Phenyl-, 2-F-phenyl-, 3-F-phenyl-, 4-F-phenyl-,
4-methoxyphenyl-, 4-ethoxyphenyl-, 4-propoxyphenyl-
, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) C
H₂-, (4-F-phenyl) CH₂-, (2-Cl-phenyl) CH₂-, (3
-Cl-phenyl) CH₂-, (4-Cl-phenyl) CH₂-, (2,3-diF-phenyl) CH₂-, (2,4-diF-phenyl) CH₂-, (
2,5-diF-phenyl) CH₂-, (2,6-diF-phenyl) CH₂-, (3
, 4-diF-phenyl) CH₂-, (3,5-diF-phenyl) CH₂-, (2
3-diCl-phenyl) CH₂-, (2,4-diCl-phenyl) CH₂-, (2
, 5-diCl-phenyl) CH₂-, (2,6-diCl-phenyl) CH₂-, (
3,4-diCl-phenyl) CH₂-, (3,5-diCl-phenyl) CH₂-,
(3-F-4-Cl-phenyl) CH₂-, (3-F-5-Cl-phenyl) C
H₂-, (3-Cl-4-F-phenyl) CH₂-, 2-furanyl-CH₂-, 3-furanyl-CH₂-, 2-thienyl-CH₂-3
-Thienyl-CH₂-, 2-pyridyl-CH₂-, 3-pyridyl-CH₂-, 4-
Pyridyl-CH₂-, 1-imidazolyl-CH₂-, 2-oxazolyl-CH₂−
, 4-oxazolyl-CH₂-, 5-oxazolyl-CH₂-, 3-isoxazo
Lil-CH₂-, 4-isoxazolyl-CH₂-, 5-isoxazolyl-CH ₂ -, Phenyl-CH₂CH₂-, (2-F-phenyl) CH₂CH₂-, (3-F-fe
Nil) CH₂CH₂-, (4-F-phenyl) CH₂CH₂-, (2-Cl-phenyl
Le) CH₂CH₂-, (3-Cl-phenyl) CH₂CH₂-, (4-Cl-phenyl
Le) CH₂CH₂− (2,3-diF-phenyl) CH₂CH₂-, (2,4-diF-phenyl) CH₂
CH₂-, (2,5-diF-phenyl) CH₂CH₂-, (2,6-diF-phenyl
Le) CH₂CH₂-, (3,4-diF-phenyl) CH₂CH₂-, (3,5-di-F
-Phenyl) CH₂CH₂-, (2,3-diCl-phenyl) CH₂CH₂-, (2
, 4-diCl-phenyl) CH₂CH₂-, (2,5-diCl-phenyl) CH₂
CH₂-, (2,6-diCl-phenyl) CH₂CH₂-, (3,4-diCl-f
CH) CH₂CH₂-, (3,5-diCl-phenyl) CH₂CH₂-, (3-F
-4-Cl-phenyl) CH₂CH₂-, (3-F-5-Cl-phenyl) CH₂
CH₂-, Furanyl-CH₂CH₂-, Thienyl-CH₂CH₂-, Pyridyl-CH₂CH₂-,
1-Imidazolyl-CH₂CH₂-, Oxazolyl-CH₂CH₂-, Isoxazo
Lil-CH₂CH₂-, 3,5-dimethylisoxazol-4-yl-CH₂C
H₂-, Phenyl-propyl-, Benzyl-CH (NH₂)-, Benzyl-CH (NHC (= O) -O-tBu)
-, Benzyloxy-CH₂-, Pyrrolidin-2-yl-, or 3-t-but
Xycarbonylcarbonylpyrrolidin-2-yl- And

R ² is H or methyl;

[0133]   R^FiveIs -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH (CH₃)₂,-
CH₂CH₂CH₂CH₃, -CH (CH₃) CH₂CH₃, -CH₂CH (CH₃)₂,
-CH₂C (CH₃)₃, -CH₂CH₂CH₂CH₂CH₃, -CH (CH₃) CH₂C
H₂CH₃, -CH₂CH (CH₃) CH₂CH₃, -CH₂CH₂CH (CH₃)₂,-
CH (CH₂CH₃)₂, -CF₃, -CH₂CF₃, -CH₂CH₂CF₃, -CH₂CH₂CH₂CF₃, -CH ₂ CH₂CH₂CH₂CF₃, -CH = CH₂, -CH₂CH = CH₂, -CH₂CH₂CH = CH₂, -CH = CH
CH₃, Cis-CH₂CH = CH (CH₃), Trans-CH₂CH = CH (C
H₃), Trans-CH₂CH = CH (C₆H_Five), -CH₂CH = C (CH₃)₂
, Cis-CH₂CH = CHCH₂CH₃, Trans-CH₂CH = CHCH₂C
H₃, Cis-CH₂CH₂CH = CH (CH₃), Trans-CH₂CH₂CH =
CH (CH₃), Trans-CH₂CH = CHCH₂(C₆H_Five), -C≡CH, -CH₂C≡CH, -CH₂C≡C (CH₃), -CH₂C≡C (C₆
H_Five), -CH₂CH₂C≡CH, -CH₂CH₂C≡C (CH₃), -CH₂CH₂C
≡ C (C₆H_Five), -CH₂CH₂CH₂C≡CH, -CH₂CH₂CH₂C≡C (CH ₃ ), -CH₂CH₂CH₂C≡C (C₆H_Five), Cyclopropyl-CH₂-, Cyclobutyl-CH₂-, Cyclopentyl-CH₂−
, Cyclohexyl-CH₂-, (2-CH₃-Cyclopropyl) CH₂-, (3-
CH₃-Cyclobutyl) CH₂-, Cyclopropyl-CH₂CH₂-, Cyclobutyl
-CH₂CH₂-, Cyclopentyl-CH₂CH₂-, Cyclohexyl-CH₂CH₂ -, (2-CH₃-Cyclopropyl) CH₂CH₂-, (3-CH₃-Cyclobutyl
) CH₂CH₂-, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) CH ₂ -, (4-F-phenyl) CH₂-, (3,5-diF-phenyl) CH₂-2
-Furanyl-CH₂-, 3-furanyl-CH₂-, 2-thienyl-CH₂-, 3-
Thienyl-CH₂-, 2-pyridyl-CH₂-, 3-pyridyl-CH₂-, 4-pi
Lysyl-CH₂-, 1-imidazolyl-CH₂-, 2-oxazolyl-CH₂-,
4-oxazolyl-CH₂-, 5-oxazolyl-CH₂-, 3-isoxazoli
Le-CH₂-, 4-isoxazolyl-CH₂-, 5-isoxazolyl-CH₂
-, Phenyl-CH₂CH₂-, (2-F-phenyl) CH₂CH₂-, (3-F-fe
Nil) CH₂CH₂-, (4-F-phenyl) CH₂CH₂-, Furanyl-CH₂C
H₂-, Thienyl-CH₂CH₂-, Pyridyl-CH₂CH₂-, 1-Imidazolyl
-CH₂CH₂-, Oxazolyl-CH₂CH₂-, Isoxazolyl-CH₂CH₂ -, Methoxy, ethoxy, propoxy, or butoxy And   R^5aIs H,   Or R^FiveAnd R^5aTogether, cyclopentyl, cyclohexyl
Or it can form cycloheptyl;   W is a bond, -CH₂-, Or -CH (CH₃) -Is;   X is a bond,

[0134]

[Chemical formula 24]

[0135] And   Y is a bond, -CH₂-V-, -V-, or -V-CH₂-Is;   V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O).
)₂-, -NH-, or -N (CH₃) -Is;   Z is H, F, Cl, Br, methyl, ethyl, n-propyl, i-propyl,
n-butyl, i-butyl, s-butyl, t-butyl, Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl
-Phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl
2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl
3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCl-phen
Nyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl
-Phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-
4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Cl-4-F-phenyl
2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2
-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl
Phenyl, 3-MeS-phenyl, 4-MeS-phenyl, 2-CF₃O-pheny
Le, 3-CF₃O-phenyl, 4-CF₃O-phenyl, Furanyl, thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl, 4
-Me-pyridyl, l-imidazolyl, oxazolyl, isoxazolyl, 1-
Benzimidazolyl, morpholino, N-piperidinyl, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) CH ₂ -, (4-F-phenyl) CH₂-, (2-Cl-phenyl) CH₂-, (3-
Cl-phenyl) CH₂-, (4-C1-phenyl) CH₂-, (2,3-di-F-
Phenyl) CH₂-, (2,4-diF-phenyl) CH₂-, (2,5-di-F-f
CH) CH₂-, (2,6-diF-phenyl) CH₂-, (3,4-diF-fe
Nil) CH₂-, (3,5-diF-phenyl) CH₂-, (2,3-diCl-phen
Nil) CH₂-, (2,4-diCl-phenyl) CH₂-, (2,5-diCl-f
CH) CH₂-, (2,6-diCl-phenyl) CH₂-, (3,4-diCl-
Phenyl) CH₂-, (3,5-diCl-phenyl) CH₂-, (3-F-4-C
l-phenyl) CH₂-, (3-F-5-Cl-phenyl) CH₂-, (3-Cl
-4-F-phenyl) CH₂-, (2-MeO-phenyl) CH₂-, (3-Me
O-phenyl) CH₂-, (4-MeO-phenyl) CH₂-, (2-PhO-F
CH) CH₂-, (3-PhO-phenyl) CH₂-, (4-PhO-phenyl
) CH₂-, (2-Me-phenyl) CH₂-, (3-Me-phenyl) CH₂−
, (4-Me-phenyl) CH₂-, (2-MeS-phenyl) CH₂-, (3-
MeS-phenyl) CH₂-, 4-MeS-phenyl) CH₂-, (2-CF₃O
-Phenyl) CH₂-, (3-CF₃O-phenyl) CH₂-, (4-CF₃OF
CH) CH₂-, (Furanyl) CH₂-, (Thienyl) CH₂-, (Pyridyl)
CH₂-, (2-Me-pyridyl) CH₂-, (3-Me-pyridyl) CH₂-,
(4-Me-pyridyl) CH₂-, (1-imidazolyl) CH₂-, (Oxazoli
Le) CH₂-, (Isoxazolyl) CH₂-, (1-benzimidazolyl) CH ₂ -, (Cyclopropyl) CH₂-, (Cyclobutyl) CH₂-, (Cycloplier
Le) CH₂-, (Cyclohexyl) CH₂-, (Morpholino) CH₂-, (N-pi
Peridinyl) CH₂-, Phenyl-CH₂CH₂-, (Phenyl)₂CHCH₂-, (2-F-phenyl) C
H₂CH₂-, (3-F-phenyl) CH₂CH₂-, (4-F-phenyl) CH₂
CH₂-, (2-Cl-phenyl) CH₂CH₂-, (3-Cl-phenyl) CH₂ CH₂-, (4-Cl-phenyl) CH₂CH₂-, (2,3-diF-phenyl)
CH₂CH₂-, (2,4-diF-phenyl) CH₂CH₂-, (2,5-di-F-f
CH) CH₂CH₂-, (2,6-diF-phenyl) CH₂CH₂-, (3,4-
Di-F-phenyl) CH₂CH₂-, (3,5-diF-phenyl) CH₂CH₂-, (
2,3-diCl-phenyl) CH₂CH₂-, (2,4-diCl-phenyl) CH ₂ CH₂-, (2,5-diCl-phenyl) CH₂CH₂-, (2,6-diCl-f
CH) CH₂CH₂-, (3,4-diCl-phenyl) CH₂CH₂-, (3,5
-DiCl-phenyl) CH₂CH₂-, (3-F-4-Cl-phenyl) CH₂C
H₂-, (3-F-5-Cl-phenyl) CH₂CH₂-, (3-Cl-4-F-
Phenyl) CH₂CH₂-, (2-MeO-phenyl) CH₂CH₂-, (3-Me
O-phenyl) CH₂CH₂-, (4-MeO-phenyl) CH₂CH₂-, (2-
Me-phenyl) CH₂CH₂-, (3-Me-phenyl) CH₂CH₂-, (4-
Me-phenyl) CH₂CH₂-, (2-MeS-phenyl) CH₂CH₂-, (3
-MeS-phenyl) CH₂CH₂-, (4-MeS-phenyl) CH₂CH₂-,
(2-CF₃O-phenyl) CH₂CH₂-, (3-CF₃O-phenyl) CH₂C
H₂-, (4-CF₃O-phenyl) CH₂CH₂-, (Furanyl) CH₂CH₂-,
(Thienyl) CH₂CH₂-, (Pyridyl) CH₂CH₂-, (2-Me-pyridyl
) CH₂CH₂-, (3-Me-pyridyl) CH₂CH₂-, (4-Me-pyridyl
) CH₂CH₂-, (Imidazolyl) CH₂CH₂-, (Oxazolyl) CH₂CH₂ -, (Isoxazolyl) CH₂CH₂-, (Benzimidazolyl) CH₂CH₂−
, (Cyclopropyl) CH₂CH₂-, (Cyclobutyl) CH₂CH₂-, (Cyclo
Pentyl) CH₂CH₂-, (Cyclohexyl) CH₂CH₂-, (Morpholino) C
H₂CH₂-, Or (N-piperidinyl) CH₂CH₂− And

R ¹¹ is, in each occurrence, H, methyl, ethyl, n-propyl, i-
Propyl, n-butyl, i-butyl, s-butyl, t-butyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, 2-F- phenyl -, 3-F- phenyl, 4-F- phenyl, 4-Cl @ - phenyl, 4-CH ₃ - phenyl, 4-MeO- phenyl -, 4-CF ₃ - phenyl,
(4-F- _{phenyl) CH 2 -, (4-} C1- _{phenyl) CH 2 -, (4-} CH 3
- _{phenyl) CH 2 -, (4-} CF 3 - _{phenyl) CH 2 -, (4-} F- _{phenyl) CH 2 CH 2 -, (} 4-C1- _{phenyl) CH 2 CH 2 -, (} 4-CH 3 - _{phenyl) CH 2 CH 2 -, (} 4-CF 3 - phenyl) CH ₂ CH ₂ -, pyridin-2-yl -, pyridin-3-yl -, 4-CF ₃ - yl - 4 -CH ₃ -
Pyridin-2-yl-, thiazol-2-yl-, azapan-1-yl, N, N
-Independently selected from dimethylamino, N, N-diethylamino, N, N-dipropylamino, and N, N-dibutylamino; and

R ¹³ in each occurrence is independently selected from H, MeO, F and Cl.

[0138]   [9] In a preferred embodiment, the present invention provides compounds of formula (Ic):

[0139]

[Chemical 25]

[0140] Alternatively, it provides a pharmaceutically acceptable salt form or prodrug thereof.

[0141]   [10] In a preferred embodiment, the present invention provides compounds of formula (Id):

[0142]

[Chemical formula 26]

[0143] Alternatively, it provides a pharmaceutically acceptable salt form or prodrug thereof.

[0144]   [11] In a preferred embodiment, the present invention provides compounds of formula (Ie):

[0145]

[Chemical 27]

[0146] Alternatively, it provides a pharmaceutically acceptable salt form or prodrug thereof.

[12] In a preferred embodiment, the present invention provides a compound selected from
Provided: 3- (2 (R) -Cyclopentylmethyl-3 (S) -hydroxyl-1-oxo
-5-Phenylpentyl) amino-1-methyl-5-phenyl-2,3-dihydr
Ro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -cyclopentylmethyl-3 (S) -hydroxyl-1-oxo
-5-Phenylpentyl) amino-1-methyl-5- (4-fluorophenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -benzyl-3 (S) -hydroxyl-1-oxo-5-phenyl
Rupentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1
, 4-benzodiazepin-2-one; 3- (2 (R) -isopropyl-3 (S) -hydroxyl-1-oxo-5-phenyl
Phenylpentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H
-1,4-benzodiazepin-2-one; 3- (2 (R) -cyclopentylmethyl-3 (S) -hydroxyl-1-oxo
-4- (3,5-Difluorophenoxy) butyl) amino-1-methyl-5-phenyl
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl) -3 (S) -hydroxyl-1-oxo-4- (
3,5-difluorophenoxy) butyl) amino-1-methyl-5-phenyl-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -cyclopentylmethyl-3 (S) -hydroxyl-1-oxo
-4-phenoxybutyl) amino-7-chloro-1-methyl-5-phenyl-2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-phen
Noxybutyl) amino-7-chloro-1-methyl-5- (4-fluorophenyl
) -2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4-cyclohexyl
Xyloxybutyl) amino-1-methyl-5-phenyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-cyclyl
Lohexyloxybutyl) amino-1-methyl-5-phenyl-2,3-dihydr
Ro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4-phenoxy
Cibutyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro
-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-phen
Noxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihi
Doro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -benzyl-3 (S) -hydroxyl-1-oxo-4-cyclo
Hexyloxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,
3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -cyclopentylmethyl-3 (S) -hydroxyl-1-oxo
-4-Cyclohexyloxybutyl) amino-7-chloro-1-methyl-5-phenyl
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-cyclyl
Lohexyloxybutyl) amino-7-chloro-1-methyl-5-phenyl-2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isopropyl-3 (S) -hydroxyl-1-oxo-4-si
Chlorohexyloxybutyl) amino-7-chloro-1-methyl-5-phenyl-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -methoxy-3 (S) -hydroxyl-1-oxo-4- (4-
Trifluoromethylbenzyloxy) butyl) amino-7-chloro-1-methyl
-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine-2-o
3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4- (2,4
-Difluorobenzyloxy) butyl) amino-7-chloro-1-methyl-5-
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -vinyl-3 (S) -hydroxyl-1-oxo-4-benzyl
Oxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihi
Doro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4-cyclohexyl
Xyloxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-5-phen
Nylpentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-3-cyclyl
Ropropylpropyl) amino-1-methyl-5-phenyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-heptyl
) Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-ben
Zodiazepine-2-one; 3- (R)-(2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-
Heptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (S)-(2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-
Heptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-nonyl)
Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzo
Diazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-hexyl
) Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-ben
Zodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-phen
Nylbutyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1
, 4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-5-phenyl
Pentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-6-phenyl
Hexyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-butyl)
Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzo
Diazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-octyl
) Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-ben
Zodiazepine-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-heptyl) a
Mino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodi
Azepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-3-phenyl
Propyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-5,5-dime
Cylhexyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-hexyl) a
Mino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodi
Azepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-3- (4-propyl)
Ropoxyphenyl) propyl) amino-1-methyl-5-phenyl-2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 2- (R) -cyclopropylmethyl-3- (S) -hydroxylheptanoic acid (2
-Oxo-1- (3-phenoxybenzyl) azapan-3- (S) -yl) ami
2 (R) -cyclopropylmethyl-5- (3,5-difluorophenyl) -3-
(S) -Hydroxypentanoic acid (2-oxo-1- (3-phenoxybenzyl)
Azapan-3- (S) -yl) amide; 4-Cyclopentyl-2- (R) -cyclopropylmethyl-3- (S) -hydro
Xybutanoic acid (2-oxo-1- (3-phenoxybenzyl) azapan-3- (
S) -yl) amide; 2- (R) -cyclopropylmethyl-3- (S) -hydroxyheptanoic acid (1-
(5-Bromo-3-pyridinyl) methyl-2-oxo-azapan-3- (S)-
Yl) amide; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5- (2-fluorophenyl) -1-methyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5- (azapan-1-yl) -1-methyl-2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-5- (3,5-difluorophenyl)
) -3 (S) -Hydroxyl-1-oxopentyl) amino-1-methyl-5-
(Pyridin-2-yl) -2,3-dihydro-1H-1,4-benzodiazepine
-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxopentyl) amino-1-methyl-5- (4-chlorophenyl) -2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5- (4-methoxyphenyl) -1-methyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5- (4-methoxyphenyl) -1-methyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(4-cyclopentyl-2- (R) -cyclopropylmethyl-3-
(S) -hydroxyl-1-oxobutyl) amino-1-methyl-5-phenyl
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-3- (S) -hydroxyl
-1-Oxohepta-6-enyl) amino-1-methyl-5-phenyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xohepta-6-enyl) amino-1-methyl-5- (4-trifluoromethyl)
Phenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-5- (3,5-dimethylyl)
Sooxazol-4-yl) -3- (S) -hydroxyl-1-oxopentyl
) Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-ben
Zodiazepine-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihi
Doro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl- (pyridin-2-yl) -2,3-dihydride
Ro-1H-1,4 benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (5-cyclopentyl-2- (R) -cyclopropylmethyl-3- (S)-
Hydroxyl-1-oxopentyl) amino-1-methyl-5- (pyridine-2
-Yl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -iso-butyl-3- (S) -hydroxyl-1-oxophenyl
Butyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,
3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-3- (S) -hydroxyl
-1-oxo-5- (thiophen-2-yl) amino-1-methyl-5-phenyl
Le-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-5- (furan-2-yl)
3- (S) -hydroxyl-1-oxopentyl) amino-1-methyl-5-phenyl
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (5-cyclopentyl-2- (R) -cyclopropylmethyl-3- (S)-
Hydroxyl-1-oxopentyl) amino-5- (4-fluorophenyl)-
1-Methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-5- (3,5-difluoro)
Phenyl) -3- (S) -hydroxy-1-oxopentyl) amino-1-methyl
Lu-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine-2-
ON; 3- (S)-(3- (S) -hydroxyl-2- (R)-(thiophen-2-i
) Methyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-3- (S) -hydroxyl
-1-Oxoheptyl) amino-7-methyl-5-phenyl-2,3-dihydro
-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-7-methoxy-1-methyl-5-phenyl-2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclobutylmethyl-3- (S) -hydroxyl-
1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R)-(3,5-difluorobenzyl) -3- (S) -hi
Droxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R)-(furan-2-yl) methyl-3- (S) -hydro.
Xyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xo-5-phenylpentyl) amino-1-methyl-5- (pyridin-2-yl
) -2,3-Dihydro-1H-benzodiazepin-2-one; 3- (2- (R) -iso-butyl-3- (S) -hydroxyl-1-oxophenyl
Butyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-dihydr
B-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -iso-butyl-3- (S) -hydroxyl-1-oxohe
Butyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-dihydr
B-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xo-5-phenylpentyl) amino-1-methyl-5-phenyl-2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-5- (furan-2-yl) -3- (
S) -hydroxyl-1-oxopentyl) amino-1-methyl-5- (4-to
Lifluoromethylphenyl) -2,3-dihydro-1H-1,4-benzodiaze
Pin-2-one; 3- (5-Cyclopentyl-2- (R) -cyclopropylmethyl-3- (S)-
Hydroxyl-1-oxopentyl) amino-1-methyl-5- (4-triflu
Oromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-
2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxooctyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xisononyl) amino-1-methyl-5- (4-trifluoromethylphenyl)-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethyl (pyridine
-2-yl))-2,3-dihydro-1H-1,4-benzodiazepine-2-o
3- (2- (R) -cyclobutylmethyl-3- (S) -hydroxyl-1-oxy
Soheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopentylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-methyl-2-pyridyl) -2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-methyl-2-pyridyl) -2,
3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxobutyl) amino-1-methyl-5- (4-trifluoromethylphenyl)-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R)-(3-butenyl) -3- (S) -hydroxyl-1
-Oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1
H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R)-(3-methylbutyl) 3- (S) -hydroxyl-
1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -ethyl-3- (S) -hydroxyl-1-oxohe
Butyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4
-Benzodiazepin-2-one; 3- (S)-(2- (R) -propyl-3- (S) -hydroxyl-1-oxo
Heptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1,4-be
3- (S)-(2- (R) -Butyl-3- (S) -hydroxyl-1-oxohexanone;
Butyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4
-Benzodiazepin-2-one; 3- (4- (S) -amino-3- (R) -hydroxyl-2- (R) -methyl-
1-oxo-5-phenylpentyl) amino-7-chloro-5- (2-fluoro
Phenyl) -1-methyl-2,3-dihydro-1H-1,4-benzodiazepine
2-one; 3- (4- (S)-(tert-butoxycarbonylamino-3- (R) -hydr
Roxyl-2- (R) -methyl-1-oxo-5-phenylpentyl) amino-
7-chloro-5- (2-fluorophenyl) -1-methyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (3- (tert-butoxycarbonylpyrrolidin-2- (R) -yl)-
3- (R) -hydroxyl-2- (R) -methyl-1-oxopropyl) amino
-7-chloro-5- (2-fluorophenyl) -1-methyl-2,3-dihydro
-1H-1,4-benzodiazepin-2-one; 3- (3- (R) -hydroxyl-2- (R) -methyl-1-oxo-3- (py
Roridin-2- (R) -yl) propyl) -amino-7-chloro-5- (2-phenyl)
Luorophenyl) -1-methyl-2,3-dihydro-1H-1,4-benzodia
Zepin-2-one; 3- (4-benzyloxy-3- (R) -hydroxyl-2- (R) -iso-
Propyl-1-oxobutyl-amino-7-chloro-1-methyl-5-phenyl
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 2- (4- (S) -amino-3- (S) -hydroxyl-2- (S) -methyl-
1-oxo-5-phenylpentyl) amino-7-chloro-5- (2-fluoro
Phenyl) -1-methyl-2,3-dihydro-1H-1,4-benzodiazepine
2-one; 2- (4- (S)-(tert-butoxycarbonylamino-3- (S) hydro)
Xyl-2- (S) -methyl-1-oxo-5-phenylpentyl) amino-7
-Chloro-5- (2-fluorophenyl) -1-methyl-2,3-dihydro-1
H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (thiazol-2-yl) -2,3-
Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-cyclopropylmethyl-5- (thiazol-2-i
) -2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-cyclopropylmethyl-5- (4-trifluorome
Cylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-2-o
3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoheptyl) amino-1-benzyl-5- (4-trifluoromethylphenyl)
) -2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (3-phenoxybenzyl) -5- (4-triflu
Oromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-
2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (3-pyridinylmethyl) -5- (4-trifluoro)
Romethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-2
-One; 3- (2- (S) -cyclopropylmethyl-3- (R) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (S) -cyclopropylmethyl-3- (R) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (R) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (S) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (S) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-3- (
S) -Methyl-1-oxoheptyl) amino-1-methyl-5- (4-triflu
Oromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-
2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (3-phenoxybenzyl) -5-methyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-benzyl-5-methyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one; 3- (3- (S) -acetoxy-2- (R) -iso-butyl-1-oxohep
Cyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-dihydro
-1H-1,4-benzodiazepin-2-one; 3- (S)-(5-cyclopentyl-2- (R) -cyclopropylmethyl-3-
(S) -Methoxy-1-oxopentyl) amino-1-methyl-5-phenyl-
2,3-dihydro-1H-1,4-benzodiazepin-2-one; 1- (1-hydroxypentyl) cyclohexanecarboxylic acid (5- (4-fluoro
Rophenyl) -1-methyl-2-oxo-2,3-dihydro-1H-1,4-be
Nazodiazepin-3-yl) amide; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5-methyl-5H, 7H-dibenzo [b, d] azepine
-6-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xooctyl) amino-5-methyl-5H, 7H-dibenzo [b, d] azepine
-6-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xynonyl) amino-5-methyl-5H, 7H-dibenzo [b, d] azepine-
6-one; 3- (2- (R) -cyclopropylmethyl-5- (furan-2-yl) -3- (
S) -Hydroxyl-1-oxopentyl) amino-5-methyl-5H, 7H-
Dibenzo [b, d] azepin-6-one; 2- (R) -cyclopropylmethyl-3- (S) -hydroxylheptanoic acid (2
-Oxo-1- (3-phenylamino-benzyl) azapan-3- (S) -yl
) Amide; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5-cyclopentyl-1-methyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5-benzyl-1-methyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5-benzyl-1-butyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5-cycloheptyl-1-methyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-benzyl-5-cycloheptyl-2,3-dihydro
-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-butyl-5-cycloheptyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (2-pyridinylmethyl) -5- (4-trifluor)
Romethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-2
-One; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (3-pyridinylmethyl) -5- (2-fluorophenyl)
Phenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (S) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxopentyl) amino-1- (3-pyridinylmethyl) -5- (4-trifluor)
Romethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-2
-One; 3- (2-1 (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-
Oxoheptyl) amino-1-methyl-5- (N, N-dibutylamino) -2,
3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-n-butyl-5-t-butyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (2-oxo-3,3-dimethylbutyl) -5-n
-Butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-benzyl-5-t-butyl-2,3-dihydro-1
H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (2-picolyl) -5-n-butyl-2,3-dihi
Doro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -isobutyl-3- (S) -hydroxyl-1-oxohepti
Amino) methyl-1-methyl-5-homopiperidino-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-1,3-dioxoheptyl) amino
-1-Methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-
1H-1,4-benzodiazepin-2-one; and 1-pentylylcyclohexanecarboxylic acid (5- (4-fluorophenyl) -1
-Methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepine-
3-yl) amide.

[13] In a preferred embodiment, the present invention provides compounds of formula (I), wherein the stereochemistry of the 3rd carbon in lactam ring B is S configuration.

[14] In a preferred embodiment, the present invention provides a compound of formula (I), wherein the stereochemistry of the 3-position carbon in lactam ring B is R configuration.

[15] In a preferred embodiment, the present invention provides compounds of formula (Ib) below, defined as follows:

[0151]

[Chemical 28]

[0152] Provide In the formula,   Ring B is

[0153]

[Chemical 29]

It is selected from [0154]; Q ¹ is 0-3 C ₁ -C ₆ alkyl substituted with R ^1a, C ₂ ~C ₆ alkenyl substituted with 0-3 R ^1a, 0 number to three C ₂ -C ₆ alkynyl substituted with R ^1a, C ₃ ~C ₁₀ cycloalkyl substituted with 0-3 R ^1b, is substituted with 0-3 R ^1b C ₃ -C ₁₀ carbocyclic ring, containing 0-3 C ₆ -C ₁₀ aryl substituted by R ^1b or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and A 5- to 10-membered heterocycle substituted with 0 to 3 R ^1b ; R ^1a in each occurrence is H, C ₁ -C ₆ alkyl, OR ¹⁴ , Cl, F
^{, Br, I, NR 15 R} 16, CF 3, 0 to 3 amino C ₃ -C ₁₀ carbocycle substituted with R ^1b, ~C C ₆ is substituted with 0-3 R ^1b ₁₀ Independently selected from aryl and 5 to 10 membered heterocycles containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. R ^1b is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, C ₁ -C ₄ haloalkyl -S-, and (C ₁ -C ₆ alkyl) -O-C (= O) - independently selected from;

[0155] R ⁵ is, OR ^14, 0-3 C ₁ -C ₆ alkyl substituted with R ^5b, C ₂ -C ₆ alkenyl substituted with 0-3 R ^5b or 0, be C ₂ -C ₆ alkynyl substituted with pieces to three R ^5b; R ^5a is, H, there methyl, ethyl, propyl, butyl or C ₂ -C ₄ alkenyl; or, R ⁵ and R ^5a can be taken together to form a C ₄ -C ₇ cycloalkyl ring; R ^5b in each occurrence is H, methyl, ethyl, propyl, butyl,
^{_{CF 3, OR 14, Cl,}} F, Br, I, = O, C 3 ~C 7 cycloalkyl substituted with NR ¹⁵ R ^16, 0 to 3 amino R ^5c, 0 to 3 amino R ^5c A C ₃ -C ₇ carbocycle substituted with phenyl, 0 to 3 phenyl substituted with R ^5c , and 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 are independently selected from 5- to 7-membered heterocyclic ring is substituted with number to three R ^5c; R ^5c, at each occurrence, H, OH, Cl, F , Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ -C ₄ alkyl, C ₁ -C ₃ alkoxy, C ₁ -C ₂ haloalkyl, and C ₁ independently of -C ₂ haloalkoxy selected; W is - (CHR ⁸⁾ _p - a is P is 0 or 1;

[0156] R ⁸ is H, methyl or ethyl; X is a bond, phenyl substituted with 0-2 R ^Xb, C ₅ -C substituted with 0-3 R ^Xb _6- cycloalkyl or a 5-6 membered heterocycle containing 1-3 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0-2 R ^Xb ; R ^Xb is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, C ₁ ~C ₆ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkyl, C ₁ ~
C ₄ haloalkoxy, and C ₁ -C ₄ are independently selected from haloalkyl -S-; Y is a _{bond, -V -, - CH 2 -V} -, - V-CH 2 -, or -CH ₂ - V-
CH _2- ; V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O.
) _2- , or -N (R ¹⁹ )-; Z is H, F, Cl, Br, C ₁ -C ₄ alkyl substituted with 0 to 2 R ¹² , 0 to 2 C ₂ is substituted with R ¹² in -C ₄ alkenyl, 0-2 C ₂ -C ₄ alkynyl substituted with R ^12, C ₆ -C ₁₀ substituted with 0-4 R ^12b aryl, contain 0-4 C ₃ -C ₆ carbocycle substituted with R ^12b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 A 5- to 6-membered heterocycle substituted with R ^12b of

R ¹¹ is, in each occurrence, H, ═O, NR ¹⁸ R ¹⁹ , C (═O) R ¹⁷ ,
C (= O) OR ¹⁷ , C (= O) NR ¹⁸ R ¹⁹ , S (= O) ₂ NR ¹⁸ R ¹⁹ , CF ₃ , C ₁ -C ₆ alkyl substituted with 0 to 1 R ^11a. , phenyl substituted with 0-3 R ^11b, 0-3 C ₃ -C ₆ carbocycle substituted with R ^11b, or nitrogen, 1 to 4 substituents selected from oxygen and sulfur, Containing 0 to 3 heteroatoms and substituted with 0 to 3 R ^11b and being pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and tetrazolyl. is independently selected from heterocyclic ring of 5 to 7 ring members selected from; R ^11a, at each occurrence, H, methyl, ethyl, propyl, butyl, methoxy, ethoxy , Propoxy, Cl, F, = O, NR 15 R 16, CF 3, 0 to 3 amino phenyl substituted with R ^11b, 0 to 3 amino C ₃ -C ₆ carbons substituted with R ^11b A ring or containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^11b and pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and are independently selected from heterocyclic ring of 5 to 7 ring members selected from tetrazolyl; R ^11b, at each occurrence, H, OH, Cl , F, NR ¹⁵ R ¹⁶ , CF ₃ , acetyl, SCH ₃ , S (═O) CH ₃ , S (═O) ₂ CH ₃ , methyl, ethyl,
Propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl,
And independently selected from C ₁ -C ₂ haloalkoxy;

[0158]   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;

R ¹³ is, in each occurrence, H, OH, C ₁ -C ₆ alkyl, C ₁ -C ₄ alkoxy, Cl, F, Br, I, CN, NO ₂ , NR ¹⁵ R ¹⁶ , and CF. Independently selected from ₃ ;

R ¹⁴ is in each occurrence independently selected from H, phenyl, benzyl, C ₁ -C ₄ alkyl, and C ₂ -C ₄ alkoxyalkyl;

R ¹⁵ is, in each occurrence, H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl;

R ¹⁶ is, in each occurrence, H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl, CH ₃ CH ₂ C (═O) —, CH ₃ C (
_{= O) -, CH 3 CH} 2 OC (= O) -, CH 3 OC (= O) -, CH 3 CH 2 S (
═O) ₂ — and CH ₃ S (═O) ₂ — independently; R ¹⁷ is H, phenyl, benzyl, C ₁ -C ₄ alkyl, or C ₂ -C ₄ alkoxyalkyl. ;

R ¹⁸ is, in each occurrence, H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl; and

R ¹⁹ is H, OH, methyl, ethyl, propyl and butyl in each occurrence.

[16] In a preferred embodiment, the present invention provides the formula (
Provides compounds of ib): In formula (I), Q ¹ is, C ₁ -C ₆ alkyl substituted with 0-3 R ^1a, C ₂ -C substituted with 0-3 R ^1a ₆ alkenyl, C ₂ -C ₆ alkynyl substituted with 0-3 R ^1a, C ₃ ~C ₆ cycloalkyl substituted with 0-3 R ^1b, 0-3 R ^1b Or a 5- to 6-membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. R ^1a is, in each ^occurrence , H, methyl, ethyl, propyl, butyl,
^{OR 14, Cl, F, Br} , I, C 3 ~C 6 carbocycle substituted with _{^{NR 15 R 16, CF 3,}} 0 to 3 amino R ^1b, is substituted with 0-3 R ^1b Phenyl, and independently from a 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. R ^1b is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, C ₁ -C ₂ haloalkoxy, (methyl) OC (= O) -
, (Ethyl) OC (= O)-, (propyl) OC (= O)-, and (butyl)
Independently selected from OC (= O)-;

[0166] R ⁵ is, OR ^14, 0 to 1 amino C ₁ -C ₄ alkyl substituted with R ^5b, C ₂ -C ₄ alkenyl substituted with 0 to 1 amino R ^5b or 0, C ₂ -C ₄ alkynyl substituted with 1 to 1 R ^5b ; R ^5a is H, methyl, ethyl, propyl or butyl; or R ⁵ and R ^5a are taken together, A cyclobutyl ring, a cyclopentyl ring, a cyclohexyl ring or a cycloheptyl ring can be formed; R ^5b in each occurrence is H, methyl, ethyl, propyl, butyl,
^{_{CF 3, OR 14, Cl,}} F, = O, C 3 ~C 7 cycloalkyl substituted with NR ¹⁵ R ^16, 0-3 R ^5c, is substituted with 0-3 R ^5c C ₃ -C ₇ carbocyclic ring contains zero or phenyl substituted with to three R ^5c, and nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 Substituted with R ^5c and is pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,
Independently selected from a 5- to 7-membered heterocycle selected from homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and tetrazolyl; R ^5c in each ^occurrence is H, OH, Cl, F, NR ¹⁵ R ¹⁶ , CF ₃
, Acetyl, SCH ₃ , S (═O) CH ₃ , S (═O) ₂ CH ₃ , methyl, ethyl,
Propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl,
And C ₁ -C ₂ are independently selected from haloalkoxy; W is a bond, -CH ₂ -, or -CH (CH ₃₎ - a and; X is a bond, with 0 to 1 amino R ^Xb Substituted phenyl, 0 to 1 C ₅ -C ₆ cycloalkyl substituted with R ^xb , or containing 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 Substituted with 1 R ^Xb and is pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,
A 5- to 6-membered heterocycle selected from pyrazolyl, imidazolyl, oxazolyl and isoxazolyl;

R ^Xb is, in each ^occurrence , H, OH, Cl, F, Br, NR ¹⁵ R ¹⁶ ,
CF _{3, acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2 CH 3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ ~ It is independently selected from C ₂ haloalkoxy; Y is a bond, -V -, - V-CH 2 -, or a -CH ₂ V-; V is a bond, -C (= O) -, - O-, -S-, -S (= O)-, -S (= O
) _2- , or -N (R ¹⁹ )-; Z is H, F, Cl, Br, C ₁ -C ₄ alkyl substituted with 0 to 2 R ¹² , 0 to 2 C ₂ is substituted with R ¹² in -C ₄ alkenyl, 0-2 C ₂ -C ₄ alkynyl substituted with R ^12, C ₆ -C ₁₀ substituted with 0-4 R ^12b aryl, contain 0-4 C ₃ -C ₆ carbocycle substituted with R ^12b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 A 5- to 6-membered heterocycle substituted with R ^12b of

R ¹¹ is in each occurrence H, NR ¹⁸ R ¹⁹ , CF ₃ , C ₁ -C ₄ alkyl substituted with 0 to 1 R ^11a , 0 to 3 R ^11b . substituted phenyl, contain 0-3 C ₃ -C ₆ carbocycle substituted with R ^11b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0 5 to 7 membered substituted with 3 to ¹¹ R ^11b and selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and tetrazolyl. Independently selected from a heterocycle; R ^11a is, in each ^occurrence , H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, Propoxy, Cl, F, = O, NR 15 R 16, CF 3, 0 or phenyl substituted with to three R ^11b, C ₃ ~C ₆ carbocycle substituted with 0-3 R ^11b , Or 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^11b and pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl , Piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and tetrazolyl independently selected from a 5- to 7-membered heterocycle; R ^11b in each ^occurrence is H, OH, Cl, F, NR ¹⁵ R ¹⁶ , CF ₃ , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁
˜C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy independently selected;

R ¹² is, in each occurrence, H, OH, Cl, F, Br, NR ¹⁵ R ¹⁶ ,
^{-C (= O) NR 15 R} 16, CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (
═O) ₂ CH ₃ , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy, phenyl substituted with ^0-4 R ^12b. , A C _{3 to} C ₆ carbocycle substituted with 0 to 4 R ^12b , or 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 to 3 is independently selected from heterocyclic ring 5-6 membered substituted with R ^12b; R ^12b, at each occurrence, H, OH, Cl, F , Br, NR 15 R 16
, CF ₃ , acetyl, SCH ₃ , S (═O) CH ₃ , S (═O) ₂ CH ₃ , methyl,
Independently selected from ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy;

R ¹³ is, in each occurrence, H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, Br, CN, NR ¹⁵ R ¹⁶ ,
It is independently selected from and CF _3;

R ¹⁴ is in each occurrence independently selected from H, phenyl, benzyl, methyl, ethyl, propyl and butyl;

R ¹⁵ in each occurrence is independently selected from H, methyl, ethyl, propyl or butyl;

R ¹⁶ in each occurrence is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and phenethyl;

R ¹⁸ is, in each occurrence, H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl; and

R ¹⁹ in each occurrence is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and phenethyl.

[0176]   [17] In a preferred embodiment, the present invention provides the formula (
Providing a compound of Ib): In the formula,   Q¹Is -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH₂CH₂CH₂CH ₃ , -CH₂CH₂CH₂CH₂CH₃, -CH₂CH₂CH₂CH₂CH₂CH₃, -CH
(CH₃)₂, -CH (CH₃) CH₂CH₃, -CH₂CH (CH₃)₂, -CH₂C
(CH₃)₃, -CF₃, -CH₂CF₃, -CH₂CH₂CF₃, -CH₂CH₂CH₂CF₃, -CH = CH₂, -CH₂CH = CH₂, -CH₂C (CH₃) = CH₂, -CH₂C
H = C (CH₃)₂, -CH₂CH₂CH = CH₂, -CH₂CH₂C (CH₃) = CH ₂ , -CH₂CH₂CH = C (CH₃)₂, Cis-CH₂CH = CH (CH₃), C
is-CH₂CH₂CH = CH (CH₃), Trans-CH₂CH = CH (CH₃
), Trans-CH₂CH₂CH = CH (CH₃), -C≡CH, -CH₂C≡CH, -CH₂C≡C (CH₃), Cyclopropyl-, cyclobutyl-, cyclopentyl-, cyclohexyl-, cyclo
Clopropyl-CH₂-, Cyclobutyl-CH₂-, Cyclopentyl-CH₂-,
Cyclohexyl-CH₂-, Cyclopropyl-CH₂CH₂-, Cyclobutyl-C
H₂CH₂-, Cyclopentyl-CH₂CH₂-, Cyclohexyl-CH₂CH₂-,
Phenyl-, 2-F-phenyl-, 3-F-phenyl-, 4-F-phenyl-,
4-methoxyphenyl-, 4-ethoxyphenyl-, 4-propoxyphenyl-
, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) C
H₂-, (4-F-phenyl) CH₂-, (2-Cl-phenyl) CH₂-, (3
-Cl-phenyl) CH₂-, (4-Cl-phenyl) CH₂-, (2,3-diF-phenyl) CH₂-, (2,4-diF-phenyl) CH₂-, (
2,5-diF-phenyl) CH₂-, (2,6-diF-phenyl) CH₂-, (3
, 4-diF-phenyl) CH₂-, (3,5-diF-phenyl) CH₂-, (2
3-diCl-phenyl) CH₂-, (2,4-diCl-phenyl) CH₂-, (2
, 5-diCl-phenyl) CH₂-, (2,6-diCl-phenyl) CH₂-, (
3,4-diCl-phenyl) CH₂-, (3,5-diCl-phenyl) CH₂-,
(3-F-4-Cl-phenyl) CH₂-, (3-F-5-Cl-phenyl) C
H₂-, (3-Cl-4-F-phenyl) CH₂-, 2-furanyl-CH₂-, 3-furanyl-CH₂-, 2-thienyl-CH₂-3
-Thienyl-CH₂-, 2-pyridyl-CH₂-, 3-pyridyl-CH₂-, 4-
Pyridyl-CH₂-, 1-imidazolyl-CH₂-, 2-oxazolyl-CH₂−
, 4-oxazolyl-CH₂-, 5-oxazolyl-CH₂-, 3-isoxazo
Lil-CH₂-, 4-isoxazolyl-CH₂-, 5-isoxazolyl-CH ₂ -, Phenyl-CH₂CH₂-, (2-F-phenyl) CH₂CH₂-, (3-F-fe
Nil) CH₂CH₂-, (4-F-phenyl) CH₂CH₂-, (2-Cl-phenyl
Le) CH₂CH₂-, (3-Cl-phenyl) CH₂CH₂-, (4-Cl-phenyl
Le) CH₂CH₂-, (2,3-diF-phenyl) CH₂CH₂-, (2,4-diF-phenyl) CH₂
CH₂-, (2,5-diF-phenyl) CH₂CH₂-, (2,6-diF-phenyl
Le) CH₂CH₂-, (3,4-diF-phenyl) CH₂CH₂-, (3,5-di-F
-Phenyl) CH₂CH₂-, (2,3-diCl-phenyl) CH₂CH₂-, (2
, 4-diCl-phenyl) CH₂CH₂-, (2,5-diCl-phenyl) CH₂
CH₂-, (2,6-diCl-phenyl) CH₂CH₂-, (3,4-diCl-f
CH) CH₂CH₂-, (3,5-diCl-phenyl) CH₂CH₂-, (3-F
-4-Cl-phenyl) CH₂CH₂-, (3-F-5-Cl-phenyl) CH₂
CH₂-, Furanyl-CH₂CH₂-, Thienyl-CH₂CH₂-, Pyridyl-CH₂CH₂-,
1-Imidazolyl-CH₂CH₂-, Oxazolyl-CH₂CH₂-, Isoxazo
Lil-CH₂CH₂-, 3,5-dimethylisoxazol-4-yl-CH₂C
H₂-, Phenyl-propyl-, Benzyl-CH (NH₂)-, Benzyl-CH (NHC (= O) -O-tBu)
-, Benzyloxy-CH₂-, Pyrrolidin-2-yl-, or 3-t-but
Xycarbonylcarbonylpyrrolidin-2-yl- And

[0177]   R^FiveIs -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH (CH₃)₂,-
CH₂CH₂CH₂CH₃, -CH (CH₃) CH₂CH₃, -CH₂CH (CH₃)₂,
-CH₂C (CH₃)₃, -CH₂CH₂CH₂CH₂CH₃, -CH (CH₃) CH₂C
H₂CH₃, -CH₂CH (CH₃) CH₂CH₃, -CH₂CH₂CH (CH₃)₂,-
CH (CH₂CH₃)₂, -CF₃, -CH₂CF₃, -CH₂CH₂CF₃, -CH₂CH₂CH₂CF₃, -CH ₂ CH₂CH₂CH₂CF₃, -CH = CH₂, -CH₂CH = CH₂, -CH₂CH₂CH = CH₂, -CH = CH
CH₃, Cis-CH₂CH = CH (CH₃), Trans-CH₂CH = CH (C
H₃), Trans-CH₂CH = CH (C₆H_Five), -CH₂CH = C (CH₃)₂
, Cis-CH₂CH = CHCH₂CH₃, Trans-CH₂CH = CHCH₂C
H₃, Cis-CH₂CH₂CH = CH (CH₃), Trans-CH₂CH₂CH =
CH (CH₃), Trans-CH₂CH = CHCH₂(C₆H_Five), -C≡CH, -CH₂C≡CH, -CH₂C≡C (CH₃), -CH₂C≡C (C₆
H_Five), -CH₂CH₂C≡CH, -CH₂CH₂C≡C (CH₃), -CH₂CH₂C
≡ C (C₆H_Five), -CH₂CH₂CH₂C≡CH, -CH₂CH₂CH₂C≡C (CH ₃ ), -CH₂CH₂CH₂C≡C (C₆H_Five), Cyclopropyl-CH₂-, Cyclobutyl-CH₂-, Cyclopentyl-CH₂−
, Cyclohexyl-CH₂-, (2-CH₃-Cyclopropyl) CH₂-, (3-
CH₃-Cyclobutyl) CH₂-, Cyclopropyl-CH₂CH₂-, Cyclobutyl
-CH₂CH₂-, Cyclopentyl-CH₂CH₂-, Cyclohexyl-CH₂CH₂ -, (2-CH₃-Cyclopropyl) CH₂CH₂-, (3-CH₃-Cyclobutyl
) CH₂CH₂-, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) CH ₂ -, (4-F-phenyl) CH₂-, (3,5-diF-phenyl) CH₂-2
-Furanyl-CH₂-, 3-furanyl-CH₂-, 2-thienyl-CH₂-, 3-
Thienyl-CH₂-, 2-pyridyl-CH₂-, 3-pyridyl-CH₂-, 4-pi
Lysyl-CH₂-, 1-imidazolyl-CH₂-, 2-oxazolyl-CH₂-,
4-oxazolyl-CH₂-, 5-oxazolyl-CH₂-, 3-isoxazoli
Le-CH₂-, 4-isoxazolyl-CH₂-, 5-isoxazolyl-CH₂
-, Phenyl-CH₂CH₂-, (2-F-phenyl) CH₂CH₂-, (3-F-fe
Nil) CH₂CH₂-, (4-F-phenyl) CH₂CH₂-, Furanyl-CH₂C
H₂-, Thienyl-CH₂CH₂-, Pyridyl-CH₂CH₂-, 1-Imidazolyl
-CH₂CH₂-, Oxazolyl-CH₂CH₂-, Isoxazolyl-CH₂CH₂ -, Methoxy, ethoxy, propoxy, or butoxy And   R^5aIs H,   Or R^FiveAnd R^5aTogether, cyclopentyl, cyclohexyl
Or it can form cycloheptyl;   W is a bond, -CH₂-, Or -CH (CH₃) -Is;   X is a bond,

[0178]

[Chemical 30]

[0179] And   Y is a bond, -CH₂-V-, -V-, or -V-CH₂-Is;   V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O).
)₂-, -NH-, or -N (CH₃) -Is;   Z is H, F, Cl, Br, methyl, ethyl, n-propyl, i-propyl,
n-butyl, i-butyl, s-butyl, t-butyl, Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl
-Phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl
2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl
3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCl-phen
Nyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl
-Phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-
4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Cl-4-F-phenyl
2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2
-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl
Phenyl, 3-MeS-phenyl, 4-MeS-phenyl, 2-CF₃O-pheny
Le, 3-CF₃O-phenyl, 4-CF₃O-phenyl, Furanyl, thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl, 4
-Me-pyridyl, l-imidazolyl, oxazolyl, isoxazolyl, 1-
Benzimidazolyl, morpholino, N-piperidinyl, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) CH ₂ -, (4-F-phenyl) CH₂-, (2-Cl-phenyl) CH₂-, (3-
Cl-phenyl) CH₂-, (4-C1-phenyl) CH₂-, (2,3-di-F-
Phenyl) CH₂-, (2,4-diF-phenyl) CH₂-, (2,5-di-F-f
CH) CH₂-, (2,6-diF-phenyl) CH₂-, (3,4-diF-fe
Nil) CH₂-, (3,5-diF-phenyl) CH₂-, (2,3-diCl-phen
Nil) CH₂-, (2,4-diCl-phenyl) CH₂-, (2,5-diCl-f
CH) CH₂-, (2,6-diCl-phenyl) CH₂-, (3,4-diCl-
Phenyl) CH₂-, (3,5-diCl-phenyl) CH₂-, (3-F-4-C
l-phenyl) CH₂-, (3-F-5-Cl-phenyl) CH₂-, (3-Cl
-4-F-phenyl) CH₂-, (2-MeO-phenyl) CH₂-, (3-Me
O-phenyl) CH₂-, (4-MeO-phenyl) CH₂-, (2-PhO-F
CH) CH₂-, (3-PhO-phenyl) CH₂-, (4-PhO-phenyl
) CH₂-, (2-Me-phenyl) CH₂-, (3-Me-phenyl) CH₂−
, (4-Me-phenyl) CH₂-, (2-MeS-phenyl) CH₂-, (3-
MeS-phenyl) CH₂-, 4-MeS-phenyl) CH₂-, (2-CF₃O
-Phenyl) CH₂-, (3-CF₃O-phenyl) CH₂-, (4-CF₃OF
CH) CH₂-, (Furanyl) CH₂-, (Thienyl) CH₂-, (Pyridyl)
CH₂-, (2-Me-pyridyl) CH₂-, (3-Me-pyridyl) CH₂-,
(4-Me-pyridyl) CH₂-, (1-imidazolyl) CH₂-, (Oxazoli
Le) CH₂-, (Isoxazolyl) CH₂-, (1-benzimidazolyl) CH ₂ -, (Cyclopropyl) CH₂-, (Cyclobutyl) CH₂-, (Cycloplier
Le) CH₂-, (Cyclohexyl) CH₂-, (Morpholino) CH₂-, (N-pi
Peridinyl) CH₂-, Phenyl-CH₂CH₂-, (Phenyl)₂CHCH₂-, (2-F-phenyl) C
H₂CH₂-, (3-F-phenyl) CH₂CH₂-, (4-F-phenyl) CH₂
CH₂-, (2-Cl-phenyl) CH₂CH₂-, (3-Cl-phenyl) CH₂ CH₂-, (4-Cl-phenyl) CH₂CH₂-, (2,3-diF-phenyl)
CH₂CH₂-, (2,4-diF-phenyl) CH₂CH₂-, (2,5-di-F-f
CH) CH₂CH₂-, (2,6-diF-phenyl) CH₂CH₂-, (3,4-
Di-F-phenyl) CH₂CH₂-, (3,5-diF-phenyl) CH₂CH₂-, (
2,3-diCl-phenyl) CH₂CH₂-, (2,4-diCl-phenyl) CH ₂ CH₂-, (2,5-diCl-phenyl) CH₂CH₂-, (2,6-diCl-f
CH) CH₂CH₂-, (3,4-diCl-phenyl) CH₂CH₂-, (3,5
-DiCl-phenyl) CH₂CH₂-, (3-F-4-Cl-phenyl) CH₂C
H₂-, (3-F-5-Cl-phenyl) CH₂CH₂-, (3-Cl-4-F-
Phenyl) CH₂CH₂-, (2-MeO-phenyl) CH₂CH₂-, (3-Me
O-phenyl) CH₂CH₂-, (4-MeO-phenyl) CH₂CH₂-, (2-
Me-phenyl) CH₂CH₂-, (3-Me-phenyl) CH₂CH₂-, (4-
Me-phenyl) CH₂CH₂-, (2-MeS-phenyl) CH₂CH₂-, (3
-MeS-phenyl) CH₂CH₂-, (4-MeS-phenyl) CH₂CH₂-,
(2-CF₃O-phenyl) CH₂CH₂-, (3-CF₃O-phenyl) CH₂C
H₂-, (4-CF₃O-phenyl) CH₂CH₂-, (Furanyl) CH₂CH₂-,
(Thienyl) CH₂CH₂-, (Pyridyl) CH₂CH₂-, (2-Me-pyridyl
) CH₂CH₂-, (3-Me-pyridyl) CH₂CH₂-, (4-Me-pyridyl
) CH₂CH₂-, (Imidazolyl) CH₂CH₂-, (Oxazolyl) CH₂CH₂ -, (Isoxazolyl) CH₂CH₂-, (Benzimidazolyl) CH₂CH₂−
, (Cyclopropyl) CH₂CH₂-, (Cyclobutyl) CH₂CH₂-, (Cyclo
Pentyl) CH₂CH₂-, (Cyclohexyl) CH₂CH₂-, (Morpholino) C
H₂CH₂-, Or (N-piperidinyl) CH₂CH₂− And

R ¹¹ is, in each occurrence, H, methyl, ethyl, n-propyl, i-
Propyl, n-butyl, i-butyl, s-butyl, t-butyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, 2-F- phenyl -, 3-F- phenyl, 4-F- phenyl, 4-Cl @ - phenyl, 4-CH ₃ - phenyl, 4-MeO- phenyl -, 4-CF ₃ - phenyl,
(4-F- _{phenyl) CH 2 -, (4-} C1- _{phenyl) CH 2 -, (4-} CH 3
- _{phenyl) CH 2 -, (4-} CF 3 - _{phenyl) CH 2 -, (4-} F- _{phenyl) CH 2 CH 2 -, (} 4-C1- _{phenyl) CH 2 CH 2 -, (} 4-CH 3 - _{phenyl) CH 2 CH 2 -, (} 4-CF 3 - phenyl) CH ₂ CH ₂ -, pyridin-2-yl -, pyridin-3-yl -, 4-CF ₃ - yl - 4 -CH ₃ -
Pyridin-2-yl-, thiazol-2-yl-, azapan-1-yl, N, N
-Independently selected from dimethylamino, N, N-diethylamino, N, N-dipropylamino, and N, N-dibutylamino; and

R ¹³ in each occurrence is independently selected from H, MeO, F and Cl.

[0182]   [18] In a preferred embodiment, the present invention provides compounds of formula (If):

[0183]

[Chemical 31]

[0184] Alternatively, it provides a pharmaceutically acceptable salt form or prodrug thereof.

[0185]   [19] In a preferred embodiment, the present invention provides compounds of formula (Ig):

[0186]

[Chemical 32]

[0187] Alternatively, it provides a pharmaceutically acceptable salt form or prodrug thereof.

[0188]   [20] In a preferred embodiment, the present invention provides compounds of formula (Ih):

[0189]

[Chemical 33]

[0190] Alternatively, it provides a pharmaceutically acceptable salt form or prodrug thereof.

In another preferred embodiment, the invention provides all embodiments disclosed herein, provided that R ⁵ and R ^5a are not H at the same time.

[0192]   In another preferred embodiment, the invention provides that Q is 0, 1 or 2 R ^1a When it is a 9-membered benzo-fused heterocyclic group substituted by³Is H
All embodiments disclosed herein are provided subject to and.

In another preferred embodiment, the invention provides that when —WXYZ is a tertiary butyl group and R ⁵ is either C ₁ -C ₄ alkyl or C ₂ alkenyl, then Q is
Provided are all embodiments disclosed herein, provided that they are not phenyl substituted with 0, 1, or 2 R ^1a .

In another preferred embodiment, the invention provides that when R ⁵ is C ₁ -C ₃ alkyl, then Q is not phenyl substituted with 0, 1 or 2 R ^1a. All embodiments disclosed herein are provided.

[0195]   In another preferred embodiment, the present invention provides the following moieties after formula (I):

[0196]

[Chemical 34]

Is C ₁ -C ₈ alkyl, C ₂ -C ₈ alkenyl, C ₂ -C ₈ alkynyl, C ₃ -C _10.
Cycloalkyl -C ₁ -C ₄ alkyl, C ₃ -C ₁₀ cycloalkyl, C ₁ -C ₄ alkyl -O-C _{1 ~C 4} alkyl, C ₁ -C ₄ alkyl -S-C _{1 ~C 4} alkyl, C ₂
-C ₄ alkyl -NR ²⁰ -C ₂ ~C ₄ alkyl, C ₂ -C ₄ alkyl -C ₆ -C ₁₀ aryl, C ₂ -C ₄ alkyl -C ₆ -C ₁₀ cycloalkyl, C ₂ -C ₈ alkenyl , C ₆ -C ₁₀ aryl -C ₁ -C ₄ alkyl, C ₆ -C ₁₀ aryl -C ₂ -C ₄ alkynyl, indol-3-yl -C ₁ -C ₃ alkyl, and imidazol-4-yl -
Provided are all embodiments disclosed herein, provided that they are not C ₁ -C ₃ alkyl, in which case all alkyl groups are replaced with OH.

In a second embodiment, the invention provides a pharmaceutical composition comprising a compound of formula (I) and a pharmaceutically acceptable carrier.

In a third embodiment, the invention provides a method for treating a neurological disorder associated with β-amyloid production. This method involves administering to a host in need of such treatment a therapeutically effective amount of a compound of formula (I).

In a preferred embodiment, the neurological disorder associated with β-amyloid production is Alzheimer's disease.

In a fourth embodiment, the invention provides a method for inhibiting the activity of γ-secretase for treating a physiological disorder associated with inhibiting the activity of γ-secretase. This method involves administering to a host in need of such inhibition a therapeutically effective amount of a compound of formula (I) which inhibits the activity of γ-secretase.

In a preferred embodiment, the physiological disorder associated with inhibiting the activity of γ-secretase is Alzheimer's disease.

In a fifth embodiment, the invention provides compounds of formula (I) for use in therapy.

In a preferred embodiment, the present invention provides compounds of formula (I) for use in treating Alzheimer's disease.

In a sixth embodiment, the present invention provides the use of a compound of formula (I) for the manufacture of a medicament for treating Alzheimer's disease.

Definitions As used herein, the term “Aβ” refers to Aβ, β amyloid peptide,
And sometimes it means the protein called β / A4 in this field. Aβ is found in the walls of amyloid plaques, meningeal and parenchymal arterioles, arterioles, capillaries, and sometimes venules, about 4 to about 43 amino acids in length.
． It is a 2 kilodalton (kD) protein. Its isolation and sequence data for the first 28 amino acids is described in US Pat. No. 4,666,829. The sequence of 43 amino acids is shown below:

[0207] 1 Asp Ala Glu Phe Arg His Asp Ser Gly Tyr 11 Glu Val His His Gln Lys Leu Val Phe Phe twenty one Ala Glu Asp Val Gly Ser Asn Lys Gly Ala 31 Ile Ile Gly Leu Met Val Gly Gly Val Val 41 Ile Ala Thr

The term “APP” as used herein refers to the protein known in the art as β-amyloid precursor protein. This protein is a precursor of Aβ and is processed into Aβ by the activity of the “secretase” enzyme used herein. Although various secretase enzymes are known in the art, they are β secretases that give rise to the N-terminus of Aβ, one within Aβ.
Α-secretase cleaving near the 6/17 peptide bond and a C-terminal Aβ fragment ending at positions 38, 39, 40, 42 and 43, or subsequently truncated to the polypeptide It is called γ-secretase (as used herein) that gives rise to a C-terminal extended precursor.

The compounds described herein may have asymmetric centers. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. Methods for preparing optically active forms are well known in the art and are performed, for example, by resolution of racemates or by synthesis from optically active starting materials. Olefins, C = N double bonds and many other geometric isomers may also be present in the compounds described herein. All such stable isomers are included in the present invention. The cis and trans geometric isomers of the compounds of the present invention have been described and these can be isolated as a mixture of isomers or as separated isomers. All chiral, diastereomeric, racemic forms and all geometric isomers of a structure are intended, unless the specific stereochemistry or isomer is specifically indicated.

The term “substituted,” as used herein, does not exceed the usual valency of the designated atoms, and when the substitution results in a stable compound. It means that any one or more hydrogens present on the designated atom are replaced by one selected from the group shown. When a substituent is keto (ie, = 0), then 2 hydrogens present on the atom are replaced.

When any variable (eg, R ^1a , R ^4a , R ^13, etc.) occurs more than one time in any constituent or chemical formula of a compound, its definition at each occurrence is different from that of any other occurrence. It is independent of its definition in its location. Thus, for example, if a group is shown to be substituted with 0-3 R ^1a , that group may be optionally substituted with up to 3 R ^1a groups, and R ^{1a at} each position is selected independently from the definition of R ^1a . Also, combinations of substituents and / or variables are possible only if the combinations result in stable compounds.

If a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any ring atom. When a substituent is described in the rest of the compounds of the indicated formula without indicating the atom to which the substituent is attached, then such substituent is attached through any atom within the substituent. can do. Combinations of substituents and / or variables are possible only if such combinations result in stable compounds.

As used herein, “alkyl” or “alkylene” shall include both branched and straight chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. For example, "C ₁ -C ₆ alkyl" denotes alkyl having 1 to 6 carbon atoms. Examples of alkyl include methyl, ethyl, n-propyl, i
-Propyl, n-butyl, i-butyl, sec-butyl, t-butyl, pentyl and hexyl, but are not limited thereto. Preferred "alkyl" group is a "C ₁ -C ₄ alkyl" include methyl, ethyl, n- propyl, i- propyl, n- butyl and i- butyl are particularly preferred. As used herein
It is understood that “C ₁ -C ₃ alkyl” specifically includes both branched and straight chain methyl, ethyl and propyl, even though it is a terminal substituent or an alkylene group linking two substituents. It

[0214]   As used herein, “alkenyl” or “alkenylene” is a straight chain
Hydrocarbon chains, in either straight or branched form, and at any stable point along the chain.
It is intended to include one or more unsaturated carbon-carbon bonds that may be present. "C ₂ ~ C₆Examples of "alkenyl" include ethenyl, 1-propenyl, 2-propenyl, 1
-Butenyl, 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 2-pethyl
Include, but are not limited to, montenyl, 3-pentenyl, hexenyl, and the like.
Yes.

As used herein, “alkynyl” or “alkynylene” refers to a hydrocarbon chain, either straight or branched, and at any stable point along the chain. And one or more possible carbon-carbon triple bonds. For example,
Ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3
-Butynyl and the like are included.

“Alkoxy” or “alkyloxy” represents an alkyl group as defined above with the indicated number of carbon atoms attached through an oxygen bridge. Examples of alkoxy are:
Includes, but not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy and s-pentoxy. Preferred alkoxy groups are methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy.
Similarly, "alkylthio" or "thioalkoxy" represent an alkyl group as defined above with the indicated number of carbon atoms attached through a sulfur bridge.

“Halo” or “halogen” as used herein refers to fluoro, chloro, bromo or iodo. Preferred halos are fluoro and chloro unless otherwise indicated. "Counterion" is used to describe a small negatively charged species such as chloride, bromide, hydroxide, acetate, sulfate.

“Haloalkyl” means both branched and straight chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms and substituted with one or more halogens (eg,
-C _v F _w , where v = 1 to 3 and w = 1 to (2v + 1)).
Examples of haloalkyl include trifluoromethyl, trichloromethyl, pentafluoroethyl, pentachloroethyl, 2,2,2-trifluoroethyl, 2,2-difluoroethyl, heptafluoropropyl and heptachloropropyl, It is not limited to these. “Haloalkoxy” shall mean a haloalkyl group as defined above with the indicated number of carbon atoms attached through an oxygen bridge. For example, trifluoromethoxy, pentafluoroethoxy, 2,2,2-trifluoroethoxy and the like. “Halothioalkoxy” shall mean a haloalkyl group as defined above with the indicated number of carbon atoms attached through a sulfur bridge.

“Cycloalkyl” shall include saturated cyclic groups having the specified number of carbon atoms. For example, "C ₃ -C ₆ cycloalkyl" refers to cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

As used herein, “carbocycle” shall mean any stable 3- to 7-membered monocyclic or bicyclic or 7- to 13-membered bicyclic or tricyclic ring. To do. All of these may be saturated or partially unsaturated or aromatic. Examples of such carbocycles are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl, [3.3.0] bicyclooctane, [4.3.0] bicyclononane, [4.4]. .0] bicyclodecane (decalin), [2.2.2] bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl or tetrahydronaphthyl (tetralin), but are not limited thereto. "C ₃
Preferred examples of -C ₁₀ carbocycle "or" C ₃ -C ₆ carbocycle "is a C ₃ -C ₆ cycloalkyl, specifically cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

As used herein, the term “heterocycle” or “heterocycle” means saturated,
Partially unsaturated or unsaturated (aromatic) and carbon atoms and 1, 2, 3 or 4 heteroatoms (independently selected from the group consisting of N, O and S Preferably a stable 5 member consisting of 1, 2 or 3 heteroatoms)
A 7-membered monocyclic or bicyclic ring or a 7- to 14-membered bicyclic or tricyclic ring is meant. This includes any bicyclic group in which any of the heterocyclic groups defined above is fused to a benzene ring. The nitrogen and sulfur heteroatoms can be optionally oxidized. The heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. The heterocyclic groups described herein can be substituted at carbon or nitrogen atoms if the resulting compound is stable. Where indicated, the nitrogen within the heterocycle can be quaternized if desired. If the total number of S and O atoms in the heterocycle exceeds 1, then it is preferred that these heteroatoms are not adjacent to one another. The total number of S and O atoms in the heterocycle is preferably 1 or less.

Examples of heterocycles include, but are not limited to: 1H-indazole, 2-pyrrolidonyl, 2H, 6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl, 4 -Piperidonyl, 4aH-carbazole, 4H-quinolidinyl, 6H-1,2,5-thiadiazinyl, acridinyl, azocinyl,
Benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, benttetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolonyl, carbazolyl, 4aH -Carbazolyl, b-carbolinyl, chromanyl,
Chromenyl, cinnolinyl, decahydroquinolinyl, 2H, 6H-1,5,2-
Jichiajiniru, dihydrofuro [2,3-b] tetrahydrofuran, furanyl, furazanyl, homopiperidinyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl , Isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2
, 5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl,
Oxazolyl, oxazolidinyl perimidinyl, phenanthridinyl, phenanthrolinyl, phenalsazinyl, phenazinyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, piperidinyl, 4-piperidonyl, pteridinyl, Purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridoxazole, pyridoimidazole, pyridothiazole, pyridinyl,
Pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolidinyl, quinoxalinyl, quinuclidinyl, carborinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiadinyl, 1, 2,3-thiadiazolyl,
1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,2
3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1
, 3,4-triazolyl, xanthenyl. Preferred 5- to 10-membered heterocycles include
Pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl,
Pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, tetrazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, 1H-indazolyl, oxazolidinyl, isoxazolidinyl, benzotriazolyl, benzisoxazolyl, oxyindolyl, Includes, but is not limited to, benzoxazolinyl, quinolinyl and isoquinolinyl.
Preferred 5- to 7-membered heterocycles include pyridinyl, pyrimidinyl, triazinyl,
It includes but is not limited to furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, tetrazolyl. More preferred 5- to 7-membered heterocycles include pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl,
Includes, but is not limited to, imidazolyl and tetrazolyl. Preferred 5- to 6-membered heterocycles include, but are not limited to, pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, tetrazolyl. Also included are fused rings, eg, fused rings containing the above heterocycles.

The terms “aryl”, “C ₆ -C ₁₀ aryl” or aromatic residue, as used herein, shall mean an aromatic moiety containing the specified number of carbon atoms. To do. Examples include phenyl, pyridinyl or naphthyl. Unless otherwise indicated, "aryl" may be unsubstituted or H, OH, O.
CH ₃ , Cl, F, Br, I, CN, NO ₂ , NH ₂ , N (CH ₃ ) H, N (CH ₃
) ₂ , CF ₃ , OCF ₃ , C (= O) CH ₃ , SCH ₃ , S (= O) CH ₃ , S (= O)
_{) 2 CH 3, CH 3,} CH 2 CH 3, 0 or is selected from CO ₂ H and CO ₂ CH ₃ ~
It can be substituted with 3 groups.

The expression “additional lactam carbon” as used herein shall mean the number of optional carbon atoms in the lactam ring B of formula (I). The following formula (Ia)
Represents a lactam ring B of formula (I):

[0225]

[Chemical 35]

Further lactam carbons are carbons within the lactam ring B other than the carbons numbered 2 and 3 in the chemical formula skeleton. This further lactam carbon may be optionally replaced by a heteroatom selected from oxygen, nitrogen and sulphur.
The lactam ring B has 1, 2, 3, 4, 5 so that the total number of constituent atoms of the lactam ring B including the atoms numbered 1, 2, and 3 in the skeleton does not exceed 10. , 6 or 7 optional carbons, and in this case one optional carbon may be optionally replaced by a heteroatom. The total number of atoms of the lactam ring B is preferably 6, 7 or 8. It is more preferable that the total number of atoms of the lactam ring B is 7. Examples of lactam ring B are shown below without limiting the invention:

[0227]

[Chemical 36]

Preferred examples of lactam ring B are B1, B2, B5, B6, B8, B9, B13 and B16. More preferred examples of the lactam ring B are B1, B6, B8 and B9.
And B13. Preferred examples of the substituent R ¹⁰ or the substituent R ¹¹ in the lactam B are methyl, ethyl, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-trifluorophenyl, (4-fluorophenyl) methyl, (4-chlorophenyl). ) Methyl and (4-trifluorophenyl) methyl. Preferred examples of the substituent R ¹³ on the condensed ring of lactam B are methyl, fluoro and chloro.

The compounds described herein may have asymmetric centers. One enantiomer of the compound of formula (I) may exhibit superior biological activity than the opposite enantiomer. For example, lactam ring B carbon 3 of formula (I ″) may be present in either the S or R configuration. Therefore, carbon 3 in formula (I ″)
The S or R configurations at are considered part of this invention. An example of such an arrangement is shown below, but is not limited to this example of ring B:

[0230]

[Chemical 37]

If desired, separation of racemates can be accomplished by methods known in the art. Further, the carbon atom to which OH and R ⁵ are attached, may represent a chiral carbon may display superior biological activity than enantiomer of the opposite side.
For example, if Q and R ⁵ are not H, then the arrangement of these two centers is (2R, 3R
), (2R, 3S), (2S, 3R) or (2S, 3S). All of these arrangements are considered part of this invention. However, (2R, 3S) and (2S, 3R) are preferred, and (2R, 3S) is more preferred.

The expression “pharmaceutically acceptable” refers, within the scope of sound medical judgment, to human and animal tissues without undue toxicity, irritation, allergic response or other problems or complications. Used herein to indicate such compounds, substances, compositions and / or dosage forms suitable for use in contact and corresponding to a reasonable benefit / risk ratio. .

As used herein, "pharmaceutically acceptable salt" refers to a derivative of the disclosed compound in which the parent compound has been modified by making its acid or base salts. Examples of pharmaceutically acceptable salts include mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. Not limited to. Pharmaceutically acceptable salts include, for example:
Included are conventional non-toxic salts or quaternary ammonium salts of the parent compound which are formed from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include salts derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid; as well as acetic acid, propionic acid, succinic acid, glycolic acid, Stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, pamoic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, sulfanilic acid, 2-acetoxybenzoic acid, fumaric acid, toluene sulfone Included are salts prepared from organic acids such as acids, methanesulfonic acid, ethanedisulfonic acid, oxalic acid, isethionic acid.

The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic residue by conventional chemical methods. Generally, such salts will react the free acid or free base form of these compounds with a stoichiometric amount of a suitable base or acid in water or an organic solvent, or a mixture of the two. A non-aqueous medium such as ether, ethyl acetate, ethanol, isopropanol or acetonitrile is generally preferred. A list of suitable salts is Remington's Pharmace
optical Sciences, 17th Edition (Mack Publishing)
Company, Easton, PA, 1985, page 1418) (the disclosure of which is hereby incorporated by reference).

“Prodrug” is intended to include any covalently bonded carrier that releases the effective parent drug according to formula (I) in vivo when the prodrug is administered to a mammalian subject. Prodrugs of compounds of formula (I) are prepared by modifying the functional groups present on the compound in such a way that the modification is cleaved to the parent compound either by routine manipulation or in vivo. . Prodrugs are cleaved to form a free hydroxyl group, a free amino group, or a free sulfhydryl group, respectively, when the prodrug or compound of formula (I) is administered to a mammalian subject. Optional groups include compounds of formula (I) to which a hydroxyl, amino or sulfhydryl group is attached. Examples of prodrugs include, but are not limited to, acetic acid derivatives, formic acid derivatives and benzoic acid derivatives of alcohol and amine functional groups present in compounds of formula (I).

“Stable compound” and “stable structure” refer to a compound which is isolated from a reaction mixture to a useful degree of purity and which has sufficient strength to withstand incorporation into an effective therapeutic agent. means.

Synthesis The compounds of this invention can be prepared in a number of ways well known to those skilled in the art of organic synthesis. The compounds of the present invention may be synthesized using the methods described below, along with synthetic methods known in the field of synthetic organic chemistry, or variations thereof as understood by those of skill in the art. You can Preferred methods include, but are not limited to, those described below. All references cited herein are incorporated by reference in their entirety.

The novel compounds of this invention can be prepared using the reactions and techniques described in this section. These reactions are appropriate for the reagents and materials used,
And in a solvent suitable for the transformation to be performed. Also, in the description of the synthetic methods described below, all reaction conditions mentioned, including solvent selection, reaction atmosphere, reaction temperature, experimental duration and work-up procedure, are standard conditions for the reaction. Must be understood that This should be easily recognized by those skilled in the art. It will be appreciated by those skilled in organic synthesis that functional groups present in various parts of the molecule must be compatible with the reagents and reactions described. Such limitations on the substituents that are compatible with the reaction conditions will be readily apparent to those skilled in the art, and in such cases alternative methods must be used.

[0239]

[Chemical 38]

Aldol derivatives are prepared according to the Evans procedure (DA Evans et al., Org. Sy.
nth. 1990, 68, 83-90). this is,
Acylation of the oxazolidinone with an acid chloride yields structure 2 outlined in Scheme 1. Asymmetric aldol reaction to obtain 3, then
Cleavage of the chiral auxiliary yields β-hydroxycarboxylic acid 4. Further examples can be found in D.W. A. Evans, Aldrichimica Acta
, 1982, 15, 23-32. An alternative synthesis of structure 4 is described by Cri
The method of Mmins (MT Crimmins et al., J. Am. Chem. Soc
． 1997, 119, 7883-7884), the method of Paterson (IP
Aterson et al., Org. React. 1997, 51, 1-200) and the method of Mukaiyama (T. Mukaiyama et al., Org. React.
1994, 1-104). anti-aldol is (a) A. K. Ghosh, J .; Am. Chem. Soc. 1996, 11
8, 2527-2528, or (b) S. Masamune et al., J. Am. C
hem. Soc. It can be synthesized according to 1997, 119, 2586.

[0241]

[Chemical Formula 39]

The carboxylic acid of formula 4 is prepared from A. R. Chamberlin, Chem. Rev. 1
997, 97, 2243-2266, DCC, EDC,
Methods commonly used in peptide synthesis such as CDI, BOP, PyBOP, HATU, HBTU and phenyl ester mediated couplings can be used to couple to the appropriate lactam intermediates. Compound 6 catalyzes acid 4 to 3-under the catalysis of EDC and HOBt to give final compound 6.
Coupling with amino-1,4-benzodiazepin-2-one 5 is synthesized as illustrated in Scheme 2 (S. Nozaki et al., Bu.
ll. Chem. Soc. Jpn. 1982, 55, 2165 to 2168).

Similarly, Schemes 2a and 2b illustrate the synthesis of bisbenzodiazepine and lactam compounds of the invention:

[0244]

[Chemical 40]

A variety of synthesizing lactam intermediates as contemplated by this invention useful in the synthesis of compounds of formula (I) containing various aminobenzodiazepinones, dibenzazepinones and other related heterocycles. Methods are known in the art, and PCT International Patent Publications WO 98/28268, WO 99/66934, W.
It is disclosed in numerous references including O00 / 07995 and WO00 / 38618, which are hereby incorporated by reference. Further references include Bock et al. Org. Chem. , 1987, 52, 3232-3.
239; Sherill et al. Org. Chem. , 1995, 60, 73
0-734; Walsh, D .; A. , Synthesis, September 1980, 6
77; Brown et al., Tetrahedron Letters, 1971,
8, 667 to 670 are included.

Synthetic methods for obtaining various aminobenzodiazepines have been extensively described in the literature and are well known to those skilled in the art. Exemplary methods are illustrated in the following references, but not limited to: (A) M. G. Bock et al., J. Org.
Chem. , 1987, 52, 3232; (b) R.I. G. Sherrill et al.,
J. Org. Chem. 1995, 60, 734; (c) M.M. G. Bock et al., J. Med. Chem. , 1989, 32, 13-16; (d) J. L. Ca
stro et al., J. Med. Chem. , 1997, 40, 2491 to 2501;
(E) M. S. Chambers et al., Bioorg. & Med. Chem. Le
tt. 1993, 3 (10), 1919-1924; H. Goge
rty et al. Med. Chem. , 1977, 20 (7), 952; (g) G.
． Simple et al., Bioorg. & Med. Chem. Lett. , 1996
, 6 (1), 51-54; (h) G.I. Simple et al., J. Med. Chem.
, 1997, 40, 331-341; (i) G.I. Sample et al., Bioorg
． & Med. Chem. Lett. , 1996, 6 (1), 55-58; (j).
G. Simple et al., Synth. Commun. , 1996, 26 (4), 7
21-727; and (k) G. A. Showell et al. Med. Chem
． , 1994, 37, 719-721. For a general synthetic description of 2-aminobenzophenones with various substitutions used in the preparation of benzodiazepines, see D. A. Walsh, Synthesis, 1980, 67
See 7.

[0247]

[Chemical 41]

The preparation of the aldehyde Q-CHO having the general structure of 9 is shown in Scheme 3 (
H. C. Arndt, Synthesis, 1979, 202-204). Allyl ether 8 can be made from the action of alkoxides obtained in DMF with allyl bromide and converted to α-alkoxy aldehydes or aryloxy aldehydes 9 using two-phase osmium tetroxide oxidation. It

[0249]

[Chemical 42]

As shown in Scheme 4, an aldehyde QC having a general structure of 12
HO can be prepared in the same manner from the corresponding allyl benzyl ether. This is because P. The procedure described by P. Kocienski (P. Kocien
ski, Tetrahedron, 1990, 46, 1767-1782).

The aldehydes used in Scheme 1 are either commercially available or prepared from commercially available alcohols or readily available alcohols, or from commercially available carboxylic acids or readily available carboxylic acids. For preparing other non-commercially available aldehydes from commercially available or readily available alcohols by oxidizing the corresponding alcohols, (
a) S. V. Ley et al., Synthesis, 1994, 639; (b) D. S
wern, Synthesis, 1981, 165-185; and (c) R.S.
C. Larock, Comprehensive Organic Trans
formations, Wiley-VCH, 1989, pp. 604-614. For the preparation of other non-commercially available aldehydes from commercially available or readily available carboxylic acids by reduction of the corresponding Weinreb amides or reduction of carboxylic acid derivatives, see (a) S. M. Wein
reb et al., Tetrahedron Lett. 1981, 22, 3815-3
818; (b) M.I. Braun, Synthesis, 1989, 856; and (c) D. A. Evans, J .; Org. Chem. 1993, 58, 244
See 6-2453.

The amino aldehydes used in the synthesis of the compounds of the present invention can be prepared by oxidation of the corresponding amino alcohol or reduction of the corresponding amino acid; Jurczak et al., Synlett, 1993, 241; and (b) S. et al. G. See Davis et al., Synlett, 1995, 700.

Sulfur-containing aldehydes used in the synthesis of compounds of the present invention are α, β-
It can be made by the conjugated addition of thiols to unsaturated aldehydes or the reaction of thiols with halo-substituted aldehydes. T. Cohen et al. Org. Ch
em. 1995, 60, 2022; Tetrahedron, 1994, 50,
12793-12810; Org. Chem. 1992, 57, 6; Pho
sporus, Sulfur, and Silicon, 1993, 74, 1
And Tetrahedron, 1994, 50, 11569-11584.

Sulfoxides and sulfones are prepared from the corresponding sulfides by oxidation. M. Hudlicky, Oxidations in Organic
See Chemistry, ACS, 1990, pp. 250-264.

The acid chlorides used in Scheme 1 are either commercially available or are prepared from commercially available or readily available carboxylic acids by the action of oxalyl chloride or thionyl chloride. R. C. Larock, Comprehe
nsi Organic Transformations, Wiley-
VCH, 1989, pages 963-964.

EXAMPLES Abbreviations for chemicals used in this example are defined as follows: "D
"MPU" is 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidone; "TBTU" is O- (1H-benzotriazol-1-yl).
-N, N, N ', N'-tetramethyluronium tetrafluoroborate; "BOP" is benzotriazol-1-yloxytris-dimethylamino)
Phosphonium hexafluorophosphate; "Bu ₂ BOTf" is dibutylboron triflate; "EDC" is 1- [3- (dimethylamine) propyl] -3-ethylcarbodiimide hydrochloride; "HOBt" is 1 -Hydroxybenzotriazole; and "TEA" is triethylamine.

“HPLC” is an abbreviation used herein for high performance liquid chromatography. The compounds of the invention are generally purified by HPLC using conditions known to those skilled in the art. However, the following conditions are generally applicable, unless otherwise indicated. Reversed phase HPLC was performed on Vydac C-18 with a gradient elution of buffer B from 10% to 100% in buffer A.
It can be carried out using a column (buffer A: water containing 0.1% trifluoroacetic acid, buffer B: 10% water, 90% containing 0.1% trifluoroacetic acid).
Acetonitrile). Alternatively, reverse-phase HPLC can be used with 1% acetonitrile in water.
It can be performed using a Vydac C-18 column with a gradient elution from 0% to 100%.

Example 1 3- (2 (R) -Cyclopentylmethyl-3 (S) -hydroxyl-1-oxo-5-phenylpentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H -1,4-benzodiazepin-2-one (R) -3- (3-cyclopentyl-1-oxopropyl) -4- (phenylmethyl) -2-oxazolidinone (2)

[0259]

[Chemical 43]

A dried round bottom flask was charged with (R) -4- (phenylmethyl) -2-oxaziridinone (1, 17.7 g, 0.100 mol). Then anhydrous tetrahydrofuran (300 mL) was added and the solution was cooled to -78 ° C. 1 solution of butyllithium (42.0 mL, 0.105 mol, 2.50 M in hexane)
Add to reaction flask over 0 minutes. After a few minutes, 3-cyclopentylpropionyl chloride (16.8 mL, 0.110 mol) was added. The resulting solution was -78 ° C for 3
Stirred for 0 minutes then warmed to ambient temperature over 30 minutes. Excess 3-cyclopentylpropionyl chloride was quenched by adding 60 mL of saturated aqueous ammonium chloride solution. Most of the tetrahydrofuran and hexane were removed on a rotary evaporator and the slurry was extracted twice with 80 mL dichloromethane. The combined organic layers were washed with 75 mL 1 M sodium hydroxide and 75 mL brine, dried over anhydrous magnesium sulfate and filtered. The solvent was removed under reduced pressure. Trituration of the residue with hexane afforded 16.5 g of the desired product 2 as a white solid. ¹ H-NMR (300 MHz, CDCl ₃ ) δ 7.18-7
． 40 (5H, m), 4.67 (1H, m), 4.12 to 4.22 (2H, m)
3.30 (1H, dd, J = 13.4, 3.1 Hz), 2.84 to 3.06 (
2H, m), 2.76 (1H, dd, J = 13.4, 9.6Hz), 1.42
1.96 (9H, m), 1.15 (2H, br, m).

3- (2 (R) -Cyclopentylmethyl-3 (S) -hydroxyl-5-phenyl-1-oxopentyl) -4 (R)-(phenylmethyl) -2-oxazolidinone (3)

[0262]

[Chemical 44]

A solution of acyloxazolidinone 2 (1.57 g, 5.00 mmol) in 20 mL of dichloromethane was cooled to −78 ° C. under a nitrogen atmosphere, to which dibutylboron triflate (1.40 mL, 5.50 mmol) was added dropwise. Then, triethylamine was added. The mixture was slowly warmed to 0 ° C. and stirred at 0 ° C. for another hour. Then, the resulting boryl enolate solution was cooled to -78 ° C,
3-Phenylpropanol (0.80 mL, 5.5 mmol) was added over 5 minutes. The solution was stirred at -78 ° C for 1 hour and then at 0 ° C for 1 hour. The reaction mixture was quenched by adding 4 mL of pH 7 aqueous phosphate buffer and 12 mL of methanol. To this cloudy solution, add 8 mL of methanol and 1
0 mL of 30% aqueous hydrogen peroxide was added at such a rate that the internal temperature was kept below 10 ° C. After stirring the solution for an additional hour, volatiles were removed on a rotary evaporator. The resulting slurry was extracted 3 times with 20 mL of diethyl ether.
The combined organic layers were washed with 20 mL of 5% aqueous sodium bicarbonate solution and 20 mL of brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. Purification by flash column chromatography (25% ethyl acetate-hexane) gave 1.11 g (56%) of aldol 3 as a colorless oil. ¹ H-NMR (300 MHz, CDCl ₃ ) δ 7.15 to 7.38 (m, 10
H), 4.72 (m, 1H), 4.12 to 4.28 (m, 3H), 3.85 (m
1H), 3.34 (1H, dd, J = 13.4, 3.1 Hz), 2.80 to 2
． 95 (1H, m), 2.60 to 2.78 (2H, m), 1.95 to 2.05 (
1H, m), 1.40 to 1.90 (10H, m), 1.10 (2H, m).

2 (R) -Cyclopentylmethyl-3 (S) -hydroxyl-5-phenylpentanoic acid (4)

[0265]

[Chemical formula 45]

[0266]   Acyl oxazolidinone 3 (226 mg, 0.500 mmol) was added to 3 mL of T
Dissolved in HF and 1 mL distilled water. The resulting solution was cooled to 0 ° C. This melt
30% hydrogen peroxide solution (0.40 mL, 4.0 mmol) was added to the solution, and then water was added.
A solution of lithium oxide (19 mg, 0.80 mmol) in 0.5 mL of distilled water
Was added. After stirring the solution for 16 hours, sodium sulfite (567 mg, 4.5
0 mmol) in 3 mL of distilled water was added. Most of the tetrahydrofuran is reduced
Removed under pressure and the resulting mixture (pH 12-13) was triturated with 20 mL methylene chloride.
Extracted twice to remove oxazolidinone auxiliary. Cool the aqueous layer in an ice bath and add 6M salt.
Acidified to pH 1 with acid. The resulting cloudy solution was extracted 5 times with 30 mL of ethyl acetate.
I put it out. The organic layers are combined, dried over anhydrous magnesium sulfate, filtered, and under reduced pressure.
Concentrated in. 230 mg (81%) of the desired acid 4 was obtained as a white solid. ¹ H-NMR (300 MHz, CDCl₃) Δ 7.18 to 7.35 (5H, m),
3.87 (1H, m), 2.81-2.87 (1H, m), 2.60-2.76
(1H, m); 2.54 to 2.60 (1H, m), 1.00 to 1.95 (m, 1
3H).

3- (2 (R) -Cyclopentylmethyl-3 (S) -hydroxyl-1-oxo-5-phenylpentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1, 4-benzodiazepin-2-one (6)

[0268]

[Chemical formula 46]

Acid 4 (250 mg, 0.900 mmol) and 3-amino-1-methyl-5.
-Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one p
-Toluene sulfonate salt (364 mg, 0.820 mmol) in a mixture of 4 m
Stir at 0 ° C. in 1 methylene chloride. 1-hydroxybenzotriazole hydrate (133 mg, 0.980 mmol), 1- [3- (dimethylamine) propyl] -3-ethylcarbodiimide hydrochloride (314 mg, 1.64 mmol)
And triethylamine (0.51 mL, 3.7 mmol) were added successively. After stirring the mixture for 16 hours, 30 mL of ethyl acetate was added. The organic layer was washed with 1M HCl (15 mL), 5% NaHCO ₃ (30 mL) and brine (30 mL).
), Dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Purification by chromatotron (30% ethyl acetate-hexane) gave two diastereomers A and B. A: 120 mg (25%); ¹ H-NNR (300
MHz, CDCl ₃ ) δ 7.20 to 7.70 (15H, m), 5.54 (1H,
d, J = 8.0 Hz), 4.02 (1H, m), 3.48 (3H, s), 2.8
3 to 3.00 (1H, m), 2.62 to 2.74 (1H, m), 2.40 to 2.
48 (1H, m), 1.00-2.00 (13H, m); MS (ESI): 52
4 (M + H), 546 (M + Na), 522 (MH), 558 (M + Cl).
B: 120 mg (25%); ¹ H-NMR (300 MHz, CDCl ₃ ) δ7.6.
0 (1H, d, J = 6.9 Hz), 7.20 to 7.45 (14H, m), 5.5
6 (1H, d, J = 8.4 Hz), 3.84 (1H, m), 3.48 (3H, s)
), 2.83 to 3.00 (1H, m), 2.62 to 2.74 (1H, m), 2.
50-2.60 (1H, m), 1.00-1.95 (13H, m); MS (ES
I): 524 (M + H), 546 (M + Na), 522 (M-H).

Examples 2-135 The general procedure of Example 1 was followed using the corresponding acid chlorides, aldehydes and substituted benzodiazepines, azepans or bizbenzodiazepines. Starting materials are either commercially available or prepared by methods known to those skilled in the art.

Example 2. 3- (2 (R) -Cyclopentylmethyl-3 (S) -hydroxyl-1-oxo-5-phenylpentyl) amino-1-methyl-5- (4-fluorophenyl) -2,3-dihydro-1H- 1,4-benzodiazepin-2-one. MS (ESI) 542 (M + H).

Example 3. 3- (2 (R) -benzyl-3 (S) -hydroxyl-1-oxo-5-phenylpentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine- 2-on. MS (ESI): 532 (
M + H).

Example 4. 3- (2 (R) -isopropyl-3 (S) -hydroxyl-1-
Oxo-5-phenylpentyl) amino-1-methyl-5-phenyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 48
4 (M + H).

Example 5. 3- (2 (R) -Cyclopentylmethyl-3 (S) -hydroxyl-1-oxo-4- (3,5-difluorophenoxy) butyl) amino-1-
Methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine-
2-on. MS (ESI): 562 (M + H).

Example 6. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4- (3,5-difluorophenoxy) butyl) amino-1-methyl-5
-Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one.
MS (ESI): 536 (M + H).

Example 7. 3- (2 (R) -Cyclopentylmethyl-3 (S) -hydroxyl-1-oxo-4-phenoxybutyl) amino-7-chloro-1-methyl-5
-Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one.
MS (ESI): 560 (M + H).

Example 8. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-phenoxybutyl) amino-7-chloro-1-methyl-5- (4-fluorophenyl) -2,3-dihydro -1H-1,4-benzodiazepine-2-
on. MS (ESI): 552 (M + H).

Example 9. 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4-cyclohexyloxybutyl) amino-1-methyl-5-phenyl-2,
3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI):
464 (M + H).

Example 10. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-
Oxo-4-cyclohexyloxybutyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ES
I): 506 (M + H).

Example 11. 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4-phenoxybutyl) amino-7-chloro-1-methyl-5-phenyl-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI
): 492 (M + H).

Example 12. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-
Oxo-4-phenoxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (E
SI): 534 (M + H).

Example 13. 3- (2 (R) -benzyl-3 (S) -hydroxyl-1-oxo-4-cyclohexyloxybutyl) amino-7-chloro-1-methyl-5
-Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one.
MS (ESI): 574 (M + H).

Example 14. 3- (2 (R) -Cyclopentylmethyl-3 (S) -hydroxyl-1-oxo-4-cyclohexyloxybutyl) amino-7-chloro-1
-Methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 566 (M + H).

Example 15. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-
Oxo-4-cyclohexyloxybutyl) amino-7-chloro-1-methyl-
5-Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 540 (M + H).

Example 16. 3- (2 (R) -isopropyl-3 (S) -hydroxyl-1
-Oxo-4-cyclohexyloxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 526 (M + H).

Example 17. 3- (2 (R) -methoxy-3 (S) -hydroxyl-1-oxo-4- (4-trifluoromethylbenzyloxy) butyl) amino-7-chloro-1-methyl-5-phenyl-2, 3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 590 (M + H).

Example 18. 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4- (2,4-difluorobenzyloxy) butyl) amino-7-chloro-
1-Methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 542 (M + H).

Example 20. 3- (2 (R) -Vinyl-3 (S) -hydroxyl-1-oxo-4-benzyloxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1 , 4-benzodiazepin-2-one. MS (E
SI): 536 (M + H).

Example 21. 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4-cyclohexyloxybutyl) amino-7-chloro-1-methyl-5-
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. M
S (ESI): 498 (M + H).

Example 23. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-
Oxo-5-phenylpentyl) amino-1-methyl-5-phenyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 49
8 (M + H).

Example 24. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-
Oxo-3-cyclopropylpropyl) amino-1-methyl-5-phenyl-2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI)
: 434 (M + H).

Example 25a. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1
-Oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1
H-1,4-benzodiazepin-2-one. MS (ESI): 450 (M + H)
.

Example 25b. 3- (R)-(2 (R) -isobutyl-3 (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine- 2-on. MS (ESI): 450 (
M + H).

Example 25c. 3- (S)-(2 (R) -isobutyl-3 (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine- 2-on. MS (ESI): 450 (
M + H).

Example 26. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-
Oxononyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one. MS (ESI): 478 (M + H).

Example 27. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-
Oxohexyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H
-1,4-benzodiazepin-2-one. MS (ESI): 436 (M + H).

Example 28. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-
Oxo-4-phenylbutyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 484
(M + H).

Example 29. 3- (2 (R) -Methyl-3 (S) -hydroxyl-1-oxo-5-phenylpentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine- 2-on. MS (ESI): 442 (
M + H).

Example 30. 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-6-phenylhexyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine- 2-on. MS (ESI): 470 (
M + H).

Example 31. 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-
Oxobutyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one. MS (ESI): 408 (M + H).

Example 32. 3-2 (R) -isobutyl-3 (S) -hydroxyl-1-oxooctyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one. MS (ESI): 464 (M + H).

Example 33. 3- (2 (R) -Methyl-3 (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1
, 4-benzodiazepin-2-one. MS (ESI): 408 (M + H).

Example 34. 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-3-phenylpropyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine- 2-on. MS (ESI): 428 (
M + H).

Example 35. 3- (2 (R) -Methyl-3 (S) -hydroxyl-1-oxo-5,5-dimethylhexyl) amino-1-methyl-5-phenyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 42
2 (M + H).

Example 36. 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxohexyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1
, 4-benzodiazepin-2-one. MS (ESI): 394 (M + H).

Example 37. 3- (2 (R) -Methyl-3 (S) -hydroxyl-1-oxo-3- (4-propoxyphenyl) propyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1 , 4-benzodiazepin-2-one. MS (
ESI): 486 (M + H).

Example 38. 2- (R) -Cyclopropylmethyl-3- (S) -hydroxylheptanoic acid (2-oxo-1- (3-phenoxybenzyl) azapan-3- (
S) -yl) amide. MS (ESI): 493 (M + H), 491 (M-H),
527 (M + Cl).

Example 39. 2 (R) -Cyclopropylmethyl-5- (3,5-difluorophenyl) -3- (S) -hydroxypentanoic acid (2-oxo-1- (3-phenoxybenzyl) azapan-3- (S)- Il) Amide. MS (ESI): 57
7 (M + H), 575 (M + H), 599 (M + Na).

Example 40. 4-Cyclopentyl-2- (R) -cyclopropylmethyl-3
-(S) -hydroxybutanoic acid (2-oxo-1- (3-phenoxybenzyl)
Azapan-3- (S) -yl) amide. MS (ESI): 519 (M + H), 5
41 (M + Na), 517 (MH).

Example 41. 2- (R) -Cyclopropylmethyl-3- (S) -hydroxyheptanoic acid (1- (5-bromo-3-pyridinyl) methyl-2-oxo-azapan-3- (S) -yl) amide. MS (ESI): 480 (M (79 Br) + H)
, 482 (M ( ⁸¹ Br + H), 478 (M ( ⁷⁹ Br) + H), 480 (M ( ⁸¹ B
r) -H).

Example 42. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5- (2-fluorophenyl) -1-
Methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS
(ESI): 466 (M + H), 488 (M + Na), 464 (MH). Chromatography: Note b and Note c.

Example 43. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5- (azapan-1-yl) -1-methyl-2,3-dihydro-1H- 1,4-benzodiazepin-2-one. MS (
ESI): 469 (M + H), 491 (M + Na), 467 (M-H). Chromatography: Note b and Note c.

Example 44. 3- (2- (R) -Cyclopropylmethyl-5- (3,5-difluorophenyl) -3 (S) -hydroxyl-1-oxopentyl) amino-
1-methyl-5- (pyridin-2-yl) -2,3-dihydro-1H-1,4-
Benzodiazepin-2-one. MS (ESI): 533 (M + H), 555 (M
+ Na), 531 (MH). Chromatography: Note b and Note c.

The 3- (3,5-difluorophenyl) propanal used in the aldol reaction was obtained from trans-5-difluorocinnamic acid from (1) 3- (3,5-
Hydrogenation to difluorophenyl) propionic acid (L. Kruse et al., J. Med.
． Chem. 1987, 30, 486-494); (2) Weinreb amide formation (M. Braun, Synthesis, 1989, 856); and (
3) Reduction to aldehydes (DA Evans, J. Org. Chem. 199).
3, 58, 2446-2453).

Example 45. 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-oxopentyl) amino-1-methyl-5- (4-chlorophenyl) -2,3-dihydro-1H-1, 4-benzodiazepin-2-one. MS (
ESI): 482 (M + H), 504 (M + Na), 480 (M-H). Chromatography: Note i and Note k.

Example 46. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5- (4-methoxyphenyl) -1-
Methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS
(ESI): 466 (M + H), 488 (M + Na), 464 (MH). Chromatography: Note b and Note c.

Example 47. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5- (4-methoxyphenyl) -1-
Methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS
(ESI): 479 (M + H), 500 (M + Na), 476 (MH). Chromatography: Remarks m.

Example 48. 3- (S)-(4-Cyclopentyl-2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-oxobutyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H -1,4-benzodiazepine-2-
on. MS (ESI): 474 (M + H), 496 (M + Na), 472 (M-).
H).

Example 49. 3- (S)-(2- (R) -cyclopropylmethyl-3- (S
) -Hydroxyl-1-oxohepta-6-enyl) amino-1-methyl-5-
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. M
S (ESI): 446 (M + H), 468 (M + Na), 444 (M-H).

Example 50. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxohepta-6-enyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3- Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 514 (M + H). Chromatography: Remark i.

Example 51. 3- (S)-(2- (R) -cyclopropylmethyl-5- (3
, 5-Dimethylisoxazol-4-yl) -3- (S) -hydroxyl-1
-Oxopentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1
H-1,4-benzodiazepin-2-one. MS (ESI): 515 (M + H)
, 537 (M + Na), 513 (MH).

The 3- (3,5-dimethyl-4-isoxazole) propanal used in the aldol reaction was prepared from (1) methyl 3- (3,5-dimethyl-4-isoxazole) propionate (M). C. Marcotullio, J. Org.
Chem. 1994, 59, 2884); (2) DIBAL-H to alcohol
Reduction (NM Yoon et al., J. Org. Chem. 1985, 50, 2443).
˜2450); and (3) TPAP / NMO oxidation to aldehyde (SVL
ey et al., Synthesis, 1994, 639).

Example 52. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1, 4-benzodiazepin-2-one. MS (E
SI): 482 (M + H), 504 (M + Na), 480 (M-H). Chromatography: Remark n and Remark o.

Example 53. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl- (pyridin-2-yl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ES
I): 449 (M + H), 471 (M + Na), 447 (M-H). Chromatography: Note b and Note c.

Example 54. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5- (4-fluorophenyl) -1-
Methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS
(ESI): 466 (M + H), 500 (M + Cl). Chromatography: Remark h.

Example 55. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H -1,4-benzodiazepine-2-
on. MS (ESI): 516 (M + H), 514 (M-H), 550 (M + C).
l). Chromatography: Remark i.

3-Cyclopropylpropionic acid converted to 3-cyclopropylpropionyl chloride used in the aldol reaction is described in A. Donetti, J .; Med
． Chem. 1972, 15 (6), 590-592.

Example 56. 3- (5-Cyclopentyl-2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-oxopentyl) amino-1-methyl-5
-(Pyridin-2-yl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 489 (M + H), 511 (M + Na), 48.
7 (M-H). Chromatography: Note b and Note c.

Example 57. 3- (2- (R) -iso-butyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H -1,4-benzodiazepin-2-one.
MS (ESI): 518 (M + H), 540 (M + Na), 516 (M-H).
Chromatography: Note b and Note c.

Example 58. 3- (S)-(2- (R) -cyclopropylmethyl-3- (S
) -Hydroxyl-1-oxo-5- (thiophen-2-yl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine-2
-On. MS (ESI); 502 (M + H), 524 (M + Na), 500 (M
-H).

Example 59. 3- (S)-(2- (R) -Cyclopropylmethyl-5- (furan-2-yl) 3- (S) -hydroxyl-1-oxopentyl) amino-1
-Methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 486 (M + H), 508 (M + Na), 484.
(M-H).

Example 60. 3- (5-Cyclopentyl-2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-oxopentyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-dihydro -1H-1,4-benzodiazepin-2-one. MS (ESI): 506 (M + H), 528 (M + Na), 5
04 (M-H). Chromatography: Remark h.

Example 61. 3- (S)-(2- (R) -cyclopropylmethyl-5- (3
, 5-Difluorophenyl) -3- (S) -hydroxy-1-oxopentyl)
Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 532 (M + H), 554 (M + Na).
), 530 (M-H).

Example 62. 3- (S)-(3- (S) -hydroxyl-2- (R)-(thiophen-2-yl) methyl-1-oxoheptyl) amino-1-methyl-5-
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. M
S (ESI): 448 (M + H), 470 (M + Na), 446 (M-H).

Example 63. 3- (S)-(2- (R) -cyclopropylmethyl-3- (S
) -Hydroxyl-1-oxoheptyl) amino-7-methyl-5-phenyl-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI
): 490 (M + H), 512 (M + Na), 488 (MH).

Example 64. 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-7-methoxy-1-methyl-5-phenyl-2,3-dihydro-1H-1, 4-benzodiazepin-2-one. MS (
ESI): 478 (M + H), 500 (M + Na), 476 (M-H). Chromatography: Remark l.

Example 65. 3- (S)-(2- (R) -Cyclobutylmethyl-3- (S)
-Hydroxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI)
: 462 (M + H), 484 (M + Na).

The 3-cyclobutylpropionic acid converted to 3-cyclobutylpropionyl chloride used in the aldol reaction is described in A. Donetti, J .; Med. C
hem. 1972, 15 (6), 590-592.

Example 66. 3- (S)-(2- (R)-(3,5-difluorobenzyl)
-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5-
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. M
S (ESI): 520 (M + H), 518 (M-H).

Example 67. 3- (S)-(2- (R)-(furan-2-yl) methyl-3
-(S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (
ESI): 474 (M + H), 472 (M-H).

Example 68. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxo-5-phenylpentyl) amino-1-methyl-5- (pyridin-2-yl) -2,3- Dihydro-1H-benzodiazepin-2-one.
MS (ESI): 514 (M + H), 536 (M + Na), 512 (MH).
Chromatography: Remark h.

Example 69. 3- (2- (R) -iso-butyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-dihydro-1H-1 , 4-benzodiazepin-2-one. MS (ES
I): 497 (M + H), 519 (M + Na), 495 (MH). Chromatography: Note b and Note c.

Example 70. 3- (2- (R) -iso-butyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-dihydro-1H-1 , 4-benzodiazepin-2-one. MS (ES
I): 468 (M + H), 502 (M + Cl). Chromatography: Remark h.

Example 71. 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-oxo-5-phenylpentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1, 4-benzodiazepin-2-one. MS (
(ESI); 421 (M + H), 443 (M + Na), 419 (M-H). Chromatography: Note b and Note c.

Example 72. 3- (2- (R) -cyclopropylmethyl-5- (furan-2
-Yl) -3- (S) -hydroxyl-1-oxopentyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H-1,
4-benzodiazepin-2-one. MS (ESI): 554 (M + H), 576
(M + Na), 552 (MH). Chromatography: Remark i.

Example 73. 3- (5-Cyclopentyl-2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-oxopentyl) amino-1-methyl-5
-(4-Trifluoromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 542 (M + H), 564 (M +
Na), 540 (MH). Chromatography: Remark i.

Example 74. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxooctyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H -1,4-benzodiazepine-2-
on. MS (ESI): 530 (M + H), 552 (M + Na), 528 (M-).
H). Chromatography: Remark i.

Example 75. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxononyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H- 1,4-benzodiazepin-2-one. MS (ESI): 544 (M + H), 566 (M + Na), 542 (M-H).
). Chromatography: Remark i.

Example 76. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-trifluoromethyl (pyridin-2-yl))-2 , 3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 517 (M + H), 539 (M + Na).
515 (MH), Chromatography: Remark i.

Example 77. 3- (2- (R) -Cyclobutylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (40trifluoromethylphenyl) -2,3-dihydro-1H- 1,4-benzodiazepin-2-one. MS (ESI): 530 (M + H), 552 (M + Na), 528 (M-H).
). Chromatography: Remark i.

Example 78. 3- (2- (R) -Cyclopentylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H- 1,4-benzodiazepine-2-
on. MS (ESI): 544 (M + H), 542 (M-H), 578 (M + C).
l). Chromatography: Remark i.

Example 79. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-methyl-2-
Pyridyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 463 (M + H). Chromatography: Remarks cc.

Example 80. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-methyl-2-
Pyridyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one.
MS (ESI): 463 (M + H). Chromatography: Remarks dd.

Example 81. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxobutyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H- 1,4-benzodiazepin-2-one. MS (ESI): 474 (M + H). Chromatography: Remark i.

Example 82. 3- (S)-(2- (R)-(3-butenyl) -3- (S)-
Hydroxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,
3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI):
448 (M + H).

Example 83. 3- (S)-(2- (R)-(3-methylbutyl) 3- (S)
-Hydroxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI)
: 464 (M + H).

Example 84. 3- (S)-(2- (R) -Ethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4- Benzodiazepin-2-one. MS (ESI): 422 (M
+ H).

Example 85. 3- (S)-(2- (R) -Propyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1,4-benzodiazepine- 2-on. MS (ESI): 436 (M + H
).

Example 86. 3- (S)-(2- (R) -Butyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4- Benzodiazepin-2-one. MS (ESI): 450 (M
+ H).

Example 87. 3- (4- (S) -amino-3- (R) -hydroxyl-2-
(R) -Methyl-1-oxo-5-phenylpentyl) amino-7-chloro-5
-(2-Fluorophenyl) -1-methyl-2,3-dihydro-1H-1,4-
Benzodiazepin-2-one. MS (ESI): 523 (M + H), 521 (M
-H). Chromatography: Remarks x.

Example 88. 3- (4- (S)-(tert-butoxycarbonylamino-
3- (R) -hydroxyl-2- (R) -methyl-1-oxo-5-phenylpentyl) amino-7-chloro-5- (2-fluorophenyl) -1-methyl-2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI)
: 645 (M + H), 621 (M-H). Chromatography: Note a and Note u.

Example 89. 3- (3- (tert-butoxycarbonylpyrrolidine-2
-(R) -yl) -3- (R) -hydroxyl-2- (R) -methyl-1-oxopropyl) amino-7-chloro-5- (2-fluorophenyl) -1-methyl-2, 3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ES
I): 523 (M + H), 521 (M-H). Chromatography: Remark u and Remark v.

Example 90. 3- (3- (R) -hydroxyl-2- (R) -methyl-1-
Oxo-3- (pyrrolidin-2- (R) -yl) propyl) -amino-7-chloro-5- (2-fluorophenyl) -1-methyl-2,3-dihydro-1H-1
, 4-benzodiazepin-2-one. MS (ESI): 473 (M + H), 47.
1 (M-H). Chromatography: Note y and Note z.

Example 91. 3- (4-benzyloxy-3- (R) -hydroxyl-2-
(R) -iso-propyl-1-oxobutyl-amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine-2-
on. MS (ESI): 534 (M + H), 556 (M + Na), 532 (M-).
H). Chromatography: Remark u and Remark v.

Example 92. 2- (4- (S) -amino-3- (S) -hydroxyl-2-
(S) -Methyl-1-oxo-5-phenylpentyl) amino-7-chloro-5
-(2-Fluorophenyl) -1-methyl-2,3-dihydro-1H-1,4-
Benzodiazepin-2-one. MS (ESI): 523 (M + H), 521 (M
-H). Chromatography: Remarks w.

Example 93. 2- (4- (S)-(tert-butoxycarbonylamino-
3- (S) hydroxyl-2- (S) -methyl-1-oxo-5-phenylpentyl) amino-7-chloro-5- (2-fluorophenyl) -1-methyl-2,
3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI):
645 (M + Na), 621 (MH). Chromatography: Note a and Note v.

Example 94. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (thiazole-2-
Yl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS
(ESI): 455 (M + H), 477 (M + Na), 453 (M-H). Chromatography: Note b and Note c.

The benzazepine is 2-aminophenyl-2′thiazolyl ketone (AF
urstner et al., Tetrahedron, 1995, 51 (3), 773-.
786)). G. Sherrill et al. (J. Org. Che
m. 1995, 60, 734).

Example 95. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-cyclopropylmethyl-5- (thiazol-2-yl) -2,3-dihydro- 1H-1,4 benzodiazepine-2
-On. MS (ESI): 495 (M + H), 517 (M + Na), 493 (M
-H). Chromatography: Remarks c.

The benzodiazepine is a 2-aminophenyl-2'thiazolyl ketone (A.
Furstner et al., Tetrahedron, 1995, 51 (3), 773.
~ 786), R. G. Sherrill et al. (J. Org. Ch
em. 1995, 60, 734).

Example 96. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-cyclopropylmethyl-5- (4
-Trifluoromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 556 (M + H), 578 (M + Na).
554 (M-H). Chromatography: Note j and Note p.

Example 97. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-benzyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H -1,4-benzodiazepine-2
-On. MS (ESI): 592 (M + H), 614 (M + Na), 590 (M
-H). Chromatography: Note b and Note c.

Example 98. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1- (3-phenoxybenzyl) -5
-(4-Trifluoromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 684 (M + H), 706 (M +
Na), 682 (MH). Chromatography: Note q and Note r.

Example 99. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1- (3-pyridinylmethyl) -5-
(4-Trifluoromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 593 (M + H), 615 (M + N)
a), 519 (M-H). Chromatography: Note q and Note r.

Example 100. 3- (2- (S) -Cyclopropylmethyl-3- (R) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H -1,4-benzodiazepine-2
-On. MS (ESI): 516 (M + H), 538 (M + Na), 514 (M
-H). Chromatography: Remark i.

This syn-aldol was made according to Scheme 1, but with (S) -4- (
Phenylmethyl) -2-oxazolidinone was used in place of the (R) -isomer shown in Scheme 1.

Example 101. 3- (2- (S) -Cyclopropylmethyl-3- (R) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H -1,4-benzodiazepine-2
-On. MS (ESI): 516 (M + H), 538 (M + Na), 514 (M
-H). Chromatography: Remark k.

This syn-aldol was made according to Scheme 1, but with (S) -4- (
Phenylmethyl) -2-oxazolidinone was used in place of the (R) -isomer shown in Scheme 1.

Example 102. 3- (2- (R) -Cyclopropylmethyl-3- (R) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H -1,4-benzodiazepine-2
-On. MS (ESI): 516 (M + H), 538 (M + Na), 514 (M
-H). Chromatography: Remark i.

[0380]

[Chemical 47]

These anti-aldols were labeled with A. K. Ghosh, J .; Am. Chem
． Soc. It was prepared by the method described in 1996, 118, 2527-2528. The carboxylic acid shown was coupled with the corresponding benzodiazepines following a procedure similar to that of the final step in Example 1.

Example 103. 3- (2- (S) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H -1,4-benzodiazepine-2
-On. MS (ESI): 516 (M + H), 538 (M + Na), 514 (M
-H). Chromatography: Remark i.

Example 102, except that the enantiomer opposite the chiral auxiliary component was used.
According to the synthetic series of.

Example 104. 3- (2- (S) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-1H -1,4-benzodiazepine-2
-On. MS (ESI): 516 (M + H), 514 (M-H). Chromatography: Remark k.

Example 102, except that the enantiomer opposite the chiral auxiliary component was used.
According to the synthetic series of.

Example 105. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-3- (S) -methyl-1-oxoheptyl) amino-1-methyl-
5- (4-trifluoromethylphenyl) -2,3-dihydro-1H-1,4-
Benzodiazepin-2-one. MS (ESI): 530 (M + H), 552 (M
+ Na), 528 (MH). Chromatography: Remark i.

Addition of a methyl group to Example 135 was carried out according to T. Imamoto et al., (A) J. Or
g. Chem. 1984, 49, 3904-3912, and (b) J. Am.
Chem. Soc. 1989, 111, 4392-4398 with an organic cerium reagent made from methylmagnesium bromide and cerium trichloride.

Example 106. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1- (3-phenoxybenzyl)-
5-Methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one.
MS (ESI): 554 (M + H). Chromatography: Notes aa and notes bb.

Example 107. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-benzyl-5-methyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 4
62 (M + H). Chromatography: Note b and Note c.

Example 108. 3- (3- (S) -acetoxy-2- (R) -iso-butyl-1-oxoheptyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-dihydro-1H-1 , 4-benzodiazepin-2-one. MS (ES
I): 510 (M + H), 532 (M + Na), 508 (MH). Chromatography: Remark h.

Example 109. 3- (S)-(5-Cyclopentyl-2- (R) -cyclopropylmethyl-3- (S) -methoxy-1-oxopentyl) amino-1-methyl-5-phenyl-2,3-dihydro- 1H-1,4-benzodiazepine-2-
on. MS (ESI): 502 (M + H), 524 (M + Na).

[0390]

[Chemical 48]

Methylation of the corresponding aldol was determined by (a) D. A. Evans et al., Tetra
hedron Lett. 1994, 35 (39), 7171-7172; (b
) G. R. It was performed according to Pettit, Synthesis, 1996, 719-725. The indicated carboxylic acids were then coupled with the corresponding benzodiazepines following a procedure similar to that of the final step in Example 1.

Example 113. 1- (1-hydroxypentyl) cyclohexanecarboxylic acid (5- (4-fluorophenyl) -1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl) amide. MS (ESI): 48
0 (M + H), 502 (M + Na), 478 (MH). Chromatography:
． Note t and note h.

[0395]

[Chemical 49]

The corresponding aldol was prepared according to (a) A. S. Kende et al., Tetrahedro
n Lett. 1989, 30 (43), 5821-5824; (b) H.M. Mu
lzer et al., Tetrahedron Lett. 1995, 36 (42), 7
643-7646. The indicated carboxylic acid was coupled with benzodiazepines following a procedure similar to that of the final step in Example 1.

Example 114. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5-methyl-5H, 7H-dibenzo [b, d] azepin-6-one. MS (ESI): 421 (M + H), 443 (
M + Na), 419 (MH). Chromatography: Remarks.

Example 115. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxooctyl) amino-5-methyl-5H, 7H-dibenzo [b, d] azepin-6-one. MS (ESI): 435 (M + H), 457 (
M + Na), 433 (MH). Chromatography: Remarks.

Example 116. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxononyl) amino-5-methyl-5H, 7H-dibenzo [
[b, d] Azepin-6-one. MS (ESI): 449 (M + H), 471 (M
+ Na), 447 (MH), chromatography: remarks.

Example 117. 3- (2- (R) -cyclopropylmethyl-5- (furan-
2-yl) -3- (S) -hydroxyl-1-oxopentyl) amino-5-methyl-5H, 7H-dibenzo [b, d] azepin-6-one. MS (ESI):
459 (M + H), 481 (M + Na), 457 (M-H). Chromatography: Remarks.

Example 118. 2- (R) -Cyclopropylmethyl-3- (S) -hydroxylheptanoic acid (2-oxo-1- (3-phenylamino-benzyl) azapan-3- (S) -yl) amide. MS (ESI): 492 (M + H), 514 (M
+ Na), 490 (MH).

Step 1: [2-oxo-1- (3-phenylamino-benzyl) azepan-3
-Yl] carbamic acid tert-butyl ester: Binap ((S)-(-) 2,2'-) dissolved in 15 mL of toluene in a 100 ml round bottom flask.
Bis (diphenylphosphino) -1,1'-binaphthyl) (0.210 g, 0.
3375 mmol) was stirred at 80 ° C. for 1 minute. To this flask cooled to room temperature under an inert atmosphere, Pd (OAC) ₂ (0.050 g, 0.225 mmol) was added and the solution was stirred at room temperature for 2 minutes. To this reaction mixture was dissolved in 15 mL of toluene [1- (3-iodobenzyl) -2-oxo-azepan-3-yl] carbamic acid tert-butyl ester (1.0 g, 2.25 mmol), aniline (1 0.047 g, 11.25 mmol) and sodium tert-butoxide (0.259 g, 2.70 mmol) were added and the solution was stirred at 80 ° C. for 18 hours. The reaction was cooled to room temperature, diluted with 200 mL water and extracted twice with 100 mL ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to an oil. The oil was purified on a flash silica gel column using 10-30% ethyl acetate / hexane as eluent to give 0.562 g (61%). MS (ESI) M + H = 432.5.

Step 2: 3-Amino-1- (3-phenylamino-benzyl) azepan-2-
On trifluoroacetate salt: In a 25 mL round bottom flask, add the ester (0.025 g, 0.06 mmol) from Step 1 above to 10 mL of 50% TF.
It was dissolved in A / CH ₂ Cl ₂ and stirred at room temperature for 1 hour. The solvent was concentrated to an oil and dried under high vacuum to give 0.025g (100%). MS (ESI
), M + H = 310.4.

Step 3: 2-Cyclopropylmethyl-3-hydroxyheptanoic acid [2-oxo-1- (3-phenylamino-benzyl) azepan-3-yl] amide: 25 m
In a L round bottom flask, 2-cyclopropylmethyl-3-hydroxyheptanoic acid (0.0125 g, 0.061 mmol) was dissolved in 1 mL DMF. The reaction mixture was charged with HATU (O- (7-azabenzotriazol-1-yl) -N,
N, N ', N'-tetramethyluronium hexafluorophosphate) (0.
029 g, 0.0734 mmol) and N-methylmorpholine (0.018 g)
, 0.018 mmol) was added and the reaction solution was stirred at room temperature for 10 minutes. To this reaction mixture was added the compound of step 2 above (0.025 g, 0.
06 mmol) was added and the reaction solution was stirred at room temperature for 18 hours. 50 mL of solution
It was diluted with water and extracted twice with 20 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated to an oil. The oil was purified on a flash silica gel column using 20-40% ethyl acetate / hexane as eluent to give 6.0 mg (20%). MS (ESI), M + H = 492.
6.

Example 119. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5-cyclopentyl-1-methyl-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI
): 440 (M + H). Chromatography: Remarks a.

Synthesis of 2-aminophenylcyclopentylmethanone: Anthranilonitrile (
To a solution of 15.0 g) in diethyl ether (600 mL) under nitrogen was added 2.0 M cyclopentylmagnesium bromide solution in diethyl ether (159 m).
L) was added at 0 ° C. The mixture was stirred at room temperature overnight (20 hours). 500 ml of 5N HCl / H ₂ O was added very slowly at 0 ° C. The mixture was stirred at room temperature for 1 hour. The aqueous layer was neutralized to pH = 12 with 50% NaOH / H ₂ O. 50 times twice
The aqueous layer was extracted with 0 mL ethyl acetate. Combine the organic layers together and add Na ₂ S
Dry with O ₄ . Excluding the solvent, 22.5 g (93.6% yield) of crude product was obtained. H ¹ -NMR (CDCl ₃ ): δ 6.62 to 7.82 (m, 4H), 3.
64-3.78 (m, 1H), 1.50-1.96 (m, 8H).

This 2-aminophenylcyclopentylmethanone was synthesized by R. G. Sherril
L et al., J. Org. Chem. Converted to benzodiazepines according to 1995, 60, 734.

Example 120. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5-benzyl-1-methyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 4
62 (M + H), 460 (M-H). Chromatography: Notes b and c
.

This benzazepine was prepared from 1- (2-aminophenyl) -2-phenylethanone (MW Partridge et al., J. Chem. Soc. 1964, 3673).
). G. Shrill, J .; Org. Chem. 19
95, 60, 734 synthetic series.

Example 121. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5-benzyl-1-butyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 5
04 (M + H), 502 (MH). Chromatography: Notes b and c
.

Example 122. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-5-cycloheptyl-1-methyl-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI
): 468 (M + H), 466 (MH). Chromatography: Note b and Note c.

Example 123. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-benzyl-5-cycloheptyl-2,3-dihydro-1H-1,4-benzodiazepine -2-On. MS (ES
I): 544 (M + H), 542 (M-H). Chromatography: Remarks a.

Example 124. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-butyl-5-cycloheptyl-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI
): 510 (M + H), 508 (MH). Chromatography: Note b and Note c.

Example 125. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1- (2-pyridinylmethyl) -5
-(4-Trifluoromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 593 (M + H), 615 (M +)
Na), 591 (MH). Chromatography: Remarks a.

Example 126. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1- (3-pyridinylmethyl) -5
-(2-Fluorophenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 543 (M + H), 541 (MH). Chromatography: Remarks d and e.

Example 127. 3- (2- (S) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxopentyl) amino-1- (3-pyridinylmethyl) -5
-(4-Trifluoromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 565 (M + H), 563 (M-
H). Chromatography: Note f and Note g.

Example 128. 3- (2-1 (R) -cyclopropylmethyl-3- (S)-
Hydroxyl-1-oxoheptyl) amino-1-methyl-5- (N, N-dibutylamino) -2,3-dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 499 (M + H). Chromatography: Remarks a.

Example 129. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-n-butyl-5-t-butyl-
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ES
I): 470 (M + H). Chromatography: Note b and Note c.

Example 130. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1- (2-oxo-3,3-dimethylbutyl) -5-n-butyl-2 , 3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI): 512 (M + H). Chromatography: Remark b.

Example 131. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-benzyl-5-t-butyl-2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI)
: 504 (M + H). Chromatography: Remarks a.

Example 132. 3- (2- (R) -Cyclopropylmethyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1- (2-picolyl) -5-n-butyl-2,3-dihydro-1H- 1,4-benzodiazepin-2-one. MS (
ESI): 505 (M + H). Chromatography: Note b and Note c.

Example 133. 3- (2- (R) -isobutyl-3- (S) -hydroxyl-1-oxoheptyl) amino-1-methyl-5-homopiperidino-2,3-dihydro-1H-1,4-benzodiazepine-2- on. MS (ESI): 471
(M + H). Chromatography: Note b and Note c.

Example 135. 3- (2- (R) -Cyclopropylmethyl-1,3-dioxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one. MS (ESI
): 514 (M + H), 536 (M + Na), 512 (MH). Chromatography: Remark i.

Example 55 was oxidized to the dicarbonyl compound by TPAP / NMO (S
． V. See Ley et al., Synthesis, 1994, 639).

Example 136. 1-Pentyrylcyclohexanecarboxylic acid (5- (4-fluorophenyl) -1-methyl-2-oxo-2,3-dihydro-1H-1,4-
Benzodiazepin-3-yl) amide. MS (ESI): 478 (M + H), 5
00 (M + Na), 476 (MH). Chromatography: Remark h.

[0426]   Chromatography notes:   Remark a: Epimer mixture in BZD.

Remark b: CHIRALPAK A with 10-35% i-PrOH / hexane
The first peak to elute on the D chiral column.

Remark c: CHIRALPAK A with 10-35% i-PrOH / hexane
The second eluting peak on the D chiral column.

Remark d: Peak first eluting on a CHIRALCEL OD chiral column with MeOH / i-PrOH / hexane in the ratio 2/200/800.

Remark e: Peak eluting second on CHIRALCEL OD chiral column with MeOH / i-PrOH / hexane in the ratio 2/200/800.

Remark f: Peak eluting first on a silica gel column with 2% MeOH / CH ₂ Cl ₂ .

Remark g: second eluting peak on a silica gel column with 2% MeOH / CH ₂ Cl ₂ .

[0433]   Note k: CHIRALPAK with acetonitrile in Cbz protected form   Made from BZD-amine, the second eluting peak on the AD column.

Remark m: CIRALPAK A with methanol in Cbz protected form
Made from BZD-amine, the first eluting peak at S.

Remark n: CHIRALPAK A with 0.1% diethylamine / methanol
Made from BZD-amine, the first eluting peak at S.

Remark o: CHIRALPAK A with 0.1% diethylamine / methanol
Made from BZD-amine, the second eluting peak at S.

Remark h: CHIRALPAK AD with 0.1% diethylamine / MeOH
Made from BZD-amine, the first eluting peak on the column.

[0438]   Note i: CHIRALPAK with acetonitrile in Cbz protected form   Made from BZD-amine, the first eluting peak on the AD column.

Remark 1: CH in Cbz protected form with 1: 4 hexane / ethanol.
Made from BZD-amine, the first eluting peak in IRALCEL OJ.

Remark j: Peak first eluting on CHIRALPAK AD column with acetonitrile / water.

Remark p: Peak eluting second on CHIRALPAK AD column with acetonitrile / water.

Remark q: CHIRALCEL OD with 10% i-propanol / hexane.
The first peak to elute at.

Remark r: CHIRALCEL OD with 10% i-propanol / hexane.
The second peak to elute.

Remark s: CHIR with 20% i-PrOH / hexane containing diethylamine.
Bisbenazapine (bisben), the first eluting peak on ALCEL OD
azapine) Made from amine.

Remark t: CHIRALPAK AD with 0.1% diethylamine / MeOH
Made from BZD-amine, the second eluting peak on the column.

[0446]   Remark w: Obtained from Example 93 by treatment with TFA.

[0447]   Remark x: Obtained from Example 88 by treatment with TFA.

Remark u: Peak eluting second on a silica gel column with 30-80% EtOAc / hexanes.

Remark v: Peak first eluting on a silica gel column with 30-80% EtOAc / Hexanes.

[0450]   Remark y: Obtained from Example 89 by treatment with TFA.

[0451]   Remark z: Obtained from Example 89 by treatment with TFA.

Remark aa: Peak eluting first in CHIRALPAK AD with 20:80 water / MeCN.

Remark bb: second eluting peak in CHIRALPAK AD with 20:80 water / MeCN.

Remark cc: Made from BZD-amine, the second eluting peak on the CHIRALCEL OD column with a ratio of 1/300/700 diethylamine / EtOH / CO ₂ in the Cbz protected form.

Remark: Made from BZD-amine, the first peak to elute on the CHIRALCEL OD column with a ratio of 1/300/700 diethylamine / EtOH / CO ₂ in the dd: Cbz protected form.

[0456]   Tables 1 to 8 below show representative examples of compounds of formula (I) of the present invention.

[0457]

[Table 1]

[0458]

[Table 2]

[0459]

[Table 3]

[0460]

[Table 4]

[0461]

[Table 5]

[0462]

[Table 6]

[0463]

[Table 7]

[0464]

[Table 8]

[0465]

[Table 9]

[0466]

[Table 10]

(Usefulness) Aβ production is involved in the pathology of Alzheimer's disease (AD). The compounds of the present invention are useful for the prevention and treatment of AD by inhibiting the production of Aβ. The method of treatment targets the formation of Aβ production via enzymes involved in the proteolytic processing of β-amyloid precursor protein. A compound that inhibits the activity of β-secretase or γ-secretase, either directly or indirectly, is
Suppresses the production of Aβ. Such inhibitors of β-secretase or γ-secretase are expected to reduce the production of Aβ and reduce or prevent neurological disorders associated with Aβ proteins such as Alzheimer's disease.

Cellular screening methods for inhibitors of Aβ production, assays for in vivo inhibition of Aβ production, and assays for detecting secretase activity are known in the art and are described in PCT International Patent Application Publication WO 98/22493, EPO. European Patent Publication 0652009, US Pat. No. 5,703,129 and US Pat. No. 5,593,846.
And numerous publications, all of which are hereby incorporated by reference.

The compounds of the invention are useful in the prevention and treatment of disorders involving the production of Aβ, such as cerebrovascular disorders.

The compounds of the invention have been shown to inhibit the production of Aβ, as demonstrated by the secretase inhibition assay described below.

The compounds of the present invention have been shown to inhibit the production of Aβ utilizing the C-terminal β-amyloid precursor protein accumulation assay described below.

Compounds of formula (I) are expected to have inhibitory activity for gamma secretase.
The γ-secretase inhibitory activity of the compounds of the present invention is demonstrated using assays for such activity, eg, using the assay described below. The compounds of the invention have been shown to inhibit the activity of gamma secretase as measured by an Aβ immunoprecipitation assay.

The compounds provided by the present invention should also be useful as standards and reagents in measuring the ability of potential pharmaceutical agents to inhibit the production of Aβ. These are provided in commercially available kits containing the compounds of the invention.

As used herein, “μg” means micrograms and “m
“G” means milligram, “g” means gram, “μL” means microliter, “mL” means milliliter, “L” means liter,
“ΜM” means micromolar concentration, “mM” means millimolar concentration, and “M
"Means molarity," nm "means nanometers," SDS "means sodium dodecyl sulfate," DMSO "means dimethyl sulfoxide,"
"EDTA" means ethylenediamine tetraacetate.

A compound is considered active if its IC ₅₀ or K _i value for inhibition of Aβ is less than about 100 μM.

Β-Amyloid Precursor Protein Accumulation Assay A new assay to assess accumulation of Aβ protein was developed to detect potential inhibitors of secretase. This assay uses the N9 cell line, which is characterized by exogenous APP expression by immunoblotting and immunoprecipitation.

The effect of test compounds on the accumulation of Aβ in conditioned medium is tested by immunoprecipitation. Briefly, N9 cells are grown to confluence in 6-well plates and washed twice with 1x Hanks buffered salt solution. Cells were starved in methionine / cysteine depleted medium for 30 minutes and then 150 uCi of S35 translabel (Translabel) (Amers).
ham) is replaced with fresh depleted medium. The test compound is DMSO (1
% Final concentration) and added with the addition of radiolabel. Cells are incubated for 4 hours at 37 ° C in a tissue culture incubator.

At the end of the incubation period, the conditioned medium was collected, 5 μl of normal mouse serum and 50 ul of protein A sepharose (Pha
claria) and premixed for 30 minutes at 4 ° C. by tumbling, followed by brief centrifugation in a microcentrifuge. The supernatant was then collected and 5 ug of monoclonal antibody (clone 1101.1; Aβ
Antibody to the internal peptide sequence in) and 50 μl of Protein A Sepharose in a new tube. After overnight incubation at 4 ° C., the sample was treated with a high salt wash buffer (50 mM Tris, pH 7.5, 500).
mM NaCl, 5 mM EDTA, 0.5% Nonidet
P-40) three times with a low salt washing buffer (50 mM Tris (pH 7.5)).
, 150 mM NaCl, 5 mM EDTA, 0.5% Nonidet P-40).
Wash 3 times with and 3 times with 10 mM Tris, pH 7.5. The pellet after the final wash is resuspended in SDS sample buffer (Laemmli, 1970) and boiled for 3 minutes. Then, the supernatant is mixed with 10 to 20% Tris / Tricine.
Fractionate on either an SDS gel or a 16.5% Tris / Tricine SDS gel. The gel is dried and exposed to X-ray film, or the gel is analyzed by phosphorimaging. The obtained image is A
Analyze for the presence of β polypeptide. Steady-state levels of Aβ in the presence of test compound are compared to wells treated with DMSO (1%) alone. Typical test compounds block the accumulation of Aβ in conditioned medium,
Therefore, it is considered active with an IC ₅₀ of less than 100 μM.

C-Terminal β-Amyloid Precursor Protein Accumulation Assay The effect of test compounds on the accumulation of C-terminal fragments varies from cell lysate to AP.
It is measured by immunoprecipitating P and its fragments. N9 cells are metabolically labeled as described above in the presence or absence of test compound. At the end of the incubation period, the conditioned medium was collected and the cells were treated with RIPA buffer (1% Triton X-100, 1% deoxycholate, 0.1%).
% SDS, 150 mM NaCl, 10 mM containing 0.125% NaN _3.
Tris, pH 8.0). Once again, the lysate was precleared with 5 ul of normal rabbit serum / 50 ul of Protein A Sepharose, then
BC-1 antiserum (15 μl) and 50 μl protein A sepharose at 4 ° C.
For 16 hours. Immunoprecipitates were washed as above and bound proteins were eluted by boiling in SDS sample buffer and Tris / Tri.
Fractionation by cineSDS-PAGE. After exposure to X-ray film or phosphor imaging, the images obtained are analyzed for the presence of C-terminal APP fragments. Steady state levels of C-terminal APP fragment are compared to wells treated with DMSO (1%) alone. Typical test compounds stimulate the accumulation of C-terminal fragments in cell lysates and are therefore considered active with an IC ₅₀ of less than 100 μM.

Aβ Immunoprecipitation Assay This immunoprecipitation assay is based on the C-terminus of Aβ by either γ-secretase (ie, direct cleavage or subsequent generation of a C-terminal extended species that is further proteolytically degraded. Is specific for the proteolytic activity required to produce N9 cells were treated with a reported γ-secretase inhibitor (MDL28
170), pulse labeled for 1 hour, then washed to remove radiolabel and MDL28170. The medium is changed and the test compound is added. Cells are tracked for various times, Aβ is isolated from conditioned medium, and C-terminal fragment is isolated from cell lysates (see above). The test compound is
It is characterized by whether stabilization of the C-terminal fragment is observed and whether Aβ arises from these accumulated precursors. A typical test compound prevents the production of Aβ from the accumulated C-terminal fragment and
An IC ₅₀ of less than M is considered active.

Dosage and Formulation The compounds of the invention can be administered orally using any pharmaceutically acceptable dosage form known in the art for such administration. The active ingredient may be provided in solid dosage forms such as dry powder, granules, tablets or capsules, or in liquid dosage forms such as syrups or aqueous suspensions. The active ingredient can be administered alone, but is generally administered with a pharmaceutical carrier. A useful textbook on pharmaceutical dosage forms is Remington's Pharmaceuti.
cal Sciences (Mack Publishing).

The compounds of the present invention may be used in tablets, capsules, each of which may include sustained release or sustained release formulations, pills, powders, granules, elixirs, tinctures, suspensions, syrups. It can be administered in oral dosage forms such as agents and emulsions. Similarly, the compounds of this invention may also be administered intravenously (bolus or infusion), intraperitoneally, subcutaneously or in the form of muscle. All of these use dosage forms that are well known to those of skill in the pharmaceutical arts. Although effective for the desired compound,
Non-toxic doses of neurological disorders associated with beta amyloid production or accumulation (
It can be used to prevent or treat Alzheimer's disease and Down's syndrome and the like.

The compounds of the present invention can be administered by any means that results in effective contact of the agent with the site of action of the agent within the body of the host, such as a human or mammal. The compounds of the present invention may be administered as individual therapeutic agents or in combination with therapeutic agents by any conventional means available for use with pharmaceuticals. The compounds of the present invention can be administered alone, but generally will be administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice.

The dosage regimens for the compounds of the present invention are, of course, dependent on the pharmacodynamic profile of the particular drug and its mode and route of administration; recipient species, age, sex, health status, medical condition. And weight; the nature and extent of symptoms; the type of concurrent treatment; the frequency of treatment; the route of administration, the renal and hepatic function of the patient, and various known factors, such as the desired effect. A physician or veterinarian of ordinary skill can readily determine and prescribe the effective amount of the drug required to prevent, arrest or arrest the progress of the condition.

Conveniently, the compounds of the invention may be administered in a single daily dose, or the total daily dosage may be administered in divided doses of two, three or four times daily. can do.

The compounds of the present invention are administered in intranasal form via topical use of suitable intranasal vehicles, or via transdermal routes, using such forms as transdermal skin patches well known to those of ordinary skill in the art. can do. For administration in the form of a transdermal delivery system,
Administration is, of course, continuous rather than intermittent in the dosing schedule.

In the methods of the present invention, the compounds detailed herein can act as active ingredients, and are typically in the intended form of administration (ie, tablets, capsules for oral administration). Agents, elixirs, syrups, etc.) and suitable pharmaceutical diluents, excipients or carriers, which are generically referred to herein as carrier materials, in line with conventional pharmaceutical practice. Given) and administered in admixture.

When administered orally, for example in the form of tablets or capsules, the active drug component is an oral, non-toxic, pharmaceutically acceptable inert carrier such as lactose, starch, sucrose, glucose, methylcellulose. , Magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like. When administered orally in liquid form, the oral drug component can be combined with any oral non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like. Moreover, when desired or necessary, suitable binders, lubricants, disintegrating agents and coloring agents can also be incorporated into the mixture. Suitable binders include starch, gelatin, natural sugars (such as glucose or β-lactose), corn sweeteners, natural and synthetic gums (such as gum arabic, tragacanth or sodium alginate), carboxymethylcellulose, polyethylene glycol, waxes. Etc. are included. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. Disintegrators include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum and the like.

The compounds of the present invention can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be made from a variety of phospholipids such as cholesterol, stearylamine or phosphatidylcholine.

The compounds of the present invention can also be coupled with soluble polymers as targetable drug carriers. Such polymers include polyvinylpyrrolidone,
Pyran copolymers, polyhydroxypropylmethacrylamide-phenol, polyhydroxyethylaspartamidephenol, or polyethyleneoxide-polylysine substituted with palmitoyl residues may be included. In addition, the compounds of the present invention provide a group of biodegradable polymers useful in achieving controlled drug release, such as polylactic acid, polyglycolic acid, copolymers of polylactic acid and polyglycolic acid, polyε-caprolactone, Polyhydroxybutyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacylates, and hydrogel cross-linkable or amphiphilic block copolymers).

Gelatin capsules may contain the active ingredient and powdered carriers, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar-coated or film-coated to mask any unpleasant taste and to protect the tablet from the atmosphere,
Alternatively, it may be enteric coated for selective disintegration in the gastrointestinal tract.

Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance. In general, water, suitable oils, saline, aqueous dextrose (glucose) and related sugar solutions, and glycols such as propylene glycol or polyethylene glycol are suitable carriers for parenterally administered solutions. Solutions for parenteral administration are preferably water-soluble salts of the active ingredient,
It contains a suitable stabilizer and, if necessary, a buffer substance. Antioxidizing agents such as sodium bisulfite, sodium sulfite or ascorbic acid, either alone or in combination, are suitable stabilizing agents. Citric acid and its salts and E
Sodium DTA is also used. In addition, parenteral solutions can contain preservatives such as benzalkonium chloride, methylparaben or propylparaben, and chlorobutanol.

Suitable pharmaceutical carriers are standard reference textbooks in the field, Reming.
ton's Pharmaceutical Sciences (Mac P
Publishing Company).

─────────────────────────────────────────────────── ─── Continued Front Page (51) Int.Cl. ⁷ Identification Code FI Theme Coat (Reference) A61P 43/00 123 A61P 43/00 123 C07D 243/14 C07D 243/14 243/26 243/26 401/04 401/04 401/06 401/06 403/04 403/04 405/12 405/12 417/04 417/04 // C07M 7:00 C07M 7:00 (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AU, BR, CA, CN, CZ, EE, HU, IL, IN, JP, KR, LT, LV, MX, NO, NZ, PL, RO, SG, SI, SK, TR, UA, VN, ZA (72) Inventor Rho Andrew Andrew Thompson The Third United States 19809 Wilmington Silverside Road Delaware 600F Term (Reference) 4C063 AA01 BB01 BB02 BB03 BB09 CC19 CC37 CC62 CC75 DD12 DD19 DD37 EE01 4C086 AA01 AA02 AA03 BC31 BC56 BC82 GA02 GA14 GA16 GA01 GA10 MA08 GA10 GA08 GA10 MA10 GA10 NA15 ZA15 ZA16 ZC20 ZC21

Claims (23)

[Claims] 1. A compound of formula (I):     [Chemical 1] Or a pharmaceutically acceptable salt form or prodrug thereof, wherein In the formula,   Q is Q¹, (C₁~ C₃Alkyl) -O-Q¹, (C₁~ C₃Alkyl) -S-Q¹, (C₁~ C₃Alkyl) -S (= O) -Q¹, (C₁~ C₃Alkyl) -S (= O)₂-Q¹, Or (C₁~ C₃Alkyl) -N (R²⁰) -Q¹ And   Q¹Is 0 to 3 R^1aC replaced by₁~ C₈Alkyl, 0 to 3 R^1aC replaced by₂~ C₈Alkenyl, 0 to 3 R^1aC replaced by₂~ C₈Alkynyl, 0 to 3 R^1bC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with And   R^1aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl, F
, Br, I, NR¹⁵R¹⁶, CF₃, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with Independently selected from;   R^1bIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, C₁~ C_FourHaloalkyl-S-, and (C₁~ C₆Alkyl
) -OC (= O)-independently selected from;   R²Is H, methyl, ethyl, propyl or butyl;   R³Is H, C₁~ C₆Alkyl, -C (= O) (C₁~ C₆Alkyl), -C (
= S) (C₁~ C₆Alkyl), or -C (= O) NR^{twenty one}R^{twenty two}And   Or R²And OR³Together form C = O or C = N-OH
Do;   R^FiveIs H, OR¹⁴, 0 to 3 R^5bC replaced by₁~ C₆Alkyl, 0 to 3 R^5bC replaced by₁~ C₆Alkoxy, 0 to 3 R^5bC replaced by₂~ C₆Alkenyl, 0 to 3 R^5bC replaced by₂~ C₆Alkynyl, 0 to 3 R^5cC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^5cC replaced by₃~ C_TenCarbocycle, 0 to 3 R^5cC replaced by₆~ C_TenAryl, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^5c5- to 10-membered heterocycle substituted with And   R^5aIs H, C₁~ C_FourAlkyl or C₂~ C_FourAlkenyl;   Or R^FiveAnd R^5aTogether, 0 to 3 R^5cReplaced by 3
Member to 7 membered cycloalkyl ring can be formed and, if desired, R^FiveOh
And R^5aThe cycloalkyl ring formed by combining
And the benzo-fused ring has 0 to 3 R^5cCan be replaced with;   R^5bIs H, C in each occurrence₁~ C₆Alkyl, CF₃, OR¹⁴,
Cl, F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, Acetyl, SCH₃, S
(= O) CH₃, S (= O)₂CH₃, C₂~ C₆Alkenyl, C₂~ C₆Alkynyl
, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, C₁
~ C_FourHaloalkyl-S-, 0 to 3 R^5cC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^5cC replaced by₃~ C_TenCarbocycle, 0 to 3 R^5cC replaced by₆~ C_TenAryl, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^5c5- to 10-membered heterocycle substituted with Independently selected from;   R^5cIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
;   R⁶Is H or C₁~ C₆Alkyl;   W is-(CR⁸R^8a)_p-Is;   p is 0, 1, 2, 3 or 4;   R⁸And R^8aIs H, F, C in each occurrence₁~ C_FourAlkyl, C₂ ~ C_FourAlkenyl, C₂~ C_FourAlkynyl, and C₃~ C₈Cycloalkyl to Germany
Standing and selected;   X is a bond, 0 to 3 R^XbC replaced by₆~ C_TenAryl, 0 to 3 R^XbC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^XbC replaced by₃~ C_TenCarbocycle, or 0 to 2 R^Xb5- to 10-membered heterocycle substituted with And   R^XbIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
;   Y is a bond or-(CR⁹R^9a)_t-V- (CR⁹R^9a)_u-Is;   t is 0, 1, 2 or 3;   u is 0, 1, 2 or 3;   R⁹And R^9aIs H, F, C in each occurrence₁~ C₆Alkyl,
Or C₃~ C₈Independently selected from cycloalkyl;   V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O).
)₂-, -N (R¹⁹)-, -C (= O) NR^19b-, -NR^19bC (= O)-,-
NR^19bS (= O)₂-, -S (= O)₂NR^19b-, -C (= O) O-, or-
OC (= O)-;   Z is H, 0 to 2 R¹²C replaced by₁~ C₈Alkyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkenyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkynyl, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with And   Ring B is saturated, partially saturated or unsaturated,
And each additional lactam carbon has 0 to 2 R¹¹Replaced by, and
If desired, -N =, -NH-, -N (R^Ten)-, -O-, -S-, -S (
= O)-and -S (= O)₂6-membered containing a heteroatom selected from
Member or 8-member lactam;   In addition, two Rs existing in adjacent atoms¹¹The substituents together are C₃~ C₆ Form a carbocyclic condensed group, a benzo condensed group, or a 5- to 6-membered heteroaryl condensed group
In this case, the 5- to 6-membered heteroaryl fused group can be N, O or
And 1 to 2 heteroatoms selected from S and S, and a benzofused group or
The 5- to 6-membered heteroaryl condensed group has 0 to 3 R's.¹³Replaced with;   R^TenIs H, C (= O) R¹⁷, C (= O) OR¹⁷, C (= O) NR¹⁸R¹⁹, S
(= O)₂NR¹⁸R¹⁹, S (= O)₂CR¹⁷, 0 to 2 R^10aC replaced by₁~ C₆Alkyl, 0 to 4 R^10bC replaced by₆~ C_TenAryl, 0 to 3 R^10bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R as required^10b5- to 10-membered heterocycle substituted with And   R^10aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl,
F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, CF₃, 0 to 4 R^10bAn aryl substituted with 0 to 3 R^10bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R as required^10b5- to 10-membered heterocycle substituted with Independently selected from;   R^10bIs H, OH, C in each occurrence.₁~ C₆Alkyl, C₁~ C_Four
Alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, Acetyl
, SCH₃, S (= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_Four Alkoxy, C₁~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_Four Independently selected from haloalkyl-S-;   R¹¹Is H, C in each occurrence₁~ C_FourAlkoxy, Cl, F, Br
, I, = O, CN, NO₂, NR¹⁸R¹⁹, C (= O) R¹⁷, C (= O) OR¹⁷,
C (= O) NR¹⁸R¹⁹, S (= O)₂NR¹⁸R¹⁹, CF₃, 0 to 1 R^11aC replaced by₁~ C₆Alkyl, 0 to 3 R^11bC replaced by₆~ C_TenAryl, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl,
F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, CF₃, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;   R¹³Is H, OH, C in each occurrence.₁~ C₆Alkyl, C₁~ C_FourA
Lucoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, And CF₃From Germany
Standing and selected;   R¹⁴Is, in each occurrence, H, phenyl, benzyl, C₁~ C₆Archi
Le and C₂~ C₆Independently selected from alkoxyalkyl;   R^14aIs H, phenyl, benzyl or C₁~ C₆Alkyl;   R¹⁵Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Le, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, (C₁~ C₆Alkyl)
-OC (= O)-, and (C₁~ C₆Alkyl) -S (= O)₂Independent of
Selected by   R¹⁶Is H, OH, C in each occurrence.₁~ C₆Alkyl, phenyl,
Benzyl, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, (C₁~ C₆Al
Kill) -OC (= O)-, and (C₁~ C₆Alkyl) -S (= O)₂From-
Independently selected;   Alternatively, -NR¹⁵R¹⁶Is piperidinyl, morpholinyl, thiomorpholinyl
, Pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinini
May be a heterocyclic ring selected from the group of   R¹⁷Is H, C₁~ C₆Alkyl or C₂~ C₆Alkoxyalkyl, 0 to 4 R^17aAn aryl substituted with, or Aryl-CH₂-(Wherein the aryl is 0-4 R^17aIs replaced by
) Is;   R^17aIs H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,
Ropoxy, butoxy, -OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃
, S (= O) CH₃, S (= O)₂CH₃, -NH₂, -N (CH₃)₂, Or C₁
~ C_FourHaloalkyl;   R¹⁸Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Le, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, and (C₁~ C₆Al
Kill) -S (= O)₂-Independently selected from;   Alternatively, -NR¹⁷R¹⁸Is piperidinyl, morpholinyl, thiomorpholinyl
, Pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinini
May be a heterocyclic ring selected from the group of   R¹⁹Is H, OH, C in each occurrence.₁~ C₆Alkyl, phenyl,
Benzyl, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, and (C₁~
C₆Alkyl) -S (= O)₂-Independently selected from;   R^19bIn each occurrence H and C₁~ C₆Independent of alkyl
Selected;   R²⁰Is H, OH, C₁~ C_FourAlkyl, phenyl, benzyl or phenethyl
And   R^{twenty one}Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Independently selected from le and phenethyl; and   R^{twenty two}Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Compounds of formula (I), characterized in that they are independently selected from ru and phenethyl.
Alternatively, its pharmaceutically acceptable salt form or prodrug. 2. The compound according to claim 1 or a pharmaceutically acceptable salt form thereof.
States or prodrugs:   Q is Q¹, (C₁~ C₃Alkyl) -O-Q¹, (C₁~ C₃Alkyl) -S-Q¹, (C₁~ C₃Alkyl) -S (= O) -Q¹, (C₁~ C₃Alkyl) -S (= O)₂-Q¹, Or (C₁~ C₃Alkyl) -N (R²⁰) -Q¹ And   Q¹Is 0 to 3 R^1aC replaced by₁~ C₆Alkyl, 0 to 3 R^1aC replaced by₂~ C₆Alkenyl, 0 to 3 R^1aC replaced by₂~ C₆Alkynyl, 0 to 3 R^1bC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with And   R^1aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl, F
, Br, I, NR¹⁵R¹⁶, CF₃, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with Independently selected from;   R^1bIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, C₁~ C_FourHaloalkyl-S-, and (C₁~ C₆Alkyl
) -OC (= O)-independently selected from;   R²Is H, methyl, ethyl, propyl or butyl;   R³Is H, C₁~ C_FourAlkyl, -C (= O) (C₁~ C_FourAlkyl), -C (
= S) (C₁~ C_FourAlkyl), or -C (= O) NR^{twenty one}R^{twenty two}And   R^FiveIs H, OR¹⁴, 0 to 3 R^5bC replaced by₁~ C₆Alkyl, 0 to 3 R^5bC replaced by₁~ C₆Alkoxy, 0 to 3 R^5bC replaced by₂~ C₆Alkenyl, 0 to 3 R^5bC replaced by₂~ C₆Alkynyl, 0 to 3 R^5cC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^5cC replaced by₃~ C_TenCarbocycle, 0 to 3 R^5cC replaced by₆~ C_TenAryl, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^5c5- to 10-membered heterocycle substituted with And   R^5aIs H, C₁~ C_FourAlkyl or C₂~ C_FourAlkenyl;   Or R^FiveAnd R^5aTogether, 0 to 3 R^5cReplaced by 3
A 1- to 7-membered cycloalkyl ring can be formed;   R^5bIs H, C in each occurrence₁~ C₆Alkyl, CF₃, OR¹⁴,
Cl, F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, Acetyl, SCH₃, S
(= O) CH₃, S (= O)₂CH₃, C₂~ C₆Alkenyl, C₂~ C₆Alkynyl
, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, C₁
~ C_FourHaloalkyl-S-, 0 to 3 R^5cC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^5cC replaced by₃~ C_TenCarbocycle, 0 to 3 R^5cC replaced by₆~ C_TenAryl, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^5c5- to 10-membered heterocycle substituted with Independently selected from;   R^5cIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
;   R⁶Is H, methyl or ethyl;   W is-(CR⁸R^8a)_p-Is;   p is 0, 1 or 2;   R⁸And R^8aIs H, F, methyl and ethyl in each occurrence?
Independently selected from   X is a bond, 0 to 3 R^XbA phenyl substituted with, 0 to 3 R^XbC replaced by₃~ C₆Cycloalkyl, or 0 to 2 R^Xb5- to 6-membered heterocycle substituted with And   R^XbIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
;   Y is a bond or-(CR⁹R^9a)_t-V- (CR⁹R^9a)_u-Is;   t is 0, 1 or 2;   u is 0, 1 or 2;   R⁹And R^9aIs H, F, methyl and ethyl in each occurrence?
Independently selected from   V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O).
)₂-, -N (R¹⁹)-, -C (= O) NH-, -NHC (= O)-, -NHS
(= O)₂-Or-S (= O)₂NH-;   Z is H, halo, 0 to 2 R¹²C replaced by₁~ C_FourAlkyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkenyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkynyl, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 6-membered heterocycle substituted with And   Ring B is saturated, partially saturated or unsaturated,
And each additional lactam carbon has 0 to 2 R¹¹Replaced by, and
If desired, -N =, -NH-, -N (R^Ten)-, -O-, -S-, -S (
= O)-and -S (= O)₂A 7-membered ring containing a heteroatom selected from
Is Tom;   In addition, two Rs existing in adjacent atoms¹¹The substituents together are C₃~ C₆ Form a carbocyclic condensed group, a benzo condensed group, or a 5- to 6-membered heteroaryl condensed group
In this case, the 5- to 6-membered heteroaryl fused group can be N, O or
And 1 to 2 heteroatoms selected from S and S, and a benzofused group or
The 5- to 6-membered heteroaryl condensed group has 0 to 3 R's.¹³Replaced with;   R^TenIs H, C (= O) R¹⁷, C (= O) OR¹⁷, C (= O) NR¹⁸R¹⁹, S
(= O)₂NR¹⁸R¹⁹, S (= O)₂R¹⁷, 0 to 2 R^10aC replaced by₁~ C₆Alkyl, 0 to 4 R^10bC replaced by₆~ C_TenAryl, 0 to 3 R^10bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R as required^10b5- to 10-membered heterocycle substituted with And   R^10aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl,
F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, CF₃, Or 0 to 4 R^10bAn aryl substituted with Independently selected from;   R^10bIs H, OH, C in each occurrence.₁~ C₆Alkyl, C₁~ C_Four
Alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, Acetyl
, SCH₃, S (= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_Four Alkoxy, C₁~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_Four Independently selected from haloalkyl-S-;   R¹¹Is H, C in each occurrence₁~ C_FourAlkoxy, Cl, F, Br
, I, = O, CN, NO₂, NR¹⁸R¹⁹, C (= O) R¹⁷, C (= O) OR¹⁷,
C (= O) OR¹⁸R¹⁹, S (= O)₂NR¹⁸R¹⁹, CF₃, 0 to 1 R^11aC replaced by₁~ C₆Alkyl, 0 to 3 R^11bC replaced by₆~ C_TenAryl, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl,
F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, CF₃, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;   R¹³Is H, OH, C in each occurrence.₁~ C₆Alkyl, C₁~ C_FourA
Lucoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, And CF₃From Germany
Standing and selected;   R¹⁴Is, in each occurrence, H, phenyl, benzyl, C₁~ C₆Archi
Le and C₂~ C₆Independently selected from alkoxyalkyl;   R¹⁵Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Le, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, (C₁~ C₆Alkyl)
-OC (= O)-, and (C₁~ C₆Alkyl) -S (= O)₂Independent of
Selected by   R¹⁶Is H, OH, C in each occurrence.₁~ C₆Alkyl, phenyl,
Benzyl, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, (C₁~ C₆Al
Kill) -OC (= O)-, and (C₁~ C₆Alkyl) -S (= O)₂From-
Independently selected;   Alternatively, -NR¹⁵R¹⁶Is piperidinyl, morpholinyl, thiomorpholinyl
, Pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinini
May be a heterocyclic ring selected from the group of   R¹⁷Is H, aryl, aryl-CH₂-, C₁~ C₆Alkyl or C₂~
C₆Alkoxyalkyl;   R¹⁸Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Le, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, and (C₁~ C₆Al
Kill) -S (= O)₂-Independently selected from;   R¹⁹Is H, OH, C in each occurrence.₁~ C₆Alkyl, phenyl,
Benzyl, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, and (C₁~
C₆Alkyl) -S (= O)₂-Independently selected from;   Alternatively, -NR¹⁷R¹⁸Is piperidinyl, morpholinyl, thiomorpholinyl
, Pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinini
May be a heterocyclic ring selected from the group of   R²⁰Is H, OH, C₁~ C_FourAlkyl, phenyl, benzyl or phenethyl
And   R^{twenty one}Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Independently selected from le and phenethyl; and   R^{twenty two}Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
2. Independently selected from le and phenethyl.
A compound or a pharmaceutically acceptable salt form or prodrug thereof. 3. The compound according to claim 2, wherein ring B is selected from: The compound according to claim 2, wherein each benzofused group is substituted with 0 to 3 R ¹³ . 4. A compound of formula (Ia) according to claim 2:     [Chemical 3] Or a pharmaceutically acceptable salt form or prodrug thereof, wherein In the formula,   Q is Q¹, (C₁~ C₃Alkyl) -O-Q¹, (C₁~ C₃Alkyl) -S-Q¹, (C₁~ C₃Alkyl) -S (= O) -Q¹, (C₁~ C₃Alkyl) -S (= O)₂-Q¹, Or (C₁~ C₃Alkyl) -N (R²⁰) -Q¹ And   Q¹Is 0 to 3 R^1aC replaced by₁~ C₆Alkyl, 0 to 3 R^1aC replaced by₂~ C₆Alkenyl, 0 to 3 R^1aC replaced by₂~ C₆Alkynyl, 0 to 3 R^1bC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with And   R^1aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl, F
, Br, I, NR¹⁵R¹⁶, CF₃, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with Independently selected from;   R^1bIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, C₁~ C_FourHaloalkyl-S-, and (C₁~ C₆Alkyl
) -OC (= O)-independently selected from;   R²Is H, methyl or ethyl;   R^FiveIs H, OR¹⁴, 0 to 3 R^5bC replaced by₁~ C₆Alkyl, 0 to 3 R^5bC replaced by₁~ C₆Alkoxy, 0 to 3 R^5bC replaced by₂~ C₆Alkenyl, 0 to 3 R^5bC replaced by₂~ C₆Alkynyl, 0 to 3 R^5cC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^5cC replaced by₃~ C_TenCarbocycle, 0 to 3 R^5cC replaced by₆~ C_TenAryl, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^5c5- to 10-membered heterocycle substituted with And   R^5aIs H, C₁~ C_FourAlkyl or C₂~ C_FourAlkenyl;   Or R^FiveAnd R^5aTogether, 0 to 3 R^5cReplaced by 3
A 1- to 7-membered cycloalkyl ring can be formed;   R^5bIs H, C in each occurrence₁~ C₆Alkyl, CF₃, OR¹⁴,
Cl, F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, Acetyl, SCH₃, S
(= O) CH₃, S (= O)₂CH₃, C₂~ C₆Alkenyl, C₂~ C₆Alkynyl
, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and
And C₁~ C_FourHaloalkyl-S-, 0 to 3 R^5cC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^5cC replaced by₃~ C_TenCarbocycle, 0 to 3 R^5cC replaced by₆~ C_TenAryl, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^5c5- to 10-membered heterocycle substituted with Independently selected from;   R^5cIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
;   W is-(CR⁸R^8a)_p-Is;   p is 0, 1 or 2;   R⁸And R^8aIs H, F, methyl and ethyl in each occurrence?
Independently selected from   X is a bond, 0 to 3 R^XbA phenyl substituted with, 0 to 3 R^XbC replaced by₃~ C₆Cycloalkyl, or Contains 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 2 R^Xb5- to 6-membered heterocycle substituted with And   R^XbIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
;   Y is a bond or-(CR⁹R^9a)_t-V- (CR⁹R^9a)_u-Is;   t is 0, 1 or 2;   u is 0, 1 or 2;   R⁹And R^9aIs H, F, methyl and ethyl in each occurrence?
Independently selected from   V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O).
)₂-, -N (R¹⁹)-, -C (= O) NH-, or -NHC (= O)-.
R;   Z is H, halo, 0 to 2 R¹²C replaced by₁~ C_FourAlkyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkenyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkynyl, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 6-membered heterocycle substituted with And   Ring B is     [Chemical 4] Selected from;   R¹¹Is H, C in each occurrence₁~ C_FourAlkoxy, Cl, F, Br
, I, = O, CN, NO₂, NR¹⁸R¹⁹, C (= O) R¹⁷, C (= O) OR¹⁷,
C (= O) NR¹⁸R¹⁹, S (= O)₂NR¹⁸R¹⁹, CF₃, 0 to 1 R^11aC replaced by₁~ C₆Alkyl, 0 to 3 R^11bC replaced by₆~ C_TenAryl, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl,
F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, CF₃, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 10-membered heterocycle substituted with Independently selected from;   R^11bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;   R¹³Is H, OH, C in each occurrence.₁~ C₆Alkyl, C₁~ C_FourA
Lucoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, And CF₃From Germany
Standing and selected;   R¹⁴Is, in each occurrence, H, phenyl, benzyl, C₁~ C₆Archi
Le and C₂~ C₆Independently selected from alkoxyalkyl;   R¹⁵Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Le, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, (C₁~ C₆Alkyl)
-OC (= O)-, and (C₁~ C₆Alkyl) -S (= O)₂Independent of
Selected by   R¹⁶Is H, OH, C in each occurrence.₁~ C₆Alkyl, phenyl,
Benzyl, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, (C₁~ C₆Al
Kill) -OC (= O)-, and (C₁~ C₆Alkyl) -S (= O)₂From-
Independently selected;   Alternatively, -NR¹⁵R¹⁶Is piperidinyl, morpholinyl, thiomorpholinyl
, Pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinini
May be a heterocyclic ring selected from the group of   R¹⁷Is H, aryl, aryl-CH₂-, C₁~ C₆Alkyl or C₂~
C₆Alkoxyalkyl;   R¹⁸Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Le, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, and (C₁~ C₆Al
Kill) -S (= O)₂-Independently selected from;   R¹⁹Is H, OH, C in each occurrence.₁~ C₆Alkyl, phenyl,
Benzyl, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, and (C₁~
C₆Alkyl) -S (= O)₂-Independently selected from;   Alternatively, -NR¹⁸R¹⁹Is piperidinyl, morpholinyl, thiomorpholinyl
, Pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinini
May be a heterocyclic ring selected from the group of   R²⁰Is H, OH, C₁~ C_FourAlkyl, phenyl, benzyl or phenethyl
The compound of formula (Ia) according to claim 2 or a pharmaceutical thereof.
Acceptable salt form or prodrug. 5. A compound of formula (Ia) according to claim 4:     [Chemical 5] And In the formula,   Ring B is     [Chemical 6] Selected from;   Q is Q¹Or (C₁~ C₃Alkyl) -O-Q¹And   Q¹Is 0 to 3 R^1aC replaced by₁~ C₆Alkyl, 0 to 3 R^1aC replaced by₂~ C₆Alkenyl, 0 to 3 R^1aC replaced by₂~ C₆Alkynyl, 0 to 3 R^1bC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with And   R^1aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl, F
, Br, I, NR¹⁵R¹⁶, CF₃, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with Independently selected from;   R^1bIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, C₁~ C_FourHaloalkyl-S-, and (C₁~ C₆Alkyl
) -OC (= O)-independently selected from;   R²Is H, methyl or ethyl;   R^FiveIs H, OR¹⁴, 0 to 3 R^5bC replaced by₁~ C₆Alkyl, 0 to 3 R^5bC replaced by₂~ C₆Alkenyl, 0 to 3 R^5bC replaced by₂~ C₆Alkynyl, 0 to 3 R^5cC replaced by₃~ C₆Cycloalkyl, 0 to 3 R^5cC replaced by₃~ C₆Carbocycle, 0 to 3 R^5cPhenyl substituted with, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^5c5- to 7-membered heterocycle substituted with And   R^5aIs H, C₁~ C_FourAlkyl or C₂~ C_FourAlkenyl;   Or R^FiveAnd R^5aTogether, C_Four~ C₇Forming a cycloalkyl ring
Can be;   R^5bIs H, C in each occurrence₁~ C₆Alkyl, CF₃, OR¹⁴,
Cl, F, Br, I, = O, CN, NO₂, NR¹⁵R¹⁶, Acetyl, SCH₃, S
(= O) CH₃, S (= O)₂CH₃, C₂~ C₆Alkenyl, C₂~ C₆Alkynyl
, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, C₁
~ C_FourHaloalkyl-S-, 0 to 3 R^5cC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^5cC replaced by₃~ C_TenCarbocycle, 0 to 3 R^5cC replaced by₆~ C_TenAryl, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^5c5- to 10-membered heterocycle substituted with Independently selected from;   R^5cIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
;   W is-(CR⁸R^8a)_p-Is;   p is 0, 1 or 2;   R⁸And R^8aIs, in each occurrence, independently from H, methyl and ethyl.
Standing and selected;   X is a bond, 0 to 3 R^XbA phenyl substituted with, 0 to 3 R^XbC replaced by₃~ C₆Cycloalkyl, or Contains 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 2 R^Xb5- to 6-membered heterocycle substituted with And   R^XbIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
;   Y is a bond or-(CR⁹R^9a)_t-V- (CR⁹R^9a)_u-Is;   t is 0, 1 or 2;   u is 0, 1 or 2;   R⁹And R^9aIs H, F, methyl and ethyl in each occurrence?
Independently selected from   V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O).
)₂-, -N (R¹⁹)-, -NHC (= O)-, or -C (= O) NH-
R;   Z is H, F, Cl, Br, 0 to 2 R¹²C replaced by₁~ C_FourAlkyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkenyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkynyl, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 6-membered heterocycle substituted with And   R¹¹Is, in each occurrence, H, ═O, NR¹⁸R¹⁹, C (= O) R¹⁷,
C (= O) OR¹⁷, C (= O) NR¹⁸R¹⁹, S (= O)₂NR¹⁸R¹⁹, CF₃, 0 to 1 R^11aC replaced by₁~ C₆Alkyl, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 7-membered heterocycle substituted with Independently selected from;   R^11aIs H, C in each occurrence₁~ C_FourAlkyl, OR¹⁴, Cl,
F, Br, = O, CN, NO₂, NR¹⁵R¹⁶, CF₃, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11b5- to 7-membered heterocycle substituted with Independently selected from;   R^11bIs H, OH, Cl, F, Br, CN, NO in each presence.₂ , NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂CH ₃ , C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~ C_Four
Haloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-;   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;   R¹³Is H, OH, C in each occurrence.₁~ C₆Alkyl, C₁~ C_FourA
Lucoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, And CF₃From Germany
Standing and selected;   R¹⁴Is, in each occurrence, H, phenyl, benzyl, C₁~ C₆Archi
Le and C₂~ C₆Independently selected from alkoxyalkyl;   R¹⁵Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Le, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, (C₁~ C₆Alkyl)
-OC (= O)-, and (C₁~ C₆Alkyl) -S (= O)₂Independent of
Selected by   R¹⁶Is H, OH, C in each occurrence.₁~ C₆Alkyl, phenyl,
Benzyl, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, (C₁~ C₆Al
Kill) -OC (= O)-, and (C₁~ C₆Alkyl) -S (= O)₂From-
Independently selected;   Alternatively, -NR¹⁵R¹⁶Is piperidinyl, morpholinyl, thiomorpholinyl
, Pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinini
May be a heterocyclic ring selected from the group of   R¹⁷Is H, aryl, aryl-CH₂-, C₁~ C₆Alkyl, C₂~ C₆A
Lucoxyalkyl;   R¹⁸Is H, C in each occurrence₁~ C₆Alkyl, phenyl, benz
Le, phenethyl, (C₁~ C₆Alkyl) -C (= O)-, and (C₁~ C₆Al
Kill) -S (= O)₂-Independently selected from;   Alternatively, -NR¹⁸R¹⁹Is piperidinyl, morpholinyl, thiomorpholinyl
, Pyrrolidinyl, homopiperidinyl, piperazinyl and N-methylpiperidinini
May be a heterocyclic ring selected from the group of   R¹⁹Is, in each occurrence, H, OH, methyl, ethyl, propyl, bromo.
Characterized by being independently selected from tyl, phenyl, benzyl and phenethyl
A compound of formula (Ia) according to claim 4. 6. The compound according to claim 5, wherein: In the formula,   Q is Q¹And   Q¹Is 0 to 3 R^1aC replaced by₁~ C₆Alkyl, 0 to 3 R^1aC replaced by₂~ C₆Alkenyl, 0 to 3 R^1aC replaced by₂~ C₆Alkynyl, 0 to 3 R^1bC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with And   R^1aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl, F
, Br, I, NR¹⁵R¹⁶, CF₃, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with Independently selected from;   R^1bIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, C₁~ C_FourHaloalkyl-S-, and (C₁~ C₆Alkyl
) -OC (= O)-independently selected from;   R²Is H, methyl or ethyl;   R^FiveIs H, OR¹⁴, 0 to 3 R^5bC replaced by₁~ C₆Alkyl, 0 to 3 R^5bC replaced by₂~ C₆Alkenyl, or 0 to 3 R^5bC replaced by₂~ C₆Alkynyl And:   R^5aIs H, methyl, ethyl, propyl, butyl, or C₂~ C_FourAlkenyl
And   Or R^FiveAnd R^5aTogether, C_Four~ C₇Forming a cycloalkyl ring
Can be;   R^5bIn each occurrence H, methyl, ethyl, propyl, butyl,
CF₃, OR¹⁴, Cl, F, Br, I, = O, NR¹⁵R¹⁶, 0 to 3 R^5cC replaced by₃~ C₇Cycloalkyl, 0 to 3 R^5cC replaced by₃~ C₇Carbocycle, 0 to 3 R^5cPhenyl substituted with, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^5c5- to 7-membered heterocycle substituted with Independently selected from;   R^5cIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C_FourAlkyl, C₁~ C₃Alkoxy, C₁~ C₂Haloalkyl, and
And C₁~ C₂Independently selected from haloalkoxy;   W is-(CHR⁸)_p-Is;   p is 0 or 1;   R⁸Is H, methyl or ethyl;   X is a bond, 0 to 2 R^XbA phenyl substituted with, 0 to 3 R^XbC replaced by_Five~ C₆Cycloalkyl, or Contains 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 2 R^Xb5- to 6-membered heterocycle substituted with And   R^XbIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
;   Y is a bond, -V-, -CH₂-V-, -V-CH₂-Or-CH₂-V-
CH₂-Is;   V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O).
)₂-Or-N (R¹⁹) -Is;   Z is H, F, Cl, Br, 0 to 2 R¹²C replaced by₁~ C_FourAlkyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkenyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkynyl, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 6-membered heterocycle substituted with And   R¹¹Is, in each occurrence, H, ═O, NR¹⁸R¹⁹, C (= O) R¹⁷,
C (= O) OR¹⁷, C (= O) NR¹⁸R¹⁹, S (= O)₂NR¹⁸R¹⁹, CF₃, 0 to 1 R^11aC replaced by₁~ C₆Alkyl, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11bSubstituted with, and pyridinyl, pyrimidinyl, triazini
, Furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl
, Homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazo
5- to 7-membered heterocycle selected from ril and tetrazolyl Independently selected from;   R^11aIs, in each occurrence, H, methyl, ethyl, propyl, butyl
, Methoxy, ethoxy, propoxy, Cl, F, = O, NR¹⁵R¹⁶, CF₃, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11bSubstituted with, and pyridinyl, pyrimidinyl, triazini
, Furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl
, Homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazo
5- to 7-membered heterocycle selected from ril and tetrazolyl Independently selected from;   R^11bIs H, OH, Cl, F, NR in each occurrence.¹⁵R¹⁶, CF₃ , Acetyl, SCH₃, S (= O) CH₃, S (= O)₂CH₃, Methyl, ethyl,
Propyl, butyl, methoxy, ethoxy, propoxy, C₁~ C₂Haloalkyl,
And C₁~ C₂Independently selected from haloalkoxy;   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;   R¹³Is H, OH, C in each occurrence.₁~ C₆Alkyl, C₁~ C_FourA
Lucoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, And CF₃From Germany
Standing and selected;   R¹⁴Is, in each occurrence, H, phenyl, benzyl, C₁~ C_FourArchi
Le and C₂~ C_FourIndependently selected from alkoxyalkyl;   R¹⁵In each occurrence H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl;   R¹⁶Is, in each occurrence, H, OH, methyl, ethyl, propyl, bromo.
Chill, phenyl, benzyl, phenethyl, CH₃CH₂C (= O)-, CH₃C (
= O)-, CH₃CH₂OC (= O)-, CH₃OC (= O)-, CH₃CH₂S (
= O)₂-, And CH₃S (= O)₂-Independently selected from;   R¹⁷Is H, phenyl, benzyl, C₁~ C_FourAlkyl or C₂~ C_FourArco
Xyalkyl;   R¹⁸In each occurrence H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl; and   R¹⁹In each occurrence H, OH, methyl, ethyl, propyl and
And the compound is independently selected from butyl. 7. A compound according to claim 6, wherein Q is Q ¹ ; Q ¹ is C ₁ -C ₆ alkyl substituted with 0 to 3 R ^1a , C ₂ -C ₆ alkenyl substituted with 0-3 R ^1a, C ₂ -C ₆ alkynyl substituted with 0-3 R ^1a, is substituted with 0-3 R ^1b C ₃ -C ₆ cycloalkyl, contains zero or phenyl substituted by to three R ^1b or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 Is a 5- to 6-membered heterocycle substituted with R ^1b of R ^1a ; R ^1a in each ^occurrence is H, methyl, ethyl, propyl, butyl,
^{OR 14, Cl, F, Br} , I, C 3 ~C 6 carbocycle substituted with _{^{NR 15 R 16, CF 3,}} 0 to 3 amino R ^1b, is substituted with 0-3 R ^1b Phenyl, and independently from a 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. R ^1b is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, C ₁ -C ₂ haloalkoxy, (methyl) OC (= O) -
, (Ethyl) OC (= O)-, (propyl) OC (= O)-, and (butyl)
OC (= O) - independently selected from; R ² is H or methyl; R ⁵ is H, C ₁ -C ₄ alkyl substituted with OR ^14, 0 or to 1 amino R ^5b is 0 or to 1 amino C ₂ -C ₄ alkynyl substituted with C ₂ -C ₄ alkenyl or 0 to 1 amino R ^5b, is substituted with R ^5b; R ^5a is, H, methyl, Is ethyl, propyl or butyl; or R ⁵ and R ^5a can be taken together to form a cyclobutyl ring, a cyclopentyl ring, a cyclohexyl ring or a cycloheptyl ring; R ^5b is H in each occurrence. , Methyl, ethyl, propyl, butyl,
^{_{CF 3, OR 14, Cl,}} F, = O, C 3 ~C 7 cycloalkyl substituted with NR ¹⁵ R ^16, 0-3 R ^5c, is substituted with 0-3 R ^5c C ₃ -C ₇ carbocyclic ring contains zero or phenyl substituted with to three R ^5c, and nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 Substituted with R ^5c and is pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,
Independently selected from a 5- to 7-membered heterocycle selected from homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and tetrazolyl; R ^5c in each ^occurrence is H, OH, Cl, F, NR ¹⁵ R ¹⁶ , CF ₃
, Acetyl, SCH ₃ , S (═O) CH ₃ , S (═O) ₂ CH ₃ , methyl, ethyl,
Propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl,
And C ₁ -C ₂ are independently selected from haloalkoxy; W is a bond, -CH ₂ -, or -CH (CH ₃₎ - a and; X is a bond, with 0 to 1 amino R ^Xb Substituted phenyl, 0 to 1 C ₅ -C ₆ cycloalkyl substituted with R ^xb , or containing 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 Substituted with 1 R ^Xb and is pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,
A 5- to 6-membered heterocycle selected from pyrazolyl, imidazolyl, oxazolyl and isoxazolyl; R ^Xb , in each ^occurrence, is H, OH, Cl, F, Br, NR ¹⁵ R ¹⁶ ,
CF _{3, acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2 CH 3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ ~ It is independently selected from C ₂ haloalkoxy; Y is a bond, -V -, - V-CH 2 -, or a -CH ₂ V-; V is a bond, -C (= O) -, - O-, -S-, -S (= O)-, -S (= O
) _2- , or -N (R ¹⁹ )-; Z is H, F, Cl, Br, C ₁ -C ₄ alkyl substituted with 0 to 2 R ¹² , 0 to 2 C ₂ is substituted with R ¹² in -C ₄ alkenyl, 0-2 C ₂ -C ₄ alkynyl substituted with R ^12, C ₆ -C ₁₀ substituted with 0-4 R ^12b aryl, contain 0-4 C ₃ -C ₆ carbocycle substituted with R ^12b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 Is a 5- to 6-membered heterocycle substituted with R ^12b ; R ¹¹ in each occurrence is H, NR ¹⁸ R ¹⁹ , CF ₃ , C substituted with 0 to 1 R ^11a. ₁ -C ₄ alkyl, phenyl substituted with 0-3 R ^11b, 0-3 C ₃ -C ₆ carbocycle substituted with R ^11b or nitrogen, selected from oxygen and sulfur Containing 1 to 4 heteroatoms selected and substituted with 0 to 3 R ^<11b > and pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl , Imidazolyl, oxazolyl, isoxazolyl and tetrazolyl independently selected from a 5- to 7-membered heterocycle; R ^11a in each ^occurrence is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, = O, NR 15 R 16, CF 3, 0 or phenyl substituted with to three R ^11b, C ₃ ~C ₆ carbocycle substituted with 0-3 R ^11b , or nitrogen containing 1 to 4 heteroatoms selected from oxygen and sulfur, and substituted with 0-3 R ^11b Then pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, is independently selected from heterocyclic ring of 5 to 7 ring members selected from isoxazolyl and tetrazolyl; R ^11b is H, OH, Cl, F, NR ¹⁵ R ¹⁶ , CF ₃ , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C _{1 in each} occurrence.
˜C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy independently; R ¹² in each occurrence is H, OH, Cl, F, Br, NR ¹⁵ R ¹⁶ ,
^{-C (= O) NR 15 R} 16, CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (
═O) ₂ CH ₃ , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy, phenyl substituted with ^0-4 R ^12b. , A C _{3 to} C ₆ carbocycle substituted with 0 to 4 R ^12b , or 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 to 3 is independently selected from heterocyclic ring 5-6 membered substituted with R ^12b; R ^12b, at each occurrence, H, OH, Cl, F , Br, NR 15 R 16
, CF ₃ , acetyl, SCH ₃ , S (═O) CH ₃ , S (═O) ₂ CH ₃ , methyl,
Independently selected from ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy; R ¹³ in each ^occurrence is H, OH, methyl, ethyl. , Propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, Br, CN, NR ¹⁵ R ¹⁶ ,
And CF ₃ independently in each occurrence; R ¹⁴ in each ^occurrence is independently selected from H, phenyl, benzyl, methyl, ethyl, propyl and butyl; R ¹⁵ in each occurrence is H, R ¹⁶ is independently selected from methyl, ethyl, propyl or butyl; R ¹⁶ is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and phenethyl in each occurrence; R ¹⁸ is , In each occurrence H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl; and R ¹⁹ in each occurrence is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and phenethyl. The compound according to claim 6. 8. A compound according to claim 7, wherein: In the formula,   Q is -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH₂CH₂CH₂CH₃ , -CH₂CH₂CH₂CH₂CH₃, -CH₂CH₂CH₂CH₂CH₂CH₃, -CH
(CH₃)₂, -CH (CH₃) CH₂CH₃, -CH₂CH (CH₃)₂, -CH₂C
(CH₃)₃, -CF₃, -CH₂CF₃, -CH₂CH₂CF₃, -CH₂CH₂CH₂CF₃, -CH = CH₂, -CH₂CH = CH₂, -CH₂C (CH₃) = CH₂, -CH₂C
H = C (CH₃)₂, -CH₂CH₂CH = CH₂, -CH₂CH₂C (CH₃) = CH ₂ , -CH₂CH₂CH = C (CH₃)₂, Cis-CH₂CH = CH (CH₃), C
is-CH₂CH₂CH = CH (CH₃), Trans-CH₂CH = CH (CH₃
), Trans-CH₂CH₂CH = CH (CH₃), -C≡CH, -CH₂C≡CH, -CH₂C≡C (CH₃), Cyclopropyl-, cyclobutyl-, cyclopentyl-, cyclohexyl-, cyclo
Clopropyl-CH₂-, Cyclobutyl-CH₂-, Cyclopentyl-CH₂-,
Cyclohexyl-CH₂-, Cyclopropyl-CH₂CH₂-, Cyclobutyl-C
H₂CH₂-, Cyclopentyl-CH₂CH₂-, Cyclohexyl-CH₂CH₂-,
Phenyl-, 2-F-phenyl-, 3-F-phenyl-, 4-F-phenyl-,
4-methoxyphenyl-, 4-ethoxyphenyl-, 4-propoxyphenyl-
, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) C
H₂-, (4-F-phenyl) CH₂-, (2-Cl-phenyl) CH₂-, (3
-Cl-phenyl) CH₂-, (4-Cl-phenyl) CH₂-, (2,3-diF-phenyl) CH₂-, (2,4-diF-phenyl) CH₂-, (
2,5-diF-phenyl) CH₂-, (2,6-diF-phenyl) CH₂-, (3
, 4-diF-phenyl) CH₂-, (3,5-diF-phenyl) CH₂-, (2
3-diCl-phenyl) CH₂-, (2,4-diCl-phenyl) CH₂-, (2
, 5-diCl-phenyl) CH₂-, (2,6-diCl-phenyl) CH₂-, (
3,4-diCl-phenyl) CH₂-, (3,5-diCl-phenyl) CH₂-,
(3-F-4-Cl-phenyl) CH₂-, (3-F-5-Cl-phenyl) C
H₂-, (3-Cl-4-F-phenyl) CH₂-, 2-furanyl-CH₂-, 3-furanyl-CH₂-, 2-thienyl-CH₂-3
-Thienyl-CH₂-, 2-pyridyl-CH₂-, 3-pyridyl-CH₂-, 4-
Pyridyl-CH₂-, 1-imidazolyl-CH₂-, 2-oxazolyl-CH₂−
, 4-oxazolyl-CH₂-, 5-oxazolyl-CH₂-, 3-isoxazo
Lil-CH₂-, 4-isoxazolyl-CH₂-, 5-isoxazolyl-CH ₂ -, Phenyl-CH₂CH₂-, (2-F-phenyl) CH₂CH₂-, (3-F-fe
Nil) CH₂CH₂-, (4-F-phenyl) CH₂CH₂-, (2-Cl-phenyl
Le) CH₂CH₂-, (3-Cl-phenyl) CH₂CH₂-, (4-Cl-phenyl
Le) CH₂CH₂− (2,3-diF-phenyl) CH₂CH₂-, (2,4-diF-phenyl) CH₂
CH₂-, (2,5-diF-phenyl) CH₂CH₂-, (2,6-diF-phenyl
Le) CH₂CH₂-, (3,4-diF-phenyl) CH₂CH₂-, (3,5-di-F
-Phenyl) CH₂CH₂-, (2,3-diCl-phenyl) CH₂CH₂-, (2
, 4-diCl-phenyl) CH₂CH₂-, (2,5-diCl-phenyl) CH₂
CH₂-, (2,6-diCl-phenyl) CH₂CH₂-, (3,4-diCl-f
CH) CH₂CH₂-, (3,5-diCl-phenyl) CH₂CH₂-, (3-F
-4-Cl-phenyl) CH₂CH₂-, (3-F-5-Cl-phenyl) CH₂
CH₂-, Furanyl-CH₂CH₂-, Thienyl-CH₂CH₂-, Pyridyl-CH₂CH₂-,
1-Imidazolyl-CH₂CH₂-, Oxazolyl-CH₂CH₂-, Isoxazo
Lil-CH₂CH₂-, 3,5-dimethylisoxazol-4-yl-CH₂C
H₂-, Phenyl-propyl-, Benzyl-CH (NH₂)-, Benzyl-CH (NHC (= O) -O-tBu)
-, Benzyloxy-CH₂-, Pyrrolidin-2-yl-, or 3-t-but
Xycarbonylcarbonylpyrrolidin-2-yl- And   R²Is H or methyl;   R^FiveIs -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH (CH₃)₂,-
CH₂CH₂CH₂CH₃, -CH (CH₃) CH₂CH₃, -CH₂CH (CH₃)₂,
-CH₂C (CH₃)₃, -CH₂CH₂CH₂CH₂CH₃, -CH (CH₃) CH₂C
H₂CH₃, -CH₂CH (CH₃) CH₂CH₃, -CH₂CH₂CH (CH₃)₂,-
CH (CH₂CH₃)₂, -CF₃, -CH₂CF₃, -CH₂CH₂CF₃, -CH₂CH₂CH₂CF₃, -CH ₂ CH₂CH₂CH₂CF₃, -CH = CH₂, -CH₂CH = CH₂, -CH₂CH₂CH = CH₂, -CH = CH
CH₃, Cis-CH₂CH = CH (CH₃), Trans-CH₂CH = CH (C
H₃), Trans-CH₂CH = CH (C₆H_Five), -CH₂CH = C (CH₃)₂
, Cis-CH₂CH = CHCH₂CH₃, Trans-CH₂CH = CHCH₂C
H₃, Cis-CH₂CH₂CH = CH (CH₃), Trans-CH₂CH₂CH =
CH (CH₃), Trans-CH₂CH = CHCH₂(C₆H_Five), -C≡CH, -CH₂C≡CH, -CH₂C≡C (CH₃), -CH₂C≡C (C₆
H_Five), -CH₂CH₂C≡CH, -CH₂CH₂C≡C (CH₃), -CH₂CH₂C
≡ C (C₆H_Five), -CH₂CH₂CH₂C≡CH, -CH₂CH₂CH₂C≡C (CH ₃ ), -CH₂CH₂CH₂C≡C (C₆H_Five), Cyclopropyl-CH₂-, Cyclobutyl-CH₂-, Cyclopentyl-CH₂−
, Cyclohexyl-CH₂-, (2-CH₃-Cyclopropyl) CH₂-, (3-
CH₃-Cyclobutyl) CH₂-, Cyclopropyl-CH₂CH₂-, Cyclobutyl
-CH₂CH₂-, Cyclopentyl-CH₂CH₂-, Cyclohexyl-CH₂CH₂ -, (2-CH₃-Cyclopropyl) CH₂CH₂-, (3-CH₃-Cyclobutyl
) CH₂CH₂-, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) CH ₂ -, (4-F-phenyl) CH₂-, (3,5-diF-phenyl) CH₂-2
-Furanyl-CH₂-, 3-furanyl-CH₂-, 2-thienyl-CH₂-, 3-
Thienyl-CH₂-, 2-pyridyl-CH₂-, 3-pyridyl-CH₂-, 4-pi
Lysyl-CH₂-, 1-imidazolyl-CH₂-, 2-oxazolyl-CH₂-,
4-oxazolyl-CH₂-, 5-oxazolyl-CH₂-, 3-isoxazoli
Le-CH₂-, 4-isoxazolyl-CH₂-, 5-isoxazolyl-CH₂
-, Phenyl-CH₂CH₂-, (2-F-phenyl) CH₂CH₂-, (3-F-fe
Nil) CH₂CH₂-, (4-F-phenyl) CH₂CH₂-, Furanyl-CH₂C
H₂-, Thienyl-CH₂CH₂-, Pyridyl-CH₂CH₂-, 1-Imidazolyl
-CH₂CH₂-, Oxazolyl-CH₂CH₂-, Isoxazolyl-CH₂CH₂ -, Methoxy, ethoxy, propoxy, or butoxy And   R^5aIs H,   Or R^FiveAnd R^5aTogether, cyclopentyl, cyclohexyl
Or it can form cycloheptyl;   W is a bond, -CH₂-, Or -CH (CH₃) -Is;   X is a bond,     [Chemical 7] And   Y is a bond, -CH₂-V-, -V-, or -V-CH₂-Is;   V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O).
)₂-, -NH-, or -N (CH₃) -Is;   Z is H, F, Cl, Br, methyl, ethyl, n-propyl, i-propyl,
n-butyl, i-butyl, s-butyl, t-butyl, Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl
-Phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl
2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl
3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCl-phen
Nyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl
-Phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-
4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Cl-4-F-phenyl
2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2
-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl
Phenyl, 3-MeS-phenyl, 4-MeS-phenyl, 2-CF₃O-pheny
Le, 3-CF₃O-phenyl, 4-CF₃O-phenyl, Furanyl, thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl, 4
-Me-pyridyl, l-imidazolyl, oxazolyl, isoxazolyl, 1-
Benzimidazolyl, morpholino, N-piperidinyl, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) CH ₂ -, (4-F-phenyl) CH₂-, (2-Cl-phenyl) CH₂-, (3-
Cl-phenyl) CH₂-, (4-C1-phenyl) CH₂-, (2,3-di-F-
Phenyl) CH₂-, (2,4-diF-phenyl) CH₂-, (2,5-di-F-f
CH) CH₂-, (2,6-diF-phenyl) CH₂-, (3,4-diF-fe
Nil) CH₂-, (3,5-diF-phenyl) CH₂-, (2,3-diCl-phen
Nil) CH₂-, (2,4-diCl-phenyl) CH₂-, (2,5-diCl-f
CH) CH₂-, (2,6-diCl-phenyl) CH₂-, (3,4-diCl-
Phenyl) CH₂-, (3,5-diCl-phenyl) CH₂-, (3-F-4-C
l-phenyl) CH₂-, (3-F-5-Cl-phenyl) CH₂-, (3-Cl
-4-F-phenyl) CH₂-, (2-MeO-phenyl) CH₂-, (3-Me
O-phenyl) CH₂-, (4-MeO-phenyl) CH₂-, (2-PhO-F
CH) CH₂-, (3-PhO-phenyl) CH₂-, (4-PhO-phenyl
) CH₂-, (2-Me-phenyl) CH₂-, (3-Me-phenyl) CH₂−
, (4-Me-phenyl) CH₂-, (2-MeS-phenyl) CH₂-, (3-
MeS-phenyl) CH₂-, 4-MeS-phenyl) CH₂-, (2-CF₃O
-Phenyl) CH₂-, (3-CF₃O-phenyl) CH₂-, (4-CF₃OF
CH) CH₂-, (Furanyl) CH₂-, (Thienyl) CH₂-, (Pyridyl)
CH₂-, (2-Me-pyridyl) CH₂-, (3-Me-pyridyl) CH₂-,
(4-Me-pyridyl) CH₂-, (1-imidazolyl) CH₂-, (Oxazoli
Le) CH₂-, (Isoxazolyl) CH₂-, (1-benzimidazolyl) CH ₂ -, (Cyclopropyl) CH₂-, (Cyclobutyl) CH₂-, (Cycloplier
Le) CH₂-, (Cyclohexyl) CH₂-, (Morpholino) CH₂-, (N-pi
Peridinyl) CH₂-, Phenyl-CH₂CH₂-, (Phenyl)₂CHCH₂-, (2-F-phenyl) C
H₂CH₂-, (3-F-phenyl) CH₂CH₂-, (4-F-phenyl) CH₂
CH₂-, (2-Cl-phenyl) CH₂CH₂-, (3-Cl-phenyl) CH₂ CH₂-, (4-Cl-phenyl) CH₂CH₂-, (2,3-diF-phenyl)
CH₂CH₂-, (2,4-diF-phenyl) CH₂CH₂-, (2,5-di-F-f
CH) CH₂CH₂-, (2,6-diF-phenyl) CH₂CH₂-, (3,4-
Di-F-phenyl) CH₂CH₂-, (3,5-diF-phenyl) CH₂CH₂-, (
2,3-diCl-phenyl) CH₂CH₂-, (2,4-diCl-phenyl) CH ₂ CH₂-, (2,5-diCl-phenyl) CH₂CH₂-, (2,6-diCl-f
CH) CH₂CH₂-, (3,4-diCl-phenyl) CH₂CH₂-, (3,5
-DiCl-phenyl) CH₂CH₂-, (3-F-4-Cl-phenyl) CH₂C
H₂-, (3-F-5-Cl-phenyl) CH₂CH₂-, (3-Cl-4-F-
Phenyl) CH₂CH₂-, (2-MeO-phenyl) CH₂CH₂-, (3-Me
O-phenyl) CH₂CH₂-, (4-MeO-phenyl) CH₂CH₂-, (2-
Me-phenyl) CH₂CH₂-, (3-Me-phenyl) CH₂CH₂-, (4-
Me-phenyl) CH₂CH₂-, (2-MeS-phenyl) CH₂CH₂-, (3
-MeS-phenyl) CH₂CH₂-, (4-MeS-phenyl) CH₂CH₂-,
(2-CF₃O-phenyl) CH₂CH₂-, (3-CF₃O-phenyl) CH₂C
H₂-, (4-CF₃O-phenyl) CH₂CH₂-, (Furanyl) CH₂CH₂-,
(Thienyl) CH₂CH₂-, (Pyridyl) CH₂CH₂-, (2-Me-pyridyl
) CH₂CH₂-, (3-Me-pyridyl) CH₂CH₂-, (4-Me-pyridyl
) CH₂CH₂-, (Imidazolyl) CH₂CH₂-, (Oxazolyl) CH₂CH₂ -, (Isoxazolyl) CH₂CH₂-, (Benzimidazolyl) CH₂CH₂−
, (Cyclopropyl) CH₂CH₂-, (Cyclobutyl) CH₂CH₂-, (Cyclo
Pentyl) CH₂CH₂-, (Cyclohexyl) CH₂CH₂-, (Morpholino) C
H₂CH₂-, Or (N-piperidinyl) CH₂CH₂− And   R¹¹In each occurrence H, methyl, ethyl, n-propyl, i-
Propyl, n-butyl, i-butyl, s-butyl, t-butyl, phenyl, benzene
Zil, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl
Xyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclo
Pentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclopropyi
Ruethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl
, 2-F-phenyl-, 3-F-phenyl, 4-F-phenyl, 4-Cl-phen
Nil, 4-CH₃-Phenyl, 4-MeO-phenyl-, 4-CF₃-Phenyl,
(4-F-phenyl) CH₂-, (4-C1-phenyl) CH₂-, (4-CH₃
-Phenyl) CH₂-, (4-CF₃-Phenyl) CH₂-, (4-F-phenyl
) CH₂CH₂-, (4-C1-phenyl) CH₂CH₂-, (4-CH₃-Pheny
Le) CH₂CH₂-, (4-CF₃-Phenyl) CH₂CH₂-, Pyridin-2-i
Ru-, pyridin-3-yl-, 4-CF₃-Pyridin-2-yl-, 4-CH₃−
Pyridin-2-yl-, thiazol-2-yl-, azapan-1-yl, N, N
-Dimethylamino, N, N-diethylamino, N, N-dipropylamino, and
And N, N-dibutylamino Independently selected from; and   R¹³Is independently selected from H, MeO, F and Cl in each occurrence.
The compound of claim 7, wherein the compound is selected. 9. A compound of formula (Ic): Alternatively, the compound according to claim 5, 6, 7 or 8, which is a pharmaceutically acceptable salt form or a prodrug thereof. 10. A compound of formula (Id): embedded image Alternatively, the compound according to claim 5, 6, 7 or 8, which is a pharmaceutically acceptable salt form or a prodrug thereof. 11. A compound of formula (Ie): embedded image Alternatively, the compound according to claim 5, 6, 7 or 8, which is a pharmaceutically acceptable salt form or a prodrug thereof. 12. The following compound: 3- (2 (R) -cyclopentylmethyl-3 (S) -hydroxyl-1-oxo.
-5-Phenylpentyl) amino-1-methyl-5-phenyl-2,3-dihydr
Ro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -cyclopentylmethyl-3 (S) -hydroxyl-1-oxo
-5-Phenylpentyl) amino-1-methyl-5- (4-fluorophenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -benzyl-3 (S) -hydroxyl-1-oxo-5-phenyl
Rupentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1
, 4-benzodiazepin-2-one; 3- (2 (R) -isopropyl-3 (S) -hydroxyl-1-oxo-5-phenyl
Phenylpentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H
-1,4-benzodiazepin-2-one; 3- (2 (R) -cyclopentylmethyl-3 (S) -hydroxyl-1-oxo
-4- (3,5-Difluorophenoxy) butyl) amino-1-methyl-5-phenyl
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl) -3 (S) -hydroxyl-1-oxo-4- (
3,5-difluorophenoxy) butyl) amino-1-methyl-5-phenyl-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -cyclopentylmethyl-3 (S) -hydroxyl-1-oxo
-4-phenoxybutyl) amino-7-chloro-1-methyl-5-phenyl-2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-phen
Noxybutyl) amino-7-chloro-1-methyl-5- (4-fluorophenyl
) -2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4-cyclohexyl
Xyloxybutyl) amino-1-methyl-5-phenyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-cyclyl
Lohexyloxybutyl) amino-1-methyl-5-phenyl-2,3-dihydr
Ro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4-phenoxy
Cibutyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro
-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-phen
Noxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihi
Doro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -benzyl-3 (S) -hydroxyl-1-oxo-4-cyclo
Hexyloxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,
3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -cyclopentylmethyl-3 (S) -hydroxyl-1-oxo
-4-Cyclohexyloxybutyl) amino-7-chloro-1-methyl-5-phenyl
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-cyclyl
Lohexyloxybutyl) amino-7-chloro-1-methyl-5-phenyl-2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isopropyl-3 (S) -hydroxyl-1-oxo-4-si
Chlorohexyloxybutyl) amino-7-chloro-1-methyl-5-phenyl-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -methoxy-3 (S) -hydroxyl-1-oxo-4- (4-
Trifluoromethylbenzyloxy) butyl) amino-7-chloro-1-methyl
-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine-2-o
3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4- (2,4
-Difluorobenzyloxy) butyl) amino-7-chloro-1-methyl-5-
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -vinyl-3 (S) -hydroxyl-1-oxo-4-benzyl
Oxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihi
Doro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-4-cyclohexyl
Xyloxybutyl) amino-7-chloro-1-methyl-5-phenyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-5-phen
Nylpentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-3-cyclyl
Ropropylpropyl) amino-1-methyl-5-phenyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-heptyl
) Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-ben
Zodiazepine-2-one; 3- (R)-(2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-
Heptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (S)-(2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-
Heptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-nonyl)
Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzo
Diazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-hexyl
) Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-ben
Zodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-4-phen
Nylbutyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1
, 4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-5-phenyl
Pentyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-6-phenyl
Hexyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-butyl)
Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzo
Diazepin-2-one; 3- (2 (R) -isobutyl-3 (S) -hydroxyl-1-oxo-octyl
) Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-ben
Zodiazepine-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-heptyl) a
Mino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodi
Azepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-3-phenyl
Propyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-5,5-dime
Cylhexyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-hexyl) a
Mino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodi
Azepin-2-one; 3- (2 (R) -methyl-3 (S) -hydroxyl-1-oxo-3- (4-propyl)
Ropoxyphenyl) propyl) amino-1-methyl-5-phenyl-2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 2- (R) -cyclopropylmethyl-3- (S) -hydroxylheptanoic acid (2
-Oxo-1- (3-phenoxybenzyl) azapan-3- (S) -yl) ami
2 (R) -cyclopropylmethyl-5- (3,5-difluorophenyl) -3-
(S) -Hydroxypentanoic acid (2-oxo-1- (3-phenoxybenzyl)
Azapan-3- (S) -yl) amide; 4-Cyclopentyl-2- (R) -cyclopropylmethyl-3- (S) -hydro
Xybutanoic acid (2-oxo-1- (3-phenoxybenzyl) azapan-3- (
S) -yl) amide; 2- (R) -cyclopropylmethyl-3- (S) -hydroxyheptanoic acid (1-
(5-Bromo-3-pyridinyl) methyl-2-oxo-azapan-3- (S)-
Yl) amide; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5- (2-fluorophenyl) -1-methyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5- (azapan-1-yl) -1-methyl-2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-5- (3,5-difluorophenyl)
) -3 (S) -Hydroxyl-1-oxopentyl) amino-1-methyl-5-
(Pyridin-2-yl) -2,3-dihydro-1H-1,4-benzodiazepine
-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxopentyl) amino-1-methyl-5- (4-chlorophenyl) -2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5- (4-methoxyphenyl) -1-methyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5- (4-methoxyphenyl) -1-methyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(4-cyclopentyl-2- (R) -cyclopropylmethyl-3-
(S) -hydroxyl-1-oxobutyl) amino-1-methyl-5-phenyl
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-3- (S) -hydroxyl
-1-Oxohepta-6-enyl) amino-1-methyl-5-phenyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xohepta-6-enyl) amino-1-methyl-5- (4-trifluoromethyl)
Phenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-5- (3,5-dimethylyl)
Sooxazol-4-yl) -3- (S) -hydroxyl-1-oxopentyl
) Amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-ben
Zodiazepine-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-7-chloro-1-methyl-5-phenyl-2,3-dihi
Doro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl- (pyridin-2-yl) -2,3-dihydride
Ro-1H-1,4 benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-
Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (5-cyclopentyl-2- (R) -cyclopropylmethyl-3- (S)-
Hydroxyl-1-oxopentyl) amino-1-methyl-5- (pyridine-2
-Yl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -iso-butyl-3- (S) -hydroxyl-1-oxophenyl
Butyl) amino-1-methyl-5- (4-trifluoromethylphenyl) -2,
3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-3- (S) -hydroxyl
-1-oxo-5- (thiophen-2-yl) amino-1-methyl-5-phenyl
Le-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-5- (furan-2-yl)
3- (S) -hydroxyl-1-oxopentyl) amino-1-methyl-5-phenyl
Phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (5-cyclopentyl-2- (R) -cyclopropylmethyl-3- (S)-
Hydroxyl-1-oxopentyl) amino-5- (4-fluorophenyl)-
1-Methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-5- (3,5-difluoro)
Phenyl) -3- (S) -hydroxy-1-oxopentyl) amino-1-methyl
Lu-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine-2-
ON; 3- (S)-(3- (S) -hydroxyl-2- (R)-(thiophen-2-i
) Methyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclopropylmethyl-3- (S) -hydroxyl
-1-Oxoheptyl) amino-7-methyl-5-phenyl-2,3-dihydro
-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-7-methoxy-1-methyl-5-phenyl-2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -cyclobutylmethyl-3- (S) -hydroxyl-
1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R)-(3,5-difluorobenzyl) -3- (S) -hi
Droxyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R)-(furan-2-yl) methyl-3- (S) -hydro.
Xyl-1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xo-5-phenylpentyl) amino-1-methyl-5- (pyridin-2-yl
) -2,3-Dihydro-1H-benzodiazepin-2-one; 3- (2- (R) -iso-butyl-3- (S) -hydroxyl-1-oxophenyl
Butyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-dihydr
B-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -iso-butyl-3- (S) -hydroxyl-1-oxohe
Butyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-dihydr
B-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xo-5-phenylpentyl) amino-1-methyl-5-phenyl-2,3-di
Hydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-5- (furan-2-yl) -3- (
S) -hydroxyl-1-oxopentyl) amino-1-methyl-5- (4-to
Lifluoromethylphenyl) -2,3-dihydro-1H-1,4-benzodiaze
Pin-2-one; 3- (5-Cyclopentyl-2- (R) -cyclopropylmethyl-3- (S)-
Hydroxyl-1-oxopentyl) amino-1-methyl-5- (4-triflu
Oromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-
2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxooctyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xisononyl) amino-1-methyl-5- (4-trifluoromethylphenyl)-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethyl (pyridine
-2-yl))-2,3-dihydro-1H-1,4-benzodiazepine-2-o
3- (2- (R) -cyclobutylmethyl-3- (S) -hydroxyl-1-oxy
Soheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopentylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-methyl-2-pyridyl) -2
, 3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-methyl-2-pyridyl) -2,
3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxobutyl) amino-1-methyl-5- (4-trifluoromethylphenyl)-
2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R)-(3-butenyl) -3- (S) -hydroxyl-1
-Oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1
H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R)-(3-methylbutyl) 3- (S) -hydroxyl-
1-oxoheptyl) amino-1-methyl-5-phenyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (S)-(2- (R) -ethyl-3- (S) -hydroxyl-1-oxohe
Butyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4
-Benzodiazepin-2-one; 3- (S)-(2- (R) -propyl-3- (S) -hydroxyl-1-oxo
Heptyl) amino-1-methyl-5-phenyl-2,3-dihydro-1,4-be
3- (S)-(2- (R) -Butyl-3- (S) -hydroxyl-1-oxohexanone;
Butyl) amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4
-Benzodiazepin-2-one; 3- (4- (S) -amino-3- (R) -hydroxyl-2- (R) -methyl-
1-oxo-5-phenylpentyl) amino-7-chloro-5- (2-fluoro
Phenyl) -1-methyl-2,3-dihydro-1H-1,4-benzodiazepine
2-one; 3- (4- (S)-(tert-butoxycarbonylamino-3- (R) -hydr
Roxyl-2- (R) -methyl-1-oxo-5-phenylpentyl) amino-
7-chloro-5- (2-fluorophenyl) -1-methyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (3- (tert-butoxycarbonylpyrrolidin-2- (R) -yl)-
3- (R) -hydroxyl-2- (R) -methyl-1-oxopropyl) amino
-7-chloro-5- (2-fluorophenyl) -1-methyl-2,3-dihydro
-1H-1,4-benzodiazepin-2-one; 3- (3- (R) -hydroxyl-2- (R) -methyl-1-oxo-3- (py
Roridin-2- (R) -yl) propyl) -amino-7-chloro-5- (2-phenyl)
Luorophenyl) -1-methyl-2,3-dihydro-1H-1,4-benzodia
Zepin-2-one; 3- (4-benzyloxy-3- (R) -hydroxyl-2- (R) -iso-
Propyl-1-oxobutyl-amino-7-chloro-1-methyl-5-phenyl
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 2- (4- (S) -amino-3- (S) -hydroxyl-2- (S) -methyl-
1-oxo-5-phenylpentyl) amino-7-chloro-5- (2-fluoro
Phenyl) -1-methyl-2,3-dihydro-1H-1,4-benzodiazepine
2-one; 2- (4- (S)-(tert-butoxycarbonylamino-3- (S) hydro)
Xyl-2- (S) -methyl-1-oxo-5-phenylpentyl) amino-7
-Chloro-5- (2-fluorophenyl) -1-methyl-2,3-dihydro-1
H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (thiazol-2-yl) -2,3-
Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-cyclopropylmethyl-5- (thiazol-2-i
) -2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-cyclopropylmethyl-5- (4-trifluorome
Cylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-2-o
3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoheptyl) amino-1-benzyl-5- (4-trifluoromethylphenyl)
) -2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (3-phenoxybenzyl) -5- (4-triflu
Oromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-
2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (3-pyridinylmethyl) -5- (4-trifluoro)
Romethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-2
-One; 3- (2- (S) -cyclopropylmethyl-3- (R) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (S) -cyclopropylmethyl-3- (R) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (R) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (S) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (S) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-methyl-5- (4-trifluoromethylphenyl)
-2,3-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-3- (
S) -Methyl-1-oxoheptyl) amino-1-methyl-5- (4-triflu
Oromethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-
2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (3-phenoxybenzyl) -5-methyl-2,3
-Dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-benzyl-5-methyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one; 3- (3- (S) -acetoxy-2- (R) -iso-butyl-1-oxohep
Cyl) amino-5- (4-fluorophenyl) -1-methyl-2,3-dihydro
-1H-1,4-benzodiazepin-2-one; 3- (S)-(5-cyclopentyl-2- (R) -cyclopropylmethyl-3-
(S) -Methoxy-1-oxopentyl) amino-1-methyl-5-phenyl-
2,3-dihydro-1H-1,4-benzodiazepin-2-one; 1- (1-hydroxypentyl) cyclohexanecarboxylic acid (5- (4-fluoro
Rophenyl) -1-methyl-2-oxo-2,3-dihydro-1H-1,4-be
Nazodiazepin-3-yl) amide; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5-methyl-5H, 7H-dibenzo [b, d] azepine
-6-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xooctyl) amino-5-methyl-5H, 7H-dibenzo [b, d] azepine
-6-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xynonyl) amino-5-methyl-5H, 7H-dibenzo [b, d] azepine-
6-one; 3- (2- (R) -cyclopropylmethyl-5- (furan-2-yl) -3- (
S) -Hydroxyl-1-oxopentyl) amino-5-methyl-5H, 7H-
Dibenzo [b, d] azepin-6-one; 2- (R) -cyclopropylmethyl-3- (S) -hydroxylheptanoic acid (2
-Oxo-1- (3-phenylamino-benzyl) azapan-3- (S) -yl
) Amide; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5-cyclopentyl-1-methyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5-benzyl-1-methyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5-benzyl-1-butyl-2,3-dihydro-1H-
1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-5-cycloheptyl-1-methyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-benzyl-5-cycloheptyl-2,3-dihydro
-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-butyl-5-cycloheptyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (2-pyridinylmethyl) -5- (4-trifluor)
Romethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-2
-One; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (3-pyridinylmethyl) -5- (2-fluorophenyl)
Phenyl) -2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (S) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxopentyl) amino-1- (3-pyridinylmethyl) -5- (4-trifluor)
Romethylphenyl) -2,3-dihydro-1H-1,4-benzodiazepine-2
-One; 3- (2-1 (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-
Oxoheptyl) amino-1-methyl-5- (N, N-dibutylamino) -2,
3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-n-butyl-5-t-butyl-2,3-dihydro-
1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (2-oxo-3,3-dimethylbutyl) -5-n
-Butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1-benzyl-5-t-butyl-2,3-dihydro-1
H-1,4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-3- (S) -hydroxyl-1-o
Xoxoheptyl) amino-1- (2-picolyl) -5-n-butyl-2,3-dihi
Doro-1H-1,4-benzodiazepin-2-one; 3- (2- (R) -isobutyl-3- (S) -hydroxyl-1-oxohepti
Amino) methyl-1-methyl-5-homopiperidino-2,3-dihydro-1H-1,
4-benzodiazepin-2-one; 3- (2- (R) -cyclopropylmethyl-1,3-dioxoheptyl) amino
-1-Methyl-5- (4-trifluoromethylphenyl) -2,3-dihydro-
1H-1,4-benzodiazepin-2-one; and 1-pentylylcyclohexanecarboxylic acid (5- (4-fluorophenyl) -1
-Methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepine-
A compound selected from 3-yl) amide. 13. The compound according to claim 12, wherein the stereochemistry of the 3-position carbon in the lactam ring B is S configuration. 14. The compound according to claim 12, wherein the stereochemistry of the 3-position carbon in the lactam ring B is R configuration. 15. A compound of formula (Ib):     [Chemical 11] And In the formula,   Ring B is     [Chemical 12] Selected from;   Q¹Is 0 to 3 R^1aC replaced by₁~ C₆Alkyl, 0 to 3 R^1aC replaced by₂~ C₆Alkenyl, 0 to 3 R^1aC replaced by₂~ C₆Alkynyl, 0 to 3 R^1bC replaced by₃~ C_TenCycloalkyl, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with And   R^1aIs H, C in each occurrence₁~ C₆Alkyl, OR¹⁴, Cl, F
, Br, I, NR¹⁵R¹⁶, CF₃, 0 to 3 R^1bC replaced by₃~ C_TenCarbocycle, 0 to 3 R^1bC replaced by₆~ C_TenAryl, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^1b5- to 10-membered heterocycle substituted with Independently selected from;   R^1bIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, C₁~ C_FourHaloalkyl-S-, and (C₁~ C₆Alkyl
) -OC (= O)-independently selected from;   R^FiveIs OR¹⁴, 0 to 3 R^5bC replaced by₁~ C₆Alkyl, 0 to 3 R^5bC replaced by₂~ C₆Alkenyl, or 0 to 3 R^5bC replaced by₂~ C₆Alkynyl And   R^5aIs H, methyl, ethyl, propyl, butyl, or C₂~ C_FourAlkenyl
And   Or R^FiveAnd R^5aTogether, C_Four~ C₇Forming a cycloalkyl ring
Can be;   R^5bIn each occurrence H, methyl, ethyl, propyl, butyl,
CF₃, OR¹⁴, Cl, F, Br, I, = O, NR¹⁵R¹⁶, 0 to 3 R^5cC replaced by₃~ C₇Cycloalkyl, 0 to 3 R^5cC replaced by₃~ C₇Carbocycle, 0 to 3 R^5cPhenyl substituted with, and Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^5c5- to 7-membered heterocycle substituted with Independently selected from;   R^5cIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C_FourAlkyl, C₁~ C₃Alkoxy, C₁~ C₂Haloalkyl, and
And C₁~ C₂Independently selected from haloalkoxy;   W is-(CHR⁸)_p-Is;   p is 0 or 1;   R⁸Is H, methyl or ethyl;   X is a bond, 0 to 2 R^XbA phenyl substituted with, 0 to 3 R^XbC replaced by_Five~ C₆Cycloalkyl, or Contains 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 2 R^Xb5- to 6-membered heterocycle substituted with And   R^XbIn each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O)₂
CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁~
C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
;   Y is a bond, -V-, -CH₂-V-, -V-CH₂-Or-CH₂-V-
CH₂-Is;   V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O).
)₂-Or-N (R¹⁹) -Is;   Z is H, F, Cl, Br, 0 to 2 R¹²C replaced by₁~ C_FourAlkyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkenyl, 0 to 2 R¹²C replaced by₂~ C_FourAlkynyl, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 6-membered heterocycle substituted with And   R¹¹Is, in each occurrence, H, ═O, NR¹⁸R¹⁹, C (= O) R¹⁷,
C (= O) OR¹⁷, C (= O) NR¹⁸R¹⁹, S (= O)₂NR¹⁸R¹⁹, CF₃, 0 to 1 R^11aC replaced by₁~ C₆Alkyl, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11bSubstituted with, and pyridinyl, pyrimidinyl, triazini
, Furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl
, Homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazo
5- to 7-membered heterocycle selected from ril and tetrazolyl Independently selected from;   R^11aIs, in each occurrence, H, methyl, ethyl, propyl, butyl
, Methoxy, ethoxy, propoxy, Cl, F, = O, NR¹⁵R¹⁶, CF₃, 0 to 3 R^11bA phenyl substituted with, 0 to 3 R^11bC replaced by₃~ C₆Carbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^11bSubstituted with, and pyridinyl, pyrimidinyl, triazini
, Furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl
, Homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazo
5- to 7-membered heterocycle selected from ril and tetrazolyl Independently selected from;   R^11bIs H, OH, Cl, F, NR in each occurrence.¹⁵R¹⁶, CF₃ , Acetyl, SCH₃, S (= O) CH₃, S (= O)₂CH₃, Methyl, ethyl,
Propyl, butyl, methoxy, ethoxy, propoxy, C₁~ C₂Haloalkyl,
And C₁~ C₂Independently selected from haloalkoxy;   R¹²In each occurrence H, OH, Cl, F, Br, I, CN, N
O₂, NR¹⁵R¹⁶, -C (= O) NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (
= O) CH₃, S (= O)₂CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁ ~ C_FourHaloalkyl, C₁~ C_FourHaloalkoxy, and C₁~ C_FourHaloalkyl-
S-, 0 to 4 R^12bC replaced by₆~ C_TenAryl, 0 to 4 R^12bC replaced by₃~ C_TenCarbocycle, or Contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and
0 to 3 R^12b5- to 10-membered heterocycle substituted with Independently selected from;   R^12bIn each occurrence H, OH, Cl, F, Br, I, CN,
NO₂, NR¹⁵R¹⁶, CF₃, Acetyl, SCH₃, S (= O) CH₃, S (= O) ₂ CH₃, C₁~ C₆Alkyl, C₁~ C_FourAlkoxy, C₁~ C_FourHaloalkyl, C₁
~ C_FourHaloalkoxy, and C₁~ C_FourIndependently selected from haloalkyl-S-
L;   R¹³Is H, OH, C in each occurrence.₁~ C₆Alkyl, C₁~ C_FourA
Lucoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, And CF₃From Germany
Standing and selected;   R¹⁴Is, in each occurrence, H, phenyl, benzyl, C₁~ C_FourArchi
Le and C₂~ C_FourIndependently selected from alkoxyalkyl;   R¹⁵In each occurrence H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl;   R¹⁶Is, in each occurrence, H, OH, methyl, ethyl, propyl, bromo.
Chill, phenyl, benzyl, phenethyl, CH₃CH₂C (= O)-, CH₃C (
= O)-, CH₃CH₂OC (= O)-, CH₃OC (= O)-, CH₃CH₂S (
= O)₂-, And CH₃S (= O)₂-Independently selected from;   R¹⁷Is H, phenyl, benzyl, C₁~ C_FourAlkyl or C₂~ C_FourArco
Xyalkyl;   R¹⁸In each occurrence H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl; and   R¹⁹In each occurrence H, OH, methyl, ethyl, propyl and
And a compound of formula (Ib), characterized in that it is butyl. 16. A compound of claim 15: In formula (I), Q ¹ is, C ₁ -C ₆ alkyl substituted with 0-3 R ^1a, 0-3 R ^1a in C ₂ -C ₆ alkenyl substituted, 0-3 C ₂ -C ₆ alkynyl substituted with R ^1a, C ₃ ~C ₆ cycloalkyl substituted with 0-3 R ^1b, Phenyl substituted with 0 to 3 R ^1b or containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b 5 Membered to 6-membered heterocycle; R ^1a in each ^occurrence is H, methyl, ethyl, propyl, butyl,
^{OR 14, Cl, F, Br} , I, C 3 ~C 6 carbocycle substituted with _{^{NR 15 R 16, CF 3,}} 0 to 3 amino R ^1b, is substituted with 0-3 R ^1b Phenyl, and independently from a 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and substituted with 0 to 3 R ^1b. R ^1b is, in each ^occurrence , H, OH, Cl, F, Br, I, CN, N
_{^{O 2, NR 15 R 16,}} CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2
CH _3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, C ₁ -C ₂ haloalkoxy, (methyl) OC (= O) -
, (Ethyl) OC (= O)-, (propyl) OC (= O)-, and (butyl)
OC (= O) - are independently selected from; R ⁵ is, C ₁ -C ₄ alkyl substituted with OR ^14, 0 to 1 amino R ^5b, is substituted with 0 to 1 amino R ^5b R _{2 is} C ₂ -C ₄ alkenyl, or C ₂ -C ₄ alkynyl substituted with 0 to 1 R ^5b ; R ^5a is H, methyl, ethyl, propyl or butyl; ⁵ and R ^5a can be taken together to form a cyclobutyl ring, a cyclopentyl ring, a cyclohexyl ring or a cycloheptyl ring; R ^5b is in each occurrence H, methyl, ethyl, propyl, butyl,
^{_{CF 3, OR 14, Cl,}} F, = O, C 3 ~C 7 cycloalkyl substituted with NR ¹⁵ R ^16, 0-3 R ^5c, is substituted with 0-3 R ^5c C ₃ -C ₇ carbocyclic ring contains zero or phenyl substituted with to three R ^5c, and nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 Substituted with R ^5c and is pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,
Independently selected from a 5- to 7-membered heterocycle selected from homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl and tetrazolyl; R ^5c in each ^occurrence is H, OH, Cl, F, NR ¹⁵ R ¹⁶ , CF ₃
, Acetyl, SCH ₃ , S (═O) CH ₃ , S (═O) ₂ CH ₃ , methyl, ethyl,
Propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl,
And C ₁ -C ₂ are independently selected from haloalkoxy; W is a bond, -CH ₂ -, or -CH (CH ₃₎ - a and; X is a bond, with 0 to 1 amino R ^Xb Substituted phenyl, 0 to 1 C ₅ -C ₆ cycloalkyl substituted with R ^xb , or containing 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 Substituted with 1 R ^Xb and is pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl,
A 5- to 6-membered heterocycle selected from pyrazolyl, imidazolyl, oxazolyl and isoxazolyl; R ^Xb , in each ^occurrence, is H, OH, Cl, F, Br, NR ¹⁵ R ¹⁶ ,
CF _{3, acetyl, SCH 3, S (= O} ) CH 3, S (= O) 2 CH 3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ ~ It is independently selected from C ₂ haloalkoxy; Y is a bond, -V -, - V-CH 2 -, or a -CH ₂ V-; V is a bond, -C (= O) -, - O-, -S-, -S (= O)-, -S (= O
) _2- , or -N (R ¹⁹ )-; Z is H, F, Cl, Br, C ₁ -C ₄ alkyl substituted with 0 to 2 R ¹² , 0 to 2 C ₂ is substituted with R ¹² in -C ₄ alkenyl, 0-2 C ₂ -C ₄ alkynyl substituted with R ^12, C ₆ -C ₁₀ substituted with 0-4 R ^12b aryl, contain 0-4 C ₃ -C ₆ carbocycle substituted with R ^12b, or nitrogen, 1 to 4 heteroatoms selected from oxygen and sulfur, and 0-3 Is a 5- to 6-membered heterocycle substituted with R ^12b ; R ¹¹ in each occurrence is H, NR ¹⁸ R ¹⁹ , CF ₃ , C substituted with 0 to 1 R ^11a. ₁ -C ₄ alkyl, phenyl substituted with 0-3 R ^11b, 0-3 C ₃ -C ₆ carbocycle substituted with R ^11b or nitrogen, selected from oxygen and sulfur Containing 1 to 4 heteroatoms selected and substituted with 0 to 3 R ^<11b > and pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl , Imidazolyl, oxazolyl, isoxazolyl and tetrazolyl independently selected from a 5- to 7-membered heterocycle; R ^11a in each ^occurrence is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, = O, NR 15 R 16, CF 3, 0 or phenyl substituted with to three R ^11b, C ₃ ~C ₆ carbocycle substituted with 0-3 R ^11b , or nitrogen containing 1 to 4 heteroatoms selected from oxygen and sulfur, and substituted with 0-3 R ^11b Then pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, is independently selected from heterocyclic ring of 5 to 7 ring members selected from isoxazolyl and tetrazolyl; R ^11b is H, OH, Cl, F, NR ¹⁵ R ¹⁶ , CF ₃ , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C _{1 in each} occurrence.
˜C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy independently; R ¹² in each occurrence is H, OH, Cl, F, Br, NR ¹⁵ R ¹⁶ ,
^{-C (= O) NR 15 R} 16, CF 3, _{acetyl, SCH 3, S (= O} ) CH 3, S (
═O) ₂ CH ₃ , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy, phenyl substituted with ^0-4 R ^12b. , A C _{3 to} C ₆ carbocycle substituted with 0 to 4 R ^12b , or 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and 0 to 3 is independently selected from heterocyclic ring 5-6 membered substituted with R ^12b; R ^12b, at each occurrence, H, OH, Cl, F , Br, NR 15 R 16
, CF ₃ , acetyl, SCH ₃ , S (═O) CH ₃ , S (═O) ₂ CH ₃ , methyl,
Independently selected from ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C ₁ -C ₂ haloalkyl, and C ₁ -C ₂ haloalkoxy; R ¹³ in each ^occurrence is H, OH, methyl, ethyl. , Propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, Br, CN, NR ¹⁵ R ¹⁶ ,
And CF ₃ independently in each occurrence; R ¹⁴ in each ^occurrence is independently selected from H, phenyl, benzyl, methyl, ethyl, propyl and butyl; R ¹⁵ in each occurrence is H, R ¹⁶ is independently selected from methyl, ethyl, propyl or butyl; R ¹⁶ is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and phenethyl in each occurrence; R ¹⁸ is , In each occurrence H, methyl, ethyl, propyl, butyl,
Independently selected from phenyl, benzyl and phenethyl; and R ¹⁹ in each occurrence is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and phenethyl. 16. The compound according to claim 15, wherein 17. A compound according to claim 16 wherein: In the formula,   Q¹Is -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH₂CH₂CH₂CH ₃ , -CH₂CH₂CH₂CH₂CH₃, -CH₂CH₂CH₂CH₂CH₂CH₃, -CH
(CH₃)₂, -CH (CH₃) CH₂CH₃, -CH₂CH (CH₃)₂, -CH₂C
(CH₃)₃, -CF₃, -CH₂CF₃, -CH₂CH₂CF₃, -CH₂CH₂CH₂CF₃, -CH = CH₂, -CH₂CH = CH₂, -CH₂C (CH₃) = CH₂, -CH₂C
H = C (CH₃)₂, -CH₂CH₂CH = CH₂, -CH₂CH₂C (CH₃) = CH ₂ , -CH₂CH₂CH = C (CH₃)₂, Cis-CH₂CH = CH (CH₃), C
is-CH₂CH₂CH = CH (CH₃), Trans-CH₂CH = CH (CH₃
), Trans-CH₂CH₂CH = CH (CH₃), -C≡CH, -CH₂C≡CH, -CH₂C≡C (CH₃), Cyclopropyl-, cyclobutyl-, cyclopentyl-, cyclohexyl-, cyclo
Clopropyl-CH₂-, Cyclobutyl-CH₂-, Cyclopentyl-CH₂-,
Cyclohexyl-CH₂-, Cyclopropyl-CH₂CH₂-, Cyclobutyl-C
H₂CH₂-, Cyclopentyl-CH₂CH₂-, Cyclohexyl-CH₂CH₂-,
Phenyl-, 2-F-phenyl-, 3-F-phenyl-, 4-F-phenyl-,
4-methoxyphenyl-, 4-ethoxyphenyl-, 4-propoxyphenyl-
, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) C
H₂-, (4-F-phenyl) CH₂-, (2-Cl-phenyl) CH₂-, (3
-Cl-phenyl) CH₂-, (4-Cl-phenyl) CH₂-, (2,3-diF-phenyl) CH₂-, (2,4-diF-phenyl) CH₂-, (
2,5-diF-phenyl) CH₂-, (2,6-diF-phenyl) CH₂-, (3
, 4-diF-phenyl) CH₂-, (3,5-diF-phenyl) CH₂-, (2
3-diCl-phenyl) CH₂-, (2,4-diCl-phenyl) CH₂-, (2
, 5-diCl-phenyl) CH₂-, (2,6-diCl-phenyl) CH₂-, (
3,4-diCl-phenyl) CH₂-, (3,5-diCl-phenyl) CH₂-,
(3-F-4-Cl-phenyl) CH₂-, (3-F-5-Cl-phenyl) C
H₂-, (3-Cl-4-F-phenyl) CH₂-, 2-furanyl-CH₂-, 3-furanyl-CH₂-, 2-thienyl-CH₂-3
-Thienyl-CH₂-, 2-pyridyl-CH₂-, 3-pyridyl-CH₂-, 4-
Pyridyl-CH₂-, 1-imidazolyl-CH₂-, 2-oxazolyl-CH₂−
, 4-oxazolyl-CH₂-, 5-oxazolyl-CH₂-, 3-isoxazo
Lil-CH₂-, 4-isoxazolyl-CH₂-, 5-isoxazolyl-CH ₂ -, Phenyl-CH₂CH₂-, (2-F-phenyl) CH₂CH₂-, (3-F-fe
Nil) CH₂CH₂-, (4-F-phenyl) CH₂CH₂-, (2-Cl-phenyl
Le) CH₂CH₂-, (3-Cl-phenyl) CH₂CH₂-, (4-Cl-phenyl
Le) CH₂CH₂-, (2,3-diF-phenyl) CH₂CH₂-, (2,4-diF-phenyl) CH₂
CH₂-, (2,5-diF-phenyl) CH₂CH₂-, (2,6-diF-phenyl
Le) CH₂CH₂-, (3,4-diF-phenyl) CH₂CH₂-, (3,5-di-F
-Phenyl) CH₂CH₂-, (2,3-diCl-phenyl) CH₂CH₂-, (2
, 4-diCl-phenyl) CH₂CH₂-, (2,5-diCl-phenyl) CH₂
CH₂-, (2,6-diCl-phenyl) CH₂CH₂-, (3,4-diCl-f
CH) CH₂CH₂-, (3,5-diCl-phenyl) CH₂CH₂-, (3-F
-4-Cl-phenyl) CH₂CH₂-, (3-F-5-Cl-phenyl) CH₂
CH₂-, Furanyl-CH₂CH₂-, Thienyl-CH₂CH₂-, Pyridyl-CH₂CH₂-,
1-Imidazolyl-CH₂CH₂-, Oxazolyl-CH₂CH₂-, Isoxazo
Lil-CH₂CH₂-, 3,5-dimethylisoxazol-4-yl-CH₂C
H₂-, Phenyl-propyl-, Benzyl-CH (NH₂)-, Benzyl-CH (NHC (= O) -O-tBu)
-, Benzyloxy-CH₂-, Pyrrolidin-2-yl-, or 3-t-but
Xycarbonylcarbonylpyrrolidin-2-yl- And   R^FiveIs -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH (CH₃)₂,-
CH₂CH₂CH₂CH₃, -CH (CH₃) CH₂CH₃, -CH₂CH (CH₃)₂,
-CH₂C (CH₃)₃, -CH₂CH₂CH₂CH₂CH₃, -CH (CH₃) CH₂C
H₂CH₃, -CH₂CH (CH₃) CH₂CH₃, -CH₂CH₂CH (CH₃)₂,-
CH (CH₂CH₃)₂, -CF₃, -CH₂CF₃, -CH₂CH₂CF₃, -CH₂CH₂CH₂CF₃, -CH ₂ CH₂CH₂CH₂CF₃, -CH = CH₂, -CH₂CH = CH₂, -CH₂CH₂CH = CH₂, -CH = CH
CH₃, Cis-CH₂CH = CH (CH₃), Trans-CH₂CH = CH (C
H₃), Trans-CH₂CH = CH (C₆H_Five), -CH₂CH = C (CH₃)₂
, Cis-CH₂CH = CHCH₂CH₃, Trans-CH₂CH = CHCH₂C
H₃, Cis-CH₂CH₂CH = CH (CH₃), Trans-CH₂CH₂CH =
CH (CH₃), Trans-CH₂CH = CHCH₂(C₆H_Five), -C≡CH, -CH₂C≡CH, -CH₂C≡C (CH₃), -CH₂C≡C (C₆
H_Five), -CH₂CH₂C≡CH, -CH₂CH₂C≡C (CH₃), -CH₂CH₂C
≡ C (C₆H_Five), -CH₂CH₂CH₂C≡CH, -CH₂CH₂CH₂C≡C (CH ₃ ), -CH₂CH₂CH₂C≡C (C₆H_Five), Cyclopropyl-CH₂-, Cyclobutyl-CH₂-, Cyclopentyl-CH₂−
, Cyclohexyl-CH₂-, (2-CH₃-Cyclopropyl) CH₂-, (3-
CH₃-Cyclobutyl) CH₂-, Cyclopropyl-CH₂CH₂-, Cyclobutyl
-CH₂CH₂-, Cyclopentyl-CH₂CH₂-, Cyclohexyl-CH₂CH₂ -, (2-CH₃-Cyclopropyl) CH₂CH₂-, (3-CH₃-Cyclobutyl
) CH₂CH₂-, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) CH ₂ -, (4-F-phenyl) CH₂-, (3,5-diF-phenyl) CH₂-2
-Furanyl-CH₂-, 3-furanyl-CH₂-, 2-thienyl-CH₂-, 3-
Thienyl-CH₂-, 2-pyridyl-CH₂-, 3-pyridyl-CH₂-, 4-pi
Lysyl-CH₂-, 1-imidazolyl-CH₂-, 2-oxazolyl-CH₂-,
4-oxazolyl-CH₂-, 5-oxazolyl-CH₂-, 3-isoxazoli
Le-CH₂-, 4-isoxazolyl-CH₂-, 5-isoxazolyl-CH₂
-, Phenyl-CH₂CH₂-, (2-F-phenyl) CH₂CH₂-, (3-F-fe
Nil) CH₂CH₂-, (4-F-phenyl) CH₂CH₂-, Furanyl-CH₂C
H₂-, Thienyl-CH₂CH₂-, Pyridyl-CH₂CH₂-, 1-Imidazolyl
-CH₂CH₂-, Oxazolyl-CH₂CH₂-, Isoxazolyl-CH₂CH₂ -, Methoxy, ethoxy, propoxy, or butoxy And   R^5aIs H,   Or R^FiveAnd R^5aTogether, cyclopentyl, cyclohexyl
Or it can form cycloheptyl;   W is a bond, -CH₂-, Or -CH (CH₃) -Is;   X is a bond,     [Chemical 13] And   Y is a bond, -CH₂-V-, -V-, or -V-CH₂-Is;   V is a bond, -C (= O)-, -O-, -S-, -S (= O)-, -S (= O).
)₂-, -NH-, or -N (CH₃) -Is;   Z is H, F, Cl, Br, methyl, ethyl, n-propyl, i-propyl,
n-butyl, i-butyl, s-butyl, t-butyl, Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl
-Phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl
2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl
3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCl-phen
Nyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl
-Phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-
4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Cl-4-F-phenyl
2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2
-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl
Phenyl, 3-MeS-phenyl, 4-MeS-phenyl, 2-CF₃O-pheny
Le, 3-CF₃O-phenyl, 4-CF₃O-phenyl, Furanyl, thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl, 4
-Me-pyridyl, l-imidazolyl, oxazolyl, isoxazolyl, 1-
Benzimidazolyl, morpholino, N-piperidinyl, Phenyl-CH₂-, (2-F-phenyl) CH₂-, (3-F-phenyl) CH ₂ -, (4-F-phenyl) CH₂-, (2-Cl-phenyl) CH₂-, (3-
Cl-phenyl) CH₂-, (4-C1-phenyl) CH₂-, (2,3-di-F-
Phenyl) CH₂-, (2,4-diF-phenyl) CH₂-, (2,5-di-F-f
CH) CH₂-, (2,6-diF-phenyl) CH₂-, (3,4-diF-fe
Nil) CH₂-, (3,5-diF-phenyl) CH₂-, (2,3-diCl-phen
Nil) CH₂-, (2,4-diCl-phenyl) CH₂-, (2,5-diCl-f
CH) CH₂-, (2,6-diCl-phenyl) CH₂-, (3,4-diCl-
Phenyl) CH₂-, (3,5-diCl-phenyl) CH₂-, (3-F-4-C
l-phenyl) CH₂-, (3-F-5-Cl-phenyl) CH₂-, (3-Cl
-4-F-phenyl) CH₂-, (2-MeO-phenyl) CH₂-, (3-Me
O-phenyl) CH₂-, (4-MeO-phenyl) CH₂-, (2-PhO-F
CH) CH₂-, (3-PhO-phenyl) CH₂-, (4-PhO-phenyl
) CH₂-, (2-Me-phenyl) CH₂-, (3-Me-phenyl) CH₂−
, (4-Me-phenyl) CH₂-, (2-MeS-phenyl) CH₂-, (3-
MeS-phenyl) CH₂-, 4-MeS-phenyl) CH₂-, (2-CF₃O
-Phenyl) CH₂-, (3-CF₃O-phenyl) CH₂-, (4-CF₃OF
CH) CH₂-, (Furanyl) CH₂-, (Thienyl) CH₂-, (Pyridyl)
CH₂-, (2-Me-pyridyl) CH₂-, (3-Me-pyridyl) CH₂-,
(4-Me-pyridyl) CH₂-, (1-imidazolyl) CH₂-, (Oxazoli
Le) CH₂-, (Isoxazolyl) CH₂-, (1-benzimidazolyl) CH ₂ -, (Cyclopropyl) CH₂-, (Cyclobutyl) CH₂-, (Cycloplier
Le) CH₂-, (Cyclohexyl) CH₂-, (Morpholino) CH₂-, (N-pi
Peridinyl) CH₂-, Phenyl-CH₂CH₂-, (Phenyl)₂CHCH₂-, (2-F-phenyl) C
H₂CH₂-, (3-F-phenyl) CH₂CH₂-, (4-F-phenyl) CH₂
CH₂-, (2-Cl-phenyl) CH₂CH₂-, (3-Cl-phenyl) CH₂ CH₂-, (4-Cl-phenyl) CH₂CH₂-, (2,3-diF-phenyl)
CH₂CH₂-, (2,4-diF-phenyl) CH₂CH₂-, (2,5-di-F-f
CH) CH₂CH₂-, (2,6-diF-phenyl) CH₂CH₂-, (3,4-
Di-F-phenyl) CH₂CH₂-, (3,5-diF-phenyl) CH₂CH₂-, (
2,3-diCl-phenyl) CH₂CH₂-, (2,4-diCl-phenyl) CH ₂ CH₂-, (2,5-diCl-phenyl) CH₂CH₂-, (2,6-diCl-f
CH) CH₂CH₂-, (3,4-diCl-phenyl) CH₂CH₂-, (3,5
-DiCl-phenyl) CH₂CH₂-, (3-F-4-Cl-phenyl) CH₂C
H₂-, (3-F-5-Cl-phenyl) CH₂CH₂-, (3-Cl-4-F-
Phenyl) CH₂CH₂-, (2-MeO-phenyl) CH₂CH₂-, (3-Me
O-phenyl) CH₂CH₂-, (4-MeO-phenyl) CH₂CH₂-, (2-
Me-phenyl) CH₂CH₂-, (3-Me-phenyl) CH₂CH₂-, (4-
Me-phenyl) CH₂CH₂-, (2-MeS-phenyl) CH₂CH₂-, (3
-MeS-phenyl) CH₂CH₂-, (4-MeS-phenyl) CH₂CH₂-,
(2-CF₃O-phenyl) CH₂CH₂-, (3-CF₃O-phenyl) CH₂C
H₂-, (4-CF₃O-phenyl) CH₂CH₂-, (Furanyl) CH₂CH₂-,
(Thienyl) CH₂CH₂-, (Pyridyl) CH₂CH₂-, (2-Me-pyridyl
) CH₂CH₂-, (3-Me-pyridyl) CH₂CH₂-, (4-Me-pyridyl
) CH₂CH₂-, (Imidazolyl) CH₂CH₂-, (Oxazolyl) CH₂CH₂ -, (Isoxazolyl) CH₂CH₂-, (Benzimidazolyl) CH₂CH₂−
, (Cyclopropyl) CH₂CH₂-, (Cyclobutyl) CH₂CH₂-, (Cyclo
Pentyl) CH₂CH₂-, (Cyclohexyl) CH₂CH₂-, (Morpholino) C
H₂CH₂-, Or (N-piperidinyl) CH₂CH₂− And   R¹¹In each occurrence H, methyl, ethyl, n-propyl, i-
Propyl, n-butyl, i-butyl, s-butyl, t-butyl, phenyl, benzene
Zil, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl
Xyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclo
Pentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclopropyi
Ruethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl
, 2-F-phenyl-, 3-F-phenyl, 4-F-phenyl, 4-Cl-phen
Nil, 4-CH₃-Phenyl, 4-MeO-phenyl-, 4-CF₃-Phenyl,
(4-F-phenyl) CH₂-, (4-C1-phenyl) CH₂-, (4-CH₃
-Phenyl) CH₂-, (4-CF₃-Phenyl) CH₂-, (4-F-phenyl
) CH₂CH₂-, (4-C1-phenyl) CH₂CH₂-, (4-CH₃-Pheny
Le) CH₂CH₂-, (4-CF₃-Phenyl) CH₂CH₂-, Pyridin-2-i
Ru-, pyridin-3-yl-, 4-CF₃-Pyridin-2-yl-, 4-CH₃−
Pyridin-2-yl-, thiazol-2-yl-, azapan-1-yl, N, N
-Dimethylamino, N, N-diethylamino, N, N-dipropylamino, and
And N, N-dibutylamino Independently selected from; and   R¹³Is independently selected from H, MeO, F and Cl in each occurrence.
The compound according to claim 16, characterized in that it is selected. 18. A compound of formula (If): Alternatively, the compound according to claim 15, 16 or 17, which is a pharmaceutically acceptable salt form or a prodrug thereof. 19. A compound of formula (Ig): Alternatively, the compound according to claim 15, 16 or 17, which is a pharmaceutically acceptable salt form or a prodrug thereof. 20. A compound of formula (Ih): Alternatively, the compound according to any of claims 15, 16 or 17, characterized in that it is a pharmaceutically acceptable salt form or prodrug thereof. 21. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
, 12, 13, 14, 15, 16, 17, 18, 19 or 20 and a pharmaceutically acceptable carrier. 22. A method for treating a neurological disorder associated with β-amyloid production, which comprises a therapeutically effective amount of a host in need of such treatment.
2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 1
A method comprising administering a compound according to 6, 17, 18, 19 or 20. 23. A method for inhibiting the activity of γ-secretase, which comprises:
14. A therapeutically effective amount of inhibiting the activity of γ-secretase in a host in need of such inhibition, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13. ,
26. A method comprising administering 14, 15, 16, 17, 18, 19 or 20 compounds.