TW200301117A - Piperazine derivatives that destabilize androgen receptors - Google Patents

Piperazine derivatives that destabilize androgen receptors Download PDF

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TW200301117A
TW200301117A TW091134064A TW91134064A TW200301117A TW 200301117 A TW200301117 A TW 200301117A TW 091134064 A TW091134064 A TW 091134064A TW 91134064 A TW91134064 A TW 91134064A TW 200301117 A TW200301117 A TW 200301117A
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trifluoromethyl
methyl
dihydro
benzonitrile
dioxo
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TW091134064A
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Arwed Cleve
Christoph Huwe
Volker Schulze
Helmut Morack
Dieter Zopf
Hoffmann Jens
Reichel Andreas
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Schering Ag
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Priority claimed from DE2001159035 external-priority patent/DE10159035A1/en
Priority claimed from DE2002138742 external-priority patent/DE10238742A1/en
Application filed by Schering Ag filed Critical Schering Ag
Publication of TW200301117A publication Critical patent/TW200301117A/en

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    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Abstract

This invention relates to new piperazine derivatives of general formula I, in which V, W, n, R, R', i, j, Y and Z have the meaning that is indicated in the description. The compounds according to the invention are distinguished by a diazacycloalkane substituent. They have at their disposal a special action with respect to the action that destabilizes the androgen receptor and can be used, for example, for treating prostate cancer.

Description

⑴ 玖、發明說明 (發明說明應敘明：發明所屬之技術領域、先前技術、内容、實施方式及圖式簡單說明） 本發明係關於使雄性激素受體（AR)去穩定的經取代六 風^:呼衍生物’及製造此等六氫吡畊衍生物的方法，其中 產物、及匕㊁根據本發明六氫p比呼衍生物的藥物製％ 與其製造藥劑的用途。 在工業國家中’攝護腺癌在肺癌之後為人類第二主要致 癌夕匕ΊΓ原因。在超過55歲的人口中，4%死亡歸因於攝護 腺腫瘤疾病’假定超過80%人口比例則增加高達80%死 鲁 亡处"亡率雖仍相當低，但其每年增加至約1 4 %。診斷攝 濩腺的人數近來增加3 〇%，然而，其可歸因於較低新病增 加數目但人口通常較老化、診斷方法改良及引入系統性篩 選程序（E. J· Small，D. μ. Reese, Curr. Opi· Oncol· 2000，12，265-* 272)。 攝1隻腺腫瘤在早期階段以依附雄性激素方式生長。只要 腫瘤局部限制於攝護腺，其即可由外科手術介入或放射性 治療除去，因而此等方法具有危險性。在腫瘤不再局部受 修 限制且已經形成轉移的情況下，腫瘤則以減緩方式藉減少 血液中睪内醋準位處理。此係以外科手術方式藉閹割或以 藥物方式藉抗雄性激素（雙卡留特酿胺（bicaiutamide)、酷酸 氯輕甲烯孕S同、氟硝丁醯胺）、LHRH促效劑（buserelin， zoladex)、LHRH對抗劑（cetroreiix)或5 α -還原酶抑制劑 (finasteride)實施。因為腎上腺雄性激素合成在外科手術閹 割仍未受影響，所以最近時常實施一種外科手術與藥物混 合的治療。然而，此項治療僅短暫的成功，因為腫瘤的更 200301117说明 玖 Description of the invention (The description of the invention should state: the technical field to which the invention belongs, the prior art, the content, the embodiments, and the drawings) ^: Hou derivatives' and methods of making such hexahydropyrine derivatives, wherein the product and the dungicide according to the present invention are used in the manufacture of a medicinal derivative of a hexahydrop bihuo derivative and its use in the manufacture of a medicament. Prostate cancer is the second leading cause of carcinogenesis in humans after lung cancer in industrial countries. Among the population over 55 years old, 4% of deaths are attributed to prostate tumor disease. 'Assuming that the proportion of population exceeds 80%, the death rate will increase by up to 80%. Although the mortality rate is still quite low, it increases to about 14%. The number of people diagnosed with the glandular glands has recently increased by 30%, however, it can be attributed to a lower increase in the number of new diseases but the population is generally older, diagnostic methods have been improved, and systemic screening procedures have been introduced (E. J. Small, D. μ Reese, Curr. Opi. Oncol. 2000, 12, 265- * 272). A glandular tumor was grown in an early stage in an androgen-dependent manner. As long as the tumor is locally confined to the prostate, it can be removed by surgical intervention or radiotherapy, so these methods are dangerous. When the tumor is no longer limited by local repair and metastasis has been formed, the tumor is treated in a slower manner by reducing the level of hyaluronate in the blood. This is a surgical method by castration or by anti-androgens (bicaiutamide, chloromethalone, fenbutramine), LHRH agonist (buserelin , Zoladex), LHRH antagonist (cetroreiix) or 5 alpha-reductase inhibitor (finasteride). Because adrenal androgen synthesis remains unaffected during surgical castration, a combination of surgical and drug treatments has recently been performed. However, this treatment has only been a short-term success because the tumor is more 200301117

(2) 新生長通常在最近二年後發生，且在大部分情況下該更新 生長為依附荷爾蒙而定（L. J. Denis, K. Griffith，Semin· in Surg One. 2000, 18, 52-74)。迄今為止，不論過去50年的深入研究 ，尚未有任何有效治療對抗此等前期階段。這些病人中5 年殘存率為15%以下。(2) New growth usually occurs after the last two years, and in most cases the renewed growth is dependent on hormones (L. J. Denis, K. Griffith, Semin. In Surg One. 2000, 18, 52-74). To date, regardless of intensive research over the past 50 years, there has not been any effective treatment to combat these early stages. The 5-year survival rate among these patients is less than 15%.

有許多指示顯示雄性激素受體在攝護腺腫瘤的發展與 生長方面，不但在腫瘤進展的早期荷爾蒙依附階段而且在 後期荷爾蒙依附階段扮演重要角色。 雄性激素受體屬於作為轉錄因子的類固醇荷爾蒙受體 的科。雄性激素受體結合雄性激素，藉其安定並保護不受 迅速分解蛋白質的降解。在荷爾蒙結合後，其被傳入核， 在該處其係藉結合至在促進質區的所謂雄性激素回應的 DNA元素活化某些基因（D. J. Lamb等人，Vitam. Horm. 2001， 62， 199-230)。There are many indications that androgen receptors play an important role in the development and growth of prostate tumors, not only during the early hormonal phase of tumor progression but also during the later hormonal phase. Androgen receptors belong to the family of steroid hormone receptors as transcription factors. The androgen receptor binds to androgens, by which it stabilizes and protects against degradation by rapidly decomposing proteins. After hormonal binding, it is introduced into the nucleus, where it activates certain genes by binding to DNA elements that promote the so-called androgen response in the plasmosome (DJ Lamb et al., Vitam. Horm. 2001, 62, 199 -230).

對攝護腺腫瘤的研究顯示雄性激素受體位點的放大係 在30%前期腫瘤偵測。在其他情況下，發現若干突變於雄 性激素受體基因，其位於雄性激素受體分子的各種結構部 分内並導致改變的受體特性。突變的受體可對雄性激素具 有較高親和力，可在構成上活性，可改變其配位體特殊性 ，使其藉其他類固醇荷爾蒙或甚至抗雄性激素活化，可藉 由與分子的交互作用自其他生長-促進信號-傳輸方法活 化，其改變與輔助因子的交互作用，或可活化其他目標基 因（J. P. Elo，T· Visakorpi，Ann· Med. 2001，33，130-41)。 抗雄性激素的鑑別法，其不但抑制天然雄性激素受體而 200301117Studies of prostate tumors have shown that the magnification of the androgen receptor site is 30% of early tumor detection. In other cases, several mutations were found in the androgen receptor gene, which are located in various structural parts of the androgen receptor molecule and lead to altered receptor characteristics. The mutated receptor can have a higher affinity for androgens, can be structurally active, can change the specificity of its ligands, enable it to be activated by other steroid hormones or even anti-androgens, and can interact with molecules by Activation of other growth-promoting signal-transmission methods, which alter interactions with cofactors, or may activate other target genes (JP Elo, T. Visakorpi, Ann. Med. 2001, 33, 130-41). Anti-androgen identification method, which not only inhibits the natural androgen receptor but also 200301117

(3) 且抑制其犬菱形式，並且改變受體分子，使之去安定，可 假定有助於治療各種階段的攝護腺腫瘤。該化合物玎防止 腫瘤生長的復發或至少相當大延後該復發。在動情激素受 體的情況下，可鑑別配位體，其使受體去安定並導致受體 含里在體外與體内的減少（s Dauvois*A，Proc Nati.Acad·(3) Inhibiting its canine diamond form and changing the receptor molecule to stabilize it can be assumed to help treat prostate tumors at various stages. This compound prevents the recurrence of tumor growth or at least considerably delays the recurrence. In the case of estrogen receptors, ligands can be identified that destabilize the receptor and cause a reduction in the receptor's inclusion in vitro and in vivo (s Dauvois * A, Proc Nati. Acad ·

Sen. USA 1992, 89, 4037-41; R· Α· McClelland等人，Eur j Cancer 1996, 32A，413-6)。 非類固醇抗雄性激素敘述於1135,411，981(苯基咪唑啶衍 生物）’ WO 97/00071(特別取代的苯基二甲基乙内醯脲及其 亞胺基或硫酮衍生物），w〇 〇〇/3743〇(苯基苯胺、苯基乙内 醯脲及苯基脲），WO 01/58855(胺基乙丙酸内酯）及EP 1 122242(經取代氰基苯基六氫吡畊）。 本發明目的為製造具有抗雄性激素作用的可行化合物 ’其可使雄性激素受體去安定’抑制攝護腺腫瘤生長，同 時具有高度視需要口服生物利用率。 對非類固醇抗雄性激素的研究顯示其優於類固醇化合 物因而車父佳。因此，使用非類固醇化合物，可達成更多選 擇性作用而較少不利的副作用。相對照於類固醇抗雄性激 素，例如，更體内泌素類的活性缺少已知非類固醇雙卡留 特酸胺及氟硝丁醯胺，此外，其用途導致血清中睪内酯準 位的增加，其在診斷上可導致保存效能。 此目的可根據本發明通式丨的新穎化合物達成·· 本發明係關於通式j化合物，其中 200301117Sen. USA 1992, 89, 4037-41; R. A. McClelland et al., Eur j Cancer 1996, 32A, 413-6). Non-steroidal antiandrogens are described in 1135,411,981 (phenylimidazolidine derivatives) 'WO 97/00071 (Specially substituted phenyldimethylhydantoin and its imino or thioketone derivatives), w00〇 / 3743〇 (phenylaniline, phenylhydantoin, and phenylurea), WO 01/58855 (aminoglycolide) and EP 1 122242 (substituted cyanophenylhexahydro Pythium). The purpose of the present invention is to produce a viable compound having an antiandrogenic effect, which can destabilize the androgen receptor and inhibit the growth of prostate tumors, while having a high oral bioavailability as needed. Studies on non-steroidal anti-androgens have shown that they are superior to steroid compounds and are therefore preferred. Therefore, the use of non-steroidal compounds can achieve more selective effects and less adverse side effects. In contrast to steroid anti-androgens, for example, the activity of more endocrins lacks the known non-steroidal dicarotide amine and flunbutamide, and its use leads to an increase in the level of galactone in serum , Which can lead to preservation efficiency in diagnosis. This object can be achieved according to the novel compounds of the general formula of the present invention. The present invention relates to compounds of the general formula j, of which 200301117

(4)(4)

V表示通式II的經取代芳香族基，V represents a substituted aromatic group of the general formula II,

其中 A 表示乙酿基、乙酿基胺基、氰基、硝基、三氟甲基或 鹵素（氟、氯）， B 表示氫原子、鹵素（氟、氯）或三氟甲基，或 A與B—起表示鍵結至芳香族環的式III或IV的環狀基，其中 E表示亞甲基或氧原子，Where A represents ethyl alcohol, ethyl amino, cyano, nitro, trifluoromethyl or halogen (fluorine, chlorine), B represents hydrogen atom, halogen (fluorine, chlorine) or trifluoromethyl, or A Together with B represents a cyclic group of formula III or IV bonded to an aromatic ring, wherein E represents a methylene group or an oxygen atom,

W表示氏V的雜環化合物，W represents a heterocyclic compound of V,

V. -10- 200301117V. -10- 200301117

(5) 其中 T 可代表碳或氮， 若 Τ表示碳時，雙鍵呈現在Q與Τ之間，Q意指=C(CH3)-基而U意指氧，η假定為整數值1，2，3，4，5，6，7或8 之一，或 若 Τ表示氮時，單鍵呈現在Q與Τ之間，Q意指-C(CH3)2-基而U意指硫，η假定為整數值2，3，4，5，6，7或8(5) Where T can represent carbon or nitrogen, if T represents carbon, the double bond appears between Q and T, Q means = C (CH3) -group and U means oxygen, η is assumed to be an integer value of 1, One of 2, 3, 4, 5, 6, 7, or 8 or if T represents nitrogen, a single bond appears between Q and T, Q means -C (CH3) 2- group and U means sulfur, η is assumed to be an integer value of 2, 3, 4, 5, 6, 7, or 8

i與j，互相獨立表示1與2之值，其中i+j可假設為2或3之值， R與R’，互相獨立可為氫原子或甲基， Y 表示雜環氮與Z間的键、羰基-c(o)-、磺醯基-s(o)2-、亞胺基羰基-C(0)N(Z，）-、亞胺基磺醯基_S(0)2N(Z’）_ 、亞胺基（噻呤甲基）基-C(S)N(Zf)-、氧羰基亞胺基（ 嘧呤甲基）基-C(S)N(Z’）C(0)0-、氧羰基-C(0)0-、硫烷 基羰基-c(o)s-，及i and j, independently of each other, represent values of 1 and 2, where i + j can be assumed to be a value of 2 or 3, R and R ', independently of each other, can be a hydrogen atom or a methyl group, and Y represents a heterocyclic nitrogen and Z Bond, carbonyl-c (o)-, sulfofluorenyl-s (o) 2-, iminocarbonyl-C (0) N (Z,)-, iminosulfonyl_S (0) 2N ( Z ') _, imino (thienylmethyl) -C (S) N (Zf)-, oxycarbonylimino (pyriminylmethyl) -C (S) N (Z') C ( 0) 0-, oxycarbonyl-C (0) 0-, sulfanylcarbonyl-c (o) s-, and

Z與Zf互相獨立表示無支鏈Ci-Cs烷基或支鏈c3-c8烷基、 C3-06環烷基，其係視需要用苯基、（C3-C6環烷基 伸烷基、支鏈或無支鏈C2-C5晞基、C3-C5炔基、（VC4 烷氧基、氰基、苯基硫烷基或羥基伸烷基、（2-甲氧基乙氧基）甲基、[2-(2-甲氧基乙氧基）乙氧基]甲 基、2-(2-甲氧基乙氧基）乙基、2-[2-(2-甲氧基乙氧基 )乙氧基]乙基、C「C4烷氧基-Ci-Q伸烷基、CVC4烷氧 基羰基-Ci-G伸烷基、金剛基、三氯乙醯基取代；芳 基、雜芳基、雜環基、芳基-CVC4伸烷基、雜芳基-CVC4 -11 - 200301117Z and Zf are independent of each other and represent an unbranched Ci-Cs alkyl group or a branched c3-c8 alkyl group and a C3-06 cycloalkyl group, and if necessary, a phenyl group, (C3-C6 cycloalkyl extended alkyl group, branched chain Or unbranched C2-C5 fluorenyl, C3-C5 alkynyl, (VC4 alkoxy, cyano, phenylsulfanyl or hydroxyalkylene, (2-methoxyethoxy) methyl, [ 2- (2-methoxyethoxy) ethoxy] methyl, 2- (2-methoxyethoxy) ethyl, 2- [2- (2-methoxyethoxy) ethyl Oxy] ethyl, C4C4alkoxy-Ci-Qalkylene, CVC4alkoxycarbonyl-Ci-Galkylene, adamantyl, trichloroethenyl substitution; aryl, heteroaryl, Heterocyclyl, aryl-CVC4 alkylene, heteroaryl-CVC4 -11-200301117

⑹ 伸烷基、芳氧基-Ci-Q伸烷基、雜芳氧基-c「c4伸烷基 、芳基伸烷氧基- 伸烷基，其為未經取代或 用最多三個支鏈或無支鏈CVC4烷基、c2-c6烯基、c3-c6 環燒基、c3_cyi：燒氧基、苯基、氰基、鹵素、甲氧 基、乙氧基、苯氧基、芊氧基、甲基硫烷基、乙基硫 烷基、苄基硫烷基、苯基硫烷基、二甲基胺基、乙醯 基胺基、三氟甲基、三氟甲氧基、三氟甲基硫烷基、伸 alkylene, aryloxy-Ci-Q alkylene, heteroaryloxy-c "c4 alkylene, arylalkyloxy-alkylene, which are unsubstituted or with up to three branches Or unbranched CVC4 alkyl, c2-c6 alkenyl, c3-c6 cycloalkyl, c3-cyi: alkoxy, phenyl, cyano, halogen, methoxy, ethoxy, phenoxy, fluorenyloxy , Methylsulfanyl, ethylsulfanyl, benzylsulfanyl, phenylsulfanyl, dimethylamino, ethylamino, trifluoromethyl, trifluoromethoxy, trifluoro Methylsulfanyl,

乙醯基、（1-亞胺基乙基）或硝基取代，或式CpFqHr(其 中 p=l，2,3,4，q〉l&q+r=2p+l)，& Z’ 除了上述定義以外表示氫原子。 根據本發明的化合物不同之處為，在各種情況下，其含 有二偶氮環鏈烷，其氮原子在各情況下以取代的形式呈 現。Ethyl, (1-iminoethyl) or nitro substitution, or formula CpFqHr (where p = 1, 2, 3, 4, q> l & q + r = 2p + l), & Z ' In addition to the above definition, it means a hydrogen atom. The compounds according to the invention differ in that in each case they contain a diazocycloalkane, the nitrogen atom of which in each case appears in a substituted form.

對Z與Zf基的無支鏈（^-(：8烷基可為，例如，甲基、乙基 、正丙基、正戊基、正己基、正庚基或正辛基；支鏈C3_C8 烷基可為，例如，異丙基、異丁基、第二丁基、第三丁基 、異戊基、新戊基、2-甲基戊基、2,2-二甲基丁基、2,3-二甲基丁基、2-甲基己基、2,2-二甲基戊基、2,2,3-三甲基 丁基或2,3,3-三甲基丁基。 對Z與义’基視需要用苯基取代的C3-C6環烷基可為環丙基 、環丁基、環戊基、環己基或苯基環丙基、苯基環丁基、 苯基環戊基或苯基環己基。 對Z與1基的（C3-C6環烷基伸烷基可為，例如，環 丙基甲基、環丁基甲基、環戊基甲基、環己基甲基、環丙 -12- 200301117Unbranched to Z and Zf groups (^-(: 8 alkyl may be, for example, methyl, ethyl, n-propyl, n-pentyl, n-hexyl, n-heptyl or n-octyl; branched C3_C8 The alkyl group may be, for example, isopropyl, isobutyl, second butyl, third butyl, isopentyl, neopentyl, 2-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 2-methylhexyl, 2,2-dimethylpentyl, 2,2,3-trimethylbutyl or 2,3,3-trimethylbutyl. The C3-C6 cycloalkyl group optionally substituted with a phenyl group for Z and the sense group may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or phenylcyclopropyl, phenylcyclobutyl, phenyl Cyclopentyl or phenylcyclohexyl. The (C3-C6 cycloalkylalkylene) for Z and 1 may be, for example, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, Cyclopropyl-12- 200301117

⑺ 基乙基、環丁基乙基、環戊基乙基、環己基乙基、環丙基 丙基、環丁基丙基、環戊基丙基、環己基丙基、環丙基丁 基、環丁基丁基、環戊基丁基或環己基丁基。⑺ Ethylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cyclopropylpropyl, cyclobutylpropyl, cyclopentylpropyl, cyclohexylpropyl, cyclopropylbutyl , Cyclobutylbutyl, cyclopentylbutyl or cyclohexylbutyl.

對Z與Z’基的支鏈或無支鏈c2-c5晞基可為，例如，乙烯 基、烯丙基、高晞丙基、（E)-丁 -2-晞基、（Z)-丁 -2-烯基、 (E)-丁 -1-烯基、（Z)-丁 -1-晞基、戊-4-晞基、（E)-戊-3-烯基 、（Z)-戊-3-烯基、（E)-戊-2-烯基、（Z)-戊-2-晞基、（E)-戊 -1-烯基、（Z)-戊-1-婦基、2-甲基乙晞基、3 -甲基丁 - 3-烯基 、2-甲基丁 - 3-晞基、（E)-2-甲基丁 - 2-烯基、（Z)-2-甲基丁 -2-烯基或3-甲基丁 - 2-烯基。 對Z與Z’基的C3-C5炔基可為，例如，丙-1-炔基、丙-2-炔基、丁 -1-炔基、丁 -2-炔基、丁 -3-炔基、戊-1-炔基、戊 -2-炔基、戊-3-炔基、戊-4-炔基、1-甲基丙-2-炔基、1-甲 基丁 - 3-炔基或1-乙基丙-2-炔基。The branched or unbranched c2-c5 fluorenyl groups for Z and Z 'groups may be, for example, vinyl, allyl, perylene, (E) -but-2-fluorenyl, (Z)- But-2-enyl, (E) -but-1-enyl, (Z) -but-1-fluorenyl, pent-4-fluorenyl, (E) -pent-3-enyl, (Z) -Pent-3-enyl, (E) -pent-2-enyl, (Z) -pent-2-enyl, (E) -pent-1-enyl, (Z) -pent-1-enyl Methyl, 2-methylethylethyl, 3-methylbutyl-3-alkenyl, 2-methylbutyl-3-alkenyl, (E) -2-methylbutyl-2-alkenyl, (Z) 2-methylbut-2-enyl or 3-methylbut-2-enyl. The C3-C5 alkynyl group for Z and Z 'groups may be, for example, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-yne Pentyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, 1-methylprop-2-ynyl, 1-methylbut-3-yn Or 1-ethylprop-2-ynyl.

對Z與Z’基的Ci-G烷氧基可為，例如，甲氧基、乙氧基 、正丙氧基、異丙氧基、正丁氧基、第二丁氧基、異丁氧 基或第三丁氧基。 在Z與Z’基内的CVC4伸烷基可為，例如，亞甲基（-CH2-) 、亞乙基[-CH(CH3)_]、伸乙基（-CH2CH2-)、1，3-伸丙基 (-CH2CH2CH2-)、1，2-伸丙基[-CH2CH(CH3)-]、1，4-伸丁基 (-CH2CH2CH2CH2-)、1，3-伸丁基[-CH2CH2CH(CH3)-]、1，2-伸 丁基[-CH2CH(CH2CH3)-]、2-甲基-1，2-伸丙基[-CH2C(CH3)2-] 或 2-甲基-1，3-伸丙基[-CH2CH(CH3)CH2-]。 對Z與Z’基的羥基-CVC4伸烷基可為羥基甲基 -13 - 200301117Ci-G alkoxy for Z and Z 'groups can be, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, second butoxy, isobutoxy Or tertiary butoxy. The CVC4 alkylene group in the Z and Z 'groups may be, for example, methylene (-CH2-), ethylene [-CH (CH3) _], ethylene (-CH2CH2-), 1, 3 -Butyl (-CH2CH2CH2-), 1,2-Butyl [-CH2CH (CH3)-], 1,4-Butyl (-CH2CH2CH2CH2-), 1,3-Butyl [-CH2CH2CH ( CH3)-], 1,2-butylene [-CH2CH (CH2CH3)-], 2-methyl-1,2-propylpropyl [-CH2C (CH3) 2-], or 2-methyl-1, 3-Propyl [-CH2CH (CH3) CH2-]. The hydroxy-CVC4 alkyl group for the Z and Z 'groups may be hydroxymethyl -13-200301117

⑻ (HOCH2-) 、 2-羥基乙基（H〇CH2CH2-) 、 1-羥基乙基 [CH3CH(〇H)·]、3-經基丙基（HOCH2CH2CH2-)、2-幾基丙基 [CH3CH(OH)CH2CH2-]、1-羥基丙基[CH3CH2CH(〇H)-]、4-羥 基丁基（HOCH2CH2CH2CH2-)、3-羥基丁基[ch3ch(oh) ch2ch2-]、2-經基丁基[ch3ch2ch(〇h)ch2-]、1-羥基丁基 [CH3CH2CH2CH(OH)_]、1-羥基-1-甲基乙基[(CH3)2C(OH)-] 或 1-羥基-1-甲基丙基[ch3ch2c(ch3)(oh)-]。HO (HOCH2-), 2-hydroxyethyl (H0CH2CH2-), 1-hydroxyethyl [CH3CH (〇H) ·], 3-Ethylpropyl (HOCH2CH2CH2-), 2-Epiylpropyl [ CH3CH (OH) CH2CH2-], 1-hydroxypropyl [CH3CH2CH (〇H)-], 4-hydroxybutyl (HOCH2CH2CH2CH2-), 3-hydroxybutyl [ch3ch (oh) ch2ch2-], 2-meryl Butyl [ch3ch2ch (〇h) ch2-], 1-hydroxybutyl [CH3CH2CH2CH (OH) _], 1-hydroxy-1-methylethyl [(CH3) 2C (OH)-] or 1-hydroxy- 1-methylpropyl [ch3ch2c (ch3) (oh)-].

對Z與Z’基的c^-cu烷氧基羰基伸烷基可為，例如， 烷氧基羰基與伸烷基的組合。The c ^ -cualkoxycarbonylalkylene group for the Z and Z 'groups may be, for example, a combination of an alkoxycarbonyl group and an alkylene group.

CVC4烷氧基羰基定義為甲氧基羰基-[MeOC(O)-]、乙氧 基羰基-[EtOC(O)-]、正丙氧基羰基-[CH3CH2CH20C(0)-]、 異丙氧基羰基-[(CH3)2CH0C(0)-]、正丁氧基羰基 -[CH3CH2CH2CH2OC(〇）-]、異丁氧基羰基-[(CH3)2CHCH2 〇c(〇）-]、第二 丁氧基談基-[ch3ch2(ch3)choc(o)-]、第三 丁氧基羰基-[(CH3)3C0C(0)-]。Ci-C#伸烷基定義為上述進 一步的Ci-CU伸垸基。例如，下列基可自此等基團的組合 產生以形成C「C4烷氧基羰基-Ci-Q伸烷基··（甲氧基羰基） 甲基-[ch3oc(o)ch2-]、（乙氧基羰基）甲基-[ch3ch2〇c(〇） ch2-]、（正丙氧基談基）甲基-[ch3ch2ch2oc(o)ch2-]、（異 丙氧基羰基）甲基-[(CH3)2CHOC(〇）CH2-]、（正丁氧基羰基） 甲基-[ch3ch2ch2ch2oc(o)ch2-]、（異 丁氧基羰基）甲基 -[(CH3)2CHCH20C(0)CH2-]、（第二丁氧基羰基）甲基 -[ch3ch2(ch3)choc(o)ch2-]、（第三 丁氧基羰基）甲基 -[(CH3)2C0C(0)CH2-]、2-(甲氧基羰基）乙基-[ch3〇c(〇） -14 - 20030111?CVC4 alkoxycarbonyl is defined as methoxycarbonyl- [MeOC (O)-], ethoxycarbonyl- [EtOC (O)-], n-propoxycarbonyl- [CH3CH2CH20C (0)-], isopropoxy Carbonyl-[(CH3) 2CH0C (0)-], n-butoxycarbonyl- [CH3CH2CH2CH2OC (〇)-], isobutoxycarbonyl-[(CH3) 2CHCH2 oc (〇)-], second butyl Oxyl- [ch3ch2 (ch3) choc (o)-], and third butoxycarbonyl-[(CH3) 3C0C (0)-]. Ci-C # alkylene is defined as the further Ci-CU alkylene group described above. For example, the following groups can be generated from a combination of these groups to form C "C4 alkoxycarbonyl-Ci-Qalkylene ... (methoxycarbonyl) methyl- [ch3oc (o) ch2-], ( Ethoxycarbonyl) methyl- [ch3ch2oc (0) ch2-], (n-propoxyalkyl) methyl- [ch3ch2ch2oc (o) ch2-], (isopropoxycarbonyl) methyl- [ (CH3) 2CHOC (〇) CH2-], (n-butoxycarbonyl) methyl- [ch3ch2ch2ch2oc (o) ch2-], (isobutoxycarbonyl) methyl-[(CH3) 2CHCH20C (0) CH2- ], (Second butoxycarbonyl) methyl- [ch3ch2 (ch3) choc (o) ch2-], (third butoxycarbonyl) methyl-[(CH3) 2C0C (0) CH2-], 2 -(Methoxycarbonyl) ethyl- [ch3〇c (〇) -14-20030111?

(9) CH2CH2-]、2-(乙氧基羰基）乙基-[CH3CH2〇C(〇）CH2CH2-]、 2-(正丙氧基羰基）乙基-[CH3CH2CH2〇C(〇）CH2CH2-]、2-(異 丙氧基羰基）乙基-[(CH3)2CH0C(0)CH2CH2_]、2-(正丁氧基 羰基）乙基-[CH3CH2CH2CH2〇C(0)CH2CH2-]、2-(異丁 氧基羰 基）乙基-[(0^13)2€11(：1120(：(〇）(3112(：112-]、2-(第二丁氧基羰基） 乙基-[CH3CH2(CH3)CHOC(〇）CH2CH2-]、2-(第三 丁氧基羰基） 乙基-[(CH3)2C〇C(〇）CH2CH2-]。(9) CH2CH2-], 2- (ethoxycarbonyl) ethyl- [CH3CH2OC (()) CH2CH2-], 2- (n-propoxycarbonyl) ethyl- [CH3CH2CH2OC (()) CH2CH2- ], 2- (isopropoxycarbonyl) ethyl-[(CH3) 2CH0C (0) CH2CH2_], 2- (n-butoxycarbonyl) ethyl- [CH3CH2CH2CH2〇C (0) CH2CH2-], 2- (Isobutoxycarbonyl) ethyl-[(0 ^ 13) 2 € 11 (: 1120 (:( 〇) (3112 (: 112-), 2- (second butoxycarbonyl) ethyl- [CH3CH2 (CH3) CHOC (〇) CH2CH2-], 2- (third butoxycarbonyl) ethyl-[(CH3) 2CoC (〇) CH2CH2-].

對Z與Z’基的芳基可為苯基、苯-1-基、莕-2-基、[1，Γ-聯苯基]-2-基、[1，Γ-聯苯基]-3-基或[1，Γ-聯苯基]-4-基。 對Ζ與Τ基的雜芳基可為ρ比咬基、σ密咬基、峻17林基、異 喹啉基、苯并呋喃基、苯并噻吩基、1，3-苯并二噚茂基、 2,1，3-苯并魂二峻基、4丨嗓基、吱喃基、魂吩基、崎唑基 、異$ σ坐基、ρ塞吐基、ρ比Ρ各基、ρ比吐基或咪Χ7坐基，其藉由 可取代的位置之一鍵合。The aryl group for the Z and Z 'groups may be phenyl, phenyl-1-yl, fluoren-2-yl, [1, Γ-biphenyl] -2-yl, [1, Γ-biphenyl]- 3-yl or [1, Γ-biphenyl] -4-yl. The heteroaryl group of the p-Z and T group may be a ρ specific group, a σ dense group, a linyl group, an isoquinolinyl group, a benzofuryl group, a benzothienyl group, and a 1,3-benzodifluorenyl group. , 2,1,3-benzyl dimethyl, 4ryl, sulfanyl, phenanthryl, oxazolyl, iso $ σ, sethyl, ρ, π, ρ, and ρ Tyl or miX7 bases are bonded via one of the substitutable positions.

對Ζ與Ζ’基的雜環基可為六氫吡啶基、嗎啉基、硫代嗎 淋基、六氫Ρ比畊基、四氫吱喃基、四氫魂吩基、咪峻咬基 或Ρ比ρ各咬基，其藉由可取代的位置之一键合。 芳基、雜芳基及雜環基的取代基，亦在各情況下，在芳 基-CVC4伸烷基、雜芳基-CVC4伸烷基、芳氧基-CVC4伸烷 基、雜芳基-氧-CVC4伸烷基、芳基-cvc4伸烷氧基-cvc4 伸燒基單元内供Z基，可為， 無支鏈或支鏈Ci-q烷基（甲基、乙基、正丙基、異丙基、 正丁基、第二丁基、異丁基以及第三丁基）及/或c2-c6烯基 (乙晞基、晞丙基、高烯丙基、（E)- 丁 -2-烯基、（Z)- 丁 -2- -15 - 200301117Heterocyclic groups for the Z and Z 'groups can be hexahydropyridyl, morpholinyl, thiomorphyl, hexahydrophenyl, tetrahydropyranyl, tetrahydrophenyl, and miridyl Or P is a ratio of each bit, which is bonded by one of the substitutable positions. Substituents for aryl, heteroaryl and heterocyclic groups, in each case also at aryl-CVC4alkylene, heteroaryl-CVC4alkylene, aryloxy-CVC4alkylene, heteroaryl -O-CVC4alkylene, aryl-cvc4alkyleneoxy-cvc4 Z group in the sintering unit, which can be unbranched or branched Ci-q alkyl (methyl, ethyl, n-propyl Base, isopropyl, n-butyl, second butyl, isobutyl, and tert-butyl) and / or c2-c6 alkenyl (ethylfluorenyl, fluorenyl, homoallyl, (E)- But-2-enyl, (Z) -but-2--15-200301117

(ίο)(ίο)

晞基、戊-4-烯基、（E)-戊-3-晞基、（Z)-戊-3-烯基、（E)-戊 -2-烯基、（Z)-戊-2-烯基、2-甲基乙烯基、3 -甲基丁 - 3-晞基、 2-甲基丁 - 3-烯基、（E)-2-甲基丁 -2-烯基、（Z)-2-甲基丁 -2-晞基、2-乙基丙-2-烯基、己-5-晞基、（E) -己-4-烯基、（Z)-己-4-烯基、（E) -己-3-烯基、（Z)-己-3-晞基、（E) -己-2-烯基、 (Z)-己-2-晞基、1-甲基戊-4-烯基、（E) - 1-甲基戊-3-晞基、 (Z)-l-甲基戊-3-烯基、1-乙基丁 -3-晞基、（E)-l-甲基戊-2-烯基、（Z) - 1-甲基戊-2-烯基）及/或C3-CV_f烷基（環丙基、環 丁基、環戊基、環己基）及/或鹵素（氟、氯、溴、碘）。 對Z與Z’基的芳基-CrC^伸烷基可為以上定義的芳基與 烷基的組合，例如：苯基甲基、1-苯基乙基、2-苯基 乙基、1-甲基-1-苯基乙基、3-苯基丙基-4-苯基丁基、（莕 -1-基）甲基、（莕-1-基）乙基、2-(莕-1-基）乙基、（莕-2-基） 甲基、（萘-2-基）乙基、2-(萘-2-基）乙基、（[1，Γ-聯苯基]-2-基）甲基、（[1，Γ-聯苯基]-3-基）甲基或（[1，Γ-聯苯基]-4-基）Fluorenyl, pent-4-enyl, (E) -pent-3-enyl, (Z) -pent-3-enyl, (E) -pent-2-enyl, (Z) -pent-2 -Alkenyl, 2-methylvinyl, 3-methylbut-3-yl, 2-methylbut-3-enyl, (E) -2-methylbut-2-enyl, (Z ) -2-methylbut-2-fluorenyl, 2-ethylprop-2-enyl, hex-5-fluorenyl, (E) -hex-4-enyl, (Z) -hexan-4- Alkenyl, (E) -hex-3-enyl, (Z) -hex-3-fluorenyl, (E) -hex-2-enyl, (Z) -hex-2-fluorenyl, 1-methyl Pent-4-enyl, (E)-1-methylpent-3-enyl, (Z) -1-methylpent-3-enyl, 1-ethylbut-3-enyl, ( E) -l-methylpent-2-enyl, (Z)-1-methylpent-2-enyl) and / or C3-CV_f alkyl (cyclopropyl, cyclobutyl, cyclopentyl, Cyclohexyl) and / or halogen (fluorine, chlorine, bromine, iodine). The aryl-CrC ^ alkyl group for the Z and Z 'groups may be a combination of an aryl group and an alkyl group as defined above, for example: phenylmethyl, 1-phenylethyl, 2-phenylethyl, 1 -Methyl-1-phenylethyl, 3-phenylpropyl-4-phenylbutyl, (fluoren-1-yl) methyl, (fluoren-1-yl) ethyl, 2- (fluoren- 1-yl) ethyl, (fluoren-2-yl) methyl, (naphthalene-2-yl) ethyl, 2- (naphthalene-2-yl) ethyl, ([1, Γ-biphenyl]- 2-yl) methyl, ([1, Γ-biphenyl] -3-yl) methyl, or ([1, Γ-biphenyl] -4-yl)

甲基。 對Ζ與Ζ’基的雜芳基-C^C^伸烷基可為以上定義的雜芳 基與CVC4烷基的組合，例如：（咐啶-2-基）甲基、（吡啶- 3-基）甲基、（吡啶-4-基）甲基、（呋喃-2-基）甲基、（呋喃-3-基）甲基、（嘍吩-2-基）甲基、（噻吩-3-基）甲基、2-(噻吩-2-基）乙基或2 -(魂吩-3-基）乙基。 對Z與Z’基的芳氧基-Ci-G伸烷基可為以上定義的芳基 與C i - C4烷基藉由醚基（-0-)的組合鍵合，例如：苯氧基甲 基、1-苯氧基乙基、2-苯氧基乙基、1-甲基-1-苯氧基乙基 -16-methyl. The heteroaryl-C ^ C ^ alkylene group for the Z and Z 'groups may be a combination of the heteroaryl group and the CVC4 alkyl group defined above, for example: (pyridin-2-yl) methyl, (pyridine-3 -Yl) methyl, (pyridin-4-yl) methyl, (furan-2-yl) methyl, (furan-3-yl) methyl, (fluoren-2-yl) methyl, (thiophene- 3-yl) methyl, 2- (thien-2-yl) ethyl or 2- (physin-3-yl) ethyl. The aryloxy-Ci-G alkyl group of the Z and Z 'groups may be an aryl group and a C i-C4 alkyl group defined above through a combination of ether groups (-0-), for example: phenoxy Methyl, 1-phenoxyethyl, 2-phenoxyethyl, 1-methyl-1-phenoxyethyl-16-

、3-苯氧基丙基、4_苯氧其 乳基丁基、[(萘-1-基）氧基]甲基、 1-[(秦-1-基）氧基]乙基、2「（言1 ·μ：\" # [(奈-1·基）氧基]乙基、[(莕-2- 基）氧基]甲基、1-[(莕-2-其〗备JL17计 土）乳基]乙基、2-[(萘-2-基）氧基] 乙基、（[1，1’_聯苯基]-2-基）荽其!甲| /Γ 土 m基]甲基、聯苯基]-3_ 基）氧基]甲基或（Π，1，-聯苯基]·4_基）氧基]甲基。 對Ζ與Ζ’基@芳氧基_Ci_c4伸㉟基可為以上定義的雜芳 基與Cl-Q燒基藉由鍵基（_〇_)的組合鍵合，例如：[卜比咬_2_ 基）氧基]甲基、[卜比咬·3-基）氧基]甲基或[(峨咬-4-基）氧基 ]甲基。 +斜Z與Z基的芳基义义伸燒氧基_C1_C4伸燒基可為以上 至我的万基與CVC4伸烷基藉由醚基卜〇·）的按序組合鍵合 伸蚝基，例如：（苯基甲氧基）甲基或2-(苯基甲氧基）乙 〇 可:基的式CpFqHr(其中P叫，2，3，4，q〉l及q+r=2p+l)的基 一:一氣甲基、五氟乙基、過氟丙基、過氟丁基或2,2,2_ 二氣乙基。 根據本發明較佳為該等通式I的化合物，其中：, 3-phenoxypropyl, 4-phenoxy its lactylbutyl, [(naphthalene-1-yl) oxy] methyl, 1-[(qin-1-yl) oxy] ethyl, 2 "(Letter 1 · μ: \ "# [(奈 -1 -yl) oxy] ethyl, [(fluoren-2-yl) oxy] methyl, 1-[(fluorene-2- 其 〖 JL17 Jito) lactyl] ethyl, 2-[(naphthalene-2-yl) oxy] ethyl, ([1,1'_biphenyl] -2-yl) 荽 its! A | / Γ 土m group] methyl, biphenyl] -3-yl) oxy] methyl or (Π, 1, -biphenyl] · 4-yl) oxy] methyl. p-Z and Z 'groups @ aryloxy The _Ci_c4 fluorenyl group may be a combination of a heteroaryl group and a Cl-Q alkyl group defined above through a combination of a bond group (_〇_), for example, [[[# 比 _2_2]] oxy] methyl, [Bibbita · 3-yl) oxy] methyl or [(erbino-4-yl) oxy] methyl. + Aryl meaning of oblique Z and Z groups May be from above to my Wanji and CVC4 alkyl group through the sequential combination of ether group butyl group, such as: (phenylmethoxy) methyl or 2- (phenylmethoxy A radical) of the formula CpFqHr (wherein P is 2, 3, 4, q> l and q + r = 2p + l): a methyl radical, pentafluoroethyl ., Over-fluoropropyl, or perfluoro butyl ethyl 2,2,2_ two gas for such preferred compounds of the present invention according to formula I, wherein:

A表示 B表示 AB 氰基， 三氟甲基 或 起表 鍵結至芳香族環的式Ilia的環狀基 > 17- 200301117 (12)A represents B represents AB cyano, trifluoromethyl or a cyclic group of the formula Ilia bonded to an aromatic ring formally > 17- 200301117 (12)

IliaIlia

n表示整數值1(僅在T表示碳的情況），2，3，4，5，6,7或8之 i與j表示值1，n is an integer value of 1 (only when T is carbon), and 2, 3, 4, 5, 6, 7, or 8 i and j are values of 1,

R與Rf表示氫原子，R and Rf represent hydrogen atoms,

Y表示羰基-C(〇）-、磺醯基-S(0)2-、亞胺基羰基-C(〇）N(Z’）-、亞胺基磺醯基-S(0)2N(Z’）-、亞胺基（嘍噚甲基）基 -C(S)N(Z’）-、氧羰基亞胺基（噻嘮甲基）基-C(S)N(Zf) C(0)0-、氧羰基-C(0)0-、硫烷基羰基-C(0)S-，及 Z與Z’互相獨立表示無支鏈Ci-Q烷基或支鏈c3-c4烷基、 (：3-(：6環烷基，其係視需要用苯基、（03-(：6環烷基hCVCU 伸燒基、支鏈或無支鏈C2-C3晞基、Ci-C#燒氧基、氰 基、苯基硫烷基或羥基-Ci-Q伸烷基、（2-甲氧基乙氧 基）甲基、[2-(2-甲氧基乙氧基）乙氧基]甲基、2-(2-甲 氧基乙氧基）乙基、2-[2-(2-甲氧基乙氧基）乙氧基]乙 基、CVCU烷氧基-CVC4伸烷基、Ci-Q烷氧基羰基-CVC4 伸烷基取代；芳基、雜芳基、雜環基、芳基-(^-匕伸 烷基、雜芳基伸烷基、芳氧基-Ci-CU伸烷基、雜 芳氧基-(VC4伸烷基、芳基伸烷氧基-CVC4伸烷 基，其為未經取代或用最多三個支鏈或無支鏈Ci-h 烷基、c2-c4烯基、c3-c6環烷基、c3-c6環烷氧基、苯 -18- 200301117Y represents carbonyl-C (〇)-, sulfofluorenyl-S (0) 2-, iminocarbonyl-C (〇) N (Z ')-, iminosulfonyl-S (0) 2N ( Z ')-, imino (fluorenylmethyl) -C (S) N (Z')-, oxycarbonylimino (thienylmethyl) -C (S) N (Zf) C ( 0) 0-, oxycarbonyl-C (0) 0-, sulfanylcarbonyl-C (0) S-, and Z and Z 'are independent of each other to indicate an unbranched Ci-Q alkyl group or a branched c3-c4 alkane Group, (: 3-(: 6-cycloalkyl group, if necessary, phenyl group, (03-(: 6-cycloalkyl hCVCU alkynyl group, branched or unbranched C2-C3fluorenyl group, Ci-C # Carbooxy, cyano, phenylsulfanyl, or hydroxy-Ci-Q alkylene, (2-methoxyethoxy) methyl, [2- (2-methoxyethoxy) ethoxy Group] methyl, 2- (2-methoxyethoxy) ethyl, 2- [2- (2-methoxyethoxy) ethoxy] ethyl, CVCU alkoxy-CVC4 butane Alkyl, Ci-Q alkoxycarbonyl-CVC4 alkylene substitution; aryl, heteroaryl, heterocyclyl, aryl-(^-alkylene, heteroarylalkylene, aryloxy-Ci- CU alkylene, heteroaryloxy- (VC4 alkylene, arylalkyloxy-CVC4 alkylene, which is unsubstituted or with up to three branched or unbranched C i-h alkyl, c2-c4 alkenyl, c3-c6 cycloalkyl, c3-c6 cycloalkoxy, benzene -18- 200301117

(13) 基、氰基、函素、甲氧基、乙氧基、苯氧基、芊氧基 、甲基硫烷基、乙基硫烷基、芊基、硫烷基、苯基硫 烷基、二甲基胺基、乙醯基胺基、三氟甲基、三氟甲 氧基、三氟甲基硫烷基或乙醯基取代，或式CpFqHr( 其中 p= 1，2，3，4，q〉1及 q+r=2p+1)，及 Zf除了上述定義以外表示氫原子。(13) aryl, cyano, functional group, methoxy, ethoxy, phenoxy, fluorenyl, methylsulfanyl, ethylsulfanyl, fluorenyl, sulfanyl, phenylsulfane Group, dimethylamino, ethynylamino, trifluoromethyl, trifluoromethoxy, trifluoromethylsulfanyl or ethenyl, or the formula CpFqHr (where p = 1, 2, 3 , 4, q> 1 and q + r = 2p + 1), and Zf represents a hydrogen atom in addition to the above definition.

關於根據本發明通式I化合物的醫藥上可相容鹽的資料 ，根據熟悉此技藝者已知方法，i. a.鹽酸、氫溴酸、硫酸 、磷酸及硝酸視為無機酸；i.a.醋酸、丙酸、己酸、辛酸 、癸酸、油酸、硬脂酸、順丁晞二酸、反丁蹄二酸、玻ί白 酸、苯甲酸、抗壞血酸、草酸、水楊酸、酒石酸、擰檬酸 、乳酸、乙醇酸、丙二酸、扁桃酸、肉桂酸、谷胺酸及天 冬胺酸視為羧酸，及i.a.甲烷磺酸、乙烷磺酸、甲苯磺酸 、苯績酸、以及萘續酸視為續酸。 下述根據本發明的實例1至745的化合物特別佳。Regarding the information of the pharmaceutically compatible salts of the compounds of the general formula I according to the present invention, according to methods known to those skilled in the art, ia hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid and nitric acid are considered as inorganic acids; ia acetic acid, propionic acid, Caproic acid, caprylic acid, capric acid, oleic acid, stearic acid, maleic acid, fumaric acid, hyaluronic acid, benzoic acid, ascorbic acid, oxalic acid, salicylic acid, tartaric acid, citric acid, lactic acid , Glycolic acid, malonic acid, mandelic acid, cinnamic acid, glutamic acid, and aspartic acid are regarded as carboxylic acids, and ia methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, benzoic acid, and naphthoic acid Treated as continued acid. The following compounds according to Examples 1 to 745 of the present invention are particularly preferred.

藥理研究 根據本發明的化合物以各種模型試驗。根據本發明通式 I的化合物具有特徵為，在此情況下，其為具有抗雄性激 素作用的化合物，使雄性激素受體去安定、抑制攝護腺腫 瘤生長且同時具有高度視需要口服生物利用率。 有關雄性激素受體活性影響的體外試驗實施如下： 在本文所呈現的圖表中，使用下列縮寫： 雙卡留特醯胺：N-[4-氰基- 3-(三氟甲基）本基]-3-[(4-氟苯 基）磺醯基]-2-羥基-2-甲基丙醯胺 -19- (14)Pharmacological studies The compounds according to the invention are tested in various models. The compound according to the general formula I of the present invention is characterized in that, in this case, it is a compound having an antiandrogenic effect, which destabilizes the androgen receptor, inhibits the growth of prostate tumors, and at the same time has a high oral bioavailability as needed rate. The in vitro tests on the effects of androgen receptor activity are carried out as follows: In the chart presented here, the following abbreviations are used: Dicarbutamide: N- [4-cyano-3- (trifluoromethyl) benzyl ] -3-[(4-fluorophenyl) sulfonamido] -2-hydroxy-2-methylpropanamide-19- (14)

R1881 ··甲基三晞醇酮，17/3 -羥基_17α -甲基雌·4,9，11-三烯 -3 -酮 C P A :酷酸氯巍甲蹄孕酮，1 7 -(乙驢氧基）-6 -氯-1 /5，2 /5 -二 氫-3，H-環丙[1，2]孕-1，4,6-三烯- 3,20-二酮 化合物B: 4-[2,5-二氫-3-甲基-4-[4-[4-(甲基磺醯基）六氫吡 畊-1-基]丁基]-2,5-二氧代- ΙΗ-说咯-1-基]-2-(三氟甲 基）苯甲腈（實例117)R1881 ·· methyltriol ketone, 17/3 -hydroxy_17α -methylestrone · 4,9,11-triene-3 -one CPA: Chloroprofen, 1 7-(B Donkeyoxy) -6-chloro-1 / 5,2 / 5-dihydro-3, H-cyclopropane [1,2] progestin-1,4,6-triene-3,20-dione compound B : 4- [2,5-Dihydro-3-methyl-4- [4- [4- (methylsulfonyl) hexahydropyridin-1-yl] butyl] -2,5-dioxo -I-S-S--1-yl] -2- (trifluoromethyl) benzonitrile (Example 117)

模塑1 : LNCaP細胞内AR藉試驗物質的去安定化Mold 1: Destabilization of AR in LNCaP cells by test substance

在25公分平方細胞培育燒瓶中，2*106LNCaP細胞於6毫升 RPMI 1640而無酚紅係用4毫莫耳谷胺及5%活性碳處理的 血清（CCS)生長並在37°C下，5%C02，於潮濕氛圍内隔夜培 育。次日，細胞係用濃度為10或1微米下的試驗物質處理， 藉此溶劑的最後濃度為〇.5%DMSO。作為對照物，細胞僅 用0.5%DMSO處理。在24小時培育時間後，培養基係用重 新力口入物質及另外24小時培育改變。在48小時後，細胞用 PBS洗滌、用PBS/20毫莫耳EDTA溶解、再用PBS-CA2 + /Mg2+ 洗滌，然後在-80°C下冷凍至少2小時作為細胞粒。然後， 細胞粒再懸浮於200微升溶解緩衝劑内（50毫莫耳參/HC1， pH7.5;150毫莫耳NaCl，l·5毫莫耳MgCl2，0·2%SDS，10%甘油 醇、1毫莫耳DTT，O.Olx完全-EDTA蛋白酶抑制劑（Roche， Mannheim))並在 4°C 下用 10U苯甲酸酶（Merck, Darmstadt)處理 10分鐘。在加入5毫莫耳EDTA後，粒化不溶性物質，25微 克細胞萃取物分離於4-12%SDS-聚丙晞醯胺膠（Invitrogen) 内。然後，蛋白質轉移至硝基纖維素（HyBondECL，Amersham) -20- 200301117In a 25 cm square cell incubation flask, 2 * 106 LNCaP cells were grown in 6 ml of RPMI 1640 without phenol red system. Serum (CCS) treated with 4 millimolar glutamine and 5% activated carbon was grown at 37 ° C. 5 % C02, cultivated overnight in a humid atmosphere. The next day, the cell line was treated with the test substance at a concentration of 10 or 1 micrometer, whereby the final concentration of the solvent was 0.5% DMSO. As a control, cells were treated with only 0.5% DMSO. After the 24-hour incubation period, the culture medium was re-introduced with material and the other 24 hours of incubation were changed. After 48 hours, the cells were washed with PBS, lysed with PBS / 20 millimolar EDTA, and then washed with PBS-CA2 + / Mg2 +, and then frozen at -80 ° C for at least 2 hours as cell pellets. The cells were then resuspended in 200 μl of lysis buffer (50 millimolars / HC1, pH 7.5; 150 millimoles NaCl, 1.5 millimoles MgCl2, 0.2% SDS, 10% glycerol Alcohol, 1 millimolar DTT, O. Olx complete-EDTA protease inhibitor (Roche, Mannheim)) and treated with 10 U benzoate (Merck, Darmstadt) for 10 minutes at 4 ° C. After adding 5 millimolar EDTA, insoluble matter was pelleted, and 25 micrograms of cell extract was separated into 4-12% SDS-polypropylamine gel (Invitrogen). The protein is then transferred to nitrocellulose (HyBondECL, Amersham) -20- 200301117

(15) 並用單無性系抗體培育對抗雄性激素受體（AR441; Santa Cruz Biotechnologies; 1 : 400 稀釋）及肌動蛋白（ICN，1 : 5000- 1 : 20,000稀釋）。在用第二抗體（抗鼠 IgG-HRP，Amersham 或-AP，Invitrogen)培育後，Western斑係由化學發光（ECL， Amersham; Western Breeze，Invitrogen)發展，而光信號係用 Chemilmager™ (Kodak)量化。雄性激素受體的量係以對肌動 蛋白的比率作為DMSO對照物的百分比計算。(15) Anti-androgen receptors (AR441; Santa Cruz Biotechnologies; 1: 400 dilution) and actin (ICN, 1: 5000-1: 20,000 dilution) were incubated with monoclonal antibodies. After culturing with a secondary antibody (anti-mouse IgG-HRP, Amersham or -AP, Invitrogen), Western plaques were developed by chemiluminescence (ECL, Amersham; Western Breeze, Invitrogen), and the light signal system was Chemilmager ™ (Kodak) Quantification. The amount of androgen receptor is calculated as the percentage of actin as a percentage of the DMSO control.

表1顯示濃度為10或1微米下的選定試驗物質對雄性激 素受體蛋白於人體攝護腺LNCaP内的含量的作用。數據對 應僅用溶劑DMSO(=對照物）處理的細胞AR含量的％比例 。細胞用引述的試驗物質的處理導致AR含量減少至對照 物的1/5(實例248的22%: 4-[2,5-二氫-3-[6-[4-(2-甲氧基苯甲 醯基）六氫吡畊-1-基]己基]-4-甲基- 2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈）的濃度處理為10微米。比較用物 質雙卡留特醯胺不會影響AR含量，而合成雄性激素R1881Table 1 shows the effect of selected test substances at a concentration of 10 or 1 micron on the content of androgen receptor protein in human prostate LNCaP. Data correspond to% AR content of cells treated with solvent DMSO (= control) only. Treatment of cells with the quoted test substance resulted in a reduction in AR content to 1/5 of the control (22% of Example 248: 4- [2,5-dihydro-3- [6- [4- (2-methoxy Benzamidine) hexahydropyridin-1-yl] hexyl] -4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile ) The concentration is treated to 10 microns. Comparative substance biscarbutamide does not affect AR content, while the synthetic androgen R1881

使AR蛋白安定化。後者可自文件中得知（J· A· Kemppainen 等人，J· Biol. Chem. 1992, 267, 968-974)。 實例248 : 4-[2,5 -二氫-3-[6-[4-(2-甲氧基苯甲醯基）六氫吡 畊-1-基]己基]-4-甲基- 2,5-二氧代-1H-吡咯-1-基]-2-(三氟 甲基）苯甲腈與實例629 : 4-[3-[5-[4-(乙基-磺醯基）六氫吡 _ -1-基]戊基]-4,4-二甲基-5-氧代-2-硫乳味咬淋-1-基]-2-( 三氟甲基）苯甲腈可減少亦在濃度為1微米的AR含量至最 多對照物的一半的值。藉減少AR含量，其假定由AR蛋白 的去安定實施，可進一步強化抗荷爾蒙對細胞增生的抑制 -21 - 20030111 (16) 作用 表1·用選定試驗物質處理後LNCaP内的AR含量（％) 實例 248 試驗物質 4-[2,5_二虱-3-[6-[4_(2-甲氧基苯甲酸基)六氫p比p井小基· 己基Η-甲基_2,5-二氧代-1Η4咯小基]_2_(三氟甲基) 苯甲腈__ 4-[3-[5-[4-(3,4-二甲氧基苯甲酿基)六氫ρ比啩小基]苯基 ]-2,5-二氫-4-甲基-2,5-二氧代-1Η-峨洛-1-基]-2-(三氟甲 基)苯甲腈 一 4-[2,5-二氫-3-甲基斗[4-[4-(甲基磺醯基吡畊小基 ]丁基]_2,5·二氧代-1H-♦各小基]_2_(三氟甲基)苯甲腈 4-[3-[4-[4-(2-氯苯甲酿基)六氫p比p井-1-基]丁基]_2,5_二 氫-4-甲基_2,5-二氧代-1仏♦各-1-基]么(三氟甲基)’苯甲 4-[3-[6-[4-[(4-氰基苯基)績酿基]六氫p比_-1-基]己基 ]_4_甲基二氧代-1H-峨咯小基]冬(三氟甲基)苯甲 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 '2,5--氧代-ΙΗ-^7比17各_3-基]己基]-N-(2,6·二氯π比淀-4-基 )六氫吡啶小羧醯胺______ 4-[3-[6-[4-[i-氯苯氧基]乙醯基]六氫吡畊·丨·基]己基 ]-2,5-二氫斗甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲 基)苯甲月斧 4-[6-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5·二氧代-1H4咯各基]己基]具〇(甲基硫烷基)苯 基]六氫吡啶-1-羧醯胺_ 4-[Η5-[4-(2，1，3-苯并。塞二K基)續晞基]六氫tr比呼-1-基]苯基]_2,5·二氫冰甲基_2,5_二氧代-1H-吡咯小基 ]-2-(三氟甲基)苯甲腈______ 4-[6-[ 1 基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-一氧代-lH-p比17各-3-基]己基]-N-(3-氣苯基)六氯u比 啶-1-羧醯胺 4-[6-[H4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-一氧代-1Η-々ίι^-3-基]己基]-N-(4-氣苯基)六氮p比 AR含量[%]Stabilizing the AR protein. The latter is known from the document (J. A. Kemppainen et al., J. Biol. Chem. 1992, 267, 968-974). Example 248: 4- [2,5 -Dihydro-3- [6- [4- (2-methoxybenzyl) hexahydropyridin-1-yl] hexyl] -4-methyl-2 , 5-Dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile and Example 629: 4- [3- [5- [4- (ethyl-sulfonyl) Hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thiomilk taste bitten-1-yl] -2- (trifluoromethyl) benzonitrile The AR content, which is also at a concentration of 1 micron, can be reduced to values up to half of the control. By reducing the AR content, it is assumed that the destabilization of the AR protein can further strengthen the anti-hormonal inhibition of cell proliferation-21-20030111 (16) Effects Table 1 · AR content in LNCaP after treatment with selected test substances (%) Example 248 Test substance 4- [2,5_dilice-3- [6- [4_ (2-methoxybenzoate) hexahydrop-p-p-sapyl group · hexylfluorene-methyl_2,5- Dioxo-1Η4role small group] _2_ (trifluoromethyl) benzonitrile__ 4- [3- [5- [4- (3,4-dimethoxybenzyl) hexahydroρ ratio Fluorenyl] phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 fluorene-erol-1-yl] -2- (trifluoromethyl) benzonitrile-1 4- [2,5-Dihydro-3-methylpyridine [4- [4- (methylsulfonylpyridine small group] butyl] _2,5 · dioxo-1H- ♦ each small group] _2_ (trifluoromethyl) benzonitrile 4- [3- [4- [4- (2-chlorobenzyl) hexahydrop ratio pwell-1-yl] butyl] _2,5_dihydro -4-methyl_2,5-dioxo-1 仏 E each-1-yl]? (Trifluoromethyl) 'benzyl 4- [3- [6- [4-[(4-cyano Phenyl) phenyl group] Hexyl p ratio -1--1-yl] hexyl] _4-methyldioxo-1H-erroyl small group] winter (trifluoromethyl) benzyl 4- [6- [1 -[4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl'2,5--oxo-ΙΗ- ^ 7 to 17 each _3-yl] hexyl] -N- (2,6 · dichloroπbidian-4-yl) hexahydropyridine carboxamide ______ 4- [3- [6- [4- [ i-chlorophenoxy] ethenyl] hexahydropyridine · 丨 · yl] hexyl] -2,5-dihydromethyl-2,5-dioxo-1H-pyrrole-1-yl]- 2- (trifluoromethyl) benzyl axe 4- [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2, 5 · Dioxo-1H4, each group] hexyl] has 0 (methylsulfanyl) phenyl] hexahydropyridine-1-carboxamidin-4 -_ [5- (4- (2,1,3- Benzo.Cycloyl) continylfluorenyl] hexahydrotrbihu-1-yl] phenyl] _2,5 · dihydroicemethyl_2,5_dioxo-1H-pyrrole small group]- 2- (trifluoromethyl) benzonitrile ______ 4- [6- [1-yl-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5- Monooxo-lH-p ratio 17 each of 3-yl] hexyl] -N- (3-gasphenyl) hexachloroupyridine-1-carboxamidin 4- [6- [H4-cyano-3 -(Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-monooxo-1Η-々 ^^ yl] hexyl] -N- (4-Ga Phenyl) hexazolium p AR content [%]

At 10 微米 22At 10 microns 22

At 1 微米 51 -22- 46 330 200301117At 1 micron 51 -22- 46 330 200301117

(17) 實例 試驗物質 AR含量 [%] At 10 微米 At 1 微米 淀-1-複S盘胺 295 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-(苯基磺醯基)六 氫吡畊-1-基]-1H-吡咯小基]-2-(三氟甲基)苯甲腈 48 296 4-[2,5-二氫-3-甲基-4-[6-[4-(甲基磺醯基)六氫吡畊-1-基 ]己基]-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲腈 48 96 4-[3-[4-[4-[4-(二甲基胺基)苯甲醯基]六氫吡畊小基]丁 基]-2,5·二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟 甲基)苯甲月膏 50 315 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]苯基六氫吡啶-1-羧 醯胺 52 121 4-[3-[4-[4-[(4-氰基苯基)磺醯基]六氫吡畊-1-基]丁基 ]-2,5-<—風j-4-甲基-2,5-> —氧代·111-11比洛-1-基]-2-(二氣甲 基)苯甲腈 53 93 4-[3-[4-[4-(環丁基羰基)六氫吡畊-1-基]丁基]-2,5-二氫 斗甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯甲腈 53 297 4-[2,5-二氫-3-甲基-4-[6-[4-[4-(甲基苯基)磺醯基]六氫 吡畊-1-基]己基]-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲 基)苯甲腈 59 351 4-[6-[1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5_二氧代-1H-吡咯-3-基]己基]-N-(2,6-二氯苯基)六氫 吡啶-1-羧醯胺 61 350 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-(2,6-二氟苯基)六氫 吡啶-1-羧醯胺 61 324 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5·二氧代-1H-吡咯-3-基]己基]-N-[2-(三氟甲基)苯基] 六氫吡啶-1-羧醯胺 62 270 4-[2,5-二氫-3-甲基-4-[6-[4-(3-甲基-1-氧代丁基)六氫吡 畊-1-基]己基]-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基) 苯甲腈 65 99 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[4-[4-[(噻-2-基)羰基] 六氫吡畊-1-基]丁基HH-吡咯-1-基]-2-(三氟甲基)苯甲 腈 66(17) Example Test substance AR content [%] At 10 micrometers At 1 micrometer lake -1- complex S disc amine 295 4- [2,5-dihydro-3-methyl-2,5-dioxo-4 -[6- [4- (phenylsulfonyl) hexahydropyridine-1-yl] -1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 48 296 4- [2,5 -Dihydro-3-methyl-4- [6- [4- (methylsulfonyl) hexahydropyridin-1-yl] hexyl] -2,5-dioxo-1H-pyrrole small] -2- (trifluoromethyl) benzonitrile 48 96 4- [3- [4- [4- [4- (dimethylamino) benzamidinyl] hexahydropyridine] butyl] -2,5 · Dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzyl cream 50 315 4- [6- [ 1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] Phenylhexahydropyridine-1-carboxyfluorenamine 52 121 4- [3- [4- [4-[(4-cyanophenyl) sulfonamido] hexahydropyridin-1-yl] butyl]- 2,5- < -wind j-4-methyl-2,5- > -oxo · 111-11 bilor-1-yl] -2- (digasmethyl) benzonitrile 53 93 4 -[3- [4- [4- (Cyclobutylcarbonyl) hexahydropyridine-1-yl] butyl] -2,5-dihydromethyl-2,5-dioxo-1H-pyrrole -1-yl] -2- (trifluoromethyl) benzonitrile 53 297 4- [2,5-dihydro-3-methyl 4--4- [6- [4- [4- (methylphenyl) sulfonamido] hexahydropyridin-1-yl] hexyl] -2,5-dioxo-1H-pyrrole-1-yl ] -2- (trifluoromethyl) benzonitrile 59 351 4- [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl -2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- (2,6-dichlorophenyl) hexahydropyridine-1-carboxamide 61 350 4- [6- [1 -[4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl]- N- (2,6-difluorophenyl) hexahydropyridine-1-carboxamide 61 324 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2 , 5-dihydro-4-methyl-2,5 · dioxo-1H-pyrrole-3-yl] hexyl] -N- [2- (trifluoromethyl) phenyl] hexahydropyridine-1- Carboxamide 62 270 4- [2,5-Dihydro-3-methyl-4- [6- [4- (3-methyl-1-oxobutyl) hexahydropyrim-1-yl] Hexyl] -2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 65 99 4- [2,5-dihydro-3-methyl-2,5- Dioxo-4- [4- [4-[(thia-2-yl) carbonyl] hexahydropyridin-1-yl] butylHH-pyrrole-1-yl] -2- (trifluoromethyl) Benzonitrile 66

-23 - 200301117-23-200301117

(18) 實例 試驗物質 AR含量 [%] At 10 微米 At 1 微米 342 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[4-(甲基硫烷基)苯 基]六氫吡啶-1-羧醯胺 67 268 4-[3-[6-[4-(4-氰基苯甲醯基)六氫吡畊小基]己基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-1 -基]-2-(三氟甲基)苯 甲腈 73 319 4-[6-[ 1-[4-氰基：(三氟甲基）苯基]-2,5-二氫冬甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-(l-甲基乙基)六氫 吡啶-1-羧醯胺 74 629 4-[3-[5-[4-(乙基磺醯基)六氫吡畊-1-基]戊基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啉小基]-2-(三氟甲基)苯甲腈 54 696 4-[6-[3-[4-氰基各(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧咪唑啉-1 -基]己基]六氫吡畊-1 -碳硫酸S-甲酯 60 524 4-[4,4-二甲基-5-氧代-3-[2-[4-[(嘍-2-基）羰基]六氫吡 畊小基]丙基]-2-硫氧咪唑啉小基]-2-(三氟甲基)苯甲 腈 61 546 4-[4,4-二甲基-3-[4-[4-(2-甲基-1-氧代丙基)六氫吡畊-1-基]丁基]-5-氧代-2-硫氧咪唑啉-1-基]-2-(三氟甲基)苯 甲腈 68 653 4-[4,4-二甲基-3-[6·[4-(2-甲基小氧代丙基)六氫吡畊小 基]己基]-5-氧代-2-硫氧咪唑啉小基]-2-(三氟甲基)苯 甲腈 71 632 4-[3-[5-[4-[(4_氰基苯基)磺醯基]六氫吡畊-1-基]戊基 ]-4,4-二甲基-5-氧代-2-硫氧咪唑啉-1-基]-2-(三氟甲基) 苯甲腈 75 雙卡硫 特醯胺 Ν-|>氰基各(三氟甲基)苯基]-3-[(4-氟苯基)磺醯基]-2-羥基-2-甲基丙醯胺 100 R181 (10 nM) 17 yS -羥基-17 α -甲基雌-4,9，11-三烯-3-酮 250(18) Example Test substance AR content [%] At 10 microns At 1 microns 342 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro 4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- [4- (methylsulfanyl) phenyl] hexahydropyridine-1-carboxamide 67 268 4- [3- [6- [4- (4-Cyanobenzyl) hexahydropyridine] hexyl] -2,5-dihydro-4-methyl-2,5-dioxy 1H-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 73 319 4- [6- [1- [4-cyano: (trifluoromethyl) phenyl] -2, 5-dihydroaspartyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- (l-methylethyl) hexahydropyridine-1-carboxamide 74 629 4- [3- [5- [4- (ethylsulfonyl) hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooximidazoline small group ] -2- (trifluoromethyl) benzonitrile 54 696 4- [6- [3- [4-cyano (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo 2-thiothioimidazoline-1 -yl] hexyl] hexahydropyridine-1 -S-methylcarbonate 60 524 4- [4,4-dimethyl-5-oxo-3- [2 -[4-[(fluoren-2-yl) carbonyl] hexahydropyridine] propyl] -2-thiooximidazoline small] -2- (trifluoromethyl) benzonitrile 61 546 4- [4,4-dimethyl-3- [4- [4- (2-methyl -1-oxopropyl) hexahydropyridin-1-yl] butyl] -5-oxo-2-thiooximidazolin-1-yl] -2- (trifluoromethyl) benzonitrile 68 653 4- [4,4-dimethyl-3- [6 · [4- (2-methyl small oxopropyl) hexahydropyridine] hexyl] -5-oxo-2-thiooxy Imidazoline small group] -2- (trifluoromethyl) benzonitrile 71 632 4- [3- [5- [4-[(4_cyanophenyl) sulfonamido] hexahydropyrine-1- Yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooximidazolin-1-yl] -2- (trifluoromethyl) benzonitrile 75 -| > Cyano (trifluoromethyl) phenyl] -3-[(4-fluorophenyl) sulfonyl] -2-hydroxy-2-methylpropanamide 100 R181 (10 nM) 17 yS -hydroxy-17 α-methylestrone-4,9,11-trien-3-one 250

模型2 : LNCaP細胞增生的抑制 關於增生檢定，6000 LNCaP細胞/井生長於微滴定板（96 -24- 200301117Model 2: Inhibition of LNCaP cell proliferation Regarding the proliferation assay, 6000 LNCaP cells / well were grown on microtiter plates (96 -24- 200301117

(19)(19)

井）於具有5%CCS的50微升RPMI 1640培養基内並如模型1般 培育。24小時後，細胞接收50微升稀釋於培養基内二次濃 縮的試驗物質。溶劑濃度為0.5% DMSO。4日後，細胞接收 另外1 00微升稀釋於培養基内一次濃縮的試驗物質。7- 8曰 後，細胞的增生速率係利用結晶紫檢定測定（Gillies等人， Anal。Biochem. 1986，159，109-113)。關於測定對抗作用，物 質處理係在0.1毫微米R1 881存在下（乙醇溶液的1: 1000稀釋 )實施。對照用細胞僅接收0.5% DMSO。關於促效作用，細 胞僅用試驗物質（無R1881)處理。(Well) in 50 microliters of RPMI 1640 medium with 5% CCS and incubated as Model 1. After 24 hours, the cells received 50 microliters of test substance diluted twice in the culture medium. The solvent concentration was 0.5% DMSO. After 4 days, the cells received another 100 microliters of test substance diluted once in the culture medium. After 7-8, the cell proliferation rate was determined using the crystal violet assay (Gillies et al., Anal. Biochem. 1986, 159, 109-113). Regarding the determination of the counteracting effect, the substance treatment was carried out in the presence of 0.1 nm R1 881 (1: 1000 dilution of ethanol solution). Control cells received only 0.5% DMSO. Regarding the potency, the cells were treated with the test substance only (without R1881).

表2顯示試驗物質對人類雄性激素依附攝護腺細胞線 LNCaP增生的抑制作用。細胞增生的抑制為對治療攝護腺 癌物質醫療用途的重要條件。根據本發明選定的七種AR-去安定化試驗物質可在具有類似於相當低IC5〇的0.1毫微 米合成雄性激素R1 881如規定的非類固醇抗雄性激素雙卡 留特醯胺存在下抑制細胞增生。在物質濃度為1微米中， 增生較在0.1毫微米R1 881存在下的細胞生長至少80%減少 。實例696 : 4-[6-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲 基-4 -氧代-2 -硫氧咪峻4 - 1 -基]己基]六氫p比啡-1 -破硫酸S -甲酯與實例653 : 4-[4,4-二甲基-3-[6-[4-(2-甲基-1-氧代丙 基）六氫p比呼-1 -基]己基]-5 -氧代-2 -硫氧咪咬琳-1 -基]-2 -( 三氟甲基）苯甲腈完全抑制在此濃度下的生長，而在此等 條件下，雙卡留特醯胺僅達到85%的抑制率。高達至試驗 濃度為10微米，任何七種試驗物質之一均未看到增生刺激 的作用。 -25 - 200301117 (20)Table 2 shows the inhibitory effect of the test substance on the proliferation of human androgen-dependent prostate cell line LNCaP. Inhibition of cell proliferation is an important condition for medical use in treating prostate cancer substances. Seven AR-destabilization test substances selected according to the present invention can inhibit cells in the presence of 0.1 nm synthetic androgen R1 881, which is similar to quite low IC50, such as the prescribed non-steroidal anti-androgen dicarotide Hyperplasia. At a substance concentration of 1 micron, the proliferation was reduced by at least 80% compared to cell growth in the presence of 0.1 nm R1 881. Example 696: 4- [6- [3- [4-Cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4 -oxo-2 -thioxanthene 4- 1-yl] hexyl] hexahydrop-biffine-1 -sulphuric acid S-methyl ester and Example 653: 4- [4,4-dimethyl-3- [6- [4- (2-methyl-1 -Oxopropyl) hexahydrop-bihexyl-1 -yl] hexyl] -5 -oxo-2 -thioxantheline-1 -yl] -2-(trifluoromethyl) benzonitrile completely inhibited Growth at this concentration, and under these conditions, biscarbutamide has an inhibition rate of only 85%. Up to a test concentration of 10 microns, no proliferative stimulatory effect was seen in any of the seven test substances. -25-200301117 (20)

表2. LNCaP細胞藉試驗物質的增生的抑制。 實例 試驗物質 IC50 [10'7Μ] %抑制率 1微米 248 4-[2,5-二氫-3-[6-[4-(2-甲氧基苯甲醯基)六氫吡畊小 基]己基H-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟 甲基)苯甲腈 2.5 97.6 315 4-[6-[1-[4-氰基冬(三氟甲基)苯基]-2,5-二氫-4-甲基 _2,5-二氧代-lH-p比p各各基]己基]-N-苯基六氯p比淀 羧醯胺 3.8 80.8 516 4-[3-[3-[4-(2-甲氧基苯甲酿基）六氫p比畊小基]丙 基]-4,4-二甲基-5-氧代2-硫氧咪吐琳小基]-2-(三氟甲 基)·苯甲腈 0.26 107 546 4-[4,4-二曱基-3-[4_[4-(2-甲基-1-氧代丙基)六氫峨p井 -1-基]丁基]-5-氧代2-硫氧咪士林-1-基]-2-(三氟甲基)_ 苯甲腈 0.8 97.5 602 4-[3-[5-[4-(2,2-二甲基-1-氧代丙基）-六氫p比基] 戊基]·4,4-二甲基_5-氧代2·硫氧咪士淋-1-基]_2_(三氟 甲基)-苯甲腈 一 0.18 92 629 4-[3-[5~[4-(乙基績gg基)-六氫叶卜井小基]戊基]二 甲基-5-氧代-2-硫氧咪嗤琳小基]-2-(三氟甲基)_苯甲 腈 1.4 94.6 638 4-[5-[j-[4-氰基-3-(三氟甲基)苯基]_5,5-二甲基-4-氧代 -2_硫氧咪唑基]戊基]-Ν-乙基六氫吡畊—μ碳硫酿 胺 0.33 95 645 4-[4,4-一甲基-3-[6-[4-甲基六氫吡畊-1-基]己基]氧 代2_硫氧咪唑基]_2_(三氟甲基)_苯甲腈 0.26 92 648 4-[6_[3-[4-氰基各(二氟甲基)苯基]d，5·二甲基冰氧代 _2-硫氧咪口坐参1 -基]己基]六氫ρ比^碳腈 0.11 99 653 4-[4,4-一甲基-3-[6-[4-(2-甲基-1-氧代丙基)六氫吡啩 小基]己基]-5-氧代硫氧咪唑啉小基]:蠢 基)-苯甲腈 Τ 0.9 108 656 4-[-3-[6-[4-(2-趙基-2-甲基-1-氧代丙基）六氫?比^3 基]己基]_4,4·二甲基氧代I硬氧咪唑啉小 基]_2_(三氟甲基)-苯甲腈 0.26 99Table 2. Inhibition of proliferation of LNCaP cells by test substances. Example Test substance IC50 [10'7M]% Inhibition rate 1 micron 248 4- [2,5-Dihydro-3- [6- [4- (2-methoxybenzylidene) hexahydropyridine small group ] Hexyl H-methyl-2,5-dioxo-1H-pyrrole small] -2- (trifluoromethyl) benzonitrile 2.5 97.6 315 4- [6- [1- [4-cyanohydrin (Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl_2,5-dioxo-lH-p ratio p each group] hexyl] -N-phenylhexachloro p ratio Carboxylamidine 3.8 80.8 516 4- [3- [3- [4- (2-methoxybenzyl) hexahydro p-pyridyl] propyl] -4,4-dimethyl-5 -Oxo 2-thiooxymetulline small group] -2- (trifluoromethyl) · benzonitrile 0.26 107 546 4- [4,4-difluorenyl-3- [4_ [4- (2- Methyl-1-oxopropyl) hexahydrop-well-1-yl] butyl] -5-oxo-2-thioxometastrin-1-yl] -2- (trifluoromethyl) _ Benzonitrile 0.8 97.5 602 4- [3- [5- [4- (2,2-dimethyl-1-oxopropyl) -hexahydrop-pyridyl] pentyl] · 4,4-dimethyl _5-oxo-2 · thioxomethylide-1-yl] _2_ (trifluoromethyl) -benzonitrile-0.18 92 629 4- [3- [5 ~ [4- (ethylethylgg ) -Hexhydro Yebujingi] pentyl] dimethyl-5-oxo-2-thioxomidazoline] -2- (trifluoromethyl) _benzonitrile 1.4 94.6 638 4- [5- [j- [4-cyano-3- ( Fluoromethyl) phenyl] _5,5-dimethyl-4-oxo-2_thiooximidazolyl] pentyl] -N-ethylhexahydropyridine—μCarbonsulfanamine 0.33 95 645 4- [4,4-monomethyl-3- [6- [4-methylhexahydropyridin-1-yl] hexyl] oxo 2-thiooximidazolyl] _2_ (trifluoromethyl) _benzonitrile 0.26 92 648 4- [6_ [3- [4-Cyano (difluoromethyl) phenyl] d, 5 · dimethyl iceoxo_2-thioxoamido 1-yl] hexyl] Hexahydrogen ratio ^ carbonitrile 0.11 99 653 4- [4,4-monomethyl-3- [6- [4- (2-methyl-1-oxopropyl) hexahydropyridine small group] hexyl ] -5-oxothiooxyimidazoline small group]: Stilbyl) -benzonitrile T 0.9 108 656 4-[-3- [6- [4- (2-Zhaoyl-2-methyl-1- Oxopropyl) hexahydro? Ratio ^ 3 group] hexyl] _4,4 · dimethyloxo I hardoximidazoline small group] _2_ (trifluoromethyl) -benzonitrile 0.26 99

-26- 200301117 LNCaP 細 胞藉試驗物哲a v , t -的抑制-26- 200301117 Inhibition of LNCaP cells

723 0.26 90 試驗物質723 0.26 90 Test substance

雙卡硫特醯胺 ^4;4^甲基_3-[8'[4-(甲基橫酿基}六氫t井-1-基]辛· 咪唑啉-1-基]_2_(三氟甲基)苯甲腈 ^[4_氛基I(三氟甲基）苯基]各[(4-氟苯基）磺醯 基丙醯胺 3.8 84.6 後型3 :其他未自攝護腺產生的細胞線增生的抑制 為了檢驗試驗物質在非攝護腺起端的細胞内的生長抑 制作用’ MaTu細胞、MaTu/Adr細胞、HaCaT細胞及A431細 胞用試驗物質處理，藉此Dicarbazetamidine ^ 4; 4 ^ methyl_3- [8 '[4- (methyltransalkyl) hexahydrot-well-1-yl] ocimimidazol-1-yl] _2_ (tri Fluoromethyl) benzonitrile ^ [4-AminoI (trifluoromethyl) phenyl] E each [(4-fluorophenyl) sulfopropylamidoamine 3.8 84.6 Post-type 3: Other not self-prostate Inhibition of generated cell line proliferation In order to test the growth inhibitory effect of the test substance in non-proliferative cells, MaTu cells, MaTu / Adr cells, HaCaT cells, and A431 cells were treated with the test substance, thereby

MaTu ·意指人類乳癌細胞線MaTu means human breast cancer cell line

MaTu/Adr :意指抗亞德利亞黴素的MaTu細胞線MaTu / Adr: means MaTu cell line resistant to adriamycin

HaCaT :意指人類成纖維細胞線 A-431 :意指人類表皮細胞線 端視細胞線而定，⑼_4〇〇〇細胞/井生長於RPMI 1640培 -27- 200301117HaCaT: Means human fibroblast line A-431: Means human epidermal cell line Depending on the cell line, _400 cells / well are grown at RPMI 1640 culture -27- 200301117

(22) 養基（A431; MaTu 及 MaTu/Adr)或 DMEM/HAM’SF12 培養基 (HaCaT)内而無具有2毫莫耳L-谷胺及10%CCS的酚紅，在24 小時培育後，其係用稀釋於培養基内的各種濃度的試驗％ 質處理。在3日處理期間後，細胞如模型2般藉結晶紫檢定 法測定。溶劑對照物包含0.1%乙醇。(22) Nutrients (A431; MaTu and MaTu / Adr) or DMEM / HAM'SF12 medium (HaCaT) without phenol red with 2 millimolar L-glutamine and 10% CCS, after 24 hours incubation, It is treated with various concentrations of test substance diluted in the medium. After the 3-day treatment period, cells were measured by the crystal violet assay as in Model 2. The solvent control contained 0.1% ethanol.

表3顯示選定實驗物質對未自攝護腺產生的人類細胞@ 生的功效。物質在濃度為10微米下試驗且數據對應溶劑對 照物細胞生長的比例與百分比。結果顯示試驗物質未對4 條不同細胞線產生抑制作用或，在各個情況下，僅略有抑 制作用。在規定抑制條件下，比較用物質雙卡留特醯胺在 所有細胞線除了 MaTu以外顯示略有抑制性。此等結果顯 示試驗物質的抗增生作用為雄性激素受體依附性並顯示 即使在高物質濃度下於微分子範圍内，亦無二次細胞毒性 作用會發生。 表4·選定試驗物質在濃度為1 0微米下對非攝護腺細胞增Table 3 shows the efficacy of selected experimental substances on human cells that are not produced by the prostate. The substance was tested at a concentration of 10 microns and the data corresponded to the proportion and percentage of cell growth of the solvent control. The results showed that the test substance did not have an inhibitory effect on 4 different cell lines or, in each case, only a slight inhibitory effect. Under the prescribed inhibitory conditions, biscarbutamide, a comparative substance, showed a slight inhibitory effect on all cell lines except MaTu. These results show that the antiproliferative effect of the test substance is androgen receptor dependence and that no secondary cytotoxic effect will occur even in the micromolecular range at high substance concentrations. Table 4. Selected test substances increase non-prostate cells at a concentration of 10 microns

生的作用 試驗物質(實例號數） 細胞線内的增生 MaTu MaTu/Adr A431 HaCaT 4-[2,5-二氫-3-甲基-4-[4-[4-(甲 基磺醯基)六氫吡畊小基]丁基 ]-2,5-二氧代-1H-吡咯-1-基 ]-2-(三氟甲基苯甲腈(117) 1〇3土 10% 94±4% 100±5% 104±6% 4-[-3-4·[4-(2-氯苯甲醯基)六氫 吡畊小基]丁基]-2,5-二氫-4-甲 基-2,5·二氧代-1Η-吡咯-1-基 ]_2·(三氟甲基)·苯甲腈(90) 96+/-3% 80 十/-2% 98+/-7% 102+/-12% 4-[2,5-二氫 _3-[6-[4-(2-甲 氧基苯甲酿基)六氫Ρ比ρ井-1-基] 己基]-4-甲基_2,5-二氧代-1沁 98+M% 88+M% 102+/-5% 104+/-7% -28- 200301117 發 (23) 吡咯-1-基]-2-(三氟甲基)·苯甲 腈(248) 4-[6-[1-[4-氰基各(三氟甲基) 苯基]-2,5-二氫斗甲基_2,5_二 氧代_1Η_吡咯-3-基]己基]-Ν-萎基六氫吡啶-1 —羧醯胺(3 i 5) 95+/-7% 90+/-10% 95+/-5% 102+/-6% 雙卡硫特酿胺 97±3% 84±6% 89 + 7% 92+3% I型4:選定試驗物質對老鼠副性慾腺生長的抗雄性激素 作用Test substance for growth (example number) Proliferation in cell line MaTu MaTu / Adr A431 HaCaT 4- [2,5-dihydro-3-methyl-4- [4- [4- (4-methylsulfonyl ) Hexahydropyracyl] butyl] -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethylbenzonitrile (117) 103 10% 94 ± 4% 100 ± 5% 104 ± 6% 4-[-3-4 · [4- (2-chlorobenzyl) hexahydropyridine] butyl] -2,5-dihydro-4- Methyl-2,5 · dioxo-1Η-pyrrole-1-yl] _2 (trifluoromethyl) · benzonitrile (90) 96 +/- 3% 80 ten / -2% 98 +/- 7% 102 +/- 12% 4- [2,5-dihydro_3- [6- [4- (2-methoxybenzyl) hexahydrogen P ratio ρ-1-1-yl] hexyl] -4-methyl_2,5-dioxo-1q 98 + M% 88 + M% 102 +/- 5% 104 +/- 7% -28- 200301117 ((23) pyrrol-1-yl) -2- (trifluoromethyl) benzonitrile (248) 4- [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydromethyl 2,5_dioxo_1Η_pyrrole-3-yl] hexyl] -N-cumyl hexahydropyridine-1 -carboxamide (3 i 5) 95 +/- 7% 90 +/- 10% 95 +/- 5% 102 +/- 6% Dicarbazetamine 97 ± 3% 84 ± 6% 89 + 7% 92 + 3% Type I 4: Anti-androgen of selected test substance on growth of parasexual glands in mice effect

副性慾腺（攝護腺與半胞）的作用與大小端視雄性激素 而定。在閹割的動物中，此等器官的生長係藉雄性激素服 用而誘導。用抗雄性激素的同時處理可抑制此生長，端視 劑量而定。The role and size of parasexual glands (prostate and hemiocytes) depend on androgens. In castrated animals, the growth of these organs is induced by the use of androgens. Simultaneous treatment with anti-androgens can inhibit this growth, depending on the dose.

為了檢驗試驗物質，閹割老鼠。在同一天用丙酸睪内醋 (〇·〇3毫克/鼠）及試驗物質（調配成2x每日30毫克/公斤S c，於 苯甲酸苄酯-蓖麻油（1 〇 : 90)内）的處理。處理實施7日，在 實驗結束時，測定半胞及攝護腺的重量。計算半胞對對昭 組（具有或不具有睪内酯）的抑制率％。關於參考物質，可 使用醋酸氯羥甲烯孕酮（30毫克/公斤s.c.)。 其結果顯示於表4。 用實驗物質的處理，實例629 : 4-[3-[5-[4-(乙基磺驢基 )-六氫吡啩-^基]戊基]·4,4-二甲基-5-氧代-2-硫氧咪唤淋 -1-基]-2-(三氟甲基）_苯甲腈及實例546 : 4-[4,4-二甲基 -3-[4-[4-(2-甲基-1-氧代丙基）六氫吡畊-1-基]丁基氧 代2**硫氧咪唑啉-1 -基]-2-(三氟甲基）-苯甲腈，導致半胞生 長之幾乎100%抑制率，而用參考物質醋酸氯羥甲埽孕嗣 -29- 200301117To test the test substance, the rats were castrated. On the same day, lactone propionate (0.03 mg / rat) and test substance (formulated to 2 x 30 mg / kg S c daily in benzyl benzoate-castor oil (10: 90)) Processing. On the 7th day of the treatment, at the end of the experiment, the weights of the half cells and the prostate were measured. Calculate the% inhibition rate of half cells on the Zhao group (with or without galactone). Regarding the reference substance, clomoxyprogesterone acetate (30 mg / kg s.c.) can be used. The results are shown in Table 4. Treatment with experimental substance, Example 629: 4- [3- [5- [4- (ethylsulfonyl) -hexahydropyridyl- ^ yl] pentyl] · 4,4-dimethyl-5- Oxo-2-thioxosulfan-1-yl] -2- (trifluoromethyl) _benzonitrile and examples 546: 4- [4,4-dimethyl-3- [4- [4 -(2-methyl-1-oxopropyl) hexahydropyrine-1-yl] butyloxo 2 ** thiooximidazoline-1 -yl] -2- (trifluoromethyl) -benzene Methonitrile, resulting in almost 100% inhibition of half-cell growth, and the reference substance chloroformin acetate -29- 200301117

(24) 的處理導致僅8 5 %抑制率。先前試驗測定的雙卡留酸胺的 抑制值亦僅為86%。 表4.選定試驗物質在劑量為2x30毫克/公斤下對半胞的睪 内酉旨刺激生長的作用 實例 試驗物質 MSB生長 %抑制率 629 4-[3-〇[4-(乙基橫醯基)-六氫?比畊小基]戊基]_4,4-二甲基 氧代硫氧咪唑啉小基]-2-(三氟甲基苯甲腈 98 546 4-[4,4-二甲基_3-[4-[4·(2·甲基小氧代丙基)六氫p比呼小基] 丁基]氧代2_硫氧咪唑4-1-基]冬(三氟甲基)-苯甲腈 98 696 4-[6-[3-[4-氰基-3-(三說甲基)苯基]_5,5_二1f基-4-氧代-2- 硫氧咪唑啉小基]己基]六氫吡畊-1-碳硫酸孓甲酯 87 CPA 17-(乙醞氧基)-6-氯-1 0，2心二氫-3Ή-環丙[1，2]孕-1，4,6- 三烯-3,20-二酮 ’ ’ 85 雙卡硫 特醯胺 N-[4-氰基冬(三氟甲基)苯基]各[(冬氟苯基)續醯基]-2-經 基-2-甲基丙酸胺 86 模型_5 :選定試驗物質對體内人類攝護腺癌異種移植物生 長的抗雄性激素作用 在本發明中，根據本發明實例117 : 4-[2,5-二氫-3-甲基 _4-[4-[4-(甲基磺醯基）六氫吡畊-基]丁基卜2,5•二氧代 -ΙΗ-ρ比哈-1-基]-2-(三氟甲基）_苯甲腈對體内腫瘤生長的 作用係利用老鼠異種移植物模數研究，其中根據本發明的 化合物以皮下方式連續給藥。 CWR22腫瘤模型[M· A. Wainstein，F· He, D· Robinson，H· J· Kung, S. Schwartz, J. M. Giaconia, N. L. Edgehouse, T. P. Pretlow, D. R. Bodner, E. D. Kursh, Cancer Res. 1994, 1;54(23), 6049-52] 為荷爾蒙依附的人類攝護腺癌模型。確立腫瘤模型且進一 步由攝護腺癌組織的"系列性轉種”傳送，其係在〇P期間於 -30- 20030111?Treatment of (24) resulted in an inhibition rate of only 85%. The inhibitory value of dicracuramate measured in previous experiments was only 86%. Table 4. The effect of selected test substances on the stimulation of half-cells' intracellular dysfunction at a dose of 2 x 30 mg / kg. Example test substance MSB growth% inhibition rate 629 4- [3-〇 [4- (ethylpyridinyl ) -Hexahydro? Phenyl] pentyl] _4,4-dimethyloxothiooximidazoline small group] -2- (trifluoromethylbenzonitrile 98 546 4- [4,4-di Methyl_3- [4- [4 · (2 · methyl small oxopropyl) hexahydrop-pyhexyl] butyl] oxo 2-thiooximidazole 4--1-yl] winter (trifluoro Methyl) -benzonitrile 98 696 4- [6- [3- [4-cyano-3- (trisylmethyl) phenyl] _5,5_di1fyl-4-oxo-2-sulfide Oximidazoline small group] hexyl] hexahydropyridine-1-carbonammonium methyl sulfate 87 CPA 17- (ethoxy) -6-chloro-1 0,2cardiodihydro-3 二 -cyclopropyl [1, 2] Pregnant-1,4,6-triene-3,20-dione '' 85 Dicarboxamide N- [4-cyano (trifluoromethyl) phenyl] each [(winter fluoro Phenyl) continyl] -2-meryl-2-methylpropionate 86 model_5: Anti-androgenic effect of selected test substances on human prostate cancer xenograft growth in vivo In the present invention, Example 117 according to the present invention: 4- [2,5-dihydro-3-methyl_4- [4- [4- (methylsulfonyl) hexahydropyridine-yl] butyl Bu 2,5 • Dioxo-IΗ-ρbiha-1-yl] -2- (trifluoromethyl) _benzonitrile on tumor growth in vivo was studied using mouse xenograft modulus, where The compound according to the present invention is continuously administered subcutaneously. CWR22 tumor model [M.A. Wainstein, F. He, D. Robinson, H.J. Kung, S. Schwartz, JM Giaconia, NL Edgehouse, TP Pretlow, DR Bodner, ED Kursh, Cancer Res. 1994, 1; 54 (23), 6049-52] is a hormone-dependent human prostate cancer model. A tumor model was established and further transformed by " series of prostate cancer tissues "Transfer, which was between -30- 20030111 during the 0P period?

(25) 免疫不足的無毛鼠内除去。亦可自病人腫瘤確立雄性激素 依附的LNCaP攝護腺癌模型。此腫瘤模型生長於細胞培育 並作為免疫不足老鼠的異種移植（Culig，Hoffman Brit· J. Cancer，1999, 242-251)。關於療法試驗，供應六週大無毛雄 鼠（NMRI氣，M&B，Bornholdtgard，丹麥）睪内醋丸（12.5毫克 ，90 曰釋出；IRA，Sarasota，弗羅里達）。LNCaP細胞（1.5x106 細胞）或小腫瘤碎片（2x2毫米）皮下植入動物的左腰窩内。 在腫瘤到達20-25毫米平方大小時，用本發明物質的處理 貝1J 開始〇[]\4.八.^\^11516111，？.1^，0.11〇1^115〇11，11.】.〖111^，8· Schwartz, J. M. Giaconia, N. L. Edgehouse, T. P. Pretlow, D. R. Bodner, E. D. Kursh, Cancer Res. 1994, 1; 54(23)，6049-52]。 其結果顯示於圖表1與2。 100 ο ο ο ο ο 8 6 4 2 S3S ·/+ EEVM 邀 ΈΟ£η1(25) Eliminated in hairless mice without immunity. Androgen-dependent LNCaP prostate cancer models can also be established from patient tumors. This tumor model was grown from cell culture and used as a xenograft in immunocompromised mice (Culig, Hoffman Brit. J. Cancer, 1999, 242-251). For therapy trials, six-week-old hairless male rats (NMRI gas, M & B, Bornholdtgard, Denmark) were supplied with vinegar pill (12.5 mg, released at 90; IRA, Sarasota, Florida). LNCaP cells (1.5x106 cells) or small tumor fragments (2x2 mm) were implanted subcutaneously into the animal's left lumbar fossa. When the tumor reaches a size of 20-25 millimeters square, the treatment with the substance of the present invention begins 1J [] \ 4. 八. ^ \ ^ 11516111 ,? .1 ^, 0.11〇1 ^ 115〇11, 11.]. [111 ^, 8. Schwartz, JM Giaconia, NL Edgehouse, TP Pretlow, DR Bodner, ED Kursh, Cancer Res. 1994, 1; 54 (23) , 6049-52]. The results are shown in Figures 1 and 2. 100 ο ο ο ο ο 8 6 4 2 S3S · / + EEVM invites ΈΟ £ η1

20 30 40 50 60 Tage [nach Tumortransplantation】 表 圖20 30 40 50 60 Tage [nach Tumortransplantation] Table Picture

C Ν L 攝護腺癌藉由物質B的生長抑制。用30毫克/ -31 - 200301117CNL prostate cancer is inhibited by the growth of substance B. With 30 mg / -31-200301117

(26) 公斤2x每日s.e.實施處理。 [註解：](26) kg 2x daily s.e. implementation treatment. [annotation:]

Tumorfl&che=腫瘤表面積 Kontrolle Vehikel=對照媒介物 Kontrolle Kastration=對照閹害1J Bicalutamid=雙卡留特驢胺 Substanz B=物質 BTumorfl & che = Tumor surface area Kontrolle Vehikel = Control vehicle Kontrolle Kastration = Control hazard 1J Bicalutamid = Diacarutide donkey amine Substanz B = Substance B

Tage[nach Tumortransplanatation]=日[在腫瘤移植後] 雖然腫瘤在未處理對照動物中迅速生長，但用本發明物 質的處理導致攝護腺腫瘤的相當大生長抑制率。在CWR22 腫瘤與LNCaP腫瘤中，此生長抑制率可比較於閹割的功效。 I OU 140 -♦—Kontrolle Vehikel -〇-Kontrolle Kastration -〇-Bicalutamid 30mg/kg 2x x-Substanz B 30mg/kg 2xTage [nach Tumortransplanatation] = day [after tumor transplantation] Although tumors grow rapidly in untreated control animals, treatment with the substance of the invention results in a considerable growth inhibition rate of prostate tumors. In CWR22 tumors and LNCaP tumors, this rate of growth inhibition is comparable to the efficacy of castration. I OU 140-♦ —Kontrolle Vehikel -〇-Kontrolle Kastration -〇-Bicalutamid 30mg / kg 2x x-Substanz B 30mg / kg 2x

I 120I 120

20 25 30 35 40 45 50 55 60 Tage [nach Tumortransplantation] 圖表2. CWR22攝護腺癌藉由物質B的生長抑制。用30毫克/ -32- 20030111720 25 30 35 40 45 50 55 60 Tage [nach Tumortransplantation] Figure 2. CWR22 prostate cancer is inhibited by the growth of substance B. With 30 mg / -32-200301117

(27) 公斤2x每曰s.e.實施處理。 [註解：](27) kg 2x per s.e. implementation treatment. [annotation:]

Tumorflache=腫瘤表面積 Kontrolle Vehikel=對照媒介物 Kontrolle Kastration=對照閹割 Bicalutamid=雙卡留特驢胺 Substanz B=物質 BTumorflache = Tumor surface area Kontrolle Vehikel = Control vehicle Kontrolle Kastration = Control castration Bicalutamid = Diacarutide Substanz B = Substance B

Tage[nach Tumortransplanatation]=日[在腫瘤移植後] 在二模型中，腫瘤生長在用抗雄性激素雙卡留特醯胺處 理的抑制較優異。攝護腺癌模型的試驗結果顯示腫瘤生長 藉根據本發明化合物的的抑制。Tage [nach Tumortransplanatation] = day [after tumor transplantation] In the two models, tumor growth is more effectively inhibited when treated with the anti-androgen dicarotamine. The test results of a prostate cancer model show that tumor growth is inhibited by the compounds according to the invention.

在本發明中，研究利用老鼠-異種移植模型根據本發明 化合物對體内腫瘤生長的作用，其中根據本發明化合物係 皮下給藥2x每日歷整個處理期間。比較於未處理對照動物 ，腫瘤生長的抑制造成。閹割鼠明顯顯示腫瘤生長的延遲 。處理耐受良好。 本發明顯示根據本發明化合物造成優於雙卡留特醯胺 者之攝護腺腫瘤生長的抑制。 劑量 通常，當每曰劑量包含每公斤體重5微克至50毫克根據 本發明化合物時，可預期滿意結果。在較大哺乳動物中， 例如，人類，推薦的每日劑量為每公斤體重10微克至30毫 克。根據本發明化合物的適當劑量為每日每公斤體重0.005 至50毫克，端視病人的年紀與體質而定，藉此所需每日劑 -33 - 200301117 (28) 量可被一次或多次給藥。 基於新穎化合物的藥劑的調配係以此技藝已知方式藉 有效成分被一般用於植物製劑的賦形藥、填料、影響分解 的物質、黏合劑、濕潤劑、潤滑劑、吸收劑、稀釋劑、調 味劑、染料等加工，且被轉化成所欲給藥形式而實施。在 此情況下，可參考 Remington’s Pharmaceutical Science，15thIn the present invention, the effect of a compound according to the present invention on tumor growth in vivo is investigated using a mouse-xenograft model, wherein the compound according to the present invention is administered subcutaneously 2x per calendar period throughout the treatment period. Inhibition of tumor growth compared to untreated control animals. Castration rats clearly showed delayed tumor growth. The treatment is well tolerated. The present invention shows that the compounds according to the present invention cause inhibition of the growth of prostate tumors better than those of dicarutamide. Dosage Generally, satisfactory results can be expected when each dose contains 5 micrograms to 50 milligrams per kilogram of body weight of a compound according to the invention. In larger mammals, such as humans, the recommended daily dose is 10 micrograms to 30 milligrams per kilogram of body weight. A suitable dose of the compound according to the present invention is 0.005 to 50 mg per kilogram of body weight per day, depending on the age and constitution of the patient, whereby the required daily dose of -33-200301117 (28) can be given one or more times medicine. Formulations of pharmaceuticals based on novel compounds are used in a manner known in the art to excipients, fillers, substances that affect decomposition, binders, wetting agents, lubricants, absorbents, diluents, Flavoring agents, dyes, and the like are processed and converted into desired administration forms. In this case, refer to Remington ’s Pharmaceutical Science, 15th

Edition. Mack Publishing Company, East Pennsylvania ( 1980) 0 關於口服，錠劑、包衣錠劑、膠囊、丸劑、粉劑、顆粒 、錠片、懸浮液、乳液或溶液特別適當。關於非經腸給藥 ’可用注射及灌注製劑。關於關節内注射，可使用對應製 備的結晶懸浮液。關於肌内注射，可使用水性及油性注射 2液或懸浮液以及對應積存製劑。關於直腸給藥，新穎化 〇物可以栓劑、膠囊、溶液（如灌腸劑形式）及全身與局部 療：用的軟膏。關於局部塗#文’可使用凝膠調配物、軟膏 當用乳⑮、.糊劑、粉劑、乳劑及自了劑°為了達到適 至2 0。/。。A ,.、，式1化。物的劑量在此等製劑中應為0.01% 本發：二塗敷亦可利用經皮系統如膏藥實施。 分。此根據本發明通式1化合物作4治療有效成 可接受佐藥及 Λ通式1化合物為與醫藥上可相容並 分。太政 介物一起作為治療有效成分沾士议响如 本發明亦包厶题一 战刀的本發明邵 活性化合物或其：：组合物’纟包含根據本發明醫藥上 上可相容佐藥及物《—以及醫藥上可相容鹽或醫藥 ^朱及賦形藥。 因此’本發明的對氮. 對象亦為醫藥組合物’其包含至少-種 -34- 200301117Edition. Mack Publishing Company, East Pennsylvania (1980) 0 Regarding oral administration, lozenges, coated lozenges, capsules, pills, powders, granules, tablets, suspensions, emulsions or solutions are particularly suitable. For parenteral administration, 'injectable and perfusion preparations are available. For intra-articular injection, a correspondingly prepared crystalline suspension can be used. For intramuscular injection, aqueous and oily injections of 2 solutions or suspensions and corresponding accumulation preparations can be used. Regarding rectal administration, novel compounds can be suppositories, capsules, solutions (such as enemas) and systemic and local treatments: ointments for use. Regarding the topical application, a gel formulation, an ointment can be used, and a cream, a paste, a powder, an emulsion, and a self-preparing agent can be used in order to reach 20. /. . A,. ,, Equation 1. The dosage of these substances should be 0.01% in these preparations. The present application: Second application can also be performed using a transdermal system such as a plaster. Minute. According to the present invention, the compound of the general formula 1 is effective for 4 treatments, and the adjuvant and the compound of the general formula 1 are compatible and pharmaceutically compatible. Taizheng mediators are used together as a therapeutically effective ingredient. The active compounds of the present invention or their :: compositions include the pharmaceutically acceptable adjuvants and substances according to the present invention. "—And medically compatible salts or medicine ^ Zhu and excipients. Therefore, ‘the paranitrogen of the present invention is also a pharmaceutical composition’ which contains at least one species -34- 200301117

(29) 視需要與醫藥上可相容佐藥及/或賦形藥一起的通式I化 合物。 此等醫藥組合物與藥劑可供口服、直腸、皮下、經皮、 靜脈内或肌内給藥。除了 一般使用的賦形藥及/或稀釋劑 以外，其亦包含至少一種通式I的化合物。(29) A compound of general formula I, if necessary, together with a pharmaceutically compatible adjuvant and / or excipient. These pharmaceutical compositions and agents can be administered orally, rectally, subcutaneously, transdermally, intravenously or intramuscularly. In addition to the commonly used excipients and / or diluents, it also contains at least one compound of the general formula I.

本發明藥劑係以已知方式用通用固態或液態賦形藥或 稀釋劑與通用醫藥技術佐藥根據所欲給藥類型以適當劑 量製成。較佳製備包括適於口服的調配形式。該調配形式 為，例如，鍵劑、薄膜鍵劑、包衣鍵劑、膠囊、丸劑、粉 劑、溶液或懸浮液或者積存形式。 包含至少一種根據本發明化合物的醫藥組合物較佳被 口月良。 亦可考慮非經腸製劑如注射溶液。 此外，例如，栓劑亦可稱為製劑。The medicament of the present invention is prepared in a known manner with a general solid or liquid excipient or diluent and a general medicinal technology adjuvant in an appropriate dose according to the type of administration desired. Preferred preparations include formulated forms suitable for oral administration. The formulation is, for example, a bonding agent, a film bonding agent, a coating bonding agent, a capsule, a pill, a powder, a solution or a suspension, or a storage form. A pharmaceutical composition comprising at least one compound according to the present invention is preferably oral. Parenteral preparations such as injection solutions are also considered. In addition, suppositories are also referred to as preparations, for example.

對應錠劑可例如藉混合有效成分與已知佐藥如惰性稀 釋物，如右旋糖、糖、山梨醇、甘露醇、聚乙晞P比洛燒酮 、爆發物如玉米澱粉或海藻酸、黏合劑如澱粉或明膠、潤 滑劑如硬脂酸鎂或滑石及/或達到積存功效的劑，例如複 基聚亞甲基、羧甲基纖維素、酞酸醋酸酯纖維素或聚醋酸 乙締S旨。鍵劑亦可由若干層構成。 包衣錠劑可用通用於錠劑塗佈的劑如聚乙烯吡咯烷酮 或蟲膠片、阿拉伯膠、滑石、氧化鈦或糖塗佈類似於錠劑 製成的核製成。在此情況下，包衣錠劑的殼亦可由若干層 構成，藉此可使用上述鍵劑中的佐藥。 -35 - 200301117Corresponding lozenges can be combined, for example, by mixing the active ingredients with known adjuvants such as inert diluents such as dextrose, sugar, sorbitol, mannitol, polyvinylaceton Agents such as starch or gelatin, lubricants such as magnesium stearate or talc, and / or agents that achieve storage effects, such as polymethylidene, carboxymethylcellulose, cellulose acetate phthalate, or polyvinyl acetate Purpose. The bonding agent may also be composed of several layers. Coated tablets can be made with tablets commonly used for tablet coating such as polyvinylpyrrolidone or shellac, acacia, talc, titanium oxide or sugar coated cores similar to tablets. In this case, the shell of the coated tablet can also be composed of several layers, whereby the adjuvant in the above-mentioned bonding agent can be used. -35-200301117

(30) 次外，具有根據本發明通式I化合物的溶液或懸浮液亦 可含有口味改善劑如糖精、環磺酸鹽或糖以及例如調味物 質如香草或橙萃取物。此外，其亦可含有懸浮佐藥如羧甲 基纖維素鈉或防腐劑如對羥基苯甲酸鹽。 含有通式I化合物的膠囊，例如，可藉通式I化合物與惰 性賦形藥如乳糖或山梨醇混合並包被於膠囊内製成。(30) In addition, a solution or suspension having a compound of the general formula I according to the present invention may also contain a taste improving agent such as saccharin, sulfonate or sugar and, for example, a flavoring substance such as vanilla or orange extract. In addition, it may contain a suspension adjuvant such as sodium carboxymethylcellulose or a preservative such as paraben. Capsules containing a compound of general formula I can be prepared, for example, by mixing a compound of general formula I with an inert excipient such as lactose or sorbitol and coating the capsule.

適當栓劑，例如，可藉混合此目的用的賦形藥如中性脂 肪或聚乙二醇或其衍生物製成。 根據本發明的化合物可與一種或多種供攝護腺癌療法 的下列有效成分組合給藥： 1) 親生殖腺-荷爾蒙（GnRH)促效劑 2) 5 α -還原酶抑制劑如finasteride 3) 細胞抑制劑 4) VEGF-活化酵素抑制劑 5) 抗助孕劑Suitable suppositories, for example, can be made by mixing excipients for this purpose, such as neutral fats or polyethylene glycols or derivatives thereof. The compounds according to the invention can be administered in combination with one or more of the following active ingredients for prostate cancer therapy: 1) gonogen-hormone (GnRH) agonist 2) 5 alpha-reductase inhibitors such as finasteride 3) cells Inhibitors 4) VEGF-activated enzyme inhibitors 5) Antifertility agents

6) 抗動情激素 7 )抗感應低聚核甞酸 8) EGF抗體 9) 動情激素 當用根據本發明化合物治療攝護腺癌時，亦可組合其用 途與此技藝已知的臨床放射學法。（Laverdiere，J.等人，1997, Inti. J. of Rad. One. Biol. Phys·，37, 247-252; Bolla，M.等人，1997, New Engl. J. Med·，377, 95-300.)。 此外，根據本發明通式I化合物可用於其他以上未述及 -36- 2003011176) Anti-estrous hormones 7) Anti-inductive oligonucleotide 8) EGF antibodies 9) Estrogenic hormones When treating prostate cancer with a compound according to the invention, its use can also be combined with clinical radiology methods known to the art . (Laverdiere, J. et al., 1997, Inti. J. of Rad. One. Biol. Phys., 37, 247-252; Bolla, M. et al., 1997, New Engl. J. Med., 377, 95 -300.). In addition, the compounds of the general formula I according to the present invention can be used for others not mentioned above -36- 200301117

(31) 的病況的治療與預防。(31) Treatment and prevention of conditions.

根據本發明通式I化合物可如下述製備。 本發明亦關於通式VIIThe compounds of formula I according to the invention can be prepared as follows. The invention also relates to formula VII

V-W-(CH2)n-I VIIV-W- (CH2) n-I VII

與通式VIIIWith Formula VIII

的中間產物 其中 V表示通式II的經取代芳香族基，Where V represents a substituted aromatic group of the general formula II,

其中 A表示乙酿塞、乙酿基胺基、氨基、硝基、三氟甲基或鹵 素（氟，氯）， B表示氫原子、函素（氟，氯）或三氟甲基，或 A與B—起表示鍵結至芳香族環的式III或IV的環狀基，其中 E表示亞甲基或氧原子， -37- 200301117 (32)Wherein A represents ethyl alcohol, ethyl amino, amino, nitro, trifluoromethyl, or halogen (fluorine, chlorine), B represents hydrogen atom, halogen (fluorine, chlorine), or trifluoromethyl, or A Together with B- represents a cyclic group of formula III or IV bonded to an aromatic ring, wherein E represents a methylene group or an oxygen atom, -37- 200301117 (32)

MeMe

ill IV W表示式V的雜環化合物，ill IV W represents a heterocyclic compound of formula V,

其中 T表示碳，雙鍵呈現於Q與T之間，Q意指=C(CH3)-基團而U 意指氧， η可假設為整數值1，2，3，4，5，6，7或8之一， i與j，互相獨立為1與2之值，藉此i+j可假設為2或3之值， 尺與Rf，互相獨立可為氫原子或甲基，Where T represents carbon, the double bond appears between Q and T, Q means = C (CH3)-group and U means oxygen, η can be assumed to be an integer value of 1, 2, 3, 4, 5, 6, One of 7 or 8, i and j, are mutually independent values of 1 and 2, whereby i + j can be assumed to be a value of 2 or 3, and ruler and Rf, independently of each other, can be hydrogen atoms or methyl groups,

以及通式VII與通式VIII的中間產物， 其中 A與B—起表示键結至芳香族環的式III或IV的環狀基，其中 E表示亞甲基或氧原子，And intermediate products of general formula VII and general formula VIII, wherein A and B together represent a cyclic group of formula III or IV bonded to an aromatic ring, wherein E represents a methylene group or an oxygen atom,

W表示式V的雜環化合物， 38-W represents a heterocyclic compound of formula V, 38-

IV 200301117IV 200301117

(33)(33)

其中among them

T表示氮，單键呈現於Q與T之間，Q意指-C(CH3)2-基團而UT represents nitrogen, a single bond appears between Q and T, Q means -C (CH3) 2- group and U

意指硫， η可假設為整數值4，5，6，7或8之一， i與j，互相獨立為1與2之值，藉此i +j可假設為2或3之值 R與R’，互相獨立可為氫原子或甲基。 本發明根據以下不限制本發明的實例詳細說明。Means sulfur, η can be assumed to be one of the integer values 4, 5, 6, 7, or 8, i and j are independent of each other to the value of 1 and 2, whereby i + j can be assumed to be the value of 2 or 3 R and R ', independently of each other, may be a hydrogen atom or a methyl group. The present invention is explained in detail based on the following examples which do not limit the present invention.

-39- 200301117-39- 200301117

(34) 合成圖表 根據以下圖表，可製成鏈長n = 4至8之順丁晞亞胺衍生 物：(34) Synthetic chart According to the following chart, cisbutimidine derivatives with chain length n = 4 to 8 can be made:

Z—N==0 Z—N=S Z—COCI Z—S〇2CI ZO-COCI ZS—COCI ZZ'N-COCI ZZ，N-S〇2CI Z(C〇)一N=r=Z—N == 0 Z—N = S Z—COCI Z—S〇2CI ZO-COCI ZS—COCI ZZ'N-COCI ZZ, N-S〇2CI Z (C〇) —N = r =

VillaVilla

試劑：（a)BrMg(CH2)nCl，CuBrMe2S，THF，然後 MeI，HMPT，THF; (b) LiOH，H20, THF，然後 HC1，萃取；（c)苯胺衍生物，EtOH，MS 4A; (d) Nal,乙基甲基酮；（e) THF; (f)三氟醋酸，CH2C12; (g) NEt3, THF。 -40- 20030111?Reagents: (a) BrMg (CH2) nCl, CuBrMe2S, THF, then MeI, HMPT, THF; (b) LiOH, H20, THF, then HC1, extraction; (c) Aniline derivative, EtOH, MS 4A; (d) ) Nal, ethyl methyl ketone; (e) THF; (f) trifluoroacetic acid, CH2C12; (g) NEt3, THF. -40- 20030111?

(35) 根據以下圖表，可製成鏈長n= 1至8之順丁烯亞胺衍生 物：(35) According to the following chart, cis-butenimine derivatives with chain length n = 1 to 8 can be made:

Z一N=-=0Z-N =-= 0

Z-COCIZ-COCI

Z-S02CIZ-S02CI

n r.n r.

zo-coci zs—COCI Ζ2·Ν—COC1 Ζ2Ή—S〇2CI Z(CO)—N=S -41 - 20030111zo-coci zs—COCI Zn2 · N—COC1 ZO2Ή—S〇2CI Z (CO) —N = S -41-20030111

(36) 反應試劑：（b)LiOH，H20，THF，隨後以HC1萃取；（c)苯胺衍生物 ,EtOH，4A 分予篩；（e) THF; (f)三氟乙酸，CH2C12; (g) NEt3, THF; (h) BrMg(CH2)m-CH = CH2, CuBrMe2S，THF，隨後 Mel，HMPT，THF; ⑴ BrMg(CH2)nOPG，CuBrMe2S，THF，隨後 Mel，HMPT，THF; (PG= 保護基）；（j)移除保護基；（k) 9-BBN，隨後NaOH，H202;⑴0s04; (m) Nal〇4; (n) Na(〇ac)3BH; (s)咪唑，碘，三甲基膦。(36) Reagent: (b) LiOH, H20, THF, followed by extraction with HC1; (c) Aniline derivative, EtOH, 4A fractionation sieve; (e) THF; (f) trifluoroacetic acid, CH2C12; (g ) NEt3, THF; (h) BrMg (CH2) m-CH = CH2, CuBrMe2S, THF, followed by Mel, HMPT, THF; ⑴ BrMg (CH2) nOPG, CuBrMe2S, THF, followed by Mel, HMPT, THF; (PG = (Protecting group); (j) removing the protecting group; (k) 9-BBN, followed by NaOH, H202; ⑴0s04; (m) Nal〇4; (n) Na (〇ac) 3BH; (s) imidazole, iodine, Trimethylphosphine.

'42- 200301117 (37) ΜΗ'42-200301117 (37) ΜΗ

Ζ一N=r=0 Ζ—N=S Z—C〇CI Z—S〇2CI ZO-COCI ZS-COCI Z2，N—C〇CI zz.n—so2ci Z(CO)—N=r=SZ_N = r = 0 Z_N = S Z_C〇CI Z_S〇2CI ZO-COCI ZS-COCI Z2, N_C〇CI zz.n_so2ci Z (CO) _N = r = S

Vlllb -43 - 200301117Vlllb -43-200301117

(38) 試劑：（d) Nal，乙基甲基酮；（e) THF; (f)三氟醋酸，CH2C12; (g) NEt3, THF; (o) CSC12, H2〇；（p) NEt3, THF; (q) 4M HC1; (r) RS02C1， NEt3, CH2C12。(38) Reagents: (d) Nal, ethyl methyl ketone; (e) THF; (f) trifluoroacetic acid, CH2C12; (g) NEt3, THF; (o) CSC12, H2〇; (p) NEt3, THF; (q) 4M HC1; (r) RS02C1, NEt3, CH2C12.

-44- 20030111?-44- 20030111?

(39) 根據以下圖表，可製成鏈長η = 2至8之乙内醯硫脲衍生 物：(39) According to the following chart, it can be made into acetoin thiourea derivatives with chain length η = 2 to 8:

Ζ一Ν=〇 Ζ一Ν——S Z—COCI 2—S〇2Ci 9 ZO-COCI ZS—COCI ZZ.N—C〇C 丨 ZZfN-S〇2CI Z(C〇)一N=SZ_N = 〇 Z_N——S Z_COCI 2_S〇2Ci 9 ZO-COCI ZS_COCI ZZ.N_C〇C 丨 ZZfN-S〇2CI Z (C〇) _N = S

試劑··⑴三氟醋酸，CH2C12; (g) NEt3, THF; (o) CSC12, H2〇；（p) NEt3, THF; (q) 4M Ha。 -45- (40) 製造方法 實例1 4-「5-Π-「4-氰基-3“三氟甲基）笨基1-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-3-基1六氢吡畊-1-羧酸1.1-二甲基乙酯 la) (Z)-2-(5-氯苯基）-3 -甲基-2-丁烯二羧酸二甲酯Reagents: ⑴ trifluoroacetic acid, CH2C12; (g) NEt3, THF; (o) CSC12, H2O; (p) NEt3, THF; (q) 4M Ha. -45- (40) Production method example 1 4- "5-Π-" 4-cyano-3 "trifluoromethyl) benzyl 1-2,5-dihydro-4-methyl-2,5- Dioxo-1H-pyrrole-3-yl 1 hexahydropyrine-1-carboxylic acid 1.1-dimethylethyl la) (Z) -2- (5-chlorophenyl) -3 -methyl-2 -Dimethyl butene dicarboxylate

關於格里納德氏（Grignard)試劑的製造，在氮氣蜃下導入 4.1克鎂碎片於22毫升四氫呋喃内，與31.3克1-溴-5-氯戊烷 於200毫升四氫呋喃内混合，將其在室溫下攪拌1小時。然 後，此混合物在氮氣壓下並在-35至-40°C下攪拌滴入34.7 克銅（I)-溴化物-二甲基硫複合物於700毫升四氫吱喃内的 懸浮液中，在-40°C下攪拌另外2小時。然後，將其冷卻至 -65至-70°C ，在此溫度下攪拌滴入20克伸乙醯基羧酸二甲 酯與48毫升六甲磷酸三醯胺於290毫升四氫呋喃内的溶液 :在5分鐘後，在-65至-70°C下，加入95毫升六甲磷酸三醯 胺於95毫升四氫呋喃内的溶液，在此溫度下，將其攪拌另 外5分鐘，滴入100克碘甲烷於280毫升四氫呋喃内，將此 混合物隔夜加熱至室溫。為了完成起見，將其冷卻至-60 °C並攪拌之，滴入410毫升飽和氯化銨溶液（具有設定在pH 為8的濃縮氣落液）、加熱至室溫並在室溫下揽掉4 5分鐘。 此混合物用醋酸乙酯萃取4次，組合有機相用飽和氯化銨 溶液（具有設定在pH為8的濃縮氨溶液）洗滌，直到有機相 為淡藍色為止，然後用水洗滌，直到有機相為無色為止。 在用飽和氯化鈉溶液洗滌、經硫酸鈉乾燥並藉蒸發濃縮後 ，用醋酸乙酯/己烷在矽膠上層析，因此，除了 7.2克 -46- 200301117Regarding the manufacture of Grignard reagent, 4.1 g of magnesium fragments were introduced into 22 ml of tetrahydrofuran under nitrogen gas, and 31.3 g of 1-bromo-5-chloropentane was mixed in 200 ml of tetrahydrofuran. Stir at room temperature for 1 hour. Then, this mixture was dropped into a suspension of 34.7 g of copper (I) -bromide-dimethylsulfide complex in 700 ml of tetrahydrofuran with stirring under nitrogen pressure at -35 to -40 ° C, Stir at -40 ° C for another 2 hours. Then, it was cooled to -65 to -70 ° C, and at this temperature, a solution of 20 g of dimethyl acetomethylcarboxylate and 48 ml of trimethylamine hexamethylphosphate in 290 ml of tetrahydrofuran was added dropwise with stirring: over 5 minutes Then, at -65 to -70 ° C, add a solution of 95 ml of trimethylamine hexamethylphosphate in 95 ml of tetrahydrofuran, and at this temperature, stir it for another 5 minutes, and add 100 g of methyl iodide to 280 ml of tetrahydrofuran. Then, the mixture was warmed to room temperature overnight. For the sake of completion, it is cooled to -60 ° C and stirred, and 410 ml of a saturated ammonium chloride solution (having a concentrated air falling liquid set at pH 8) is added dropwise, heated to room temperature and stirred at room temperature. Drop 4 5 minutes. This mixture was extracted 4 times with ethyl acetate, and the combined organic phase was washed with a saturated ammonium chloride solution (with a concentrated ammonia solution set at pH 8) until the organic phase was light blue, and then washed with water until the organic phase was Until colorless. After washing with saturated sodium chloride solution, drying over sodium sulfate, and concentration by evaporation, chromatography on silica gel with ethyl acetate / hexane, therefore, except for 7.2 g -46- 200301117

(41) (E)-2-(5 -氯苯基）-3 -甲基-2-丁晞二叛酸二甲g旨以外，在各 情況下，可得10.0克淡黃色油的標題化合物。 iH-NMR (300 MHz，CDC13): 5[ppm] = 3.76 s(3H, OCH3); 3.75 s(3H? 〇CH3); 3.53 t(J=6.5 Hz, 2H, CHC12); 2.35 tbr (J=7 Hz, 2H, CH2 烯烴）；1.95 (s，3H，CH3); 1.78 m(2H，CH2); 1.47 m (4H，CH2)。 lb) 3-(5 -氯苯基）-4-甲基- 2,5-呋喃二酮 86毫升水與1 64毫升氫氧化鋰於水（1莫耳/升）内的溶液 加入在氮氣壓下攪拌的7· 16克2-(5-氯苯基）-3-甲基-2-丁締 二羧酸（Z)-二甲酯中，在室溫下將其攪拌2曰。為了完成 起見’其係藉蒸發濃縮，殘餘物溶解於290毫升水中，用 鹽S父（2莫耳/升）設定在pH2而在冰浴内冷卻並用二乙链萃 取3次。組合的有機相用飽和氯化鈉溶液洗滌、經疏酸鈉 乾燥並藉悉發濃縮’可得淡黃色油的標題化合物。 ^-NMR (300 MHz, CDC13): 5 [ppm] = 3.54t(J=6.5 Hz, 2H? CH2C1); 2.48 tbr (J=7.5 Hz，2H，CH2埽烴）；2.08 sbr(3H，CH3); 181 m(2H，CH2); 1.63 m(2H，CH2); 1.51 m(2H，CH2)。 lc) 4·[3_(5 -氯苯基）-2,5-二氫-4-甲基 _2,5-二氧代-iH-吡咯 -1-基]-2-(三氟甲基）苯甲腈 9.46克3-(5 -氯苯基）-4-甲基-2,5-呋喃二酮與813克心胺基 -2-(二氣甲基）苯甲腈於22毫升乙醇内的混合物係在氮氣 壓下與2.5克活性分子師（〇 · 3毫微米）混合，在9 〇 下授拌2 曰。為了完成起見，在冷卻後過濾出分子篩、用乙醇洗滌 、組合的乙醇溶液藉蒸發濃縮。殘餘物溶解於醋酸乙酯内 並用水及飽和氯化鈉溶液洗滌。在經硫酸鈉乾燥並藉蒸發 -47- 200301117(41) Except for (E) -2- (5-chlorophenyl) -3-methyl-2-butyridene dimetanoic acid dimethyl g, in each case, 10.0 g of the title compound was obtained as a pale yellow oil. . iH-NMR (300 MHz, CDC13): 5 [ppm] = 3.76 s (3H, OCH3); 3.75 s (3H? 〇CH3); 3.53 t (J = 6.5 Hz, 2H, CHC12); 2.35 tbr (J = 7 Hz, 2H, CH2 olefins); 1.95 (s, 3H, CH3); 1.78 m (2H, CH2); 1.47 m (4H, CH2). lb) 3- (5-chlorophenyl) -4-methyl-2,5-furandione A solution of 86 ml of water and 164 ml of lithium hydroxide in water (1 mole / liter) was added under nitrogen pressure. In 7.16 g of 2- (5-chlorophenyl) -3-methyl-2-butanedicarboxylic acid (Z) -dimethyl ester with stirring, this was stirred at room temperature for 2 days. For the sake of completion ', it was concentrated by evaporation, and the residue was dissolved in 290 ml of water, set at pH 2 with salt S parent (2 moles / liter), cooled in an ice bath and extracted 3 times with diethyl chain. The combined organic phases were washed with a saturated sodium chloride solution, dried over sodium sulphate and concentrated 'to give the title compound as a pale yellow oil. ^ -NMR (300 MHz, CDC13): 5 [ppm] = 3.54t (J = 6.5 Hz, 2H? CH2C1); 2.48 tbr (J = 7.5 Hz, 2H, CH2 hydrocarbon); 2.08 sbr (3H, CH3) 181 m (2H, CH2); 1.63 m (2H, CH2); 1.51 m (2H, CH2). lc) 4 · [3_ (5-chlorophenyl) -2,5-dihydro-4-methyl_2,5-dioxo-iH-pyrrole-1-yl] -2- (trifluoromethyl ) Benzonitrile 9.46 g of 3- (5-chlorophenyl) -4-methyl-2,5-furandione and 813 g of amidino-2- (digasmethyl) benzonitrile in 22 ml of ethanol The mixture inside was mixed with 2.5 g of active molecular division (0.3 nm) under nitrogen pressure, and was stirred at 90 ° C for 2 days. For the sake of completion, after cooling, the molecular sieve is filtered, washed with ethanol, and the combined ethanol solution is concentrated by evaporation. The residue was dissolved in ethyl acetate and washed with water and saturated sodium chloride solution. Dried over sodium sulfate and evaporated -47- 200301117

(42) 濃縮後，其係用醋酸乙酯/己烷/甲苯在矽膠上層析，如此 可得11.69克白色固體的標題化合物。 1H-NMR (300 MHz，CDC13): 5 [ppm] = 8.06 sbr(lH,芳基）；7.91 s(2H，芳基）；3.56 t(J=7 Hz，2H，CH2C1); 2.53 t(J=7.5 Hz，2H，CH2 晞烴）；2.11 s(3H，CH3); 1.83 m(2H，CHA U、1.50 m(4H，CH2)。 Id) 4-[2,5-二氫- 3- (5-破戊基）-4-甲基-2,5-二氧代-1H-说嘻 -1-基]-2-(三氟甲基）苯甲腈(42) After concentration, it was chromatographed on silica gel with ethyl acetate / hexane / toluene to obtain 11.69 g of the title compound as a white solid. 1H-NMR (300 MHz, CDC13): 5 [ppm] = 8.06 sbr (lH, aryl); 7.91 s (2H, aryl); 3.56 t (J = 7 Hz, 2H, CH2C1); 2.53 t (J = 7.5 Hz, 2H, CH2 fluorene); 2.11 s (3H, CH3); 1.83 m (2H, CHA U, 1.50 m (4H, CH2). Id) 4- [2,5-dihydro- 3- ( 5-Polypentyl) -4-methyl-2,5-dioxo-1H-succin-1-yl] -2- (trifluoromethyl) benzonitrile

11.68 克 4-[3-(5-氯苯基）-2,5-二氫-4-甲基-2,5-二氧代-1H- 吡咯-1-基]-2-(三氟甲基）苯甲腈與18.2克碘化鈉於180毫升 乙基甲基酮内的混合物係在氮氣壓下，在80°C下授拌19小 時。在冷卻後，其係用醋酸乙酯稀釋並用水以及飽和氯化 鈉溶液洗條。在經硫酸納乾燥並藉蒸發濃縮後，如此可得 11.26克白色固體的標題化合物。11.68 g of 4- [3- (5-chlorophenyl) -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl A mixture of benzonitrile and 18.2 g of sodium iodide in 180 ml of ethyl methyl ketone was stirred under nitrogen pressure at 80 ° C. for 19 hours. After cooling, it was diluted with ethyl acetate and the bars were washed with water and a saturated sodium chloride solution. After drying over sodium sulfate and concentration by evaporation, this gave 11.26 g of the title compound as a white solid.

^-NMR (300 MHz, CDC13): 5 [ppm] = 8.06 sbr(lH，芳基）；7.91 s(2H，芳基）；3.20 t(J=7 Hz，2H, CH2I); 2.52 t(J=7.5 Hz，2H，CH2烯 烴）；2.11 s(3H，CH3); 1.86 m(2H，CH2); 1.63 (2H，CH2); 1.50 m(2H， CH2)。 le) 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]_2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]苯基]六氫吡畊-i-羧酸丨，^ 二甲基乙酯 1.56克六氫说味-1-羧酸丨，^二甲基乙酯在氮氣壓下加入 2.0克4-[2,5-二氫- 3-(5-碘戊基）_4_甲基_2,5_二氧代-1H-吡咯 -1-基]-2-(三敦甲基）苯甲腈於53毫升四氫呋喃内的溶液中 ’此混合物在室溫下攪拌7日。為了完成起見，其係用醋 -48- (43) (43)200301117^ -NMR (300 MHz, CDC13): 5 [ppm] = 8.06 sbr (lH, aryl); 7.91 s (2H, aryl); 3.20 t (J = 7 Hz, 2H, CH2I); 2.52 t (J = 7.5 Hz, 2H, CH2 olefins); 2.11 s (3H, CH3); 1.86 m (2H, CH2); 1.63 (2H, CH2); 1.50 m (2H, CH2). le) 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] _2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole -3-yl] phenyl] hexahydropyridine-i-carboxylic acid 丨, dimethyl ethyl ester 1.56 g of hexahydrocyclo-1-carboxylic acid 丨, dimethyl ethyl ester 2.0 was added under nitrogen pressure G 4- [2,5-dihydro- 3- (5-iodopentyl) _4_methyl_2,5_dioxo-1H-pyrrole-1-yl] -2- (tridenylmethyl) A solution of benzonitrile in 53 ml of tetrahydrofuran 'The mixture was stirred at room temperature for 7 days. For the sake of completion, it is made with vinegar -48- (43) (43) 200301117

酸乙酯稀釋並用半飽和碳酸氫鈉溶液洗滌。在經硫酸鈉乾 燥並藉蒸發濃縮後，其係用甲醇/二氯甲烷在矽膠上層析 ，如此可得2.2克淡黃色油的標題化合物。 j-NMRGOOMHtCDC^): <5[ppm] = 8.〇6sbr(1H，芳基）；7 9〇 m(2H，芳基）；3.43m(4H，六氫峨旬；25〇tbr(j=75Hz，2H,cH2 締烴）；2·40·2·31 m(4H,六氫,比口井）；2秦2 31叫况CH2六氯?比喷）; 2.09 s(3H，CH3);1.66-1.36 (m，6H，CH2); 1.45 (9H，Ch3)。 實例2 二氫-3-甲基氪吡畊-1-某）茉某 峨嘻-1-基1-2“三氣甲某）苹甲植^ 60毫升三襄醋酸係在氮氣壓下滴入4·5克氰基 -3-(三氣甲基）苯基]_2,5_二氫_4_曱基_2,5·二氧代_ιη-吡嘻 -3-基]苯基]六氫吡啡I羧酸u_二甲基乙酯於12〇毫升二 氯甲垸内的溶液中並在冰浴内冷#，其係在室溫下擾掉^ 小時。為了完成起見’反應溶液用25〇毫升甲苯稀釋，混 合物藉蒸發濃縮。殘餘物溶解於醋酸乙酯内並用飽和碳$ 氫鈉溶液洗滌。在經硫酸鈉乾燥並藉蒸發濃縮後，其係用 甲醇/二氯甲烷在矽膠上層析，如此可得35克白色固體的 標題化合物。 H-NMR (300 MHz’ CD3〇D): 5 [ppm] = 8，13 dbr(J=2H，1H，芳 基）；8.08 dbr(J=8.5 Hz，1H，芳基）；8·01 dd(J=8.5 Hz+2 Hz，1H，芳 基）；3.18m(4H，六氫吡畊）；2.69m(4H，六氫吡畊）；2.53tbr(j=75Ethyl acetate was diluted and washed with a half-saturated sodium bicarbonate solution. After drying over sodium sulfate and concentration by evaporation, it was chromatographed on silica gel with methanol / dichloromethane to give 2.2 g of the title compound as a pale yellow oil. j-NMRGOOMHtCDC ^): < 5 [ppm] = 8.〇6sbr (1H, aryl); 790m (2H, aryl); 3.43m (4H, hexahydroenzyme; 25〇tbr (j = 75Hz, 2H, cH2 associating hydrocarbons); 2.40 · 2 · 31 m (4H, hexahydro, than a well); 2 Qin 2 31 is called CH2 hexachloro? Specific spray); 2.09 s (3H, CH3) ; 1.66-1.36 (m, 6H, CH2); 1.45 (9H, Ch3). Example 2 Dihydro-3-methylpyridine-1-a) Momo Echi-1-yl 1-2 "three gas methyl" Pingjia plant ^ 60 ml of Sanxiang acetic acid was dripped under nitrogen pressure 4 · 5 g cyano-3- (trifluoromethyl) phenyl] _2,5_dihydro_4_fluorenyl_2,5 · dioxo_ιη-pyridin-3-yl] phenyl] A solution of hexahydropyridine I carboxylic acid u-dimethyl ethyl ester in 120 ml of dichloroformamidine and chilled in an ice bath #, which is disturbed at room temperature for ^ hours. For the sake of completion ' The reaction solution was diluted with 25 ml of toluene, and the mixture was concentrated by evaporation. The residue was dissolved in ethyl acetate and washed with a saturated sodium bicarbonate solution. After drying over sodium sulfate and concentration by evaporation, it was methanol / dichloromethane Chromatography on silica gel gave 35 g of the title compound as a white solid. H-NMR (300 MHz 'CD3OD): 5 [ppm] = 8, 13 dbr (J = 2H, 1H, aryl); 8.08 dbr (J = 8.5 Hz, 1H, aryl); 8.01 dd (J = 8.5 Hz + 2 Hz, 1H, aryl); 3.18m (4H, hexahydropyridine); 2.69m (4H, hexahydro Pythium); 2.53tbr (j = 75

Hz，2H，CH2烯烴）；2.47 tbr(J=7.5 Hz，2H，CH# 氫吡畊）；2.07 S(3H CH3); 1.69-1.53 m(4H，CH2); 1·44 (m，2H，CH2) 〇 -49- 200301117 (44) 實例3 4-「2,5-二氫-3-甲基-4-「5-「4-f2-(甲基硫烷基）笨某1六氫吡 畊-1-基1笨基卜2,5-二氣代-1H-吡咯-1-基1-2-(三氟甲基）苯_ 甲月青 9毫克1-(2-硫代甲基苯基）六氫吡畊於0.5毫升四氫呋喃 内加入10毫克4-[2,5-二氫- 3-( 5-碘戊基）-4-甲基- 2,5-二氧代 -1H-说咯-1-基]-2-(三氟甲基）苯甲腈於0.4毫升四氫呋喃内 的溶液中，混合物係在室溫下攪拌2日。為了完成起見， 反應混合物用醋酸乙酯稀釋並用半飽和碳酸氫鈉溶液洗 滌。在有機相藉蒸發濃縮後，其係用甲醇/二氯甲烷在矽 膠上層析，如此可得6毫克淡黃色油的標題化合物。 ESI-MS : 557。 實例4 4-「3-「5-「4-(氰基苯甲醯基）六氫吡畊-1-基1苯某1-2,5-二氫 -4-甲基-2,5-二氣代-1H-吡咯- l-基 1-2-(三氟甲基）笨甲腈 0.2毫升三乙胺於四氫呋喃（1.5莫耳/升）内的溶液與7毫 克4-氰基苯甲酿氯於0.4毫升四氫吱喃内加入9毫克4-[2,5-二氫-3-甲基- 2,5-二氧代-4-[5-(六氫吡畊-1-基）-苯基]-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈於0·4毫升四氫呋喃内的 溶液中，混合物係在室溫下攪拌8小時。為了完成起見， 反應混合物用醋酸乙醋稀釋並用半飽和碳酸氫鋼溶液洗 滌。在有機相藉蒸發濃縮後，其係用甲醇/二氯甲烷在矽 膠上層析，如此可得7毫克淡黃色油的標題化合物。 ESI-MS : 564。 200301117 (45) 實例5 4-「3-「5-「4-(3-氣笨基）磺醯基1六氢吡畊-1-基1笨基卜2,5-二 氤 -4-甲基-2,5-二 氣代-ΙΗ-说咯-1-基1-2-( 三氟甲基） 苯 甲腈 0.： ί毫升三乙胺 於四氫呋喃（1.5莫耳/升 )内的溶液與8毫 克 4- 氟苯基績S盛 氯於0.4毫升四氫呋喃内 加入9毫 :克4- [2,5- 二 氫 -3 -甲基- 2,5-二氧代-4-[5-(六氫吡畊 -1-基）-苯 基: ]-1H- 吡 咯 -1-基]-2-(三 .氟甲基）苯甲腈於0.4毫 升四氫 呋 喃 内的 溶 液 中，混合物 係在室溫下攪拌8小時。 為了完 成 起 見， 反 應 混合物用醋 酸乙酯稀釋並用半飽和 碳酸氫 納 溶 液洗 滌 0 在有機相藉 蒸發濃縮後，其係用甲 醇/二氯 甲 烷 在矽 膠 上 層析，如此 可得6毫克白色固體的標 題化合 物 0 ESI-MS : 593。 實 例 6 4- 「5-「1-「4-氰基- 3-(三氟甲基）笨基1-2,5- —~- ML - 4 - 甲 基 - 2,5- 二 氧 代-1Η-吡咯- • 3-基1苯羞二甲基胺基）苯基L 六氫 叶匕 畊 -1 -藉醯胺Hz, 2H, CH2 olefins); 2.47 tbr (J = 7.5 Hz, 2H, CH # hydropyridine); 2.07 S (3H CH3); 1.69-1.53 m (4H, CH2); 1.44 (m, 2H, CH2) 〇-49- 200301117 (44) Example 3 4- "2,5-dihydro-3-methyl-4-" 5- "4-f2- (methylsulfanyl) benzyl 1 hexahydropyridine Geng-1-yl 1 benzyl 2,5-digaso-1H-pyrrole-1-yl 1- (trifluoromethyl) benzene_methylate 9 mg 1- (2-thiomethyl Phenyl) hexahydropyrine is added to 0.5 ml of tetrahydrofuran and 10 mg of 4- [2,5-dihydro-3- (5-iodopentyl) -4-methyl-2,5-dioxo-1H- Say -1--1-yl] -2- (trifluoromethyl) benzonitrile in 0.4 ml of tetrahydrofuran, and the mixture was stirred at room temperature for 2 days. To complete, the reaction mixture was diluted with ethyl acetate It was washed with a half-saturated sodium bicarbonate solution. After the organic phase was concentrated by evaporation, it was chromatographed on silica gel with methanol / dichloromethane to obtain 6 mg of the title compound as a pale yellow oil. ESI-MS: 557. Examples 4 4- "3-" 5- "4- (cyanobenzyl) hexahydropyrine-1-yl 1 benzene 1,2,5-dihydro-4-methyl-2,5-di Gas-substituted-1H-pyrrole-l-yl 1- (trifluoromethyl) benzonitrile 0 .2 ml of triethylamine in tetrahydrofuran (1.5 mol / L) and 7 mg of 4-cyanobenzoyl chloride in 0.4 ml of tetrahydrofuran and 9 mg of 4- [2,5-dihydro- 3-methyl-2,5-dioxo-4- [5- (hexahydropyrine-1-yl) -phenyl] -1H-pyrrole-1-yl] -2- (trifluoromethyl) In a solution of benzonitrile in 0.4 ml of tetrahydrofuran, the mixture was stirred at room temperature for 8 hours. For the sake of completion, the reaction mixture was diluted with ethyl acetate and washed with a half-saturated hydrogen carbonate solution. Evaporated in the organic phase After concentration, it was chromatographed on silica gel with methanol / dichloromethane to give 7 mg of the title compound as a pale yellow oil. ESI-MS: 564. 200301117 (45) Example 5 4- "3-" 5- " 4- (3-Aminobenzyl) sulfofluorenyl 1 hexahydropyridin-1-yl 1benzyl 2,5-difluoren-4-methyl-2,5-digas--1Η-speak- 1-yl 1- (trifluoromethyl) benzonitrile 0: a solution of 1 ml of triethylamine in tetrahydrofuran (1.5 mol / L) and 8 mg of 4-fluorophenylsulfonium chloride at 0.4 9 ml of tetrahydrofuran were added: g of 4- [2,5-dihydro-3 -methyl-2,5-dioxo-4- [5- (hexahydropyrine-1-yl) -phenyl: In a solution of] -1H-pyrrole-1-yl] -2- (tri.fluoromethyl) benzonitrile in 0.4 ml of tetrahydrofuran, the mixture was stirred at room temperature for 8 hours. For the sake of completion, the reaction mixture was diluted with ethyl acetate and washed with a half-saturated sodium bicarbonate solution. After the organic phase was concentrated by evaporation, it was chromatographed on silica gel with methanol / dichloromethane to obtain 6 mg of a white solid. The title compound 0 ESI-MS: 593. Example 6 4- "5-" 1- "4-Cyano-3- (trifluoromethyl) benzyl 1-2,5- — ~-ML-4 -methyl-2,5-dioxo- 1Η-pyrrole- • 3-yl-1benzyldimethylamino) phenyl L hexahydrophyllol-1 -boramide

0.2毫升三乙胺於四氫呋喃（1.5莫耳/升）内的溶液與7毫 克4-(二甲基胺基）苯基異氰酸酯於0.4毫升四氫呋喃内加 入9毫克4-[2,5-二氫-3-甲基- 2,5-二氧代-4-[5-(六氫吡畊-1-基）-苯基]-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈於0.4毫升 四氫呋喃内的溶液中，混合物係在室溫下攪拌8小時。為 了完成起見，反應混合物用醋酸乙酯稀釋並用半飽和碳酸 氫鈉溶液洗滌。在有機相藉蒸發濃縮後，其係用甲醇/二 氣甲烷在矽膠上層析，如此可得3毫克淡黃色油的標題化 -51 - (46) 合物。 ESI-MS : 597。 實例7 4-「2,5-二氫-3-甲基-4-「3-M-Π -甲基乙基磺醯基）六氫吡畊 -1-基1丙基1-2,5-二氣代-1Η-吡咯-1-基12“三氟甲基）笨甲 7a) (Z)-2-甲基- 3-(丙-2-烯基）-2-丁烯二羧酸二甲酯A solution of 0.2 ml of triethylamine in tetrahydrofuran (1.5 mol / L) and 7 mg of 4- (dimethylamino) phenyl isocyanate were added to 0.4 ml of tetrahydrofuran and 9 mg of 4- [2,5-dihydro- 3-methyl-2,5-dioxo-4- [5- (hexahydropyrine-1-yl) -phenyl] -1H-pyrrole-1-yl] -2- (trifluoromethyl) A solution of benzonitrile in 0.4 ml of tetrahydrofuran was stirred at room temperature for 8 hours. For completion, the reaction mixture was diluted with ethyl acetate and washed with a half-saturated sodium bicarbonate solution. After concentrating the organic phase by evaporation, it was chromatographed on silica gel with methanol / dichloromethane. This gave 3 mg of the title compound -51-(46) as a pale yellow oil. ESI-MS: 597. Example 7 4- "2,5-Dihydro-3-methyl-4-" 3-M-Π-methylethylsulfonyl) hexahydropyrine-1-yl1propyl1-2,5 -Diodo-1Η-pyrrole-1-yl 12 "trifluoromethyl) benzyl 7a) (Z) -2-methyl-3- (prop-2-enyl) -2-butene dicarboxylic acid Dimethyl ester

氯化烯丙基鎂於四氫呋喃（8.5毫升，c= 2.0M)内的溶液在 氮氣壓下並在-35至-40°C下攪掉滴入3.47克銅（I)-溴化物-二甲基硫複合物於70毫升四氫呋喃内的懸浮液中，在-40 °C下攪拌2小時。然後，將其冷卻至- 70°C，在此溫度下攪 拌滴入2.0克伸乙醯基羧酸二甲酯與4.8毫升六甲磷酸三醯 胺於29毫升四氫呋喃内的溶液。在5分鐘後，在- 70°C下， 加入9.5毫升六甲磷酸三醯胺於9.5毫升四氫呋喃内的溶液 。在此溫度下，將其攪拌5分鐘，然後滴入4.2毫升碘甲烷 於28毫升四氫呋喃内，將此混合物隔夜加熱至室溫。為了 完成起見，將其冷卻至- 60°C並攪拌之，滴入200毫升飽和 氯化銨溶液（具有設定在pH為8的濃縮氨溶液）、加熱至室 溫並在室溫下攪拌45分鐘。此混合物用醋酸乙酯萃取4次 ，組合有機相用飽和氯化銨溶液（具有設定在pH為8的濃縮 氨溶液）洗滌，直到有機相為淡藍色為止，然後用水洗滌 ，直到有機相為無色為止。在用飽和氯化鈉溶液洗滌、經 硫酸鈉乾燥並藉蒸發濃縮後，用醋酸乙酯/己烷在矽膠上 層析，除了 950毫克（E)-2-甲基-3-(丙-2-烯基）-2-丁烯二羧 -52- 200301117A solution of allyl magnesium chloride in tetrahydrofuran (8.5 ml, c = 2.0M) was stirred under nitrogen pressure at -35 to -40 ° C and 3.47 g of copper (I) -bromide-dimethyl The suspension of the sulfur compound in 70 ml of tetrahydrofuran was stirred at -40 ° C for 2 hours. Then, it was cooled to -70 ° C, and at this temperature, a solution of 2.0 g of dimethyl amidinocarboxylate and 4.8 ml of trimethylamine hexamethylphosphate in 29 ml of tetrahydrofuran was added dropwise with stirring. After 5 minutes, at -70 ° C, a solution of 9.5 ml of trimethylamine hexamethylphosphate in 9.5 ml of tetrahydrofuran was added. At this temperature, it was stirred for 5 minutes, and then 4.2 ml of methyl iodide in 28 ml of tetrahydrofuran was added dropwise, and the mixture was warmed to room temperature overnight. To complete, cool it to -60 ° C and stir it, dropwise add 200 ml of saturated ammonium chloride solution (with a concentrated ammonia solution set at pH 8), heat to room temperature and stir at room temperature for 45 minute. This mixture was extracted 4 times with ethyl acetate, and the combined organic phase was washed with a saturated ammonium chloride solution (with a concentrated ammonia solution set at pH 8) until the organic phase was light blue, and then washed with water until the organic phase was Until colorless. After washing with saturated sodium chloride solution, drying over sodium sulfate and concentration by evaporation, chromatography on silica gel with ethyl acetate / hexane, except for 950 mg (E) -2-methyl-3- (propane-2 -Alkenyl) -2-butene dicarboxyl-52- 200301117

(47) 酸二甲酯以外，在各情況下，可得980毫克淡黃色油的標 題化合物。 lH-NMR (300 MHz, CDC13)： 5 [ppm] = 5.8 m(lH); 5.1 m(2H); 3.77 s(3H); 3.75 s(3H); 3.10 d(J=6.58 Hz，2H); 1.96 s(3H)。 ESI-MS: 198 7b) 3 -甲基- 4-(丙-2-烯基）-2,5-呋喃二酮(47) In addition to dimethyl acid, in each case 980 mg of the title compound was obtained as a pale yellow oil. lH-NMR (300 MHz, CDC13): 5 [ppm] = 5.8 m (lH); 5.1 m (2H); 3.77 s (3H); 3.75 s (3H); 3.10 d (J = 6.58 Hz, 2H); 1.96 s (3H). ESI-MS: 198 7b) 3-methyl-4- (prop-2-enyl) -2,5-furandione

1 0毫升水與1 6毫升氫氧化鋰於水（1莫耳/升）内的溶液加 入在氮氣壓下攪拌的980毫克7a製造的化合物於10毫升四 氫呋喃内的溶液中，在室溫下將其攪拌2日。為了完成起 見，其係藉蒸發濃縮，殘餘物溶解於30毫升水中，用鹽酸 (2莫耳/升）設定在pH2而在冰浴内冷卻並用二乙醚萃取3次 。組合的有機相用飽和氯化鋼溶液洗條、經硫酸鋼乾燥並 藉蒸發濃縮，如此可得7 5 0毫克淡黃色油的標題化合物。 ESI-MS : 152 7c) 4-[2,5-二氫-3-甲基-2,5-二氧代-4-(丙-2-烯基）-1Η-吡A solution of 10 ml of water and 16 ml of lithium hydroxide in water (1 mole / liter) was added to a solution of 980 mg of the 7a compound prepared in 10 ml of tetrahydrofuran, which was stirred under nitrogen pressure. It was stirred for 2 days. For completeness, it was concentrated by evaporation. The residue was dissolved in 30 ml of water, set at pH 2 with hydrochloric acid (2 moles / liter), cooled in an ice bath and extracted 3 times with diethyl ether. The combined organic phases were washed with a saturated steel chloride solution, dried over sulfuric acid steel, and concentrated by evaporation to obtain 750 mg of the title compound as a pale yellow oil. ESI-MS: 152 7c) 4- [2,5-Dihydro-3-methyl-2,5-dioxo-4- (prop-2-enyl) -1pyridine

咯-1-基]-2-(三氟甲基）苯甲腈 750毫克7b製成的化合物與920毫克4-胺基-2-(三氟甲基） 苯甲腈於10毫升乙醇内的混合物係在氮氣壓下與0.5克活 性分子篩（0.3毫微米）混合，並在90°C下攪拌2曰。為了完 成起見，在冷卻後過濾出分子篩、用乙醇洗滌、組合的乙 醇溶液藉蒸發濃縮。殘餘物溶解於醋酸乙酯内並用水及飽 和氯化鈉溶液洗滌。在經硫酸鈉乾燥並藉蒸發濃縮後，其 係用醋酸乙酯/己烷在矽膠上層析，如此可得73 1毫克無色 油的標題化合物。 -53- 200301117Pyr-1-yl] -2- (trifluoromethyl) benzonitrile 750 mg of compound made from 7b and 920 mg of 4-amino-2- (trifluoromethyl) benzonitrile in 10 ml of ethanol The mixture was mixed with 0.5 g of active molecular sieve (0.3 nm) under nitrogen pressure and stirred at 90 ° C for 2 days. For the sake of completion, the molecular sieve is filtered off after cooling, washed with ethanol, and the combined ethanol solution is concentrated by evaporation. The residue was dissolved in ethyl acetate and washed with water and saturated sodium chloride solution. After drying over sodium sulfate and concentration by evaporation, it was chromatographed on silica gel with ethyl acetate / hexane to give 73 1 mg of the title compound as a colorless oil. -53- 200301117

(48) ESI-MS : 320 7d) 4-[2,5-二氫- 3-(3-羥基丙基）-4-甲基- 2,5-二氧代-1H-吡 咯-1-基]-2-(三氟甲基）苯甲腈 720毫克7c製成的化合物於15毫升THF内的溶液係在氮 氣壓下，在-78°C下與5.9毫升9-硼雙環（3.3.1)壬烷0.5莫耳溶(48) ESI-MS: 320 7d) 4- [2,5-Dihydro- 3- (3-hydroxypropyl) -4-methyl-2,5-dioxo-1H-pyrrole-1-yl ] -2- (trifluoromethyl) benzonitrile 720 mg of the compound prepared in 7c in 15 ml of THF was under a nitrogen pressure at -78 ° C with 5.9 ml of 9-borabicyclo ) Nonane 0.5 Molar Soluble

液混合。溶液緩慢加熱至室溫並在室溫下攪拌隔夜。強力 攪拌的溶液在〇°C下與3.1毫升10%氫氧化鈉溶液並與2.7毫 升33%過氧化氫溶液混合，及其在室溫下攪拌12小時。為 了完成起見，其係與水（20毫升）混合並用醋酸乙酯萃取3 次。組合的有機相係用飽和氯化鋼溶液洗條、經硫酸鈉乾 燥、藉蒸發濃縮，用醋酸乙酯/己烷在矽膠上層析，如此 可得623毫克淡黃色油的標題化合物。 ESI-MS : 338 7e) 4-[2,5-二氫-3-(3-碘丙基）-4-甲基-2,5-二氧代-111-吡咯 -1-基]-2-(三氟甲基）苯甲腈液 混。 Liquid mixing. The solution was slowly warmed to room temperature and stirred overnight at room temperature. The vigorously stirred solution was mixed with 3.1 ml of a 10% sodium hydroxide solution and 2.7 ml of a 33% hydrogen peroxide solution at 0 ° C, and stirred at room temperature for 12 hours. For completion, it was mixed with water (20 ml) and extracted 3 times with ethyl acetate. The combined organic phase was washed with a saturated steel chloride solution, dried over sodium sulfate, concentrated by evaporation, and chromatographed on silica gel with ethyl acetate / hexane to obtain 623 mg of the title compound as a pale yellow oil. ESI-MS: 338 7e) 4- [2,5-dihydro-3- (3-iodopropyl) -4-methyl-2,5-dioxo-111-pyrrole-1-yl] -2 -(Trifluoromethyl) benzonitrile

610毫克7d製成的化合物於565毫克三苯膦内與183豪客 1H-咪唑於50毫升THF内的溶液係在氮氣壓下與545毫克碘 混合。溶液在室溫下攪拌隔夜，然後與20毫升水及10升20% 硫代硫酸那溶液混合並用醋酸乙酯萃取3次。組合的有機 相係用飽和氯化鈉溶液洗條、經硫酸鋼乾燥、藉蒸發濃縮 ，用醋酸乙酯/己烷在矽膠上層析，如此可得572毫克淡黃 色油的標題化合物。 ESI-MS : 448 7f) 4-[3-[l-[4-氰基- 3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -54- 200301117 (49) -2,5-二氧代-1H-叶匕咯-3-基]丙基]六氫批畊-1-羧酸1，1-二甲基乙酯 以類似於le所述的反應實施標題化合物的製造。使用 550毫克7e製成的化合物，可得372毫克標題化合物。 ESI-MS : 506 7g) 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[3-(六氫吡畊-1-基）A solution of 610 mg of 7d compound in 565 mg of triphenylphosphine and 183 Hawker 1H-imidazole in 50 ml of THF was mixed with 545 mg of iodine under nitrogen pressure. The solution was stirred at room temperature overnight, then mixed with 20 ml of water and 10 liters of a 20% thiosulfate solution and extracted 3 times with ethyl acetate. The combined organic phase was washed with a saturated sodium chloride solution, dried over sulfuric acid steel, concentrated by evaporation, and chromatographed on silica gel with ethyl acetate / hexane to obtain 572 mg of the title compound as a pale yellow oil. ESI-MS: 448 7f) 4- [3- [l- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-54- 200301117 (49 ) -2,5-Dioxo-1H-phyllol-3-yl] propyl] hexahydropyridine-1-carboxylic acid 1,1-dimethylethyl ester is carried out in a reaction similar to that described in le Manufacture of the title compound. Using 550 mg of the compound made from 7e, 372 mg of the title compound was obtained. ESI-MS: 506 7g) 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [3- (hexahydropyrine-1-yl)

丙基]-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈 350毫克7f製成的化合物係用3毫升三氟醋酸於10毫升二 氯甲烷内在室溫下攪拌6小時。反應混合物在真空中藉蒸 發濃縮並在真空中用甲苯藉蒸發濃縮若干次、溶解於甲醇 中、用陰離子交換器（Bio-Rad AG 1-Χ8,ΟΗ形式）設定pH為8 至9、過濾並在真空中藉蒸發濃縮。可得227毫克標題化合 物作為粗產物，其進一步以此形式反應。 ESI-MS ： 406 7h) 4-[2,5-二氫-3-甲基-4-[3-[4-(1-甲基乙基磺醯基）六氫Propyl] -1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 350 mg 7f Compound made with 3 ml of trifluoroacetic acid in 10 ml of dichloromethane and stirred at room temperature for 6 hour. The reaction mixture was concentrated by evaporation in vacuo and concentrated by evaporation in toluene several times in vacuo, dissolved in methanol, set to pH 8 to 9 using an anion exchanger (Bio-Rad AG 1-X8, 0Η), filtered and Concentrate by evaporation in vacuo. 227 mg of the title compound was obtained as a crude product, which was further reacted in this form. ESI-MS: 406 7h) 4- [2,5-dihydro-3-methyl-4- [3- [4- (1-methylethylsulfonyl) hexahydro]

吡畊-1-基]丙基]-2,5-二氧代-1H-吡咯-1-基]-2-(三氟 甲基）苯甲腈 25毫克7克製成的化合物係用11微升甲基乙基磺醯氯與 25微升三乙胺於2毫升四氫呋喃内在室溫下攪拌16小時。 反應混合物在真空中藉蒸發濃縮。用己烷/醋酸乙酯構成 的混合物在矽膠上實施柱式層析術可得23毫克無色油的 標題化合物。 ESI-MS ： 512 實例8 -55 - 200301117 (50) 4-「2,5-二氫-3-甲基-4-174-(1-甲基乙基磺醯基）六i.吡畊-1-基1甲基1-2,5-二氣代-111-说咯-1-基12-(三氟甲基）笨甲月青 8a) (Z)-2-乙烯基-3-甲基-2-丁烯二羧酸二甲酯 以類似於7 a所述的方式反應氯化乙晞基鎂與5克伸乙醯 二羧酸二甲酯以得1.8克淡黃色油的標題化合物。 ESI-MS : 184 8b) 4-[3-乙晞基- 2,5-二氫-4·甲基- 2,5-二氧代-1H-吡咯-1- 基]-2-(三氟甲基）苯甲腈 以類似於7b與7c所述的方式反應1.8克8a所製成的化合 物以得1.1克淡黃色油的標題化合物。 ESI-MS : 306 8c) 4-[3-(l，2-二羥基乙基）-2,5-二氫-4-甲基-2,5-二氧代 -1H·吡咯-1-基]-2-(三氟甲基）苯甲腈 1.1克8b所製成的化合物於50毫升丙酮内的溶液在室溫 下與640毫克N-甲基嗎啉-N-氧化物於10毫升水與0.9毫升 四氧化鉞10%溶液内的溶液混合。將其在室溫下攪拌30小 時，然後與飽和硫代硫酸鈉溶液混合並用醋酸乙酯萃取3 次。組合的有機相係用飽和氯化鈉溶液洗滌、經硫酸鈉乾 燥、藉蒸發濃縮，用二氯甲烷/甲醇在矽膠上層析，如此 可得770毫克無色油的標題化合物。 ESI-MS ： 340 8d) 4-[3 -甲醯基- 2,5-二氫-4-甲基- 2,5-二氧代-1H-批咯-1- 基]-2-(三氟甲基）苯甲腈 750毫克8c所製成的化合物於50毫升二氯甲烷内的溶液 200301117Pycnogenol-1-yl] propyl] -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 25 mg 7 g Compound compound 11 One microliter of methyl ethylsulfonyl chloride and 25 microliters of triethylamine were stirred in 2 ml of tetrahydrofuran at room temperature for 16 hours. The reaction mixture was concentrated in vacuo by evaporation. Column chromatography on silica gel using a hexane / ethyl acetate mixture gave 23 mg of the title compound as a colorless oil. ESI-MS: 512 Example 8 -55-200301117 (50) 4- "2,5-dihydro-3-methyl-4-174- (1-methylethylsulfonyl) hexa i. 1-yl 1 methyl 1-2,5-digaso-111-syl-1-yl 12- (trifluoromethyl) benzylazine 8a) (Z) -2-vinyl-3-methyl Dimethyl-2-butene dicarboxylate was reacted in a manner similar to that described in 7a with 5 g of dimethyl ethylene diacetate to give 1.8 g of the title compound as a pale yellow oil. ESI-MS: 184 8b) 4- [3-Ethylfluorenyl-2,5-dihydro-4 · methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoro Methyl) benzonitrile was reacted in a similar manner to that described in 7b and 7c with 1.8 g of 8a to give 1.1 g of the title compound as a pale yellow oil. ESI-MS: 306 8c) 4- [3- (l , 2-dihydroxyethyl) -2,5-dihydro-4-methyl-2,5-dioxo-1H · pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 1.1 A solution of 8 g of the compound prepared in 50 ml of acetone was mixed with a solution of 640 mg of N-methylmorpholine-N-oxide in 10 ml of water and 0.9 ml of a 10% solution of osmium tetraoxide at room temperature. It was stirred at room temperature for 30 hours, then mixed with a saturated sodium thiosulfate solution and Extract 3 times with ethyl acetate. The combined organic phase was washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated by evaporation, and chromatographed on silica gel with dichloromethane / methanol, thus obtaining 770 mg of a colorless oil. The title compound: ESI-MS: 340 8d) 4- [3-methylamino-2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl] -2 -(Trifluoromethyl) benzonitrile 750 mg 8c compound in 50 ml of dichloromethane 200301117

(51) 在室溫下連續與619毫克高碘酸鈉與5毫升碳酸氫鈉10%溶 液内混合。將其在室溫下攪拌5小時，然後與硫酸鈉混合 並用50毫升二氯甲烷稀釋。過濾混合物並藉蒸發濃縮。可 得705毫克標題化合物作為粗產物，其進一步以此形式反 應。 ESI-MS : 308 8e) 4-[2,5-二氫-3-甲基-4-[[4-(甲基乙基磺醯基）六氫吡畊(51) Mix continuously with 619 mg of sodium periodate and 5 ml of sodium bicarbonate in a 10% solution at room temperature. It was stirred at room temperature for 5 hours, then mixed with sodium sulfate and diluted with 50 ml of dichloromethane. The mixture was filtered and concentrated by evaporation. As a crude product, 705 mg of the title compound was obtained, which was further reacted in this form. ESI-MS: 308 8e) 4- [2,5-Dihydro-3-methyl-4-[[4- (methylethylsulfonyl) hexahydropyridine

-1-基]甲基]-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基） 苯甲腈-1-yl] methyl] -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile

25毫克8d所製成的化合物於1毫升1，2-二氯乙烷内在室 溫下與19毫克1-(1-甲基乙基磺醯基）六氫吡畊混合並攪拌 15分鐘。以份方式加入25毫克參乙醯氧基氫硼化鈉，將其 在室溫下攪拌2小時。反應混合物係與10毫升碳酸氫鈉溶 液混合，在室溫下攪拌15分鐘並用醋酸乙酯萃取3次。組 合的有機相係用飽和氯化鈉溶液洗條、經硫酸鈉乾燥、藉 蒸發濃縮，用二氯甲烷/甲醇在矽膠上層析。可得17毫克 無色油的標題化合物。 ESI-MS ： 484 實例9 4-「2,5-二i, -3-甲基-4-「7-「4-Π·甲基乙基磺醯基）六氫吡畊 -1-基1庚基卜2,5-二氣代-111-吡咯-1-基12-(三氣甲基）笨甲 11. 9a) (Z)-2-[7-[ (4-甲氧基苯基）甲氧基]庚基]-3-甲基-2-丁 烯二羧酸二甲酯 -57- 200301117 (52) 以類似於la所述的方式反應12.4克l-[ [(7-氯庚基）氧基] 甲基]甲氧基苯與5.0克伸乙醯二羧酸二甲酯以得4.18克 淡黃色油的標題化合物。 t ESI-MS : 378 9b) 4-[2,5-二氫-3-[7-[(4-甲氧基苯基）甲氧基]庚基]-4-甲25 mg of the 8d compound was mixed with 1 mg of 1- (1-methylethylsulfonyl) hexahydropyridine in 1 ml of 1,2-dichloroethane at room temperature and stirred for 15 minutes. 25 mg of sodium acetoacetoxyborohydride was added in portions, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was mixed with 10 ml of a sodium bicarbonate solution, stirred at room temperature for 15 minutes, and extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated by evaporation, and chromatographed on silica gel with dichloromethane / methanol. 17 mg of the title compound was obtained as a colorless oil. ESI-MS: 484 Example 9 4- "2,5-Di-i, -3-methyl-4-" 7- "4-Π · methylethylsulfonyl) hexahydropyridine-1-yl-1 Heptylb 2,5-digas-111-pyrrole-1-yl 12- (trigasmethyl) benzyl 11.9a) (Z) -2- [7- [(4-methoxyphenyl ) Methoxy] heptyl] -3-methyl-2-butene dicarboxylic acid dimethyl-57- 200301117 (52) 12.4 g of l- [[((7-chloro Heptyl) oxy] methyl] methoxybenzene and 5.0 g of dimethyl ethylene glycol dicarboxylate to give 4.18 g of the title compound as a pale yellow oil. T ESI-MS: 378 9b) 4- [2,5- Dihydro-3- [7-[(4-methoxyphenyl) methoxy] heptyl] -4-methyl

基- 2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈 以類似於7b與7c所述的方式反應4.10克9a所製成的化合 物以得3.35克無色油的標題化合物。 ESI-MS ： 514 9c) 4-[2,5-二氫-3-(7-羥基庚基）-4-甲基-2,5-二氧代-1士吡 咯-1-基]-2-(三氟甲基）苯甲腈 3.30克9b所製成的化合物於100毫升二氯甲烷内與10毫 升水及1.90克4,5-二氯-3,6-二氧代環己-1，4-二烯-1，2-二碳 腈混合，將其在室溫下攪拌5小時。反應混合物與20毫升 碳酸氫鈉溶液混合並用二氯甲烷萃取3次。組合的有機相 係用飽和氯化鈉溶液洗滌、經硫酸鈉乾燥、藉蒸發濃縮，-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile reacted in a manner similar to that described in 7b and 7c 4.10 g This gave 3.35 g of the title compound as a colorless oil. ESI-MS: 514 9c) 4- [2,5-dihydro-3- (7-hydroxyheptyl) -4-methyl-2,5-dioxo-1spyrrole-1-yl] -2 -(Trifluoromethyl) benzonitrile 3.30 g of 9b compound in 100 ml of dichloromethane with 10 ml of water and 1.90 g of 4,5-dichloro-3,6-dioxocyclohexane-1 The 4-diene-1,2-dicarbonitrile was mixed and stirred at room temperature for 5 hours. The reaction mixture was mixed with 20 ml of a sodium bicarbonate solution and extracted three times with dichloromethane. The combined organic phase was washed with a saturated sodium chloride solution, dried over sodium sulfate, and concentrated by evaporation.

用二氯甲烷/甲醇在矽膠上層析。可得2.05克無色油的標題 化合物。 ESI-MS : 394 9d) 4-[3-(7-碘庚基）-2,5-二氫-4-甲基-2,5-二氧代-1^1-吡咯 -1-基]-2-(三氟甲基）苯甲腈 以類似於7e所述的方式反應2.0克9c所製成的化合物以 得1.99克無色油的標題化合物。 ESI-MS : 504 -58- 200301117Chromatography on silica gel with dichloromethane / methanol. 2.05 g of the title compound were obtained as a colorless oil. ESI-MS: 394 9d) 4- [3- (7-iodoheptyl) -2,5-dihydro-4-methyl-2,5-dioxo-1 ^ 1-pyrrole-1-yl] 2- (Trifluoromethyl) benzonitrile was reacted in a manner similar to that described in 7e to 2.0 g of the compound prepared in 9c to give 1.99 g of the title compound as a colorless oil. ESI-MS: 504 -58- 200301117

(53) 9e) 4-[7-[ l-[4-氰基- 3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-批咯-3-基]庚基]六氫吡畊-1-羧酸1，1-二甲基乙酯 以類似於le所述的反應實施標題化合物的製造。使用 1.95克9c製成的化合物，可得1.01克標題化合物。 ESI-MS : 562 9f) 4-[2,5-二氫-3-甲基- 2,5-二氧代-4-[7-(六氫吡畊-1-基） 庚基]-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈 以類似於7g所述的反應實施標題化合物的製造。使用1 ·〇 克9e製成的化合物，可得707毫克標題化合物。 ESI-MS ： 462 9g) 4-[2,5-二氫-3-甲基-4-[7-[4-(1-甲基乙基磺醯基）六氫 外匕畊-1-基]庚基]-2,5-二氧代-1H-吡咯-1-基]-2-(三氟 甲基）苯甲腈 以類似於7h所述的反應實施標題化合物的製造。使用25 毫克9f製成的化合物，可得20毫克標題化合物。 ESI-MS : 568 實例10 4-「5-「3-Π ,3-二氫-1-氣代異笨并呋喃-5-基）-5.5-二甲基- 4-氣代-2-硫氣咪唑啉-1 -基1笨基1六氫吡畊-1 - #酸1,1 -二甲 基乙酯 10a) 5-[3-(5-羥基苯基）-5-亞胺基-4,4-二甲基-2-硫氧咪唑 啉-1 -基]異苯并呋喃-1 ( 3H)-酮 5克5-胺基異苯并呋喃-1(3H)-酮，其製造敘述於R. N. 200301117 (54)(53) 9e) 4- [7- [l- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo -1H-pyrrol-3-yl] heptyl] hexahydropyrine-1-carboxylic acid 1,1-dimethylethyl ester was prepared in a reaction similar to that described in Le. Using 1.95 g of the compound made from 9c, 1.01 g of the title compound was obtained. ESI-MS: 562 9f) 4- [2,5-dihydro-3-methyl- 2,5-dioxo-4- [7- (hexahydropyrine-1-yl) heptyl] -1H -Pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile The production of the title compound was carried out in a reaction similar to that described in 7 g. Using 1.0 g of the compound made from 9e, 707 mg of the title compound was obtained. ESI-MS: 462 9g) 4- [2,5-dihydro-3-methyl-4- [7- [4- (1-methylethylsulfonyl) hexahydrocarbyl-1-yl ] Heptyl] -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile The production of the title compound was carried out in a reaction similar to that described in 7h. Using 25 mg of the compound made from 9f, 20 mg of the title compound can be obtained. ESI-MS: 568 Example 10 4- "5-" 3-", 3-Dihydro-1-Gasto-isobenzofuran-5-yl) -5.5-dimethyl-4-Gasto-2-sulfide Imidazoline-1 -yl 1benzyl 1 hexahydropyrine-1-#acid 1,1-dimethyl ethyl ester 10a) 5- [3- (5-hydroxyphenyl) -5-imino- 4,4-dimethyl-2-thiooximidazoline-1 -yl] isobenzofuran-1 (3H) -one 5 g of 5-aminoisobenzofuran-1 (3H) -one, its manufacture Narrated in RN 200301117 (54)

Warrener，L. Liu，R. A. Russell，Tetrahedron 1998, 54, 7485-7496 ，與28毫补硫代光氣於宅升水中，在氮氣壓下’在室溫 下攪;摔1小時。過濾反應混合物。殘餘物用水洗丨條，然後 在60°C下於真空中乾燥30分鐘。如此所得的粗異硫代氰酸 醋係與氰胺組合，其係在室溫下藉4小時攪拌520微升丙酮 氰醇與617微升5_胺基戊-卜醇製成’用4·7毫升三乙胺於100 毫升四氫咬喃内將其加熱至沸騰歷30分鐘。在真空中藉蒸 發濃縮後，< 得標題化合物作為粗產物，其直接被進一步 反應。Warrener, L. Liu, R. A. Russell, Tetrahedron 1998, 54, 7485-7496, and 28 m of thiophosgene in house liter water, stirred under nitrogen pressure at room temperature; dropped for 1 hour. The reaction mixture was filtered. The residue was washed with water and then dried under vacuum at 60 ° C for 30 minutes. The thus obtained crude isothiocyanate was combined with cyanamide, which was made by stirring 520 microliters of acetone cyanohydrin and 617 microliters of 5-aminopentyl-butanol at room temperature by stirring for 4 hours 7 ml of triethylamine were heated in 100 ml of tetrahydrofuran to boil for 30 minutes. After concentration by evaporation in vacuo, < the title compound was obtained as a crude product, which was directly reacted further.

10b) 3-(1，3 -二氫- I—氧代異苯并唉喃-5-基）-1-(5-¾基苯基） _5 5-二甲基-2-繞氧味嗤11林-4-酉同 由10a製成的粗產物係在室溫下用17毫升4莫耳水性鹽 酸於1 50毫补甲醇内攪拌隔夜。然後，將反應混合物澆入 飽和碳酸氫鈉水溶液内並用醋酸乙酯萃取。有機相係用飽 和氯化鈉水溶液洗滌、經硫酸鈉乾燥、過濾及在真空中藉 蒸發濃縮。用由己境/醋酸乙醋構成的混合物在矽膠上實 施柱式層析術以得4·0克無色發泡體的標題化合物。 iH-NMR (300 MHz，CDC13): 5 [ppm] = 8.03 d(J=8 Hz，1H，芳 基）；7.53(1仙1：(>8以+11^，111，芳基）；7.52(1(】=11^，111，芳基）; 5·37 s(lH，CH2〇)； 3.71 m(2H，CH2OH); 3·69 m(2H，CH2N); 1.89 m (2H，CH2); 1.66 m(2H，CH2); 1.58 s(6H，CH3);1.49 m(2H，CH2)。 10c) 3-(l，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1-[5-[[(4-甲基苯基）-磺醯基]氧基]戊基卜2-硫氧咪唑 琳-4-酮 •60- 200301117 (55) 3.9克由10b製成的化合物係在室溫下用12.3克對甲苯磺 酸氯與1 5毫升三乙胺於1 〇〇毫升二氯甲烷内攪拌1小時。將 反應混合物繞入飽和竣酸氫鋼水溶液内並用二氣甲燒萃 取。有機相係用飽和氯化鈉水溶液洗滌、經硫酸鈉乾燥、 過濾及在真空中藉蒸發濃縮。用由己烷/醋酸乙酯構成的 混合物在矽膠上實施柱式層析術以得5· 15克無色發泡體 的標題化合物。10b) 3- (1,3-dihydro-I-oxoisobenzopyran-5-yl) -1- (5-¾ylphenyl) _5 5-dimethyl-2-pyridine 11 Lin-4- 酉 and the crude product made from 10a were stirred at room temperature with 17 ml of 4 mol aqueous hydrochloric acid in 150 mmol of methanol overnight. Then, the reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic phase was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered and concentrated in vacuo by evaporation. Column chromatography was performed on silica gel using a mixture consisting of ethyl acetate / ethyl acetate to obtain 4.0 g of the title compound as a colorless foam. iH-NMR (300 MHz, CDC13): 5 [ppm] = 8.03 d (J = 8 Hz, 1H, aryl); 7.53 (1 cent 1: (> 8 to + 11 ^, 111, aryl); 7.52 (1 () = 11 ^, 111, aryl); 5.37 s (lH, CH2〇); 3.71 m (2H, CH2OH); 3.69 m (2H, CH2N); 1.89 m (2H, CH2 ); 1.66 m (2H, CH2); 1.58 s (6H, CH3); 1.49 m (2H, CH2). 10c) 3- (l, 3-dihydro-1-oxoisobenzofuran-5-yl ) -5,5-dimethyl-1- [5-[[((4-methylphenyl) -sulfofluorenyl] oxy] pentylb 2-thiooximidazole-4-one • 60- 200301117 (55) 3.9 g of a compound made of 10b was stirred at room temperature with 12.3 g of p-toluenesulfonic acid chloride and 15 ml of triethylamine in 100 ml of dichloromethane for 1 hour. The reaction mixture was wound into saturation The acid-hydrogen steel solution was extracted and extracted with dichloromethane. The organic phase was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated by evaporation in a vacuum. A mixture of hexane / ethyl acetate was used in silica gel. Column chromatography was performed above to obtain 5.15 g of the title compound as a colorless foam.

閃點164.9°C (甲醇） 1H-NMR (300 MHz，CDC13): 5 [ppm] = 8.04 d(J=8 Hz，lH，芳Flash point 164.9 ° C (methanol) 1H-NMR (300 MHz, CDC13): 5 [ppm] = 8.04 d (J = 8 Hz, 1H, aromatic

基）；7.81 d(J=9 Hz，2H，甲苯基）；7.54 dbr(J=8 Hz，1H，芳基）；7.53 51^(11芳基）；7.37〇1(】=9以，211，甲苯基）;5.38 5(111，0^20);4.08 t(J=6 Hz，2H，CH2OTs); 3.68 m(2H，CH2N); 1·86 m(2H，CH2); 1·76 m(2H，CH2); 1.58 s(6H，CH3);1.49 m(2H，CH2)。 lOd) 3-(l，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1-(5-埃戊基）-2-硫氧-咪唑4 - 4-酮 5.15克由10c製成的化合物係用3克碘化鈉於1〇〇毫升丙 酮内加熱至彿騰歷1小時。反應混合物在室溫下過滤並在 真空中藉蒸發濃縮。用由己烷/醋酸乙酯構成的混合物在 矽膠上實施柱式層析術以得4.16克淡黃色發泡體的標題 化合物。 !H-NMR (300 MHz，CDC13): 5 [ppm] = 8.03 d(J=8 Hz, 1H，芳 基）；7.53 ddbr(J=8 Hz+2 Hz，1H，芳基）；7·52 sbr(lH，芳基）；5·37 s(lH，CH2〇)； 3·70 m(2H，CH2N); 3.23 t(J=7 Hz，2H，CH2I); 1·89 m(4H，CH2); 1.59 s(6H，CH3);1.53 m(2H，CH2)。 -61 - 200301117Radical); 7.81 d (J = 9 Hz, 2H, tolyl); 7.54 dbr (J = 8 Hz, 1H, aryl); 7.53 51 ^ (11 aryl); 7.37〇1 () = 9 to 211 , Tolyl); 5.38 5 (111, 0 ^ 20); 4.08 t (J = 6 Hz, 2H, CH2OTs); 3.68 m (2H, CH2N); 1.86 m (2H, CH2); 1.76 m (2H, CH2); 1.58 s (6H, CH3); 1.49 m (2H, CH2). lOd) 3- (l, 3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-1- (5-epentyl) -2-thiooxy-imidazole 5.15 g of 4- 4-ketone compound made of 10c was heated with 3 g of sodium iodide in 100 ml of acetone for 1 hour. The reaction mixture was filtered at room temperature and concentrated in vacuo by evaporation. Column chromatography was performed on silica gel using a mixture of hexane / ethyl acetate to obtain 4.16 g of the title compound as a pale yellow foam. ! H-NMR (300 MHz, CDC13): 5 [ppm] = 8.03 d (J = 8 Hz, 1H, aryl); 7.53 ddbr (J = 8 Hz + 2 Hz, 1H, aryl); 7.52 sbr (lH, aryl); 5.37 s (lH, CH2〇); 3.70 m (2H, CH2N); 3.23 t (J = 7 Hz, 2H, CH2I); 1.89 m (4H, CH2) ); 1.59 s (6H, CH3); 1.53 m (2H, CH2). -61-200301117

(56) 10勾4-[5-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲 基-4-氧代-2-硫氧咪唑4 - 1 -基]戊基]六氫吡畊-1 -叛酸 1,1-二甲基乙酯 1克由10d製成的化合物係在室溫下用790毫克六氫吡呼 -1 -羧酸1，1 -二甲基乙酯與591微升三乙胺攪拌3日。反應混 合物在真空中藉蒸發濃縮。用由己烷/醋酸乙酯構成的混 合物在石夕膠上實施柱式層析術以得9 0 3毫克淡黃色發泡體(56) 10 ticks 4- [5- [3- (1,3-Dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2- Thioximidazole 4-1 -yl] pentyl] hexahydropyrine-1-1,1-dimethylethyl acetic acid 1 g of compound made from 10 d at room temperature with 790 mg of hexahydropyr The -1-carboxylic acid 1,1-dimethylethyl ester was stirred with 591 µl of triethylamine for 3 days. The reaction mixture was concentrated in vacuo by evaporation. Column chromatography was performed on Shixi gum with a mixture of hexane / ethyl acetate to obtain 903 mg of light yellow foam.

的標題化合物。 ^-NMR (300 MHz, CDC13)： 5 [ppm] = 8.04 d(J=8 Hz, 1H,芳 基）；7.54 dbr (J=8 Hz，1H，芳基）；7.52 sbr (1H，芳基）；5.37 s(lH， CH2〇）；3.69m(2H，CH2N);3.44m(4H，六氫吡畊）；2.38m(4H，六 氫吡畊）；2.36 m(2H，（：112六氫吡畊）；1.86 m(2H，CH2); 1.58s(6H， CH3);1.57 m(2H，CH2); 1.46 s(9H，'Bu); 1.42 m(2H，CH2) 〇 實例11 3-(1,3-二氫-1-氣代異笨并呋喃-5-某）-l-f 5-(六氤吡畊-1-某） 戊基1-5,5-二甲某-2-硫氣咪唑啉-4-酮Title compound. ^ -NMR (300 MHz, CDC13): 5 [ppm] = 8.04 d (J = 8 Hz, 1H, aryl); 7.54 dbr (J = 8 Hz, 1H, aryl); 7.52 sbr (1H, aryl) ); 5.37 s (lH, CH2〇); 3.69m (2H, CH2N); 3.44m (4H, hexahydropyridine); 2.38m (4H, hexahydropyridine); 2.36m (2H, (: 112 six Hydropyridine); 1.86 m (2H, CH2); 1.58s (6H, CH3); 1.57 m (2H, CH2); 1.46 s (9H, 'Bu); 1.42 m (2H, CH2) 〇 Example 11 3- (1,3-Dihydro-1-gasoisobenzofuran-5-some) -lf 5- (hexamethylpyrine-1-some) Amyl 1-5,5-dimethylmethyl-2-sulfide Imidazolin-4-one

450毫克10e製成的化合物係在室溫下用653微升三氟醋 酸於8.5毫升二氯甲烷内攪掉24小時。反應混合物在真空中 藉蒸發濃縮並在真空中用甲苯藉蒸發濃縮若干次、溶解於 甲醇中、用陰離子交換器（Bio-Rad AG 1-Χ8,ΟΗ形式）設定pH 為8至9、過濾並在真空中藉蒸發濃縮。可得313毫克標題 化合物作為粗產物，其進一步以此形式反應。 iH-NMR (300 MHz，CD3OD): 5 [ppm] = 7.96 d(J=8 Hz，1H，芳 基）；7·57 dbr (J=8 Hz，1H，芳基）；7.65 sbr(lH，芳基）；5.43 s(lH， -62- 200301117450 mg of the 10e compound was stirred at room temperature with 653 µl of trifluoroacetic acid in 8.5 ml of dichloromethane for 24 hours. The reaction mixture was concentrated by evaporation in vacuo and concentrated by evaporation in toluene several times in vacuo, dissolved in methanol, set to pH 8 to 9 using an anion exchanger (Bio-Rad AG 1-X8, 0Η), filtered and Concentrate by evaporation in vacuo. 313 mg of the title compound was obtained as a crude product, which was further reacted in this form. iH-NMR (300 MHz, CD3OD): 5 [ppm] = 7.96 d (J = 8 Hz, 1H, aryl); 7.57 dbr (J = 8 Hz, 1H, aryl); 7.65 sbr (lH, Aryl); 5.43 s (lH, -62- 200301117

(57) CH20); 3.75 m(2H? CH2N); 2.87 m(4H,六氫吡畊）；2.48 m(4H，六 氫吡畊）；2.39 m(2H，（：&六氫吡畊）；1.88 m(2H，CH2); 1.61 m(2H， CH2); 1.58 s(6H，CH3);1.42 m(2H，CH2)。 實例12 4-「5-「3-(1,3-二氤-1-氣代異笨并呋喃-5-墓）-5,5-二甲基-4-氣代-2-硫氣咪唑啉-1 -基1戊基1 - N-乙基六氫吡畊-1 -碳硫 代醯胺(57) CH20); 3.75 m (2H? CH2N); 2.87 m (4H, hexahydropyridine); 2.48 m (4H, hexahydropyridine); 2.39 m (2H, (: & hexahydropyridine) 1.88 m (2H, CH2); 1.61 m (2H, CH2); 1.58 s (6H, CH3); 1.42 m (2H, CH2). Example 12 4- "5-" 3- (1,3-Difluorene) -1-Gasto-isobenzofuran-5-tomb) -5,5-dimethyl-4-Gasto-2-thio-imidazoline-1 -yl 1pentyl 1 -N-ethylhexahydropyridine Plow-1 -carbothioamide

20毫克11製成的化合物係與7.7毫升異硫代氰基乙烷及 12.4微升三乙胺於3毫升四氫呋喃内加熱至80°C歷6小時。 反應混合物在真空中藉蒸發濃縮。用己烷/醋酸乙酯構成 的混合物在碎膠上實施柱式層析術以得11毫克無色油的 標題化合物。 lH-NMR (300 MHz, CDC13)： 5 [ppm] = 8.02 d(J=8 Hz，1H，芳20 mg of the compound 11 was heated with 7.7 ml of isothiocyanoethane and 12.4 µl of triethylamine in 3 ml of tetrahydrofuran to 80 ° C for 6 hours. The reaction mixture was concentrated in vacuo by evaporation. Column chromatography was performed on the crushed gel with a mixture of hexane / ethyl acetate to obtain 11 mg of the title compound as a colorless oil. lH-NMR (300 MHz, CDC13): 5 [ppm] = 8.02 d (J = 8 Hz, 1H, aromatic

基）；7.53 dbr (J=8 Hz，1H，芳基）；7.51 sbr (1H，芳基）；5·47 tbr (J=5 Hz，1H，NH); 5.37 s(lH，CH2〇）； 3.81 m(4H，六氫吡畊）；3.70 qd(J=7 Hz+5 Hz，2H，CH2N); 3.67 m(2H，CH2N); 2.47 m(4H，六氫 吡畊）；2.38 m(2H，CH2 六氫吡畊）；1.86 m(2H，CH2); 1.57 s(6H， CH3);1.57 m(2H，CH2); 1.41 m(2H，CH2); 1_24 t(J=7 Hz，3H，CH3)。 實例13 4-「5-「3-Π,3-二氤-1-氣代異苯并咭喃-5-基5,5-二曱基- 4- 氧代-2-硫氣咪唑啉-1 -基1戊基1六氤吡畊-1 -碳硫酸S-甲酯 15.5毫克11製成的化合物係與6.2毫升氯硫代甲酸S-甲酯 及10微升三乙胺於1毫升四氫呋喃内回流4小時。反應混合 物在真空中藉蒸發濃縮。用己烷/醋酸乙酯構成的混合物 -63- 200301117Base); 7.53 dbr (J = 8 Hz, 1H, aryl); 7.51 sbr (1H, aryl); 5.47 tbr (J = 5 Hz, 1H, NH); 5.37 s (lH, CH2〇); 3.81 m (4H, hexahydropyridine); 3.70 qd (J = 7 Hz + 5 Hz, 2H, CH2N); 3.67 m (2H, CH2N); 2.47 m (4H, hexahydropyridine); 2.38 m (2H , CH2 hexahydropyridine); 1.86 m (2H, CH2); 1.57 s (6H, CH3); 1.57 m (2H, CH2); 1.41 m (2H, CH2); 1_24 t (J = 7 Hz, 3H, CH3). Example 13 4- "5-" 3-Π, 3-Difluoren-1-oxoisobenzopyran-5-yl 5,5-difluorenyl- 4-oxo-2-thioimidazoline- 1-yl-1 pentyl 1 hexamethylpyridine-1-carbonic acid S-methyl ester 15.5 mg 11. Compound system made with 6.2 ml S-methyl chlorothioformate and 10 μl triethylamine in 1 ml tetrahydrofuran The mixture was refluxed for 4 hours. The reaction mixture was concentrated by evaporation in vacuo. A mixture consisting of hexane / ethyl acetate-63- 200301117

(58) 在矽膠上實施柱式層析術以得8毫克無色油的標題化合 物。 lH-NMR (300 MHz, CDC13)： 5 [ppm] = 8.03 d(J=8 Hz，1H，芳 基）；7.53 dbi: (J = 8 Hz，1H，芳基）；7.52 sbr (1H，芳基）；5.37 s(lH， CH20);3.69m(2H，CH2N);3.56m(4H，六氫吡畊）；2.43m(4H，六 氫吡畊）；2·38 m(2H，CH2 六氫吡畊）；2.33 s(3H，CH3);1.86 m(2H， CH2); 1.57 s(6H，CH3);1.56 m(2H，CH2); 1.42 m(2H，CH2)。(58) Column chromatography was performed on silicone to obtain 8 mg of the title compound as a colorless oil. lH-NMR (300 MHz, CDC13): 5 [ppm] = 8.03 d (J = 8 Hz, 1H, aryl); 7.53 dbi: (J = 8 Hz, 1H, aryl); 7.52 sbr (1H, aromatic Base); 5.37 s (lH, CH20); 3.69m (2H, CH2N); 3.56m (4H, hexahydropyridine); 2.43m (4H, hexahydropyridine); 2.38 m (2H, CH2 six Hydropyridine); 2.33 s (3H, CH3); 1.86 m (2H, CH2); 1.57 s (6H, CH3); 1.56 m (2H, CH2); 1.42 m (2H, CH2).

實例14 4-「5-「3-(1,3-二氪-1-氫代異笨并呋喃-5-基）-5.5-二曱某 氣代-2-硫氣咪唑啉-1-某1戊基1-N.N-二乙基六氫吡畊」卜 羧醯胺 15.5毫克11製成的化合物係與9.8毫升二甲基脲醯氯及10 微升三乙胺於1毫升四氫呋喃内回流4小時。反應混合物在 真空中藉蒸發濃縮。用己烷/醋酸乙酯構成的混合物在矽 膠上實施柱式層析術以得6毫克無色油的標題化合物。Example 14 4- "5-" 3- (1,3-Difluoren-1-hydroisoisobenzofuran-5-yl) -5.5-difluorin 1 pentyl 1-NN-diethylhexahydropyridine, a compound of 15.5 mg of carboxamide, 9.8 ml of dimethylurea chloride and 10 μl of triethylamine refluxed in 1 ml of tetrahydrofuran 4 hour. The reaction mixture was concentrated in vacuo by evaporation. Column chromatography was performed on silica gel using a hexane / ethyl acetate mixture to obtain 6 mg of the title compound as a colorless oil.

1H-NMR (300 MHz，CDC13):占[ppm] = 8.03 d(J=8 Hz，lH，芳 基）；7.53 dbr(J=8 Hz，1H，芳基）；7.52 sbr(lH，芳基）；5.37 S(1H， CH2〇）； 3.69 m(2H，CH2N); 3.23 m(4H，六氫吡畊）；3· 19 q(J=4H， CH2N); 2.43 m(4H,六氫吡畊）；2.37 m(2H，（：112六氫吡畊）；1.86 m(2H，CH2); 1.59 m(2H，CH2); 1·58 s(6H，CH3);1.41 m(2H，CH2); 1.11 t(J=7 Hz，6H，CH3)。 實例15 4-门-「2-l~4-(2-甲氣某装甲醯基）六氫吡畊-1- & 1乙基 二甲基-5-氣代-2-硫氣咪唑啉基1-2-(三顧.甲某）笨甲晴 -64- 2003011171H-NMR (300 MHz, CDC13): accounted for [ppm] = 8.03 d (J = 8 Hz, 1H, aryl); 7.53 dbr (J = 8 Hz, 1H, aryl); 7.52 sbr (lH, aryl) ); 5.37 S (1H, CH2〇); 3.69 m (2H, CH2N); 3.23 m (4H, hexahydropyridine); 3.19 q (J = 4H, CH2N); 2.43 m (4H, hexahydropyridine) Tillage); 2.37 m (2H, (: 112 hexahydropyridine); 1.86 m (2H, CH2); 1.59 m (2H, CH2); 1.58 s (6H, CH3); 1.41 m (2H, CH2) 1.11 t (J = 7 Hz, 6H, CH3). Example 15 4-Gate-"2-l ~ 4- (2-methyl-an armored fluorenyl) hexahydropyrine -1- & 1 ethyl di Methyl-5-Gas-2-thio-imidazolidinyl 1- 2- (Three Gu. Jia Mou) Ben Jia Qing-64- 200301117

(59) 15a) 4-[2-[3-[4-氰基- 3-(三氟甲基）苯基]-4-亞胺基-5,5-二 甲基-2-硫氧咪唑啉-1 -基]乙基]六氫吡畊-1 -羧酸1，1 -二甲基乙酯(59) 15a) 4- [2- [3- [4-cyano-3- (trifluoromethyl) phenyl] -4-imino-5,5-dimethyl-2-thioximidazole Phenyl-1 -yl] ethyl] hexahydropyridine-1 -carboxylic acid 1,1-dimethylethyl ester

687克4-胺基-2-(三氟甲基）苯甲腈與311微升硫代光氣於 4毫升N，N-二甲基甲醯胺内係在室溫下，在氮氣壓下攪拌1 小時。反應混合物係用醋酸乙酯稀釋、用水洗滌及在真空 中藉蒸發濃縮。如此所得粗異硫代氰酸酯係與氰胺組合， 其係在室溫下用930毫克4-(2-胺基乙基）六氫吡畊-1-羧酸 1，1-二甲基乙酯與406毫克分子篩3A於20毫升四氫呋喃内 ，藉攪拌2小時自743微升丙酮氰醇製成並過濾，及其與0.57 毫升三乙胺於40毫升四氫呋喃内加熱至沸騰歷1小時。在 真空中藉蒸發濃縮後，可得標題化合物作為粗產物，其直 接進一步反應。687 g of 4-amino-2- (trifluoromethyl) benzonitrile and 311 μl of thiophosgene in 4 ml of N, N-dimethylformamide at room temperature under nitrogen pressure Stir for 1 hour. The reaction mixture was diluted with ethyl acetate, washed with water and concentrated in vacuo by evaporation. The crude isothiocyanate thus obtained was combined with cyanamide, which was 930 mg of 4- (2-aminoethyl) hexahydropyrine-1-carboxylic acid 1,1-dimethyl at room temperature. Ethyl ester and 406 mg of molecular sieve 3A in 20 ml of tetrahydrofuran were prepared and filtered from 743 microliters of acetone cyanohydrin by stirring for 2 hours, and heated with 0.57 ml of triethylamine in 40 ml of tetrahydrofuran to boil for 1 hour. After concentration in vacuo by evaporation, the title compound was obtained as a crude product, which was directly reacted further.

15b) 4-[2-[3-[4-氰基- 3-(三氟甲基）苯基]-5,5-二甲基-4-氧 代-2-硫氧咪唑啉-1-基]乙基]六氫吡畊-1-羧酸1，1-二 甲基乙酯 由15a製成的粗產物係在室溫下與3.7毫升4莫耳水性鹽 酸於40毫升甲醇内攪拌隔夜。將反應混合物澆入飽和碳酸 氫鈉水溶液内並用醋酸乙酯萃取。有機相係用飽和氯化鈉 水溶液洗滌、經硫酸鈉乾燥、過濾及在真空中藉蒸發濃縮 。用由己烷/醋酸乙酯構成的混合物在矽膠上實施柱式層 析術以得553毫克無色發泡體的標題化合物。 iH-NMR (300 MHz，CDC13): 6 [PPm] = 7 · 9 5 d (J = 8 Η z，1 Η， 芳基）；7.88 d(J= 2Hz，1H，芳基）；7 · 7 7 d db i* (J = 8 H z + 2 H z， -65- 200301117 (60)15b) 4- [2- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazoline-1- [Ethyl] ethyl] hexahydropyridine-1-carboxylic acid 1,1-dimethyl ethyl ester The crude product of 15a was stirred overnight with 3.7 ml of 4 mol aqueous hydrochloric acid in 40 ml of methanol at room temperature. . The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic phase was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered and concentrated in vacuo by evaporation. Column chromatography was performed on silicone using a mixture consisting of hexane / ethyl acetate to obtain 553 mg of the title compound as a colorless foam. iH-NMR (300 MHz, CDC13): 6 [PPm] = 7 · 9 5 d (J = 8 Η z, 1 Η, aryl); 7.88 d (J = 2 Hz, 1H, aryl); 7 · 7 7 d db i * (J = 8 H z + 2 H z, -65- 200301117 (60)

1 Η,芳基）；3.85 m(2H，CH2N); 3.44 m(4H，六氫吡 4); 2.781 fluorene, aryl); 3.85 m (2H, CH2N); 3.44 m (4H, hexahydropyridine 4); 2.78

m(2H，CH2N); 2.52 m(4H，六氫口比畊）；1.59s(6H，CH3);1.46 m(9H 【Bu)。m (2H, CH2N); 2.52 m (4H, hexahydro mouth specific farming); 1.59s (6H, CH3); 1.46 m (9H [Bu).

15(：)4-[4,4-二甲基-5-氧代-3-[2-(六氫吡畊-1-基）乙基]-2-硫氧咪唑啉-1 -基]-2-(三氟甲基）苯甲腈 553毫克15b製成的化合物係在室溫下與809微升三氟酷 酸於10毫升二氯甲烷内攪拌24小時。反應混合物在真空中 藉蒸發濃縮並在真空中用甲苯藉蒸發濃縮若干次、溶解於 甲醇中、用陰離子交換器（Bio-Rad AG 1-Χ8,ΟΗ形式）設定PH 為8至9、過濾並在真空中藉蒸發濃縮。可得426毫克標題 化合物作為粗產物，其進一步以此形式反應。 ^-NMR (300 MHz, CDC13): 5 [ppm] = 7.95 d(J=8 Hz，1H，芳 基）；7.89(1(>2 1^，111，芳基）；7.77(1此1：卩=8 1^+2 1^，111，芳基）; 3.85 m(2H，CH2N); 2.91 m(4H，六氫吡畊）；2·76 m(2H，CH2N); 2·55 m(4H，六氫吡畊）；1.5 9 s(6H，CH3)。15 (:) 4- [4,4-dimethyl-5-oxo-3- [2- (hexahydropyrine-1-yl) ethyl] -2-thiooximidazoline-1 -yl] A compound made of 553 mg of 2- (trifluoromethyl) benzonitrile 15b was stirred with 809 µl of trifluoroacrylic acid in 10 ml of dichloromethane at room temperature for 24 hours. The reaction mixture was concentrated by evaporation in vacuo and concentrated by evaporation in toluene several times in vacuo, dissolved in methanol, set to a pH of 8 to 9 using an anion exchanger (Bio-Rad AG 1-X8, 0Η), filtered and Concentrate by evaporation in vacuo. 426 mg of the title compound was obtained as a crude product, which was further reacted in this form. ^ -NMR (300 MHz, CDC13): 5 [ppm] = 7.95 d (J = 8 Hz, 1H, aryl); 7.89 (1 (> 2 1 ^, 111, aryl); 7.77 (1 this 1 : 卩 = 8 1 ^ + 2 1 ^, 111, aryl); 3.85 m (2H, CH2N); 2.91 m (4H, hexahydropyridine); 2.76 m (2H, CH2N); 2.55 m (4H, hexahydropyridine); 1.5 9 s (6H, CH3).

15d) 4-[3-[2-[4(2-甲氧基苯甲酿基）六氫p比。井-1-基]乙基 ]-4,4-二甲基-5-氧代-2-石危氧咪唆淋-1-基]-2-(三氟甲 基）苯甲腈 20毫克15c製成的化合物係與14毫升2-甲氧基苯甲醯氯 及13.1微升三乙胺於1毫升四氫呋喃内回流4小時。反應混 合物在真空中藉蒸發濃縮。用己烷/醋酸乙酯構成的混合 物在石夕膠上實施柱式層析術以得1 6毫克無色油的標題化 合物。 H-NMR (300 MHz, CDC13)： 5 [ppm] = 7.95 d(J = 8 Hz，1H，芳 -66, 20030111715d) 4- [3- [2- [4 (2-methoxybenzyl) hexahydro p ratio. Well-1-yl] ethyl] -4,4-dimethyl-5-oxo-2-stone oxamidol-1-yl] -2- (trifluoromethyl) benzonitrile 20 mg The compound made in 15c was refluxed with 14 ml of 2-methoxybenzidine chloride and 13.1 µl of triethylamine in 1 ml of tetrahydrofuran for 4 hours. The reaction mixture was concentrated in vacuo by evaporation. Column chromatography was performed on a syrup with a hexane / ethyl acetate mixture to obtain 16 mg of the title compound as a colorless oil. H-NMR (300 MHz, CDC13): 5 [ppm] = 7.95 d (J = 8 Hz, 1H, Fang -66, 200301117

(61) 基）；7.88〇1卩=2 1^，1：»，芳基）；7.76(1(11^(>1=8 1^ + 2 112，1只，芳基）; 7·35 ddd(J = 8 Hz+7 Hz+2 Hz，1H，芳基）；7.23 dd(J=7 Hz + 2 Hz，1H， 芳基）；6.99 dd(J=7 Hz+7 Hz，1H，芳基）；6.91 dbr (J=8 Hz，1H，芳 基）；3.85 m(2H，CH2N); 3.84 m(lH，六氫吡畊）；3·83 s(3H，〇CH3); 3.81m(lH，六氫吡畊）；3.28m(2H，六氫吡畊）；2.80m(2H，CH2N); 2.67 m(lH，六氫吡畊）；2.60 m(lH，六氫吡畊）；2.55 m(lH，六氫 吡畊）；2.47 m(lH，六氫吡畊）；1.5 9 s(6H, CH3)。(61) group); 7.88〇1 卩 = 2 1 ^, 1: », aryl); 7.76 (1 (11 ^ (> 1 = 8 1 ^ + 2 112, 1 only, aryl); 7. · 35 ddd (J = 8 Hz + 7 Hz + 2 Hz, 1H, aryl); 7.23 dd (J = 7 Hz + 2 Hz, 1H, aryl); 6.99 dd (J = 7 Hz + 7 Hz, 1H, Aryl); 6.91 dbr (J = 8 Hz, 1H, aryl); 3.85 m (2H, CH2N); 3.84 m (lH, hexahydropyridine); 3.83 s (3H, 0CH3); 3.81m (lH, hexahydropyridine); 3.28m (2H, hexahydropyridine); 2.80m (2H, CH2N); 2.67m (lH, hexahydropyridine); 2.60m (lH, hexahydropyridine); 2.55 m (lH, hexahydropyridine); 2.47 m (lH, hexahydropyridine); 1.5 9 s (6H, CH3).

以類似於前述化合物方式製造下列根據本發明的化合 物。The following compounds according to the present invention were produced in a similar manner to the aforementioned compounds.

-67- (62) 20030111? 誦 表5.根據本發明通式w化合物，其中v=三氟甲基苯甲腈 τ稀·亞胺， 實例 名稱 類似於 實例合成 ESI-MS 16 4-[3-[(4二乙醯基π氫吡畊小基）甲基]-2，^二氫斗甲基 -2,5-二氧代-1Η-峨哈小基]_2-(二氟甲基)苯甲腈 8 420 17 4-[2,5-一氫-3-[[4-( f氧基乙醯基）六氫吡畊小基]甲 基]甲基-2,5-二氧代-11^吡哈小基]_2-(三氟甲基)苯 甲猜 8 450 18 4 - [2>一氫-3-[4-[[(2-甲氧基乙氧基)_乙醯基]六氫吡畊 -1-基]甲基]-4-甲基-2,5-二氧代-1H-吡嘻小基]_2-(二氟 甲基)苯甲腈 8 494 19 二氫-3·[[4-[[2-(2-甲氧基乙氧基乙氧基]乙醯 基]六氫吨呼-1·基]甲基]冰甲基-2,5_二氧代各小 基]_2_(三氟甲基)苯甲腈 8 538 20 4-[2,5-二氫各[[4-(2-甲氧基苯甲醯基)_六氫吡畊小基] 甲基]冰甲基-2,5-二氧代-1Η-吡咯-1-基]_2_(三氟甲基) 苯甲腈 8 512 21 4-[2,5~二氫_3_甲基冰[[4-(甲基磺醯基)·六氯口比味小基] 甲基]-2,5_二氧代-ΙΗ-说略-1-基]_2_(二氟甲基)苯甲腈 8 456 22 4-〇[[4-(乙基磺醯基)六氫咖井小基]甲基]_2，^二氫·‘ 甲基二2士二氧代-1Η-♦各-1-基]-2-(三氟甲基)苯甲腈 8 470 23 4-[2,5-二氫_3_[[4-(2-甲氧基乙基)續醯基]-六氫吡_小 基]甲基Μ-甲基-2,5_二氧代-11^比ρ各-1-基]_2_(三氟甲 基)苯甲腈 8 500 24 4-[2十二氫-H[4-[[2-[2-(2-甲氧基乙氧基）乙氧基]·乙 基]磺醯基]-六氫吡畊小基]甲基]1甲基-2,5_二氧代 -1H-吡洛小基]冬(三氟甲基)苯甲腈 8 588 25 4-[2,5-二氫-3-甲基-2,5-二氧代冰[[4-(苯基磺醯基)六氫 吡畊-1-拳]甲基]-1H-吡咯小基]-2-(三氟甲基)苯甲腈 8 518 -68 - (63) 表6.根據本發明通式i的化合物，其中v=三氟甲基苯甲腈 ，馬來亞胺， 實例 名稱 26 4-[3-[2-(4-乙醯基六氫吡畊小基)乙基]-2,5-二氯-4-甲基 ：^，5-二氧代-1H-♦各小基]-2-(三氣甲某)茉甲賠 類似於 實例合成 7⑷-67- (62) 20030111? Table 5. Compounds of general formula w according to the present invention, where v = trifluoromethylbenzonitrile τ · imine, Example name is similar to Example Synthesis ESI-MS 16 4- [3 -[(4-Diethylfluorenyl π hydropyridine small group) methyl] -2, ^ dihydromethyl-2,5-dioxo-1fluorene-ehaha small group] _2- (difluoromethyl ) Benzonitrile 8 420 17 4- [2,5-monohydro-3-[[4- (foxyethylamidino) hexahydropyridyl] methyl] methyl-2,5-dioxy -11-pyridyl] -2- (trifluoromethyl) benzyl 8 450 18 4-[2> Monohydro-3- [4-[[(2-methoxyethoxy) _ethyl Fluorenyl] hexahydropyridin-1-yl] methyl] -4-methyl-2,5-dioxo-1H-pyridyl] _2- (difluoromethyl) benzonitrile 8 494 19 Dihydro-3 · [[4-[[2- (2-methoxyethoxyethoxy] ethenyl] hexahydrotoxyl-1 · yl] methyl] icemethyl-2,5_ Dioxo each small group] _2_ (trifluoromethyl) benzonitrile 8 538 20 4- [2,5-dihydro each [[4- (2-methoxybenzyl)) _ hexahydropyracine Small group] methyl] methylmethyl-2,5-dioxo-1 代 -pyrrole-1-yl] _2_ (trifluoromethyl) benzonitrile 8 512 21 4- [2,5 ~ dihydro_3 _Methyl ice [[4- (methylsulfonyl) · hexachloropyridine] Methyl] -2,5_dioxy代 -ΙΗ- 说 略 -1-yl] _2_ (difluoromethyl) benzonitrile 8 456 22 4-〇 [[4- (ethylsulfonyl) hexahydrocalyxyl] methyl] _2, ^ Dihydro · 'methyldi-2-dioxo-1Η- ♦ each-1-yl] -2- (trifluoromethyl) benzonitrile 8 470 23 4- [2,5-dihydro_3_ [ [4- (2-Methoxyethyl) continyl] -hexahydropyridyl] methyl M-methyl-2,5_dioxo-11 ^ ratio ρ each-1-yl] _2_ (Trifluoromethyl) benzonitrile 8 500 24 4- [2Dodecane-H [4-[[2- [2- (2-methoxyethoxy) ethoxy] · ethyl] sulfonate Fluorenyl] -hexahydropyridine] methyl] 1methyl-2,5-dioxo-1H-pyrrolyl] winter (trifluoromethyl) benzonitrile 8 588 25 4- [2 , 5-Dihydro-3-methyl-2,5-dioxo [[4- (phenylsulfonyl) hexahydropyroxy-1-punch] methyl] -1H-pyrrole small group]- 2- (trifluoromethyl) benzonitrile 8 518 -68-(63) Table 6. Compounds of general formula i according to the invention, where v = trifluoromethylbenzonitrile, maleimine, example name 26 4- [3- [2- (4-Ethylhexylpyridinyl) ethyl] -2,5-dichloro-4-methyl: ^, 5-dioxo-1H- ♦ each Base) -2- (Three Qijia Mo) Mojak is similar to the example synthesis 7⑷

ESI-MS 434 27 28 Τ[2,5-_τ^73-甲基_2,5_二氧^(氧代丙基)六氫 乙基Η Η-吡‘1-基l·2·(三氟甲基)苯甲腈 7⑷ 448 29 1[3-[2-[4·(環丙基談基)六氫<十1·基]乙基]·2,5-二氫 土工^，5-二氧代-1Η-♦各-1-基]-2-(三氟甲某)苽甲賠 4H二备田备波/寬六甘、、发.，α — 7⑷ 460 4-[2,5-二氫-3-[2-[4-(甲氧基乙醯基)六氫吡畊基]乙 基]甲基-2,5-二氧代-111-♦各小基]1(三氟甲基)苯 甲猜 7(4) 464 30 4-[2>二氫-H2-[4-(3_甲氧基-1-氧代丙基六氫吡畊 -1-基]乙基]-4-甲基-2,5-二氧代-1如比p各小基1-2-(三顧 甲基)苯甲腈 7⑷ 478 31 7⑷ 508 4-[2,5-二氫-3-〇[4-(2-甲氧基乙氧基)乙醯基]六氫吡畊 -1-基]乙基H-甲基-2,5-二氧代-1H-♦各-1-基n(三i 甲基)苯甲腈ESI-MS 434 27 28 Τ [2,5-_τ ^ 73-methyl_2,5_dioxo (oxopropyl) hexahydroethylfluorene Η-pyridine'1-yl l · 2 · (tri Fluoromethyl) benzonitrile 7⑷ 448 29 1 [3- [2- [4 · (Cyclopropylyl) hexahydro < 10-yl] ethyl] · 2,5-dihydrogeo ^ 5 -Dioxo-1Η- ♦ Each-1-yl] -2- (trifluoromethyl) 苽 甲 H4H Er Bei Tian Bei Bo / Kuan Liu Gan, 发., Α — 7⑷ 460 4- [2,5- Dihydro-3- [2- [4- (methoxyethylfluorenyl) hexahydropyridyl] ethyl] methyl-2,5-dioxo-111- ♦ each small group] 1 (trifluoro (Methyl) benzyl 7 (4) 464 30 4- [2 > Dihydro-H2- [4- (3-methoxy-1-oxopropylhexahydropyridine-1-yl] ethyl] 4-methyl-2,5-dioxo-1 such as 1- (tris (methyl) benzo) benzonitrile of each smaller group than p 7⑷ 478 31 7⑷ 508 4- [2,5-dihydro-3- 〇 [4- (2-methoxyethoxy) ethenyl] hexahydropyridin-1-yl] ethyl H-methyl-2,5-dioxo-1H- ♦ each-1-yl n (triimethyl) benzonitrile

4-[2,5-二氫-3-甲基-4-[2-〇( 六 μ 乙基]_2,5-二氧代-111-吡哈-1-基]氟甲基)苯甲 腈 35 4-[3-[2-[4-(乙基橫醯基)六負乙基]_2,5_二^ 土f基-2,5-二氧代-1Η-♦各二 1-基]-2-(三氣甲基)苯甲腈 ^ JL .,~ -:----— 36 37 4-[3-[2-〇(環丙基磺醯基基]乙基]_2,5:二 甲基-2,5-二氧代-1Η-吡嘻-1-基]_2·(三氟甲基)苯甲 月耷_ 4:[2,5-二氫-Η2-[4-(2-甲氧 470 484 496 基]乙基]冬甲基_2,5-二氧代-11^比咯-1-基]_2-(:顧甲 基)苯甲腈4- [2,5-dihydro-3-methyl-4- [2-〇 (hexaμethyl) _2,5-dioxo-111-pyrha-1-yl] fluoromethyl) benzyl Nitrile 35 4- [3- [2- [4- (Ethylhexyl) hexaminylethyl] _2,5_di ^ earth fyl-2,5-dioxo-1Η- ♦ each di 1- Phenyl] -2- (trifluoromethyl) benzonitrile ^ JL., ~-: ----- 36 37 4- [3- [2-〇 (cyclopropylsulfonyl) ethyl) _2 , 5: dimethyl-2,5-dioxo-1Η-pyridine-1-yl] _2 (trifluoromethyl) benzidine 耷 4: [2,5-dihydro-Η2- [ 4- (2-Methoxy 470 484 496 group) ethyl] winter methyl_2,5-dioxo-11 ^ pyrrol-1-yl] _2-(: Gumethyl) benzonitrile

-69- (64)2g^3〇1117 實例 名稱 40 41 基]六氫吡畊小基]乙基]冰甲基-2,5-二氧代-1H-吡咯-1- 產氟甲基)苯甲腈 __ 4_[2,5-二氫-H2-[4-[[2_l>(2-甲氧基乙氧基)-乙氧基]乙 基]磺醯基]六氫吡畊-1-基]乙基]-4-甲基-2,5-二氧代 小基]-2_(三氟甲基)苯甲腈__ 4-[2,5·*—氣冬甲基-2,5-二氧代-4-[2·[4-(苯基橫S盛基)六 全比畊-1-基]乙基]-1H-吡洛-1 -基]-2-(三氟甲基)苯甲腈 4-[2,5-二氫各甲基-2,5-二氧代-4-[2-[4-[(苯基甲基)磺 醯基]六氫吡畊-1-基]乙基]-1H-吡咯小基]-2-(三氟甲 基)苯甲腈 4-[2,5-一風-3-甲基-4-[2-[4-[(l-甲基-1H-咪+4-基)石黃醯 基]六氫吡畊小基]乙基]-2,5-二氧代-1H-吡咯小 基]_2_(三氟甲基)苯曱腊 類似於 成-69- (64) 2g ^ 3〇1117 Example name 40 41 group] Hexahydropyridine small group] Ethyl] Icemethyl-2,5-dioxo-1H-pyrrole-1-fluoromethyl) Benzonitrile__ 4_ [2,5-dihydro-H2- [4-[[2_l > (2-methoxyethoxy) -ethoxy] ethyl] sulfonyl] hexahydropyridine- 1-yl] ethyl] -4-methyl-2,5-dioxo small group] -2_ (trifluoromethyl) benzonitrile__ 4- [2,5 · * —asparagine methyl- 2,5-dioxo-4- [2 · [4- (phenyl transverse S-Shengyl) hexalobiene-1-yl] ethyl] -1H-pyrro-1-yl] -2- ( Trifluoromethyl) benzonitrile 4- [2,5-dihydro each methyl-2,5-dioxo-4- [2- [4-[(phenylmethyl) sulfonamido] hexahydro Pyrogen-1-yl] ethyl] -1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4- [2,5-monowind-3-methyl-4- [2- [ 4-[(l-methyl-1H-imid + 4-yl) luteinyl] hexahydropyridine] ethyl] -2,5-dioxo-1H-pyrrole small] _2_ (trifluoromethyl Base) Benzowax is similar to

ESI-MS 602 532 546 536 43 4-[2·[1-[4-氰基-3-(三轨甲基）苯基]-2,5-二氫-4-甲基 _2,5-二氧代-1H-口比洛各基]乙基]甲基乙基)六氫 吡畊-1-羧醯胺 7(6) 477 44 4-[2-[1^4-[基-3-( 1"氟 T 基）苯基]-2,5- -2,5-二氧代-1H-♦各-3-基]乙基]善乙基六氫吡畊小碳 硫代醯胺 7(12) 45 46 4-〇[l-[4-氰基各(三氟甲基）苯基]_2,5_二氫冰甲基 :2,5-二氧代-11^·峨咯各基]乙基]六氫吡畊一·羟酸甲酯 4-[2_[H4-氰基各(三氟甲基）苯基]_2,5-二氫冰甲基 •2,5_一氧代-1H-P比嘻各基]乙基]六氫p比畊七碳硫酸s_ 甲酯 7(13) 7(13) 479ESI-MS 602 532 546 536 43 4- [2 · [1- [4-cyano-3- (tri-rail methyl) phenyl] -2,5-dihydro-4-methyl_2,5- Dioxo-1H-orbiloxyl] ethyl] methylethyl) hexahydropyridine-1-carboxamide 7 (6) 477 44 4- [2- [1 ^ 4- [yl-3 -(1 " fluoroT-based) phenyl] -2,5- -2,5-dioxo-1H- ♦ each-3-yl] ethyl] shenylhexahydropyridine 7 (12) 45 46 4-〇 [l- [4-cyano (trifluoromethyl) phenyl] _2,5-dihydroglacial methyl: 2,5-dioxo-11 ^ · erro Each group] ethyl] hexahydropyridine methyl ester 4- [2_ [H4-cyano (trifluoromethyl) phenyl] _2,5-dihydroglacial methyl • 2,5_a Oxo-1H-P ratio of Heptyl] ethyl] hexahydro p ratio phenyl heptacarbon sulfate s_ methyl ester 7 (13) 7 (13) 479

47 4一[2_[1_[4_氰基各(三氟甲基）苯基]_2,5_二氫冰甲基 -2,5-二氧代-1仏峨咯冬基]乙基]Ν，Ν_二甲基六氫吡$ -1-磺醯胺 499 -70- (65) 200301117 9 表7.根據本發明通式〗的化合物’其中^三氟甲基苯甲赌 ，W=馬來亞胺，η = 3 貧例 名稱 類似於 貫例合成 ESI-MS 48 4 [3 [3 (4乙驗基/、風^比基)丙基]_2,5_二氫外_甲基 -2,5_二氧代-111-♦各小基]_2-(二氟甲基)苯甲腈 ‘7(4) 448 49 4」2 5氫一氧代叫3,仆氧代丙基)六 A吡口井小基)丙基)-1H-♦各小基从（：氟甲基)苯甲腈 7(4) 462 50 4 [3 [3 [4 (環丙基致基)六氩^；比啩基]丙基] :]氟 4 苯= 7(4) 474 51 4〇—氫-ΗΗ4-(甲氧基乙醯基)六氫吡畊小基]丙 基]·4_甲基-2,5-二氧代仙-吡咯小基]·2_(三氟甲基)苯 甲腈 7(4) 478 52 4-[2,5_二氫-3-[3-[4-(3-甲氧基-1-氧代丙基)-六氫吡畊 小基]丙基Η-甲基_2,5_二氧代-1Η_♦各小基二翁 甲基)苯甲腈 7⑷ 492 53 4 [2>一氫甲氧基乙氧基)乙醯基]六氫吡啡 -1-基]丙基]-4·甲基-2,5_二氧代_1Η-Ρ比ρ各小基]_2_(二氣 甲基)苯甲腈 — 7(4) 522 54 4-[2,5-一氫各[3-[4-[[2_(2·甲氧基乙氧基）乙醯基]六氫 峨畊-1-基]丙基]冰甲基_2,5·二氧代-1Η-吡咯 基]-2-(三氟甲基)苯甲腈 7(4) 566 55 4-[2,5-一氫-3-[3-[4-(2-甲氧基苯甲醯基> 六氫吡畊_^ 基]丙基]斗甲基二氧代-11^比咯小基]冬(三敦甲 基)苯甲腈 7(4) 540 56 4-[2,5-一氫-j-甲基-4_|>[4-(甲基磺醯基)_六氫吡畊小 基]丙基]-2,5_二氧代-1心比ρ各-1-基]_2_(三氟甲基)苯甲 腈 7 484 57 4-〇|>[4-(乙基磺醯基)六氫吡畊_1_基]丙基]j，5二氫 -4-甲基_2,5_二氧代-1Η-♦各-1-基]_2-(三氟甲基)苯甲腈 7 498 58 4-[3-[3-[4-(環丙基橫臨基)六氫ρ比呼小基]丙基]·2,5_二 氫冰甲基_2,5_二氧代-lH-p比ρ各-1-基]·2_(三氟甲基)苯甲 腈 7 510 59 4-[2,5-二氫-3-[3-[4-(2-甲氧基乙基)確酿基]六氫ρ比十ι_ 基]丙基]冰甲基-2,5·二氧代_1Η-ρ比哈-1-基]-2-(三氟甲 基)苯甲腈 7 528 60 4-[2,5-二氫-3-[3-[4-[[2-(2-(甲氧基乙氧基)_乙基)續酿 7 572 -71 - 200301117 (66) 實例 名稱 類似於 實例合成 ESI-MS 基氫吡_小基]丙基]-4-甲基-2,5_二氧代-1H4咯-1-基]_2_(三氟甲基)苯甲腈 61 4-[2,5-二氫-3-[3-[4-[[2-[2-(2-甲氧基乙氧基)-乙氧基]乙 基]磺醯基]六氫吡_小基]丙基]斗甲基-2,5-二氧代 -1H-吡咯-1·基ι_2_(三氟甲基)苯甲腈 7 616 62 4_[2,5-二氫各甲基_2,5-二氧代冰〇[4-(苯基磺醯基)六 氫吡畊-1-基1丙基HH-吡咯-1-基]-2-(二氟甲基)苯甲腈 7 546 63 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[3-[4-[(苯基甲基)磺 醯基]六氫吡畊-1-基]丙基]-1H-吡p各小基]-2-(三氟甲 基)苯甲腈 7 560 64 4-[2,5-一氣-3-甲基-4-[3-[4-[(l-甲基-1H-味吐-4-基)石黃酿 基]六氫吡畊小基]丙基]-2,5-二氧代-1H-吡咯小 基]-2_(三氟甲基)苯甲腈 7 550 65 4-[3-[1-[4-氰基：(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]丙基]-N-(l-甲基乙基)六氫 吡畊-1-羧醯胺 7(6) 491 66 4-|>[H4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-*7比p各-3-基]丙基]-N-乙基7^氮p比呼-1-碳 硫代醯胺 7(12) 493 67 4-[3-[H4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-ρ比咯-3-基]丙基]六氫?比畊-1-叛酸甲酯 7(13) 464 68 4-[3-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯各基]丙基]六氫吡畊-1-碳硫酸S-甲酯 7(13) 480 69 4-[3-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-lH-p比洛各基]丙基]-Ν，Ν-二甲基六氫p比畊 -1-磺醯胺 7 513 -72- (67) 表8.根據本發明通式w化合物，其中v<氟甲基苯甲赌 ，馬來亞月安，n=4 賞例 名稱 類似於 實例合成 ESI-MS 70 4-[4-[1-[4-氰基各(三氟甲 代孤翁冬基]_ 丁基]六氫㈣叛U_二 1 521 71 '[‘:5 "~a·氫m4_[4_[4_[2_(甲基硫垸基)_苯基]六氫 丁基]_2,5-二氧代-1H_吡咯小基]-2-(三氟甲 3 543 72 4-[3-[4-[4-(3> 一氯?比咬_4_基）六氫吡畊_丨_基]丁 3 566 73 4 [3 [4 [4'%戊基乙g盈基)π氫p比啩小基]丁基]_2 5 一 氫冰甲基-2,5-二氧代-1Η-吡略小基]-2-(三氟甲基)苯^ 腈 4 531 74 H -[ -[4_(2,6- 一敦丰甲酸基）六氫p比_小基]丁 基]-2,5-一氫-4-甲基-2,5-二氧代-出-咖各-1-基1-2-(二顧 甲基)苯甲腈 4 561 75 4 [3 [4-[4-(2,6- 一氯本甲酿基）六氫p比vr井小基]丁 基]-2,5-二氫-4-甲基-2,5-二氧代-1如比洛小基1_2-(二藏 甲基)苯甲腈 4 593 76 4-[3-[4-[4-(3-氟苯甲醯基)六氫吡畊小基]丁基]·2 5-一 氫冰甲基-2>二氧代-1Η-咖各小基]-2_(三氟甲基)苯甲 腈 4 543 77 4-[2,5-一氫-3-[4-〇(3-甲氧基苯甲醯基)六氫叶卜井小基] 丁基H-甲基-2,5-二氧代-1知比p各小基]_2_(三氟甲基） 苯甲腈 4 555 78 4-[2,5-一氫-3-甲基-4-[4-[4-(3-甲基苯甲醯基)_六氫吡畊 -1-基]丁基]_2,5·二氧代-1H-咖各-1-基]—2-(三乳甲基)苯 甲腈 4 539 79 4_ [3 - [4_ [4_(4_氟苯甲驢基)六氫峨VT井-基]丁基]_2,5_二 氧代-1H-♦各-1-基]-2-(三氟甲基)苯甲腈 ’ 4 543 80 4-[2,5-一氫各甲基-4-[4-[4-[(各-1-基)-幾基]六氫p比P井 -1-基]丁基]-2,5-二氧代·1Η·ρ比洛小基]-2-(三乳甲基)苯 甲腈 4 575 81 ‘ 4-[2,5-二氫-3-甲基-4-[4-[4-[(莕-2-基)-羰基]六氫p比畊 4 575 -73- 20030111? (68) 實例 名稱 類似於 實例合成 ESI-MS 小基]丁基]-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯 甲腈 82 4-[3-[4-[4-(3-氰基苯甲醯基)六氫吡畊-1-基]丁基]-2,5-二氮-4-甲基-2,5-二氧代-lH-p比洛-1-基]-2-(二氣甲基)豕 甲腈 4 550 83 4-[3-[4-[4-(環己基羰基)六氫吡畊-1-基]丁基]-2,5-二氫 -4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基)苯甲腈 4 531 84 4-〇[4-[4-(呋喃-2-基)羰基]六氫吡畊-1-基]丁基]_2,5-二 氫斗甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基)苯甲 腈 4 515 85 4-[3-[4-[4-(環戊基羰基)六氫吡畊-1-基]丁基]-2,5-二氫 -4-甲基-2,5-二氧代-1Η-吡咯-1 -基]-2-(三氟甲基)苯甲腈 4 517 86 4-[2,5-二氫-3-甲基斗[4-[4-[(5-甲基異呤唑-3-基)羰基] 六氫吡畊-1-基]丁基]-2,5-二氧代-1Η-吡咯小基]-2-(三 氟甲基)苯甲腈 4 530 87 4-[2,5-二氯-3-甲基-2,5-二氧代-4-[4-[4-(本基-乙醒基) 六氫吡畊小基]丁基ΗΗ-吡咯-1-基]-2-(三氟甲基)苯甲 腈 4 539 88 4-[2,5-二氫：[4-[4-(2-甲氧基苯甲醯基)六氫吡畊-1-基] 丁基]斗甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基) 苯甲腈 4 555 89 4-[2,5-二鼠-3-[4-[4-(甲氧基乙酿基）：7^鼠口比1?井-1-基]丁 基]-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基)苯 甲腈 4 492 90 4-[3-[4-[4-(2-氯苯甲醯基)六氫吡畊-1-基]丁基]-2,5-二 氫斗甲基-2,5-二氧代-1Η-吡咯小基]-2-(三氟甲基)苯甲 腈 4 559 91 4-|>[4·[4-(2-氟苯甲醯基)六氫吡畊小基]丁基]-2,5-二 氫-4-甲基-2,5-二氧代-1Η-吡咯小基]-2-(三氟甲基)苯甲 腈 4 543 92 4-[3-[4-(4-苯甲醯基六氫吡畊-1-基)丁基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯小基]_2_(三氟甲基)苯甲腈 4 525 93 4-[3-[4-[4-(環丁基羰基)六氫吡畊-1-基]丁基]-2,5-二氫 斗甲基_2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基)苯甲腈 4 503 94 4-[2,5-二氫各甲基-2,5-二氧代-4-[4-[4-[(吡啶-3-基)羰 基]六氫吡啩-1-基]丁基]-1Η-吡咯-1-基]-2-(三氟甲基) 4 526 -74- (69) (69)20030111? 實例 名稱 類似於 實例合成 ESI-MS 苯甲腈 _ 95 4_[2,5_二氫各甲基_2,5_二氧代冬[4-[4-[(吡啶冰基)羰 基]厂氫P比吩-1-基]丁基]小基]-2-(三氟甲基) 苯甲腈 4 526 96 4-[3-[4-[4-[4-(二甲基胺基)苯甲醯基]六氫吡畊小基]丁 基]-2,5-一氣-4-甲基-2,5-二氧代-lH-p比嘻-1-基]-2-(二氣 甲基)苯甲腈 4 568 97 4_[2,5·—氫甲基_2,5_二氧代-4_[4-[4-[(苯基-硫燒基) 乙醯基]六氫吡畊-1-基]丁基]-1H-吡咯小基]·2_(三氟甲 基)苯甲腈 4 571 98 4_[2,5_ 一氫-3-甲基-2,5-二氧代-4-[4-[4-(苯氧基-乙酉盛 基)六氫吡畊-1-基]丁基]-1Η-吡咯小基]-2-(三氟甲基) 苯甲腈 4 555 99 冬[2,5-—氫甲基 _2,5_ 二氧代-4-[4-[4_[(4-2-基)-羰基] 六氫说畊小基]丁基]-1Η-吡咯-1-基]冬(三氟甲基)苯甲 腈 4 531 100 4-[2,5-一氫~3_甲基-2,5-二氧代-4-[4-[4-(3-苯基小氧代 丙基）六氫吡畊-1-基]丁基]-1Η-吡咯-1-基]-2-(三氟甲 基)苯甲腈 4 553 101 4-[Η4·[4-[(1，3-苯并二呤茂各基)羰基六氫吡畊小基] 丁基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-♦各小基]-2-(三 氟甲基)苯甲腈 一 4 569 102 4-[2,5-二氫各[4-[4-[(4-甲氧基苯基）乙醯基]六氫;^ -1-基]丁基Μ-甲基-2,5-二氧代-lH^比嘻小基]-2-(二氟 甲基)苯甲腈 一 4 569 103 4-[2,5-一氫-3-甲基-4-[4-[4-(2-甲基苯甲醯基 > 六氫吡畊 小基]丁基]-2,5-二氧代-lH-p比嘻小基]_2-(三氟甲基)苯 甲腈 4 539 104 4- [3 - [4- [4-(4-鼠豕甲醯基卜、氫p比p井· 1-基]丁基]，5-二 氫冰甲基-2,5-二氧代-收♦各-1-基]-2_(三氟甲基)苯甲 腈 4 559 105 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[4-[4-[〇 塞-2-基)-乙醯 基]六氫叶卜井小基]丁基]-1Η-ρ比洛小基]冬(三氟甲基） 苯甲腈 一 ^ 4 545 106 4-[3-[4-[4-(3·氯苯甲酿基）六氫P比p井小基]丁基]_2,5·二 氫-4-甲基-2,5-二氧代-1H-吡洛小基]_2-(三氟甲基)菜甲 4 559 -75- 20030111747 4- [2_ [1_ [4_cyano (trifluoromethyl) phenyl] _2,5_dihydroicemethyl-2,5-dioxo-1pyrrolidyl] ethyl] Ν, Ν_dimethylhexahydropyridine-1-sulfonamide 499 -70- (65) 200301117 9 Table 7. Compounds according to the general formula of the present invention 'wherein trifluoromethyl benzyl, W = Maleimine, η = 3 The name of the rare case is similar to the conventional synthesis of ESI-MS 48 4 [3 [3 (4 ethylenyl /, hydrazyl) propyl] _2,5_dihydroexo_methyl -2,5_dioxo-111- ♦ each small group) _2- (difluoromethyl) benzonitrile '7 (4) 448 49 4' '2 5Hydroxy-oxo is called 3, and oxopropyl ) Hexyl A pyridoletyl) propyl) -1H- ♦ Each small group is from (: fluoromethyl) benzonitrile 7 (4) 462 50 4 [3 [3 [4 (cyclopropylyl) hexa Argon ^; pyridyl] propyl]:] fluoro 4 benzene = 7 (4) 474 51 4 0-hydro-pyridine 4- (methoxyethyridyl) hexahydropyridine] propyl] · 4_ Methyl-2,5-dioxo-pyrrole small group] · 2- (trifluoromethyl) benzonitrile 7 (4) 478 52 4- [2,5_dihydro-3- [3- [4 -(3-methoxy-1-oxopropyl) -hexahydropyridine] propylpropyl-methyl-2,5_dioxo-1 代 _ ♦ each small dioxomethyl) benzonitrile 7⑷ 492 53 4 [2 > Monohydromethoxyethoxy ) Ethylfluorenyl] hexahydropyridin-1-yl] propyl] -4 · methyl-2,5_dioxo_1Η-P ratio ρ each small group] _2_ (digasmethyl) benzonitrile — 7 (4) 522 54 4- [2,5-monohydrogen each [3- [4-[[2_ (2 · methoxyethoxy) ethenyl] hexahydroghen-1-yl] propyl Yl] Icemethyl_2,5 · dioxo-1Η-pyrrolyl] -2- (trifluoromethyl) benzonitrile 7 (4) 566 55 4- [2,5-monohydro-3- [ 3- [4- (2-methoxybenzyl) > hexahydropyridyl- ^ yl] propyl] pyridyldioxo-11 ^ pyrrolyl] dong (trimethyl) benzene Nitrile 7 (4) 540 56 4- [2,5-monohydro-j-methyl-4_ | > [4- (methylsulfonyl) _hexahydropyridine] propyl] -2 , 5-dioxo-1 heart ratio ρ each-1-yl] _2_ (trifluoromethyl) benzonitrile 7 484 57 4-〇 | > [4- (ethylsulfonyl) hexahydropyridine _1_yl] propyl] j, 5dihydro-4-methyl_2,5_dioxo-1Η- ♦ each-1-yl] _2- (trifluoromethyl) benzonitrile 7 498 58 4- [3- [3- [4- (Cyclopropylhexyl) hexahydroρ than huphyl] propyl] · 2,5_dihydroicemethyl_2,5_dioxo-lH -p ratio ρ each-1-yl] · 2- (trifluoromethyl) benzonitrile 7 510 59 4- [2,5-dihydro-3- [3- [4- (2-methoxyethyl ) Bingji] Hexahydro ρ than Deca_yl] propyl] Icemethyl-2,5 · Di Oxo_1Η-ρ biha-1-yl] -2- (trifluoromethyl) benzonitrile 7 528 60 4- [2,5-dihydro-3- [3- [4-[[2- (2- (methoxyethoxy) _ethyl) Continued 7 572 -71-200301117 (66) Example name is similar to the example Synthesis of ESI-MS Hydroxypyridyl] propyl) -4-methyl -2,5_dioxo-1H4pyr-1-yl] _2_ (trifluoromethyl) benzonitrile 61 4- [2,5-dihydro-3- [3- [4-[[2- [ 2- (2-methoxyethoxy) -ethoxy] ethyl] sulfonyl] hexahydropyridyl] propyl] pyridyl-2,5-dioxo-1H-pyrrole- 1 · yl_2_ (trifluoromethyl) benzonitrile 7 616 62 4_ [2,5-dihydromethyl_2,5-dioxo-ice 〇 [4- (phenylsulfonyl) hexahydropyridine Phen-1-yl-1propylHH-pyrrole-1-yl] -2- (difluoromethyl) benzonitrile 7 546 63 4- [2,5-dihydro-3-methyl-2,5- Dioxo-4- [3- [4-[(phenylmethyl) sulfonamido] hexahydropyridin-1-yl] propyl] -1H-pyridyl each small group] -2- (trifluoro Methyl) benzonitrile 7 560 64 4- [2,5-Mono-3-methyl-4- [3- [4-[(l-methyl-1H-tomito-4-yl) Methyl] hexahydropyridine] propyl] -2,5-dioxo-1H-pyrrole small] -2_ (trifluoromethyl) benzonitrile 7 550 65 4- [3- [1- [ 4-cyano: (trifluoromethyl) phenyl] -2,5-dihydro-4- -2,5-dioxo-1H-pyrrole-3-yl] propyl] -N- (l-methylethyl) hexahydropyridine-1-carboxamide 7 (6) 491 66 4- | > [H4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H- * 7 ratio p each -3 -Yl] propyl] -N-ethyl 7 ^ nitrogen p than 1-carbo-1-carbothioamide 7 (12) 493 67 4- [3- [H4-cyano-3- (trifluoromethyl) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-r-pyrrol-3-yl] propyl] hexahydro? Phenyl-1-metanoic acid methyl ester 7 (13) 464 68 4- [3- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H -Pyrrolyl] propyl] hexahydropyrine-1-carbon sulfate S-methyl ester 7 (13) 480 69 4- [3- [1- [4-cyano-3- (trifluoromethyl) benzene Yl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-p-Bilgoyl] propyl] -N, N-dimethylhexahydropeptyl-1- Sulfamethoxamine 7 513 -72- (67) Table 8. Compounds of general formula w according to the present invention, where v < fluoromethylbenzyl, Malayalam, n = 4. MS 70 4- [4- [1- [4-cyano each (trifluoromethyl lone dongyl) _butyl] hexahydrobenzene U_Di 1 521 71 '[': 5 " ~ a · m4_ [4_ [4_ [2_ (methylthiofluorenyl) _ [Hexyl] hexahydrobutyl] _2,5-dioxo-1H_pyrrole small group] -2- (trifluoromethyl 3 543 72 4- [3- [4- [4- (3 > _4_yl) hexahydropyridine_ 丨 _yl] butan 3 566 73 4 [3 [4 [4 '% amyl ethyl g glycyl) π hydrogen p than fluorene small group] butyl] _2 5 monohydro ice Methyl-2,5-dioxo-1'-pyridyl] -2- (trifluoromethyl) benzene ^ nitrile 4 531 74 H-[-[4_ (2,6-Yidhonthoate) Hexahydro p-ratio_small group] butyl] -2,5-monohydro-4-methyl-2,5-dioxo-exo-cago-1-yl 1- 2- (dimethylol) benzyl Nitrile 4 561 75 4 [3 [4- [4- (2,6-Chloroformyl) hexahydro p ratio vr well small base] butyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1 such as bilo small group 1_2- (di Tibetan methyl) benzonitrile 4 593 76 4- [3- [4- [4- (3-fluorobenzylfluorenyl) hexahydro] Pycnogenol] butyl] · 2 5-monohydroglacial methyl-2 > dioxo-1Η-caffeine small group] -2_ (trifluoromethyl) benzonitrile 4 543 77 4- [2, 5-monohydro-3- [4-〇 (3-methoxybenzylidene) hexahydroyebullyl] butyl H-methyl-2,5-dioxo-1 Small group] _2_ (trifluoromethyl) benzonitrile 4 555 78 4- [2,5-monohydro-3-methyl-4- [4- [4- (3-methylbenzylfluorenyl) _ Hexahydropyrim-1-yl] butyl] _2,5 · Oxo-1H-caco-1-yl] -2- (trilactonemethyl) benzonitrile 4 539 79 4_ [3-[4_ [4_ (4_fluorobenzodonyl) hexahydrofluorene VT well- Yl] butyl] _2,5_dioxo-1H- ♦ each-1-yl] -2- (trifluoromethyl) benzonitrile '4 543 80 4- [2,5-monohydrogen each methyl -4- [4- [4-[(Each-1-yl) -kisyl] hexahydrop is smaller than P-1-1-yl] butyl] -2,5-dioxo · 1Η · ρbilo Yl] -2- (trimethylol) benzonitrile 4 575 81 '4- [2,5-dihydro-3-methyl-4- [4- [4-[(fluoren-2-yl)- (Carbonyl) hexahydropeptide 4 575 -73- 20030111? (68) Example name similar to the example ESI-MS Small group] Butyl] -2,5-dioxo-1H-pyrrole-1-yl]- 2- (trifluoromethyl) benzonitrile 82 4- [3- [4- [4- (3-cyanobenzyl) hexahydropyrine-1-yl] butyl] -2,5- Diazol-4-methyl-2,5-dioxo-lH-p bilo-1-yl] -2- (digasmethyl) fluoronitrile 4 550 83 4- [3- [4- [ 4- (cyclohexylcarbonyl) hexahydropyridin-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2 -(Trifluoromethyl) benzonitrile 4 531 84 4-〇 [4- [4- (furan-2-yl) carbonyl] hexahydropyridine-1-yl] butyl] _2,5-dihydro Methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzyl Nitrile 4 515 85 4- [3- [4- [4- (cyclopentylcarbonyl) hexahydropyridine-1-yl] butyl] -2,5-dihydro-4-methyl-2,5- Dioxo-1Η-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4 517 86 4- [2,5-dihydro-3-methylbucket [4- [4-[( 5-methylisopurazol-3-yl) carbonyl] hexahydropyrine-1-yl] butyl] -2,5-dioxo-1 ''-pyrrole small group] -2- (trifluoromethyl) Benzonitrile 4 530 87 4- [2,5-Dichloro-3-methyl-2,5-dioxo-4- [4- [4- (benzyl-ethenyl) hexahydropyridine Yl] butylphosphonium-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 539 88 4- [2,5-dihydro: [4- [4- (2-methoxybenzene (Methylfluorenyl) hexahydropyridine-1-yl] butyl] pyridyl-2,5-dioxo-1fluorenyl-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 555 89 4- [2,5-Dimur-3- [4- [4- (methoxyethynyl): 7 ^ rat mouth ratio 1? Well-1-yl] butyl] -4-methyl- 2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 492 90 4- [3- [4- [4- (2-chlorobenzylfluorenyl) ) Hydroxypyrine-1-yl] butyl] -2,5-dihydromethyl-2,5-dioxo-1Η-pyrrole small] -2- (trifluoromethyl) benzonitrile 4 559 91 4- | > [4 · [4- (2-Fluorobenzyl) hexahydropyridine] butyl] -2,5-dihydro-4-methyl -2,5-dioxo-1'-pyrrolepyridyl] -2- (trifluoromethyl) benzonitrile 4 543 92 4- [3- [4- (4-Benzylpyridinylhexahydropyridine- 1-yl) butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole small group] _2_ (trifluoromethyl) benzonitrile 4 525 93 4- [ 3- [4- [4- (Cyclobutylcarbonyl) hexahydropyridine-1-yl] butyl] -2,5-dihydromethyl-2,5-dioxo-1pyridine-1 -Yl] -2- (trifluoromethyl) benzonitrile 4 503 94 4- [2,5-dihydromethyl-2,5-dioxo-4- [4- [4-[(pyridine -3-yl) carbonyl] hexahydropyridin-1-yl] butyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) 4 526 -74- (69) (69) 20030111? The name of the example is similar to the example of synthesis of ESI-MS benzonitrile _ 95 4_ [2,5_dihydro each methyl_2,5_dioxodong [4- [4-[(pyridyl ice-based) carbonyl] plant hydrogen P than phen-1-yl] butyl] small group] -2- (trifluoromethyl) benzonitrile 4 526 96 4- [3- [4- [4- [4- (dimethylamino) Benzamidine] hexahydropyridine] butyl] -2,5-monogas-4-methyl-2,5-dioxo-lH-p Gas methyl) benzonitrile 4 568 97 4_ [2,5 · —Hydroxymethyl_2,5_dioxo-4_ [4- [4-[(phenyl-sulfanyl) ethenyl] hexan Pyridin-1-yl] butyl] -1H-pyrrole small group] · 2_ (Trifluoromethyl) benzonitrile 4 571 98 4_ [2,5_ Monohydro-3-methyl-2,5-dioxo-4- [4- [4- (phenoxy-acetamido) Hexahydropyridin-1-yl] butyl] -1Η-pyrrolepyryl] -2- (trifluoromethyl) benzonitrile 4 555 99 Winter [2,5-—hydromethyl_2,5_ dioxo 4--4- [4- [4 _ [(4-2-yl) -carbonyl] hexahydrocarbyl] butyl] -1Η-pyrrole-1-yl] dong (trifluoromethyl) benzonitrile 4 531 100 4- [2,5-monohydro ~ 3_methyl-2,5-dioxo-4- [4- [4- (3-phenyl small oxopropyl) hexahydropyrine-1 -Yl] butyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 553 101 4- [Η4 · [4-[(1,3-benzodiazepines each Carbonyl) hexahydropyridine] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 代-♦ each small group] -2- (trifluoromethyl) Benzonitrile 4 569 102 4- [2,5-dihydro each [4- [4-[(4-methoxyphenyl) ethylfluorenyl] hexahydro; ^-1-yl] butyl M- Methyl-2,5-dioxo-lH ^ pyridyl] -2- (difluoromethyl) benzonitrile-4 569 103 4- [2,5-monohydro-3-methyl-4 -[4- [4- (2-methylbenzylidene > hexahydropyridine small group) butyl] -2,5-dioxo-lH-p than hexyl small group] _2- (trifluoro (Methyl) benzonitrile 4 539 104 4- [3-[4- [4- (4-Morcine Hydrazine, hydrogen p ratio p-well · 1-yl] butyl], 5-dihydroglacial methyl-2,5-dioxo-received 1-1-yl] -2_ (trifluoromethyl) Benzonitrile 4 559 105 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [4- [4- [〇 塞 -2-yl) -ethenyl] Hexahydroyebujingi] butyl] -1Η-ρbiloxyl] winter (trifluoromethyl) benzonitrile ^ 4 545 106 4- [3- [4- [4- (3 · chloro Benzyl) hexahydro P than p well small group] butyl] _2,5 · dihydro-4-methyl-2,5-dioxo-1H-pyro small group] _2- (trifluoromethyl Base) Dish 4 4 559 -75- 200301117

(70) 實例 名稱 類似於 實例合成 ESI-MS 腈 107 4-[3-[4-[4-(4-氰基苯甲醯基）六氫吡畊-1-基]丁基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯 甲腈 4 550 108 4-[2,5-二氫-3-[4-[4-(3-甲氧基-1-氧代丙基)六氫吡畊小 基]丁基]斗甲基-2,5-二氧代-1H-吡咯小基]_2_(三氟甲 基)苯甲腈 4 506 109 4-[2,5-二氫-3-[4-[4-[(2-甲氧基乙氧基）乙醯基]六氫吡 畊小基]丁基]-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三 氟甲基)苯甲腈 4 536 110 4-[2,5-二氫-3-[4-[4-[〇(2-甲氧基乙氧基)-乙氧基]-乙驢 基]六氫吡畊-1-基]丁基]-4-甲基-2,5-二氧代-1H-吡咯小 基]-2-(三氟甲基)苯甲腈 4 580 111 4-[4-[4-[4-(環丙基磺醯基)六氫吡畊小基]丁基]-2,5-二 氫-3-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲 腈 5 524 112 4-[2,5-二氫-3-[4-[4-(2-甲氧基乙基)磺醯基]六氫吡畊小 基]丁基]斗甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲 基)苯甲腈 5 542 113 4-[2,5-二氫-3-[4-[4-[[2-(2-甲氧基乙氧基)乙基]-磺醯基] 六氫吡畊小基]丁基]-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯甲猜 5 586 114 4-[2,5-二氫各[4-[4-[[2-〇(2-甲氧基乙氧基)乙氧基]-乙 基]磺醯基]六氫吡畊小基]丁基M-甲基-2,5-二氧代 -1H-吡咯-1-基]-2-(三氟甲基)苯甲腈 5 630 115 4-[4-[1·[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]-丁基]N，N-二甲基六氫吡畊 -1-續酿胺 5 527 116 4-[2,5-二氫各甲基-2,5-二氧代-4-[4-[4-(苯基-磺醯基) 六氫吡畊小基]丁基]-1Η-吡咯小基]-2-(三氟甲基)苯甲 腈 5 561 117 4-[2,5-二氫-3-甲基-4-[4-[4-[4-(甲基磺醯基)-六氫吡畊 -1-基]丁基]-2,5-二氧代-lH-t7比p各-1-基]-2-(二氣甲基)苯 甲腈 5 499 118 4-[2,5-二氫各甲基-4-[4-[4-[(4-(甲基苯基)-磺醯基)六氫 吡4小基]丁基]-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲 5 575 -76- (71) 200301117 實例 名稱(70) Example name similar to Example Synthesis ESI-MS Nitrile 107 4- [3- [4- [4- [4- (4-cyanobenzyl) hexahydropyridine-1-yl] butyl] -2, 5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 550 108 4- [2,5-dihydro -3- [4- [4- (3-methoxy-1-oxopropyl) hexahydropyridine] butyl] pyridyl-2,5-dioxo-1H-pyrrole ] _2_ (trifluoromethyl) benzonitrile 4 506 109 4- [2,5-dihydro-3- [4- [4-[(2-methoxyethoxy) ethenyl] hexahydropyridine Phenyl] butyl] -4-methyl-2,5-dioxo-1H-pyrrolepyridyl] -2- (trifluoromethyl) benzonitrile 4 536 110 4- [2,5-di Hydrogen-3- [4- [4- [〇 (2-methoxyethoxy) -ethoxy] -ethylamyl] hexahydropyridin-1-yl] butyl] -4-methyl- 2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 580 111 4- [4- [4- [4- (cyclopropylsulfonyl) hexahydro) Pycnogenol] butyl] -2,5-dihydro-3-methyl-2,5-dioxo-1H-pyrroleminyl] -2- (trifluoromethyl) benzonitrile 5 524 112 4- [2,5-Dihydro-3- [4- [4- (2-methoxyethyl) sulfofluorenyl] hexahydropyridine] butyl] pyridyl-2,5-di Oxo-1H-pyrrole small group] -2- (trifluoromethyl) benzyl 5 542 113 4- [2,5-Dihydro-3- [4- [4-[[2- (2-methoxyethoxy) ethyl] -sulfonyl] hexahydropyridine] Butyl] -4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzyl 5 586 114 4- [2,5-dihydrogen each [4- [4-[[2-〇 (2-methoxyethoxy) ethoxy] -ethyl] sulfonyl] hexahydropyridine] butyl M-methyl-2,5 -Dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 5 630 115 4- [4- [1 · [4-cyano-3- (trifluoromethyl) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] -butyl] N, N-dimethylhexahydropyrine-1- Continued amine 5 527 116 4- [2,5-Dihydro each methyl-2,5-dioxo-4- [4- [4- (phenyl-sulfonyl) hexahydropyracyl] Butyl] -1Η-pyrrole small group] -2- (trifluoromethyl) benzonitrile 5 561 117 4- [2,5-dihydro-3-methyl-4- [4- [4- [4 -(Methylsulfonyl) -hexahydropyridin-1-yl] butyl] -2,5-dioxo-lH-t7 to p each-1-yl] -2- (digasmethyl) Benzonitrile 5 499 118 4- [2,5-Dihydro each methyl-4- [4- [4-[(4- (methylphenyl) -sulfonyl) hexahydropyridyl] small] butyl Base] -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl 5 575 -76- (71) 200301117 Example name

類似於 成 119 基)苯甲腈____ - N-[4-[[4-[4-0[4-氰基-3-(三 甲基-2,5-二氧代-1H-♦各各基]丁基]六氣:井: 醯基]苯基]乙醯胺 ^ 120 4-[3-[4-[4_[(4-氯苯基)磺醯基] Ϊί_4_甲基』，5二氧代專抓1都2在氟^基/苯 121 122 123 124 125 128 4-[3_[4-[4-[(4_氰基苯基）磺 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡哈+基>2广九 甲基)苯甲腈 ___ 亂 4_[2广二，_3·甲基-4-[4-[4-[(^ϊ^ϋϊ^ϊ^ 丁基]_2,5.二氧代·1Η·+各]·基]-2-(三氟甲基』 4-[3-[4-[4-[(喹啉-8-基）磺醯丁 基]-2,5-二氫-4-甲基-2,5-二氧代-1私♦各+基]·2=: # 甲基)苯甲腈 _ 、-乳 ΐ|>-[4-[4-[(2-氰基苯基）續疏基]六井-卜 基]-2,5-二氫·4-甲基_2,5_二氧代._咖各* f 甲基)苯甲腈 __ 土』（一鼠 巧仰基)磺 基]-2,5·二氫-4-甲基-2,5-二氧代-1H-咖各(二蠢 甲基)苯甲腈 _ V-亂 異嘮唑 -1-基]丁基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯《4 基]4(三氟甲基)苯甲腈____ 七[3-[4-[4-[(5_氣-I，3·二甲基_1Η-ί7比ρ各_4-基)橫醯基]六 氫t井小基]丁基]_2,5-二氫_4_甲基_2,5_二氧代]H—比 多-1-基]_2_(三氟甲基)苯甲腈Similar to 119) benzonitrile____-N- [4-[[4- [4-0 [4-cyano-3- (trimethyl-2,5-dioxo-1H- ♦ each Each group] butyl] hexazine: well: fluorenyl] phenyl] ethanamine ^ 120 4- [3- [4- [4 _ [(4-chlorophenyl) sulfofluorenyl] Ϊί_4_methyl ”, 5 dioxo specific 1 all 2 fluoro ^ / benzene 121 122 123 124 125 128 4- [3_ [4- [4-[(4_cyanophenyl) sulfo] -2,5-dihydro -4-Methyl-2,5-dioxo-1H-pyrha + yl> 2-Canamethyl) benzonitrile ___ RAN 4_ [2Candi, _3 · methyl-4- [4- [4-[(^ ϊ ^ ϋϊ ^ ϊ ^ butyl) _2,5. Dioxo · 1Η · + each] · yl] -2- (trifluoromethyl ′ 4- [3- [4- [4 -[(Quinoline-8-yl) sulfofluorenylbutyl] -2,5-dihydro-4-methyl-2,5-dioxo-1, each of the + groups] · 2 =: # methyl ) Benzonitrile_, -lactam | >-[4- [4-[(2-cyanophenyl) continyl] hexai-butyl] -2,5-dihydro · 4-methyl _2,5_dioxo._Cago * f methyl) benzonitrile_ (Earth) (monomolyl) sulfo] -2,5 · dihydro-4-methyl-2,5 -Dioxo-1H-caco (dimethyl) benzonitrile_V-ranisoxazol-1-yl] butyl] -2,5-dihydro-4-methyl-2,5- Dioxo-1Η-pyrrole "4-based] 4 (trifluoromethyl) benzonitrile ____ hepta [3- [4- [4-[(5_ 气 -I, 3 · 二Base_1Η-ί7 ratio ρ each _4-yl) transverse fluorenyl] hexahydro t well small group] butyl] _2,5-dihydro_4_methyl_2,5_dioxo] H- ratio Poly-1-yl] _2_ (trifluoromethyl) benzonitrile

613 4'[2,5-·^氫各甲基·4_[4_[4-[(1-甲基-1H-咪唑冰基)績醯 基]六氫吡畊基]丁基]-2,5-二氧代-1Η-吡咯小 基]-2-(三氣甲基)苯甲腈 565 129 130 4-[3-[4-[4-( 丁基磺醯基)六氫吡畊小基]丁基]-2,5_二氫 二氧代-1Η-♦ 各-1-基]-2·(三氟甲基)笨甲腈 4-[4-[1 -J4-氰基各(三氟甲基）苯基]_2,5-二氫冰甲基 2,5 一氧代-lH-p比ρ各-3-基]-丁基]-Ν-苯基六氯ρ比呼-1— 羧醯胺 541 540 -77- 200301117613 4 '[2,5- · ^ Hydroxymethyl 4_ [4_ [4-[(1-methyl-1H-imidazolyl) phenyl]] hexahydropyridyl] butyl] -2, 5-dioxo-1'-pyrrole small group] -2- (trifluoromethyl) benzonitrile 565 129 130 4- [3- [4- [4- (butylsulfonyl) hexahydropyridine) Yl] butyl] -2,5-dihydrodioxo-1Η- ♦ each-1-yl] -2 · (trifluoromethyl) benzonitrile 4- [4- [1 -J4-cyano each (Trifluoromethyl) phenyl] _2,5-dihydroglacial methyl 2,5 monooxo-lH-p ratio ρ each-3-yl] -butyl] -N-phenylhexachloro ρ bihu -1— Carboxamide 541 540 -77- 200301117

貧例 名稱 類似於 貫^列合'成J ESI-MS 131 4-[4-〇J4-氰基各(一氟甲基）苯基]_2,5-二氫冰甲基 _2,5-二氧代比咯各基]-丁基]-N-(茶_基> 六氫吡呼 -1-羧醯胺 6 590 132 4-[4-[ 1-J4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 2,5 一氧代-lH-p比p各基]-丁基]-N-(茶-基)·六氯p比p井 -1-羧醯胺 6 590 133 N-(2-氯苯基)-4-[4-[1-[4-氰基-3-(二氟甲基)苯基]·2,5-二 氫斗甲基-2,5-二氧代-1H-吡咯-3-基]-丁基]六氫吡畊小 竣醯胺 6 574 134 4-[4-[ 1-J4-氰基各(二氟甲基）苯基]-2,5-二氫斗甲基 _2,5_二氧代-1H-吡咯各基]-丁基]善[2_(三氟甲基)·苯 基]六氫吡畊小羧醯胺 丨 6 608 135 4-[4-[ 1 -[4-氰基-3-(二氟甲基）苯基]-2,5-二氫-4-甲基 _2,5_二氧代-1H-P比咯各基]-丁基]善(3_甲氧基-苯基)六 氫吡畊-1-羧醯胺 6 570 136 N-(4-氯苯基氰基各(三氟甲基苯基]_2,5- 二氫甲基-2,5-二氧代-111-说咯各基]-丁基]六氫吡畊 小羧醯胺 6 574 137 4-[4-[Η4-氰基各(二氟甲基）苯基]-2,5·二氫-4-甲基 -2,5-二氧代-iH-p比咯-3-基]-丁基]-Ν-[4-苯氧基-苯基]六 氫吡畊-1-羧醯胺 6 632 138 4-[4-[Η4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲ί _2,5_二氧代-1H-P比咯各基]-丁基]善[4_(甲基硫烷基)苯 基]六氫吡畊-1-羧醯胺 6 586 139 Ν-([1，1·-聯苯基]-4-[4-[l-[4-氰基-3-(三氟甲基 > 苯 基]_2,5-二氫斗甲基-2,5-二氧代-1H-吡咯-3-基]-丁基] 六氫吡畊-1-羧醯胺 6 616 140 4-[4-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯各基]-丁基]-N-(2,5-二甲氧基苯 基)六氫吡畊-1-羧醯胺 6 600 141 4_1>[H4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]-丁基]-N-[2-(l-甲基乙基)苯 基]六氫吡畊小羧醯胺 6 582 142 4_[4-[H4-氰基·3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-丨η-吡咯-3-基]-丁基]-Ν-(2,4,6-三甲基苯 基)六氫吡哜小羧醯胺 6 582 -78- 200301117The name of the rare case is similar to that of 贯 ^ 成 合 合成 'J ESI-MS 131 4- [4-〇J4-cyano ((fluorofluoro) phenyl)] _ 2,5-dihydroicemethyl_2,5- Dioxopyrrole groups] -butyl] -N- (Tea_yl > hexahydropyridine-1-carboxamide 6 590 132 4- [4- [1-J4-cyano-3- ( Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl 2,5 monooxo-lH-p ratio p each group] -butyl] -N- (tea-yl) · hexachloro p ratio p well-1-carboxamidine 6 590 133 N- (2-chlorophenyl) -4- [4- [1- [4-cyano-3- (difluoromethyl) phenyl] · 2 , 5-Dihydromethyl-2,5-dioxo-1H-pyrrole-3-yl] -butyl] hexahydropyrimoxamine 6 574 134 4- [4- [1-J4- Cyano (difluoromethyl) phenyl] -2,5-dihydromethyl-2,5_dioxo-1H-pyrroleyl] -butyl] zan [2_ (trifluoromethyl) · Phenyl] hexahydropyridoxamine 丨 6 608 135 4- [4- [1-[4-cyano-3- (difluoromethyl) phenyl] -2,5-dihydro-4 -Methyl_2,5_dioxo-1H-P than pyrrolyl] -butyl] s (3-methoxy-phenyl) hexahydropyridine-1-carboxamide 6 570 136 N- (4-Chlorophenylcyano (trifluoromethylphenyl) _2,5-dihydromethyl-2,5-dioxo-111-sulloyl) -butyl] hexahydropyridine Carboxamide 6 574 137 4- [4- [Η 4-cyano (difluoromethyl) phenyl] -2,5 · dihydro-4-methyl-2,5-dioxo-iH-ppyrrol-3-yl] -butyl]- Ν- [4-phenoxy-phenyl] hexahydropyridine-1-carboxamide 6 632 138 4- [4- [fluorene 4-cyano (trifluoromethyl) phenyl] -2,5- Dihydro-4-methylί _2,5_dioxo-1H-P than allyl] -butyl] shan [4_ (methylsulfanyl) phenyl] hexahydropyridine-1-carboxamide 6 586 139 N-([1,1 · -biphenyl] -4- [4- [l- [4-cyano-3- (trifluoromethyl > phenyl) _2,5-dihydro Methyl-2,5-dioxo-1H-pyrrole-3-yl] -butyl] hexahydropyridine-1-carboxamide 6 616 140 4- [4- [1- [4-cyano each (Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-yl] -butyl] -N- (2,5-dimethyl (Oxyphenyl) hexahydropyridine-1-carboxamide 6 600 141 4_1 > [H4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1H-pyrrole-3-yl] -butyl] -N- [2- (l-methylethyl) phenyl] hexahydropyridoxamine 6 582 142 4_ [ 4- [H4-cyano · 3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo- 丨 η-pyrrole-3-yl]- Butyl] -N- (2,4,6-trimethylphenyl) hexahydropyridoxamine 6 582 -78-2 00301117

(73) 實例 名稱 類似於 實例合成 ESI-MS 143 (r)_4_[4-[1-[4-氰基-3-(三氟甲基)苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]-丁基]-N-(l-苯基乙基)-六氫 吡畊小羧醯胺 6 568 144 4-[4-[ 1 -[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]-丁基]-Ν-[2-(1，1-二甲基乙 基)苯基]X鼠ρ比命-1-幾酿胺 6 596 145 4-[4-[1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]-丁基]-Ν-己基六氫吡畊-1- 羧醯胺 6 548 表9.根據本發明通式I的化合物，其中V=三氟甲基苯甲(73) Example name similar to Example Synthesis ESI-MS 143 (r) _4_ [4- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4- Methyl-2,5-dioxo-1'-pyrrole-3-yl] -butyl] -N- (l-phenylethyl) -hexahydropyridoxamine 6 568 144 4- [4 -[1-[4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1Η-pyrrole-3-yl] -Butyl] -N- [2- (1,1-dimethylethyl) phenyl] X Murine p-l- 1-chimonamine 6 596 145 4- [4- [1- [4-cyano (Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] -butyl] -N-hexylhexahydro Pycnogenol-1-carboxamide 6 548 Table 9. Compounds of general formula I according to the invention, where V = trifluoromethylbenzyl

腈，W =馬來亞胺，η = 5 實例 名稱 類似於 實例合成 ESI-MS 146 4-[2,5-二氯-3-甲基-2,5-二氧ι代-4-[5-[4-(ρ比呼-2-基)-7Τ 氫吡畊小基]戊基]-1Η-吡咯小基]-2-(三氟甲基)苯曱腈 3 513 147 4-[3-[5-[4-(2,4-二氟苯基）六氫吡畊小基]戊基]-2,5-二 氫斗甲基-2,5-二氧代-1Η-吡咯小基]-2-(三氟甲基)苯甲 腈 3 547 148 4-[3-[5-[4-(呋喃-2-基)羰基]六氫吡畊-1-基]戊基]-2,5-二 氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基)苯甲 腈 4 529 149 4-[2,5-二氫-3-曱基-4-[5-[4-[(5-曱基異噚唑-3-基)-羰基] 六氫吡畊小基]戊基]-2,5-二氧代-1Η-吡咯小基]-2-(三 氟甲基)苯甲腈 4 544 150 4-[2,5-二氮-3-甲基-2,5-二氧代-4-[5-[4-(本基乙酸基)_ 六氫吡畊小基]戊基]-1Η-吡咯小基]冬(三氟甲基)苯甲 腈 4 553 151 4-[2,5-二氫-3-[5-[4-(4-甲氧基苯甲醯基)六氫吡畊-1-基] 戊基]-4-甲基-2,5-二氧代-lH-p比ρ各-1-基]-2-(二鼠曱基) 苯甲腈 4 569 152 4-[2,5-二氫-3-[5-[4-(2-甲氧基苯甲醯基)六氫吡畊-1-基] 戊基]-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基) 苯甲腈 4 569Nitrile, W = maleimine, η = 5 Example name is similar to Example Synthesis ESI-MS 146 4- [2,5-dichloro-3-methyl-2,5-dioxo-4- [5 -[4- (ρ 比 胡 -2-yl) -7T hydropyridine] pentyl] -1Η-pyrrole small] -2- (trifluoromethyl) benzonitrile 3 513 147 4- [3 -[5- [4- (2,4-difluorophenyl) hexahydropyridine] pentyl] -2,5-dihydromethyl-2,5-dioxo-1 代 -pyrrole small Yl] -2- (trifluoromethyl) benzonitrile 3 547 148 4- [3- [5- [4- (furan-2-yl) carbonyl] hexahydropyridin-1-yl] pentyl]- 2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 529 149 4- [2,5- Dihydro-3-fluorenyl-4- [5- [4-[(5-fluorenylisoxazol-3-yl) -carbonyl] hexahydropyridine] pentyl] -2,5-dioxo Substituted-1Η-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 544 150 4- [2,5-Diaza-3-methyl-2,5-dioxo-4- [5 -[4- (benzylacetoxy) _ hexahydropyridine] pentyl] -1] -pyrrolepyridyl] winter (trifluoromethyl) benzonitrile 4 553 151 4- [2,5-dihydro -3- [5- [4- (4-methoxybenzylidene) hexahydropyrine-1-yl] pentyl] -4-methyl-2,5-dioxo-lH-p ratio ρ each-1-yl] -2- (dimuridine) benzonitrile 4 569 152 4- [2,5- Hydrogen-3- [5- [4- (2-methoxybenzylidene) hexahydropyridine-1-yl] pentyl] -4-methyl-2,5-dioxo-1Η-pyrrole -1-yl] -2- (trifluoromethyl) benzonitrile 4 569

-79- 200301117 (74) 實例 名稱 類似於 實例合成 ESI-MS 153 4-[2,5-二氫各[5-[4-(甲氧基乙醯基）六氫吡畊小基]戊 基]-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯 甲腈 4 507 154 ‘[3-[5-[4-(2-氯苯甲醯基)六氫吡畊-1-基]戊基]_2,5-二 氫-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲 腈 4 573 155 4-[3-[5-[4-(2-氟苯甲醯基)六氫吡畊小基]戊基]-2,5-二 氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯甲 腈 4 557 156 4-[3-[5-(4-苯甲醯基六氫吡畊小基)戊基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲腈 4 539 157 4-[3-[5-[4_(環丁基羰基)六氫吡畊小基]戊基]_2,5_二氫 斗甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲腈 4 517 158 4-[3-[5-[4-(3,4-二甲氧基苯甲醯基）六氫吡畊小基]戊 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟 甲基)苯甲腈 4 599 159 4-[2,5-二氫-3-甲基-2,5-二氧代冬[5-[4-[(吡啶：基)羰 基]六氫吡畊小基]戊基]-1Η-吡咯小基]-2-(三氟甲基) 苯甲腈 4 540 160 4-[3_|>[4-(環丙基羰基)六氫吡畊小基]戊基]-2,5-二氫 -4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯甲腈 4 503 161 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-[(吡啶-4-基)羰 基]六氫吡畊小基]戊基HH-吡咯小基]-2-(三氟甲基) 苯甲腈 4 540 162 4-[3-[5-[4-4-(二甲基胺基)苯甲醯基]六氫吡畊小基]戊 基]-2,5-二氮-4-甲基~2,5_ 二氧代-111-0比11各-1-基]-2-(二氣 甲基)苯甲腈 4 582 163 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-[(苯基硫烷基) 乙醯基]六氫吡畊小基]戊基HH-吡咯-1-基]-2-(三氟甲 基)苯曱腈 4 585 164 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-(苯氧基硫烷基 乙醯基)六氫吡畊-1-基]戊基HH-吡咯小基]-2-(三氟甲 基)苯甲腈 4 569 165 4-[2,5-二氮-3-甲基-2,5-二氧代-4-[5-[4-[( 口塞-2-基)-談基] 六氫吡畊-1-基]戊基]-1Η-吡咯小基]_2-(三氟甲基)苯甲 腈 4 545 -80- 200301117-79- 200301117 (74) Example name is similar to Example Synthesis ESI-MS 153 4- [2,5-Dihydro each [5- [4- (methoxyethylamidino) hexahydropyridine small]] pentyl ] -4-methyl-2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 507 154 '[3- [5- [4- (2-chloro Benzamidine) hexahydropyridin-1-yl] pentyl] _2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl Phenyl) benzonitrile 4 573 155 4- [3- [5- [4- (2-fluorobenzyl) hexahydropyridine] pentyl] -2,5-dihydro-4-methyl -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 557 156 4- [3- [5- (4-benzylfluorenylhexahydropyridine) Phenyl) pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 539 157 4 -[3- [5- [4- (Cyclobutylcarbonyl) hexahydropyridine small group] pentyl] _2,5-dihydronormethyl-2,5-dioxo-1H-pyrrole small group]- 2- (trifluoromethyl) benzonitrile 4 517 158 4- [3- [5- [4- (3,4-dimethoxybenzyl) hexahydropyridine] pentyl]- 2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 599 159 4- [2,5- Dihydro-3-methyl-2,5-dioxo [5 -[4-[(pyridine: carbonyl) carbonyl] hexahydropyridine] pentyl] -1Η-pyrrole small] -2- (trifluoromethyl) benzonitrile 4 540 160 4- [3_ | > [4- (cyclopropylcarbonyl) hexahydropyridine small group] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl]- 2- (trifluoromethyl) benzonitrile 4 503 161 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [5- [4-[(pyridine-4 -Yl) carbonyl] hexahydropyridine] pentylHH-pyrrolepyridyl] -2- (trifluoromethyl) benzonitrile 4 540 162 4- [3- [5- [4-4- (bis Methylamino) benzamyl] hexahydropyridyl] pentyl] -2,5-diaza-4-methyl ~ 2,5-dioxo-111-0 to 11 each 1-1-yl ] -2- (Digasmethyl) benzonitrile 4 582 163 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [5- [4-[(benzene Sulfanyl) ethanyl] hexahydropyridine] pentylHH-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 585 164 4- [2,5-dihydro -3-methyl-2,5-dioxo-4- [5- [4- (phenoxysulfanylethylamidino) hexahydropyrimyl-1-yl] pentylHH-pyrrole small] -2- (trifluoromethyl) benzonitrile 4 569 165 4- [2,5-diaza-3-methyl-2,5-dioxo-4- [5- [4-[(mouth stopper -2-yl) -Hanyl] hexahydropyridin-1-yl] pentyl] -1Η-pyrrole small group] _2- (tri Methyl) benzonitrile 4545-80- 200 301 117

166 類似於 成 4166 similar to 4

4-[2,5-二氫-3-甲基-2,5-二氧代-ΙΪΪΓ[4·(3-苯基 丙基）六氫吡畊-1-基]戊基]-1Η-吡咯-1-基]-2-(三氟甲 基)苯甲腈___ 167 583 4-[3_[5-[4-[(1，3-苯并二4茂基)幾基]六氫Ρ比Ρ井+基] 戊基]-2,5-二氫冰甲基-2,5-二氧代-11^比咯小基]-2-( 氟甲基)苯甲腈__ 4-[2,5-一風τ3-[5-[4-[(4-甲氧基苯基)-乙酿基]六氫叶匕口井 小基]戊基Μ-甲基_2,5-二氧代-1!^比咯小基]_2_(三氟 甲基)苯甲腈 4-[2,5-一氣-3-甲基-4-[5-[4-(2-甲基苯甲酷基)六氫ρ比呼 1-基]戊基ΗΗ-吡咯-1-基]冬(三氟甲基)苯甲腈 4-—[2,5-二氫：3-甲基·2,5·二氧代·ΖΪ5·[4·[(备 基]六氫吡畊小基]戊基]-1Η-吡咯-1-基]I(三氟甲基) 苯甲腈 171 4-[3-〇[4-[(4-氯苯氧基）乙酸基]六氫吡呼小基]戊 基]_2,5-一氮-4·甲基_2,5_二氧代-1H-P比嘻-1-基]-；2-(三氟 甲基)苯甲腈 4 603 172 4-[3-[5-[4-(3-環戊基-1-氧代丙基）六氫ρ比畊小基]戊 基]-2,5-一鼠-4-甲基-2,5-二氧代-lH-p比17各-1-基]-2-(三氟 甲基)苯甲腈 ~ ~ 4 559 173 4-[3-[5-[4-(3-氯苯甲醯基)六氫吡畊-μ基]戊基]_2,5·二 氫冰甲基-2,5-二氧代-1如比‘1-基]_2_(三氟甲基)苯甲 4 573 腈 174 4-[3-[5-[4-(3,3·二甲基-1·氧代丁基)六氫吡畊+基]戊 基]_2,5-二氫《4-甲基_2,5_二氧代-IH-p比ρ各-1-基]-2_(三氟 甲基)苯甲腈 4 533 175 176 4-[2,5-二氫-3-甲基冰[5-[4-(3-甲基小氧代丁基)_六氫 畊-1-基]戊基]-1Η_吡咯-1-基]_2_(三氟甲基)苯甲腈 4-[2,5-二氫斗甲基-2,5-二氧代-3-[5-[4-[(苯基-甲氧基) 乙醯基]六氫吡畊-1-基]戊基]-1Η-吡咯-1-基]_2_(三氟甲 基)苯甲腈 4 4 519 583 177 4-[Η5-[4-(環戊基乙醯基)六氫吡畊-1-基]戊基]-2,5-二 氫-4-甲基-2,5-二氧代-1Η-咖各小基]-2-(三氟甲基)苯甲 腈 4 545 178 4-〇[5-[4-(2,6-二氟苯甲醯基）六氫吡畊+基]戊 基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基1-2-(三氟 4 575 -81- 200301117 (76) 實例 名稱 類似於 實例合成 ESI-MS 甲基)苯甲腈 179 4-〇[5-[4-(2,6-二氯苯甲醯基）六氫吡畊小基]戊 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-1·基]-2-(三氟 甲基)苯甲腈 4 607 180 4-[2,5-二氫-3-甲基-2,5-二氧代-3-〇[4-[2-(三氟甲基）乙 醯基]六氫吡畊小基]戊基HH-吡咯-1-基]-2-(三氟甲 基)苯甲腈 4 607 181 4-[3-[5-[4-(3-氟苯甲醯基)六氫吡畊-1-基]戊基]-2,5-二 氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯甲 腈 4 557 182 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-[3-(三氟甲基）乙 醯基]六氫吡畊小基]戊基HH-吡咯-1·基]-2-(三氟甲 基)苯甲腈 4 607 183 4-[2,5-二氫-3-甲基-4-[5-[4-(4-甲基苯甲醯基)-六氫吡啩 小基]戊基]-2,5-二氧代-1H-吡咯-1-基]冬(三氟甲基)苯 甲腈 4 553 184 4-[2,5-二氫-3-甲基-4-[5-[4_[(萘-1-基)-羰基]六氫吡畊 小基]戊基]-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯 甲腈 4 589 185 4-[2,5-二氫-3-甲基冰[5-[4-[(莕-2-基)-羰基]六氫吡畊 小基]戊基]-2,5-二氧1代-11^比17各-1-基]-2-(二氟甲基)苯 甲腈 4 589 186 4-〇[5-[4-(3-氰基苯甲醯基)六氫吡畊-1-基]戊基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯 甲腈 4 564 187 4-[3-[5-[4-(ί募己基談基)7T鼠卩比^井··!·-基]戊基]·2,5-二鼠 -4-甲基-2,5-二氧代-1Η-吡咯小基]-2-(三氟甲基)苯甲腈 4 545 188 4-[3 - [5-(4-乙酸基7Τ鼠ρ比17井-1-基)戊基]-2,5-二鼠-4-甲基 -2,5-二氧代-1Η-吡咯小基]-2-(三氟甲基)苯甲腈 4 476 189 4-[2,5-二氫-3-〇[4-(3-甲氧基-1-氧代丙基)六氫吡畊-1-基]戊基]4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲 基)苯甲腈 4 520 190 4-[2,5-二氫-3-[5-[4-[(2-甲氧基乙氧基)-乙醯基]六氫吡 畊-1-基]戊基]-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三 氟甲基)苯甲腈 4 550 191 4-[2,5-二氫-3-[5-[4-[[(2-(2-甲氧基乙氧基)-乙氧基)-乙 4 5944- [2,5-dihydro-3-methyl-2,5-dioxo-ΙΪΪΓ [4 · (3-phenylpropyl) hexahydropyrine-1-yl] pentyl] -1Η- Pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile ___ 167 583 4- [3_ [5- [4-[(1,3-Benzodi-4ocenyl) jinyl] hexahydro P P + well + yl] pentyl] -2,5-dihydroicemethyl-2,5-dioxo-11 ^ pyrrolyl] -2- (fluoromethyl) benzonitrile__ 4- [2,5- 一 风 τ3- [5- [4-[(4-methoxyphenyl) -ethynyl] hexahydro leaf dagger well small base] pentyl M-methyl_2,5- Dioxo-1! ^ Pyrrolyl] _2_ (trifluoromethyl) benzonitrile 4- [2,5-monogas-3-methyl-4- [5- [4- (2-methylbenzene (Metalyl) hexahydroρ Bihu 1-yl] pentylfluorene-pyrrole-1-yl] winter (trifluoromethyl) benzonitrile 4 -— [2,5-dihydro: 3-methyl · 2 , 5 · Dioxo · ZΪ5 · [4 · [(preparation group) hexahydropyridine] pentyl] -1] -pyrrole-1-yl] I (trifluoromethyl) benzonitrile 171 4- [ 3-〇 [4-[(4-chlorophenoxy) acetoxy] hexahydropyridyl] pentyl] _2,5-monoazine-4 · methyl_2,5_dioxo-1H- P than 1-1-yl]-; 2- (trifluoromethyl) benzonitrile 4 603 172 4- [3- [5- [4- (3-cyclopentyl-1-oxopropyl) hexa Hydrogen-rhobicyl] pentyl] -2,5-monorat-4-methyl-2,5-dioxo-lH-p ratio 17 each -1 -Yl] -2- (trifluoromethyl) benzonitrile ~ ~ 4 559 173 4- [3- [5- [4- (3-chlorobenzylidene) hexahydropyridine-μyl] pentyl ] _2,5 · Dihydroglacial methyl-2,5-dioxo-1 such as than '1-yl] _2_ (trifluoromethyl) benzyl 4 573 nitrile 174 4- [3- [5- [4 -(3,3 · dimethyl-1 · oxobutyl) hexahydropyridine + yl] pentyl] _2,5-dihydro 《4-methyl_2,5_dioxo-IH-p Specific ρ each-1-yl] -2_ (trifluoromethyl) benzonitrile 4 533 175 176 4- [2,5-dihydro-3-methyl ice [5- [4- (3-methyl small (Oxobutyl) _hexahydro-1-yl] pentyl] -1Η_pyrrole-1-yl] _2_ (trifluoromethyl) benzonitrile 4- [2,5-dihydromethyl-2 , 5-dioxo-3- [5- [4-[(phenyl-methoxy) ethenyl] hexahydropyridine-1-yl] pentyl] -1Η-pyrrole-1-yl] _2_ (Trifluoromethyl) benzonitrile 4 4 519 583 177 4- [Η5- [4- (cyclopentylethylfluorenyl) hexahydropyridin-1-yl] pentyl] -2,5-dihydro- 4-methyl-2,5-dioxo-1Η-caffeine small group] -2- (trifluoromethyl) benzonitrile 4 545 178 4-〇 [5- [4- (2,6-di Fluorobenzyl) hexahydropyridine + yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl 1-2- (tri Fluoride 4 575 -81- 200301117 (76) Example name is similar to Example Synthesis ESI-MS A ) Benzonitrile 179 4-〇 [5- [4- (2,6-Dichlorobenzyl) hexahydropyridine] pentyl] -2,5-dihydro-4-methyl-2 , 5-dioxo-1H-pyrrole-1 · yl] -2- (trifluoromethyl) benzonitrile 4 607 180 4- [2,5-dihydro-3-methyl-2,5-di Oxo-3-〇 [4- [2- (trifluoromethyl) ethenyl] hexahydropyridine] pentylHH-pyrrole-1-yl] -2- (trifluoromethyl) benzyl Nitrile 4 607 181 4- [3- [5- [4- (3-fluorobenzylidene) hexahydropyridine-1-yl] pentyl] -2,5-dihydro-4-methyl-2 , 5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 557 182 4- [2,5-dihydro-3-methyl-2,5-di Oxo-4- [5- [4- [3- (trifluoromethyl) ethenyl] hexahydropyridine] pentylHH-pyrrole-1 · yl] -2- (trifluoromethyl) Benzonitrile 4 607 183 4- [2,5-Dihydro-3-methyl-4- [5- [4- (4-methylbenzylidene) -hexahydropyridine small group] pentyl] -2,5-dioxo-1H-pyrrole-1-yl] winter (trifluoromethyl) benzonitrile 4 553 184 4- [2,5-dihydro-3-methyl-4- [5- [4-[(naphthalene-1-yl) -carbonyl] hexahydropyridine] pentyl] -2,5-dioxo-1H-pyrrole small] -2- (trifluoromethyl) benzonitrile 4 589 185 4- [2,5-Dihydro-3-methylice [5- [4-[(fluoren-2-yl) -carbonyl] hexahydropyridine ] Pentyl] -2,5-dioxo 1-11-11 ratio 17 each-1-yl] -2- (difluoromethyl) benzonitrile 4 589 186 4-〇 [5- [4- (3 -Cyanobenzyl) hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl]- 2- (trifluoromethyl) benzonitrile 4 564 187 4- [3- [5- [4- (ίHexyl alkynyl) 7T rat mole ratio ^ Well ...!-Yl] pentyl] 2 , 5-Dimur-4-methyl-2,5-dioxo-1H-pyrrole small] -2- (trifluoromethyl) benzonitrile 4 545 188 4- [3-[5- (4 -Acetyl 7T mouse p ratio 17 wells-1-yl) pentyl] -2,5-dimur-4-methyl-2,5-dioxo-1H-pyrrole small] -2- (trifluoro (Methyl) benzonitrile 4 476 189 4- [2,5-dihydro-3-〇 [4- (3-methoxy-1-oxopropyl) hexahydropyrine-1-yl] pentyl ] 4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 520 190 4- [2,5-dihydro-3- [ 5- [4-[(2-methoxyethoxy) -ethenyl] hexahydropyridin-1-yl] pentyl] -4-methyl-2,5-dioxo-1H-pyrrole -1-yl] -2- (trifluoromethyl) benzonitrile 4 550 191 4- [2,5-dihydro-3- [5- [4-[[((2- (2-methoxyethyl (Oxy) -ethoxy) -ethyl 4 594

-82- 200301117-82- 200301117

(77) 實例 名稱 類似於 實例合成 ESI-MS 醯基]六氫吡畊小基]戊基l·4-甲基二氧代-1H-吡咯 -1-基]冬(三氟甲基)苯甲腈 192 4-[4-[5-[4-(環丙基磺醯基)六氫咕畊小基]戊基]-2,5-二 氫各甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲 腈 5 538 193 4-[2,5-二氫-3-[5-[4-(2-甲氧基乙基)-磺醯基]六氫吡畊 -1-基]戊基]-4-甲基-2,5-二氧1代-11'1-^7比17各-1-基]-2-(二氣 甲基)苯甲腈 5 556 194 4-[2,5-二氫各[5-[4-[[(2-(2-甲氧基乙氧基)-乙基)-乙醯 基]六氫吡畊-1-基]戊基]-4-甲基-2,5·二氧代-1H-吡咯-1-基]_2_(三氟甲基)苯甲腈 5 600 195 4-[2,5-二氫各[5_[4-[[(2-(2-甲氧基乙氧基)-乙氧基)-乙 基]磺醯基]六氫吡畊-1-基]戊基]-4-甲基-2,5-二氧代 -1Η-吡咯小基]-2-(三氟甲基)苯甲腈 5 644 196 4-〇[1-[4-氰基各(三氟甲基)苯基]戊基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯各基]戊基]-Ν，Ν-二甲基六氫吡 畊-1-磺醯胺 5 541 197 4-[2,5-二氫-3-曱基-2,5-二氧代-4-[5-[4-[(1-甲基乙基)_ 磺醯基]六氫吡畊小基]戊基HH-吡咯小基]-2-(三氟甲 基)苯甲腈 5 541 198 4-[2,5-二氯-3-甲基-2,5-二氧代-4-[5-[4-(秦基橫S盛基)六 氫吡畊小基]戊基HH-吡咯小基]-2-(三氟甲基)苯甲腈 5 575 199 4-[2,5-二氫-3-甲基-4-[5-[4-(甲基磺醯基）六氫吡畊-1-基]戊基]-2,5-二氧代-1Η-吡咯小基]-2-(三氟甲基)苯甲 腈 5 513 200 4_[3_[5-[4-[(4-氯苯基)磺醯基]六氫吡畊小基]戊基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基)苯 甲腈 5 609 201 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-[(苯基甲基)-磺 醯基]六氫吡畊-1-基]戊基]-1Η-吡咯-1-基]-2-(三氟甲 基)苯甲腈 5 589 202 4-[3-[5-[4-[(4-氰基苯基）磺酿基]六氫说畊-1 -基]戊 基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟 甲基)苯甲腈 5 600 203 4-[4-[5-[4-[(喹啉-8-基）磺醯基]六氫吡畊小基]戊 基]-2,5-二氫各甲基-2,5-二氧代-1Η-吡咯小基]-2-(三氟 5 626 -83- 200301117 (78) 實例 名稱 類似於 實例合成 ESI-MS 甲基)苯甲腈 204 4-[3-[5-[4-[(2-氟苯基)磺醯基]六氫吡畊小基]戊基]_2,5_ 二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯 甲腈 5 593 205 4-[3-〇[4-[(2,5-二甲氧基苯基)磺醯基]-六氫吡畊小基] 戊基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三 氟甲基)苯甲腈 5 635 206 4-[3-[5-[4-[(3-氰基苯基）磺醯基]六氫吡畊-1-基]戊 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟 甲基)苯甲腈 5 600 207 4-|>[>[4-[(2，1，3-苯并嘧二唑-4-基)磺醯基]六氫吡畊 小基]戊基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯小 基]-2-(三氟甲基)苯f腈 5 633 208 4-[5-[1-[4-氰基-3-(三氟甲基)苯基]戊基]-2,5-二氫_4_甲 基-2,5-二氧代-1H-吡咯-3-基]戊基]-Ν-(1，1-二甲基-乙 基)六氫p比17井-1 -致酿胺 6 534 209 4-[5-[1-[4-氰基-3-(三氟甲基)苯基]戊基]-2,5-二氫I甲 基-2,5-二氧代-lH-p比p各-3-基]戊基]-N-(奈-1-基)ττ氮p比 畊-1-羧醯胺 6 604 210 Ν-(4-氰基苯基)冰[5-[1-[4-氰基各(三氟甲基)苯基]戊 基]-2,5-二氮-4-甲基-2,5-二氧1代-11^-^7比17各-3-基]戊基]7^ 氮口比_ -1 -瘦酿胺 6 579 211 Ν-(2-氯基苯基)-4-[5-[1-[4-氰基-3-(三氟甲基)苯基]戊 基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-3-基]戊基]六 氫吡畊-1-羧醯胺 6 588 212 4-[5-[1-[4-氣基-3-(三氟甲基)苯基]戊基]-2,5-二氫-4-甲 基-2,5-二氧代基]戊基]-Ν-[2-(二氣甲基)苯 基]六氫p比。井-1-複酿胺 6 622 213 4-[5-[1-[4-氰基-3-(三氟甲基)苯基]戊基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]戊基]-Ν-(2-甲基-苯基)六 氫吡畊-1-羧醯胺 6 568 214 4-[5-[1-[4-氣基-3-(二氣甲基)本基]戊基]-2,5-二鼠-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]戊基]-Ν-(3-甲基-苯基)六 氫吡畊-1-羧醯胺 6 568 215 4-[5-[1-[4-氣基-3-(二氟甲基)苯基]戊基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]戊基]-Ν-(4-氟苯基)-六氫 6 572(77) Example name similar to Example Synthesis ESI-MS fluorenyl] hexahydropyridine] pentyl 1.4-methyldioxo-1H-pyrrole-1-yl] winter (trifluoromethyl) benzene Nitrile 192 4- [4- [5- [4- (Cyclopropylsulfonyl) hexahydrogallyl] pentyl] -2,5-dihydromethyl-2,5-dioxo -1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 5 538 193 4- [2,5-dihydro-3- [5- [4- (2-methoxyethyl)- Sulfonyl] hexahydropyridin-1-yl] pentyl] -4-methyl-2,5-dioxo 1'-11'1- ^ 7 to 17 each-1-yl] -2- (di Gas methyl) benzonitrile 5 556 194 4- [2,5-dihydro each [5- [4-[[((2- (2-methoxyethoxy) -ethyl) -ethylfluorenyl] Hexahydropyrim-1-yl] pentyl] -4-methyl-2,5 · dioxo-1H-pyrrole-1-yl] _2_ (trifluoromethyl) benzonitrile 5 600 195 4- [ 2,5-dihydro each [5_ [4-[[((2- (2-methoxyethoxy) -ethoxy) -ethyl] sulfofluorenyl] hexahydropyridin-1-yl] pentyl Yl] -4-methyl-2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 5 644 196 4-〇 [1- [4-cyano each ( Trifluoromethyl) phenyl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrroleyl] pentyl] -N, N-dimethylhexa Pyridoxine-1-sulfamethoxamine 5 541 197 4- [2,5-Di Hydroxy-3-fluorenyl-2,5-dioxo-4- [5- [4-[(1-methylethyl) _sulfofluorenyl] hexahydropyridine] pentylHH-pyrrole Yl] -2- (trifluoromethyl) benzonitrile 5 541 198 4- [2,5-dichloro-3-methyl-2,5-dioxo-4- [5- [4- (秦Sulfonyl) hexahydropyridine] pentyl HH-pyrrole small] -2- (trifluoromethyl) benzonitrile 5 575 199 4- [2,5-dihydro-3-methyl -4- [5- [4- (methylsulfonyl) hexahydropyridin-1-yl] pentyl] -2,5-dioxo-1Η-pyrrole small] -2- (trifluoromethyl ) Benzonitrile 5 513 200 4_ [3_ [5- [4-[(4-chlorophenyl) sulfonamido] hexahydropyridine] pentyl] -2,5-dihydro-4-methyl -2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 5 609 201 4- [2,5-dihydro-3-methyl-2, 5-dioxo-4- [5- [4-[(phenylmethyl) -sulfofluorenyl] hexahydropyridin-1-yl] pentyl] -1Η-pyrrole-1-yl] -2- (Trifluoromethyl) benzonitrile 5 589 202 4- [3- [5- [4-[(4-cyanophenyl) sulfonyl] hexahydrocyclo-1 -yl] pentyl] -2 , 5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 5 600 203 4- [4- [5- [4-[(Quinolin-8-yl) sulfofluorenyl] hexahydropyridyl] pentyl] -2,5-dihydromethyl-2,5-dioxo- 1Η-pyrrole small group] -2- (trifluoro 5 626 -83- 200301117 (78) Example name is similar to the example ESI-MS methyl) benzonitrile 204 4- [3- [5- [4-[( 2-fluorophenyl) sulfonyl] hexahydropyridine] pentyl] _2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (Trifluoromethyl) benzonitrile 5 593 205 4- [3-〇 [4-[(2,5-dimethoxyphenyl) sulfonyl] -hexahydropyridine] pentyl]- 2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 5 635 206 4- [3- [5 -[4-[(3-cyanophenyl) sulfofluorenyl] hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo- 1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 5 600 207 4- | > [> [4-[(2,1,3-benzopyridazol-4-yl) Sulfonyl] hexahydropyridine] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole small] -2- (trifluoromethyl) Benzene nitrile 5 633 208 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] pentyl] -2,5-dihydro_4-methyl-2,5 -Dioxo-1H-pyrrole-3-yl] pentyl] -N- (1,1-dimethyl-ethyl) hexahydro p ratio 17 well-1 -brewing amine 6 534 209 4- [5 -[1- [4-cyano-3- (trifluoromethyl) phenyl] pentyl] -2, 5-dihydro I methyl-2,5-dioxo-lH-p ratio p each 3-yl] pentyl] -N- (naphthalen-1-yl) ττ nitrogen p bien-1-carboxyl Amine 6 604 210 N- (4-cyanophenyl) ice [5- [1- [4-cyano (trifluoromethyl) phenyl] pentyl] -2,5-diaza-4-methyl -2,5-dioxo 1-11-11- ^ 7 to 17 each 3-yl] pentyl] 7 ^ nitrogen ratio_ -1 -leanamine 6 579 211 Ν- (2-chlorobenzene ) -4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxy -1H-pyrrole-3-yl] pentyl] hexahydropyridine-1-carboxamide 6 588 212 4- [5- [1- [4-Gasyl-3- (trifluoromethyl) phenyl ] Pentyl] -2,5-dihydro-4-methyl-2,5-dioxo] pentyl] -N- [2- (digasmethyl) phenyl] hexahydro p ratio. Jing-1-Fermented amine 6 622 213 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] pentyl] -2,5-dihydro-4-methyl -2,5-dioxo-1'-pyrrole-3-yl] pentyl] -N- (2-methyl-phenyl) hexahydropyridine-1-carboxamide 6 568 214 4- [5- [1- [4-Amino-3- (diaminomethyl) benzyl] pentyl] -2,5-dimur-4-methyl-2,5-dioxo-1H-pyrrole-3- Yl] pentyl] -N- (3-methyl-phenyl) hexahydropyridine-1-carboxamide 6 568 215 4- [5- [1- [4-Gasyl-3- (difluoromethyl) Phenyl) phenyl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] pentyl] -N- (4-fluorophenyl) -Hexane 6 572

-84- 200301117 (79) 實例 名稱 類似於 實例合成 ESI-MS 吡畊-1-羧醯胺 216 4-[5-[1-[4-氰基-3-(三氟甲基)苯基]戊基]-2,5-二氫_4_甲 基-2,5-二氧代-1H-吡咯-3-基]戊基]-N-(4-甲氧基-苯基) 六氫吡畊小羧醯胺 6 584 217 N-(3-氰基苯基:ΗΗ>[1-[4-氰基各(三氟甲基)苯基]戊 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-3-基]戊基]六 氫吡畊-1-羧醯胺 6 579 218 4-[5-[1-[4-氰基各(三氟甲基)苯基]戊基]_2,5-二氫_4_甲 基-2,5-二氧代-1H-吡咯-3-基]戊基]-N-(3,5-二甲氧基-苯 基)六氫吡畊-1-羧醯胺 6 614 219 4-[5-[1-[4-氰基各(三氟甲基)苯基]戊基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯-3-基]戊基]-N-(2-苯基乙基)六 氫吡畊-1-羧醯胺 6 582 220 Ν-([1，Γ-聯苯基]-2-基>4-[5-[1-[4-氰基各(三氟甲基)苯 基]戊基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-3-基]戊 基]六氫吡畊小羧醯胺 6 630 221 4-[5-[1-[4-氣基-3-(三氟甲基)苯基]戊基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯各基]戊基]-N-[2-(l-甲基-乙基) 戊基]六氫吡畊-1-羧醯胺 6 596 222 4-〇[H4-氰基各(三氟曱基)苯基]戊基]_2,5-二氫冰甲 基-2,5-二氧代-1H-吡咯-3-基]戊基]-N-(2,6-二氯吡啶-4-基)苯基乙基)六氫?比1:1井-1-致酿胺 6 623 223 (R)-4-[5-[l-[4-氣基-3-(三氟甲基）苯基]戊基]-2,5-二氫 -4-甲基-2,5-二氧代-1H-吡咯-3-基]戊基]苯基乙 基)六氫吡畊小羧醯胺 6 582 224 4-[5-[1-[4_氣基-3-(三氟甲基)苯基]戊基]·2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]戊基]-Ν-[3-(三氟甲基)硫 烷基]苯基]六氫吡畊-1-羧醯胺 6 654 225 4-[5_[1-[4-氣基_3-(三氟甲基)苯基]戊基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯各基]戊基]-Ν-[(3-甲基苯基)甲 基]六氫p比呼-1-叛s盛胺 6 582 226 4-[5-[1-[4-氣基-3-(二氣甲基)苯基]戊基]-2,5-二氯-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]戊基]-Ν-[(4-甲氧基苯基) 甲基]六氫吡畊小羧醯胺 6 598 227 4-[5-[1-[4-氰基-3-(三氟甲基)苯基]戊基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]戊基]-N-(l，l，3,3-四甲基 6 590-84- 200301117 (79) Example name similar to Example Synthesis ESI-MS Pycnogenol-1-Carboxamidine 216 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] Amyl] -2,5-dihydro-4_methyl-2,5-dioxo-1H-pyrrole-3-yl] pentyl] -N- (4-methoxy-phenyl) hexahydro Pycnogenol Carboxamide 6 584 217 N- (3-cyanophenyl: pyrene> [1- [4-cyano (trifluoromethyl) phenyl] pentyl] -2,5-dihydro- 4-methyl-2,5-dioxo-1H-pyrrole-3-yl] pentyl] hexahydropyridine-1-carboxamide 6 579 218 4- [5- [1- [4-cyano Each (trifluoromethyl) phenyl] pentyl] _2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] pentyl] -N- (3, 5-dimethoxy-phenyl) hexahydropyridine-1-carboxamide 6 614 219 4- [5- [1- [4-cyano (trifluoromethyl) phenyl] pentyl]- 2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] pentyl] -N- (2-phenylethyl) hexahydropyridine-1-carboxyl Hydrazine 6 582 220 N-([1, Γ-biphenyl] -2-yl> 4- [5- [1- [4-cyano ((trifluoromethyl) phenyl] pentyl]- 2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] pentyl] hexahydropyridoxamine 6 630 221 4- [5- [1- [4-Amino-3- (trifluoromethyl) phenyl] pentyl] -2,5-dihydro-4- -2,5-dioxo-1H-pyrrole groups] pentyl] -N- [2- (l-methyl-ethyl) pentyl] hexahydropyridine-1-carboxamide 6 596 222 4-〇 [H4-cyano (trifluorofluorenyl) phenyl] pentyl] _2,5-dihydroicemethyl-2,5-dioxo-1H-pyrrole-3-yl] pentyl] -N- (2,6-dichloropyridin-4-yl) phenylethyl) hexahydro? Ratio 1: 1 well-1-fermenting amine 6 623 223 (R) -4- [5- [l- [4-Amino-3- (trifluoromethyl) phenyl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] pentyl Phenyl] phenylethyl) hexahydropyridoxamine 6 582 224 4- [5- [1- [4-Gas-3- (trifluoromethyl) phenyl] pentyl] · 2,5 -Dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] pentyl] -N- [3- (trifluoromethyl) sulfanyl] phenyl] hexahydropyridine Phen-1-carboxamide 6 654 225 4- [5_ [1- [4-Gas_3- (trifluoromethyl) phenyl] pentyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1'-pyrrole groups] pentyl] -N-[(3-methylphenyl) methyl] hexahydrop-bihu-1-benzylamine 6 582 226 4- [ 5- [1- [4-Amino-3- (diaminomethyl) phenyl] pentyl] -2,5-dichloro-4-methyl-2,5-dioxo-1H-pyrrole- 3-yl] pentyl] -N-[(4-methoxyphenyl) methyl] hexahydropyridoxamine 6 598 227 4- [5- [ 1- [4-cyano-3- (trifluoromethyl) phenyl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl ] Pentyl] -N- (l, l, 3,3-tetramethyl 6 590

-85- 200301117 (80) 實例 名稱 類似於 實例合成 ESI-MS 丁基)六氫吡畊-1-羧醯胺 表10.根據本發明通式I的化合物，其中v=三氟甲基苯甲 腈，馬I亞脖，n = 6 實例 ，， ，^ ，1、乂欣，η = 〇 名稱 類似於 實例合成 ESI-MS 228 4-L6-[Η4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-一氧代-1Η-Ρ比ρ各-3-基]己基]-六氫叶卜井-1-致酸1，1-二甲基乙酯 1 549 229 4-[2,5-一氣-3-甲基-4-[6-(4-甲基六氫外卜井-l-基）己 基]-2,5·二氧代-1Η-晚咯-1-基]-2-(三氟甲基)苯甲腈 3 463 230 Η4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-峨咯各基1己基]-六氫吡畊-1邊酸乙酯 3 521 231 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-⑽啶-2-基)六氫 叶匕4小基]己基]-1Η-吡嘻小基]·2_(三氟甲基)苯甲腈 3 526 232 4-[6-[ 1 -[4-氰基各(三氟曱基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯各基]己基>六氫吡畊小羧酸(苯 基甲酯） 3 583 233 4-L2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-(嘧啶-2-基)六氫 2匕:井+基]己基ΗΗ-ρ比洛小基]_2_(三氟甲基)苯甲腈 3 527 234 4-L2,5-二氫-3-[6-[4-(2-甲氧基苯基）六氫吡畊-丨·基]己 基]冰甲基-2,5-二氧代-1Η-吡咯-1-基；μι(三氟甲基)苯 甲腈 3 555 235 4 L2,5 一氣-3-甲基-4-[6-[4-(2-硝基苯基）六氫ρ比啡小 基]己基]·4-甲基_2,5-二氧代]Η_ρ比咯小基]冬(三氟甲 基)苯甲月膏 3 570 236 4_[2,5· 一氫各甲基-2,5_二氧代-1>[4-(吡畊冬基)-六氫 咖井小吳]己基]-1Η-♦各小基]_2_(:氟甲基)苯甲腈 3 527 237 4-[2,5-一氫·3_甲基冰卜㈣2乂甲基硫烷基苯基)六氫 叶匕_-1-基]己基]-2,5_二氧代]Η-p比哈小基]1(:翁甲 基)苯甲腈 、一弗^ 3 571 238 甲基^二氧代 心t基Γ氣17比呼小基]己基]_1Η"比咯基]冬(三氟甲 基)苯甲月膏 3 594 239 ‘ 4-[—5- 一氫-3-[6-[4-(2-甲氧基乙基）六氩ρ比畊· 1 ·基 基)苯 3 507-85- 200301117 (80) Example name similar to Example Synthesis of ESI-MS butyl) hexahydropyridine-1-carboxamide Table 10. Compounds of general formula I according to the invention, where v = trifluoromethyl benzyl Nitrile, MA I, N = 6 Example,,, ^, 1, 乂 欣, η = 〇 Name is similar to the example ESI-MS 228 4-L6- [Η4-cyano-3- (trifluoromethyl) ) Phenyl] -2,5-dihydro-4-methyl-2,5-monooxo-1Η-P ratio ρ each-3-yl] hexyl] -hexahydroyebui-1-acid 1 , 1-Dimethyl ethyl ester 1 549 229 4- [2,5-Mono-3-methyl-4- [6- (4-methylhexahydrocarbyl-l-yl) hexyl] -2, 5 · Dioxo-1Η-later-1-yl] -2- (trifluoromethyl) benzonitrile 3 463 230 Η4-cyano-3- (trifluoromethyl) phenyl] -2,5 -Dihydro-4-methyl-2,5-dioxo-1fluorene-erroyl 1-hexyl] -hexahydropyrine-1 ethyl acetate 3 521 231 4- [2,5-dihydro- 3-methyl-2,5-dioxo-4- [6- [4-pyridin-2-yl) hexahydropyridine 4-small] hexyl] -1Η-pyridine small] 2_ (tri Fluoromethyl) benzonitrile 3 526 232 4- [6- [1-[4-cyano (trifluorofluorenyl) phenyl] -2,5-dihydro-4-methyl-2,5- Dioxo-1Η-pyrrole groups] hexyl > Hydroxypyridine small carboxylic acid (phenyl Methyl ester) 3 583 233 4-L2,5-dihydro-3-methyl-2,5-dioxo-4- [6- [4- (pyrimidin-2-yl) hexahydro-2: well + Group] hexylfluorene-ρbiloxyl] _2_ (trifluoromethyl) benzonitrile 3 527 234 4-L2,5-dihydro-3- [6- [4- (2-methoxyphenyl) Hexahydropyridine- 丨 · yl] hexyl] Icemethyl-2,5-dioxo-1Η-pyrrole-1-yl; μ (trifluoromethyl) benzonitrile 3 555 235 4 L2,5 one gas- 3-methyl-4- [6- [4- (2-nitrophenyl) hexahydroρ-pyridinyl] hexyl] · 4-methyl_2,5-dioxo] pyridyl-pyrrolyl ] Winter (trifluoromethyl) benzyl moon cream 3 570 236 4_ [2,5 · Hydroxymethyl-2,5_dioxo-1 > [4- (Pyrogynyl) -hexahydrocaffeine Jing Xiaowu] Hexyl] -1Η- ♦ Each small group] _2 _ (: fluoromethyl) benzonitrile 3 527 237 4- [2,5-monohydro · 3-methylbenzyl hydrazone 2 乂 methylsulfanyl Phenyl) Hexyl-1-yl] hexyl] -2,5_dioxo] pyrene-p bihalidyl] 1 (: onylmethyl) benzonitrile, monofluoro ^ 3 571 238 methyl ^ Dioxo heart t radical Γ gas 17 Bihu Xiaoji] hexyl] _1Η " pyrrolyl] winter (trifluoromethyl) benzyl cream 3 594 239 '4-[— 5-monohydro-3- [6 -[4- (2-Methoxyethyl) hexagonal ρ Bigen · 1 · yl) benzene 3 507

-86- 200301117 (81) 實例 名稱 類似於 實例合成 ESI-MS 甲腈 240 4-[3-[6-[4-(3,5-二氯吡啶-4-基）六氫吡畊-1-基]己 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟 甲基)苯甲腈 3 594 241 4-[3-[6-(4-乙醯基六氫吡畊-1-基）己基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲腈 4 491 242 4-[3-[6-[4-[(呋喃-2-基)羰基]六氫吡畊小基]己基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯 甲腈 4 543 243 4-[2,5-二氫各甲基-2,5-二氧代-4-[6-[4-[(四氫呋喃-2-基)羰基]六氫吡畊小基]己基HH-吡咯-1-基]-2-(三氟 甲基)苯甲腈 4 547 244 4-[3-[6-[4_(環戊基羰基)六氫吡畊小基]己基]-2,5-二氫 -4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯甲腈 4 545 245 4-[2,5-二氫-3-甲基斗[6-[4-[(5-甲基異呤唑-3-基)-羰基] 六氫吡畊-1-基]己基]-2,5-二氧代-1H-吡咯小基]-2-(三 氟甲基)苯甲腈 4 558 246 4-[2,5-二氮-3-甲基-2,5-二氧代-4-[6-[4-(冬基乙酿基)~ 六氫吡畊-1-基]己基]-1H-吡咯小基]-2-(三氟甲基)苯甲 腈 4 567 247 4-[2,5-二氫·3-[6-[4-(4-甲氧基苯甲醯基)六氫吡畊-1-基] 己基]-4-甲基-2,5-二氧代基]-2-(二氣甲基) 苯甲腈 4 583 248 4-[2,5-二氫-3-[6-[4-(2-甲氧基苯甲醯基)六氫吡畊小基] 己基]冰甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基) 苯甲腈 4 583 249 4-[2,5-二氫-3-[6-[4-(甲氧基乙醯基)六氫吡畊-1-基]己 基]斗甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯 甲腈 4 521 250 4-[3-[6-[4-(2-氯苯甲醯基)六氫吡畊-1-基]己基]-2,5-二 氫-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲 腈 4 587 251 4-[3-[6·[4-(2-氟苯甲醯基)六氫吡畊小基]己基]-2,5-二 氫-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲 腈 4 571 252 4-[3-[6-[4-苯甲醯基六氫吡畊-1-基]己基]-2,5-二氫-4-甲 4 553-86- 200301117 (81) Example name similar to Example Synthesis ESI-MS Toluene 240 4- [3- [6- [4- (3,5-Dichloropyridin-4-yl) hexahydropyrine-1- Yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 3 594 241 4- [3- [6- (4-Ethylhexylpyridin-1-yl) hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole small group] 2- (trifluoromethyl) benzonitrile 4 491 242 4- [3- [6- [4-[(furan-2-yl) carbonyl] hexahydropyridine] hexyl] -2,5- Dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 543 243 4- [2,5-Dihydrodimethyl -2,5-dioxo-4- [6- [4-[(tetrahydrofuran-2-yl) carbonyl] hexahydropyridine] hexylHH-pyrrole-1-yl] -2- (trifluoro Methyl) benzonitrile 4 547 244 4- [3- [6- [4- (Cyclopentylcarbonyl) hexahydropyridine] hexyl] -2,5-dihydro-4-methyl-2,5 -Dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 545 245 4- [2,5-dihydro-3-methyl bucket [6- [4- [ (5-methylisopurazol-3-yl) -carbonyl] hexahydropyridin-1-yl] hexyl] -2,5-dioxo-1H-pyrrole small] -2- (trifluoromethyl ) Benzonitrile 4 558 246 4- [2,5-Diaza-3-methyl -2,5-dioxo-4- [6- [4- (winteryl ethyl alcohol) ~ hexahydropyridine-1-yl] hexyl] -1H-pyrrole small group] -2- (trifluoromethyl Phenyl) benzonitrile 4 567 247 4- [2,5-dihydro · 3- [6- [4- (4-methoxybenzyl) hexahydropyridine-1-yl] hexyl] -4 -Methyl-2,5-dioxo] -2- (digasmethyl) benzonitrile 4 583 248 4- [2,5-dihydro-3- [6- [4- (2-methyl Oxybenzyl) hexahydropyridine] hexyl] ice methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 583 249 4- [2,5-Dihydro-3- [6- [4- (methoxyethylfluorenyl) hexahydropyridin-1-yl] hexyl] methyl-2,5-dioxo- 1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 521 250 4- [3- [6- [4- (2-chlorobenzylfluorenyl) hexahydropyrrol-1-one Group] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 587 251 4- [3 -[6 · [4- (2-Fluorobenzyl) hexahydropyridine] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole small Yl] -2- (trifluoromethyl) benzonitrile 4 571 252 4- [3- [6- [4-Benzylamidinohexahydropyridin-1-yl] hexyl] -2,5-dihydro -4-A 4 553

-87- 200301117 (82) 實例 名稱 253 差:2,5:三[代-1 H-^^小基]基)苯甲腈 類似於 實例合成-87- 200301117 (82) Example Name 253 Poor: 2,5: Tris [Hydroxy-1 H-^^ small group] benzonitrile Similar to Example Synthesis

ESI-MS 254 4-[3-[6-[4-(環丁基羰基)六氫吡畊+基]己基]_2,5_二氫 I4:..?7基_2,5_二氧代-1Η巧比哈小基]_2_(三氟甲基)苯甲硬 4 531 4-[3-[6-[4-(^4_二甲i基苯甲酿吡畊小基瓦 基]-2,5-二氫-4-甲基-2,5-二氧代-lH-p比咯-1-基]-2-(三氟 甲基)苯甲腈 255 4-[2,5-二 ¢3-甲基：2,5-二氧代:4-[6^(苯基硫 乙fe基]六氮p比啡-1-基]己基]-IH-p比p各-1-基]-2-(三氣甲 _基)苯甲猜 256 4-[^，5-二氫各甲基-2,5-二氧代斗[6-[4^：氧基乙 六氫叶I：啡-1-基]己基]-1H-吡嘻-1-基]4(三氟甲基)苯甲 月青 257 4^，5-二氫-3-甲基-2,5-二氧代 氮基]己基]氣甲基)苯甲 腈 4 4 4 4 613 599 583 559 258 260 4-[2,5-二氫甲基-2,5-二氧代 丙基）六氫吡畊-1-基]己基]-1Η-吡咯-1-基]_2-(三氟甲 基)苯甲腈 ___4-[)-[6-[4-[(1，3-冬并二17号茂-5-基)窥基]六氫?比17井-1-基] 己基]二氫斗甲基-2,5-二氧代-1知比咯小基]冬f 氟甲基)苯甲月膏__ 4-[2,5-一風-3-[6-[4-[(4-甲氧基苯基)-乙酸基]六氫々匕?井 -1-基]己基]-4-甲基-2,5-二氧代-lH-p比嘻小基]2-(三氟 甲基)苯甲腈 — 4 581 597 261 4-[2,5-一氫-3-甲基_4-[6-[4-(2-甲基苯甲酸基)_六氫p比ρ井 基]己基]·2,5_二乳代-lH-p比p各-1-基]_2_(三氟甲基)笨 甲腈 4 567 262 263 4-[3-[6-〇(4-氯苯甲醯基)六氫吡畊己 氫-4_甲基-2,5-二氧代-111^比洛-1-基]_2-(三氟曱基)苯甲^____ f[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4^^^ 基]六鼠ρ比17井-1-基]己基]-1Η-0比洛-1-基]三氟甲其) 苯甲腈 ^ 4 587 573 264 4-〇[6-|>(4-氯苯氧基）乙醯基六氫吡畊小基]己 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-口比咯-1_基](三氣 甲基)苯甲腈 ~ -88- 617 200301117 (83) 實例 名稱 類似於 實例合成 ESI-MS 265 4-[3-[6-[4-(3-環戊基小氧代丙基）六氫吡畊小基]己 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟 甲基)苯甲腈 4 573 266 4-[3-[6-[4-(3-氯苯甲醯基)六氫吡畊小基]己基]-2,5-二 氫斗甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲 腈 4 587 267 4-[2,5-二氫-3-甲基-2,5-二氧代斗[6-[4-[4-(三氟甲基)苯 甲醯基]六氫吡畊小基]己基HH-吡咯小基]_2_(三氟甲 基)苯甲腈 4 621 268 4-[3-[6-[4-(4-氰基苯甲醯基)六氫吡畊-1-基]己基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯 甲腈 4 578 269 4-[3-[6-[4-(3,3-二甲基-1-氧代丁基）六氫吡畊-1-基]己 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟 甲基)苯甲腈 4 547 270 4-[2,5-二氫-3-甲基-4-[6-[4-(3-甲基-1-氧代丁基:六氫 吡畊-1-基]己基]-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲 基)苯甲腈 4 533 271 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-[(苯基-甲氧基) 乙醯基]六氫吡畊小基]己基HH-吡咯-1-基]-2-(三氟甲 基)苯甲腈 4 597 272 4-[3-[6-[4-(環戊基乙醯基)六氫吡畊-1-基]己基]-2,5-二 氫斗甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲 腈 4 559 273 4-j>[6-[4-(2,6-二氟苯甲醯基）六氫吡畊小基]己 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟 甲基)苯甲腈 4 589 274 4-[3-[6-[4-(2,6-二氯苯甲醯基）六氫吡畊小基]己 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟 甲基)苯甲腈 4 621 275 4-[2,5-二氫各甲基-2,5-二氧代-4·[6-[4-[2-(三氟甲基)苯 甲醯基]六氫吡畊小基]己基]-1Η-吡咯小基]-2-(三氟甲 基)苯甲腈 4 621 276 4-[3-[6-[4-(3-氟苯甲醯基)六氫吡畊-1-基]己基]-2,5-二 鼠-4-甲基-2,5-二氧代-lH-p比p各-1-基]-2-(二鼠甲基)苯甲 腈 4 571ESI-MS 254 4- [3- [6- [4- (Cyclobutylcarbonyl) hexahydropyridine + yl] hexyl] _2,5_dihydro I4: ..? 7 group_2,5_dioxy -1 -1 Biao Biha Xiaoji] _2_ (trifluoromethyl) benzyl hard 4 531 4- [3- [6- [4-(^ 4_Dimethyl i-benzyl pyridine small Kiwaki] -2,5-dihydro-4-methyl-2,5-dioxo-lH-p than pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 255 4- [2,5 -Di ¢ 3-methyl: 2,5-dioxo: 4- [6 ^ (phenylthioethylfeyl) hexazolium p-pyridin-1-yl] hexyl] -IH-p ratio p each -1 -Yl] -2- (trifluoromethyl-yl) benzyl 256 4-[^, 5-dihydro each methyl-2,5-dioxo [6- [4 ^: oxyethylene hexahydro Leaf I: phranyl-1-yl] hexyl] -1H-pyridine-1-yl] 4 (trifluoromethyl) benzidine 257 4 ^, 5-dihydro-3-methyl-2,5- Dioxo nitrogen] hexyl] gas methyl) benzonitrile 4 4 4 4 613 599 583 559 258 260 4- [2,5-dihydromethyl-2,5-dioxopropyl) hexahydropyridine Phen-1-yl] hexyl] -1Η-pyrrole-1-yl] _2- (trifluoromethyl) benzonitrile ___ 4-[)-[6- [4-[(1,3-Winter and two 17 No.cene-5-yl) peptyl] hexahydro? Than 17 well-1-yl] hexyl] dihydromethyl-2,5-dioxo-1 Zhibiro small group] winter f fluoromethyl) Benzyl month cream __ 4- [2,5- 一 风 -3- [6- [4-[(4-methoxyphenyl) -acetic acid [Hydroxy] hexahydrofluorene? -1-yl] hexyl] -4-methyl-2,5-dioxo-lH-p than hexyl] 2- (trifluoromethyl) benzonitrile — 4 581 597 261 4- [2,5-monohydro-3-methyl_4- [6- [4- (2-methylbenzoic acid group) _hexahydro p-ratio sphyl] hexyl] · 2,5 _Dilactyl-lH-p ratio p each-1-yl] _2_ (trifluoromethyl) benzonitrile 4 567 262 263 4- [3- [6-〇 (4-chlorobenzylfluorenyl) hexahydro Pycnohexyl hydrogen-4_methyl-2,5-dioxo-111 ^ bilol-1-yl] _2- (trifluorofluorenyl) benzyl ^ ____ f [2,5-dihydro-3- Methyl-2,5-dioxo-4- [6- [4 ^^^ yl] hexamorine ρ than 17 well-1-yl] hexyl] -1Η-0bilol-1-yl] trifluoromethyl Its) benzonitrile ^ 4 587 573 264 4-〇 [6- | > (4-chlorophenoxy) ethenylhexahydropyridine] hexyl] -2,5-dihydro-4-methyl -2,5-dioxo-1H-pyrrol-1-yl] (trifluoromethyl) benzonitrile ~ -88- 617 200301117 (83) Example name is similar to Example Synthesis ESI-MS 265 4- [3- [6- [4- (3-Cyclopentyl small oxopropyl) hexahydropyridine] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo -1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 573 266 4- [3- [6- [4- (3-chlorobenzylidene) hexahydropyridine small group] hexyl ] -2,5-Dihydromethyl-2,5- Oxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 587 267 4- [2,5-dihydro-3-methyl-2,5-dioxo [6- [4- [4- (trifluoromethyl) benzylidene] hexahydropyridine] hexylHH-pyrrole small] _2_ (trifluoromethyl) benzonitrile 4 621 268 4- [3- [ 6- [4- (4-cyanobenzyl) hexahydropyridine-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole Small group] -2- (trifluoromethyl) benzonitrile 4 578 269 4- [3- [6- [4- (3,3-Dimethyl-1-oxobutyl) hexahydropyridine- 1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 547 270 4- [2,5-Dihydro-3-methyl-4- [6- [4- (3-methyl-1-oxobutyl: hexahydropyridin-1-yl] hexyl] -2,5- Dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 533 271 4- [2,5-dihydro-3-methyl-2,5-dioxo- 4- [6- [4-[(phenyl-methoxy) ethenyl] hexahydropyridine] hexylHH-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 597 272 4- [3- [6- [4- (Cyclopentylethenyl) hexahydropyridine-1-yl] hexyl] -2,5-dihydromethyl-2,5-dioxo -1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 559 273 4-j > [6- [4- (2, 6-difluorobenzyl) hexahydropyridine] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (Trifluoromethyl) benzonitrile 4 589 274 4- [3- [6- [4- (2,6-dichlorobenzyl) hexahydropyridine] hexyl] -2,5-di Hydrogen-4-methyl-2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 621 275 4- [2,5-dihydro each methyl-2 , 5-dioxo-4 · [6- [4- [2- (trifluoromethyl) benzylidene] hexahydropyridine] hexyl] -1Η-pyrrole small] -2- (tri Fluoromethyl) benzonitrile 4 621 276 4- [3- [6- [4- (3-Fluorobenzyl) hexahydropyridine-1-yl] hexyl] -2,5-dimur-4 -Methyl-2,5-dioxo-lH-p than p each-1-yl] -2- (dimuryl) benzonitrile 4 571

-89- 200301117 (84) 實例 名稱 類似於 實例合成 ESI-MS 277 4-[2,5-二氫-3-[6-[4-(3-甲氧基苯甲醯基)-六氫吡畊-1-基]己基]冰甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲 基)苯甲腈 4 583 278 4 - [2,5-二鼠-3-甲基-2,5-二氧代-4-[6-[4-[3_(二鼠甲基)冬 甲醯基]六氫吡畊小基]己基HH-吡咯小基]-2-(三氟甲 基)苯甲腈 4 621 279 4-[2,5-二氫-3-甲基-4-[6-[4-(3-甲基苯甲醯基)六氫吡畊 -1-基]己基]-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯 甲腈 4 567 280 4-[3-[6-[4-(4-氟苯甲醯基)六氫吡畊小基]己基]-2,5-二 氫斗甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲 腈 4 571 281 4-[2,5-二氫-3-甲基-4-[6-[4-(4-甲基苯甲醯基)六氫吡畊 -1-基]己基]-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯 甲腈 4 567 282 4-[2,5-二氫-3-甲基-4-[6-[4-[(莕小基)-羰基]六氫吡畊 -1-基]己基]-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯 甲腈 4 603 283 4-[2,5-二氮-3-甲基-4-[6-[4-[(奈-2-基)-談基]7T鼠叶匕p井 小基]己基]-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯 甲腈 4 603 284 4-[3-[6-[4-(3-夜基豕甲酿基）7T鼠^比呼-1-基]己基]-2,5_ 二氫4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯 甲腈 4 578 285 4-[3-[6-[4-(環己基羰基)六氫吡畊小基]己基]-2,5-二氫 -4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲腈 4 559 286 4-[3-[6-[4-[[4-(1，1-二甲基乙基)苯氧基]乙醯基]六氫吡 ρ井-1-基]己基]-2,5-二氮-4-甲基-2,5-二氧代-lH-p比嘻-1_ 基]冬(三氟甲基)苯甲腈 4 639 287 4·[2,5-二氫-3-[6-[4-(3-甲氧基小氧代丙基)六氫吡畊-1-基]己基]-4-甲基-2,5-二乳代-]·!·!-#!^各-1-基]-2-(二氣甲 基)苯甲腈 4 534 288 4-[2,5-二氫-3-[6-[4-[(2-甲氧基乙氧基)-乙醯基]六氫吡 畊小基]己基]-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三 氟甲基)苯甲腈 4 564 289 4-[2,5_二氮-3_[6-[4-[[2-(2-甲氧基乙氧基)-乙酿基]:ΓΤ氫 4 608-89- 200301117 (84) Example name is similar to Example Synthesis ESI-MS 277 4- [2,5-Dihydro-3- [6- [4- (3-methoxybenzyl) -hexahydropyridine Phen-1-yl] hexyl] Icemethyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 583 278 4-[2,5- Dimur-3-methyl-2,5-dioxo-4- [6- [4- [3_ (dimuryl) benzylidene] hexahydropyridine] hexylHH-pyrrole ] -2- (trifluoromethyl) benzonitrile 4 621 279 4- [2,5-dihydro-3-methyl-4- [6- [4- (3-methylbenzylidene)) hexa Hydropyrine-1-yl] hexyl] -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 567 280 4- [3- [6- [4- (4-Fluorobenzyl) hexahydropyridine] hexyl] -2,5-dihydromethyl-2,5-dioxo-1H-pyrrole small] -2- ( Trifluoromethyl) benzonitrile 4 571 281 4- [2,5-Dihydro-3-methyl-4- [6- [4- (4-methylbenzylhydrazyl) hexahydropyroxy-1 -Yl] hexyl] -2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 4 567 282 4- [2,5-dihydro-3-methyl- 4- [6- [4-[(fluorenyl) -carbonyl] hexahydropyridine-1-yl] hexyl] -2,5-dioxo-1H-pyrrole small] -2- (trifluoromethyl (Yl) benzonitrile 4 603 283 4- [2,5-diaza-3-methyl- 4- [6- [4-[(Nai-2-yl) -talkyl] 7T mouse leaf dwelling well small base] hexyl] -2,5-dioxo-1H-pyrrole small base] -2- ( Trifluoromethyl) benzonitrile 4 603 284 4- [3- [6- [4- (3-N-methylpyridyl) 7T mouse ^ bihu-1-yl] hexyl] -2,5_ dihydro 4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 578 285 4- [3- [6- [4- (cyclohexyl Carbonyl) hexahydropyridine] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole small] -2- (trifluoromethyl) benzonitrile 4 559 286 4- [3- [6- [4-[[4- (1,1-Dimethylethyl) phenoxy] ethenyl] hexahydropyridine-1-yl] hexyl]- 2,5-diazol-4-methyl-2,5-dioxo-lH-p-bicyclo-1_yl] dong (trifluoromethyl) benzonitrile 4 639 287 4 · [2,5-di Hydrogen-3- [6- [4- (3-methoxy small oxopropyl) hexahydropyrine-1-yl] hexyl] -4-methyl-2,5-dilacto-] !! ·!-#! ^ Each-1-yl] -2- (digasmethyl) benzonitrile 4 534 288 4- [2,5-dihydro-3- [6- [4-[(2-methyl (Oxyethoxy) -ethenyl] hexahydropyridine] hexyl] -4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl ) Benzonitrile 4 564 289 4- [2,5_diaza-3_ [6- [4-[[2- (2-methoxyethoxy) -ethynyl]]: ΓΤ hydrogen 4 608

-90- 20030111-90- 20030111

29〇 4-[4-[6_〇(環丙基橫醯基)六氫P比畊小基]己基]_2,5-_ 氫各甲基_2,5-二氧代-1Η^比咯-1·基]_2—(三氟甲基)苯甲 月青________ 4-[2,5- —風-3-[6-[4-(2-甲氧基乙基)-橫g盔基]六氫p比呼 小基]己基]·4-甲基·2,5·二氧代-IH-p比嘻-1-基]_2_(三氣 甲基)苯甲腈___ ~Τ[2,5-^^·3·[6-[4-[[2-(2-甲氧Ε氧基)-乙基]-石 基]7Τ氳ρ比。井-1-基]己基]基_2,5_二氧代]Η-ρ比各小 基]_2_(三氟甲基)苯甲腈__ 293 4-[2,5-二氲-3-[6-[4-[[2-[2-(2-甲氧基乙氧基)_ 乙氧基]· 乙基]橫醯基]六氫吡基]己基]冬甲基_2,5_二氧代 -1Η-吡咯小基]冬(三氟甲基)苯甲腈 291 292 294 4-[6-[1-[4-氣基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 二氧代-1Η-吡咯各基]己基]-Ν，Ν-二甲基六氫吡畊 小績8盈胺 570 614 658 555 295 4 [2,5-一鼠-3-甲基-2,5-一氧代-4-[6-[4-(苯基-橫酿基) 「氫吡畊小基]己基]-1Η-吡咯-1-基]-2_(三氟甲基)苯甲 腈 589 296 4-[2,5_一風各甲基-4_[6-[4-(甲基績g蠢基）六氫ρ比Ρ井小 基]己基]_2,5-二氧代-1H-峨咯小基]_2_(三氟甲基)苯甲 腈 527 297 4-p，5-二氫-3-甲基-4-[6-[4-[(4-甲基苯基)-磺醯基]六氫 吡畊小基]己基]_2,5·二氧代_1H_P比咯小基]冬(三氟甲 基)苯甲腈 603 ❿ 298 N-[4-[[4-[6-〇[4-氰基各(三氟甲基)苯基]_2,5_二氫冰 甲基-2,5-二氧代-1仏峨咯士基]己基]六氫吡畊]-基]磺 酿基]-苯基]乙醯胺 646 299 4-[2,5-二氫-3-甲基-2,5-二氧-4-[6-[4-[(苯基甲基)-磺醯 基]六氫吡畊-1-基]己基HH-吡咯-1-基]冬(三氟甲基) 苯甲腈 603 300 4-[3-[6-[4-[(4·氰基苯基）碍酿基]六氫叶卜井七基]己 基]-2,5-二氫斗甲基-2,5-二氧代-1H-咐咯小基]·2-(三氟 甲基)苯甲腈 614 301 4-[2,5_二氫-3-甲基-4_[6-[4_[(茶_2·基)·績醯基]六氫吡畊 639 -91 - (86)200301117 實例29〇4- [4- [6-〇 (cyclopropyl transverse fluorenyl) hexahydro P than piao small group] hexyl] _2,5-_ hydrogen each methyl_2,5-dioxo-1 Pyr-1.yl] _2- (trifluoromethyl) benzylazine ________ 4- [2,5- —Wind-3- [6- [4- (2-methoxyethyl) -transg Helmetyl] Hexyl p-Hexyl] Hexyl] · 4-methyl · 2,5 · Dioxo-IH-p than Hil-1-yl] _2_ (trifluoromethyl) benzonitrile ___ ~ Τ [2,5-^^ · 3 · [6- [4-[[2- (2-methoxyEoxy) -ethyl] -litho] 7 Tρρ ratio. Well-1-yl] hexyl] yl_2,5_dioxo] pyrene-ρ than each small group] _2_ (trifluoromethyl) benzonitrile_ 293 4- [2,5-difluorene-3 -[6- [4-[[2- [2- (2-methoxyethoxy) _ethoxy] · ethyl] pyridinyl] hexahydropyridyl] hexyl] dongmethyl_2, 5-dioxo-1Η-pyrrole small group] winter (trifluoromethyl) benzonitrile 291 292 294 4- [6- [1- [4-Gasyl-3- (trifluoromethyl) phenyl]] -2,5-dihydro-4-methyldioxo-1Η-pyrrole group] hexyl] -N, N-dimethylhexahydropyridine, 8-aminoamine 570 614 658 555 295 4 [2, 5-monorat-3-methyl-2,5-monooxo-4- [6- [4- (phenyl-transmethyl), hydropyridyl] hexyl] -1Η-pyrrole-1- Phenyl] -2_ (trifluoromethyl) benzonitrile 589 296 4- [2,5_yifeng each methyl-4_ [6- [4- (methyl phenyl g) yl) hexahydrogen ρ is smaller than P well Group] hexyl] _2,5-dioxo-1H-erroyl small group] _2_ (trifluoromethyl) benzonitrile 527 297 4-p, 5-dihydro-3-methyl-4- [6- [4-[(4-methylphenyl) -sulfofluorenyl] hexahydropyridine] hexyl] _2,5 · dioxo_1H_Ppyrrolidine] winter (trifluoromethyl) benzonitrile 603 ❿ 298 N- [4-[[4- [6-〇 [4-cyano (trifluoromethyl) phenyl] _2,5-dihydroicemethyl-2,5-dioxo-1 Sagaroski] hexyl] VI Pycnogenol] -yl] sulfonyl] -phenyl] acetamidin 646 299 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [6- [4- [ (Phenylmethyl) -sulfofluorenyl] hexahydropyridin-1-yl] hexylHH-pyrrole-1-yl] dong (trifluoromethyl) benzonitrile 603 300 4- [3- [6- [ 4-[(4 · Cyanophenyl) alkynyl] Hexahydrobuboheptyl] hexyl] -2,5-dihydromethyl-2,5-dioxo-1H- ] · 2- (trifluoromethyl) benzonitrile 614 301 4- [2,5_dihydro-3-methyl-4_ [6- [4 _ [(Tea_2. Hydroponic 639 -91-(86) 200301117 Examples

小基]己基]2,5-二氧瓦：1^^7^^77 甲腈 土 •氣甲基)苯 類似於 實例合成Small base] hexyl] 2,5-dioxo: 1 ^^ 7 ^^ 77 Carbononitrile • Gas methyl) benzene Similar to example

ESI-MS 302 303 -1-基]己基]-2,5-二氫-4-甲基-2 5 j^、f ♦井 基]冬(三氟甲基)苯甲腊二一虱代]沁吡咯小 4-[2,5-一 風甲基-- 基]六氫㈣小基]己基HH-咐上if :基)-石』 5 682ESI-MS 302 303-1-yl] hexyl] -2,5-dihydro-4-methyl-2 5 j ^, f Qin pyrrole small 4- [2,5-monophosphine methyl--yl] hexahydrofluorenyl small group] hexyl HH-Hy

-92- (87)-92- (87)

實例 名稱 類似於 實例合成 ESI-MS 基]六氫吡畊小基]己基]-2,5-二氧代-1H-吡咯小 基]-2-(三氟甲基)苯甲腈 314 4-[6-[1-[4-氛基-3-(三氣甲基）苯基]-2,5-二氯-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-(1，1-二甲基乙基)六 氫ρ比ρ井-1-複酿胺 6 548 315 4-[6-[ 1 -[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]苯基六氫吡畊小羧 醯胺 6 568 316 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基](莕小基)六氫吡畊 -1-羧醯胺 6 618 317 4-[6-[Η4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-(莕-2-基)六氫吡畊 -1-羧醯胺 6 618 318 Ν-(4-氰基苯基)-4_[6-[Η4-氰基各(三氟甲基)苯基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-3-基]己基]六氫吡畊 6 593 319 4-[6-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-N-(l-甲基乙基)-六氫 吡畊小羧醯胺 6 534 320 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-[3-(三氟甲基)苯基] 六氫批ρ井-1 -竣si胺 6 636 321 4-[6-[1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-(2-氟苯基)-六氫吡 畊-1-羧醯胺 6 586 322 N-(2-氯苯基)-4-[6-[1-[4-氰基三氟甲基)苯基]-2,5-二 氫-4-甲基-2,5-二氧代-1H-吡咯-3-基]己基]六氫吡畊小 羧醯胺 6 602 323 4-[6-[1-[4-夜基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-(2-甲氧基-苯基)六 氫吡畊-1-羧醯胺 6 598 324 4-[6-[1-[4-乱基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]三氟甲基)苯基] 六氫咐/井-1-複S產胺 6 636 325 4-[6-[H4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 6 582 -93 - 20030111? (88) 實例 名稱 類似於 實例合成 ESI-MS -2,5-二氧代-1H-吡咯-3-基]己基]-N-(2-甲基-苯基)六氫 吡畊-1-羧醯胺 326 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-(3-氟苯基)-六氫吡 畊-1-羧醯胺 6 586 327 N-(3-氯苯基)-4-[6-[1-[4-氰基-3-(三氟甲基)苯基]_2,5-二 氫-4-甲基-2,5-二氧代-1H-吡咯-3-基]己基]六氫吡畊-1- 羧醯胺 6 602 328 4-[6-[ H4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 二氧代-1H-吡咯-3-基]己基]-N-(3-甲氧基-苯基)-六 氫口比^1井小叛酿胺 6 598 329 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-(3-甲基苯基)-六氫 p比17井-1-叛胺 6 582 330 4-[6-[1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-(4-氟苯基)-六氫吡 口井-1-複酸胺 6 586 331 Ν-(4-氯苯基)-4-[6-[1-[4·氰基各(三氟甲基)苯基]-2,5-二 鼠-4-甲基-2,5-二氧1代-111-^7比17各-3-基]己基]7^鼠?比'：7井-1- 羧醯胺 6 602 332 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-(4-甲氧基-苯基)-六 氫吡畊小羧醯胺 6 598 333 4-[6-[1-[4-氣基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-[4-(三氟甲基)苯基] 六氫吡畊小羧醯胺 6 636 334 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯·3-基]己基]-Ν-(4-甲基苯基)六氫 吡畊小羧醯胺 6 582 335 4-[6-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-(丙-2-烯基)-六氫吡 畊小羧醯胺 6 532 336 4-[6-[1-[4-氣基-3-(二氣甲基）本基]-2,5-二鼠-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-環己基-六氫吡畊 -1-叛8盛胺 6 574 337 4-[6-[1-[4-氣基-3-(二氟甲基）本基]-2,5-二氯-4-甲基 6 582 -94- 200301117 (89) 實例 名稱 類似於 實例合成 ESI-MS -2,5-二氧代-1H-吡咯各基]己基]-N-(苯基甲基)-六氫吡 畊小羧醯胺 338 N-(3-氰基苯基)-4_[6-[1-[4-氰基-3-(三氟甲基)苯基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-3-基]己基]六氫吡畊 6 593 339 4-[6-[H4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-(3,5-二甲氧基-苯 基)-穴鼠卩比p井-I-叛酿胺 6 628 340 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[3-(甲基硫烷基)苯 基]六氫p比呼-1 -致S盛胺 6 614 341 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-(4-苯氧基-苯基)六 氫吡畊小羧醯胺 6 660 342 4-[6-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[4-(甲基硫烷基)苯 基]六氫吡畊-1-羧醯胺 6 614 343 4-[6-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[4-(l-甲基乙基)苯 基]六氫吡畊小羧醯胺 6 610 344 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-111-?比17各-3-基]己基]~^-(2-表基乙基)-7^鼠 吡畊-1-羧醯胺 6 596 345 N-([l，l’-聯苯基]i基)-4-[6-[1-[4-氰基各(三氟甲基)苯 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-3-基]己基]六 氫吡畊-1-羧醯胺 6 644 346 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代各-3-基]己基]-Ν-[4-(本基-甲氧基)豕 基]六氫吡畊小羧醯胺 6 674 347 Ν-(2-氰基苯基)-4-[6-[1-[4-氰基-3-(三氟甲基)苯基]-2,5· 二氫-4-甲基-2,5-二氧代-1Η-吡咯-3-基]己基]六氫吡畊 -1-羧醯胺 6 593 348 4-[6-[1-[4-夜基-3-(二氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-[2-(噻-2-基)-乙基] 六氫吡畊小竣醯胺 6 602 349 (1R-反式)-4-[6-[1-[4-夜基-3-(二氟甲基)苯基]-2,5-二氫 6 608The name of the example is similar to the example Synthesis of ESI-MS group] Hexahydropyridine] Hexyl] -2,5-dioxo-1H-pyrrolepyridyl] -2- (trifluoromethyl) benzonitrile 314 4- [6- [1- [4-Amino-3- (trifluoromethyl) phenyl] -2,5-dichloro-4-methyl-2,5-dioxo-1'-pyrrole-3- Yl] hexyl] -N- (1,1-dimethylethyl) hexahydro ρ ratio ρ well -1- compound amine 6 548 315 4- [6- [1-[4-cyano each (trifluoro (Methyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] hexyl] phenylhexahydropyridine 6 568 316 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1Η-pyrrole- 3-yl] hexyl] (fluorenyl) hexahydropyridine-1-carboxamide 6 618 317 4- [6- [fluorene 4-cyano-3- (trifluoromethyl) phenyl] -2,5 -Dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] hexyl] -N- (fluoren-2-yl) hexahydropyridine-1-carboxamide 6 618 318 Ν- (4-cyanophenyl) -4_ [6- [Η4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo -1Η-pyrrole-3-yl] hexyl] hexahydropyridine 6 593 319 4- [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4 -Methyl-2,5-dioxo-1'-pyrrole -3-yl] hexyl] -N- (l-methylethyl) -hexahydropyridoxamine 6 534 320 4- [6- [1- [4-cyano-3- (trifluoromethyl) ) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] hexyl] -N- [3- (trifluoromethyl) phenyl ] Hexahydro batch ρ-1-Junsi amine 6 636 321 4- [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl -2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- (2-fluorophenyl) -hexahydropyridine-1-carboxamide 6 586 322 N- (2-chlorobenzene ) -4- [6- [1- [4-cyanotrifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3 -Yl] hexyl] hexahydropyridoxamine 6 602 323 4- [6- [1- [4-Etyl-3- (trifluoromethyl) phenyl] -2,5-dihydro-4 -Methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- (2-methoxy-phenyl) hexahydropyridine-1-carboxamide 6 598 324 4- [6- [1- [4-Eryl-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3- [Hexyl] hexyl] trifluoromethyl) phenyl] Hexane 5-Dihydro-4-methyl 6 582 -93-20030111? (88) Example name is similar to Example Synthesis ESI- MS -2,5-Dioxo-1H-pyrrole-3-yl] hexyl] -N- (2-methyl-phenyl) hexahydropyridine-1-carboxamide 326 4- [6- [1 -[4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl]- N- (3-fluorophenyl) -hexahydropyridine-1-carboxamide 6 586 327 N- (3-chlorophenyl) -4- [6- [1- [4-cyano-3- ( Trifluoromethyl) phenyl] _2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] hexahydropyridine-1-carboxamide 6 602 328 4- [6- [H4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyldioxo-1H-pyrrole-3-yl] hexyl]- N- (3-methoxy-phenyl) -hexahydrokou ratio ^ 1 well small amine 6 598 329 4- [6- [1- [4-cyano-3- (trifluoromethyl) benzene Group] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- (3-methylphenyl) -hexahydro p ratio 17 I-1--1-amine 6 582 330 4- [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-di Oxo-1Η-pyrrole-3-yl] hexyl] -N- (4-fluorophenyl) -hexahydropyrrolidone-1-fatty acid amine 6 586 331 Ν- (4-chlorophenyl) -4- [6- [1- [4 · cyano (trifluoromethyl) phenyl] -2,5-dimur-4-methyl-2,5-dioxo 1-111- ^ 7 to 17 each -3 -Yl] hexyl] 7 ^ murine ratio: 7-well-1-carboxamide 6 602 332 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2 , 5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] hexyl] -N- (4-methoxy-phenyl) -hexahydropyridine Amine 6 598 333 4- [6- [1- [4-Gas-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo- 1Η-pyrrole-3-yl] hexyl] -N- [4- (trifluoromethyl) phenyl] hexahydropyridoxamine 6 636 334 4- [6- [1- [4-cyano- 3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole · 3-yl] hexyl] -N- (4-methyl Phenyl) hexahydropyridoxamine 6 582 335 4- [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1'-pyrrole-3-yl] hexyl] -N- (prop-2-enyl) -hexahydropyridoxamine 6 532 336 4- [6- [1- [ 4-amino-3- (difluoromethyl) benzyl] -2,5-dimur-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] hexyl] -N- Cyclohexyl-hexahydropyridine-1-amino-8 amine 6 574 337 4- [6- [1- [4-Gasyl-3- (difluoromethyl) benzyl] -2,5-dichloro- 4-methyl 6 582 -94- 200301117 (89) Example name is similar to Example Synthesis ESI-MS -2,5-dioxo-1H-pyrrole groups] hexyl] -N- (phenylmethyl) -hexahydropyroxypyramine 338 N- (3-cyanophenyl) -4_ [6 -[1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] Hexyl] hexahydropyridine 6 593 339 4- [6- [H4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxy -1H-pyrrole-3-yl] hexyl] -N- (3,5-dimethoxy-phenyl) -Hombor mole ratio p-I-Iertamine 6 628 340 4- [6- [ 1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- [3- (methylsulfanyl) phenyl] hexahydrop-peptone-1 -S-induced amine 6 614 341 4- [6- [1- [4-cyano-3- (trifluoro (Methyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- (4-phenoxy-phenyl) Hexahydropyridoxamine 6 660 342 4- [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5 -Dioxo-1H-pyrrole-3-yl] hexyl] -N- [4- (methylsulfanyl) phenyl] hexahydropyridine-1-carboxamide 6 614 343 4- [6- [ 1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole- 3-yl] hexyl] -N- [4- (l-methylethyl) phenyl] hexahydropyridoxamine 6 610 344 4- [6- [1- [4-cyano-3- (Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-? Than 17 each 3-yl] hexyl] ~ ^-(2-Table Ethyl) -7 ^ muridine-1-carboxamide 6 596 345 N-([l, l'-biphenyl] iyl) -4- [6- [1- [4-cyano each (Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] hexahydropyridine-1-carboxamide 6 644 346 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo each- 3-yl] hexyl] -N- [4- (benzyl-methoxy) fluorenyl] hexahydropyridoxamine 6 674 347 Ν- (2-cyanophenyl) -4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5 · dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] hexyl ] Hexahydropyridine-1-carboxamide 6 593 348 4- [6- [1- [4-Ethyl-3- (difluoromethyl) phenyl] -2,5-dihydro-4-methyl -2,5-dioxo-1'-pyrrole-3-yl] hexyl] -N- [2- (thia-2-yl) -ethyl] hexahydropyroxypyramine 6 602 349 (1R -Trans) -4- [6- [1- [4-nightyl-3- (difluoromethyl) phenyl] -2,5-dihydro 6 608

-95- 20030111?-95- 20030111?

(90) 實例 名稱 類似於 實例合成 ESI-MS -4-甲基-2,5-二氧代-1H-吡咯-3-基]己基]-N-(2-苯基環 丙基)六氫吡畊-1-羧醯胺 350 4-[6-[H4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 _2,5_二氧代-1H4咯各基]己基]-Ν·(2,6-二氟苯基)六氫 外匕畊小幾si胺 6 604 351 4-[6-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4·甲基 _2,5-二氧代-1H-♦各各基]己基]善(2,6-二氯苯基)六氫 p比畊小幾酿胺 6 636 352 4-[6-[1-[4_氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5_二氧代-1Η-吡咯各基]己基]-Ν-(2,4-二甲氧基-苯 基)六氫吡畊-1-羧醯胺 6 628 353 4-[6-[Η4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 _2,5·二氧代-1Η-吡咯各基]己基]-Ν·(2,5-二甲氧基-苯 基)六氫吡畊-1-幾醯胺 6 628 354 4·[6-[1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 _2,5_二氧代-1Η-吡咯各基]己基]-Ν-(2,6-二甲基-苯基) 六氫吡ρ井小羧醯胺 6 596 355 4-[6-[1-|>氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 _2,5-二氧代-1Η-吡咯各基]己基]-Ν-(三氣乙醯基)六氫 吡畊-1-幾醯胺 6 637 356 (S)4-[6-[l-[4-氰基-3-(三氟甲苯基)·2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-N-(l-苯基乙基)六氫 ρ比呼小幾酿胺 6 596 357 (R)4-[6-[H4-氰基各(三氟甲基)苯基]-2,5·二氫冰甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[l-(莕-1-基）乙基] 六氫吡畊小羧醯胺 6 646 358 4-[6-[ 1 -[4-氰基各(三氟甲基）苯基]-2,5-二氫冰甲基 _2,5_二氧代-1H-吡咯！基]己基]-N-(2,4,6·三氯苯基)六 氫吡畊-1-羧醯胺 6 671 359 4-[6-[H4-氰基各(三氟甲基）苯基]-2,5-二氫冰甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[2-(l-甲基乙基)苯 基]六氫吡畊小羧醯胺 6 610 360 4-[6-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 _2,5-二氧代-1H-吡咯各基]己基]-N-(3,5-二氯苯基)六氫 吡畊-1-幾醯胺 6 636 361 4-[6-[ 1 -[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 6 610(90) Example name similar to Example Synthesis ESI-MS-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- (2-phenylcyclopropyl) hexahydro Pycnogenol-1-carboxamide 350 4- [6- [H4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl_2,5_dioxo- 1H4 allyl] hexyl] -N · (2,6-difluorophenyl) hexahydrogenium amine amine 6 604 351 4- [6- [1- [4-cyano (trifluoromethyl Group) phenyl] -2,5-dihydro-4 · methyl_2,5-dioxo-1H- ♦ each group] hexyl] s (2,6-dichlorophenyl) hexahydro p ratio Gengxiaojiu amine 6 636 352 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5_ Dioxo-1Η-pyrrole groups] hexyl] -N- (2,4-dimethoxy-phenyl) hexahydropyridine-1-carboxamide 6 628 353 4- [6- [Η4-cyano Di (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl_2,5 · dioxo-1Η-pyrroleyl] hexyl] -N · (2,5-dimethyl Oxy-phenyl) hexahydropyrine-1-chitamine 6 628 354 4 · [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro- 4-methyl_2,5_dioxo-1'-pyrrole groups] hexyl] -N- (2,6-dimethyl-phenyl) hexahydropyridine 6 596 355 4- [6- [1- | > Di (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl_2,5-dioxo-1Η-pyrrole, each group] hexyl] -N- (trifluoroethanyl) Hexahydropyr-1--1-chitamine 6 637 356 (S) 4- [6- [l- [4-cyano-3- (trifluorotolyl) · 2,5-dihydro-4-methyl -2,5-dioxo-1Η-pyrrole-3-yl] hexyl] -N- (l-phenylethyl) hexahydroρ than chlorhexamine 6 596 357 (R) 4- [6- [H4-cyano (trifluoromethyl) phenyl] -2,5 · dihydroicemethyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- [l- (Fluoren-1-yl) ethyl] hexahydropyridoxamine 6 646 358 4- [6- [1-[4-cyano ((trifluoromethyl) phenyl)]-2,5-di Hydroxymethyl-2,5_dioxo-1H-pyrrole! Methyl] hexyl] -N- (2,4,6 · trichlorophenyl) hexahydropyridine-1-carboxamide 6 671 359 4- [6- [H4-cyano (trifluoromethyl) benzene Yl] -2,5-dihydroglacial methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- [2- (l-methylethyl) phenyl] hexahydro Pycnogenol 6 610 360 4- [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl_2,5-di Oxo-1H-pyrrole groups] hexyl] -N- (3,5-dichlorophenyl) hexahydropyridine-1-chiamine 6 636 361 4- [6- [1-[4-cyano Each (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl 6 610

-96 - 200301117 (91)-96-200301117 (91)

實例 名稱 類似於 實例合成 ESI-MS -2,5-二氧代-1H-吡咯各基]己基]-N-(2,4,6-三甲基-苯 基)六氫吡畊-1-羧醯胺 362 4-[6-[ 1 -[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[4-[(三氟甲基)硫烷 基]苯基]六氫吡畊-1-羧醯胺 6 668 363 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯各基]己基]-N-[(2,4-二氯苯基）甲 基]六氫p比呼-1-複醯胺 6 651 364 4-[6-[ 1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[2-(甲基硫烷基)苯 基]六氫吡畊-1-羧醯胺 6 614 365 4-[6-[H4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二乳代- lH-p比p各-3-基]己基]-N-(2,6-二氣p比淀-4- 基)六氫?比p井-1 -複S盛胺 6 637 366 (R)4-[6_[ 1-[4_氰基-3-(三氟甲苯基)-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-Ν·(1-苯基乙基)六氫 吡畊-1-羧醯胺 6 596 367 ⑸4-[6-〇[4-氰基-3-(三氟甲基)苯基]-2,5·二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-N-[l-(莕小基）乙基] 六氫井小致si胺 6 646 368 4-[6-[H4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[l-甲基小[3-(1-甲 基乙烯基)苯基]六氫吡畊-1-羧醯胺 6 650 369 4-[6-[1-[4-來基-3-(二氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[2-(三氟甲氧基)苯 基]六氫吡畊小羧醯胺 6 652 370 4-[6-[1-[4-氣基-3-(二氣甲基）木基]-2,5-二氯-4-甲基 二氧代-1H-吡咯各基]己基]-N-(三環[3·3.1·ΐΛ7]癸 -1-基)六氫吡畊-1-羧醯胺 6 626 371 4-[6-[1-[4-氣基-3-(二氣甲基）木基]-2,5-二氯-4-甲基 •2,5_二氧代-1Η-吡咯各基]己基]-Ν-[4-(二甲基胺基)苯 基]六氫吡畊小羧醯胺 6 611 372 4-[6-[1-[4-氣基-3-(二氣甲基）豕基]-2,5-二氯-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-Ο[(三氟甲基)硫烷 基]苯基]六氫吡畊-1-羧醯胺 6 668 373 4-[6-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 6 596Example name is similar to Example Synthesis of ESI-MS -2,5-dioxo-1H-pyrrole groups] hexyl] -N- (2,4,6-trimethyl-phenyl) hexahydropyrine-1- Carboxamide 362 4- [6- [1-[4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H- Pyrrol-3-yl] hexyl] -N- [4-[(trifluoromethyl) sulfanyl] phenyl] hexahydropyridine-1-carboxamide 6 668 363 4- [6- [1- [ 4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole groups] hexyl] -N-[( 2,4-dichlorophenyl) methyl] hexahydrop-p-l-hu-l-pyridamine 6 651 364 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl ] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- [2- (methylsulfanyl) phenyl] hexahydro Pycnogenol-1-carboxamide 6 614 365 4- [6- [H4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dilactate Substituted-lH-p ratio p each-3-yl] hexyl] -N- (2,6-digas p ratio lake-4-yl) hexahydro? Ratio p well-1-complex S amine 6 637 366 ( R) 4- [6_ [1- [4-cyano-3- (trifluorotolyl) -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3- Group] hexyl] -N · (1-phenylethyl) hexahydropyridine-1-carboxamide 6 596 367 ⑸4- [ 6-〇 [4-cyano-3- (trifluoromethyl) phenyl] -2,5 · dihydro-4-methyl-2,5-dioxo-1Η-pyrrole-3-yl] hexyl ] -N- [l- (fluorenyl) ethyl] hexahydrogen siamine 6 646 368 4- [6- [H4-cyano (trifluoromethyl) phenyl] -2,5- Dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- [l-methyl small [3- (1-methylvinyl) phenyl] hexa Pyridoxine-1-carboxamide 6 650 369 4- [6- [1- [4-Lycyl-3- (difluoromethyl) phenyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- [2- (trifluoromethoxy) phenyl] hexahydropyridoxamine 6 652 370 4- [6- [1- [4-Amino-3- (diaminomethyl) muyl] -2,5-dichloro-4-methyldioxo-1H-pyrroleyl] hexyl] -N- (tricyclic [3 · 3.1 · ΐΛ7] dec-1-yl) hexahydropyridine-1-carboxamide 6 626 371 4- [6- [1- [4-Gasyl-3- (digasylmethyl) woodyl ] -2,5-Dichloro-4-methyl • 2,5-dioxo-1Η-pyrrole groups] hexyl] -N- [4- (dimethylamino) phenyl] hexahydropyridine Microcarboxamide 6 611 372 4- [6- [1- [4-Gas-3- (diaminomethyl) fluorenyl] -2,5-dichloro-4-methyl-2,5-di Oxo-1Η-pyrrole-3-yl] hexyl] -N-Ο [(trifluoromethyl) sulfanyl] phenyl] hexahydro Geng -1- 2carboxamide 66683734- [6- [1- [4-cyano each (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-6596

-97- 200301117-97- 200301117

(92) 實例 名稱 類似於 實例合成 ESI-MS -2,5-二氧代-1H-吡咯-3-基]己基]-N-[(2-甲基苯基)甲基] 六氫井小複酿胺 374 4-[6-[H4-氰基-3-(三氟甲基）苯基]-2,5-二氫冰甲基 -2,5-二氧代-1H-吡咯-3-基]己基]-N-[(3-甲基苯基)甲基] 六氫?比ρ井-1 -複s盛胺 6 596 375 4-[6-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-[(4-甲基苯基)甲基] 六氫吡畊小羧醯胺 6 596 376 4-[6-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二乳代-ΙΗ-ί7比洛-3-基]己基]-Ν-[(4-甲氧基本基）甲 基]六氫吡畊小羧醯胺 6 612 377 4-[6-[1-[4-丧基-3-(二氣甲基）苯基]-2,5-二鼠-4-甲基 -2,5-二氧代-1沁吡咯-3-基]己基]-泎(1，1，3,3-四甲基丁 基)六氫吡畊小羧醯胺 6 604 200301117 (93)(92) Example name similar to Example Synthesis ESI-MS -2,5-Dioxo-1H-pyrrole-3-yl] hexyl] -N-[(2-methylphenyl) methyl] Hexahydrogen Revamped amine 374 4- [6- [H4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydroicemethyl-2,5-dioxo-1H-pyrrole-3 -Yl] hexyl] -N-[(3-methylphenyl) methyl] hexahydro? Ratio ρ well-1-bis amine 6 596 375 4- [6- [1- [4-cyano each (Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] hexyl] -N-[(4-methylbenzene (Methyl) methyl] hexahydropyridoxamine 6 596 376 4- [6- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl -2,5-Dilacto-ΙΗ-ί7bilo-3-yl] hexyl] -N-[(4-methoxybenzyl) methyl] hexahydropyridoxamine 6 612 377 4- [6- [1- [4-Benzyl-3- (difluoromethyl) phenyl] -2,5-dimur-4-methyl-2,5-dioxo-1 Yl] hexyl] -fluorene (1,1,3,3-tetramethylbutyl) hexahydropyridoxamine 6 604 200301117 (93)

表11.根據本發明通式I的化合物，其中v =三氟甲基苯甲 腈，W=馬來亞胺，n = 7 實例 名稱 類似於 實例合成 ESI-MS 378 4-[3-[7-(4-乙醯基六氫吡畊-1-基)庚基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)-苯甲腈 9(4) 504 379 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[7-(4-(l-氧代丙基)-六 氫吡畊-1-基)庚基HH-吡咯-1-基]冬(三氟甲基)苯甲腈 9(4) 518 380 4-[3-[7-[4-(環丙基羰基)六氫吡畊-1-基]庚基]-2,5-二氫 -4-甲基-1H-吡咯-1-基]-2-(三氟甲基)苯甲腈 9(4) 530 381 4-[2,5-二氫-3-[7-[4-(甲氧基乙醯基)六氫吡畊-1-基]庚 基]-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯 甲腈 9⑷ 534 382 4-[2,5-二氫-3-[7-[4-(甲氧基-1-氧代丙基）六氫吡畊-1-基]庚基]-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2_(三氟甲 基)苯甲腈 9(4) 548 383 4-[2,5-二氮-3-[7-[4-[(2-甲氧基乙氧基）乙酿基]7^氮叶匕 畊-1-基]庚基]冰甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三 氟甲基)苯甲腈 9(4) 578 384 4-[2,5-二氫-3-[7-[4-[|>(2-甲氧基乙氧基）乙氧基]-乙醯 基]六氫吡畊小基]庚基]斗甲基-2>二氧代-1H-吡咯小 基]-2-(三氟甲基)苯甲腈 9(4) 622 385 4-[2,5-二氫-3-[7-[4-(2-甲氧基苯甲醯基)六氫吡畊小基] 庚基]冰甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基) 苯甲腈 9(4) 596 386 4-[2,5-二氫-3-甲基-4-[7-[4-(甲基磺醯基）六氫吡畊-1-基]庚基]-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯甲 腈 9 540 387 4-〇[7-[4-(乙基磺醯基)六氫吡畊-1-基]庚基]-2,5-二氫 -4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲腈 9 554 388 4-[3-[7-[4-(银丙基續酿基)鼠卩比呼-1-基]庚基]-2,5-二 氫斗甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯甲 腈 9 566 389 4-[2,5-二氫-3-〇[4-(2-甲氧基苯乙基)磺醯基]六氫吡畊 -I-基]庚基]-4-甲基-2,5-二氧代-lH-p比洛-1-基]-2-(二氣 甲基)苯甲腈 9 584 390 4-[2,5-二氫-3-[7-[4-[[2-(2-甲氧基乙氧基)乙基Η夤醯基] 9 628Table 11. Compounds of general formula I according to the present invention, where v = trifluoromethylbenzonitrile, W = maleimine, n = 7 Example names are similar to the examples ESI-MS 378 4- [3- [7 -(4-Ethylhexylpyridin-1-yl) heptyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2 -(Trifluoromethyl) -benzonitrile 9 (4) 504 379 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [7- (4- (l -Oxopropyl) -hexahydropyridine-1-yl) heptylHH-pyrrole-1-yl] dong (trifluoromethyl) benzonitrile 9 (4) 518 380 4- [3- [7- [4- (cyclopropylcarbonyl) hexahydropyridin-1-yl] heptyl] -2,5-dihydro-4-methyl-1H-pyrrole-1-yl] -2- (trifluoromethyl ) Benzonitrile 9 (4) 530 381 4- [2,5-Dihydro-3- [7- [4- (methoxyethenyl) hexahydropyridin-1-yl] heptyl] -4 -Methyl-2,5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 9⑷ 534 382 4- [2,5-dihydro-3- [7- [4 -(Methoxy-1-oxopropyl) hexahydropyrine-1-yl] heptyl] -4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2_ ( Trifluoromethyl) benzonitrile 9 (4) 548 383 4- [2,5-diaza-3- [7- [4-[(2-methoxyethoxy) ethynyl] 7 ^ nitrogen Dagger-1-yl] heptyl] icemethyl-2,5-dioxo-1H-pyrrole-1- Yl] -2- (trifluoromethyl) benzonitrile 9 (4) 578 384 4- [2,5-dihydro-3- [7- [4- [| > (2-methoxyethoxy Group) ethoxy] -acetamido] hexahydropyridine] heptyl] methyl-2 > dioxo-1H-pyrrole small] -2- (trifluoromethyl) benzonitrile 9 (4) 622 385 4- [2,5-Dihydro-3- [7- [4- (2-methoxybenzylidene) hexahydropyridine] heptyl] icemethyl-2, 5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 9 (4) 596 386 4- [2,5-dihydro-3-methyl-4- [ 7- [4- (methylsulfonyl) hexahydropyridin-1-yl] heptyl] -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) Benzonitrile 9 540 387 4-〇 [7- [4- (ethylsulfonyl) hexahydropyridine-1-yl] heptyl] -2,5-dihydro-4-methyl-2,5 -Dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 9 554 388 4- [3- [7- [4- (Silveryl-continued group) muridine bihu- 1-yl] heptyl] -2,5-dihydromethyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 9 566 389 4 -[2,5-Dihydro-3-〇 [4- (2-methoxyphenethyl) sulfonyl] hexahydropyridine-I-yl] heptyl] -4-methyl-2,5 -Dioxo-lH-p bilo-1-yl] -2- (digasmethyl) benzonitrile 9 584 390 4- [2,5-dihydro-3- [7- [4-[[2- (2-methoxyethoxy) ethylfluorenyl] 9 628

-99- (94) 實例 名稱 ~~~~ 類似於 貫* ^[列合^ ESI-MS a氫吡畊小基]庚基H-甲基_2,5_二氧代吡咯] 基]-2-(三氟甲基)苯甲腈 >% 4 \jr J4\^ 391 4-[2,5-一氫-3-[ /-[4-L|>(2-甲氧基乙氧基）乙氧基]-乙基-磺醯基]六氫吡畊-1-基]庚基]甲基_2,5_二氧代^ 咯小基]_2_(三氟甲基)苯甲腊 9 672 392 4-[2,5-二氫各甲基_2,5-二氧代斗[7_[；4_(苯基磺醯基)_ 六氫吡畊-1-基]庚基]-1Η-吡咯-1-基]_2_(三氟甲基)苯甲 腊 9 602 393 4-[2,5-二氫·3·甲基_2,5·二氧代斗!^4-[(苯基甲基)_石黃 醯基]-六氫吡畊小基]庚基]-1Η-吡咯-1-基]-2-(三氟甲 基)苯甲腈 9 616 394 4-[2,5-二氫-3-甲基-4-[7-[4-[(1-甲基-1Η-咪唑-4-基)續醯 基]六氣峨呼小基]庚基]-2,5-二氧代-1Η- ρ比ρ各小 基]-2-(三氟甲基)苯甲腈 9 606 395 4-[7-[ 1-0氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]庚基]-N-(l-甲基乙基)-六氫 吡畊-1-幾醯胺 9(6) 547 396 4-[7-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫冰甲基 -2,5-二氧代-1Η-吡咯-3-基]庚基]-Ν-乙基六氫吡畊小碳 硫醯胺 9(12) 549 397 4-[7-[Η4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]庚基]-六氫吡畊小羧酸甲酯 9(13) 520 398 4_[7_[Η4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5-二氧代-1Η-吡咯-3-基]庚基]六氫吡畊-1-碳硫酸S- 甲酯 9(13) 536 399 4·Ι>[Η4-氰基-3-(三氟甲基）苯基]-2,5-二氫甲基 -2,5·二氧代-1Η_吡咯·3-基]庚基]-Ν，Ν-二甲基六氫吡畊 -1-磺醯胺 9 569 -100 - 200301117 (95)-99- (94) Example name ~~~~ Similar to Guan * ^ [Column combination ^ ESI-MS a hydropyridine small group] heptyl H-methyl_2,5_dioxopyrrolyl]-] 2- (trifluoromethyl) benzonitrile >% 4 \ jr J4 \ ^ 391 4- [2,5-monohydro-3- [/-[4-L | > (2-methoxyethyl (Oxy) ethoxy] -ethyl-sulfofluorenyl] hexahydropyridin-1-yl] heptyl] methyl_2,5_dioxo ^ pyroxy] _2_ (trifluoromethyl) benzene Methyl wax 9 672 392 4- [2,5-Dihydro each methyl_2,5-dioxo [7 _ [; 4_ (phenylsulfonyl) _hexahydropyrine-1-yl] heptyl ] -1Η-pyrrole-1-yl] _2_ (trifluoromethyl) benzyl 9 602 393 4- [2,5-dihydro · methyl · 2,5 · dioxo! ^ 4- [(Phenylmethyl) _arthanthenyl] -hexahydropyridine] heptyl] -1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 9 616 394 4- [2 , 5-dihydro-3-methyl-4- [7- [4-[(1-methyl-1fluorenyl-imidazol-4-yl) continyl]] hexakiethoxyhexyl] heptyl] -2 , 5-dioxo-1Η-ρ ratio ρ each small group] -2- (trifluoromethyl) benzonitrile 9 606 395 4- [7- [1-0cyano-3- (trifluoromethyl ) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] heptyl] -N- (l-methylethyl) -hexahydro Pycnogenol-1-Epiridamine 9 (6) 547 396 4- [7- [1- [4-cyano (trifluoromethyl) phenyl] -2,5-dihydroglacial methyl-2,5-dioxo-1′-pyrrole-3-yl] heptyl] -N-ethyl Hexahydropyridine 9 (12) 549 397 4- [7- [Η4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2, 5-Dioxo-1Η-pyrrole-3-yl] heptyl] -hexahydropyridine methyl carboxylate 9 (13) 520 398 4_ [7_ [Η4-cyano (trifluoromethyl) phenyl ] -2,5-Dihydro-4-methyl-2,5-dioxo-1Η-pyrrole-3-yl] heptyl] hexahydropyridine-1-carbon sulfate S-methyl ester 9 (13) 536 399 4 · > [Η4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydromethyl-2,5 · dioxo-1Η_pyrrole · 3-yl] heptane Phenyl] -N, N-dimethylhexahydropyroxy-1-sulfanilamide 9 569 -100-200301117 (95)

表12.根據本發明通式I的化合物，其中V=三氟甲基苯甲 腈，馬來亞胺，n = 8 實例 名稱 類似於 實例合成 ESI-MS 400 4-[3-[8-(4-乙醯基六氫吡畊-1-基)辛基]-2,5-二氫-4-甲基 -2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)-苯甲腈 9(4) 518 401 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[8-(4-(l-氧代丙基)-六 氫吡畊小基)辛基]-1Η-吡咯-1-基]-2-(三氟甲基)苯甲腈 9(4) 532 402 4-[3-[8-[4-(環丙基羰基)六氫吡畊-1-基]辛基]-2,5-二氫 -4-甲基-1H-吡咯小基]-2-(三氟甲基)苯甲腈 9(4) 544 403 4-[2,5-二氫-3-[8-[4-(甲氧基乙醯基)六氫吡畊小基]辛 基]-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯 甲腈 9(4) 548 404 4-[2,5-二氫-3-[8-[4-(甲氧基-1-氧代丙基)六氫吡畊小 基]辛基]-4-甲基-2,5-二氧代-1H-吡咯小基]-2-(三氟甲 基)苯甲腈 9(4) 562 405 4-[2,5-二氫-3-[8-[4-[(2-甲氧基乙氧基）乙醯基]六氫吡 畊小基]辛基]冬甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三 氟甲基)苯甲腈 9(4) 592 406 4-[2,5-二氯-3-[8-[4-[[2-(2-甲氧基乙氧基）乙氧基]-乙臨 基]六氫吡畊小基]辛基]-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基)苯甲腈 9(4) 636 407 4-[2,5-二氫-3-[8-[4-(2-甲氧基苯甲醯基)六氫吡畊4-基] 辛基]-4-甲基-2,5-二氧代-111-^7比?7各-1-基]-2-(二氣甲基) 苯甲腈 9(4) 610 408 4-[2,5-二氫-3-甲基冰[8-[4-(甲基磺醯基）六氫吡畊-1-基]辛基]-2,5-二氧代-1H-吡咯小基]-2-(三氟甲基)苯甲 腈 9 554 409 4-[3·[8-[4-(乙基磺醯基)六氫吡畊-1-基]辛基]-2,5-二氫 -4-甲基-2,5-二氧代-1Η-^ρ各-1-基]-2-(二氣甲基)苯甲猜 9 568 410 4-[3-[8-|>(環丙基磺醯基)六氫吡畊小基]辛基]-2,5-二 鼠-4-甲基-2,5-二基]-2-(二氣甲基)本甲 腈 9 580 411 4-[2,5-二氫-3-[8-[4-(2-甲氧基苯乙基)磺醯基]六氫吡畊 小基]辛基]-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟 甲基)苯甲腈 9 598 412 4-[2,5-二氫-3-[8-[4-[[2-(2-甲氧基乙氧基)乙基]-磺醯基] 9 642Table 12. Compounds of general formula I according to the invention, where V = trifluoromethylbenzonitrile, maleimine, n = 8 Example names are similar to the examples ESI-MS 400 4- [3- [8- ( 4-ethenylhexahydropyridin-1-yl) octyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole small group] -2- (trifluoro Methyl) -benzonitrile 9 (4) 518 401 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [8- (4- (l-oxopropane Yl) -hexahydropyridine) octyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 9 (4) 532 402 4- [3- [8- [4 -(Cyclopropylcarbonyl) hexahydropyridin-1-yl] octyl] -2,5-dihydro-4-methyl-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 9 (4) 544 403 4- [2,5-Dihydro-3- [8- [4- (methoxyethylamyl) hexahydropyridyl] octyl] -4-methyl-2, 5-dioxo-1H-pyrrole small group] -2- (trifluoromethyl) benzonitrile 9 (4) 548 404 4- [2,5-dihydro-3- [8- [4- (methyl Oxy-1-oxopropyl) hexahydropyridine] octyl] -4-methyl-2,5-dioxo-1H-pyrrolepyridyl] -2- (trifluoromethyl) benzene Nitrile 9 (4) 562 405 4- [2,5-dihydro-3- [8- [4-[(2-methoxyethoxy) ethenyl] hexahydropyridine]] octyl ] Hydroxymethyl-2,5-dioxo-1H-pyrrole-1-yl ] -2- (trifluoromethyl) benzonitrile 9 (4) 592 406 4- [2,5-dichloro-3- [8- [4-[[2- (2-methoxyethoxy ) Ethoxy] -ethynyl] hexahydropyridine] octyl] -4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl ) Benzonitrile 9 (4) 636 407 4- [2,5-dihydro-3- [8- [4- (2-methoxybenzyl) hexahydropyridine 4-yl] octyl] 4-methyl-2,5-dioxo-111- ^ 7 ratio? 7 each-1-yl] -2- (digasmethyl) benzonitrile 9 (4) 610 408 4- [2, 5-dihydro-3-methylice [8- [4- (methylsulfonyl) hexahydropyridin-1-yl] octyl] -2,5-dioxo-1H-pyrrole small] 2- (trifluoromethyl) benzonitrile 9 554 409 4- [3 · [8- [4- (ethylsulfonyl) hexahydropyridine-1-yl] octyl] -2,5- Dihydro-4-methyl-2,5-dioxo-1Η- ^ ρ each-1-yl] -2- (difluoromethyl) benzyl 9 568 410 4- [3- [8- | > (Cyclopropylsulfonyl) hexahydropyridine] octyl] -2,5-dimur-4-methyl-2,5-diyl] -2- (difluoromethyl) benzyl Nitrile 9 580 411 4- [2,5-Dihydro-3- [8- [4- (2-methoxyphenethyl) sulfonyl] hexahydropyridine] octyl] -4- Methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 9 598 412 4- [2,5-dihydro-3- [8- [ 4-[[2- (2-methoxy Ethoxy) ethyl] -sulfonyl] 9 642

-101 - (96)-101-(96)

實例 名稱 類似於 實例合成 ESI-MS 六氫吡畊-1-基]辛基]斗甲基-2,5_二氧代]沁吡咯 基]-2-(三氟甲基)苯甲腈 413 4-[2,5-二氫各化㈣叫2·甲氧基乙氧基)乙氧基]_乙基: 磺醯基]六氫吡畊-1-基]辛基]甲基_2,5_二氧代] 咯-1-基]_2-(三氟甲基)苯甲腈 19 686 414 4_[2,5-二氲各甲基·2,5_二氧代冰[§κ苯基橫醯基)_ 六氫吡畊-1-基]辛基ΗΗ-吡咯小基]冬(三氟甲基)苯甲 腈 9 616 415 4:[2,5-二氫-3-甲基-2,5-二氧代-4-[8-[4-[(苯基甲基)·磺 酉监基]-7Τ風ρ比ρ井-1-基]辛基]比ρ各-1-基]_2-(三氟甲 基)苯甲腈 一 9 630 416 4-[2,5-一氣-3-甲基-4-[8-[4-[(1-甲基-1Η-咪峻-4-基)石黃 g| 基]六氫吡畊-1-基]辛基]-2,5-二氧代-1Η-吡咯小 基]:(三氟甲基)苯甲腈 9 620 417 4-[8-[ 1 -^4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 -2,5_二氧代-1〜比咯_3_基]辛基]-N-(l-甲基乙基)-六氫 吡畊-1-羧醯胺 6 561 418 4-[8-[ 1-[4-氰基各(三氟甲基）苯基]-2,5-二氫-4-甲基 _2,5-一氧代-lH-p比洛各基]辛基]善乙基六氫ρ比畊小碳 硫酿胺· 9(12) 563 419 4-[8_[ 1 f -氰基各(三氟甲基）苯基]_2,5—二氫斗甲基 _2,5_ 一氧代-lH-p比咯_3—基]辛基]-六氫吡畊幾酸甲酯 9(13) 534 420 氰基各(三氟甲基）苯基]-2,5_二氫斗甲基 _2,5· 一氧代-lH-p比p各各基]辛基]六氫峨畊小碳硫酸s— 甲酯 9(13) 550 421 4-[8-[ 1 -^4-氰基各(三氟甲基）苯基]-2,5_二氫冬甲基 -2,5-二氧代-1如比咯-3-基]辛基]·ν，Ν-二甲基六氫吡畊 -1-績3蠢胺 9 583 200301117 表13· 腈 (97) 根 據本發明通式！的化合物，其三氟甲基苯甲 a^a ΕΙίζ. « 實例 ~--- |類似於 實例合成 ESI-MS 422 ^4?，5--虱:3 仰^ 基]己基HH2,5-二氧代，ιη-吡pm]-2-(二氟甲 基)苯基]乙醯胺 1一亂T κ 4 Ϊ-7 4 615 4 563 424 π γ Lv L 、> , /土、饮忍"、乳 p 比 p开 基]己基]_2,5_ 二 氫-4-甲基-2,5-二氧代-1H-♦各+基设(三氣甲基 基]乙醯胺_ __ N-[4-[2,5-Z 氫-3-甲基[(备 2:基 >羰 基]ττ氫ρ比_-1-基]己基]-lHw比哈]_基]_2_(三氟甲美） 苯基]乙S盔胺 4 591 425 N-[4-[3-[6-[4-[4-(二甲基胺基]六氫吡畊-1-基]己基]-2,5-二氫-4·甲基-2,5-二氧代-1Η-吡咯-μ 基]_2_(三氟甲基)苯基]乙醯胺 4 628 426 N-[4-[3K4-乙醯基六氫吡畊+基）己基]-2,5_二氫_4_ 甲基-2,5-二氧代-111-吡咯-1-基]q三氟甲基)苯基]乙醯胺___ 叫4-[2,5-二氫各甲基_4_[6_[J^甲基磺醯基六氯㈣ -1-基]己基]-2,5_二氧代-1H_吡咯小基]_2_(三氟甲基)苯 基]乙醯胺 _N-[4-[3-[6-[4-[(2，l，3-苯并嘍二唑-4-基)磺醯基]-六氫吡 呼小基]己基]_2,5-二氫_4_甲基_2,5_二氧代dH-#1:(1- 圣>2-(三氟甲基)苯基]乙醯胺__ 4_[6-[1-[4-(乙醯基胺基)各(三氟甲基)苯基]_2,5_二氫冰 甲基—氧代基]己基]-N-(p比咬-4-基)六 氫吡畊-1-羧醯胺 4 523 -103 - 200301117 (98) 表14·根據本發明通式化合物，其中^硝基三氟甲基苯Example name is similar to Example Synthesis of ESI-MS Hexahydropyridin-1-yl] octyl] Methyl-2,5-dioxo] pyrrolidinyl] -2- (trifluoromethyl) benzonitrile 4- [2,5-Dihydroanisocyanate called 2.methoxyethoxy) ethoxy] _ethyl: sulfofluorenyl] hexahydropyridin-1-yl] octyl] methyl_2 , 5_dioxo] pyr-1-yl] _2- (trifluoromethyl) benzonitrile 19 686 414 4_ [2,5-Difluorenylmethyl · 2,5_dioxoice [§κ Phenylpyridinyl) _Hexahydropyrine-1-yl] octylpyrene-pyrrole small group] winter (trifluoromethyl) benzonitrile 9 616 415 4: [2,5-dihydro-3-formyl -2,5-dioxo-4- [8- [4-[(phenylmethyl) · sulfonyl] -7T wind ρ ratio ρ well-1-yl] octyl] ratio ρ each- 1-yl] _2- (trifluoromethyl) benzonitrile 9 630 416 4- [2,5-monogas-3-methyl-4- [8- [4-[(1-methyl-1Η- Imijun-4-yl) stone yellow g | yl] hexahydropyridine-1-yl] octyl] -2,5-dioxo-1Η-pyrrole small group] :( trifluoromethyl) benzonitrile 9 620 417 4- [8- [1-^ 4-cyano (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 ~ ratio P_3_yl] octyl] -N- (l-methylethyl) -hexahydropyrine-1-carboxamide 6 561 418 4- [8- [1- [4-cyano Fluoromethyl) phenyl ] -2,5-Dihydro-4-methyl_2,5-monooxo-lH-p Billokyl] octyl] Sinethylhexahydror phenyl small carbon-sulfur amine · 9 (12 ) 563 419 4- [8_ [1 f -cyano (trifluoromethyl) phenyl] _2,5-dihydromethyl-2,5_ monooxo-lH-p than slightly _3-yl] Octyl] -Hexahydropigenic acid methyl ester 9 (13) 534 420 Cyano (trifluoromethyl) phenyl] -2,5-dihydropyridinemethyl-2,5 · monooxo-lH -p ratio p of each group] octyl] hexahydroarsenyl small carbon sulfate s- methyl ester 9 (13) 550 421 4- [8- [1-^ 4-cyano (trifluoromethyl) phenyl ] -2,5_Dihydroaspartyl-2,5-dioxo-1 such as birrol-3-yl] octyl] · ν, N-dimethylhexahydropyridine-1-chi 3 Amine 9 583 200301117 Table 13. Nitrile (97) According to the general formula of the invention! Compound, its trifluoromethyl benzyl a ^ a ΕΙίζ. «Examples ~ --- | Similar to the Example Synthesis of ESI-MS 422 ^ 4 ?, 5--Lice: 3 Yang ^ yl] Hexyl HH2,5-Di Oxo, ιη-pyridine] -2- (difluoromethyl) phenyl] acetamidamine 1 乱 T κ 4 Ϊ-7 4 615 4 563 424 π γ Lv L, > ", milk p than p open radical] hexyl] _2,5_ dihydro-4-methyl-2,5-dioxo-1H- ♦ each + radical (trimethylol) acetamidamine _ __ N- [4- [2,5-Z hydrogen-3-methyl [(Preparation 2: group> carbonyl) ττhydroρ ratio_-1-yl] hexyl] -1Hwbiha] _yl] _2_ (tri Flumemet) Phenyl] ethylamine 4 591 425 N- [4- [3- [6- [4- [4- [Dimethylamino] hexahydropyridine-1-yl] hexyl]- 2,5-dihydro-4 · methyl-2,5-dioxo-1Η-pyrrole-μyl] _2_ (trifluoromethyl) phenyl] ethanamine 4 628 426 N- [4- [3K4 -Ethenylhexahydropyridine + yl) hexyl] -2,5-dihydro-4_methyl-2,5-dioxo-111-pyrrole-1-yl] qtrifluoromethyl) phenyl] Acetylamine ___ is called 4- [2,5-dihydromethyl_4_ [6_ [J ^ methylsulfonylhexachlorofluoren-1-yl] hexyl] -2,5_dioxo-1H _Pyrrole small group] _2_ (trifluoromethyl) phenyl] acetamidamine_N- [4- [3- [6- [4-[(2, l, 3-benzoxadiazole-4- ) Sulfonyl] -hexahydropyridyl] hexyl] _2,5-dihydro-4_methyl_2,5_dioxodH- # 1: (1-Saint > 2- (trifluoro (Methyl) phenyl] ethylammonium amine__ 4_ [6- [1- [4- (ethylamylamino) phenyl (trifluoromethyl) phenyl] _2,5_dihydromethyl-oxo [Hexyl] -hexyl] -N- (p-ratio-4-yl) hexahydropyridine-1-carboxamide 4 523 -103-200301117 (98) Table 14. Compounds of the general formula according to the present invention, wherein Fluoromethylbenzene

表15·根據本發明通式！的化合物，其中v=雙三氟甲基苯 馬&亞胺，『 土Table 15 · General formula according to the invention! Compound, where v = bistrifluoromethylbenzene, horse & imine,

104- 200301117 (") Ι^ΙΜ 表16.根據本發明通式I的化合物，其中v=氟三氟甲基苯 w= 4 亞胺，n = 6 實例 名稱 ^- 類似於 實例合成 ESI-MS 442 H3-氟-4-(三氟甲基）苯基]-3-[6-[4-(2、^J^甲酿 基)六氫吡。井小基]己基]-4-甲基-1H-咐咯ς； 一阴 4 576 443 3_[6-[4-(環丁基羰基）六氫吡畊-1 氟 _4-(三氟甲基)苯基]-If基-1Η-吡咯-2,5- -西同 4 524 444 Η3·氟-4·(三氟甲基)苯基]-3-甲基_4-[6-[4+塞_2_基)談 基]六氫说啡-1-基]己基]-lH-p比咯-2,5-二酉同 4 552 445 |5-[6-[4-[4_(二甲基胺基）苯甲酿基]六氫叶卜井小基]己 基Η-ί>氟_4_(三氟甲基)苯基]I甲基-1Η-吡咯-2,5-二 酮 ， 「4 589 446 3-[6_(4-乙醯基六氫吡m)己基]-Η3-氟冬(三氟甲 基)苯基]冰甲基-lH-p比哈_2,5·二酉同 4 484 447 H3-氟-4-(二氟甲基）苯基]各甲基冰[6_[4_(甲基磺醯 基)六氫吡畊小基]己基]-1Η-吡洛_2,5_二酮 5 520 448 : 3-[6-[4-[(2,1，3-苯并噻二唑_4_基)磺醯基]六氫吡畊+ 基]己基Η-〇氟·4-(三氟甲基)苯基ρμ甲基-1Η_吡咯 -2,5-二酮 5 640104- 200301117 I ^ IM Table 16. Compounds of general formula I according to the present invention, where v = fluorotrifluoromethylbenzene w = 4 imine, n = 6 Example name ^-Similar to Example Synthesis ESI- MS 442 H3-Fluoro-4- (trifluoromethyl) phenyl] -3- [6- [4- (2, ^ J ^ methylamino) hexahydropyridine. Jing Xiaoji] hexyl] -4-methyl-1H-Croyl; an anion 4 576 443 3_ [6- [4- (cyclobutylcarbonyl) hexahydropyracine-1 fluoro_4- (trifluoromethyl (Phenyl) phenyl] -Ifyl-1Η-pyrrole-2,5- -Xidong 4 524 444 Η3 · fluoro-4 · (trifluoromethyl) phenyl] -3-methyl_4- [6- [ 4 + Set_2_yl) Tanyl] Hexahydrophenan-1-yl] hexyl] -lH-p than Pyrrole-2,5-Dipyridine 4 552 445 | 5- [6- [4- [4_ (Dimethylamino) benzyl] Hexhydroyebujingi] Hexylfluorene-ί > fluoro-4_ (trifluoromethyl) phenyl] Imethyl-1fluorene-pyrrole-2,5-di Ketones, "4 589 446 3- [6- (4-Ethylfluorenylmethane) hexyl] -fluorene 3-fluorodong (trifluoromethyl) phenyl] icemethyl-lH-p biha_2,5 · Difluorene with 4 484 447 H3-fluoro-4- (difluoromethyl) phenyl] Ethyl methyl ice [6_ [4_ (methylsulfonyl) hexahydropyridyl] hexyl] -1Η-pyridine Iso_2,5_dione 5 520 448: 3- [6- [4-[(2,1,3-benzothiadiazole_4-yl) sulfonyl] hexahydropyridine + yl] hexyl Η-〇fluoro · 4- (trifluoromethyl) phenylρμmethyl-1Η_pyrrole-2,5-dione 5 640

-105 - 200301117 (100) 根據本發明通式I的化合物，其中v=異苯并呋喃酮 ，W =馬來亞胺，n = 4 實例 名稱 類似於 實例合成 ESI-MS 449 3十^(4-乙醒基六氫吡畊小基)丁基H-(1，3-二氫小氧代 -異苯并呋喃-5-基)斗甲基-1H-♦各-2,5- -酮 4 425 450 1二(1，3-二氫-1-氧代異苯并呋喃·5_基>3_甲基-4_[4·[4-(1-氧代丙基)六氫吡畊小基]丁基]_1Η-吡洛-2,5· 一酮 4 440 451 1 (1，3_一氫氧代異苯并峡喃基)-3-[4-[4-[(2-甲氧 基乙氧基）乙醯基]-六氫吡畊小基]丁基]冰甲基_1Η4 咯-2,5-二酮 4 500 452 ^1，3^氫小氧代異苯并呋喃-5-基)-3-[4-[4-[(2_(2-甲 氧基乙氧基)乙氧基)乙醯基]六氫吡十基]丁基]冰甲 基-lH-p比洛-2,5-二酮 4 544 453 1-(1，3-二氫-1-氧代異苯并呋喃基）_3_甲基 [4_ [4_(甲基磺醯基）六氫吡畊-卜基]丁基]_丨比咯 -2,5-二酮 5 462 454 4-[4-[1-(1，3-二氫-1-氧代異苯苯并呋喃士基)-2,5-二氫 甲基-2,5-二氧代-ΙΗ-峨咯-3·基]丁基]善乙基_六氫 吡畊-1-碳硫醯胺 12 471 455 二氫-1-氧代異苯苯并吱喃-5-基)-2,5-二氫 甲基_2,5_二氧代-ΙΗ-咐咯-3-基]丁基]善丙基_六氫 吡畊-1-碳硫醯胺 12 485 456 4-[4-[1-(1，3-一氫-1-氧代異苯苯并呋喃：基)#•二氫 冰甲基-2,5-二氧代也-♦各各基]丁基]-Ν-(丙1烯基) 六氫吡畊-1-碳硫醯胺 12 483-105-200301117 (100) Compounds of general formula I according to the present invention, wherein v = isobenzofuranone, W = maleimine, n = 4 Example names are similar to the examples for the synthesis of ESI-MS 449 3 ^ (4 -Ethyl hexahydropyridine) butyl H- (1,3-dihydro small oxo-isobenzofuran-5-yl) methyl-1H- ♦ each -2,5- -one 4 425 450 1 bis (1,3-dihydro-1-oxoisobenzofuran · 5-yl > 3-methyl-4_ [4 · [4- (1-oxopropyl) hexahydropyridine Gengxiaoji] butyl] _1Η-pyrolo-2,5 · monoone 4 440 451 1 (1,3_monohydrooxoisobenzoxanyl) -3- [4- [4-[(2 -Methoxyethoxy) ethenyl] -hexahydropyridine] butyl] icelmethyl 1Η4 azole-2,5-dione 4 500 452 ^ 1,3 ^ hydro small oxoisobenzene Benzofuran-5-yl) -3- [4- [4-[(2- (2-methoxyethoxy) ethoxy) ethenyl] hexahydropyridyl] butyl] icemethyl- lH-p bilo-2,5-dione 4 544 453 1- (1,3-dihydro-1-oxoisobenzofuranyl) _3_methyl [4_ [4_ (methylsulfonyl) Hexahydropyridine-butyl] butyl] _ 丨 pyrrole-2,5-dione 5 462 454 4- [4- [1- (1,3-dihydro-1-oxoisobenzobenzofuran) (Shiji) -2,5-dihydromethyl-2,5-dioxo-ΙΗ-Η -3.yl] butyl] sinethyl_hexahydropyridine-1-carbothioamide 12 471 455 dihydro-1-oxoisobenzobenzo-5-yl) -2,5-di Hydroxymethyl_2,5_dioxo-lΗ-pyrrol-3-yl] butyl] synyl_hexahydropyridine-1-carboxamidine 12 485 456 4- [4- [1- (1,3-monohydro-1-oxoisobenzobenzofuran: yl) # • dihydroglacial methyl-2,5-dioxo- each each group] butyl] -N- (propyl 1 alkenyl) hexahydropyridine-1-carboxamidine 12 483

-106- 200301117 (ιοί) 表18.根據本發明通式i的化合物，其中v =異苯 、个汁p天喃酉同 W =馬來亞胺，η = 5 實例 457 458 459 乙 si 基六細 f-異苯并呋喃_5_基)-4·甲基-1H-吡咯-2,5-二酮_!^(\，3-二氫小氧代異苯并呋喃―5-基)各甲基-4-[5-[4-(l-jL代丙基)7τ風^比啡-1-基]戊基]-iH-t?比哈-2,5-二酉同_ 1-(1，3-二氫-1-氧代異苯并呋喃—5_基)冬[^卜阶甲氧 基乙氧基）乙酿基]-六氫^比十1-基]戊基]甲基-1H^比 咯-2,5-二酮_1，3-二氫小氧代異苯并吱喃-5-基)-3-[5-[4·[(2-(2- f 氧基乙氧基）乙氧基)乙酿基]六氫p比P井小基]戊基]冰甲 基-lH-p比洛-2,5-二酮 1-(1，3-二氫小氧代異苯并呋喃各基）各甲基4-[5*>[4-(甲基〜g盛基）六氫Ρ比ρ井小基]戊基ρΐΗ-ρ比Ρ各 -2,5-二酮 類似於 成 4-106- 200301117 (ιοί) Table 18. Compounds of general formula i according to the present invention, where v = isobenzene, p-isopropylamidine and W = maleimine, η = 5 Example 457 458 459 ethyl si Fine f-isobenzofuran_5_yl) -4 · methyl-1H-pyrrole-2,5-dione _! ^ (\, 3-dihydro small oxoisobenzofuran-5-yl) Each methyl-4- [5- [4- (l-jL-substituted propyl) 7τ 风 ^ biffin-1-yl] pentyl] -iH-t? Biha-2,5-difluorene is the same as _ 1 -(1,3-dihydro-1-oxoisobenzofuran-5-yl) dong [^ Border methoxyethoxy) ethynyl] -hexahydro ^ bidecyl1-yl] pentyl ] Methyl-1H ^ pyrrole-2,5-dione-1,3-dihydro small oxoisobenzonan-5-yl) -3- [5- [4 · [(2- (2 -f oxyethoxy) ethoxy) ethynyl] hexahydro p than P well small group] pentyl] icel methyl-1H-p bilo-2,5-dione 1- (1,3 -Dihydro small oxoisobenzofuran groups) each methyl 4- [5 * > [4- (methyl ~ g Sheng group) hexahydrogen P ratio ρ well small group] pentyl ρΐΗ-ρ ratio P Each -2,5-dione is similar to 4

ESI-MS 439 462 463 3;[5-[4_(環丙基磺醯基)六氫吡畊小基]戊基]-1-(1，3-二 氧代異苯并呋喃-5-基)冰甲基-1H-P比‘2,5-二酮 1-(1，3-二氫-1-氧代異苯并呋喃 j 基)-3-〇[4-[[2-〇(2-甲氧基乙氧基）乙氧基]乙基]續酿基]六氫说。井-基]戊 基]-4_甲基-11^比嘻-2,5-二酮 502 608 464 4-〇[1-(1，3-二氫-1-氧代異苯并呋喃士基)_2,5-二氫-4· 甲基_2,5-二氧代-lH-p比咯各基]戊基]-N-乙基-六氫吡 呼-1-碳硫醯胺 12 471 465 -[5-[1-(1，3-二氫-1-氧代異苯并呋喃士基>2,5-二氫冰 甲基-2,5-二氧代-111-吡咯各基]戊基]善丙基六氫吡畊 -1-碳硫酸胺 12 485 466 4-[5-〇(1，3-二氫小氧代異苯并呋喃-5_基)-2,5-二氫冰 甲基-2,5_二氧代-11^吡咯各基]戊基]-Ν·(丙_2_埽基)六 氫吡畊-1-碳硫醯胺 12 483 -107- (102)200301117 表19·根據本發明通式丨的化合物，其中異苯并呋 W二，來亞胺，η = 6 喃酮， 實例 名稱 467 氫-1·氧代異苯并吱喃 苯甲醯基)六氫♦井小基]己基]冰甲基]H-p比咯_2 5_1 酮 ’ 一 類似於 實例合成ESI-MS 439 462 463 3; [5- [4_ (Cyclopropylsulfonyl) hexahydropyridine] pentyl] -1- (1,3-dioxoisobenzofuran-5-yl ) Ice methyl-1H-P ratio '2,5-dione 1- (1,3-dihydro-1-oxoisobenzofuran jyl) -3-〇 [4-[[2-〇 ( 2-methoxyethoxy) ethoxy] ethyl] continuyl] hexahydro said. Well-yl] pentyl] -4-methyl-11 ^ bihex-2,5-dione 502 608 464 4-〇 [1- (1,3-dihydro-1-oxoisobenzofuran Group) _2,5-dihydro-4 · methyl_2,5-dioxo-lH-p pyrrolyl] pentyl] -N-ethyl-hexahydropyridine-1-carbothioamide 12 471 465-[5- [1- (1,3-Dihydro-1-oxoisobenzofuranyl) > 2,5-dihydroicemethyl-2,5-dioxo-111- Pyrrole groups] pentyl] propanylhexahydropyridine-1-carbon sulfate 12 485 466 4- [5-〇 (1,3-dihydro small oxoisobenzofuran-5-yl) -2 , 5-Dihydroglacial methyl-2,5-dioxo-11 ^ pyrrole groups] pentyl] -N · (propyl_2_fluorenyl) hexahydropyridine-1-carbothioamide 12 483 -107- (102) 200301117 Table 19. Compounds according to the general formula of the present invention, in which isobenzofuryl diimide, η = 6 ketone, example name 467 hydrogen-1 · oxoisobenzophenone Benzyl amidino) Hexahydroxylylene] Hexyl] Icemethyl] Hp ratio _2 5_1 Ketone '-similar to the example synthesis

ESI-MS 4 546 468 469 470 471 472 ----/土、-丄丄丄-叮/分-Z，：)-二朗1-(1，3-二氫小氧代異苯并呋喃_5•基）_3_甲其 冬[6-[4仆塞-2-基)羰基]-六氫吡m]己基HH-吡^ -2,5-二酮 _ 代異苯^ 基胺基)苯甲醯基]六氫吡畊-;^基]己基甲基_1Η 咯-2,5-二酮 _ 并冬并吱喃-5-基比ρ各-2,5-二酉同4-[4-[1-(1，3-二氫-1-氧代異苯并呋喃巧_基)_2,5_二氫_4_ 甲基-2,5_二氧代-1H-吡咯冰基]己基]·Ν，Ν< p基六 吡畊-1-磺醯胺 559 473 474 475 476 477 1-(1，3-二氫-1-氧代異苯幷呋喃_5_基甲基 -4- [6- [4-(甲基磺醯基）六氫吡畊小基]己基]_丨Η•吡咯 -2,5-二酉同 Κ6 [4 (2，1，3-表并π塞一 α坐冰基)石黃醯基]六氫叶卜井小基] 己基]二氫-1-氧代異苯并呋喃士基)斗甲基_1Η 吡咯-2,5-二酮 Γ-(1，3-二氫-1¾戈異苯基)各师·(乙基-石黃 ^基)六氫咐土组甲基-讯吡咯_2,5·二酮、 4-[6_[1-(1，3-^氫小氧代異苯并呋喃_5·基)·2,5_二氯冰 甲基-2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-乙基-六氫吡 畊-1-碳硫醯月f 夫喃-5-基)-2,5-二氫斗 甲基-2,5-二氧代-1Η_吡咯-3-基]己基]-Ν-丙基-六氫吡 |畊-1-碳硫醯1 夫喃：基>2,5-二氨-4, 甲基_2,5_二氧代-1Η-吡洛各基]己基]善(丙·2·缔基)六 風ρ比哨1 -1 -碳硬g蠢胺 5 5 12 12 49〇 61〇 -108- 513 12 478 200301117 (103) 實例 名稱 類似於 實例合成 ESI-MS 479 4-[6-[l-(l，3-二氫-1-氧代異苯并呋喃-5-基)-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-3-基]己基]-N-(苯基甲基)六 氫吡畊小碳硫醯胺 12 561 480 4-[6-[1-(1，3-二氫-1-氧代異苯并咬喃-5-基)-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-3-基]己基]-N-[(4-甲基苯基) 甲基]六氫吡畊-1 -碳硫醯胺 12 575 481 N-[(4-氯苯基）甲基]-4-[6-[l-(l，3-二氫小氧代異苯并呋 喃-5-基)-2,5-二鼠-4-甲基-2,5-二氧1代-111-^7比^7各-3-基]己 基]六氫吡畊-1 -碳硫醯胺 12 595 482 4-[6-[1-(1，3-二氯-1-氧代異苯并咬喃-5-基)-2,5-二氯-4_ 甲基-2,5-二氧代-1H-吡咯-3-基]己基]-N-苯基六氫吡畊 -1-碳硫醯胺 12 547 483 4-[6-[1-(1，3-二氮-1-氧1代異苯并咬喃-5-基)-2,5-二氮-4-甲基-2,5-二氧代-1H-吡咯-3-基]己基]-N-(2,6-二甲基苯 基)六氫吡畊-1 -碳硫醯胺 12 575 -109- (104) 表2 0 .根據本發明通式j的化合物，其中甲基苯并嘮畊酮 W=馬土亞胺，n = 6 實例 名稱 類似於 實例合成 ESI-MS 484 3-[6-(4-(2-甲氧基苯甲醯基)六氫吡哜小基）己基]冰甲 基小(4-甲基-1-氧代-lH-2,3-苯并今井各基)-1H-吡洛 -2,5-二酮 4 573 485 環丁基羰基)六氫吡畊-μ基)己基]-4-甲基-1-(4-甲基-1-氧代-1Η-2,3-苯并今井-6-基)-1Η-ρ比洛-2,5- -酉同 4 521 486 3- T基-1-(4-甲基-1-氧代_1H-2,3-苯并呤畊_6- 基M-[6_[4-[(.2-基)羰基]六氫t井小基]己基>1Η4 咯-2,5-二酮 4 549 487 3-[6-1>[4-(二甲基胺基）苯甲醯基]六氫吡畊小基]己 基Η-甲基小(4·甲基小氧代-1Η_2,3-苯并呤畊冬 基)-1Η-ρ 比 ρ各-2,5-二酮 4 586 488 乙醯基/、氫吡畊4·基）己基]甲基―丨气冬甲基 -1-氧代-1Η-2,3-苯并。号畊-6-基VlH-p比嘻-2,5- -酮 4 481 489 3甲基甲基+氧代-1Η-2,3-苯并噚畊_6_ 基)-4-[6-[4_(甲基磺醯基)六氫吡_小基]己基]_1Η_ρ比咯 -2,5-二酮 5 517 (105)200301117 W :馬來亞胺，n: 實例 表21·根據本發明通式；[的化合物，其中v = 2 & _ ，一虱· 1 -莽酉同ESI-MS 4 546 468 469 470 471 472 ---- / Earth,-丄 丄 丄 -ding / minute-Z,:)-Dilang 1- (1,3-dihydro small oxoisobenzofuran_ 5 • yl) _3_methyl Qidong [6- [4 仆 塞 -2-yl) carbonyl] -hexahydropyridine m] hexyl HH-pyridine -2,5-dione_isoisophenyl ^ amino) Benzamidine] hexahydropyridine-; ^ yl] hexylmethyl_1Ηrole-2,5-diketone_ benzopyridin-5-yl ratio ρ each -2,5-difluorene is the same as 4- [4- [1- (1,3-dihydro-1-oxoisobenzofuranyl group) _2,5_dihydro_4_methyl-2,5_dioxo-1H-pyrroleyl ] Hexyl] · N, N < p-Hexapyrine-1-sulfamethoxamine 559 473 474 475 476 477 1- (1,3-dihydro-1-oxoisobenzoylfuran-5-ylmethyl- 4- [6- [4- (methylsulfonyl) hexahydropyridyl] hexyl] _ 丨 Η • pyrrole-2,5-difluorene is the same as κ6 [4 (2,1,3-epoxy Said-α-sorphyl group) stilbene group] hexahydro yebujing small group] hexyl] dihydro-1-oxo-isobenzofuranyl) methyl methyl 1 Η pyrrole-2,5-dione Γ- ( 1,3-dihydro-1¾-geisophenyl) each division ((ethyl-stone yellow yl) hexahydro-ordered soil group methyl-xylpyrrole_2,5 · dione, 4- [6_ [1- (1,3- ^ Hydroxyoxoisobenzofuran-5yl) 2,5_dichlorobenzylmethyl-2,5-di -1H-pyrrole-3-yl] hexyl] -N-ethyl-hexahydropyragon-1-carbothione f-furan-5-yl) -2,5-dihydromethyl-2, 5-dioxo-1'-pyrrole-3-yl] hexyl] -N-propyl-hexahydropyridine | Geng-1-carbosulfanil 1 sulfanyl:> 2,5-diamino-4, methyl Radical _2,5_dioxo-1Η-pyrrolyl] hexyl] xanyl (propane · 2 · alkenyl) hexafluoro ρ ratio 1 -1 -carbon hard g amine 5 5 12 12 49〇61. -108- 513 12 478 200301117 (103) Example name similar to Example Synthesis ESI-MS 479 4- [6- [l- (l, 3-dihydro-1-oxoisobenzofuran-5-yl)- 2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- (phenylmethyl) hexahydropyridine small carbothioamide 12 561 480 4- [6- [1- (1,3-Dihydro-1-oxoisobenzoan-5-yl) -2,5-dihydro-4-methyl-2,5-dioxo 1H-pyrrole-3-yl] hexyl] -N-[(4-methylphenyl) methyl] hexahydropyridine-1 -carboxamidine 12 575 481 N-[(4-chlorophenyl ) Methyl] -4- [6- [l- (l, 3-dihydro small oxoisobenzofuran-5-yl) -2,5-dimur-4-methyl-2,5-di Oxygen 1-111- ^ 7 to ^ 7 each-3-yl] hexyl] hexahydropyridine-1 -carboxamidine 12 595 482 4- [6- [1- (1,3-dichloro-1 -Oxoisobenzoyl-5-yl ) -2,5-Dichloro-4_methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N-phenylhexahydropyridine-1-carboxamidine 12 547 483 4- [6- [1- (1,3-Diazol-1-oxo-l-isobenzoan-5-yl) -2,5-diazol-4-methyl-2,5-dioxo -1H-pyrrole-3-yl] hexyl] -N- (2,6-dimethylphenyl) hexahydropyrimidin-1 -carboxamidine 12 575 -109- (104) Table 2 0. According to The compound of general formula j in the present invention, wherein methylbenzopyridone W = matuimine, n = 6 Example name is similar to the example ESI-MS 484 3- [6- (4- (2-methoxy Benzamidine) hexahydropyridinium) hexyl] ice methyl small (4-methyl-1-oxo-lH-2,3-benzoimide groups) -1H-pyrrol-2,5 -Dione 4 573 485 cyclobutylcarbonyl) hexahydropyridine-μyl) hexyl] -4-methyl-1- (4-methyl-1-oxo-1fluorene-2,3-benzoimide- 6-yl) -1Η-ρbilo-2,5- -pyridine with 4 521 486 3-Tyl-1- (4-methyl-1-oxo_1H-2,3-benzoxine 6- group M- [6_ [4-[(. 2-yl) carbonyl] hexahydrot-well small group] hexyl > 1Η4 Η-2,5-dione 4 549 487 3- [6-1 > [4 -(Dimethylamino) benzylidene] hexahydropyridine] hexylpyrene-methyl small (4-methyl small oxo-1'_2,3-benzopyridine) -1 Η-ρ ratio ρ each -2,5-dione 4 586 488 ethenyl /, hydropyridine 4 · yl) hexyl] methyl — 丨 aspartyl-1-oxo-1Η-2,3- Benzo. No. Geng-6-yl VlH-p than hex-2,5- -one 4 481 489 3methylmethyl + oxo-1, -2,3-benzopyrene_6_yl) -4- [6- [4- (methylsulfonyl) hexahydropyridyl] small group] hexyl] _1Η_ρbiro-2,5-dione 5 517 (105) 200301117 W: maleimine, n: Examples Table 21 · According to the invention Compound of general formula [wherein v = 2 &

490 491 492 、计、、：千u,、 P-J•丞尸甲氧基-苯 ^巷)六氲基)己基]-4H1H.t各_2,5-二酮 基外甲基]Η-吡咯-2.5-二獅 一 ^ \~~z~~T!~m——· -—-— 類似於tn±ji 4490 491 492, Calculate, Calculate, PJ, cadaverylmethoxy-phenyl ^) hexamethyl) hexyl] -4H1H.t each _2,5-diketoexomethyl] pyridine-pyrrole -2.5- 二 狮 一 ^ \ ~~ z ~~ T! ~ M—— · -——-— Similar to tn ± ji 4

ESI-MS 493 夺 5·ΙΓ?ϊ:4-[6-[4-ϋί 產基]己基ΗΗ-吡咯-2,5-二酮 1 (2,3 一氣-1-氧代-1Η-印-5-基)-3-[6-[4-[4-(二甲其脸基）苯甲醯基]六氫吡畊-丨-基]己基]-4_甲基_丨乩&咯 -2,5-二酮 4 557 494 495 496 6 己基]而 ^ 虱代 1 (2,3 一氫1-氧代-111-印-5-基)-3-甲基-4-[6·"[4-(甲其石生 ^基)六氫^己基ΗΗ-吡咯-2,5-二酮 土只^小吩二以·氧代.私基>4_f基 -2,5-二 i同 ^ 5 -111 - 200301117 (106) 表22.根據本發明通式I的化合物，其中V =三氟甲基苯甲腈 ，W =乙内驢硫月尿，η == 2 實例 名稱 類似於 實例合成 ESI-MS 497 4-[3-[2-(4-乙醯基六氫吡畊-1-基）乙基]-4,4-二甲基-5-氧 代-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 15⑷ 468 498 4-[4,4-二甲基-5-氧代-3-[2-[4-(1-氧代丙基)六氫吡畊-1-基]乙基]-2-硫氧咪唑啶-1_基]-2-(三氟甲基)-苯甲腈 15(4) 482 499 4-[4,4-二甲基-3-[2-[4-(2-甲基-1-氧代丙基)六氫吡畊-1-基]乙基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯 甲腈 15(4) 496 500 4-[4,4-二甲基-5-氧代-3-[2-[4-(1-氧代丁基)六氫吡畊-1-基]乙基]-2-硫氧咪唑啶小基]-2-(三氟曱基)-苯甲腈 15⑷ 496 501 4-[3-[2-[4-(環丙基羰基)六氫吡畊-1-基]乙基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 15(4) 494 502 4-[3-[2-[4-(環丁基羰基)六氫吡畊-1-基]乙基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 15⑷ 508 503 4-[4,4-二甲基-5-氧代-3-|>[4-[〇塞-2-基)乙醯基]-六氫吡 口井-1-基]乙基]-2-硫氧味°坐淀-1-基]-2_(二氣甲基)-本甲 腈 15⑷ 550 504 4-[4,4-二甲基-5-乳代-3-[2-[4-[(^塞-2-基)談基]-7Τ鼠ρ比口井 -1-基]乙基]-2-硫氧味ρ坐淀-1-基]-2-(二氣甲基)-冬甲猜 15(4) 536 505 4-[4,4-二曱基-5-氧代-3-[2-[4-[(ρ比淀-4-基)談基]-7Τ氮ρ比 ρ井-1-基]乙基]-2-硫氧味。坐淀-1-基]-2-(二氣甲基)-冬甲 腈 15(4) 531 506 4-[4,4-二甲基-3-〇[4-(甲基磺醯基)六氫吡畊-1-基]乙 基]-5-氧代-2-硫氧味吐淀-1-基]-2-(二氣甲基)-苯甲猜 15(5) 504 507 4-[3-[2-[4-(乙基績酿基)ττ氮卩比呼-1-基]乙基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 15(5) 518 508 4-[4,4·二甲基-5-氧代-3-[2-[4-(丙基磺醯基)-六氫吡畊 基]乙基]硫氧味峻淀-l-基]-2-(二氣甲基)-本甲猜 15(5) 532 509 4-[4,4-二甲基-5-^R-3-[2-[4-(冬基橫酿基)-ττ鼠叶匕口井 小基]乙基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 15(5) 566 510 4-[3-[2-[4-[(4-氰基苯基）磺醯基]六氫吡畊小基]乙 基]-4,4-二甲基-5-乳代-2-硫氧味ρ坐淀-1-基]-2-(二氣甲 基)-苯甲腈 15(5) 591 511 4-[2-[3-(4-氰基-3-(三氟甲基)苯基)-5,5-二甲基-4-氧代 15(12) 513ESI-MS 493 5 · ΙΓ? Ϊ: 4- [6- [4-ϋί producing group] hexylfluorene-pyrrole-2,5-dione 1 (2,3 monogas-1-oxo-1Η-India- 5-yl) -3- [6- [4- [4- (dimethylformyl) benzylidene] hexahydropyridine- 丨 -yl] hexyl] -4_methyl_ 丨 乩 & slightly -2,5-dione 4 557 494 495 496 6 hexyl] and ^ 1 (2,3 monohydro 1-oxo-111-in-5-yl) -3-methyl-4- [6 · " [4- (Metholinolyl) Hexahydro ^ hexylfluorene-pyrrole-2,5-dione is only phenone dioxo.Private group> 4_f group-2,5-di i Same as ^ 5 -111-200301117 (106) Table 22. Compounds of general formula I according to the present invention, where V = trifluoromethylbenzonitrile, W = acetothioneuria, η == 2 Example names are similar Example Synthesis of ESI-MS 497 4- [3- [2- [4- (Ethylhexylpyridin-1-yl) ethyl] -4,4-dimethyl-5-oxo-2-thiooxy Imidazolidine small group] -2- (trifluoromethyl) -benzonitrile 15⑷ 468 498 4- [4,4-dimethyl-5-oxo-3- [2- [4- (1-oxo (Propyl) hexahydropyridine-1-yl] ethyl] -2-thioximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 15 (4) 482 499 4- [4 , 4-dimethyl-3- [2- [4- (2-methyl-1-oxopropyl) hexahydropyrine-1-yl] ethyl] -5-oxo-2-sulfide Imidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 15 (4) 496 500 4- [4,4-dimethyl-5-oxo-3- [2- [4- (1-oxobutyl) hexahydropyridin-1-yl] ethyl] -2-thiooximidazolidine small group] -2- (trifluorofluorenyl) -benzonitrile 15⑷ 496 501 4- [3 -[2- [4- (Cyclopropylcarbonyl) hexahydropyridin-1-yl] ethyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] 2- (trifluoromethyl) -benzonitrile 15 (4) 494 502 4- [3- [2- [4- (cyclobutylcarbonyl) hexahydropyridine-1-yl] ethyl] -4 , 4-Dimethyl-5-oxo-2-thioximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 15⑷ 508 503 4- [4,4-dimethyl-5- Oxo-3- | > [4- [〇 塞 -2-yl) ethenyl] -hexahydropyranoyl-1-yl] ethyl] -2-thiooxy ] -2_ (Digas methyl) -benzonitrile 15⑷ 550 504 4- [4,4-dimethyl-5-lacto-3- [2- [4-[(^ plug-2-yl) Base] -7T mouse ρ than koukai-1-yl] ethyl] -2-thiooxy odor zozo-1-yl] -2- (difluoromethyl) -dongjiachai 15 (4) 536 505 4- [4,4-Difluorenyl-5-oxo-3- [2- [4-[(ρ 比 Lake-4-yl) Hanyl] -7T nitrogen ρ ratio ρ-I-1-yl] B Radical] -2-thiooxygen. Zyodo-1-yl] -2- (difluoromethyl) -aspartonitrile 15 (4) 531 506 4- [4,4-dimethyl-3-〇 [4- (methylsulfonyl) Hexahydropyridin-1-yl] ethyl] -5-oxo-2-thioxotriol-1-yl] -2- (difluoromethyl) -benzyl 15 (5) 504 507 4 -[3- [2- [4- (Ethylpyridyl) ττazepine-1Hyl-1-ethyl] ethyl] -4,4-dimethyl-5-oxo-2-thioximidazole Small group] -2- (trifluoromethyl) -benzonitrile 15 (5) 518 508 4- [4,4 · dimethyl-5-oxo-3- [2- [4- (propylsulfonate (Fluorenyl) -hexahydropyridinyl] ethyl] thioxazone-l-yl] -2- (difluoromethyl) -benacyl 15 (5) 532 509 4- [4,4-di Methyl-5- ^ R-3- [2- [4- (Winter-based transverse brewing group) -ττ rat leaf dagger well small base] ethyl] -2-thiooximidazole small base] -2- ( Trifluoromethyl) -benzonitrile 15 (5) 566 510 4- [3- [2- [4-[(4-cyanophenyl) sulfonamido] hexahydropyridine] ethyl]- 4,4-Dimethyl-5-lacto-2-thioxol odorase-1-yl] -2- (digasmethyl) -benzonitrile 15 (5) 591 511 4- [2- (3- (4-cyano-3- (trifluoromethyl) phenyl) -5,5-dimethyl-4-oxo 15 (12) 513

-112- 200301117-112- 200301117

(107) 實例 名稱 類似於 實例合成 ESI-MS -2-硫乳味吐淀-1 -基]乙基]-N-乙基六鼠p比p井-1 -石反硫酿 胺 512 4-[2-[3-(4-氰基-3-(三氟甲基)苯基)-5,5-二甲基-4-氧代 -2-硫氧咪吐淀-1-基]乙基]-N-丙基六氫p比呼-1-碳硫酿 胺 15(12) 527 513 4-[2-[3-(4-氰基各(三氟甲基)苯基)-5,5-二甲基-4-氧代 -2-硫氧咪唑啶-1-基]乙基]-N-(丙-2-烯基)-六氫吡畊小 碳硫醯胺 15(12) 525 514 4-[2-[3-(4-來基-3-(二氟甲基)苯基)-5,5-二甲基-4-氧代 -2-硫乳味吐淀-1-基]乙基]7T氮ρ比。井-1-碳硫§^S-甲酉旨 15(13) 500 515 4-[2-[3-(4-氰基-3-(三氟甲基)苯基)-5,5-二甲基-4-氧代 -2-硫氧味σ坐淀-1-基]乙基]7T氮?比0井-1-碳硫乙酉旨 15(13) 514(107) The name of the example is similar to that of the example Synthesis ESI-MS-2-Sulfur Milky Tweed-1-yl] ethyl] -N-ethylhexamidine p ratio p-well-1 [2- [3- (4-Cyano-3- (trifluoromethyl) phenyl) -5,5-dimethyl-4-oxo-2-thioxomidol-1-yl] ethyl Phenyl] -N-propylhexahydrop-pyhexyl-1-carbonsulfanamine 15 (12) 527 513 4- [2- [3- (4-cyano ((trifluoromethyl) phenyl) -5 , 5-Dimethyl-4-oxo-2-thiooximidazol-1-yl] ethyl] -N- (prop-2-enyl) -hexahydropyridine ) 525 514 4- [2- [3- (4- (Lycyl-3- (difluoromethyl) phenyl) -5,5-dimethyl-4-oxo-2-sulfur milky scented lake- 1-yl] ethyl] 7T nitrogen ρ ratio. Well-1-Carbosulfur § ^ S-formamidine 15 (13) 500 515 4- [2- [3- (4-cyano-3- (trifluoromethyl) phenyl) -5,5-di Methyl-4-oxo-2-thiooxy sigma sino-l-l-yl] ethyl] 7T nitrogen? Than 0 well-1-carbon sulfur ethyl ester 15 (13) 514

-113 - 20030111 (108) 表23.根據本發明通式I的化合物，其中v =三氟甲基苯甲腈 ，W =乙内酿硫月尿，η = 3 實例 名稱 類似於 實例合成 ESI-MS 516 4-[3-[3-[4-(2-甲氧基苯甲醯基）六氫吡畊-1-基]丙 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 基)-苯甲腈 15⑷ 574 517 4-[3-[3-(4-乙醯基六氫吡畊-1 -基)丙基]-4,4-二甲基-5-氧 代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 15⑷ 482 518 4-[4,4-二甲基-5-氧代-3-[3-[4-(1-氧代丙基)-六氫吡畊 小基]丙基]-2-硫氧咪唑啶-1 -基]-2-(三氟甲基)-苯甲腈 15(4) 496 519 4-[4,4-二甲基-3-[3-[4-(2-甲基-1-氧代丙基)-六氫吡畊 小基]丙基]-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)- 苯甲腈 15⑷ 510 520 4-[4,4-二甲基-5-氧代-3-[3-[4(1-氧代丁基)-六氫吡畊-1-基]丙基]-2-硫氧咪唑啶-1 -基]-2-(三氟甲基)-苯甲腈 15(4) 510 521 4-[3-[3-[4-(環丙基羰基)六氫吡畊小基]丙基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 15⑷ 508 522 4-[3-|>[4-(環丁基羰基)六氫吡畊-1-基]丙基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 15⑷ 522 523 4-[4,4-二甲基-5-氧代各[3-[4[(噻-2-基）乙醯基]六氫吡 畊小基]丙基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲 腈 15(4) 564 524 4-[4,4-二甲基-5-氧代-3-[3-[4-[( 口塞-2-基)藏基]7Τ氯口比口井 -1-基]丙基]-2-硫乳味°坐淀-1-基]-2-(二氣甲基)-苯甲猜 15(4) 550 525 4-[4,4-二甲基-5-氧代-3-[3-[4-[(V比咬-4-基)談基]六風口比 畊-1-基]丙基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲 腈 15⑷ 545 526 4-[3-[3-[4-(3-甲氧-1-氧代丙基）六氫吡畊小基]丙 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 基)-苯甲腈 15(4) 526 527 4-[3-[3-[4-[(2-甲氧基乙氧基）乙醯基]六氫吡畊-1-基]丙 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 15⑷ 556 528 4-[3-[3-[4-[(2-(2-甲氧基乙氧基）乙氧基）乙醯基]六氫吡 畊-1-基]丙基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 15⑷ 600-113-20030111 (108) Table 23. Compounds of general formula I according to the present invention, where v = trifluoromethylbenzonitrile, W = thioneurid, and η = 3 Example names are similar to the examples of synthetic ESI- MS 516 4- [3- [3- [4- [2-Methoxybenzyl) hexahydropyridine-1-yl] propyl] -4,4-dimethyl-5-oxo- 2-thiooximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 15574 574 517 4- [3- [3- (4-ethylamidohexahydropyridine-1 -yl) propyl ] -4,4-Dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 15⑷ 482 518 4- [4,4-Di Methyl-5-oxo-3- [3- [4- (1-oxopropyl) -hexahydropyridine] propyl] -2-thiooximidazol-1-yl] -2- (Trifluoromethyl) -benzonitrile 15 (4) 496 519 4- [4,4-dimethyl-3- [3- [4- (2-methyl-1-oxopropyl) -hexa Hydropyridine] propyl] -5-oxo-2-thioximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 15⑷ 510 520 4- [4,4-dimethyl -5-oxo-3- [3- [4 (1-oxobutyl) -hexahydropyridin-1-yl] propyl] -2-thiooximidazol-1-yl] -2- ( Trifluoromethyl) -benzonitrile 15 (4) 510 521 4- [3- [3- [4- [Cyclopropylcarbonyl] hexahydropyridyl] propyl] -4,4-dimethyl -5- oxygen 2-thiothioimidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 15⑷ 508 522 4- [3- | > [4- (cyclobutylcarbonyl) hexahydropyridine -1-yl] propyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine-1-yl] -2- (trifluoromethyl) -benzonitrile 15⑷ 522 523 4 -[4,4-dimethyl-5-oxo each [3- [4 [(thia-2-yl) ethenyl] hexahydropyridine] propyl] -2-thiooximidazole small Yl] -2- (trifluoromethyl) -benzonitrile 15 (4) 564 524 4- [4,4-dimethyl-5-oxo-3- [3- [4-[(mouth plug- 2-based) Tibetan group] 7T chloride mouth than Ichii-1-yl] propyl] -2-sulfur milk taste ° sitting lake-1-yl] -2- (difluoromethyl) -benzyl 15 ( 4) 550 525 4- [4,4-Dimethyl-5-oxo-3- [3- [4-[(V than Bite-4-yl) Tanji] Liufengkou Bake-1-yl] Propyl] -2-thiooximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 15⑷ 545 526 4- [3- [3- [4- (3-methoxy-1-oxo Propyl) hexahydropyridine] propyl] -4,4-dimethyl-5-oxo-2-thioximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 15 (4) 526 527 4- [3- [3- [4-[(2-methoxyethoxy) ethenyl] hexahydropyridin-1-yl] propyl] -4,4-dimethyl Methyl-5-oxo-2-thioxazomidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 15⑷ 556 528 4- [3- [3- [4-[(2- (2-methoxyethoxy) ethoxy) ethenyl] hexahydropyridin-1-yl] propyl] -4, 4-dimethyl-5-oxo-2-thioximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 15⑷ 600

-114- (109)20030111? 實例 529 530 531 532 535 536 537 538 539 名稱-114- (109) 20030111? Example 529 530 531 532 535 536 537 538 539 Name

類似於 ΐί[^成 !5(5) 4-[4,4-二甲基-3甲基磺Uy六氫吡^ 基h5_M-2:竺％^坐啶小基]冬(三氟甲基茨甲腊 4-[3-[^-[4-(乙基六勤冰77基]喊 基:5-%β-2_硫啶小基]-2·(三氟甲基)-苯甲腈 4-「4本二甲其-5-¥^Γ「：Γ「二〜#二Γ—κ 4-[4,4-二 T 基fj^[3_[4_(丙基g 喊)六 .¾.苎產l·2-石淀小基]冬(三氟甲基)-笨甲腈 4-[3-[3-[4-[(2- ^基)磺醯基[^氮说 ^TjTjT^ 基>4,4-二甲基氧代-2-硫氧咪唑啶-1-基]-2-(三象甲 基)-苯甲腈 鼠肀 4_[4,4_二甲基(苯基3酿基)六^ 4]丙基]土卷鋒兔！咬小基]冬(三氟甲基V苯曱月t 4-[3-[3-[4-[(4-氰磺醯基]六氫吡 基Μ，4-二Τ基士氧代_2·硫氧咪α坐咬小基]_2_(三氟曱 基)-苯甲腈_ 4-[3-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基冰氧代 _2_硫氧咪唆淀-1-基]丙基]-Ν-乙基六氫峨畊-1-碳硫酿 胺 " 4-[3-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧咪唆淀-1 -基]丙基]-Ν-丙基六氫ρ比ρ井小碳瑞酉蠢 胺 μ 4-[3-[3-[4-氣基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧味唆咬-1-基]丙基]-Ν-(丙-2-缔基)-六氮p比哨*-1· 碳硫醯胺 4-[3-[3-[4_氣基-3-(三氟甲基)苯基]_5,5_二甲基-4·-氧代 -2-硫氧味唆咬-1-基]丙基]六氮ρ比呼-1-碳硫酸S-甲酉旨 4-[3-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基冰氧代 -2-硫氧咪唑啶-1-基]丙基]六氫吡畊-1-碳硫酸S-乙酯Similar to ΐί [^ 成! 5 (5) 4- [4,4-dimethyl-3methylsulfonyl Uy hexahydropyridinyl group h5_M-2: Zhu% ^ sitting pyridine small group] winter (trifluoromethyl Citrona 4- [3-[^-[4- (Ethyl hexaquinone 77-based) hydrazine: 5-% β-2_thiopyridyl] -2 · (trifluoromethyl) -benzyl Nitrile 4- "4-benzyl its-5- ¥ ^ Γ": Γ 「二 ～ # 二 Γ—κ 4- [4,4-Di-T group fj ^ [3_ [4_ (propylg shout) six. ¾. 1,2-Shidian small base] winter (trifluoromethyl) -benzonitrile 4- [3- [3- [4-[(2- ^ yl) sulfofluorenyl [^ nitrogen ^ TjTjT ^ group> 4,4-dimethyloxo-2-thiooximidazol-1-yl] -2- (trimethyl) -benzonitrile cymbal 4_ [4,4_dimethyl (Phenyl 3 phenyl group) hexa ^ 4] propyl] soil roll rabbit! Bite small group] winter (trifluoromethyl V benzene hydrazone t 4- [3- [3- [4-[(4-cyano Sulfofluorenyl] hexahydropyridyl M, 4-di-T-thiomethyloxo_2 · thioxamidine α sitting bite small group] _2_ (trifluorofluorenyl) -benzonitrile 4- [3- [3- [4-Cyano-3- (trifluoromethyl) phenyl] -5,5-dimethylglacial oxo_2-thioxanmidino-1-yl] propyl] -N-ethylhexa Hydrogen phen-1-carbosulfanamine " 4- [3- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo -2-Thioximidate-1 -yl] propyl] -N-propylhexahydrogen Benzylamine μ 4- [3- [3- [4-Gas-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooxytidum bite- 1-yl] propyl] -N- (propan-2-enyl) -hexaaza p-peptide * -1 · Carbothioamide 4- [3- [3- [4_ 气 基 -3- (三Fluoromethyl) phenyl] -5,5_dimethyl-4 · -oxo-2-thiooxystilbene-1-yl] propyl] hexazine pihex-1-carbon sulfate S-formamidine Purpose 4- [3- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethylglacial oxo-2-thioximidazol-1-yl] propene S-ethyl] hexahydropyridine-1-carbon sulfate

15(5) 562 15(12) 15(12) 15(12) 15(13) 15(13) 527 541 539 514 528 -115- 20030111715 (5) 562 15 (12) 15 (12) 15 (12) 15 (13) 15 (13) 527 541 539 514 528 -115- 200301117

(no) 表24.根據本發明通式I的化合物，其中V =三氟甲基苯甲腈 ，W =乙内酿硫月尿，η = 4 實例 名稱 類似於 實例合成 ESI-MS 540 4-〇[4-[4-(2-甲氧基苯甲醯基)六氫吡畊小基]丁基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 4 588 541 4-[4-[3-[4-氰基各(三氟甲基)苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶小基]丁基]六氫吡畊小碳腈 4 479 542 4-[3-[4-(4-乙醯基六氫吡畊小基)丁基]-4,4-二甲基-5-氧 代-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 4 496 543 rel-4-[3-[4-[(2R，5S)-4-乙醯基-2,5-二甲基六氫吡畊小基] 丁基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 4 524 544 4-[3-[4-(4-乙醯基六氫-ΜΗ-1，4-二氮呼-1-基）丁基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 510 545 4-[4,4-二甲基-5-氧代各[4-[4-(1-氧代丙基)六氫吡畊-1-基]丁基]-2-硫氧咪唑啶-1 -基]-2-(三氟甲基)-苯甲腈 4 510 546 4-[4,4-二甲基-3-[4-[4-(2-甲基-1-氧代丁基)六氫吡畊小 基]丁基]-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲 腈 4 524 547 rel-4-[3-|>[(2R，5S)-2,5-二甲基-1-氧代丙基]六氫吡畊小 基]丁基]-4,4-二甲基-5-氧代-2-硫氧味17坐淀-1-基]-2-(二氣 甲基)-苯甲腈 4 552 548 4-[3-[4-[4-(2-無基-2-甲基-1-氧代丙基)7^氮^7比'7井-1-基]丁 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腊 4 540 549 4-〇[4-[4-(2,2-二甲基小氧代丙基）六氫吡畊-1 -基]丁 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 4 538 550 rel 冰[3-[4-[(2R，5S)-4-(2,2-二甲基-1-氧代丙基)-2,5-二甲 基六氫吡畊小基]丁基]-4,4-二甲基-5-氧代-2-硫氧咪唑 啶小基]-2-(三氟甲基)-苯甲腈 4 566 551 4-[3-[4-[4-(2,2-二甲基小氧代丙基）六氫-1H-M-二氮呼 小基]丁基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 552 552 4-[4,4-二甲基-5-氧代-3-[4-[4-(l-氧代丁基)六氫吡畊小 基]丁基]-2-硫氧味吐症-1-基]-2_(二氣甲基)-苯甲月青 4 524(no) Table 24. Compounds of general formula I according to the present invention, where V = trifluoromethylbenzonitrile, W = thiourea, and η = 4 Example names are similar to Example Synthesis ESI-MS 540 4- 〇 [4- [4- (2-methoxybenzylidene) hexahydropyridine] butyl] -4,4-dimethyl-5-oxo-2-thioximidazolidine ] -2- (trifluoromethyl) -benzonitrile 4 588 541 4- [4- [3- [4-cyano (trifluoromethyl) phenyl] -5,5-dimethyl-4 -Oxo-2-thioximidazolidine small group] butyl] hexahydropyridine small carbonitrile 4 479 542 4- [3- [4- (4-ethylfluorenylhexahydropyridine small) butyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 4 496 543 rel-4- [3- [4- [ (2R, 5S) -4-Ethyl-2,5-dimethylhexahydropyridine] butyl] -4,4-dimethyl-5-oxo-2-thioximidazolidine- 1-yl] -2- (trifluoromethyl) -benzonitrile 4 524 544 4- [3- [4- (4-ethylfluorenylhexahydro-Mfluorene-1,4-diazepine-1-yl ) Butyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 510 545 4- [4, 4-dimethyl-5-oxo each [4- [4- (1-oxopropyl) hexahydropyridin-1-yl] butyl] -2-thiooximidazol-1-yl]- 2- (three Methyl) -benzonitrile 4 510 546 4- [4,4-dimethyl-3- [4- [4- (2-methyl-1-oxobutyl) hexahydropyridine] butyl [] Yl] -5-oxo-2-thioximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 4 524 547 rel-4- [3- | > [(2R, 5S)- 2,5-dimethyl-1-oxopropyl] hexahydropyridine] butyl] -4,4-dimethyl-5-oxo-2-thiooxytride 17 Yl] -2- (difluoromethyl) -benzonitrile 4 552 548 4- [3- [4- [4- (2-Unradical-2-methyl-1-oxopropyl) 7 ^ nitrogen ^ 7 than '7-well-1-yl] butyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzene Methyl wax 4 540 549 4-〇 [4- [4- (2,2-dimethyl small oxopropyl) hexahydropyridine-1 -yl] butyl] -4,4-dimethyl-5 -Oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 538 550 rel ice [3- [4-[(2R, 5S) -4- (2 , 2-dimethyl-1-oxopropyl) -2,5-dimethylhexahydropyridine] butyl] -4,4-dimethyl-5-oxo-2-thiooxy Imidazolidine small group] -2- (trifluoromethyl) -benzonitrile 4 566 551 4- [3- [4- [4- (2,2-dimethyl small oxopropyl) hexahydro-1H -M-diazepinyl] butyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl ) -Benzonitrile 4 552 552 4- [4,4-dimethyl-5-oxo-3- [4- [4- (l-oxobutyl) hexahydropyridine] butyl] -2-thiooxytene-1-1-yl] -2_ (digasmethyl) -benzylpyrene 4 524

-116- 200301117 (111) 實例 名稱 類似於 實例合成 ESI-MS 553 4-[3-[4-[4-(環丙基羰基)六氫吡畊-1-基]丁基]-4,4-二甲基 -5-氧代-2-硫氧咪唑啶小基]-2-(三氟f7基)-苯甲腈 4 522 554 rel_4-[3-[4-[(2R，5S)-4-(環丙基羰基)-2,5-二甲基六氫吡畊 -1基]丁基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三 氟甲基)-苯甲腈 4 550 555 4-[3-[4-[4-(環丁基羰基)六氫吡畊小基]丁基]-4,4-二甲基 -5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 536 556 4-[4,4-二甲基-5-氧代各[4-[4-心塞-2-基）乙醯基]六氫吡畊 -1 -基]丁基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 4 578 557 4-[3-[4-[4-(甲氧基乙醯基)六氫吡畊小基]丁基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 526 558 4-[3-[4-[4-(3-甲氧基-1-氧代丙基）ττ氮^比啡-丨-基]丁 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 基)-苯甲猜 4 540 559 4-[3-[4-[六氫-4-(3-甲氧基-1-氧代丙基)-1Η-1，4-二氮呼-1-基]丁基]-4,4-二甲基-5-氧代-2-硫氧味σ坐淀-1-基]-2-(二氣 甲基)-苯甲腈 4 554 560 4-[3-[4-[4-[(2-甲氧基乙氧基）乙醯基]六氫吡畊-1-基]丁 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 基)-苯甲腈 4 570 561 4-[3-[4-[4-[(2-(2-甲氧基乙氧基)乙氧基)乙醯基]六氫吡畊 基]丁基]二甲基-5-乳代-2-硫氧j味吐途-1_ 基]-2-(二氟甲基)-苯甲猜 4 614 562 4-[4,4-二甲基-5-氧代-2-硫氧-3-[4-[4-(三氟乙醯基)六氫 吡畊小基]丁基]咪唑啶-1 -基]-2-(三氟甲基)-苯甲腈 4 550 563 4-[3-[4-[六氫-4-(三氟乙醯基)-1Η-1，4-二氮呼-1-基]丁 基]-4,4-二甲基硫乳味哇淀-1-基]-2-(二氟)甲 基)-苯甲腈 4 564 564 4-[3-[4-[4-[(1，3-二甲基-1H-吡唑-5-基)羰基]六氫吡畊-1-基]丁基]-4,4-二甲基硫氧-味咬淀-1-基]-2-(二 氟甲基)-苯甲腈 4 576 565 4-[3-[4-[4-[(呋喃-3-基)羰基]六氫吡畊小基]丁基]-4,4-二 甲基-5-氧代-2-硫氧味吐咬-1-基]-2-(二氣甲基)-苯甲猜 4 548 566 4-[3-[4-[4·[(2,5-二甲基呋喃-3-基)羰基]六氫吡畊-1-基]丁 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 基)-苯甲腈 4 576 -117- (112) 實例 名稱 類似於 實例合成 ESI-MS 567 4-[3-[4-[4-[(異呤唑-5-基)羰基]六氫吡畊小基]丁基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 549 568 4-[4,4-二甲基-3-[4-[4-[(5-甲基異崎唑-3-基)羰基]六氫吡 畊小基]丁基]-5-氧代-2-硫氧-咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 4 563 569 4-[4,4-二甲基-5-氧代-3-[4-[4-[(噻-3-基)羰基]-六氫吡畊 -1 -基]丁基]-2-硫氧咪唑啶小基]冬(三氟甲基)-苯甲腈 4 564 570 4-[4,4-二甲基-3-[4-[4-[(4-甲基-1，2,3-噻二唑-4-基)羰基] T?氮说ρ井-1-基]丁基]-5-氧代-2-硫氧味。圭淀-1-基]-2-(二 氟甲基)-苯甲腈 4 580 / 571 4-[3_[4-[4_[(咬喃_2_基)談基]7^ 鼠卩比 17井-1-基]丁基]_4,4_二 甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 548 572 ‘[Η4-[4-[(呋喃_2_基)羰基]六氫-1Η-1，4-二氮呼小基]丁 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 4 562 573 4-[4,4-二甲基-5-氧代_3-[4-[4-[(噻-2-基)羰基]-六氫吡畊 -1-基]丁基]-2-硫氧味。坐淀-1-基]-2-(二氣甲基)-苯甲猜 4 564 574 4-[3-[4-[ 7^ 鼠-4-[(卩塞-2-基)談基]-1Η-1，4-二氣呼·1-基]丁 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]冬(三氟甲 基)-苯甲腈 4 578 575 4-[4,4-二甲基-5-氧代-3-[4-[4-[(吡啶-4-基)羰基]-六氫吡 口井-1-基]丁基]·*2-硫氣味11 坐淀-1-基]_2_(二氣甲基)-苯甲猜 4 559 576 4-[4,4-二甲基各[4-[4-(甲基磺醯基）六氫吡畊小基]丁 基]-5-氧代-2-硫乳味吐淀-1-基]-2-(二氣甲基)-苯甲猜 5 532 577 rel-4-[4,4-二甲基各[4-[(2R，5S)-2,5-二甲基-4-(甲基磺醯 基）六氫吡畊-1-基]丁基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲猜 5 560 578 4-[3-[4-[六氫-4-(甲基磺醯基)-1 Η-1，4-二氮呼-1 -基]丁 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲猜 5 546 579 4-[3-[4-[4-(乙基磺醯基)六氫吡畊小基]丁基]-4,4-二甲基 -5-氧代-2-硫氧^味峻咬-1-基]-2-(二氣甲基)-苯甲猜 5 546 580 4-[4,4-二甲基-5-氧代-3-[4-[4-(丙基石菱酿基)-ττ氮ρ比口井-1_ 基]丁基]-2-硫乳味σ坐淀-1-基]-2-(三氣甲基)-苯甲猜 5 560 581 4-〇[4-[4-[(2-甲氧基乙基）磺醯基]六氫吡畊-1 -基]丁 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 5 576 200301117 (113) 實例 名稱 類似於 實例合成 ESI-MS 基>苯甲腈 582 4-[4,4-二甲基-5-氧代-3-[4-[4-(苯基磺醯基)-六氫吡畊-1-基]丁基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 5 594 583 4-[3-[4-[4-[(4-氰基苯基）磺醯基]六氫吡畊小基]丁 基]-4,4-二甲基-5-氧代-2-硫氧味p坐淀-1 -基]-2-(二氣甲 基)-苯甲腈 5 619 584 4-[4,4-二甲基-3-[4-[4-[(l-甲基-1H-咪唑-4-基)-磺醯基]六 氫吡畊-1-基]丁基]-5-氧代-2-硫氧咪唑啶小基]-2-(三氟 甲基)-苯甲腈 5 598 585 4-[3-[4-[4-[(3,5-二甲基異吟唑-4-基)磺醯基]六氫吡畊小 基]丁基]-4,4-二甲基-5-氧代-2-硫氧味峻淀-1-基]-2-(二氣 甲基)-苯甲腈 5 613 586 4-[4-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代_2_ 硫氧咪唑啶小基]丁基]乙基六氫吡畊小碳硫醯胺 12 541 587 4-[4-[3-[4-氣基-3_(三氟甲基)苯基]-5,5-二甲基-4-氧代-2- 硫氧味吐淀-1-基]丁基]-N-丙基7T風^比p井-1-碳硫醒胺 12 555 588 4-[4-〇[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代-2-硫氧味。坐淀-1-基]丁基]-N-(丙-2-缔基)-六鼠p比17井-1-竣硫 醯胺 12 553 589 4-[4-〇[4-氰基各(三氟甲基)苯基]-5,5-二甲基-4-氧代-2-硫氧咪吐淀-1-基]丁基]六氫井小碳硫酸S-甲酯 13 528 590 4-[4-[3-[4-氣基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代-2-硫氧i味°坐淀-1-基]丁基]六氮-1H-1，4-二氣吁-1-碳硫酸S-甲酯 13 542 591 4-[4-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基斗氧代-2-硫乳味。坐淀-1-基]丁基]7T氣ρ比哨'-1-碳硫酸S-乙酉旨 13 542 592 4-[4-[3-[4-氣基-3-(二氟甲基)苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶小基]丁基]六氫吡呼小磺醯胺N，N-二甲酯 14 561-116- 200301117 (111) Example name similar to Example Synthesis ESI-MS 553 4- [3- [4- [4- (Cyclopropylcarbonyl) hexahydropyridine-1-yl] butyl] -4,4 -Dimethyl-5-oxo-2-thioximidazolidine small group] -2- (trifluorof7 group) -benzonitrile 4 522 554 rel_4- [3- [4-[(2R, 5S)- 4- (cyclopropylcarbonyl) -2,5-dimethylhexahydropyridine-1yl] butyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine-1- Yl] -2- (trifluoromethyl) -benzonitrile 4 550 555 4- [3- [4- [4- (cyclobutylcarbonyl) hexahydropyridyl] yl] butyl] -4,4- Dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 536 556 4- [4,4-dimethyl-5-oxo [4- [4-cardio-2-yl) ethenyl] hexahydropyridine-1 -yl] butyl] -2-thioximidazolidine] -2- (trifluoromethyl) -Benzonitrile 4 578 557 4- [3- [4- [4- (methoxyethylamidino) hexahydropyridine] butyl] -4,4-dimethyl-5-oxo- 2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 526 558 4- [3- [4- [4- (3-methoxy-1-oxopropane Yl) ττ nitrogen ^ biffine- 丨 -yl] butyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine small group] -2- (trifluoromethyl) -benzyl Guess 4 540 559 4- [3- [4- [hexahydro-4- (3 -Methoxy-1-oxopropyl) -1Η-1,4-diazeth-1-yl] butyl] -4,4-dimethyl-5-oxo-2-thiooxy Zyodo-1-yl] -2- (digasmethyl) -benzonitrile 4 554 560 4- [3- [4- [4-[(2-methoxyethoxy) ethenyl] hexa] Pyridin-1-yl] butyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 4 570 561 4- [3- [4- [4-[(2- (2-methoxyethoxy) ethoxy) ethenyl] hexahydropyridyl] butyl] dimethyl-5-lacto -2-thiooxyj 味 吐 途 -1_yl] -2- (difluoromethyl) -benzyl 4 614 562 4- [4,4-dimethyl-5-oxo-2-thiooxy- 3- [4- [4- (trifluoroacetamidyl) hexahydropyridyl] butyl] imidazolidine-1 -yl] -2- (trifluoromethyl) -benzonitrile 4 550 563 4- [3- [4- [hexahydro-4- (trifluoroethylfluorenyl) -1) -1,4-diazahu-1-yl] butyl] -4,4-dimethylsulfide milk taste -1-yl] -2- (difluoro) methyl) -benzonitrile 4 564 564 4- [3- [4- [4-[(1,3-dimethyl-1H-pyrazole-5- Carbonyl) carbonyl] hexahydropyridin-1-yl] butyl] -4,4-dimethylthiooxy-amidate-1-yl] -2- (difluoromethyl) -benzonitrile 4 576 565 4- [3- [4- [4-[(furan-3-yl) carbonyl] hexahydropyridine] butyl] -4,4-dimethyl-5- Substituted for 2-thiooxyl bite-1-yl] -2- (difluoromethyl) -benzyl 4 548 566 4- [3- [4- [4 · [(2,5-dimethyl Furan-3-yl) carbonyl] hexahydropyridine-1-yl] butyl] -4,4-dimethyl-5-oxo-2-thioximidazolidine small group] -2- (trifluoromethyl ) -Benzonitrile 4 576 -117- (112) Example name similar to Example Synthesis ESI-MS 567 4- [3- [4- [4-[(Isordinazol-5-yl) carbonyl] hexahydropyridine Gengxiaoji] butyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 549 568 4- [4,4-dimethyl-3- [4- [4-[(5-methylisoazazol-3-yl) carbonyl] hexahydropyridine] butyl] -5-oxo-2 -Thioxo-imidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 563 569 4- [4,4-dimethyl-5-oxo-3- [4- [4 -[(Thi-3-yl) carbonyl] -hexahydropyridine-1 -yl] butyl] -2-thioximidazolidine small group] winter (trifluoromethyl) -benzonitrile 4 564 570 4- [4,4-dimethyl-3- [4- [4-[(4-methyl-1,2,3-thiadiazol-4-yl) carbonyl] T? Nitrogen ] Butyl] -5-oxo-2-thiooxy. Guiyodo-1-yl] -2- (difluoromethyl) -benzonitrile 4 580/571 4- [3_ [4- [4 _ [(Oran_2_yl) Hanyl] 7} rat mole ratio 17-well-1-yl] butyl] -4,4_dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 548 572 ' [Η4- [4-[(furan_2_yl) carbonyl] hexahydro-1Η-1,4-diazepinyl] butyl] -4,4-dimethyl-5-oxo-2- Thioxazolyl-1-yl] -2- (trifluoromethyl) -benzonitrile 4 562 573 4- [4,4-dimethyl-5-oxo_3- [4- [4- [ (Thi-2-yl) carbonyl] -hexahydropyridin-1-yl] butyl] -2-thiooxy. Zyodo-1-yl] -2- (difluoromethyl) -benzyl 4 564 574 4- [3- [4- [7 ^ mus-4-[(threon-2-yl) danyl] -1Η-1,4-diapnea · 1-yl] butyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine small group] winter (trifluoromethyl) -benzene Carbonitrile 4 578 575 4- [4,4-dimethyl-5-oxo-3- [4- [4-[(pyridin-4-yl) carbonyl] -hexahydropyridyl-1-yl] Butyl] · * 2-sulfur odor 11 Zyodo-1-yl] _2_ (digasmethyl) -benzyl 4 559 576 4- [4,4-dimethyl each [4- [4- (甲Sulfofluorenyl) hexahydropyridine] butyl] -5-oxo-2-sulfide milk taste tumbling-1-yl] -2- (difluoromethyl) -benzyl 5 532 577 rel -4- [4,4-dimethyl each [4-[(2R, 5S) -2,5-dimethyl-4- (methylsulfonyl) hexahydropyridine-1-yl] butyl ] -5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzyl 5 560 578 4- [3- [4- [hexahydro-4- (methyl Sulfosulfanyl) -1 fluorene-1,4-diazepine-1 -yl] butyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl]- 2- (trifluoromethyl) -benzyl 5 546 579 4- [3- [4- [4- (ethylsulfonyl) hexahydropyridine] butyl] -4,4-dimethyl Iso-5-oxo-2-thiooxy ^ Weijun bite-1-yl] -2- (difluoromethyl) -benzyl 5 546 580 4- [4,4- Methyl-5-oxo-3- [4- [4- (propyl shihshin base) -ττ nitrogen ρ than Hakai-1_yl] butyl] -2-sulfur milk flavor σ sitting lake-1-yl ] -2- (trimethyl) -benzyl 5 560 581 4-〇 [4- [4-[(2-methoxyethyl) sulfonyl] hexahydropyridine-1 -yl] butyl Group] -4,4-dimethyl-5-oxo-2-thioximidazolidine small group] -2- (trifluoromethyl 5 576 200301117 (113) Example name is similar to the example synthetic ESI-MS group> Benzonitrile 582 4- [4,4-dimethyl-5-oxo-3- [4- [4- (phenylsulfonyl) -hexahydropyridin-1-yl] butyl] -2 -Thiothioimidazolidine small group] -2- (trifluoromethyl) -benzonitrile 5 594 583 4- [3- [4- [4-[(4-cyanophenyl) sulfonyl] hexahydro] Pycnogenol] butyl] -4,4-dimethyl-5-oxo-2-thioxol p-azide-1 -yl] -2- (digasmethyl) -benzonitrile 5 619 584 4- [4,4-dimethyl-3- [4- [4-[(l-methyl-1H-imidazol-4-yl) -sulfofluorenyl] hexahydropyridin-1-yl] but Yl] -5-oxo-2-thioximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 5 598 585 4- [3- [4- [4-[(3,5- Dimethylisoindazol-4-yl) sulfofluorenyl] hexahydropyridyl] butyl] -4,4-dimethyl-5-oxo-2-thioxotriol-1-yl ] -2- (Digas methyl) -benzonitrile 5 613 5 86 4- [4- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo_2_thiooximidazole small group] butyl ] Ethylhexahydropyridine 12 541 587 4- [4- [3- [4-Amino-3_ (trifluoromethyl) phenyl] -5,5-dimethyl-4- Oxo-2-thiooxytitutoto-1-yl] butyl] -N-propyl 7T ^^ p-well-1-carbon thiopentamine 12 555 588 4- [4-〇 [4-cyano -3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooxy. Zyodo-1-yl] butyl] -N- (propan-2-enyl) -hexamidine p ratio 17 wells 1-1-thiothiamine 12 553 589 4- [4-〇 [4-cyano each (Trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thioxomidol-1-yl] butyl] hexahydrowell small carbon sulfate S-methyl 13 528 590 4- [4- [3- [4-Gas-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooxy 1-yl] butyl] hexazine-1H-1,4-difluoro-1-carbon sulfate S-methyl 13 542 591 4- [4- [3- [4-cyano-3- (trifluoro Methyl) phenyl] -5,5-dimethyl oxo-2-thio milky taste. Zyodo-1-yl] butyl] 7T gas ρ than whistle'-1-carbon sulfuric acid S-acetamidine 13 542 592 4- [4- [3- [4-Gasyl-3- (difluoromethyl) Phenyl] -5,5-dimethyl-4-oxo-2-thioximidazolidine small group] Butyl] hexahydropyridoxamine N, N-dimethyl ester 14 561

-119- (114) 表25.根據本發明通式I的化合物，其中V =三氟甲基苯甲腈 ，W =乙内酿硫月尿，η = 5 實例 名稱 類似於 實例合成 ESI-MS 593 4-[3-[5-[4-(2-甲氧基苯甲醯基）六氫吡畊-1-基]戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲猜 4 602 594 4-[5-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧咪唑啶-1-基]戊基]六氫吡畊-1-碳腈 4 493 595 4-[3-[5-(4-乙酸基7Τ氮^7比?井--基)戊基]-4,4-二甲基-5-氧 代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 510 596 rel-4-[3-[5-[(2R，6S)-4-乙醯基-2,6-二甲基六氫吡畊-1-基]戊基]-4,4-二甲基-5-氧代-2-硫氧味。坐淀-1-基]-2-(二 氟甲基)-苯甲腈 4 538 597 4-[3-[5-(4-乙醯基六氫-1-1Η-1，4-二氮呼-1-基）戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 4 524 598 4-[4,4-二甲基-5-氧代-3-[5-[4-(1-氧代丙基)六氫吡畊-1-基]戊基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 4 524 599 4-[4,4-二甲基-3-[5-[4-(2-甲基-1-氧代丙基)六氫吡畊小 基]戊基]-5-氧代-2-硫氧味嗤淀-1-基]-2-(二氣甲基)-苯 甲腈 4 538 600 4-[3-[5-[六氫-4-(2-甲基小氧代丙基)-1Η-1，4-二氮呼小 基]戊基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三 氟甲基)-苯甲腈 4 552 601 4-[3-[5-[4-(2-羥基-2-甲基-1-氧代丙基)-六氫吡畊-1-基] 戊基]-4,4-二甲基-5-氧代-2-硫氧味吐淀-1-基]-2-(二氣 甲基)-苯甲腈 4 554 602 4-[3-[5-[4-(2,2-二甲基-1-氧代丙基)六氫吡畊-1-基]戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 基)-苯甲腊 4 552 603 4-[3-[5-[4-(2,2-二甲基-1-氧代丙基)六氫-1Η-1，4-二氮呼 小基]戊基]-4,4-二甲基-5-氣代-2-硫氧味哇淀-1-基]-2-(三氟甲基)苯甲腈 4 566 604 4-[4,4-二甲基-5-氧代-3-[5-[4-(1-氧代丁基)六氫吡啩小 基]戊基]-2-硫氧味σ坐淀-1-基]-2-(二氣甲基)-苯甲猜 4 538 605 4-[3-[5-[4-(環丙基羰基)六氫吡畊-1-基]戊基]-4,4-二甲 4 536-119- (114) Table 25. Compounds of general formula I according to the present invention, where V = trifluoromethylbenzonitrile, W = thioneurin, and η = 5 593 4- [3- [5- [4- (2-methoxybenzylidene) hexahydropyridine-1-yl] pentyl] -4,4-dimethyl-5-oxo-2 -Thiothioimidazol-1-yl] -2- (trifluoromethyl) -benzyl 4 602 594 4- [5- [3- [4-cyano-3- (trifluoromethyl) phenyl ] -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] pentyl] hexahydropyridine-1-carbonitrile 4 493 595 4- [3- [5- ( 4-acetoxy 7T nitrogen ^ 7 ratio 井 --yl) pentyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl ) -Benzonitrile 510 596 rel-4- [3- [5-[(2R, 6S) -4-ethenyl-2,6-dimethylhexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooxy odor. Zyodo-1-yl] -2- (difluoromethyl) -benzonitrile 4 538 597 4- [3- [5- (4-Ethylfluorenylhexahydro-1-1Η-1,4-diazepine Homo-1-yl) pentyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 524 598 4- [4,4-dimethyl-5-oxo-3- [5- [4- (1-oxopropyl) hexahydropyrine-1-yl] pentyl] -2-thiooximidazole Pyridyl] -2- (trifluoromethyl) -benzonitrile 4 524 599 4- [4,4-dimethyl-3- [5- [4- (2-methyl-1-oxopropyl) Base) hexahydropyridine] pentyl] -5-oxo-2-thiooxy misolake-1-yl] -2- (digasmethyl) -benzonitrile 4 538 600 4- [3 -[5- [hexahydro-4- (2-methyl small oxopropyl) -1Η-1,4-diazepinyl] pentyl] -4,4-dimethyl-5-oxo 2-thiothioimidazolidine small group] -2- (trifluoromethyl) -benzonitrile 4 552 601 4- [3- [5- [4- (2-hydroxy-2-methyl-1-oxyl Propyl) -hexahydropyridine-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooxytendrine-1-yl] -2- (digas ) -Benzonitrile 4 554 602 4- [3- [5- [4- (2,2-dimethyl-1-oxopropyl) hexahydropyrimidin-1-yl] pentyl] -4 , 4-dimethyl-5-oxo-2-thiooximidazolidine small group] -2- (trifluoromethyl) -benzyl 4 552 603 4- [3- [5- [4- (2 , 2-two Yl-1-oxopropyl) hexahydro-1Η-1,4-diazepinyl] pentyl] -4,4-dimethyl-5-oxo-2-thioxocarb -Yl] -2- (trifluoromethyl) benzonitrile 4 566 604 4- [4,4-dimethyl-5-oxo-3- [5- [4- (1-oxobutyl) Hexahydropyridinyl] pentyl] -2-thiooxyzine σ sitting lake-1-yl] -2- (difluoromethyl) -benzyl 4 538 605 4- [3- [5- [4 -(Cyclopropylcarbonyl) hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-4 536

-120- 200301117 (115) 實例 名稱 類似於 實例合成 ESI-MS 基-5-氧代-2-硫氧咪唑啶-1·基]-2-(三氟甲基)-苯甲腈 606 4-[3-[5-[4-(環丁基羰基)六氫吡畊小基]戊基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 550 607 4-[4,4-二甲基-5-氧代-3-〇[4-[(噻-2-基)乙醯基]-六氫吡 畊小基]戊基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲 腈 4 592 608 4-[3-[5-[4-(甲氧基乙醯基)六氫吡畊-1-基]戊基]-4,4-二 甲基-5-氧代-2-硫氧咪唑淀小基]-2-(三氟甲基)-苯甲腈 4 540 609 4-[3-〇[4-(3-甲氧基小氧代丙基）六氫吡畊-1 -基]戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 基)-苯甲腈 4 554 610 4-0[5-[4-[(2-甲氧基乙氧基）乙醯基]六氫吡畊-1-基]戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 基)-苯甲腈 4 584 611 4-[3-[5-[4-[(2-(2-甲氧基乙氧基）乙氧基）乙醯基]六氫吡 畊小基]戊基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 628 612 4-[4,4-二甲基-5-氧代-2-硫氧各[5-[4-(三氟乙醯基)六氫 吡畊小基]戊基]咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 564 613 4-[3-[5-[4-[(1，3-二甲基-1H-吡咯-5-基)羰基]六氫吡畊 -1 -基]戊基]-4,4-二甲基-5-氧代-2-硫氧-味σ坐淀-1 _ 基]-2-(三氟甲基)-苯甲腈 4 590 614 4_[3-[5_[4-[(呋喃-3-基)羰基]六氫吡畊-1-基]戊基Η，4-二甲基-5-氧代-2-硫氧味吐淀-1-基]-2-(二氣甲基)-苯甲 腈 4 562 615 4-[3-[5-[4-[(呋喃-3-基)羰基]六氫-1Η-Μ-二氮呼小基] 戊基]-4,4-二甲基-5-氧代-2-硫氧味σ坐淀-1-基]-2-(二氣 甲基)-苯甲腈 4 576 616 4-[3-[5-[4-[(2,5-二甲基呋喃-3-基)羰基]六氫吡畊-1-基] 戊基]-4,4-二甲基-5-氧ι代-2-硫氧j味17坐咬-1-基]-2-(二氣 甲基)-苯甲腈 4 590 617 4-[3-[5-[4-[(異嘮唑-5-基）羰基]六氫吡畊-1-基]戊 基]-4,4-二甲基-5-氧代-2-硫氧味峻淀-1-基]-2-(二氣甲 基)-苯甲月青 4 563 618 4-[4,4-二甲基-3-[5-[4-[(5-甲基異呤唑-3-基)羰基]六氫 叶匕ρ井-1-基]戊基]-5-乳代-2-疏氧^-味吐淀-1-基]-2-(二氣 4 577-120- 200301117 (115) Example name similar to Example Synthesis [3- [5- [4- (Cyclobutylcarbonyl) hexahydropyridine] yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 550 607 4- [4,4-dimethyl-5-oxo-3-〇 [4-[(thia-2-yl) ethenyl] -Hexahydropyridine] pentyl] -2-thioximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 592 608 4- [3- [5- [4- (Methoxyethenyl) hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thioximidazolium small group] -2- (trifluoromethyl ) -Benzonitrile 4 540 609 4- [3-〇 [4- (3-methoxy-small oxopropyl) hexahydropyrimyl-1 -yl] pentyl] -4,4-dimethyl -5-oxo-2-thiooxyimidazolidine small group] -2- (trifluoromethyl) -benzonitrile 4 554 610 4-0 [5- [4-[(2-methoxyethoxy ) Ethylfluorenyl] hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine small group] -2- (trifluoromethyl)- Benzonitrile 4 584 611 4- [3- [5- [4-[(2- (2-methoxyethoxy) ethoxy) ethenyl] hexahydropyridine] pentyl]- 4,4-dimethyl-5- Oxo-2-thiooxyimidazolidine-1-yl] -2- (trifluoromethyl) -benzonitrile 4 628 612 4- [4,4-dimethyl-5-oxo-2-thiooxy Each [5- [4- (trifluoroacetamidyl) hexahydropyridyl] yl] pentyl] imidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 564 613 4- [ 3- [5- [4-[(1,3-dimethyl-1H-pyrrole-5-yl) carbonyl] hexahydropyridine-1 -yl] pentyl] -4,4-dimethyl-5 -Oxo-2-thiooxy-taste σ sitting lake -1 -yl] -2- (trifluoromethyl) -benzonitrile 4 590 614 4_ [3- [5_ [4-[(furan-3-yl ) Carbonyl] hexahydropyridine-1-yl] pentylfluorene, 4-dimethyl-5-oxo-2-thiooxytituto-1-yl] -2- (digasmethyl) -benzene Carbonitrile 4 562 615 4- [3- [5- [4-[(furan-3-yl) carbonyl] hexahydro-1H-M-diazolyl] pentyl] -4,4-dimethyl -5-oxo-2-thiooxy odor σ sitting lake-1-yl] -2- (digas methyl) -benzonitrile 4 576 616 4- [3- [5- [4-[(2, 5-dimethylfuran-3-yl) carbonyl] hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooxy 1-yl] -2- (digasmethyl) -benzonitrile 4 590 617 4- [3- [5- [4-[(Isoxazol-5-yl) carbonyl] hexahydropyridine-1- Yl] pentyl] -4,4-dimethyl-5-oxo-2-thioxotriol-1-yl] -2- (difluoromethyl) -benzyl Qing 4 563 618 4- [4,4-dimethyl-3- [5- [4-[(5-methylisopurazol-3-yl) carbonyl] hexahydropyridine-1-yl] Pentyl] -5-lacto-2-oxo ^ -weitudian-1-yl] -2- (digas 4 577

-121 - 200301117 (116) 實例 名稱 類似於 實例合成 ESI-MS 甲基)-苯甲腈 619 4-[4,4-二甲基-5-氧代各[5-[4-[(嘧-3-基)羰基]-六氫吡畊 -1-基]戊基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 578 620 4-[3-[5-[六氫 [(噻-3-基)羰基]-1H-1，4-二氮呼-1-基]戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 4 592 621 4-[4,4-二甲基-3-[5-[4-[(4-甲基-1，2,3-噻二唑-4-基)羰基] 六氫吡畊小基]戊基]-5-氧代-2-硫氧咪唑啶小基]-2-(三 氟甲基)-苯甲猜 4 594 622 4-[3_[5-[4_[(呋喃基)羰基]六氫-1H-1，4-二氮呼小基] 戊基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟 甲基)-苯甲腈 4 576 623 4-[4,4-二甲基-5-氧代-3-[5-[4-[(。塞-2-基)談基]-六氮π比哨· -1-基]戊基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 4 578 624 4-[3-[5-[六氫-4-[(噻-2-基)羰基]-1Η-1，4-二氮呼-1-基]戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)**苯甲猜 4 592 625 4-[4,4-二甲基-5-氧代-3-[5-[4-[(吡啶-4-基)羰基]-六氫吡 畊小基]戊基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲 腈 4 573 626 4-[4,4-二甲基-3-[5-[4-(甲基基磺醯基)六氫吡畊小基] 戊基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲 腈 4 546 627 rel-4_[3-[5-[(2R，6S)-2,6-二甲基_4_(甲基磺醯基)六氫吡 呼-1 -基]戊基]-4,4-二甲基-5-氧代-2-硫氧味咬症-1 _ 基]-2-(三氟甲基)-苯甲腈 4 574 628 4-[3-[5-[六氫-4-(甲基磺醯)-1 Η-1，4-二氮呼小基]戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 基)-苯甲腈 5 560 629 4-[3-[5-[4-(乙基石黃酸基)7T氮^比p井-1-基]戊基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 5 560 630 4-[4,4-二甲基-5-氧代各[5-[4-(丙基磺醯基)六氫吡畊-1-基]戊基]-2-硫氧-咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 5 574 631 4-[4,4-二甲基-5-氧代-3-[5-[4-(苯基磺醯基)-六氫吡畊 -1-基]戊基]-2-硫氧味17坐淀-1-基]-2-(二氣甲基)-苯甲猜 5 608 632 4-[3-[5-[4-[(4-氰基苯基）磺醯基]六氫吡畊-1-基]戊 5 633-121-200301117 (116) Example name similar to Example Synthesis of ESI-MS methyl) -benzonitrile 619 4- [4,4-dimethyl-5-oxo each [5- [4-[(pyrimide- 3-yl) carbonyl] -hexahydropyridin-1-yl] pentyl] -2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 578 620 4- [ 3- [5- [hexahydro [(thia-3-yl) carbonyl] -1H-1,4-diazeth-1-yl] pentyl] -4,4-dimethyl-5-oxo- 2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 592 621 4- [4,4-dimethyl-3- [5- [4-[(4- Methyl-1,2,3-thiadiazol-4-yl) carbonyl] hexahydropyridine] pentyl] -5-oxo-2-thiooximidazolidine small] -2- (trifluoro (Methyl) -benzyl 4 594 622 4- [3_ [5- [4 _ [(furanyl) carbonyl] hexahydro-1H-1,4-diazepinyl] pentyl] -4,4-di Methyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 576 623 4- [4,4-dimethyl-5-oxo -3- [5- [4-[(. Ce-2-yl) danyl] -hexazine π ratio whistle -1-yl] pentyl] -2-thiooximidazolidine small group] -2- ( Trifluoromethyl) -benzonitrile 4 578 624 4- [3- [5- [hexahydro-4-[(thia-2-yl) carbonyl] -1Η-1,4-diazepine-1-yl ] Pentyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- ( Fluoromethyl) ** Benzoyl 4 592 625 4- [4,4-Dimethyl-5-oxo-3- [5- [4-[(pyridin-4-yl) carbonyl] -hexahydropyridine Phenyl] pentyl] -2-thioximidazolidine small] -2- (trifluoromethyl) -benzonitrile 4 573 626 4- [4,4-dimethyl-3- [5- [ 4- (methylsulfofluorenyl) hexahydropyridine] pentyl] -5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 546 627 rel-4_ [3- [5-[(2R, 6S) -2,6-dimethyl-4- (methylsulfonyl) hexahydropyridine-1 -yl] pentyl] -4, 4-dimethyl-5-oxo-2-thiooxytidose bite-1_yl] -2- (trifluoromethyl) -benzonitrile 4 574 628 4- [3- [5- [hexahydro- 4- (methylsulfonium) -1 fluorene-1,4-diazepinyl] pentyl] -4,4-dimethyl-5-oxo-2-thioximidazolidine small] -2 -(Trifluoromethyl) -benzonitrile 5 560 629 4- [3- [5- [4- (ethylxanthoxanoyl) 7T nitrogen ^ p-well-1-yl] pentyl] -4,4 -Dimethyl-5-oxo-2-thiooximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 5 560 630 4- [4,4-dimethyl-5-oxo Each [5- [4- (propylsulfonyl) hexahydropyridin-1-yl] pentyl] -2-thiooxy-imidazol-1-yl] -2- (trifluoromethyl) -benzene Nitrile 5 574 631 4- [4,4-dimethyl-5-oxo-3- [5- [4- (phenylsulfonyl)- Pyridin-1-yl] pentyl] -2-thiooxy 17 azeo-1-yl] -2- (difluoromethyl) -benzyl 5 608 632 4- [3- [5- [ 4-[(4-cyanophenyl) sulfofluorenyl] hexahydropyridin-1-yl] penta 5 633

-122- 200301117 (117) 實例 名稱 類似於 實例合成 ESI-MS 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-卜基]-2-(三氟甲 基)-苯甲腈 633 4-[3-[5-[4-[(2-甲氧基乙氧基)磺醯基]六氫吡畊-1-基]戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 5 590 634 4-[3-[5-[4-[(2-(2-甲氧基乙氧基）乙基)磺醯基]六氫吡畊 -1-基]戊基]-4,4-二甲基-5-氧代-2-硫氧味吐淀-1_ 基]-2-(三氟甲基)-苯甲腊 5 634 635 4-[3-[5-[4-[(2-[2-(2-甲氧基乙氧基）乙基]磺醯基)-六氫 吡畊-1-基)戊基)-4,4-二甲基-5-氧代-2-硫氧-咪唑啶小 基]-2-(二氟甲基)-苯甲赌 5 678 636 4-[4,4-二甲基-3-[5-[4-[(l-甲基-1H-咪唑-4-基)-磺醯基] 六氫吡畊小基]戊基]-5-氧代-2-硫氧咪唑啶小基]-2-(三 氟甲基)-苯甲腈 5 612 637 4-[3-[5-[4-[(3,5-二甲基異哼唑-4-基)磺醯基]六氫吡畊 -1-基]戊基]-4,4-二甲基-5-氧代-2-硫氧味σ坐淀-1_ 基]-2-(三氟甲基)-苯甲猜 5 627 638 4-[5-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫乳味吐淀-1-基]戊基]-Ν-乙基7Τ鼠ρ比^-1-碳硫酷 胺 12 555 639 4-[5-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧咪唑啶小基]戊基]-Ν-丙基六氫吡畊小碳硫醯 胺 12 569 640 4-[5-[3-[4-氰基各(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧咪唑啶-1-基]戊基]-Ν-(丙-2-烯基)-六氫吡畊小 碳硫醯胺 12 567 641 4-[5-[3-[4-氣基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧味σ坐淀-1-基]戊基]κ氮峨。井-1-碳硫酸S-甲酉旨 13 542 642 4-[5-[3-[4-氣基-3-(三敦甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧味σ坐淀-1-基]戊基]7T氣-1H-1，4-二氮p平-1-碳硫 酸S-甲酯 13 556 643 4-[5-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧咪峻淀-1 -基]戊基]六氫ρ比呼-1 -碳硫酸S-乙酉旨 13 556 644 4-[5-[3-[4-*fL基-3-(三敦甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧咪唑啶-1-基]戊基]六氫吡畊小磺醯胺Ν，Ν-二甲 酯 14 575-122- 200301117 (117) Example name is similar to Example Synthetic ESI-MS group] -4,4-dimethyl-5-oxo-2-thiooximidazolidine-butyl] -2- (trifluoromethyl ) -Benzonitrile 633 4- [3- [5- [4-[(2-methoxyethoxy) sulfonyl] hexahydropyridin-1-yl] pentyl] -4,4-di Methyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 5 590 634 4- [3- [5- [4-[(2- (2-Methoxyethoxy) ethyl) sulfofluorenyl] hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooxytaste -1_yl] -2- (trifluoromethyl) -benzyl 5 634 635 4- [3- [5- [4-[(2- [2- (2-methoxyethoxy) ethyl ] Sulfofluorenyl) -hexahydropyridin-1-yl) pentyl) -4,4-dimethyl-5-oxo-2-thiooxy-imidazolidine small group] -2- (difluoromethyl ) -Benzene 5 678 636 4- [4,4-dimethyl-3- [5- [4-[(l-methyl-1H-imidazol-4-yl) -sulfonyl] hexahydropyridine Phenyl] pentyl] -5-oxo-2-thioximidazolidine small] -2- (trifluoromethyl) -benzonitrile 5 612 637 4- [3- [5- [4- [ (3,5-dimethylisohumazol-4-yl) sulfofluorenyl] hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooxy Flavor σ sitting lake-1_yl] -2- (trifluoromethyl) -benzyl 5 627 638 4- [5- [3- [4-Cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-sulfide milky scented lake-1-yl] pentan Yl] -N-ethyl 7T rat p ratio ^ -1-Carbothioamide 12 555 639 4- [5- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5, 5-dimethyl-4-oxo-2-thiooximidazolidine small group] pentyl] -N-propylhexahydropyridine small carbothioamide 12 569 640 4- [5- [3- [4 -Cyano (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] pentyl] -N- (prop-2-ene ) -Hydroxypyridine, small carbamide, 12 567 641 4- [5- [3- [4-Gas-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4 -Oxo-2-thiooxy sigma sino lake-1-yl] pentyl] κazepine. I-1-Carbon sulfate S-formamidine purpose 13 542 642 4- [5- [3- [4-Gasyl-3- (tridenylmethyl) phenyl] -5,5-dimethyl-4- Oxo-2-thiooxy sigma sino-l-l-yl] pentyl] 7T gas-1H-1,4-diazepine p flat-1-carbon sulfate S-methyl 13 556 643 4- [5- [ 3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thioxoamido-1 -yl] pentyl] hexahydro ρ Bihu-1 -Carbon sulfate S-Ethylamine 13 556 644 4- [5- [3- [4- * fLyl-3- (tridenylmethyl) phenyl] -5,5-dimethyl- 4-oxo-2-thiooxyimidazolidin-1-yl] pentyl] hexahydropyrimoxamine N, N-dimethyl ester 14 575

-123- (118) 200301117 表2 6 ·根據本發明通式i的化合物，其中v 乙内醯硫脲 實例 氟 甲基苯甲腈-123- (118) 200301117 Table 2 6 · Compounds of general formula i according to the invention, wherein v hydantoin thiourea Example Fluorine Methylbenzonitrile

名稱 類似於 ESI-MS 496 524 616 507 645 646 647 648 649 650 l[4:4-二甲基-3-[6_[4-(甲基六井小基）己 -2-硫氧咪吐淀-1-基]_2-(三氟甲基)_苯甲腊_ i-[4,4-二甲基·3·[6·[4_(1_ 甲基乙基）六氫 < gl·5-氧代_2·硫氧咪唑淀-1-基]冬(三氟甲基V策^ 4-[3-[6-[4-(2·甲氧基苯甲醯基)^ 代冬硫氧咪唑淀小基]冬(三氟甲基)_苯甲腈 4-[6-〇[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代-2 硫氧咪峻基]己基]六氫p比味小碳腈 1[3例4-乙酿基六氫*井小基]己基].4,4二 -2_硫氧咪唑啶-1-基]_2_(三氟甲基)-苯甲腈 rel-4-[>[6-[(2R，5S)-4-乙酿基-2,5-二甲基-六^ 己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]κ三翕甲 基)-苯甲腈_ 二 代1-4-[3-[6-[(2邮)-4-乙醯基-2,6-二甲 己基M，4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]_2_(三螽甲 基)-苯甲腈 一 成 3 4 4 4 4 4 552 652 653 4-[4，冬二甲基_5_氧代_3|[4♦氧代丙基)·六氫吡呼-卜 基]己基]-2-硫氧咪唑啶-1-基]-2—(三氟甲基)_苯甲腈 654 4-[4,4-二甲基各[6-[4-(2-甲基小氧代丙 己基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲某v芡甲睛土 rel-4-[3-[6-[(2R，5S)-2,5·:甲基-4-(2-甲基-1-氧代丙基）氫 毗畊-1-基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶] 基]-2-(三氟甲基)-苯甲腈 4 580 655 4-[3-[6-[六氫-4-(2-甲基-1-氧代丙基^平小基] 己基]-4,4-二甲基-5-氧代-2-硫氧咪峻啶-1-基]-2-(三氟甲 基)-苯甲腈 一 4 566 656 4-[3-[6-[4-(2-經基-2-甲基-1-氧代丙基)六氫吡畊」·基]己 基]-4,4-二甲基-5-氧代-2-硫氧咪。坐咬小基]_2-(三氟甲基)_ 苯甲腈 一 ι 4 568 657 4-[3-[6-[4-(2,2-二甲基-1—氧代丙基）六+基]己 基]-4,4-二甲基-5-氧代-2-硫氧咪吐淀-1-基]_2-(三氟甲基)· 苯甲腈 _ ^ 4 566 658 rel-4-[3-[6-[(2R，5S)-4-(2,2-二甲基-1-氧代丙基)_2,5·二甲基 4 594 -124- (119) 實例 名稱 類似於 實例合成 ESI-MS 六氫吡畊小基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 659 rel-4-[3-[6-[(2R，6S)-4-(2,2-二甲基-1-氧代丙基)-2,6-二甲基 六氫吡畊小基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小 基]-2-(三氟甲基)-苯甲腈 4 594 660 4-[4,4-二甲基-5-氧代-3-[6-[4-(l-氧代丁基)六氫吡畊小基] 己基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 4 552 661 4-[3-[6-[4-(環丙基羰基)六氫吡畊-1-基]己基]-4,4-二甲基 -5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 550 662 rel-4-[3-[6-[(2R，5S)-4-(環丙基羰基)-2,5-二甲基六氫吡畊 -1-基]己基]-4,4-二甲基-5-氧代-2-硫氧味。坐淀-1-基]-2-(二 氟曱基)-苯甲腈 4 578 663 4-[3-[6-[4-(壤丁基談基)ττ氮p比17井-1-基]己基]-4,4-二甲基 -5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 564 664 4-[3-[6-[4-(甲氧基乙醒基）κ鼠说^-1-基]己基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 554 665 4-[3-[6-[4-(3-甲氧基-1-氧代丙基）κ鼠p比哨 -1-基]己 基]-4,4-二甲基-5-氧代-2-硫氧味σ坐淀-1-基]-2-(二氣甲基)- 苯甲腈 4 568 666 rel-4-[3-[6-[(2R,5S)-4-(3- Τ 氧基小氧代丙基)-2,5-二甲基 六氫吡畊-1-基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲月青 4 596 667 4-[3-[6-[六鼠-4-(3-甲氧基-1-氧代丙基)-111-1，4-二鼠呼-1-基]己基]-4,4-二甲基-5-氧代-2-硫氧味唆淀-1-基]-2-(二氣 甲基)-苯甲腈 4 582 668 4-[3-[6-[4-[(2-甲氧基乙氧基）乙醯基]六氫吡畊小基]己 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)- 苯甲腈 4 598 669 4-[3-[6-[4-[(2-(2-甲氧基乙氧基）乙氧基）乙醯基]六氫吡畊 小基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三 氟甲基)-苯甲腈 4 642 670 4-[4,4-二甲基-5-氧代-2-硫乳-3-[6-[4-(二氣乙酿基)ττ氮叶匕 • 1 -基]己基]咪吐淀小基]-2-(三氟甲基)-苯甲腈 4 578 671 rel_4_[3-[6-[(2R，5S)-2,5-二甲基-4-(三氟乙醯基）六氫吡畊 -1-基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三 氟甲基)-苯甲腈 4 606 200301117 (120) 實例 名稱 類似於 實例合成 ESI-MS 672 4-[4,4-二甲基-5-氧代-3-[6-[4-[(噻-2-基）乙醯基]六氫吡畊 -1-基]己基]2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 4 606 673 rel-4-[3_[6-[(2R，5S)-4-[(呋喃各基)羰基]-2,5-二甲基六氫吡 畊小基]己基M，4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 604 674 rel斗[3-[6_[(2R，5S)-4-[(異吟唑-5-基)羰基]-2,5-二甲基六氫 叶匕p井-1-基]己基]-4,4-二甲基-5-乳代-2-硫氧味°坐淀-1 · 基]-2-(三氟甲基)-苯甲腈 4 605 675 4_[3-[6-[4-[(呋喃-2-基)羰基]六氫吡畊小基]己基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 576 676 rel-4-[3-[6-[(2R，5S)-4-[(呋喃-2-基)羰基]-2,5·二甲基六氫吡 哨· -1-基]己基]-4,4-二甲基-5-氧代-2-硫氧味峻淀-1_ 基]-2-(三氟甲基)-苯甲腈 4 604 677 4-[3-[6-[4-[(咬喃-2-基)談基]r?氮-1Η-1，4-二氮吁-1-基]己 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)- 苯甲腈 4 590 678 4-[4,4-二甲基-5-氧代-3-[6-[4-[(嘧-2-基)羰基]六氫吡畊小 基]己基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 4 592 679 reM-[3-[6-[(2R，5S)-2,5-二甲基-4-[(噻-2-基)羰基]六氫吡畊 -1-基]己基]-4,4-二甲基-5-氧1代-2-硫氧味哇淀-1-基]-2-(二 氟甲基)-苯甲腈 4 620 680 4-[3-[6-[ττ 氮-4-[(p塞-2-基）談基]-ΙΗ-1,4-二氛呼-1-基]己 基]-4,4-二甲基-5-氧代-2-硫氧味。坐淀-1-基]-2-(二氣甲基)- 苯甲腈 4 606 681 4-[4,4-二甲基-5-氧代-3-[6-[4-[(吡啶-4-基)羰基]-六氫吡畊 基]己基]-2-硫氣味哇淀-1-基]-2-(二鼠甲基)-苯甲猜 4 587 682 4-[4,4-二甲基各[6-[4-(甲基磺醯基）六氫吡畊-1 -基]-己 基]-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 5 560 683 rel斗[3-[6-[(2R，5S)-2,5-二甲基冰（甲基磺醯基）六氫吡畊 小基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三 氟甲基)-苯甲腈 5 588 684 rel-4-[3-[6-[(2R，6S)-2,6-二甲基-4-(甲基磺醯基）六氫吡畊 小基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三 氟甲基)-苯甲腈 5 588 685 4-[3-[6-[六氫-4-(甲基磺醯基)-1Η-1，4-二氮呼-1-基]己 基]-4,4-二甲基-5-氧代-2-硫氧味吐症-1-基]-2-(二氣甲基)- 5 574The name is similar to ESI-MS 496 524 616 507 645 646 647 648 649 650 l [4: 4-dimethyl-3- [6_ [4- (methyl six well small base) hexamethane-2-thioxanthine -1-yl] _2- (trifluoromethyl) _benzyl_ i- [4,4-dimethyl · 3 · [6 · [4_ (1_ methylethyl) hexahydro < gl · 5 -Oxo_2 · thioximidazolium-1-yl] winter (trifluoromethyl V ^^ 4- [3- [6- [4- (2 · methoxybenzylidene)) Oximidazole small group] winter (trifluoromethyl) _benzonitrile 4- [6-〇 [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4 -Oxo-2 thioximido] hexyl] hexahydro p specific odor carbonitrile 1 [3 cases 4-ethynyl hexahydro * well small base] hexyl]. 4,4bis-2_thiooximidazole Pyridin-1-yl] _2_ (trifluoromethyl) -benzonitrile rel-4-[> [6-[(2R, 5S) -4-ethynyl-2,5-dimethyl-hexa ^ Hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] κtris (methyl) -benzonitrile_ 2nd generation 1-4-[3- [6- [(2 Posts) -4-Ethyl-2,6-dimethylhexyl M, 4-dimethyl-5-oxo-2-thiooximidazol-1-yl] _2_ (trimethyl) -Benzonitrile 10% 3 4 4 4 4 4 552 652 653 4- [4, Winter dimethyl_5_oxo_3 | [4 ♦ oxopropyl) · hexahydropyrrol-butyl] hexyl ] -2-thioxazomidazole-1- Group] -2— (trifluoromethyl) _benzonitrile 654 4- [4,4-dimethyl each [6- [4- (2-methyl small oxopropylhexyl] -5-oxo- 2-thiooximidazol-1-yl] -2- (trifluoromethane v acetochlorine rel-4- [3- [6-[(2R, 5S) -2,5 ·: methyl-4 -(2-methyl-1-oxopropyl) hydropyridin-1-yl] hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine] yl] -2- (Trifluoromethyl) -benzonitrile 4 580 655 4- [3- [6- [hexahydro-4- (2-methyl-1-oxopropyl ^ pyridyl] hexyl] -4,4 -Dimethyl-5-oxo-2-thioxanmidin-1-yl] -2- (trifluoromethyl) -benzonitrile 4 566 656 4- [3- [6- [4- (2-Cycloyl-2-methyl-1-oxopropyl) hexahydropyridine "· yl] hexyl] -4,4-dimethyl-5-oxo-2-thioxanthine. Seated bite Small group] _2- (trifluoromethyl) _ benzonitrile 4 568 657 4- [3- [6- [4- (2,2-dimethyl-1-oxopropyl) hexaphenyl group ] Hexyl] -4,4-dimethyl-5-oxo-2-thioxomiduridine-1-yl] _2- (trifluoromethyl) · benzonitrile ^ 4 566 658 rel-4- [3- [6-[(2R, 5S) -4- (2,2-dimethyl-1-oxopropyl) _2,5 · dimethyl 4 594 -124- (119) Example names are similar Example Synthesis of ESI-MS Hexahydropyridine] hexyl] -4,4-dimethyl-5-oxo-2-thiooxy Oxazidin-1-yl] -2- (trifluoromethyl) -benzonitrile 659 rel-4- [3- [6-[(2R, 6S) -4- (2,2-dimethyl-1 -Oxopropyl) -2,6-dimethylhexahydropyridine] hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine small group] -2- ( Trifluoromethyl) -benzonitrile 4 594 660 4- [4,4-dimethyl-5-oxo-3- [6- [4- (l-oxobutyl) hexahydropyridine ] Hexyl] -2-thioximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 4 552 661 4- [3- [6- [4- (cyclopropylcarbonyl) hexahydropyridine -1-yl] hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 550 662 rel- 4- [3- [6-[(2R, 5S) -4- (cyclopropylcarbonyl) -2,5-dimethylhexahydropyridine-1-yl] hexyl] -4,4-dimethyl -5-oxo-2-thiooxygen. Zyodo-1-yl] -2- (difluorofluorenyl) -benzonitrile 4 578 663 4- [3- [6- [4- (phosphinobutyl) ττ nitrogen p ratio 17 wells -1- Yl] hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 564 664 4- [3- [6- [4- (methoxyethoxyl) [kappa] ^-1-yl] hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 554 665 4- [3- [6- [4- (3-methoxy-1-oxopropyl) κ mouse p-specific-1-yl ] Hexyl] -4,4-dimethyl-5-oxo-2-thiooxy sigma sitting -1-yl] -2- (digas methyl) -benzonitrile 4 568 666 rel-4- [3- [6-[(2R, 5S) -4- (3-Toxy small oxopropyl) -2,5-dimethylhexahydropyridine-1-yl] hexyl] -4,4 -Dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzazine 4 596 667 4- [3- [6- [六 鼠- 4- (3-methoxy-1-oxopropyl) -111-1,4-dimurant-1-yl] hexyl] -4,4-dimethyl-5-oxo-2-sulfide Oxamido-1-yl] -2- (difluoromethyl) -benzonitrile 4 582 668 4- [3- [6- [4-[(2-methoxyethoxy) ethenyl) ] Hexylpyridine] hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine small] -2- (trifluoromethyl) -benzyl 4 598 669 4- [3- [6- [4-[(2- (2-methoxyethoxy) ethoxy) ethenyl] hexahydropyridine] hexyl] -4,4- Dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 642 670 4- [4,4-dimethyl-5-oxo 2-Sulfur-3--3- (6- [4- (Digas-Ethyl)), ττ, Nitrogen, 1-yl] hexyl] midotyl, and 2- (trifluoromethyl) -benzene Nitrile 4 578 671 rel_4_ [3- [6-[(2R, 5S) -2,5-dimethyl-4- (trifluoroacetamidyl) hexahydropyridine-1-yl] hexyl] -4, 4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 606 200301117 (120) Example name Similar to Example Synthesis ESI-MS 672 4- [4,4-dimethyl-5-oxo-3- [6- [4-[(thia-2-yl) ethenyl] hexahydropyridin-1-yl] hexyl] 2- Thioximidazole small group] -2- (trifluoromethyl) -benzonitrile 4 606 673 rel-4- [3_ [6-[(2R, 5S) -4-[(furanyl) carbonyl]]- 2,5-dimethylhexahydropyridine] hexyl M, 4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzene Nitrile 4 604 674 rel bucket [3- [6 _ [(2R, 5S) -4-[(isoninazol-5-yl) carbonyl] -2,5-dimethylhexahydropyridine Yl] hexyl] -4,4-dimethyl -5-lacto-2-thiooxy odor ° Satoshi-1 · yl] -2- (trifluoromethyl) -benzonitrile 4 605 675 4_ [3- [6- [4-[(furan-2 -Yl) carbonyl] hexahydropyridine] hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzene Nitrile 4 576 676 rel-4- [3- [6-[(2R, 5S) -4-[(furan-2-yl) carbonyl] -2,5 · dimethylhexahydropyridine · -1- Methyl] hexyl] -4,4-dimethyl-5-oxo-2-thiooxytamine junji-1_yl] -2- (trifluoromethyl) -benzonitrile 4 604 677 4- [3- [6- [4-[(Bran-2-yl) yl] r? Nitro-1H-1,4-diazyl-1-yl] hexyl] -4,4-dimethyl-5-oxy 2-thiothioimidazolidine small group] -2- (trifluoromethyl) -benzonitrile 4 590 678 4- [4,4-dimethyl-5-oxo-3- [6- [4 -[(Pyrim-2-yl) carbonyl] hexahydropyridine small group] hexyl] -2-thiooximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 4 592 679 reM- [3 -[6-[(2R, 5S) -2,5-dimethyl-4-[(thia-2-yl) carbonyl] hexahydropyridin-1-yl] hexyl] -4,4-dimethyl -5-oxo 1-generation-2-thioxanthrin-1-yl] -2- (difluoromethyl) -benzonitrile 4 620 680 4- [3- [6- [ττ nitrogen-4- [ (p-s-2-yl) yl] -l-l-l, 4-dilanol-1-yl] hexyl] -4,4-dimethyl-5-oxo-2-thiooxy. Zyodo-1-yl] -2- (digasmethyl) -benzonitrile 4 606 681 4- [4,4-dimethyl-5-oxo-3- [6- [4-[(pyridine -4-yl) carbonyl] -hexahydropyridinyl] hexyl] -2-sulfide odorate-1-yl] -2- (dimuryl) -benzyl 4 587 682 4- [4,4 -Dimethyl each [6- [4- (methylsulfonyl) hexahydropyridine-1 -yl] -hexyl] -5-oxo-2-thiooximidazolidine small group] -2- (tri Fluoromethyl) -benzonitrile 5 560 683 rel [3- [6-[(2R, 5S) -2,5-Dimethyl ice (methylsulfonyl) hexahydropyridine] hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 5 588 684 rel-4- [3- [6- [ (2R, 6S) -2,6-dimethyl-4- (methylsulfonyl) hexahydropyridine] hexyl] -4,4-dimethyl-5-oxo-2-thiooxy Imidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 5 588 685 4- [3- [6- [hexahydro-4- (methylsulfonamido) -1Η-1,4 -Diazetidin-1-yl] hexyl] -4,4-dimethyl-5-oxo-2-thiooxyemetic-1-yl] -2- (difluoromethyl)-5 574

-126- (121)-126- (121)

實例 名稱 類似於 實例合成 ESI-MS 苯甲腈 686 4-[3-[6-|>(乙基磺醯基）六氫吡畊-1-基]己基]-4,4-二甲基 _5_氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 5 574 687 rel-4-[3-[6-[(2R，5S)-4-(乙基磺醯基)-2,5-二甲基六氫吡畊 -1-基]己基]-4,4-二甲基-5-氧代-2-硫氧味哇淀-1-基]-2-(二 氟甲基)-苯甲腈 5 602 688 4-[4,4-二甲基-5-氧代-3-[6-[4-(丙基橫酿基)-7T鼠?比p井-1 _ 基]己基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 5 588 689 4-[4,4-二甲基-3-[6-[4-[(l-甲基乙基)-磺醯基]六氫吡畊小 基]己基]-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 5 588 690 4-〇[6-[4-[(2-甲氧基乙基）磺醯基]六氫吡畊-1-基]己 基]-4,4-二甲基-5-氧代-2-硫氧味咬淀-1-基]-2-(二氣甲基)_ 苯甲腈 5 604 691 4-[4,4-二甲基-5-氧代-3-[6-[4-(苯基磺醯基)-六氫吡畊-1-基]己基]-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 5 622 692 4-[3-[6-[4-[(4-氰基苯基)磺醯基]六氫吡畊-1-基]己基]-4,4-一甲基-5-氧代-2-硫氧味哇淀-1-基]-2-(二氣甲基)-本甲腊 5 647 693 4-[6-[3-[4-氣基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代-2- 硫氧咪唑啶小基]己基]乙基六氫吡畊小碳硫醯胺 12 569 694 ‘[6-[3-[4-氰基各(三氟甲基)苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶小基]己基]-N-丙基六氫吡畊小碳硫醯胺 12 583 695 4_[6-[3-[4-氣基-3-(二氟甲基)苯基]-5,5-二甲基-4-氧代-2- 硫氧味吨淀-1-基]己基]-N-(丙-2-缔基)-ττ氮p比p井-1-碳硫酿 胺 12 581 696 4-[6-[3-[4-氰基各(三氟甲基)苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-1-基]己基]六氫吡畊小碳硫酸S-甲酯 13 556 697 4-[6-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-1-基]己基]六氫-1H-1，4-二氮呼-1-碳硫酸S-甲 酯 13 570 698 4-[6-[3-[4-氰基-3-(三氟甲基)苯基]-5,5·二甲基-4-氧代-2-硫氧咪唑啶-1-基]己基]六氫吡畊-1-碳硫酸S-乙酯 13 570 (122)Example name is similar to Example Synthesis ESI-MS Benzonitrile 686 4- [3- [6- | > (Ethylsulfonyl) hexahydropyridine-1-yl] hexyl] -4,4-dimethyl _5_oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 5 574 687 rel-4- [3- [6-[(2R, 5S)- 4- (ethylsulfonyl) -2,5-dimethylhexahydropyridine-1-yl] hexyl] -4,4-dimethyl-5-oxo-2-thioxohydride- 1-yl] -2- (difluoromethyl) -benzonitrile 5 602 688 4- [4,4-dimethyl-5-oxo-3- [6- [4- (propyl transverse alcohol) ) -7T rat? Than p-1 -1 -yl] hexyl] -2-thioximidazolidine small group] -2- (trifluoromethyl) -benzonitrile 5 588 689 4- [4,4-dimethyl 3--3- [6- [4-[(l-methylethyl) -sulfofluorenyl] hexahydropyridine] hexyl] -5-oxo-2-thiooximidazolidine] -2 -(Trifluoromethyl) -benzonitrile 5 588 690 4-〇 [6- [4-[(2-methoxyethyl) sulfonyl] hexahydropyridine-1-yl] hexyl] -4 , 4-dimethyl-5-oxo-2-thiooxy odor bitate-1-yl] -2- (digasmethyl) _benzonitrile 5 604 691 4- [4,4-dimethyl -5-oxo-3- [6- [4- (phenylsulfonyl) -hexahydropyridine-1-yl] hexyl] -2-thiooximidazolidine small group] -2- (trifluoromethyl ) -Benzonitrile 5 622 692 4- [3- [6- [4-[(4-cyano ) Sulfofluorenyl] hexahydropyridin-1-yl] hexyl] -4,4-monomethyl-5-oxo-2-thioxotriol-1-yl] -2- (difluoromethyl (Methyl) -benzyl wax 5 647 693 4- [6- [3- [4-Gas-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2- Thioxazolyl small group] hexyl] ethylhexahydropyridine small carbothioamide 12 569 694 '[6- [3- [4-cyano (trifluoromethyl) phenyl] -5,5- Dimethyl-4-oxo-2-thiooximidazolidine small group] hexyl] -N-propylhexahydropyridine small carbothioamide 12 583 695 4_ [6- [3- [4-Gasyl- 3- (difluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thioxanthene-1-yl] hexyl] -N- (prop-2-enyl) -ττ nitrogen p ratio p-well-1 carbon-sulfur amine 12 581 696 4- [6- [3- [4-cyano (trifluoromethyl) phenyl] -5,5-dimethyl-4 -Oxo-2-thiooximidazol-1-yl] hexyl] hexahydropyridine S-methyl sulfate 13 556 697 4- [6- [3- [4-cyano-3- (trifluoro (Methyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] hexyl] hexahydro-1H-1,4-diazepine-1-carbon sulfuric acid S-methyl ester 13 570 698 4- [6- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5 · dimethyl-4-oxo-2-thiooxy Imidazol-1-yl] hexyl] hexahydropyridine-1-carbon sulfate S-ethyl 13570 (122)

表27.根據本發明通式I的化合物，其中V =三氟甲基苯甲腈 ，W =乙内驢硫月尿，η = 7 實例 名稱 類似於 實例合成 ESI-MS 699 4-[4,4-二甲基各[7-[4-(甲基六氫吡畊小基)庚基]-5-氧 代-2-硫氧味。坐淀-1-基]-2-(二氣甲基)-豕甲月青 3 510 700 4-[7-[3-[4-夜基-3-(二氟甲基)苯基]-5,5-二甲基-4·-氧代 •2_硫氧味吐淀-1-基]庚基]7Τ鼠说^7井-1-碳猜 4 521 701 4-[3-[7-[4-乙酿基鼠叶!^井-1-基]庚基]-4,4-二甲基-5-氧 代-2-硫氧咪唑啶-1-基]-2-(三氟甲基>苯甲腈 4 538 702 rel-4-[3-[7-[(2R，6S)-4-乙醯基-2,6-二甲基-六氫吡畊-1-基]庚基]-4,4-二甲基-5-氧代-2-硫氧味吐症-l-基]-2-(二 氟甲基)-苯甲腈 4 566 703 4-[3-[7-[4-(2-羥基-2-甲基-1-氧代丙基)六氫吡畊-1-基] 庚基]-4,4-二甲基-5-氧代-2-硫乳味吐淀-1-基]-2-(二氣 甲基)-苯甲腈 4 582 704 4-[3-[7-[4-(2,2-二甲基-1-氧代丙基)六氫吡畊小基]庚 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 4 580 705 rel-4-[3-[7-[(2R，6S)-4-(2,2-二甲基小氧代丙基)-2,6-二 曱基六氫吡畊小基]庚基]-4,4-二甲基-5-氧代-2-硫氧咪 峻淀-l-基]-2-(二氟甲基)-苯甲腊 4 608 706 4-[3-[7-[4-(甲氧基乙醯基)六氫吡畊小基]庚基]-4,4-二 甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 568 707 4-[4,4-二甲基-5-氧代-2-硫氧-3-[7-[4-(三氟乙醯基)六氫 吡畊小基]庚基]咪唑淀小基]-2-(三氟甲基)-苯甲腈 4 592 708 rel_4_[3-[7-[(2R，6S)-2,6-二甲基-4-(三氟乙醯基）六氫吡 p井-1-基]庚基]-4,4-二甲基-5-乳代-2-硫氧1味峻淀-1-基]-2-(三氟甲基)-苯甲腈 4 620 709 4-[4,4-二甲基-3-[7-[4-(甲基磺醯基)六氫吡畊-1-基]庚 基-5-乳代-2-硫氣味17坐淀-1-基]-2-(二氣甲基)-苯甲猜 5 574 710 rel-4-[3-[7-[(2R，6S)-2,6-二甲基磺醯基]六氫吡畊-1-基] 庚基]-4,4-二〒基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟 甲基)-苯甲腈 5 602 711 4-[3-[7-[4-[(2-甲氧基乙基)磺醯基]六氫吡畊小基]庚 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲 基)-苯甲猜 5 618 200301117 (123) 誦 表28.根據本發明通式I的化合物，其中V=三氟甲基苯甲 腈，W =乙内酿硫脲，η = 8 實例 名稱 類似於 實例合成 ESI-MS 712 4-[8-[3-[4-氰基-3-(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧咪唑啶-1-基]辛基]六氫吡畊小碳腈 4 535 713 rel-4-|>[8-[(2R，6S)-4-乙醯基-2,6-二甲基六氫吡畊-1-基]辛基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三 氟甲基)-苯甲腈 4 580 714 4-[4,4-二曱基-3-[8-[4-(2-甲基小氧代丙基)-六氫吡畊 小基]辛基]-5-氧代-2-硫氧咪唑啶-1-基]_2_(三氟甲基)-苯甲腈 4 580 715 4-[3-[8-[4-(2-羥基-2-甲基-1-氧代丙基)-六氫吡畊-1-基] 辛基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟 甲基)-苯甲腈 4 596 716 rel 冰[3-[8-[(2R，6S)-4-(2,2-二甲基小氧代丙基)-2,6-二 甲基六氫吡畊-1-基]辛基]-4,4-二甲基-5-氧代-2-硫氧咪 唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 622 717 4-〇[8-[4-(環丙基羰基)六氫吡畊-1-基]辛基]-4,4-二甲 基-5-氧代-2-硫氧咪唑啶小基]-2-(三氟甲基)-苯甲腈 4 578 718 4-[H8-[4-(環丁基羰基)六氫吡畊-1-基]辛基]_4,4-二甲 基-5-氧代-2-硫氧味^7坐淀-1-基]-2-(二氣甲基)-本甲赌 4 592 719 4-[3-[8-[4-(甲氧基乙醯基)六氫吡畊小基]辛基]-4,4-二 甲基-5-氧代-2-硫氧咪唑淀-1-基]-2-(三氟甲基)-苯甲腈 4 582 720 4-[4,4-二甲基-5-氧代-2-硫氧-3-[8-[4-(三氟乙醯基)六氫 吡畊-1-基]辛基]咪唑啶-1-基]-2-(三氟甲基)-苯甲腈 4 606 721 4-[4,4-二甲基-5-氧代-3-[8-[4-[(噻-2-基)羰基]-六氫吡畊 小基]辛基]-2-硫氧咪唑啶-1-基]-2-(三氟T基)_苯甲腈 4 620 722 4-[4,4-二甲基-5-氧代-3-[8-[4-[(p比嗅-4-基)談基]-7T氣口比 畊小基]辛基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基)-苯甲 腈 4 615 723 4-[4,4-二甲基各[8-[4-(甲基磺醯基)六氫吡畊-1-基]-辛 基-5-氧代-2-硫氧味。坐淀-1-基]-2-(二氣甲基)-苯甲赌 5 588 724 4-[4,4-二甲基-5-氧代-3-[8-[4-[(丙基磺醯基)-六氫吡畊 -1-基]辛基]-2-硫氧味吐淀-1-基]-2-(二氣甲基)-苯甲赌 5 616 725 4-[4,4-二甲基-3-[8-[4-[(l-甲基乙基)-磺醯基]六氫吡畊 基]-辛基-5-氧代-2·硫氧味峻淀-1-基]-2-(二氣甲基)- 5 616Table 27. Compounds of general formula I according to the present invention, where V = trifluoromethylbenzonitrile, W = acetothioneuria, η = 7 Example names are similar to the examples ESI-MS 699 4- [4, 4-dimethyl each [7- [4- (methylhexahydropyridyl) heptyl] -5-oxo-2-thiooxy odor. Zyodo-1-yl] -2- (difluoromethyl) -pyridazine 3 510 700 4- [7- [3- [4-Ethyl-3- (difluoromethyl) phenyl]- 5,5-Dimethyl-4 · -oxo • 2_thiooxytitrine-1-yl] heptyl] 7T rat said ^ 7 well-1-carbon guess 4 521 701 4- [3- [7 -[4-Acetyl-rat-leaf! ^ I-1-yl] heptyl] -4,4-dimethyl-5-oxo-2-thioximidazol-1-yl] -2- (tri Fluoromethyl > benzonitrile 4 538 702 rel-4- [3- [7-[(2R, 6S) -4-ethylfluorenyl-2,6-dimethyl-hexahydropyridine-1-yl ] Heptyl] -4,4-dimethyl-5-oxo-2-thiooxycarbazone-l-yl] -2- (difluoromethyl) -benzonitrile 4 566 703 4- [3 -[7- [4- (2-hydroxy-2-methyl-1-oxopropyl) hexahydropyrine-1-yl] heptyl] -4,4-dimethyl-5-oxo- 2-Sulfur milky flavonoid-1-yl] -2- (digasmethyl) -benzonitrile 4 582 704 4- [3- [7- [4- (2,2-dimethyl-1- (Oxopropyl) hexahydropyridine] heptyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl)- Benzonitrile 4 580 705 rel-4- [3- [7-[(2R, 6S) -4- (2,2-dimethyl small oxopropyl) -2,6-difluorenylhexahydropyridine Gengxiaoji] heptyl] -4,4-dimethyl-5-oxo-2-thioxoamido-l-yl] -2- (difluoromethyl) -benzyl 4 608 706 4 -[3- [7- [4- (Methoxyethenyl) hexahydropyridyl] heptyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl ) -Benzonitrile 4 568 707 4- [4,4-dimethyl-5-oxo-2-thiooxy-3- [7- [4- (trifluoroacetamidyl) hexahydropyridine Yl] heptyl] imidazolium small group] -2- (trifluoromethyl) -benzonitrile 4 592 708 rel_4_ [3- [7-[(2R, 6S) -2,6-dimethyl-4- (Trifluoroethenyl) hexahydropyridyl-1-yl] heptyl] -4,4-dimethyl-5-lacto-2-thiooxy 1 Weijundian-1-yl] -2- (Trifluoromethyl) -benzonitrile 4 620 709 4- [4,4-dimethyl-3- [7- [4- (methylsulfonyl) hexahydropyridin-1-yl] heptyl -5-lacto-2-sulfur odor 17-sedition-1-yl] -2- (difluoromethyl) -benzyl 5 574 710 rel-4- [3- [7-[(2R, 6S) -2,6-dimethylsulfanyl] hexahydropyridin-1-yl] heptyl] -4,4-difluorenyl-5-oxo-2-thiooximidazol-1-yl]- 2- (trifluoromethyl) -benzonitrile 5 602 711 4- [3- [7- [4-[(2-methoxyethyl) sulfonyl] hexahydropyridine] heptyl] -4,4-Dimethyl-5-oxo-2-thioximidazolidine small group] -2- (trifluoromethyl) -benzyl 5 618 200301117 (123) Rec. 28. According to the present invention Compound of formula I, where V = trifluoromethylbenzonitrile W = Ethyl thiourea, η = 8 Example name is similar to Example Synthesis ESI-MS 712 4- [8- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5 -Dimethyl-4-oxo-2-thiooximidazol-1-yl] octyl] hexahydropyridine small carbonitrile 4 535 713 rel-4- | > [8-[(2R, 6S) -4-Ethyl-2,6-dimethylhexahydropyrimidin-1-yl] octyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl ] -2- (trifluoromethyl) -benzonitrile 4 580 714 4- [4,4-Difluorenyl-3- [8- [4- (2-methyl small oxopropyl) -hexahydro Pycnogenol] octyl] -5-oxo-2-thiooximidazol-1-yl] _2_ (trifluoromethyl) -benzonitrile 4 580 715 4- [3- [8- [4- (2-Hydroxy-2-methyl-1-oxopropyl) -hexahydropyridin-1-yl] octyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine -1-yl] -2- (trifluoromethyl) -benzonitrile 4 596 716 rel ice [3- [8-[(2R, 6S) -4- (2,2-dimethyl small oxopropane Yl) -2,6-dimethylhexahydropyridin-1-yl] octyl] -4,4-dimethyl-5-oxo-2-thioximidazol-1-yl] -2- (Trifluoromethyl) -benzonitrile 4 622 717 4-〇 [8- [4- (Cyclopropylcarbonyl) hexahydropyrine-1-yl] octyl] -4,4-dimethyl-5 -Oxo-2-thiooxyimidazolidine small group] -2- (trifluoromethyl) -benzyl 4 578 718 4- [H8- [4- (Cyclobutylcarbonyl) hexahydropyridin-1-yl] octyl] _4,4-dimethyl-5-oxo-2-thiooxy Yodo-1-yl] -2- (difluoromethyl) -benzyl 4 592 719 4- [3- [8- [4- (methoxyethenyl) hexahydropyridyl]] octyl ] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) -benzonitrile 4 582 720 4- [4,4-di Methyl-5-oxo-2-thiooxy-3- [8- [4- (trifluoroacetamidyl) hexahydropyridin-1-yl] octyl] imidazol-1-yl] -2- (Trifluoromethyl) -benzonitrile 4 606 721 4- [4,4-dimethyl-5-oxo-3- [8- [4-[(thia-2-yl) carbonyl] -hexahydro Pycnogenol] octyl] -2-thiooximidazol-1-yl] -2- (trifluoroTyl) _benzonitrile 4 620 722 4- [4,4-dimethyl-5-oxo Generation-3- [8- [4-[(p 比 ol-4-yl) Hanyl] -7T gas port than small small base] octyl] -2-thiooximidazol-1-yl] -2- ( Trifluoromethyl) -benzonitrile 4 615 723 4- [4,4-dimethyl each [8- [4- (methylsulfonyl) hexahydropyridin-1-yl] -octyl-5 -Oxo-2-thiooxygen odor. Zyodo-1-yl] -2- (difluoromethyl) -benzoate 5 588 724 4- [4,4-dimethyl-5-oxo-3- [8- [4-[(propyl Sulfosulfenyl) -hexahydropyridine-1-yl] octyl] -2-thioxotriol-1-yl] -2- (difluoromethyl) -benzyl 5 616 725 4- [ 4,4-dimethyl-3- [8- [4-[(l-methylethyl) -sulfofluorenyl] hexahydropyridyl] -octyl-5-oxo-2 · thiooxygen Junyudo-1-yl] -2- (digasmethyl)-5 616

-129- 20030111?-129- 20030111?

(124) 實例 名稱 類似於 實例合成 ESI-MS 苯甲腈 726 4-[3-[8-[4-[(2-甲氧基乙基)磺醯基]六氫吡畊-1-基]辛 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 5 632 727 4-[3-[8-[4-[(4-氰基苯基）磺醯基]六氫吡畊小基]辛 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基)-苯甲腈 5 675 728 4-[8-[3-[4-氰基-3-(三氟甲基)1苯基]-5,5-二甲基-4-氧代 -2-硫氧味。坐淀-1-基]辛基]-N-乙基7T氮p比硫酿 胺 12 597 729 4-[8-[3-[4-篆基-3-(二氟甲基)1苯基]-5,5-二甲基-4-氧代 -2-硫氧味嗤違-1-基]辛基]-N-(丙-2-基)-：?τ鼠?比^井-1-竣 硫醯胺 12 609 730 4-[8-[3-[4-氰基各(三氟甲基)苯基]-5,5-二甲基-4-氧代 -2-硫氧咪唑啶小基]辛基]六氫吡畊-1-碳硫酸S-甲酯 13 584 731 4-[8-[3-[4-氰基各(三氟甲基)苯基]-5,5-二甲基冰氧代 -2-硫氧咪唑啶小基]辛基]六氫吡畊小磺醯胺Ν，Ν-二甲 酯 14 617(124) Example name similar to Example Synthesis ESI-MS Benzonitrile 726 4- [3- [8- [4-[(2-methoxyethyl) sulfonamido] hexahydropyridine-1-yl] Octyl] -4,4-dimethyl-5-oxo-2-thioximidazolidine-1-yl] -2- (trifluoromethyl) -benzonitrile 5 632 727 4- [3- [ 8- [4-[(4-cyanophenyl) sulfonamido] hexahydropyridine] octyl] -4,4-dimethyl-5-oxo-2-thioximidazolidine-1 -Yl] -2- (trifluoromethyl) -benzonitrile 5 675 728 4- [8- [3- [4-cyano-3- (trifluoromethyl) 1phenyl] -5,5- Dimethyl-4-oxo-2-thiooxy odor. Zyodo-1-yl] octyl] -N-ethyl7T nitrogen p ratio sulfame 12 597 729 4- [8- [3- [4-fluorenyl-3- (difluoromethyl) 1phenyl ] -5,5-Dimethyl-4-oxo-2-thiooxo miso-1-1-yl] octyl] -N- (prop-2-yl)-: 1-Junthionamine 12 609 730 4- [8- [3- [4-cyano (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooxy Imidazolidine small] octyl] hexahydropyridine-1-carbon sulfate S-methyl 13 584 731 4- [8- [3- [4-cyano ((trifluoromethyl) phenyl) -5], 5-Dimethylglaxo-2-thioximidazolidine small group] octyl] hexahydropyridoxamine N, N-dimethyl ester 14 617

-130- 200301117-130- 200301117

表2 9 .根據本發明通式I的化合物，其中V=異苯并呋喃酮Table 2 9. Compounds of general formula I according to the invention, wherein V = isobenzofuranone

，W =乙内酿硫月尿，η = 3 實例 名稱 類似於 實例合成 ESI-MS 732 3-(1，3-二氫-1-氧代異苯并咬喃-5-基)-5,5-二甲基 -1-[3-[4-[(噻-2-基)羰基]六氫吡畊-1-基]丙基]-2-硫氧咪 α坐淀-4-酮 15⑷ 513 733 3-(1,3-二氮-1-氧代異苯并咬喃-5-基)-1-[3-[4-[4-(二甲 基胺基)苯甲醯基]六氫吡畊-1-基]丙基]-5,5-二甲基-2-石瓦氧味峻淀-4-酉同 15⑷ 550 734 Ν-[(4-氯苯基)甲基]-4-[3-[3-(1，3-二氫-1-氧代-異苯并呋 喃-5-基)-5,5-二甲基硫氧-味u坐淀-1-基]丙基] 六氫吡畊-1-碳硫醯胺 15(12) 586 735 4-[3-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧味峻淀-1-基]丙基]氮ρ比p井-1-旋硫feS-乙酯 15(13) 491 736 4-[3-[3-(1，3-二氯-l-乳代異苯并咬喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶-1-基]丙基]-N，N-二乙基六氫吡 畊-1-羧酸醯胺 15(14) 502, W = stilbene thiourea, η = 3 Example name is similar to Example Synthesis ESI-MS 732 3- (1,3-dihydro-1-oxoisobenzoan-5-yl) -5, 5-Dimethyl-1- [3- [4-[(thia-2-yl) carbonyl] hexahydropyridin-1-yl] propyl] -2-thioxoamyl α-zo-4-one 15 513 733 3- (1,3-Diaza-1-oxoisobenzoyl-5-yl) -1- [3- [4- [4- (dimethylamino) benzyl) Hexahydropyridin-1-yl] propyl] -5,5-dimethyl-2-shiwa oxojundo-4-pyrene 15⑷ 550 734 N-[(4-chlorophenyl) methyl] -4- [3- [3- (1,3-dihydro-1-oxo-isobenzofuran-5-yl) -5,5-dimethylthiooxy-tamizo-1-yl ] Propyl] hexahydropyridine-1-carboxamidine 15 (12) 586 735 4- [3- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-Dimethyl-4-oxo-2-thiooxytidamine-1-yl] propyl] nitrogen ρ ratio p-well-1-Sulphone-feS-ethyl ester 15 (13) 491 736 4 -[3- [3- (1,3-Dichloro-l-lactoisobenzoyl-5-yl) -5,5-dimethyl-4-oxo-2-thioximidazolidine- 1-yl] propyl] -N, N-diethylhexahydropyrine-1-carboxamide 15 (14) 502

-131 - 200301117 (126) 表3 0.根據本發明通式I的化合物，其中v=異苯并呋喃酮 ，W=乙内酿硫月尿，n=4 實例 名稱 類似於 實例合成 ESI-MS 737 3-(1，3-二氫-1-氧代異苯并呋喃_5_基)-5,5-二甲基 小[4-[4-[〇塞_2_基)羰基]六氫吡畊小基]丁基]_2_硫氧· 味峻淀-4-酉同 ： 4 527 738 3-(1，3-二氫-1-氧代異苯并吱喃i基)小[4_[444_(2β甲氧 基苯Τ醯基)六氫吡畊小基]丁基]·5,5_二Τ基冬硫氧味 唑啶-4-酮 I 4 551 739 3-(1，3-一氫-1-氧代異秦并咬喃-5»基)-1-[4-[4-[4-(二甲 基胺基)苯甲醯基]六氫吡呼-1-基]丁基]_5,5_二甲基1 硫氧咪吐淀-4-酉同 —---- 4 —-—_ 564 • 740 1-[4·[4-[(2，1，3-苯并噻二唑-4-基)磺醯基]-六氫吡啡+ 基]丁基]-3_(1，3-二氫-1-氧代異苯并味喃-基)·5,5-二 甲基-2-硫氧咪嗤淀-4-g同_ -~~^ 5 ----— 615 741 N-(2,6-二氯咐淀冰基)·4·[4·[3·(1，3_二氫-1.氧代·異苯_ 并嗅喃-5-基)-5,5-二甲基-4-氧代-2-硫氧-咪唑淀基] 丁基]六氫吡哜-1-羧酸醯胺____ ' ~~ 6 742丨 Φ*[^·[3·(1，3-二氫-1-氧代異苯并吱喃-5-基)_5,5_二甲基· 冰氧代硫氧咪唑淀小基]丁基]六氫吡畊+碳硫酸s· 甲酯 ------—--— 13 ---- 491 743 ‘ 氧代異苯并呋喃:二甲基、 本氧代-2-硫氧咪唑淀小基]丁基]六氫,比啡+碳硫酸孓 乙酯 ---~-----L —---- 13 —---_ ^505^ ------ • -132- (127) 表3 1 ·根據本發明通式！的化合物，其中v =異苯并呋喃酮 ，W=乙内酿硫月尿，η 實例 名稱 類似於 實例合成 ESI-MS 744 3-(1，3- 一氫小氧代異苯并峡喃j·基)j，5_二甲基 二1 γ[4-(2-甲基-1-氧代丙基)六氫ι基]戊硫 氧咪唑啶-4-酮 4 501 745 3-(1，3- 一成小氧代異冬并咬喃-5-基)-5,5-二甲基 -1-[5_[4-[〇塞冬基)乙醯基]六氫吡,井+基]戊基]么疏氧 -咪唑啶-4-酮 4 555 746 3-(1,3- 一氫-1-氧代異苯并呋喃基)·5,5_二甲基 -1-[5-[4-[〇塞-2_基)羰基]六氫吡畊·r基]戊基於硫氧-咪唑啶-4-酮 4 541 747 3-(1，3-二氫-1-氧代異苯并 小!>!>乙基-橫醯基]六氫♦井小基]戊基]_5,5_二甲基 -2-硫氧-咪唑啶-4-酮 5 523 —748 ---- 4-[[4-^-[3-(1，3-二氫-1-氧代異苯并呋喃·5_基^5,5-二甲 基冰氧代_2_硫氧咪唑啶-1-基]戊基]六氫吡畊]•基]磺 醯基]苯甲腈 ' 5 596 749 L--- 4-[5-[3-(1，3-二氫-1-氧代異苯并呋喃_5_基)-5>二甲基 冬氧代-2_硫氧咪唑啶-1-基]戊基]六氫吡畊-μ碳硫酸孓 乙酯 13 519 -133- (128) 表32·根據本發明通式〗的化合物，其中異苯并呋喃酮 乙内酿硫職，η 實例 名稱 類似於 實例合成 ESI-MS 750 3-(1，3· 一氫-1-氧代異苯并呋喃：基)小[6-[木(2·甲氧基 苯甲醯基)六氫吡，1-基]己基]_5,5_二甲基1硫氧咪嗤 淀-4-酉同 .'成 579 751 3-(1，3-一氫-1-氧代異苯并吱喃-5-基)-1-[6-[4-[4-(二甲 基胺基)私甲驗基]7T氫p比p井-1-基]己基]_5,5_二甲基-2-石克氧咪。坐淀-4-酉同 4 592 752 3-[[4^6-[3-(1，3-^氫-1-氧代異苯并呋喃-5_基)_5,5_二甲 基4-氧代-2-硫氧咪吱竞^；^基]己基]六氫?比味_1_基]幾 基]苯甲腈 4 574 753 乙醯基八氫峨呼]_基)己基]各(1，3-二氯小氧代 異苯并呋喃-5-基)-5,5-二甲基-2-硫氧咪唑啶-4-酮 4 487 754 3-(1，3-二~·1-氧代異苯并呋喃各基)-5,5-二甲基 -Η6·[4-(1-氧代丙基)六氫吡呼小基]己基峰硫氧咪唆 淀-4-酉同 4 501 755 3-(1，3-二氫小氧代異苯并呋喃基)-5,5_二甲基 -Η6-|>(2-甲基-1-氧代丙基)六氫吡畊+基]己基]硫 氧咪唑啶-4-酮 4 515 756 3-(1，3-二氫-1-氧代吳苯并呋喃基)_5,5_二甲基 -1-[6-[4·(1-氧代丁基)六氫吡呼小基]己基•硫氧-味 唑啶-4-酮 4 515 757 1 [6 〇(環丙基羰基)7Τ氫吡畊基]己基]各(U-二氫 -1-氧代異苯并吱喃_5_基>5,5_二甲基1硫氧咪唑啶斗 酮 4 513 758 1 [^[4;(琢j基鉸基)六氫咐呼小基]己基奸⑻二氫 -1-氧代異苯并呋喃基>5,5_二甲基_2•硫氧·味唑啶_4一 酮 4 527 759 3-(1，3-二氫-1-氧代異苯并呋喃-5_基)_5,5·二甲基 -1-[6-[4-[(咐哫_4_基)羰基]六氳吡畊小基]己基]_2•硫氧 咪口全啶-4-酉同 4 550 760 : 3-(1,3-二氫-1-氧代異笨并呋喃_5_基)-5,5•二甲基 小[6_[4-[(备2_基)羰基]六氩吡畊小基]己基]冬硫氧咪 吐咬-4-g同 4 555 761 : 氫小氧代異笨并呋喃-5-其VS S--甲某 4 569 -------工 y ’____ > 134- (129)200301117-131-200301117 (126) Table 3 0. Compounds of general formula I according to the present invention, where v = isobenzofuranone, W = dithiourea, and n = 4 Example names are similar to the example synthetic ESI-MS 737 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl small [4- [4- [〇 塞 _2_yl) carbonyl] hexa Hydropyridine small group] butyl] _2_thiooxy · Weijun Lake-4- 酉 Identical: 4 527 738 3- (1,3-dihydro-1-oxoisobenzofuranyl) small [ 4_ [444_ (2βmethoxyphenytyl) hexahydropyridine] butyl] · 5,5_diTyltoxythiazolidine-4-one I 4 551 739 3- (1, 3-monohydro-1-oxoisocyanato-5 »yl) -1- [4- [4- [4- [4- (dimethylamino) benzylidene] hexahydropyridine-1- Propyl] butyl] _5,5_dimethyl1 thioxotoluate-4-pyridine —---- 4 —-—_ 564 • 740 1- [4 · [4-[(2,1, 3-benzothiadiazol-4-yl) sulfofluorenyl] -hexahydropyridine + yl] butyl] -3_ (1,3-dihydro-1-oxoisobenzosulfan-yl) · 5,5-Dimethyl-2-thioxanthemidate-4-g Same as _-~~ ^ 5 ----- 615 741 N- (2,6-dichloro command lake ice base) · 4 · [4 · [3 · (1,3_dihydro-1.oxo · isophenyl_acene-5-yl) -5,5-dimethyl-4-oxo-2-thiooxy- Imidazolyl] butyl] hexahydropyridine-1-carboxylic acid hydrazine ____ '~~ 6 742 丨 Φ * [^ · [3 · (1,3-dihydro-1-oxoisobenzoic acid) (An-5-yl group) _5,5_dimethyl · icercylthiooximidazolide small group] butyl] hexahydropyridine + carbon sulfate s · methyl ester ---------- 13- --- 491 743 'Oxo-isobenzofuran: dimethyl, oxo-2-thiooximidazolide small group] butyl] hexahydro, birphine + ethyl carbosulfate --- ~- --- L —---- 13 —---_ ^ 505 ^ ------ • -132- (127) Table 3 1 · According to the general formula of the present invention! Compound, where v = isobenzofuranone, W = thiourea urinate, η Example name is similar to Example Synthesis ESI-MS 744 3- (1,3-monohydro small oxoisobenzoxan j · Yl) j, 5_dimethylbis 1 γ [4- (2-methyl-1-oxopropyl) hexahydrol] pentylthioimidazol-4-one 4 501 745 3- (1 , 3- Yicheng small oxoisochrysene and sulfan-5-yl) -5,5-dimethyl-1- [5_ [4- [〇 sedonyl] ethenyl] hexahydropyridine, well + Yl] pentyl] morphoxo-imidazolidin-4-one 4 555 746 3- (1,3-monohydro-1-oxoisobenzofuryl) · 5,5_dimethyl-1- [ 5- [4- [〇Se-2_yl) carbonyl] hexahydropyridine · r-yl] pentylthio-imidazolidine-4-one 4 541 747 3- (1,3-dihydro-1-oxyl Substituted isobenzophenone! ≫! ≫ Ethyl-pyridyl] hexahydroxylyl] pentyl] _5,5_dimethyl-2-thiooxy-imidazol-4-one 5 523 — 748 ---- 4-[[4-^-[3- (1,3-Dihydro-1-oxoisobenzofuran · 5_yl ^ 5,5-dimethylglacial oxo_2_ Thioxazolyl-1-yl] pentyl] hexahydropyridine] • yl] sulfofluorenyl] benzonitrile '5 596 749 L --- 4- [5- [3- (1,3-dihydro -1-oxoisobenzofuran_5-yl) -5 > dimethyl ortho-oxo-2_thiooximidazol-1-yl] [Hydroxy] Hydroxypyridine-μCarbonium Ethyl Ethyl Sulfate 13 519 -133- (128) Table 32. Compounds according to the general formula of the present invention, in which isobenzofuranone ethyl is internally sulfurated, η Example names are similar Example Synthesis of ESI-MS 750 3- (1,3 · monohydro-1-oxoisobenzofuran: yl) small [6- [Wood (2 · methoxybenzyl) hexahydropyridine, 1- Group] hexyl] _5,5_dimethyl-1thioxanthemidazol-4--4-same. '579 751 3- (1,3-monohydro-1-oxoisobenzofuran-5-yl ) -1- [6- [4- [4- (dimethylamino) methynyl] 7T hydrogen p ratio p well-1-yl] hexyl] _5,5_dimethyl-2-stone g Imidamidine. Sitaka-4- 酉 Ident. 4 592 752 3-[[4 ^ 6- [3- (1,3- ^ hydro-1-oxoisobenzofuran-5_yl) _5,5_ di Methyl 4-oxo-2-thiooxyimidamine; ^ yl] hexyl] hexahydro? Bisex_1_yl] kisyl] benzonitrile 4 574 753 ethenyl octahydroehu] ) Hexyl] each (1,3-dichloro small oxoisobenzofuran-5-yl) -5,5-dimethyl-2-thioximidazolidine-4-one 4 487 754 3- (1, 3-Di ~ · 1-oxoisobenzofuran) -5,5-dimethyl-fluorene6 · [4- (1-oxopropyl) hexahydropyridyl] Hexyl peak唆 定 -4- 酉 同 4 501 755 3- (1,3-dihydro small (Oxo-isobenzofuranyl) -5,5_dimethyl-fluorene6- | > (2-methyl-1-oxopropyl) hexahydropyridine + yl] hexyl] thioximidazolidine-4 -Ketone 4 515 756 3- (1,3-dihydro-1-oxowubenzofuranyl) _5,5_dimethyl-1- [6- [4 · (1-oxobutyl) hexa Hydropyridine] Hexylthiothio-azamidin-4-one 4 515 757 1 [6 0 (cyclopropylcarbonyl) 7T hydropyridyl] hexyl] each (U-dihydro-1-oxo Isobenzoic acid_5_yl > 5,5_dimethyl1thioximidazolone 4 513 758 1 [^ [4; Perylene dihydro-1-oxoisobenzofuranyl> 5,5_dimethyl_2 • thiooxy · weizolidine_4 monoone 4 527 759 3- (1,3-dihydro-1- Oxo-isobenzofuran-5_yl) _5,5 · dimethyl-1- [6- [4-[(commanded_4_yl) carbonyl] hexamethylpyridine] hexyl] _2 • sulfur Oxamidin-4-pyridine with 4 550 760: 3- (1,3-dihydro-1-oxoisobenzofuran_5_yl) -5,5 • dimethyl small [6_ [4 -[(Prepared 2_yl) carbonyl] hexahydropyridine small group] hexyl] sulfoximide tetra-4-g with 4 555 761: small hydrogen oxo-isobenzofuran-5-its VS S-- A certain 4 569 ------- Worker '____ > 134- (129) 200301117

小〇〇[〇塞基)乙醯基]六氫t井+基]己基]_2_硫 -咪唑啶-4-酮_ 3-(1，3-二氫·1·氧代異苯 喃 _5_ 基 -1-[6·[4-(甲基磺醯基)六氫吡畊小基]己基]_2·硫氧^ 唑啶-4-酮_ 3_(1，3-一氫·ι·氧代異苯并Ρ夫喃冬基(乙 基)六氫t井小基]己基]_5,5-二甲基-2-硫氧_咪唑淀、^ 嗣 764 3-(1>二氫-1-氧代異苯并呋喃基)_5,5-二甲基 小[6-[4-(丙基磺醯基)六氫吡畊小基]己基]_2·硫氧，味 σ坐淀-4-酉同 551 765 766 3- (1，3-二氫小氧代異苯并呋喃冬基)-5,5•二甲基小[6-[4_(苯基磺醯基)六氫吡畊-1-基]己基]-2-石克氧-咪 峻咬>4-酉同 4- [[4-[6-[3-(1，3-二氫-1-氧代異苯并咬喃j基)_5,5-二甲 基冰氧代硫氧咪吐淀小基]己基]六氫ρ比呼]_基]石_ 醯基]苯甲腈 、 585 610 767 1-[6-[4-[(2，1，3-苯并噻二唑冰基)磺醯基六氫吡畊·卜 基]己基]各(1，3-二氫-1-氧代異苯并呋喃基)-5> 甲基-2-硫氧咪峻淀-4-酮 643 768 4-[6二[3-(1，3-二氫小氧代異苯并呋喃-5_基>5,5-二甲基 _4_氧代硫氧咪唑啶小基]己基]善[3_(甲基硫烷基) 苯基]六氫说畊-l-叛酸醯胺 610 769 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃士基>5,5_二甲基 氧代I硫氧咪唑咬小基]己基]-Ν·(3-氟苯基)六氫吡 畊-1-羧酸醯胺 582 770 4-[6-[3-(1，3-二氫-1-氧代異苯并吱喃_5_基)-5,5-二甲基 4_氧代冬硫氧咪唑啶小基]己基]善(4-氟苯基)六氫吡 畊-1-羧酸醯胺 6 582 771 4-[6-[3-(1，3-二氫-1-氧代異苯并咬喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶-1-基]己基]-Ν-乙基-六氫吡畊小 碳硫驢胺 12 532 772 4-[6-[3-(1，3-二氫小氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧味哇淀-1-基]己基]-Ν-丙基-六氮ρ比呼小 碳硫醯胺 12 546 773 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 12 544 -135 - 200301117〇〇〇 [〇〇 基] ethylenyl] hexahydrot well + yl] hexyl] _2_thio-imidazolidin-4-one_ 3- (1,3-dihydro · 1 · oxoisobenzoan_ 5_yl-1- [6 · [4- (methylsulfonyl) hexahydropyridyl] hexyl] _2 · thiooxy ^ oxazol-4-one_ 3_ (1,3-monohydro · ι · Oxo-isobenzopyranoyl (ethyl) hexahydrot-well small group] hexyl] _5,5-dimethyl-2-thiooxy_imidazolium, ^ 嗣 764 3- (1 > dihydro- 1-oxoisobenzofuranyl) _5,5-dimethyl small [6- [4- (propylsulfonyl) hexahydropyridine] hexyl] _2 · thiooxy, taste σ sitting lake- 4-pyridoxine 551 765 766 3- (1,3-dihydro small oxoisobenzofuranyl) -5,5 • dimethyl small [6- [4_ (phenylsulfonyl) hexahydropyridine Geng-1-yl] hexyl] -2-stone grams of oxygen-Mijun bite> 4- 酉 and 4-[[4- [6- [3- (1,3-dihydro-1-oxoisobenzene And sulfanyl group) _5,5-Dimethyl ice oxothioxanthine small base] hexyl] hexahydroρ bihu] _yl] stone_fluorenyl] benzonitrile, 585 610 767 1- [ 6- [4-[(2,1,3-benzothiadiazolebenzyl) sulfofluorenylhexahydropyridine · butyl] hexyl] each (1,3-dihydro-1-oxoisobenzo Furanyl) -5 > Methyl-2-thioxanmidol-4-one 643 768 4- [6-Di [3- (1,3-dihydro small Isobenzofuran-5-yl> 5,5-dimethyl-4_oxothiooximidazolidine small group] hexyl] Zan [3_ (methylsulfanyl) phenyl] Hexahydro- L-ammonium amide 610 769 4- [6- [3- (1,3-dihydro-1-oxoisobenzofuranyl) > 5,5_dimethyloxo I thiooximidazole bite Small group] hexyl] -N · (3-fluorophenyl) hexahydropyrine-1-carboxamide 582 770 4- [6- [3- (1,3-dihydro-1-oxoisobenzene Succinyl_5_yl) -5,5-dimethyl4_oxotothioximidazolidine small group] hexyl] xan (4-fluorophenyl) hexahydropyridine-1-carboxylic acid amine 6 582 771 4- [6- [3- (1,3-Dihydro-1-oxoisobenzoan-5-yl) -5,5-dimethyl-4-oxo-2-thiooxy Imidazol-1-yl] hexyl] -N-ethyl-hexahydropyridine small carbon thiosutanamine 12 532 772 4- [6- [3- (1,3-dihydro small oxoisobenzofuran- 5-yl) -5,5-dimethyl-4-oxo-2-thioxanthrin-1-yl] hexyl] -N-propyl-hexaaza-rhobiathiocarbamidine 12 546 773 4- [6- [3- (1,3-Dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl 12 544 -135-200301117

(130) 實例 名稱 類似於 實例合成 ESI-MS -4-氧代-2-硫氧咪唑啶小基]己基](丙-2-晞基)六氫 吡畊小碳硫醯胺 774 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶小基]己基]-N-苯基-六氫吡畊-1- 碳硫醯胺 12 580 775 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶小基]己基]-N-(苯基甲基)六氫吡 畊-1-碳硫醯胺 12 594 776 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧味σ坐淀-1-基]己基]7T鼠p比呼-1-碳硫酸S-甲酯 13 519 777 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶-1-基]己基]六氫吡畊-1-碳硫酸S-乙酯 13 533 778 4-[6-〇(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧味唆淀-1-基]己基]-N，N-二乙基7T鼠^7比 畊-1-羧酸醯胺 14 544(130) The name of the example is similar to the example Synthesis of ESI-MS-4-oxo-2-thiooximidazolidine small group] hexyl] (propyl-2-fluorenyl) hexahydropyridine small carbon thiostilamine 774 4- [ 6- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazolidine small group] hexyl ] -N-phenyl-hexahydropyridine-1-carboxamidine 12 580 775 4- [6- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazolidine small group] hexyl] -N- (phenylmethyl) hexahydropyridine-1-carboximidine 12 594 776 4- [6- [3- (1,3-Dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooxy odor σ sitting lake- 1-yl] hexyl] 7T mouse p-bihu-1-carbon sulfate S-methyl 13 519 777 4- [6- [3- (1,3-dihydro-1-oxoisobenzofuran-5- Yl) -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] hexyl] hexahydropyridine-1-carbon sulfate S-ethyl ester 13 533 778 4- [6- 〇 (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooxoamido-1-yl] hexyl] -N, N-diethyl 7T mouse ^ 7 Bigen-1-carboxylic acid amidine 14 544

-136- (131) 表33.根據本發明通式㈤化合物，其中v=異苯并呋喃酮 ，W =乙内酿硫月尿，η = 7 實例 779 780 781 782 783 784 785 789 790 名稱 3-(1，3-二氫小氧代異苯并呋喃基)―叩乂 苯甲驢基)六氫㈣+基]庚基二甲基么硫 ^ 啶-4-酮 卜 氧代 --- 二-」一，πυ 干Vg /|、n-十明3-(1，3-二氫-1-氧代異苯并呋喃j基)_5,5_二甲基 -ΗΉ>(1-氧代丙基)六氳吡呼小基]庚基降硫氧_咪 唑啶-4-酮 3-(1,3-二氫-1-氧代異苯并呋喃_5_基)二甲基 小[7-[4-(2-甲基-氧代丙基)六氫吡畊小基]庚基]·2_硫 氧咪唑啶-4-酮 3-(1，3-二氫-1-氧代異苯并呋喃_5_基)_5,5_二甲基 氧代丁基)六氫吡_小基]庚基降硫氧-咪 咬淀-4-嗣 ΗΗ4·(環丙基羰基)六氳吡f L基]庚基]各(1，3二氫小氧代異苯并咬喃_5-基)-5,5_二甲基1硫氧-咪唑各4 酮 H=[4-(環丁基羰基)六氫吡畊+基]庚基]各(1，3·二氫 -1-氧代異苯并呋喃_5-基)-5,5-二甲基-2-硫氧-咪唑啶斗 酉同ϋ二氫+瓦^異苯并呋喃基)-5,5-二甲基 -1-[7_[4-[(魂1基)羰基]六氫吡畊小基]庚基]士硫氧 咪唑啶-4-酮 3-(1,3-二氫-1- ϋ異苯并呋喃_5•基)_5,5_二甲基 -1-[7-[4-[(备2-基)乙醯基]六氫吡呼小基]庚基]1硫氧 -咪唑啶-4-酮⑽二 ^^7^¥¥^^：基>5,5-二 τ 基丨 -1-[7-[4-(甲基磺醯基)六氫吡畊-卜基]庚基]-2_硫氧_咪1 ，坐啶-4-嗣 3-(1，3-二氫-1-氧代異苯并呋喃基)小[7_[4_(乙基-磺 酿基)六氫t井-1-基]庚基]_5,5_二甲基-2·硫氧·咪唑啶 -4-嗣1111，3·二氫二異苯并吱:南-5-基）-5,5-二甲基| 類似於 實例合成 4 4 4 4 4 4 4-136- (131) Table 33. Compounds of general formula VIII according to the present invention, where v = isobenzofuranone, W = thioneurouria, η = 7 Example 779 780 781 782 783 784 785 789 790 Name 3 -(1,3-dihydro small oxoisobenzofuranyl)-stilbenzyl) hexahydrofluorenyl + yl] heptyl dimethyl mothion ^ pyridin-4-one oxo --- Di- "1, πυ dry Vg / |, n-decamine 3- (1,3-dihydro-1-oxoisobenzofuran jyl) _5,5_dimethyl-fluorene > (1-oxo Propyl) hexamethylpyridyl) heptylthioxidazole_imidazolidine-4-one 3- (1,3-dihydro-1-oxoisobenzofuran_5-yl) dimethyl small [7- [4- (2-methyl-oxopropyl) hexahydropyridine] heptyl] · 2-thiooximidazol-4-one 3- (1,3-dihydro-1- Oxo-isobenzofuran_5_yl) _5,5_dimethyloxobutyl) hexahydropyridine_small group] heptylthiothio-imidazo-4--4- (cyclopropylcarbonyl) ) Hexapyridine f L group] heptyl] each (1,3 dihydro small oxoisobenzoan-5-yl) -5,5_dimethyl 1 thiooxy-imidazole each 4 ketones H = [ 4- (cyclobutylcarbonyl) hexahydropyridine + yl] heptyl] each (1,3 · dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-2 -Thiooxo-imidazolidine Dihydro + Wa ^ isobenzofuranyl) -5,5-dimethyl-1- [7_ [4-[(Soul 1yl) carbonyl] hexahydropyridyl] heptyl] thiothiaximidazole -4-keto 3- (1,3-dihydro-1-fluorene isobenzofuran_5 • yl) _5,5_dimethyl-1- [7- [4-[(备 2- 基) ethyl Fluorenyl] hexahydropyridyl] heptyl] 1thio-imidazolidine-4-one fluorenyl di ^^ 7 ^ ¥¥ ^^: group> 5,5-diτyl group -1--1- [7 -[4- (methylsulfonyl) hexahydropyridine-butyl] heptyl] -2_thiooxy_imid 1, pyridin-4- 嗣 3- (1,3-dihydro-1-oxy Substituted isobenzofuryl) small [7_ [4_ (ethyl-sulfonyl) hexahydrot-well-1-yl] heptyl] _5,5_dimethyl-2 · thiooxy · imidazolidine-4-嗣 1111,3 · Dihydrodiisobenzocryl: South-5-yl) -5,5-dimethyl | Similar to Example Synthesis 4 4 4 4 4 4 4

ESI-MS 593 501 515 529 529 527 541 -137- 565 200301117 (132)ESI-MS 593 501 515 529 529 527 541 -137- 565 200301117 (132)

實例 名稱 類似於 實例合成 ESI-MS -l-[7-[4-(丙基績酿基)ττ氮井-1-基]庚基]-2-硫乳-味 。坐淀-4-酉同 791 3-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -1-[7-[4-(本基績8產基)7^鼠^?比^7井-1-基]庚基]-2-硫氧-味 唑啶-4-酮苯甲腈 5 599 792 4-[7-[3-(1，3-二氫小氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶小基]庚基]-N-乙基-六氫吡畊-1- 羧酸醯胺 12 546 793 4-[7-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶-1-基]庚基]-N-丙基-六氫吡畊-1- 羧酸醯胺 12 560 794 4-[7-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶-1-基]庚基]-N-(丙基-2-烯基)六 氫吡畊-1-羧酸醯胺 12 558 795 4-[7-[3_(1，3-二氫小氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧味α坐淀-1 -基]庚基]t?氮p比p井-1 -碳硫feS-甲酯 13 533 796 4-[7-|>(1，3-二氫小氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫乳味哇淀-1-基]庚基]六裘^比p井-1-碳硫feS-乙酯 13 547Example Name Similar to Example Synthesis ESI-MS -l- [7- [4- (propyl phenyl group) ττ nitrogen well-1-yl] heptyl] -2-thioemulsion-taste. Zyodo-4-hydrazone with 791 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-1- [7- [4- (本8 bases) 7 ^ mouse ^? Ratio ^ 7 well -1-yl] heptyl] -2-thiooxy-amidazolidine-4-one benzonitrile 5 599 792 4- [7- [3- (1,3-dihydro small oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazolidine small] heptyl] -N-ethyl -Hexahydropyrine-1-carboxamide 12 546 793 4- [7- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-di Methyl-4-oxo-2-thioximidazolidine-1-yl] heptyl] -N-propyl-hexahydropyrine-1-carboxamide 12 560 794 4- [7- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazolidine-1-yl] heptyl]- N- (propyl-2-enyl) hexahydropyridine-1-carboxylic acid amine 12 558 795 4- [7- [3_ (1,3-dihydro small oxoisobenzofuran-5-yl ) -5,5-Dimethyl-4-oxo-2-thiooxy odor α azido-1 -yl] heptyl] t? Nitrogen p ratio p well-1 -carbon sulfur feS-methyl ester 13 533 796 4- [7- | > (1,3-dihydro small oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiolactone -Yl] heptyl] hexadecyl ^ than p well-1-carbon sulfur feS-ethyl ester 13 547

-138 - (133)200301117 表34. «本發明通式丨的化合物，其中v=異苯并咬喃嗣 w=乙内醯硫脲 5·;二氫-1·氧代異苯 苯甲《)六氫咖井-1-基]辛基]-5,5_二甲基_2·硫氧咪 呢-4-酮 ^0,3-二氫-1-氧代異苯二甲 基胺基)苯甲醯基]六氫吡畊+基]辛基ι·5 5_二 硫氧咪唑啶-4-酮 ，一 土 乙醯基六氫吡 夫喃-5-基)-5,5-二甲基 3O，3-二氫]•減 # 料 5"^Ti7jy^TZ u -.Ί_ΓχΓ/Ι (Λ / li til 甘、、_ I .1 · 小[8-[4-(l-氧代丙基)六氫吡呼基]辛基峰硫^ 唑啶-4-酮 4 529 801 ι-[8·[4_(環丙基羰基)六氫吡m]辛基] 」-氧代異苯并吱喃-5基)·5,5•二甲基」 酮 541 802 ΪΗ^-ΙΧ環丙基羰基)六氫吡畊：二氯 -1-氧代異苯并唉喃基>5,5-二甲基-2-硫氧-咪唑啶-4- 酮 555 803 3-(1，3-二氫-1-氧代異苯并呋喃j基)-5,5•二甲基 基)羰基]六氫吡啩-1-基]辛基]-2-硫氧_ 咪唑啶-4-酮 4 583 804 3-(1，3-二氫小氧代異苯并呋喃基)-5,5-二甲基 -1-[8_1>[(魂-2-基)乙醯基]六氫吡畊+基]辛基>2_硫氧 •咪唑啶-4-酮 597 805 3-(1，3-二氫小氧代異苯并呋喃基)-5,5_二甲基 小[8-[4-[〇比淀冬基)羰基]六氫?比畊小基]辛基]-2-硫氧 -咪唑啶-4-銅 4 578 806 3-(1，3-二氫小氧代異苯并呋喃基)-5,5-二甲基 小[8-[4_(甲基磺醯基)六氫吡畊-1-基]辛基]-2-硫氧-咪 唑啶-4·酮 3-(1，3_二氫小氧代異苯并呋喃_5·基)-1-[8-[4-(乙基磺醯 基)六氫吡畊小基]辛基]_5,5_二甲基硫氧-咪唑啶斗 酮 551 808 3-(1，3-二氫小氧代異苯并呋喃-5-基)-5,5-二甲基 579 -139- 565 807 200301117 (134) 實例 名稱 類似於 實例合成 ESI-MS -l-[8-[4-(丙基續SSi基)τς*氮^7比。井-1-基]辛基]-2-硫氧-味 口坐淀-4-酉同 809 3-(1，3-二氫小氧代異苯并呋喃-5-基)-5,5-二甲基 -1-[8-[4-[(2,2,2-三氟乙基)-磺醯基]六氫吡畊小基]-辛 基]味哇淀-4-酮 5 619 810 3-(1,3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -1-[8-[4-(本基橫酿基鼠ρ比57井-1-基]辛基]-2-硫氧-味 唑啶-4-酮 5 613 811 4-[8-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶-1-基]辛基]-Ν-[3-(甲基硫烷基) 苯基]六氫咐p井-1 -致酸酸胺 6 638 812 4-[8-[3-(1，3-二氮-1-氧代異苯并咬喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶小基]辛基]-N-(3-氟苯基)六氫吡 畊-1-羧酸醯胺 6 610 813 4-[8-[3-(1，3-二氮-1-氧代異苯并咬喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶-1-基]辛基]-N-乙基六氫吡畊-1- 碳硫醯胺 12 560 814 4-[8-[3-(1，3-二鼠-1-氧1代異表并咬喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧味峻淀-1-基]辛基]-N-丙基氮0比0井-1- 碳硫醯胺 12 574 815 4-[8-[3-(1，3-二氫小氧代異苯并呋喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶-1-基]辛基]-N-(丙-2-乙烯基)六 氫吡畊-1-碳硫醯胺 12 572 816 4-[8-[3·(1，3-二氫-1-氧代異苯并咬喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶-1-基]辛基]-Ν-(苯基甲基)六氫吡 畊小碳硫醯胺 12 622 817 4-[8-[3-(1，3-二氫-1-氧代異苯并咬喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶小基]辛基]-Ν-苯基-六氫吡畊-1-碳硫醯胺 12 608 818 4-[8-[3-(1，3-二鼠-1-氧1代異苯并咬喃-5-基)-5,5-二甲基 -4-乳代-2-硫氧味吐淀-1-基]辛基]7^鼠^7比呼-1-碳^硫5^3- 甲酯 13 547 819 4-[8-[3-(1，3-二鼠-1-氧代異苯并咬喃-5-基)-5,5-二甲基 -4-氧代-2-硫氧咪唑啶-1-基]辛基]六氫吡畊-1-碳硫酸S-乙酯 13 561 820 4-[8-Ρ-(1，3-二氫-1-氧代異苯并呋喃-5-基)-5,5-二甲基 14 572-138-(133) 200301117 Table 34. «Compounds of the general formula of the present invention, in which v = isobenzopyran 嗣 w = hydantoin thiourea 5. · dihydro-1 · oxoisobenzoyl" ) Hexahydrocai-1-yl] octyl] -5,5_dimethyl_2 · thioximidine-4-one ^ 0,3-dihydro-1-oxoisophenyldimethylamine Benzyl) benzyl] hexahydropyridine + yl] octyl ι · 5 5_dithiooximidazol-4-one, monoethyridylhexahydropyran-5-yl) -5,5 -Dimethyl 3O, 3-dihydro] • MIN # 料 5 " ^ Ti7jy ^ TZ u -.Ί_ΓχΓ / Ι (Λ / li til GAN, _ I .1 · small [8- [4- (l- Oxopropyl) hexahydropyridyl] octyl peak sulfur oxazol-4-one 4 529 801 ι- [8 · [4_ (cyclopropylcarbonyl) hexahydropyridine m] octyl] "-oxoisobenzene Benzene-5 group), 5,5, dimethyl "ketone 541 802 ΪΗ ^-1 × cyclopropylcarbonyl) hexahydropyridine: dichloro-1-oxoisobenzopyranyl > 5, 5-dimethyl-2-thiooxy-imidazolidin-4-one 555 803 3- (1,3-dihydro-1-oxoisobenzofuran jyl) -5,5 • dimethylyl) Carbonyl] hexahydropyridin-1-yl] octyl] -2-thioxo_imidazolidin-4-one 4 583 804 3- (1,3-dihydro small oxoisobenzofuryl) -5, 5-dimethyl-1- [8_1 > [(Soul-2 -Yl) ethenyl] hexahydropyridine + yl] octyl> 2-thiothioimidazol-4-one 597 805 3- (1,3-dihydro small oxoisobenzofuryl)- 5,5-Dimethyl small [8- [4- [〇 Bidongyl] carbonyl] hexahydro? Phenyl] octyl] -2-thiooxy-imidazolidine-4-copper 4 578 806 3 -(1,3-dihydro small oxoisobenzofuranyl) -5,5-dimethyl small [8- [4- (methylsulfonyl) hexahydropyridin-1-yl] octyl] -2-thioxo-imidazolidine-4 · one 3- (1,3_dihydro small oxoisobenzofuran-5-yl) -1- [8- [4- (ethylsulfonyl) hexa Pyridoxine] octyl] _5,5_dimethylthiooxy-imidazolidinone 551 808 3- (1,3-dihydro small oxoisobenzofuran-5-yl) -5,5 -Dimethyl 579 -139- 565 807 200301117 (134) Example name is similar to the example ESI-MS -l- [8- [4- (propyl-continued SSi group) τς * nitrogen ^ 7 ratio. Jing-1-yl] octyl] -2-thiooxy-weikou zidian-4-pyridine 809 3- (1,3-dihydro small oxoisobenzofuran-5-yl) -5,5 -Dimethyl-1- [8- [4-[(2,2,2-trifluoroethyl) -sulfofluorenyl] hexahydropyridine] -octyl] weiwadian-4-one 5 619 810 3- (1,3-dihydro-1-oxo-isobenzofuran-5-yl) -5,5-dimethyl-1- [8- [4- (benzyl-based rat ρ) Than 57-1--1-yl] octyl] -2-thiooxy-azamidin-4-one 5 613 811 4- [8- [3- (1,3-dihydro-1-oxoisobenzo) Furan-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazolidine-1-yl] octyl] -N- [3- (methylsulfanyl) phenyl] Hexahydrogen p-well-1 -acid amine 6 638 812 4- [8- [3- (1,3-diaza-1-oxoisobenzoan-5-yl) -5,5- Dimethyl-4-oxo-2-thiooximidazolidine small group] octyl] -N- (3-fluorophenyl) hexahydropyridine-1-carboxylic acid sulfonamide 6 610 813 4- [8- [3- (1,3-Diaza-1-oxoisobenzoan-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] Octyl] -N-ethylhexahydropyridine-1-carboxamidine 12 560 814 4- [8- [3- (1,3-dirat-1-oxo 1-epoxy and 5 -Yl) -5,5-dimethyl-4-oxo-2-thioxotriol-1-yl] octyl] -N-propyl nitrogen 0 to 0 well-1- Thiamidine 12 574 815 4- [8- [3- (1,3-dihydro small oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-sulfide Oximidazol-1-yl] octyl] -N- (prop-2-vinyl) hexahydropyridine-1-carboxamidine 12 572 816 4- [8- [3 · (1,3-di Hydrogen-1-oxoisobenzoyl-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazolidine-1-yl] octyl] -N- (phenyl (Methyl) hexahydropyridine small carbothioamide 12 622 817 4- [8- [3- (1,3-dihydro-1-oxoisobenzoan-5-yl) -5,5- Dimethyl-4-oxo-2-thiooximidazolidine small group] octyl] -N-phenyl-hexahydropyridine-1-carboxamidine 12 608 818 4- [8- [3- ( 1,3-dimur-1-oxo-l-isobenzoan-2-yl) -5,5-dimethyl-4-lacto-2-thioxototyl-1-yl] octyl ] 7 ^ rat ^ 7 Bihu-1-carbon ^ sulfur 5 ^ 3-methyl ester 13 547 819 4- [8- [3- (1,3-Dirat-1-oxoisobenzoate-5) -Yl) -5,5-dimethyl-4-oxo-2-thioximidazol-1-yl] octyl] hexahydropyridine-1-carbon sulfate S-ethyl ester 13 561 820 4- [ 8-P- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl 14 572

-140- (135) 200301117-140- (135) 200301117

實例 名稱 類似 fnESI_MSInstance name like fnESI_MS

表35·根據本發明通式I的化合物，其中V=甲基苯并7号呼 ϊ同’ w=乙肉給沒Table 35. Compounds of the general formula I according to the present invention, wherein V = methylbenzo 7 is the same as w ′

表36.根據本發明通式I的化合物，其中v=甲基苯并呤畊 酮，W=乙，n 貧例 ------------ —_二〜11 ——\J 名稱 類似於 實例合成 ESI-MS 822 6 [4’4""一甲基氧代-3-[6-[4-(甲基橫酿基)-六氫ρ比口井 小基]己基]冬硫氧咪唑啶+基]冰甲基-；111-2,3_苯并呤 畊小酮 5 550Table 36. Compounds of the general formula I according to the present invention, wherein v = methylbenzopyridone, W = ethyl, n. Poor ------------ —_di ~ 11 —— \ J name is similar to the example of synthesis ESI-MS 822 6 [4'4 " " monomethyloxo-3- [6- [4- (methyl transverse alcohol) -hexahydro ρ than koujing small group] hexyl ] Hydroxythioimidazolidine + yl] Icemethyl-; 111-2,3_benzopyridinone 5 550

表37·根據本發明通式i的化合物，其中v=2,3-二氫-^茚酮 W=乙内酿硫月尿，n==6 貧例 名稱 類似於 實例合成 ESI-MS 823 1-[6-^-乙酸基六氫吡t ^基)己基]各(2,3_二氮小氧代 •1H-印-5-基)-5,5-二^^2-硫氧咪峻淀-4-酮 4 485 824 3_(2,3-二;氫:^氧代-11^ 茚-5-基)-5,5-二甲基-l-[6-[4-(2-甲基-1-氧代丙基)六氫吡畊-卜基]己基]硫氧咪唑啶 -4-酮 4 513 825 3-(2,3-二氫-1-氧代茚彳基)-5,5-二甲基小[6_[4_ [(备2_基)羧基]六氫♦井小基]己基]-2_硫氧咪唑啶冰 酮 4 553 -141 - (136)Table 37. Compounds of general formula i according to the present invention, wherein v = 2,3-dihydro- ^ indone W = branyl thiosulfonuria, n == 6 Poor name similar to Example Synthesis ESI-MS 823 1 -[6-^-acetoxyhexahydropyridinyl) hexyl] each (2,3_diaza small oxo • 1H-in-5-yl) -5,5-di ^^ 2-thioximide Junjing-4-one 4 485 824 3_ (2,3-di; hydrogen: ^ oxo-11 ^ inden-5-yl) -5,5-dimethyl-l- [6- [4- (2 -Methyl-1-oxopropyl) hexahydropyridine-butyl] hexyl] thioximidazol-4-one 4 513 825 3- (2,3-dihydro-1-oxoindenyl) -5,5-dimethyl small [6_ [4_ [(prepared 2_yl) carboxyl] hexahydro] well small base] hexyl] -2_thiooximidazolyl ketone 4 553 -141-(136)

實例 名稱 類似於 實例合成 ESI-MS 826 3-(2,3-二氫-1-氧代-1H-茚-5-基)-5,5-二甲基小[6-[4-[(吡啶4-基)羰基]六氫吡畊小基]己基]-2-硫氧咪唑啶 -4-酮 4 548 827 3-(2,3-二氫-1-氧代-1H-茚-5-基)-5,5-二甲基小[6-[4-(甲 基石菱S盛基氮说^7井-1-基]己基]-2-硫氧味σ坐咬-4-嗣 5 521 828 3-(2,3-二氫小氧代-1Η-茚-5-基)-5,5-二甲基-1-[6-[4-(丙 基石菱酿基)ττ氮17比ρ井-1-基]己基]-2-硫氧味σ坐淀-4-酉同 5 549 829 4-[6-[3-(2,3-二氫-1-氧代-1Η-雖-5-基)-5,5-二甲基-4-氧 代-2-硫氧味。坐咬-1-基]己基]-Ν-乙基六鼠?比0井-1-碳硫 醯胺 12 530 830 4-[6-[3-(2,3-二氫-1-氧代-1Η-茚-5-基)-5,5-二甲基-4-氧 代-2-硫氧咪唑啶小基]己基]六氫吡畊小碳硫酸S-甲酯 13 517The name of the example is similar to the example Synthesis ESI-MS 826 3- (2,3-dihydro-1-oxo-1H-inden-5-yl) -5,5-dimethyl small [6- [4-[( Pyridine 4-yl) carbonyl] hexahydropyridine] hexyl] -2-thiooximidazol-4-one 4 548 827 3- (2,3-dihydro-1-oxo-1H-indene-5 -Yl) -5,5-dimethyl small [6- [4- (methyl Shi Ling S Sheng Ji nitrogen said ^ 7 well-1-yl] hexyl] -2-thiooxy odor σ sitting bite-4-嗣 5 521 828 3- (2,3-dihydro small oxo-1 Η-inden-5-yl) -5,5-dimethyl-1- [6- [4- (propyllithhenyl) ττ Nitrogen 17 ratio ρ well-1-yl] hexyl] -2-thiooxy odor σ sitting lake 4- 酉 with 5 549 829 4- [6- [3- (2,3-dihydro-1-oxo- 1Η-Although-5-yl) -5,5-dimethyl-4-oxo-2-thiooxy odor. Seated-1-yl] hexyl] -N-ethylhexamorine? -Carbothioamide 12 530 830 4- [6- [3- (2,3-Dihydro-1-oxo-1fluoren-inden-5-yl) -5,5-dimethyl-4-oxo 2-thiothioimidazolidine small group] hexyl] hexahydropyridine small carbon sulfate S-methyl ester 13 517

-142-142

Claims (1)

200301117 拾、申請專利範圍 1.本發明係關於通式I化合物，其中200301117 Patent application scope 1. The present invention relates to compounds of general formula I, in which V表示通式II的經取代芳香族基， ky II 其中 A 表示乙醯基、乙酿基胺基、氰基、硝基、三氟甲基 或鹵素（氟、氯）， B 表示氫原子、鹵素（氟、氯）或三氟甲基，或 A與B—起表示鍵結至芳香族環的式III或IV的環狀基， 其中E表示亞甲基或氧原子，V represents a substituted aromatic group of the general formula II, ky II where A represents an ethylamidine group, an ethylamino group, a cyano group, a nitro group, a trifluoromethyl group or a halogen (fluorine, chlorine), B represents a hydrogen atom, Halogen (fluorine, chlorine) or trifluoromethyl, or A and B together represents a cyclic group of formula III or IV bonded to an aromatic ring, where E represents a methylene or oxygen atom, IIIIII 〇 W表示式V的雜環化合物， IV 200301117〇 W represents a heterocyclic compound of formula V, IV 200301117 其中 τ可代表碳或氮， 若Τ表示碳時，雙鍵呈現在Q與Τ之間，Q意指-C(CH3)-基而U意指氧，η假定為整數值1，2，3，4 ’ 5 ’ 6，7 或8之一，或 若Τ表示氮時，單鍵呈現在Q與Τ之間，Q意指=C(CH3)2-基而U意指硫，η假定為整數值2，3，4，5，6，7或8 之一， i與j，互相獨立表示1與2之值，其中i+j可假設為2或3 之值， R與R’，互相獨立可為氫原子或甲基， Y表示雜環氮與Z間的键、羰基-C(〇）-、磺醯基-S(〇）2-、亞胺基羰基-C(0)N(Z>、亞胺基磺醯基 -S(〇）2N(Zf)-、亞胺基（噻嘮甲基）基-C(S)N(Z]-、氧 羰基亞胺基（噻哼甲基）基- C(S)N(Zf)C(0)0-、氧羰基 -C(0)0-、硫烷基羰基-C(0)S-，及 Z與Z’互相獨立表示氫原子，支鏈或無支鏈Ci-Cs烷基、 C3-C6環烷基，其係視需要用苯基、（C3-C6環烷基）-c「c4伸烷基、支鏈或無支鏈c2-c5烯基、c3-c5炔基 、Ci-q烷氧基、氰基、苯基硫烷基或羥基-Ci-Cdt 烷基、（2-甲氧基乙氧基）甲基、[2-(2-甲氧基乙氧基 )乙氧基]甲基、2-(2-甲氧基乙氧基）乙基、2-[2-(2-甲氧基乙氧基）乙氧基]乙基、Ci-Q烷氧基-CVC4伸 烷基、CVC4烷氧基羰基-匚丨-匕伸烷基、金剛基、三 200301117Where τ can represent carbon or nitrogen, if T represents carbon, the double bond appears between Q and T, Q means -C (CH3)-group and U means oxygen, η is assumed to be an integer value of 1, 2, 3 , 4 '5' 6, 7, or 8, or if T represents nitrogen, a single bond appears between Q and T, Q means = C (CH3) 2- group and U means sulfur, η is assumed to be Integer value is one of 2, 3, 4, 5, 6, 7, or 8, i and j are independent of each other to represent the value of 1 and 2, where i + j can be assumed to be the value of 2 or 3, and R and R ', each other Independently, it may be a hydrogen atom or a methyl group, Y represents a bond between a heterocyclic nitrogen and Z, carbonyl-C (〇)-, sulfofluorenyl-S (〇) 2-, iminocarbonyl-C (0) N ( Z >, iminosulfofluorenyl-S (〇) 2N (Zf)-, imino (thiomethyl) -C (S) N (Z)-, oxycarbonylimino (thiomethyl Group) -C (S) N (Zf) C (0) 0-, oxycarbonyl-C (0) 0-, sulfanylcarbonyl-C (0) S-, and Z and Z 'independently represent hydrogen Atoms, branched or unbranched Ci-Cs alkyl, C3-C6 cycloalkyl, which are optionally used with phenyl, (C3-C6 cycloalkyl) -c "c4 extended alkyl, branched or unbranched Chain c2-c5 alkenyl, c3-c5 alkynyl, Ci-q alkoxy, cyano, phenylsulfanyl or hydroxy -Ci-Cdt alkyl, (2-methoxyethoxy) methyl, [2- (2-methoxyethoxy) ethoxy] methyl, 2- (2-methoxyethoxy Group) ethyl, 2- [2- (2-methoxyethoxy) ethoxy] ethyl, Ci-Qalkoxy-CVC4alkylene, CVC4alkoxycarbonyl- 羰 丨 -dagger Alkyl, adamantyl, tri 200301117 氯乙醯基取代；芳基、雜芳基、雜環基、芳基-Ci-Q 伸烷基、雜芳基-Ci-Q伸烷基、芳氧基-Ci-Q伸烷基 、雜芳氧基-CVC4伸烷基、芳基-C「C4伸烷氧基-Ci-Q 伸烷基，其為未經取代或用最多三個支鏈或無支鏈 CVC4烷基、c2-c6晞基、c3-c6環烷基、苯基、氰基 、鹵素、甲氧基、乙氧基、苯氧基、芊氧基、甲基 硫燒基、乙基硫院基、爷基硫燒基、苯基硫燒基、 二甲基胺基、乙酿基胺基、三氟甲基、三氟甲氧基 、三氟甲基硫烷基、乙醯基、（1 -亞胺基乙基）或硝 基取代，或式 CpFqHr(其中 p=l，2,3,4，q〉l 及 q+r-2p+l) 之基，及 二’除了上述定義以外表示氫原子，以及其藥理上可相 容鹽。 2. 如申請專利範圍第1項之通式I化合物，其特徵為i=j=l。 3. 如申請專利範圍第1或2項之通式I化合物，其中R與R’ 意指Η。 4. 如申請專利範圍第1或2項之通式I化合物，其中Τ=碳。 5·如申請專利範圍第1或2項之通式I化合物，其中Τ=氮。 6.如申請專利範圍第4項之通式I化合物，其中 i十1， 11=1，2，3，4，5，6，7或8， R與R’為氫， A 表不乙酿基、乙酸基胺基、氣基、硝基、三氣甲基 或鹵素（氟、氯），及 20030111?Chloroethenyl substitution; aryl, heteroaryl, heterocyclyl, aryl-Ci-Q alkylene, heteroaryl-Ci-Q alkylene, aryloxy-Ci-Q alkylene, hetero Aryloxy-CVC4 alkylene, aryl-C "C4alkyloxy-Ci-Q alkylene, which are unsubstituted or with up to three branched or unbranched CVC4 alkyl, c2-c6 Fluorenyl, c3-c6 cycloalkyl, phenyl, cyano, halogen, methoxy, ethoxy, phenoxy, fluorenyl, methylsulfanyl, ethylsulfanyl, hexylsulfanyl Methyl, phenylthio, dimethylamino, ethylamino, trifluoromethyl, trifluoromethoxy, trifluoromethylsulfanyl, ethenyl, (1-iminoethyl Group) or a nitro substitution, or a group of the formula CpFqHr (where p = 1, 2, 3, 4, q> l and q + r-2p + l), and two 'represents a hydrogen atom in addition to the above definition, and its Pharmacologically compatible salts. 2. For example, the compound of the general formula I in the scope of patent application item 1 is characterized by i = j = 1. 3. For the compound of the general formula I in the scope of patent application category 1 or 2, where R And R 'means Η. 4. For example, the compound of the general formula I in the scope of the application for patent 1 or 2, where T = carbon. Compounds of general formula I in item 1 or 2 of the patent scope, where T = nitrogen. 6. For example, compounds of general formula I in item 4 of the scope of patent application, where i ten 1, 11 = 1, 2, 3, 4, 5, 6, 7, or 8, R and R 'are hydrogen, A represents ethyl alcohol, acetate amino, amino, nitro, trimethyl or halogen (fluorine, chlorine), and 20030111? B 表示氫原子、鹵素（氟、氯）或三氟甲基，或 A與B—起表示鍵結至芳香族環的式III或IV的環狀基， 其中E表示亞甲基或氧原子B represents a hydrogen atom, a halogen (fluorine, chlorine) or a trifluoromethyl group, or A and B together represent a cyclic group of formula III or IV bonded to an aromatic ring, wherein E represents a methylene group or an oxygen atom 7.如申請專利範圍第5項之通式I化合物，其中 i中1， n=2，3，4，5，6，7或 8， R與IT為氫， A 表示乙酿基、乙臨基胺基、氰基、硝基、三氟甲基 或鹵素（氟、氯），及7. The compound of the general formula I according to item 5 of the scope of patent application, in which 1, n = 2, 3, 4, 5, 6, 7, or 8 in R, R and IT are hydrogen, and A represents ethyl group and ethyl group. Amino, cyano, nitro, trifluoromethyl or halogen (fluorine, chlorine), and B 表示氫原子、鹵素（氟、氯）或三氟甲基，或 A與B—起表示鍵結至芳香族環的式III或IV的環狀基， 其中E表示亞甲基或氧原子 MeB represents a hydrogen atom, a halogen (fluorine, chlorine) or a trifluoromethyl group, or A and B together represent a cyclic group of formula III or IV bonded to an aromatic ring, wherein E represents a methylene group or an oxygen atom Me III IV 8.如申請專利範圍第1項之化合物，即 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η -吡咯-3 -基]戊基]六氫吡畊-1 -羧酸 1，1 -二甲基乙酯 20030111?III IV 8. If the compound in the first item of the patent application scope, that is, 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4- Methyl-2,5-dioxo-1 fluorene-pyrrole-3 -yl] pentyl] hexahydropyrine-1 -carboxylic acid 1,1-dimethylethyl ester 20030111? 4-[2,5-二氫-3 -甲基-4-[5-[4-[2-(甲基硫烷基）苯基] 六氫说口井-1 -基]戊基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[5-[4-(4-氰基苯甲醯基）六氫吡畊-1-基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -说咯-1-基]-2-(三 氟甲基）苯甲腈 4 - [ 3 - [ 5 - [ 4 - [( 3 -氟苯基）磺醯基]六氫吡畊-1 -基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η -吡咯-3 -基]戊基]六氫吡畊-1 -羧醯 胺 4-[2,5 -二氫-3 -甲基- 4- [3-[4-(1-甲基乙基磺醯基）六 氫口比畊-1 -基]丙基]-2，5 -二氧代-1 Η - 口比咯-1 -基]-2 -(三 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-4-[[4-(1-甲基乙基磺醯基）六氫 吡畊-1 -基]甲基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2 -(三氟 甲基）苯甲腈 4-[2,5-二氫-3-甲基-4-[7-[4-(1-甲基乙基磺醯基）六 氫吡畊-1 -基]庚基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯甲腈 4-[5-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]戊基]六氫吡畊-1-羧 酸1，1 -二甲基乙酯 2003011174- [2,5-dihydro-3 -methyl-4- [5- [4- [2- (methylsulfanyl) phenyl] hexahydrogenator-well-1 -yl] pentyl]- 2,5-dioxo-1 fluorene-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4- (4-cyanobenzyl) Hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1Η-syl-1-yl] -2- (trifluoromethyl ) Benzonitrile 4-[3-[5-[4-[(3-fluorophenyl) sulfonamido] hexahydropyridine-1 -yl] pentyl] -2,5 -dihydro-4-methyl -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [5- [1- [4-cyano-3- (trifluoromethyl) ) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 fluorene-pyrrole-3 -yl] pentyl] hexahydropyridine-1 -carboxamide-4 [2,5 -Dihydro-3 -methyl- 4- [3- [4- (1-methylethylsulfonyl) hexahydropyridine-1 -yl] propyl] -2,5- Dioxo-1 hydrazone-bispyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4-[[4- (1 -Methylethylsulfonyl) hexahydropyridine-1 -yl] methyl] -2,5-dioxo-1 -1 -pyrrole-1 -yl] -2-(trifluoromethyl) benzyl Nitrile 4- [2,5-dihydro-3-methyl-4- [7- [4- (1-methylethylsulfonyl) hexahydro] Pycnogenol-1 -yl] heptyl] -2,5-dioxo-1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [5- [3- (1 , 3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] pentyl] hexahydropyridine P--1-carboxylic acid 1,1-dimethylethyl ester 200301117 4-[5-[3-(l，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4 -氧代-2 -硫氧咪唑啶-1 -基]戊基]-N -乙基六氫吡 畊-1 -碳硫醯胺 4-[5-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4 -氧代-2 -硫氧咪唆淀-1 -基]戊基]六氫p比呼-1 -碳 硫酸S -甲酯 4-[5-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]戊基]-N，N-二甲基六 氫吡畊-1 -羧醯胺 4-[3-[2-[4-(2-甲氧基苯甲醯基）六氫吡畊-1-基]乙 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4-[3-[(4-乙醯基六氫吡畊-1-基）甲基卜2,5-二氫-4-甲 基- 2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-[[4-(甲氧基乙醯基）六氫吡畊-1-基]甲 基]-4 -甲基-2,5 -二氧代-1H -吡咯-1-基]-2-(三氟甲基） 苯甲月青 4-[2,5-二氫-3-[4-[[(2-(甲氧基乙氧基）乙醯基）六氫 吡畊-1 -基]甲基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[[4-[[(2-(2 -甲氧基乙氧基）乙氧基）乙 醯基]六氫说畊-1 -基]甲基]-4 -甲基-2，5 -二氧代-1 Η -吡 咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-[[4-(2-(甲氧基苯甲醯基）六氫吡畊-1- 20030111?4- [5- [3- (l, 3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-4 -oxo-2 -thioximidazolidine- 1-yl] pentyl] -N-ethylhexahydropyridine-1 -carbothioamide 4- [5- [3- (1,3-dihydro-1-oxoisobenzofuran-5- Radical) -5,5 -dimethyl-4 -oxo-2 -thioxanthemidate-1 -yl] pentyl] hexahydropeptone-1 -carbon sulfate S-methyl ester 4- [5- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] pentane Phenyl] -N, N-dimethylhexahydropyridine-1 -carboxamidin 4- [3- [2- [4- (2-methoxybenzylhydrazyl) hexahydropyridine-1-yl ] Ethyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [3-[(4- Acetylhexahydropyridin-1-yl) methyl 2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl Phenyl) benzonitrile 4- [2,5-dihydro-3-[[4- (methoxyethylfluorenyl) hexahydropyridin-1-yl] methyl] -4 -methyl-2,5 -Dioxo-1H -pyrrole-1-yl] -2- (trifluoromethyl) benzazine 4- [2,5-dihydro-3- [4-[[(2- (methoxy Ethoxy) ethanyl) hexahydropyridine-1 -yl] methyl] -4 -methyl-2,5-di Oxo-1 fluorene-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro- 3-[[4-[[((2- (2-methoxy Ethoxy) ethoxy) ethenyl] hexanoxy-1 -yl] methyl] -4 -methyl-2,5-dioxo-1 fluorene -pyrrole-1-yl] -2 -(Trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-[[4- (2- (methoxybenzylhydrazyl) hexahydropyridine-1-20030111? 基）甲基]-4 -甲基-2,5-二氧代-1H -说咯-1-基]-2-(三氟 甲基）苯甲腈 4 - [ 2，5 -二氫-3 -甲基-4 - [[ 4 -(甲基磺醯基）六氫吡畊-1 -基]甲基]-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基）苯 甲月膏 4-[3-[[4-(乙基磺醯基）六氫吡畊-1-基]甲基]-2,5-二 氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基）苯(Methyl) methyl] -4 -methyl-2,5-dioxo-1H -syl-1-yl] -2- (trifluoromethyl) benzonitrile 4-[2,5-dihydro- 3 -methyl-4-[[4-(methylsulfonyl) hexahydropyridine-1 -yl] methyl] -2,5-dioxo-1H-pyrrole-1-yl] -2- (Trifluoromethyl) benzyl moon cream 4- [3-[[4- (ethylsulfonyl) hexahydropyridine-1-yl] methyl] -2,5-dihydro-4-methyl -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzene 甲腈 4-[2,5 -二氫- 3- [[4-(2 -甲氧基乙基）磺醯基]-六氫吡畊 -1-基]甲基]-4 -甲基-2,5-二氧代-1H -吡咯-1-基]-2-(三 氟甲基）苯甲腈Nitrile 4- [2,5 -dihydro- 3- [[4- (2-methoxyethyl) sulfonamido] -hexahydropyridin-1-yl] methyl] -4 -methyl- 2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[2,5-二氫- 3-[[4-[[2-[2-(2 -甲氧基乙氧基）乙氧基] 乙基]磺醯基]六氫吡畊-1 -基]甲基]-4 -甲基-2，5 -二氧 代-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基- 2,5-二氧代-4-[[4-(苯基磺醯基） 六氫吡畊-1 -基]甲基]-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯 甲月青 4-[3-[2-(4 -乙醯基六氫吡畊-1-基）乙基]-2,5-二氫-4-甲基-2,5-二氧代-lH-说咯-l-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[2-(4-(1-氧代丙基） 六氫吡畊-1 -基）乙基]-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯 甲月膏 4-[3-[2-[4-(環丙基羰基）六氫吡畊-1-基]乙基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 2003011174- [2,5-dihydro- 3-[[4-[[2- [2- (2- (methoxyethoxy) ethoxy] ethyl] sulfofluorenyl] hexahydropyridine-1 -Yl] methyl] -4 -methyl-2,5-dioxo-1 Η -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro -3-methyl-2,5-dioxo-4-[[4- (phenylsulfonyl) hexahydropyridine-1 -yl] methyl] -1 hydrazone -pyrrole-1 -yl]- 2- (trifluoromethyl) benzyl cyanine 4- [3- [2- (4- (ethylamidinohexahydropyridine-1-yl) ethyl] -2,5-dihydro-4-methyl -2,5-dioxo-lH-syl-l-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-di Oxo-4- [2- (4- (1-oxopropyl) hexahydropyridine-1 -yl) ethyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) Benzyl month cream 4- [3- [2- [4- (cyclopropylcarbonyl) hexahydropyridine-1-yl] ethyl] -2,5-dihydro-4-methyl-2,5- Dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) 200301117 苯甲月青 4-[2,5 -二氫-3-[2-[4-(甲氧基乙醯基）六氫吡畊-1-基] 乙基]-4 -甲基-2,5 -二氧代-1H -吡咯-1-基]-2-(三氟甲基） 苯甲月青 4-[2,5 -二氫- 3- [2-[4-(3 -甲氧基-1-氧代丙基）六氫吡 畊-1 -基]乙基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈Benzylpyrene 4- [2,5 -dihydro-3- [2- [4- (methoxyethylamidino) hexahydropyrine-1-yl] ethyl] -4 -methyl-2, 5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzazine 4- [2,5 -dihydro- 3- [2- [4- (3- -methoxy Yl-1-oxopropyl) hexahydropyridine-1 -yl] ethyl] -4 -methyl-2,5-dioxo-1 hydrazone -pyrrole-1 -yl] -2- (trifluoro Methyl) benzonitrile 4-[2,5 -二氫- 3- [2-[4-[(2 -甲氧基乙氧基）乙醯基]六氫 吡畊-1 -基]乙基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈4- [2,5 -dihydro- 3- [2- [4-[(2-methoxyethoxy) ethenyl] hexahydropyridine-1 -yl] ethyl] -4 -methyl -2,5 -dioxo-1 hydrazone -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4-[2,5-二氫- 3-[2-[4-[[(2-(2 -甲氧基乙氧基）乙氧基） 乙醯基]六氫吡畊-1-基]乙基]-4 -甲基- 2,5-二氧代-ΙΗ-吡咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[2,5 -二氫- 3-[2-[4-(2 -甲氧基苯甲醯基）六氫吡畊 -1-基]乙基]-4 -甲基-2,5-二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-4-[2-[4-(甲基磺醯基）六氫吡畊 -1 -基]乙基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2 -(三氟甲基） 苯甲月膏 4-[3-[2-[4-(乙基磺醯基）六氫吡畊-1-基]乙基]-2,5-二氫-4 -甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[3-[2-[4-(環丙基磺醯基）六氫吡畊-1-基]乙基]-2,5 -二氫-4 -甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟 2003011174- [2,5-Dihydro- 3- [2- [4-[[(2- (2-methoxyethoxy) ethoxy) ethenyl] hexahydropyridine-1-yl] Ethyl] -4 -methyl-2,5-dioxo-l-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5 -dihydro-3-[ 2- [4- (2-methoxybenzylidene) hexahydropyridin-1-yl] ethyl] -4 -methyl-2,5-dioxo-1Η-pyrrole-1-yl] 2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4- [2- [4- (methylsulfonyl) hexahydropyridine-1 -yl ] Ethyl] -2,5-dioxo-1 pyrene-pyrrole-1 -yl] -2-(trifluoromethyl) benzyl cream 4- [3- [2- [4- (ethylsulfonate Fluorenyl) hexahydropyridin-1-yl] ethyl] -2,5-dihydro-4 -methyl-2,5-dioxo-1fluorenyl-pyrrole-1-yl] -2- (trifluoro (Methyl) benzonitrile 4- [3- [2- [4- (cyclopropylsulfonyl) hexahydropyridine-1-yl] ethyl] -2,5-dihydro-4 -methyl- 2,5 -dioxo-1'-pyrrole-1-yl] -2- (trifluoro200301117 甲基）苯甲腈 4-[2,5 -二氫- 3- [2-[4-(2 -甲氧基乙基）磺醯基]六氫吡 呼-1 -基]乙基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3- [2-[4-[[2-(2-甲氧基乙氧基）乙基]磺 醯基]六氫吡畊-1 -基]乙基]-4 -甲基-2，5 -二氧代-1 Η - 口比 咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[2-[4-[[2-[2-(2 -甲氧基乙氧基）乙氧基]φ 乙基]磺醯基]六氫吡畊-1 -基]乙基]-4 -甲基-2，5 -二氧 代-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[2-[4-(苯基磺醯 基）六氫吡畊-1 -基]乙基]-1 Η -吡咯-1 -基]-2 -(三氟甲基） 苯甲月青 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[2-[4-(苯基甲基） 磺醯基]六氫吡畊-1 -基]乙基]-1 Η -吡咯-1 -基]-2 -(三氟Methyl) benzonitrile 4- [2,5 -dihydro- 3- [2- [4- (2-methoxyethyl) sulfonyl] hexahydropyridine-1 -yl] ethyl]- 4-methyl-2,5-dioxo-1 fluorene-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro- 3- [2- [ 4-[[2- (2-methoxyethoxy) ethyl] sulfofluorenyl] hexahydropyridine-1 -yl] ethyl] -4 -methyl-2,5-dioxo-1 Η-oxopyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro- 3- [2- [4-[[2- [2- (2- Methoxyethoxy) ethoxy] φethyl] sulfofluorenyl] hexahydropyridine-1 -yl] ethyl] -4 -methyl-2,5-dioxo-1fluorene-pyrrole-1 -Yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [2- [4- (phenylsulfonate Fluorenyl) hexahydropyridine-1 -yl] ethyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzazine 4- [2,5-dihydro-3- Methyl-2,5-dioxo-4- [2- [4- (phenylmethyl) sulfofluorenyl] hexahydropyridine-1 -yl] ethyl] -1 hydrazone -pyrrole-1 -yl ] -2-(Trifluoro 甲基）苯甲腈 4-[2,5 -二氫-3-甲基- 4- [2-[4-[(1-甲基-1Η -咪唑-4-基） 磺醯基]六氫吡畊-1 -基]乙基]· 2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]乙基]-&(1-甲基乙基） 六氫吡畊-1 -羧醯胺 4-[2-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]乙基]-Ν -乙基六氫吡畊 200301117Methyl) benzonitrile 4- [2,5-dihydro-3-methyl- 4- [2- [4-[(1-methyl-1Η-imidazol-4-yl) sulfonamido] hexahydro Pycnogenol-1 -yl] ethyl] · 2,5-dioxo-1 Η -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2- [1- [4 -Cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] ethyl]-& (1-methylethyl) hexahydropyridine-1 -carboxamide 4- [2- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro -4-methyl-2,5-dioxo-1'-pyrrole-3-yl] ethyl] -N -ethylhexahydropyroxy 200301117 -1 -碳硫酿胺 4-[2-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯-3-基]乙基]六氫吡畊-1-羧酸 甲酉旨 4-[2-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η -吡咯-3 -基]乙基]六氫吡畊-1 -碳硫 酸S -甲酯-1 -Carbosulfanamine 4- [2- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-di Oxo-1H-pyrrole-3-yl] ethyl] hexahydropyridine-1-carboxylic acid formamidine 4- [2- [1- [4-cyano-3- (trifluoromethyl) phenyl ] -2,5-dihydro-4-methyl-2,5-dioxo-1 Η-pyrrole-3 -yl] ethyl] hexahydropyridine-1 -carbon sulfate S-methyl ester 4-[2-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]乙基]-11^二甲基六氫 吡畊-1 -磺醯胺 4-[3-[3-(4 -乙醯基六氫吡畊-1-基）丙基]-2,5-二氫-4-甲基-2,5-二氧代-lH-吡咯-l-基]-(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[3-[4-(1-氧代丙基） 六氫吡畊-1 -基]丙基]-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯 甲月青4- [2- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole- 3-yl] ethyl] -11 ^ dimethylhexahydropyridine-1 -sulfamethoxamine 4- [3- [3- (4- (ethylhydratylhexahydropyridine-1-yl) propyl]- 2,5-dihydro-4-methyl-2,5-dioxo-lH-pyrrole-l-yl]-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- Methyl-2,5-dioxo-4- [3- [4- (1-oxopropyl) hexahydropyridine-1 -yl] propyl] -1 hydrazone -pyrrole-1 -yl]- 2-(trifluoromethyl) benzidine 4-[3-[3-[4-(環丙基羰基）六氫吡畊-1-基]丙基]-2,5-二氫-4 -甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[2,5-二氫-3-[3-[4-(甲氧基乙醯基）六氫吡畊-1-基] 丙基]-4 -甲基-2,5-二氧代- lH-p比咯-1-基]-2-(三氟甲基） 苯甲腈 4-[2,5 -二氫- 3- [3-[4-(3 -甲氧基-1-氧代丙基）六氫吡 畊-1-基]丙基]-4-甲基-2,5 -二氧代-1Η- 口比咯-1-基]-2-(三氟甲基）苯甲腈 -10- 2003011174- [3- [3- [4- (Cyclopropylcarbonyl) hexahydropyridin-1-yl] propyl] -2,5-dihydro-4 -methyl-2,5 -dioxo- 1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- [3- [4- (methoxyethylfluorenyl) hexahydropyrrolidine -1-yl] propyl] -4-methyl-2,5-dioxo-lH-p than pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5 -Dihydro- 3- [3- [4- (3- (methoxy-1-oxopropyl) hexahydropyridin-1-yl] propyl] -4-methyl-2,5-dioxo -1Η-O-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile-10- 200301117 4-[2,5-二氫- 3-[3-[4-[(2-甲氧基乙氧基）乙醯基]六氫 吡畊-1 -基]丙基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈4- [2,5-Dihydro- 3- [3- [4-[(2-methoxyethoxy) ethenyl] hexahydropyridine-1 -yl] propyl] -4 -methyl -2,5 -dioxo-1 hydrazone -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4-[2,5 -二氫- 3-[3-[4-[[2-(2 -甲氧基乙氧基）乙氧基] 乙醯基]六氫吡畊-1-基]丙基]-4 -甲基- 2,5 -二氧代-ΙΗ-吡咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[2,5 -二氫-3-[3-[4-(2-甲氧基苯甲醯基）六氫吡畊 -1-基]丙基]-4 -甲基-2,5-二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4 - [ 2，5 -二氫-3 -甲基-4 - [ 3 - [ 4 -(甲基磺醯基）六氫吡畊 -1-基]丙基]-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲月青 4-[3-[3-[4-(乙基磺醯基）六氫吡畊-1-基]丙基]-2,5-二氫-4 -甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基） 苯甲月青4- [2,5 -dihydro- 3- [3- [4-[[2- (2-methoxyethoxy) ethoxy] ethenyl] hexahydropyridin-1-yl] propane Yl] -4 -methyl-2,5 -dioxo-l-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5 -dihydro-3- [3 -[4- (2-methoxybenzylidene) hexahydropyridine-1-yl] propyl] -4 -methyl-2,5-dioxo-1Η-pyrrole-1-yl]- 2- (trifluoromethyl) benzonitrile 4-[2,5-dihydro-3 -methyl-4-[3-[4-(methylsulfonyl) hexahydropyridine-1-yl] Propyl] -2,5-dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzazine 4- [3- [3- [4- (ethylsulfonyl ) Hydroxypyrine-1-yl] propyl] -2,5-dihydro-4 -methyl-2,5-dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl ) Benzyl green 4-[3-[3-[4-(環丙基磺醯基）六氫吡畊-1-基]丙 基]-2,5 -二氫-4-甲基-2,5 -二氧代·1Η-ρ比咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫- 3-[3-[4-(2 -甲氧基乙基）磺醯基]六氫吡 畊-1-基]丙基]-4-甲基-2,5 -二氧代-1Η- 口比咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-[3-[4-[[2-(2_甲氧基乙氧基）乙基]磺 醯基]六氫吡畊-1 -基]丙基]-4 -甲基-2，5 -二氧代-1 Η -叶匕 咯-1-基]-2-(三氟甲基）苯甲腈 -11 - 2003011174- [3- [3- [4- (Cyclopropylsulfonyl) hexahydropyridine-1-yl] propyl] -2,5-dihydro-4-methyl-2,5 -dioxy · 1Η-ρbirol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro- 3- [3- [4- (2-methoxyethyl ) Sulfofluorenyl] hexahydropyridin-1-yl] propyl] -4-methyl-2,5-dioxo-1fluorene-pyrrol-1-yl] -2- (trifluoromethyl) Benzonitrile 4- [2,5-dihydro-3- [3- [4-[[2- (2-methoxyethoxy) ethyl] sulfonyl] hexahydropyridine-1 -yl ] Propyl] -4 -methyl-2,5 -dioxo-1 hydrazone-leafyl-1-yl] -2- (trifluoromethyl) benzonitrile-11-200301117 4-[2,5-二氫- 3-[3-[4-[[2-[2-(2 -甲氧基乙氧基）乙氧基] 乙基）磺醯基]六氫吡畊-1-基]丙基]-4 -甲基-2,5-二氧 代-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[3-[4-(苯基-磺醯 基）六氫吡畊-1 -基]丙基-1 Η -吡咯-1 -基]-2 -(三氟甲基） 苯甲腈4- [2,5-Dihydro- 3- [3- [4-[[2- [2- [2- (2-methoxyethoxy) ethoxy] ethyl) sulfofluorenyl] hexahydropyridine -1-yl] propyl] -4-methyl-2,5-dioxo-1 fluorene-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5- Dihydro-3-methyl-2,5-dioxo-4- [3- [4- (phenyl-sulfonamido) hexahydropyridine-1 -yl] propyl-1 hydrazone -pyrrole-1 -Yl] -2-(trifluoromethyl) benzonitrile 4-[2,5 -二氫-3 -甲基-2,5-二氧代-4-[3-[4-[(苯基甲基） 磺醯基]六氫吡畊-1 -基]丙基]-1 Η -吡咯-1 -基]-2 -(三氟 甲基）苯甲腈 4-[2,5 -二氫-3-甲基- 4- [3-[4-[(1-甲基-1Η -咪唑-4-基） 磺醯基]六氫吡畊-1 -基]丙基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]丙基]*^-(1-甲基乙基）- 六氫吡畊-1 -羧醯胺4- [2,5 -Dihydro-3 -methyl-2,5-dioxo-4- [3- [4-[(phenylmethyl) sulfonamido] hexahydropyridine-1 -yl ] Propyl] -1 fluorene-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl- 4- [3- [4- [ (1-methyl-1fluorenyl-imidazol-4-yl) sulfofluorenyl] hexahydropyridine-1 -yl] propyl] -2,5-dioxo-1 hydrazone -pyrrole-1 -yl] -2 -(Trifluoromethyl) benzonitrile 4- [3- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2, 5-dioxo-111-pyrrole-3-yl] propyl] * ^-(1-methylethyl) -hexahydropyridine-1 -carboxamide 4-[3-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]丙基]-Ν -乙基六氫吡畊 -1 -碳硫醯胺 4-[3-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]丙基]六氫吡畊-1-羧酸 甲醋 4-[3-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η -吡咯-3 -基]丙基]六氫吡畊-1 -碳硫 酸S -甲酯 -12- 2003011174- [3- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole- 3-yl] propyl] -N-ethylhexahydropyridine-1 -carbothioamide 4- [3- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2 , 5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] propyl] hexahydropyridine-1-carboxylic acid methyl acetate 4- [3- [1- [ 4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 Η-pyrrole-3 -yl] propyl] hexa Hydropyrine-1 -Carbon sulfate S -Methyl ester-12- 200301117 4-[3-[1-[4-氛基-3-(三氟甲基）苯基]-2,5-二氮-4-甲 基-2,5-二氧代-1H-吡咯-3-基]丙基]-N，N_二甲基六氫 吡畊-1 -磺醯胺 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η -吡咯-3 -基]丁基]六氫吡畊-1 -羧酸 1，1 -二甲基乙酯4- [3- [1- [4-Amino-3- (trifluoromethyl) phenyl] -2,5-diaza-4-methyl-2,5-dioxo-1H-pyrrole- 3-yl] propyl] -N, N-dimethylhexahydropyridine-1 -sulfamethoxamine 4- [4- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 Η-pyrrole-3 -yl] butyl] hexahydropyridine-1 -carboxylic acid 1,1-dimethylethyl ester 4-[2,5-二氫-3-甲基-4-[4-[4-[2-(甲基硫烷基）苯基] 六氫吡畊-1-基]丁基]-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[3-[4-[4-(3,5 -二氯吡啶-4 -基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -口比咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[4-[4-(環戊基乙醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈4- [2,5-dihydro-3-methyl-4- [4- [4- [2- (methylsulfanyl) phenyl] hexahydropyridin-1-yl] butyl] -2 , 5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4- (3,5-dichloropyridine-4 -yl ) Hydroxypyrine-1-yl] butyl] -2,5 -dihydro-4-methyl-2,5 -dioxo-1H -pyrrol-1-yl] -2- (trifluoro Methyl) benzonitrile 4- [3- [4- [4- (cyclopentylethylfluorenyl) hexahydropyridine-1-yl] butyl] -2,5-dihydro-4-methyl- 2,5 -dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[4-[4-(2,6-二氟苯甲醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[4-[4-(2,6-二氯苯甲醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[4-[4-(3-氟苯甲醯基）六氫、比畊-1-基]丁 基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-1·基]-2-(三 氟甲基）苯甲腈 -13 - 2003011174- [3- [4- [4- (2,6-difluorobenzylidene) hexahydropyridin-1-yl] butyl] -2,5-dihydro-4-methyl-2, 5 -dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4- (2,6-dichlorobenzylfluorenyl) hexa Hydropyrine-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzene Nitrile 4- [3- [4- [4- (3-fluorobenzylidene) hexahydro, pike-1-yl] butyl] -2,5-dihydro-4-methyl-2, 5-dioxo-1'-pyrrole-1 · yl] -2- (trifluoromethyl) benzonitrile-13-200301117 4-[2,5 -二氫-3-[4-[4-(3-甲氧基苯甲醯基）六氫吡畊 -1-基]丁基]-4 -甲基-2,5 -二氧代-1H-叶匕咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5·二氫-3-甲基-4-[4-[4-(3-甲基苯甲醯基）六氫 吡畊-1-基]丁基]-2,5-二氧代- ΙΗ-说咯-1-基]-2-(三氟 甲基）苯甲腈4- [2,5 -Dihydro-3- [4- [4- (3-methoxybenzylidene) hexahydropyridine-1-yl] butyl] -4 -methyl-2,5 -Dioxo-1H-leafyl-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5 · dihydro-3-methyl-4- [4- [4- (3-methylbenzylidene) hexahydropyridin-1-yl] butyl] -2,5-dioxo- 1Η-syl-1-yl] -2- (trifluoromethyl) benzene Nitrile 4-[3-[4-[4_(4-氟苯甲醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代·1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基- 4-[4-[4-[(莕-1-基）羰基]六氫吡 畊-1-基]丁基]-2,5-二氧代-1Η-说咯-1-基]-2-(三氟甲 基）苯甲腈 4-[2,5-二氫-3-甲基-4-[4-[4-[(莕-2-基）羰基]六氫吡 畊-1-基]丁基]-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲 基）苯甲腈4- [3- [4- [4_ (4-fluorobenzylidene) hexahydropyrine-1-yl] butyl] -2,5-dihydro-4-methyl-2,5 -dioxy -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl- 4- [4- [4-[(荇 -1 -Yl) carbonyl] hexahydropyridine-1-yl] butyl] -2,5-dioxo-1fluorene-syl-1-yl] -2- (trifluoromethyl) benzonitrile 4- [ 2,5-dihydro-3-methyl-4- [4- [4-[(fluoren-2-yl) carbonyl] hexahydropyridine-1-yl] butyl] -2,5-dioxo -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[4-[4-(3-氰基苯甲醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -口比咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[4-[4-(環己基羰基）六氫吡畊-1-基]丁基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[3-[4-[4-(呋喃-2 -基）羰基]六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 -14- 2003011174- [3- [4- [4- (3-Cyanobenzyl) hexahydropyrine-1-yl] butyl] -2,5-dihydro-4-methyl-2,5- Dioxo-l-pyridol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4- (cyclohexylcarbonyl) hexahydropyridine-1-yl ] Butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4- (furan-2-yl) carbonyl] hexahydropyridine-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1Η- Pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile-14- 200301117 4 - [ 3 - [ 4 - [ 4 -(環戊基羰基）六氫吡畊-1 -基]丁基]-2，5 -二氫-4-甲基-2,5-二氧代-1H -吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[2,5 -二氫-3-甲基- 4- [4-[4-[(5-甲基異吟唑-3 -基）羰 基]六氫吡畊-1 -基]丁基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈4-[3-[4-[4- (cyclopentylcarbonyl) hexahydropyridine-1 -yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo- 1H -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl- 4- [4- [4-[(5-methyliso Indazole-3 -yl) carbonyl] hexahydropyridine-1 -yl] butyl] -2,5-dioxo-1 hydrazone -pyrrole-1 -yl] -2- (trifluoromethyl) benzyl Nitrile 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[4-[4-(苯基乙醯 基）六氫说畊-1-基]丁基]-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲月青 4-[2,5 -二氫-3-[4-[4-(2-甲氧基苯甲醯基）六氫吡畊 -1-基]丁基]-4 -甲基-2,5-二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-[4-[4-(甲氧基乙醯基）六氫吡畊-1-基] 丁基]-4 -甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲腈4- [2,5-Dihydro-3-methyl-2,5-dioxo-4- [4- [4- (phenylethylfluorenyl) hexahydro-1-yl] butyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzazine 4- [2,5 -dihydro-3- [4- [4- (4-methoxybenzylidene) ) Hydroxypyrine-1-yl] butyl] -4-methyl-2,5-dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [ 2,5-dihydro-3- [4- [4- (methoxyethylfluorenyl) hexahydropyridine-1-yl] butyl] -4 -methyl-2,5-dioxo-1Η -Pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[4-[4-(2-氯苯甲醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[4-[4-(2-氟苯甲醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[4-(4-苯甲醯基六氫吡畊-1-基）丁基]-2,5-二氫 -4 -甲基- 2,5-二氧代-1Η “比咯-1-基]-2-(三氟甲基）苯甲 腈 -15 - 2003011174- [3- [4- [4- (2-chlorobenzylidene) hexahydropyridin-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-di Oxo-1′-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4- (2-fluorobenzylhydrazyl) hexahydropyridine-1- Yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3 -[4- (4-benzylidene hexahydropyrine-1-yl) butyl] -2,5-dihydro-4 -methyl-2,5-dioxo-1Η -Yl] -2- (trifluoromethyl) benzonitrile-15-200301117 4-[3-[4-[4-(環丁基羰基）六氫吡畊-1-基]丁基]-2,5-二氫-4-甲基-2,5-二氧代-1H -吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[4-[4-[卜比啶-3-基） 羰基]六氫吡畊-1 -基]丁基]-1 Η -说咯-1 -基]-2 -(三氟甲 基）苯甲腈4- [3- [4- [4- (cyclobutylcarbonyl) hexahydropyridine-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo- 1H -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [4- [4 -[Bibidin-3-yl) carbonyl] hexahydropyridine-1 -yl] butyl] -1 hydrazone -single-1 -yl] -2-(trifluoromethyl) benzonitrile 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[4-[4-[(吡啶-4-基） 羰基]六氫吡畊-1-基]丁基]-1Η-吡咯-1-基]-2-(三氟甲 基）苯甲腈 4·[3-[4-[4-[4_(二甲基胺基）苯甲醯基]六氫吡畊-1-基] 丁基]-2,5 -二氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[4-[4-[(苯基硫烷 基）乙醯基]六氫吡畊-1 -基]丁基]-1 Η - Ρ比咯-1 -基]-2 -(三 氟甲基）苯曱腈4- [2,5 -Dihydro-3-methyl-2,5-dioxo-4- [4- [4-[(pyridin-4-yl) carbonyl] hexahydropyridine-1-yl] Butyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 · [3- [4- [4- [4 -_ (dimethylamino) benzyl]] Hydropyrine-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzene Nitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [4- [4-[(phenylsulfanyl) ethenyl] hexahydropyridine- 1-yl] butyl] -1 fluorene-P-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[4-[4-[(苯氧基乙 醯基）六氫吡畊-1 -基]丁基]-1 Η -吡咯-1 -基]-2 -(三氟甲 基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[4-[4-[〇塞-2-基） 羰基]六氫吡畊-1 -基]丁基]-1 Η -吡咯-1 -基]-2 -(三氟甲 基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[4-[4-(3-苯基-1-氧代丙基）六氫吡畊-1 -基]丁基]-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯甲腈 -16- 2003011174- [2,5-Dihydro-3-methyl-2,5-dioxo-4- [4- [4-[(phenoxyethylfluorenyl) hexahydropyridine-1 -yl] butyl Yl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [ 4- [4- [〇Se-2-yl) carbonyl] hexahydropyridine-1 -yl] butyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4 -[2,5-Dihydro-3-methyl-2,5-dioxo-4- [4- [4- (3-phenyl-1-oxopropyl) hexahydropyrine-1- Yl] butyl] -1 fluorene-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile-16- 200301117 4-[3-[4-[4-[(l，3-苯并二哼茂-5 -基）羰基]六氫吡畊 -1-基]丁基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫- 3- [4-[4-[(4-甲氧基苯基）乙醯基]六氫吡 畊-1 -基]丁基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈4- [3- [4- [4-[(l, 3-Benzodihumo-5-yl) carbonyl] hexahydropyridine-1-yl] butyl] -2,5 -dihydro-4 -Methyl-2,5 -dioxo-1H -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5 -dihydro- 3- [4- [4- [(4-methoxyphenyl) ethenyl] hexahydropyridine-1 -yl] butyl] -4 -methyl-2,5-dioxo-1 fluorene -pyrrole-1 -yl]- 2- (trifluoromethyl) benzonitrile 4-[2,5 -二氫-3-甲基-4-[4-[4-(2 -甲基苯甲醯基）六氫 吡畊-1-基]丁基]-2,5-二氧代- lml:咯-1-基]-2-(三氟 甲基）苯甲腈 4-[3-[4-[4-(4-氯苯甲醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -口比咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[4-[4-[(噻-2-基） 乙SS基]六氯说17井-1-基]丁基]-lH-p比p各-1-基]-2-(三氣 甲基）苯甲腈4- [2,5 -Dihydro-3-methyl-4- [4- [4- (2-methylbenzylidene) hexahydropyrine-1-yl] butyl] -2,5- Dioxo-lml: role-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4- (4-chlorobenzylhydrazyl) hexahydropyracine-1 -Yl] butyl] -2,5 -dihydro-4-methyl-2,5 -dioxo-1H-acetol-1-yl] -2- (trifluoromethyl) benzonitrile 4 -[2,5-Dihydro-3-methyl-2,5-dioxo-4- [4- [4-[(thia-2-yl) ethylSS-yl] hexachloro said 17 wells-1- Yl] butyl] -1H-p ratio p each-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[4-[4-(3-氯苯甲醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -口比咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[4-[4-(4-氰基苯甲醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4 - [ 2,5 - 一鼠- 3- [4-[4-(3-甲氧基-1-氧代丙基）ττ鼠p比 畊-1 -基]丁基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 -17- 2003011174- [3- [4- [4- (3-chlorobenzylidene) hexahydropyridin-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-di Oxo-1H-oxopyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4- (4-cyanobenzyl) hexahydropyridine -1-yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 -[2,5-one mouse-3- [4- [4- (3-methoxy-1-oxopropyl) ττ mouse p pike-1 -yl] butyl] -4 -methyl- 2,5-dioxo-1 pyrene-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile-17- 200301117 4-[2,5 -二氫- 3- [4-[4-[(2 -甲氧基乙氧基）乙醯基]六氫 吡畊-1 -基]丁基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈4- [2,5 -Dihydro- 3- [4- [4-[(2-methoxyethoxy) ethenyl] hexahydropyridine-1 -yl] butyl] -4 -methyl -2,5 -dioxo-1 hydrazone -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4-[2,5 -二氫-3-[4-[4-[[2-(2 -甲氧基乙氧基）乙氧基） 乙醯基]六氫吡畊-1-基]丁基]-4 -甲基-2,5 -二氧代-ΙΗ-吡咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[4-[4-[4-(環丙基磺醯基）六氫吡畊-1-基]丁 基]-2,5 -二氫-3-甲基-2,5 -二氧代-1Η -口比咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5 -二氫- 3- [4-[4-(2 -甲氧基乙基）磺醯基]六氫吡 畊-1-基]丁基]-4-甲基-2,5-二氧代-1Η- ρ比咯-1-基]-2-(三氟甲基）苯甲腈4- [2,5 -Dihydro-3- [4- [4-[[2- (2-methoxyethoxy) ethoxy) ethenyl] hexahydropyridin-1-yl] but Yl] -4 -methyl-2,5 -dioxo-l-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4- [4- [4- (cyclopropyl Sulfofluorenyl) hexahydropyridin-1-yl] butyl] -2,5 -dihydro-3-methyl-2,5 -dioxo-1fluorene -pyrrol-1-yl] -2 -(Trifluoromethyl) benzonitrile 4- [2,5 -dihydro- 3- [4- [4- (2-methoxyethyl) sulfonyl] hexahydropyridine-1-yl] Butyl] -4-methyl-2,5-dioxo-1'-ρ-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[2,5-二氫- 3-[4-[4-[[2-(2 -甲氧基乙氧基）乙基）磺 醯基]六氫吡畊-1 -基]丁基]-4 -甲基-2，5 -二氧代-1 Η -吡 咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[4-[4-[[2-[2-(2 -甲氧基乙氧基）乙氧基] 乙基）磺醯基]六氫吡畊-1-基]丁基]-4 -甲基- 2,5-二氧 代-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]丁基]-11^-二甲基六氫 吡畊-1 -磺醯胺 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[4-[4-(苯基磺醯 基）六氫咕畊-1 -基]丁基]-1 Η -说咯-1 -基]-2 -(三氟甲基） 苯甲月f -18- 2003011174- [2,5-dihydro- 3- [4- [4-[[2- (2-methoxyethoxy) ethyl) sulfofluorenyl] hexahydropyridine-1 -yl] butyl ] -4 -methyl-2,5 -dioxo-1 Η -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-[4 -[4-[[2- [2- (2-methoxyethoxy) ethoxy] ethyl) sulfofluorenyl] hexahydropyridin-1-yl] butyl] -4 -methyl- 2,5-dioxo-1 pyrene-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4- [1- [4-cyano-3- (trifluoromethyl) ) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] butyl] -11 ^ -dimethylhexahydropyridine-1- Sulfonamide 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [4- [4- (phenylsulfonyl) hexahydrocohen-1 -yl] Butyl] -1 hydrazone-sulphone-1 -yl] -2-(trifluoromethyl) benzyl f -18- 200301117 4-[2,5 -二氫-3-甲基-4-[4-[4-(甲基磺醯基）六氫吡畊 -1-基]丁基]-2,5-二氧代-1HK:咯-1-基]-2-(三氟甲基） 苯甲月f 4-[2,5 -二氫-3-甲基-4-[4-[4-[(4-甲基苯基）磺醯基] 六氫说畊-1-基]丁基]-2,5-二氧代-1H-说咯-1-基]-2-(三氟甲基）苯甲腈 心4-[[4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫 -4 -甲基-2，5 -二氧代-1 Η -吡咯-3 -基]丁基]六氫吡畊-1 - 基]磺醯基]苯基]乙醯胺 4-[3-[4-[4-[(4 -氯苯基）磺醯基]六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[4-[4-[(4-氰基苯基）磺醯基]六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3·甲基- 4-[4-[4-[(莕-2-基）磺醯基]六氫 口比畊-1 -基]丁基]-2，5 -二氧代-1 Η - ρ比咯-1 -基]-2 -(三氟 甲基）苯甲腈 4-[3-[4-[4-[(喹啉-8-基）磺醯基]六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[4-[4-[(2-氰基苯基）磺醯基]六氫吡畊-1-基]丁 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 基）苯甲腈 -19-4- [2,5 -dihydro-3-methyl-4- [4- [4- (methylsulfonyl) hexahydropyridin-1-yl] butyl] -2,5-dioxo -1HK: role-1-yl] -2- (trifluoromethyl) benzyl f 4- [2,5-dihydro-3-methyl-4- [4- [4-[(4-methyl Phenyl) sulfonyl] hexahydrol-1-yl] butyl] -2,5-dioxo-1H-syl-1-yl] -2- (trifluoromethyl) benzonitrile Heart 4-[[4- [4- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4 -methyl-2,5-dioxo -1 hydrazone -pyrrole-3 -yl] butyl] hexahydropyridine-1 -yl] sulfofluorenyl] phenyl] ethanamine 4- [3- [4- [4-[(4-chlorophenyl ) Sulfofluorenyl] hexahydropyridin-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 ''-pyrrole-1-yl] -2- ( Trifluoromethyl) benzonitrile 4- [3- [4- [4-[(4-cyanophenyl) sulfonyl] hexahydropyridin-1-yl] butyl] -2,5 -di Hydrogen-4-methyl-2,5-dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3 · methyl- 4- [4- [4-[(fluoren-2-yl) sulfofluorenyl] hexahydropyridine-1 -yl] butyl] -2,5 -dioxo-1 Η-ρ 比 咯 -1 -Yl] -2-(trifluoromethyl) benzonitrile 4- [3- [4- [4-[(quinolin-8-yl) sulfonyl] hexahydropyridine-1-yl] butyl ] -2,5 -dihydro 4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4-[(2-cyano Phenyl) sulfofluorenyl] hexahydropyridin-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1fluorene-pyrrole-1-yl]- 2- (triyl) benzonitrile 20030111? 4-(3-[4-[4-[(3-氰基苯基）磺醯基]六氫吡畊-1-基]丁 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-口比咯-1-基]-2-(三 氟甲基）苯甲腈 4 - [ 3 - [ 4 - [ 4 - [( 3，5 -二甲基異呤唑-4 -基）磺醯基]六氫吡 畊-1-基]丁基]-2,5 -二氫-4 -甲基-2,5 -二氧代-1H -吡咯 -1-基]-2-(三氟甲基）苯甲腈 4-[3-[4-[4-[(5 -氯-1，3-二甲基-1H -吡唑-4-基）磺醯基] 六氫吡畊-1-基]丁基]-2,5-二氫-4-甲基-2,5-二氧代 -1H-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基- 4- [4-[4-[(l -甲基-1H -咪唑-4-基） 磺醯基]六氫吡畊-1 -基]丁基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[4-[4-( 丁基磺醯基）六氫吡畊-1-基]丁基]-2,5-二氫-4-甲基-2，5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]丁基]-Ν-苯基六氫吡畊 -1 -複S&胺 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-11吡咯-3-基]丁基]->^(莕-1-基）六氫 吡畊-1 -羧醯胺 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-lH-^：咯-3-基]丁基]-N-(莕-2-基）六氫 吡畊-1 -羧醯胺 -20- 20030111720030111? 4- (3- [4- [4-[(3-cyanophenyl) sulfofluorenyl] hexahydropyridine-1-yl] butyl] -2,5-dihydro-4-methyl -2,5-dioxo-1H-pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[4-[4-[(3,5 -dimethyl Isopurazol-4-yl) sulfofluorenyl] hexahydropyridin-1-yl] butyl] -2,5-dihydro-4 -methyl-2,5 -dioxo-1H -pyrrole- 1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4-[(5-chloro-1,3-dimethyl-1H-pyrazol-4-yl) Sulfonyl] hexahydropyridin-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (tri Fluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl- 4- [4- [4-[(l-methyl-1H-imidazol-4-yl) sulfonyl] hexa Hydropyridine-1 -yl] butyl] -2,5-dioxo-1 Η -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [ 4- (Butylsulfonyl) hexahydropyridin-1-yl] butyl] -2,5-dihydro-4-methyl-2,5-dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1H-pyrrole-3-yl] butyl] -N-phenylhexahydropyrine-1-complex S & amine 4- [4- [1- [4-cyano-3 -( Fluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-11pyrrole-3-yl] butyl]-> ^ (fluoren-1-yl) hexa Pyridoxine-1 -carboxamide 4- [4- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5 -Dioxo-lH-^: pyr-3-yl] butyl] -N- (fluoren-2-yl) hexahydropyrine-1 -carboxamide-20- 200301117 N-(2-氯苯基）-4-[4-[l-[4-氰基-3-(三氟甲基）苯 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-3-基]丁基] 六氫？比p井-1 -竣酿胺 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1^吡咯-3-基]丁基]-^[2-(三氟甲基） 苯基]六氫吡畊-1 -羧醯胺 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-；^-吡咯-3-基]丁基]-1(3-甲氧基苯基）· 六氫？比p井-1 -竣si胺 N-(4-氯苯基）-4-[4-[1-[4-氰基-3-(三氟甲基）苯 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -吡咯-3-基]丁基] 六氫吡畊-1 -羧醯胺 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]丁基]^-(4-苯氧基苯基） 六氫吡畊-1 -羧醯胺N- (2-chlorophenyl) -4- [4- [l- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2, 5-dioxo-1H-pyrrole-3-yl] butyl] hexahydro? Than p-well-1-Junnamine 4- [4- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5 -Dioxo-1 ^ pyrrole-3-yl] butyl]-^ [2- (trifluoromethyl) phenyl] hexahydropyrine-1 -carboxamide 4- [4- [1- [4 -Cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-; ^-pyrrole-3-yl] butyl] -1 (3-methoxyphenyl) · Hexahydro? Than p-well-1-Junsiamine N- (4-chlorophenyl) -4- [4- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5 -di Hydrogen-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] butyl] hexahydropyrine-1 -carboxamidine 4- [4- [1- [4-cyano- 3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] butyl] ^-(4-phenoxy Phenyl) hexahydropyrine-1 -carboxamide 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯-3-基]丁基]-N-[4-(甲基硫烷 基）苯基]六氫吡畊-1-羧醯胺 Ν-[(1，Γ-聯苯基）-2-基]-4-[4-[l-[4 -氰基-3-(三氟甲 基）苯基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -吡咯-3-基] 丁基]六氫吡畊-1-羧醯胺 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]丁基]-〜（2,5-二甲氧基 苯基）六氫吡畊-1 -羧醯胺 -21 - 20030111?4- [4- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole- 3-yl] butyl] -N- [4- (methylsulfanyl) phenyl] hexahydropyridine-1-carboxamide N-[(1, Γ-biphenyl) -2-yl] -4- [4- [l- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole -3-yl] butyl] hexahydropyridine-1-carboxamide 4- [4- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro -4-methyl-2,5-dioxo-111-pyrrole-3-yl] butyl]-~ (2,5-dimethoxyphenyl) hexahydropyridine-1 -carboxamide- 21-20030111? 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-说咯-3-基]丁基]以-[2-(1-甲基乙基） 苯基]六氫吡畊-1 -羧醯胺 4-[4-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯-3-基]丁基]-N-(2,4,6-三甲基 苯基）六氫说_ - 1 -致S盛胺 (R)-4-[4-[l-[4-氰基- 3-(三氟甲基）苯基]-2,5-二氫-4-甲基-2,5-二氧代-111-吡咯-3-基]丁基]-^(1-苯基乙基） 六氫吡畊-1 -羧醯胺 4-[4-[1-[4-氰基- 3-(三氟甲基）苯基]·2,5-二氫-4 -甲 基-2,5-二氧代-111-口比咯-3-基]丁基]-1^-[2-(1，1-二甲基 乙基）苯基]六氫吡畊-1 -羧醯胺 4-[4-[1-[4-氣基- 3- (二氣甲基）冬基]-2,5-> — 鼠-4 -甲 基-2,5-二氧代-1Η-说咯-3-基]丁基]-Ν -己基六氫吡畊 -1 -叛S&胺 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[5-[4-(吡畊-2-基） 六氫吡畊-1 -基]戊基]-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯 甲月f 4-[3-[5-[4-(2,4-二氟苯基）六氫吡畊-1-基]戊基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基） 苯甲月f 4-[3-[5-[4-[(呋喃-2 -基）羰基]六氫吡畊-1-基]戊 基]-2,5-二氫-4-甲基-2,5-二氧代-111-吡咯-1-基]-2-(三 氟甲基）苯甲腈 -22- 2003011174- [4- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-speak -3-yl] butyl]-[2- (1-methylethyl) phenyl] hexahydropyridine-1 -carboxamidin 4- [4- [1- [4-cyano-3- (Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] butyl] -N- (2,4,6 -Trimethylphenyl) hexahydrogenation--1-Causes Samine (R) -4- [4- [l- [4-cyano-3- (trifluoromethyl) phenyl] -2, 5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] butyl]-^ (1-phenylethyl) hexahydropyridine-1 -carboxamide 4 -[4- [1- [4-cyano-3- (trifluoromethyl) phenyl] · 2,5-dihydro-4 -methyl-2,5-dioxo-111- -3-yl] butyl] -1 ^-[2- (1,1-dimethylethyl) phenyl] hexahydropyridine-1 -carboxamide 4- [4- [1- [4- Gaso-3- (diaminomethyl) hexyl] -2,5- > — mouse-4-methyl-2,5-dioxo-1Η-salrol-3-yl] butyl]- Ν-hexylhexahydropyracin-1 -S-amine 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [5- [4- (pyracin-2 -Yl) hexahydropyridine-1 -yl] pentyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzyl f 4- [3- [5- [4- ( 2,4-difluorophenyl) hexahydropyridine-1-yl ] Pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzyl f 4- [3 -[5- [4-[(furan-2-yl) carbonyl] hexahydropyridine-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo- 111-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile-22- 200301117 4-[2,5 -二氫-3-甲基- 4_[5-[4-[(5 -甲基異噚唑-3-基）羰 基]六氫吡畊-1 -基]戊基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-(苯基乙醯 基）六氫吡畊-1 -基]戊基]-1 Η -吡咯-1 -基]-2 -(三氟甲基） 苯甲月青4- [2,5-dihydro-3-methyl-4_ [5- [4-[(5-methylisoxazol-3-yl) carbonyl] hexahydropyridine-1 -yl] pentyl] -2,5 -dioxo-1 Η -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-di Oxo-4- [5- [4- (phenylethylfluorenyl) hexahydropyridine-1 -yl] pentyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzene Jiayueqing 4-[2,5 -二氫- 3- [5-[4-(4-甲氧基苯甲醯基）六氫吡畊 -1-基]戊基]-4 -甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5 -二氫-3-[5-[4-(2-甲氧基苯甲醯基）六氫吡畊 -1-基]戊基]-4 -甲基-2,5 -二氧代-1Η -叶匕咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-[5-[4-(甲氧基乙醯基）六氫吡畊-1-基] 戊基]_4_甲基·2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基） 苯甲月青4- [2,5 -Dihydro- 3- [5- [4- (4-methoxybenzylidene) hexahydropyridin-1-yl] pentyl] -4 -methyl-2,5 -Dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- [5- [4- (2-methoxybenzene (Methylfluorenyl) hexahydropyridin-1-yl] pentyl] -4 -methyl-2,5-dioxo-1fluorene-pyrrol-1-yl] -2- (trifluoromethyl) benzene Nitrile 4- [2,5-dihydro-3- [5- [4- (methoxyethylfluorenyl) hexahydropyridin-1-yl] pentyl] _4_methyl · 2,5 -di Oxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzazine 4-[3-[5-[4-(2-氯苯甲醯基）六氫吡畊-1-基]戊 基]-2,5 -二氫-4-甲基-2,5-二氧代-111-吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[5-[4-(2-氟苯甲醯基）六氫吡畊-1-基]戊 基]-2,5 -二氫-4-甲基-2,5-二氧代-111-吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[5-(4-苯甲醯基六氫吡畊-1-基）戊基]-2,5-二氫 -4 -甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基）苯甲 腈 -23-4- [3- [5- [4- (2-Chlorobenzyl) hexahydropyridine-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-di Oxo-111-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4- (2-fluorobenzylfluorenyl) hexahydropyroxy-1-ene Yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3 -[5- (4-benzylidenehexahydropyridin-1-yl) pentyl] -2,5-dihydro-4 -methyl-2,5 -dioxo-1fluorene -pyrrole-1- Phenyl] -2- (trifluoromethyl) benzonitrile-23- 200301117 4-[3-[5-[4-(環丁基羰基）六氫吡畊-1_基]戊基]-2,5-二氮-4 -甲基-2，5 --一氧i代-1 Η - ?比洛-1-基]-2-(二氣甲基） 苯甲月膏 4-[3-[5-[4-(3,4 -二甲氧基苯甲醯基）六氫吡畊-1-基] 戊基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[5-[4-(吡畊-3-基） 羰基]六氫吡畊-1-基]戊基]-1Η-吡咯-1-基]-2-(三氟甲 基）苯甲腈 4 —[3-[5-[4_(環丙基羰基）六氫吡畊-1-基]戊基]-2,5-二氫-4-甲基-2,5-二氧代-1^1-吡咯-1-基]-2-(三氟甲基） 苯甲月膏 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-(吡畊-4-基） 羰基]六氫吡畊-1-基]戊基]-1Η-吡咯-1-基]-2-(三氟甲 基）苯甲腈 4-[3-[5-[4-[4-(二甲基胺基）苯甲醯基]六氫吡畊-1-基] 戊基]-2,5 -二氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4 - [ 2，5 -二氫-3 -甲基-2，5 -二氧代-4 - [ 5 - [ 4 -(苯基硫烷 基）乙醯基]六氫吡畊-1 -基]戊基]-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[5-[4-(苯氧基乙 醯基）六氫吡畊-1 -基]戊基]-1 Η -吡咯-1 -基]-2 -(三氟甲 基）苯甲腈 -24- 200301117200301117 4- [3- [5- [4- (Cyclobutylcarbonyl) hexahydropyridine-1_yl] pentyl] -2,5-diaza-4 -methyl-2,5 --monooxy i-generation -1 Η-? bilo-1-yl] -2- (difluoromethyl) benzyl cream 4- [3- [5- [4- (3,4-dimethoxybenzidine) Yl) hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl Benzoylnitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [5- [4- (pyracin-3-yl) carbonyl] hexahydropyracine -1-yl] pentyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4 — [3- [5- [4_ (cyclopropylcarbonyl) hexahydropyridine- 1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 ^ 1-pyrrole-1-yl] -2- (trifluoromethyl) benzyl Paste 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [5- [4- (pyridin-4-yl) carbonyl] hexahydropyridine-1-yl ] Pentyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4- [4- (dimethylamino) benzyl) ] Hexahydropyridine-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl ) Benzonitrile 4-[2,5-dihydro-3 -methyl-2,5-dioxo-4-[5-[4-(phenylsulfanyl) ethenyl ] Hexahydropyridine-1 -yl] pentyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5 -dihydro-3-methyl- 2,5-dioxo-4- [5- [4- (phenoxyethenyl) hexahydropyridine-1 -yl] pentyl] -1 hydrazone -pyrrole-1 -yl] -2-( Trifluoromethyl) benzonitrile-24- 200301117 4-[2,5-二氮-3-甲基-2,5-二氧代-4-[5-[4-(0塞-2-基）談 基]六氫吡畊-1 -基]戊基]-1 Η -说咯-1 -基]-2 -(三氟甲基） 苯甲月f 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-(3-苯基-1-氧代丙基）六氫吡畊-1 -基]戊基]-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯甲腈4- [2,5-Diaza-3-methyl-2,5-dioxo-4- [5- [4- (0Cet-2-yl) yl] hexahydropyrimyl-1 -yl ] Pentyl] -1 hydrazone-single-1 -yl] -2-(trifluoromethyl) benzyl f 4- [2,5-dihydro-3-methyl-2,5-dioxo -4- [5- [4- (3-phenyl-1-oxopropyl) hexahydropyridine-1 -yl] pentyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoro Methyl) benzonitrile 4 - [ 3 - [ 5 - [ 4 - [(1，3 -苯并二呤茂-5 -基）羰基]六氫吡畊 -1-基]戊基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫- 3- [5-[4-[(4 -甲氧基苯基）乙醯基]六氫吡 畊-1-基]戊基]-4-曱基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-4-[5-[4-(2 -甲基苯甲醯基）六氫 吡畊-1 -基]戊基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈4-[3-[5-[4-[(1,3-benzobenzodino-5 -yl) carbonyl] hexahydropyridin-1-yl] pentyl] -2,5 -dihydro-4 -Methyl-2,5 -dioxo-1Η -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5 -dihydro- 3- [5- [4- [(4-methoxyphenyl) ethylfluorenyl] hexahydropyridin-1-yl] pentyl] -4-fluorenyl-2,5-dioxo-1fluorenyl-pyrrole-1-yl] -2 -(Trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4- [5- [4- (2-methylbenzylhydrazyl) hexahydropyroxy-1- Yl] pentyl] -4-methyl-2,5-dioxo-1 fluorene-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[5-[4-(嘧-2-基）乙 醯基]六氫吡畊-1 -基]戊基]-1 Η -吡咯-1 -基]-2 -(三氟甲 基）苯甲腈 4-[3-[5-[4-[(4-氯苯氧基）乙醯基]六氫吡畊-1-基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -口比咯-1-基]-2-(三 氟甲基）苯甲腈 4 - [ 3 - [ 5 - [ 4 - (3 -環戊基-1 -氧代丙基）六氫吡畊-1 -基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 -25 - 2003011174- [2,5 -dihydro-3-methyl-2,5-dioxo-4- [5- [4- (pyrim-2-yl) ethenyl] hexahydropyridine-1 -yl ] Pentyl] -1 fluorene-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [3- [5- [4-[(4-chlorophenoxy) ethenyl] Hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrol-1-yl] -2- (trifluoromethyl Phenyl) benzonitrile 4-[3-[5-[4-(3-cyclopentyl-1 -oxopropyl) hexahydropyridine-1 -yl] pentyl] -2,5 -dihydro- 4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile-25-200301117 4-[3-[5-[4-(3-氯苯甲醯基）六氫吡畊-1-基]戊 基]-2,5-二氫-4-甲基-2,5-二氧代-1!^-吡咯-1-基]-2_(三 氟甲基）苯甲腈 4-[3-[5-[4-(3,3-二甲基-1-氧代丁基）六氫吡畊-1-基] 戊基]-2,5 -二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈4- [3- [5- [4- (3-chlorobenzylidene) hexahydropyridine-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-di Oxo-1! ^-Pyrrole-1-yl] -2_ (trifluoromethyl) benzonitrile 4- [3- [5- [4- (3,3-dimethyl-1-oxobutyl) ) Hydroxypyrine-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl ) Benzonitrile 4-[2,5-二氫-3 -甲基- 4-[5-[4-(3 -甲基-1-氧代 丁基）六 氫吡畊-1 -基]戊基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯甲腈 4-[2,5-二氫-4-甲基-2,5-二氧代-3-[5-[4-[(苯基甲氧 基）乙醯基]六氫吡畊-1 -基]戊基]-1 Η -咐咯-1 -基]-2 -(三 氟甲基）苯甲腈 4-[3-[5-[4-(環戊基乙醯基）六氫吡畊-1-基]戊 基]-2,5 -二氫-4-甲基-2,5-二氧代-1Η ^比咯-1-基]-2-(三 氟甲基）苯甲腈4- [2,5-Dihydro-3 -methyl- 4- [5- [4- (3- (methyl-1-oxobutyl) hexahydropyridine-1 -yl] pentyl] -2 , 5 -dioxo-1 Η -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-4-methyl-2,5-dioxo -3- [5- [4-[(Phenylmethoxy) ethenyl] hexahydropyridine-1 -yl] pentyl] -1 咐-咐 -1 -yl] -2-(trifluoro Methyl) benzonitrile 4- [3- [5- [4- (cyclopentylethylfluorenyl) hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1H ^ pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[5-[4-(2,6-二氟苯甲醯基）六氫吡畊-1-基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代- lH-p比咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[5-[4-(2,6-二氯苯甲醯基）六氫吡畊-1-基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基- 2,5-二氧代-4-[5-[4-[2-三氟甲基] 苯甲醯基]六氫吡畊-1 -基]戊基]-1 Η - 4咯-1 -基]-2 -(三 氟甲基）苯甲腈 -26- 2003011174- [3- [5- [4- (2,6-difluorobenzylidene) hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4-methyl-2, 5-dioxo-lH-p-pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4- (2,6-dichlorobenzylfluorenyl) ) Hydroxypyrine-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl ) Benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [5- [4- [2-trifluoromethyl] benzamyl] hexahydro Pycnogenol-1 -yl] pentyl] -1 hydrazone -4role-1 -yl] -2-(trifluoromethyl) benzonitrile-26- 200301117 4-[3-[5-[4-(3-氟苯甲醯基）六氫吡畊-1-基]戊 基]-2,5-二氫-4-甲基-2,5-二氧代-1H -咕咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基- 2,5-二氧代- 4-[5-[4-[3-三氟甲基] 苯甲醯基]六氫吡畊-1 -基]戊基]-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯甲腈4- [3- [5- [4- (3-fluorobenzylidene) hexahydropyridine-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5-di Oxo-1H -coro-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl- 2,5-dioxo- 4- [ 5- [4- [3-trifluoromethyl] benzylidene] hexahydropyridine-1 -yl] pentyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzene Nitrile 4-[2,5 -二氫-3 -甲基-4-[5-[4-(4-甲基苯甲醯基）六氫 吡畊-1 -基]戊基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2 -(三氟 甲基）苯甲腈 4-[2,5 -二氫-3-甲基-4-[5-[4-[(莕-1-基）羰基]六氫吡 畊-1 -基]戊基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2 -(三氟甲 基）苯甲腈 4-[2,5-二氫-3-甲基-4-[5-[4-[(莕-2-基）羰基]六氫吡 畊-1-基]戊基]-2,5-二氧代- ΙΗ-说咯-1-基]-2-(三氟甲 基）苯甲腈4- [2,5 -Dihydro-3 -methyl-4- [5- [4- (4-methylbenzylidene) hexahydropyridine-1 -yl] pentyl] -2,5- Dioxo-1 fluorene-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4- [5- [4-[( Fluoren-1-yl) carbonyl] hexahydropyridine-1 -yl] pentyl] -2,5-dioxo-1 fluorene -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4- [5- [4-[(fluoren-2-yl) carbonyl] hexahydropyridin-1-yl] pentyl] -2,5- Dioxo-l-syl-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[5-[4-(3-氰基苯甲醯基）六氫吡畊-1-基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η-吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[5-[4-(環己基羰基）六氫吡畊-1-基]戊基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲月青 4-[3-[5-(4 -乙醯基六氫吡畊-1-基）戊基]-2,5-二氫-4-甲基-2,5-二氧代-lH-吡咯-l-基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫- 3- [5-[4-(3 -甲氧基-1-氧代丙基）六氫吡 -27- 2003011174- [3- [5- [4- (3-Cyanobenzyl) hexahydropyridine-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5- Dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4- (cyclohexylcarbonyl) hexahydropyridine-1-yl] pentane Group] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzazine 4- [3- [ 5- (4-Ethylhexylpyridin-1-yl) pentyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-pyrrole-l-yl]- 2- (trifluoromethyl) benzonitrile 4- [2,5 -dihydro- 3- [5- [4- (3- (methoxy-1-oxopropyl) hexahydropyridine-27- 200301117 畊-1 -基]戊基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[5-[4-[(2 -甲氧基乙氧基）乙醯基]六氫 吡畊-1 -基]戊基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈Geng-1 -yl] pentyl] -4 -methyl-2,5-dioxo-1 hydrazone -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2,5 -Dihydro- 3- [5- [4-[(2-methoxyethoxy) ethenyl] hexahydropyridine-1 -yl] pentyl] -4 -methyl-2,5-di Oxo-1 pyrene-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4-[2,5 -二氫- 3-[5-[4-[[2-(2-甲氧基乙氧基）乙氧基] 乙醯基]六氫吡畊-1-基]戊基]-4 -甲基-2,5 -二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4 - [ 4 - [ 5 - [ 4 -(環丙基磺醯基）六氫吡畊-1 -基]戊 基]-2,5 -二氫-3-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-[5-[4-(2 -甲氧基乙基）磺醯基]六氫吡 畊-1 -基]戊基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈4- [2,5 -dihydro- 3- [5- [4-[[2- (2-methoxyethoxy) ethoxy] ethenyl] hexahydropyridin-1-yl] pentane Yl] -4 -methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[4-[5-[4-(cyclopropyl Sulfofluorenyl) hexahydropyridine-1 -yl] pentyl] -2,5-dihydro-3-methyl-2,5-dioxo-1fluorene-pyrrole-1-yl] -2- ( Trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- [5- [4- (2-methoxyethyl) sulfonyl] hexahydropyridine-1 -yl] pentyl ] -4 -methyl-2,5-dioxo-1 fluorene -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4-[2,5-二氫- 3-[5-[4-[[2-(2-甲氧基乙氧基）乙基]磺 醯基]六氫吡畊-1 -基]戊基]-4 -甲基-2，5 -二氧代-1 Η -吡 咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[5-[4-[[2-[2-(2 -甲氧基乙氧基）乙氧基] 乙基]磺醯基]六氫吡畊-1-基]戊基]-4-甲基-2,5-二氧 代-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lH-咕咯-3-基]戊基]-N，N-二甲基六氫 吡畊-1 -磺醯胺 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-[(1-甲基乙 -28- 20030111?4- [2,5-Dihydro- 3- [5- [4-[[2- (2-methoxyethoxy) ethyl] sulfofluorenyl] hexahydropyridine-1 -yl] pentyl ] -4 -methyl-2,5-dioxo-1 Η -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-[5 -[4-[[2- [2- (2-methoxyethoxy) ethoxy] ethyl] sulfofluorenyl] hexahydropyridin-1-yl] pentyl] -4-methyl- 2,5-dioxo-1 pyrene-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [5- [1- [4-cyano-3- (trifluoromethyl) ) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-gall-3-yl] pentyl] -N, N-dimethylhexahydropyridine- 1-sulfamethoxamine 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [5- [4-[(1-methylethyl-28- 20030111? 基）磺醯基]六氫吡畊-1 -基]戊基]-1 Η -说咯-1 -基]-2 -(三 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-(苯基磺醯 基）六氫吡畊-1-基]戊基]-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲腈 4 - [ 2，5 -二氫-3 -甲基-4 - [ 5 - [ 4 ·(曱基磺醯基）六氫吡畊 -1-基]戊基]-2,5 -二氧代-1Η-吡咯-1-基]-2-(三氟甲基）Sulfofluorenyl] hexahydropyridine-1 -yl] pentyl] -1 hydrazone -single-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro -3-methyl-2,5-dioxo-4- [5- [4- (phenylsulfonyl) hexahydropyridin-1-yl] pentyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[2,5-dihydro-3 -methyl-4-[5-[4 · (fluorenylsulfonyl) hexahydropyridine-1-yl ] Pentyl] -2,5-dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) 苯甲腈 4-[3-[5-[4-[(4-氯苯基）磺醯基]六氫吡畊-1-基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[5-[4-(苯基甲基） 磺醯基]六氫吡畊-1 -基]戊基]-1 Η -吡咯-1 -基]-2 -(三氟 甲基）苯甲腈Benzonitrile 4- [3- [5- [4-[(4-chlorophenyl) sulfonamido] hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4-methyl -2,5 -dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo 4- [5- [4- (phenylmethyl) sulfofluorenyl] hexahydropyridine-1 -yl] pentyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl ) Benzonitrile 4-[3-[5-[4-[(4-氰基苯基）磺醯基]六氫吡啩-1-基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -叶匕咯-1-基]-2-(三 氟甲基）苯甲腈 4 - [ 4 - [ 5 - [ 4 -[(喹啉-8 -基）磺醯基]六氫吡畊-1 -基]戊 基]-2,5 -二氫-3-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[5-[4-[(2-氟苯基）磺醯基]六氫吡啡-1-基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代- lH-p比咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[5-[4-[(2,5-二甲氧基苯基）磺醯基]六氫吡畊-1- -29- 2003011174- [3- [5- [4-[(4-cyanophenyl) sulfonamido] hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4-methyl-2 , 5 -dioxo-1H-leafyl-1-yl] -2- (trifluoromethyl) benzonitrile 4-[4-[5-[4-[(quinoline-8 -yl) sulfonate Fluorenyl] hexahydropyridine-1 -yl] pentyl] -2,5-dihydro-3-methyl-2,5-dioxo-1pyridyl-1-pyrrol-1-yl] -2- (trifluoro Methyl) benzonitrile 4- [3- [5- [4-[(2-fluorophenyl) sulfonamido] hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4 -Methyl-2,5-dioxo-lH-p than pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4-[(2,5 -Dimethoxyphenyl) sulfofluorenyl] hexahydropyroxy-1--29- 200301117 基]戊基]-2,5 -二氫-4-甲基-2,5-二氧代- ΙΗ-说咯-1-基]-2-(三氟甲基）苯甲腈 4-[3-[5-[4-[(3-氰基苯基）磺醯基]六氫吡畊-1-基]戊 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -说咯-1-基]-2-(三 氟甲基）苯甲腈[] Yl] pentyl] -2,5-dihydro-4-methyl-2,5-dioxo- 1H-syl-1-yl] -2- (trifluoromethyl) benzonitrile 4- [ 3- [5- [4-[(3-cyanophenyl) sulfonamido] hexahydropyridin-1-yl] pentyl] -2,5-dihydro-4-methyl-2,5- Dioxo-1H -Hydro-1-yl] -2- (trifluoromethyl) benzonitrile 4 - [ 3 - [ 5 - [ 4 - [(2，1，3 -苯并噻二唑-4 -基）磺醯基]六氫吡 畊-1-基]戊基]-2,5 -二氫-4 -甲基-2,5 -二氧代-1H -吡咯 -1-基]-2-(三氟甲基）苯甲腈 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111^比咯-3-基]戊基]以-(1，1-二甲基乙 基）六氫吡畊-1-羧醯胺 4-[ 5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4 -甲 基-2,5-二氧代-111-吡咯-3-基]戊基]-^4-(莕-1-基）六氫 吡畊-1 -羧醯胺4-[3-[5-[4-[(2,1,3-Benzothiadiazol-4-yl) sulfofluorenyl] hexahydropyridin-1-yl] pentyl] -2,5- Dihydro-4 -methyl-2,5-dioxo-1H -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [5- [1- [4-cyano- 3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111 ^ pyrrol-3-yl] pentyl] to-(1,1 -Dimethylethyl) hexahydropyridine-1-carboxamide 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro- 4-methyl-2,5-dioxo-111-pyrrole-3-yl] pentyl]-^ 4- (fluoren-1-yl) hexahydropyrimidine-1 -carboxamide N-(4-氰基苯基）-4-[5-[1-[4-氰基-3-(三氟甲基）苯 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -口比咯-3-基]戊基] 六氫p比畊-1 -竣醯胺 N-(2-氯基苯基）-4-[5-[1-[4-氰基-3-(三氟甲基）苯 基]-2,5-二氫-4-甲基-2,5-二氧代-1H -吡咯-3-基]戊基] 六氫说畊-1 -叛酷胺 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111^比咯-3-基]戊基]->^[2-(三氟甲基） 苯基]六氫吡畊-1 -羧醯胺 4-[5-[1-[4-氣基-3-(二氣甲基）尽基]-2,5-二鼠-4-甲 •30- 200301117N- (4-cyanophenyl) -4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2 , 5 -dioxo-1H -pyrrol-3-yl] pentyl] hexahydropeptone-1 -endoamine N- (2-chlorophenyl) -4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] pentyl] hexa HYDROGEN-1-Benzylamine 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5 -Dioxo-111 ^ pyrrol-3-yl] pentyl]-> ^ [2- (trifluoromethyl) phenyl] hexahydropyridine-1 -carboxamide 4- [5- [1 -[4-Amino-3- (diaminomethyl) hexyl] -2,5-Dimur-4-methyl • 30- 200301117 基-2,5-二氧代-1H-咕咯-3-基]戊基]-N-(2 -甲基苯基） 六氫吡畊-1 -羧醯胺 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1?1-吡咯-3-基]戊基]以-(3-甲基苯基） 六氫p比17井-1 -致酷胺 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-外1：咯-3-基]戊基]-〜（4-氟苯基）六-2,5-dioxo-1H-gallyl-3-yl] pentyl] -N- (2-methylphenyl) hexahydropyridine-1 -carboxamide 4- [5- [1 -[4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1? 1-pyrrole-3-yl] pentane Group] to-(3-methylphenyl) hexahydro p ratio 17 wells-1-hydrazine 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl]- 2,5-dihydro-4-methyl-2,5-dioxo-111-external 1: role-3-yl] pentyl]-~ (4-fluorophenyl) hexa 氫吡畊-1 -羧醯胺 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-1H-说咯-3-基]戊基]·Ν-(4 -甲氧基苯基） 六氫p比ρ井-1 -叛酿胺 Ν-(3-^基冬基）-4-[5-[1-[4-氣基-3-(二氣甲基）冬 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-3-基]戊基] 六氫ρ比_ -1 -叛酿胺Pyridoxine-1 -carboxamide 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5 -Dioxo-1H-Hydroxy-3-yl] pentyl] · N- (4-methoxyphenyl) Hexahydro p ratio ρ Well-1-Spermatylamine N- (3- ^ Dylyl ) -4- [5- [1- [4-Gasyl-3- (difluoromethyl) dongyl] -2,5-dihydro-4-methyl-2,5 -dioxo-1Η- Pyrrole-3-yl] pentyl] hexahydroρ ratio _ -1-benzamine 4-[5-[1-[4-氰基-3-(三氟甲基）苯基卜2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]戊基]-1^-(3,5-二甲氧基 苯基）六氫ρ比17井-1 -幾St胺 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]戊基]以-(2-苯基乙基） 六氫吡畊-1 -羧醯胺 N-([l，l’-聯苯基]-2基）-4-[5-[1-[4-氰基- 3-(三氟甲基） 苯基]-2,5-二氫-4-甲基-2,5 -二氧代-1H -吡咯-3-基]戊 基]六氫吡畊-1 -羧醯胺 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 -31 - 2003011174- [5- [1- [4-cyano-3- (trifluoromethyl) phenylphenyl 2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3 -Yl] pentyl] -1 ^-(3,5-dimethoxyphenyl) hexahydroρ ratio 17 wells -1 -chi-Stamine 4- [5- [1- [4-cyano-3- (Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] pentyl] to-(2-phenylethyl ) Hexahydropyridine-1 -carboxamide N-([l, l'-biphenyl] -2yl) -4- [5- [1- [4-cyano-3- (trifluoromethyl) ) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] pentyl] hexahydropyridine-1 -carboxamide 4- [5 -[1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-31-200301117 基-2,5-二氧代-111-说咯-3-基]戊基]-^^-[2-(1-甲基乙基） 苯基]六氫吡畊-1 -羧醯胺 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-1H-吡咯-3-基]戊基]-N-(2,6-二氯吡啶 -4 -基）六氫吡畊-1 -羧醯胺 (R)-4-[5-[l-[4-氰基- 3-(三氟甲基）苯基]-2,5-二氫- 4-甲基-2,5-二氧代-111^比咯-3-基]戊基]->^(1-苯基乙基）-2,5-dioxo-111-salrol-3-yl] pentyl]-^^-[2- (1-methylethyl) phenyl] hexahydropyridine-1 -carboxamide 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1H-pyrrole- 3-yl] pentyl] -N- (2,6-dichloropyridine-4 -yl) hexahydropyridine-1 -carboxamide (R) -4- [5- [l- [4-cyano -3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111 ^ pyrrol-3-yl] pentyl]-> ^ ( 1-phenylethyl) 六氫说_ -1 -叛si胺 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-1H-吡咯-3-基]戊基]-N-(3-[(三氟甲基） 硫烷基]苯基）六氫吡畊-1 -羧醯胺 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111^比咯-3-基]戊基]-?^[(3-甲基苯基） 甲基]六氫吡畊-1 -羧醯胺Hexahydrogen _ -1-tamamine 4- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2, 5-dioxo-1H-pyrrole-3-yl] pentyl] -N- (3-[(trifluoromethyl) sulfanyl] phenyl) hexahydropyramine-1 -carboxamidine 4- [ 5- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111 ^ pyrrole-3- Yl] pentyl]-? ^ [(3-methylphenyl) methyl] hexahydropyridine-1 -carboxamide 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]戊基]-^[(4-甲氧基苯 基）甲基]六氫吡畊-1 -羧醯胺 4-[5-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-口比咯-3-基]戊基]*^-(1，1，3,3-四甲 基丁基）六氫17比_ -1 -致酿胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯-3-基]己基]六氫吡畊-1-羧酸 1，1 -二甲基乙酯 4-[2,5 -二氫-3-甲基-4-[6-(4-甲基六氫吡畊-1-基）己 -32- 2003011174- [5- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole- 3-yl] pentyl]-^ [(4-methoxyphenyl) methyl] hexahydropyridine-1 -carboxamidine 4- [5- [1- [4-cyano-3- (tri Fluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrol-3-yl] pentyl] * ^-(1,1,3 , 3-tetramethylbutyl) hexahydro 17 ratio -1 -brewing amine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5- Dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] hexahydropyrine-1-carboxylic acid 1,1-dimethylethyl ester 4- [2,5 -Dihydro-3-methyl-4- [6- (4-methylhexahydropyridin-1-yl) hex-32- 200301117 基]-2，5 -二氧代-1 Η -说咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η -吡咯-3 -基]己基]六氫吡畊-1 -羧酸 乙酉旨 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[6-[4-(吡啶-2-基） 六氫吡畊-1 -基]己基]-1 Η - ρ比咯-1 -基]-2 -(三氟甲基）苯 甲腈Yl] -2,5 -dioxo-1 fluorene -syl-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [6- [1- [4-cyano-3- ( Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 fluorene-pyrrole-3 -yl] hexyl] hexahydropyridine-1 -carboxylic acid ethylamidine 4- [2,5 -dihydro-3-methyl-2,5-dioxo-4- [6- [4- (pyridin-2-yl) hexahydropyridine-1 -yl] hexyl] -1 Η-ρbiro-1 -yl] -2-(trifluoromethyl) benzonitrile 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η -吡咯-3 -基]己基]六氫吡畊-1 -羧酸 (苯基甲酯） 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-(嘧啶-2-基） 六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯 甲腈 4-[2,5-二氫- 3-[6-[4-(2 -甲氧基苯基）六氫吡畊-1-基] 己基]-4 -甲基-2,5-二氧代-1Η -吡咯-1-基]-2-(三氟甲基）4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 Η-pyrrole -3 -yl] hexyl] hexahydropyridine-1 -carboxylic acid (phenylmethyl) 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [6- [4- (pyrimidin-2-yl) hexahydropyrimyl-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5- Dihydro- 3- [6- [4- (2-methoxyphenyl) hexahydropyridine-1-yl] hexyl] -4 -methyl-2,5-dioxo-1Η-pyrrole-1 -Yl] -2- (trifluoromethyl) 4-[2,5 -二氫-3-甲基-4-[6-(4-(2 -硝基苯基）六氫吡畊 -1-基）己基]-2,5-二氧代-1Η -吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[6-[4-(吡畊-2-基） 六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯 甲腈 4 - [ 2,5 --一鼠-3-甲基-4-[6-(4-[2-(甲基硫坑基）冬基] 六氫口比畊-1-基）己基]-2,5 -二氧代-1Η- 口比咯-Ι α - 2003011174- [2,5-dihydro-3-methyl-4- [6- (4- (2-nitrophenyl) hexahydropyridin-1-yl) hexyl] -2,5-dioxo -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [6- [ 4- (Pyridin-2-yl) hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4-[2,5- -Monorat-3-methyl-4- [6- (4- [2- (methylsulfanyl) dongyl] hexahydropyridine-1-yl) hexyl] -2,5 -dioxo -1Η- Bibi-I α-200301117 基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氮-3-甲基-2,5 -二乳代-4-[6_[4-[3-(二氣甲 基）吡啶-2 -基]六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫-3-[6-[4-(2 -甲氧基乙基）六氫吡畊-1-基] 己基]-4 -甲基-2，5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲腈Yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-diaza-3-methyl-2,5 -dilacto-4- [6_ [4- [3- (digas (Methyl) pyridine-2 -yl] hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2,5 -di Hydrogen-3- [6- [4- (2-methoxyethyl) hexahydropyridine-1-yl] hexyl] -4 -methyl-2,5-dioxo-1pyridine-1-pyrrole-1- Phenyl] -2- (trifluoromethyl) benzonitrile 4-[3-[6-[4-(3,5-二氯吡啶-4-基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4_[3-[6-[4-(4-乙醯基六氫吡畊-1-基）己基]-2,5-二氫 —4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[6-[4-[(呋喃-2-基）六氫吡畊-1-基]己基]-2,5-二 氫-4-甲基- 2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯4- [3- [6- [4- (3,5-Dichloropyridin-4-yl) hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2, 5 -dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4_ [3- [6- [4- (4-ethylfluorenylhexahydropyridine-1-yl ) Hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [ 6- [4-[(furan-2-yl) hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1fluorene-pyrrole-1 -Yl] -2- (trifluoromethyl) benzene 甲月膏 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-[(四氫呋喃 -2-基）羰基]六氫吡畊-1-基]己基]-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[3-[6-[4-(環戊基羰基）六氫吡畊-1-基]己基]-2,5-二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[2,5-二氫-3-甲基- 4-[6-(4-[(5 -甲基異吟唑-3-基）羰 基]六氫吡畊-1-基）己基]-2,5 -二氧代-1Η -吡咯-1- -34- 200301117Jiayue paste 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [6- [4-[(tetrahydrofuran-2-yl) carbonyl] hexahydropyroxy-1 -Yl] hexyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4- (cyclopentylcarbonyl) hexahydropyridine-1- Group] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2, 5-dihydro-3-methyl- 4- [6- (4-[(5-methylisoindazol-3-yl) carbonyl] hexahydropyridin-1-yl) hexyl] -2,5- Dioxo-1Η -pyrrole-1- -34- 200301117 基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-(苯基乙醯 基）六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三氟甲基） 苯甲腈 4-[2,5 -二氫- 3- [6-[4-(4-甲氧基苯甲醯基）六氫吡畊 -1-基]己基]-4 -甲基-2,5-二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈Yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [6- [4- (phenylacetamidine Hexyl) pyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5 -dihydro-3-[6- [4- (4-methoxybenzylidene) hexahydropyridin-1-yl] hexyl] -4-methyl-2,5-dioxo-1Η-pyrrole-1-yl] -2- (Trifluoromethyl) benzonitrile 4-[2,5 -二氫-3-[6-[4-(2-甲氧基苯甲醯基）六氫吡畊 -1-基]己基]-4 -甲基-2,5-二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-[6-[4-(甲氧基乙醯基）六氫吡畊-1-基] 己基]-4 -甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[3-[6-[4-(2-氯苯甲醯基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -口比咯-1-基]-2-(三4- [2,5 -dihydro-3- [6- [4- (2-methoxybenzyl) hexahydropyridine-1-yl] hexyl] -4 -methyl-2,5- Dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- [6- [4- (methoxyethyridinyl) Hexahydropyridin-1-yl] hexyl] -4 -methyl-2,5 -dioxo-1H -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4- (2-Chlorobenzyl) hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H- Pyrrol-1-yl] -2- (tri 氟甲基）苯甲腈 4-[3-[6-[4-(2-氟苯甲醯基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[6-(4-苯甲醯基六氫吡畊-1-基）己基]-2,5-二氫 -4 -甲基-2,5 -二氧代-1Η “比咯-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[6-[4-(環丁基羰基）六氫吡畊-1-基]己基]-2,5-二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基） -35 - 200301117Fluoromethyl) benzonitrile 4- [3- [6- [4- (2-fluorobenzylidene) hexahydropyridine-1-yl] hexyl] -2,5-dihydro-4-methyl -2,5 -dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- (4-benzylidene hexahydropyridine-1) -Yl) hexyl] -2,5-dihydro-4 -methyl-2,5 -dioxo-1 '"bipyr-1-yl] -2- (trifluoromethyl) benzonitrile 4- [ 3- [6- [4- (Cyclobutylcarbonyl) hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1Η-pyrrole- 1-yl] -2- (trifluoromethyl) -35-200301117 苯甲月青 4-[3-[6-[4-(3,4_二甲氧基苯甲醯基）六氫吡畊-1-基] 己基]-2,5 -二氫-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈 4 - [ 2，5 -二氫-3 -甲基-2，5 -二氧代-4 - [ 6 - [ 4 -[(苯基硫烷 基）乙醯基]六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯甲腈Benzylpyrene 4- [3- [6- [4- (3,4-dimethoxybenzylidene) hexahydropyrine-1-yl] hexyl] -2,5 -dihydro-4- Methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[2,5-dihydro-3 -methyl-2,5- Dioxo-4-[6-[4-((phenylsulfanyl) ethenyl] hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2-(tri Fluoromethyl) benzonitrile 4-[2,5 -二氫-3 -甲基-2,5-二氧代-4-[6-[4-(苯氧基乙 醯基）六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三氟甲 基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-[〇塞-2-基） 羰基]六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三氟甲 基）苯甲腈4- [2,5 -Dihydro-3 -methyl-2,5-dioxo-4- [6- [4- (phenoxyethylfluorenyl) hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [6- [4- [〇Se-2-yl) carbonyl] hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-(3-苯基-1-氧代丙基）六氫吡畊-1-基]己基]-1Η-吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[6-[4-(1，3-苯并二吟茂-5-基）羰基]六氫吡畊-1-基]己基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[6-[4-[(4 -甲氧基苯基）乙醯基]六氫吡 畊-1 -基]己基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-4-[6-[4-(2-甲基苯甲醯基）六氫 吡畊-1 -基]己基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2 -(三氟 -36- 2003011174- [2,5-Dihydro-3-methyl-2,5-dioxo-4- [6- [4- (3-phenyl-1-oxopropyl) hexahydropyracine-1 -Yl] hexyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4- (1,3-benzobisindomo-5- ) Carbonyl] hexahydropyridine-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoro Methyl) benzonitrile 4- [2,5-dihydro- 3- [6- [4-[(4-methoxyphenyl) ethenyl] hexahydropyridine-1 -yl] hexyl]- 4-methyl-2,5-dioxo-1 fluorene-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4 -[6- [4- (2-methylbenzylidene) hexahydropyridine-1 -yl] hexyl] -2,5-dioxo-1 Η -pyrrole-1 -yl] -2-( Trifluoro-36- 200301117 甲基）苯甲腈 4-[3-[6-[4-(4-氯苯甲醯基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -口比咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-[(噻-2-基） 乙醯基]六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三氟 甲基）苯甲腈Methyl) benzonitrile 4- [3- [6- [4- (4-chlorobenzylidene) hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl- 2,5 -dioxo-1H -pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-di Oxo-4- [6- [4-[(thia-2-yl) ethynyl] hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoro Methyl) benzonitrile 4-[3-[6-[4-[(4-氯苯氧基）乙醯基]六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[6-[4-(3 -環戊基-1-氧代丙基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈. 4-[3-[6-[4-(3-氯苯甲醯基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5-二氧代-111-吡咯-1-基]-2-(三4- [3- [6- [4-[(4-chlorophenoxy) ethenyl] hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2, 5-dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4- (3-cyclopentyl-1-oxopropyl) ) Hydroxypyrine-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) Benzonitrile. 4- [3- [6- [4- (3-chlorobenzylidene) hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2, 5-dioxo-111-pyrrole-1-yl] -2- (tri 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基- 2,5-二氧代- 4-[6-[4-[4-三氟甲基] 苯甲醯基]六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯甲腈 4-[3-[6-[4-(4-氰基苯甲醯基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[6-[4-(3,3-二甲基-1-氧代丁基）六氫吡畊-1-基] 己基]-2,5 -二氫-4-甲基-2,5-二氧代-1Η-吡咯-Ι α- 200301117Fluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo- 4- [6- [4- [4-trifluoromethyl] benzamidine ] Hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [3- [6- [4- (4-cyano Benzamidine) hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (tri Fluoromethyl) benzonitrile 4- [3- [6- [4- (3,3-dimethyl-1-oxobutyl) hexahydropyrine-1-yl] hexyl] -2,5- Dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1 α- 200301117 基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-4-[6-[4-(3 -甲基-1-氧代丙基）六 氫吡畊-1 -基]己基]-2，5 -二氧代-1 Η -说咯-1 -基]-2 -(三 氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-2,5-二氧代-4-[6-[4-[(苯基甲氧 基）乙醯基]六氫吡畊-1 -基]己基]-1 Η -说咯-1 -基]-2 -(三 氟甲基）苯甲腈 4 - [ 3 - [ 6 - [ 4 -(環戊基乙醯基）六氫吡畊-1 -基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[6-[4-(2,6-二氟苯甲醯基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5-二氧代-111-吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[6-[4-(2,6-二氯苯甲醯基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-[2-三氟甲基] 苯甲醯基]六氫吡畊· 1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯甲腈 4-[3-[6-[4-(3-氟苯甲醯基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5 -二氫- 3-[6-[4-(3-甲氧基苯甲醯基）六氫吡畊 -1-基]己基]-4 -甲基-2,5 -二氧代-1Η -批咯-1-基]-2-(三 -38- 200301117Yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4- [6- [4- (3-methyl-1-oxopropyl) Hexahydropyrimyl-1 -yl] hexyl] -2,5 -dioxo-1 Η -Sale-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5 -di Hydrogen-3-methyl-2,5-dioxo-4- [6- [4-[(phenylmethoxy) ethenyl] hexahydropyridine-1 -yl] hexyl] -1 Η- Say -1 -yl] -2-(trifluoromethyl) benzonitrile 4-[3-[6-[4-(cyclopentylethylfluorenyl) hexahydropyridine-1 -yl] hexyl]- 2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4 -(2,6-difluorobenzylidene) hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-1 -Yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4- (2,6-dichlorobenzylidene) hexahydropyridin-1-yl] hexyl]- 2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro- 3-methyl-2,5-dioxo-4- [6- [4- [2-trifluoromethyl] benzamidine] hexahydropyridine · 1-yl] hexyl] -1 Η-pyrrole -1 -yl] -2-(trifluoromethyl) benzonitrile 4- [3- [6- [4- (3-fluorobenzylhydrazyl) hexa Pyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzyl Nitrile 4- [2,5 -dihydro- 3- [6- [4- (3-methoxybenzylidene) hexahydropyrine-1-yl] hexyl] -4 -methyl-2,5 -Dioxo-1Η-pyrrol-1-yl] -2- (tri-38- 200301117 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-[3-三氟甲基] 苯甲醯基]六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-4-[6-[4_(3 -甲基苯甲醯基）六氫 吡畊-1 -基]己基]-2,5 -二氧代-1 Η -吡咯-1 -基]-2 -(三氟 甲基）苯甲腈Fluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [6- [4- [3-trifluoromethyl] benzamidine ] Hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5 -dihydro-3-methyl-4 -[6- [4_ (3-methylbenzylidene) hexahydropyridine-1 -yl] hexyl] -2,5 -dioxo-1 Η -pyrrole-1 -yl] -2-(tri Fluoromethyl) benzonitrile 4-[3-[6-[4-(4-氟苯甲醯基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-4-[6-[4-(4-甲基苯甲醯基）六氫 吡畊-1-基]己基]-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟 甲基）苯甲腈 4-[2,5-二氫-3-甲基- 4-[6-[4-[(莕-1-基）羰基]六氫吡 畊-1 -基]己基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2 -(三氟甲4- [3- [6- [4- (4-fluorobenzylidene) hexahydropyridine-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5 -dioxy -1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4- [6- [4- (4-methyl Benzamidine) hexahydropyridin-1-yl] hexyl] -2,5-dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2, 5-dihydro-3-methyl- 4- [6- [4-[(fluoren-1-yl) carbonyl] hexahydropyridine-1 -yl] hexyl] -2,5-dioxo-1 Η -Pyrrole-1 -yl] -2-(trifluoromethyl 基）苯甲腈 4-[2,5-二氫-3-甲基- 4-[6-[4-[(莕-2-基）羰基]六氫吡 畊-1-基]己基]-2,5-二氧代·1Η-吡咯-1-基]-2-(三氟甲 基）苯曱腈 4-[3-[6-[4-(3-氰基苯甲醯基）六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[6-[4-(環己基羰基）六氫吡畊-1-基]己基]-2,5-二氫-4 -甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） -39- 200301117Phenyl) benzonitrile 4- [2,5-dihydro-3-methyl- 4- [6- [4-[(fluoren-2-yl) carbonyl] hexahydropyridin-1-yl] hexyl]- 2,5-dioxo · 1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4- (3-cyanobenzyl) yl] hexa Pyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzyl Nitrile 4- [3- [6- [4- (cyclohexylcarbonyl) hexahydropyridine-1-yl] hexyl] -2,5-dihydro-4 -methyl-2,5-dioxo-1Η -Pyrrole-1-yl] -2- (trifluoromethyl) -39- 200301117 苯甲腈 4-[2,5 -二氫- 3- [6-[4-(3 -甲氧基-1-氧代丙基）六氫吡 畊-1 -基]己基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫- 3- [6-[4-[(2 -甲氧基乙氧基）乙醯基]六氫 吡畊-1 -基]己基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈Benzonitrile 4- [2,5 -dihydro- 3- [6- [4- (3- (methoxy-l-oxopropyl) hexahydropyrine-1 -yl] hexyl] -4 -methyl -2,5 -dioxo-1 hydrazone -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2,5 -dihydro- 3- [6- [4- [ (2-Methoxyethoxy) ethenyl] hexahydropyridine-1 -yl] hexyl] -4 -methyl-2,5-dioxo-1 fluorene -pyrrole-1 -yl] -2 -(Trifluoromethyl) benzonitrile 4-[2,5 -二氫- 3-[6-[4-[[2-(2 -甲氧基乙氧基）乙氧基] 乙醯基]六氫吡畊-1-基]己基]-4 -甲基-2,5-二氧代-lH-吡咯-l-基]-2-(三氟甲基）苯甲腈 4 - [ 4 - [ 6 - [ 4 -(環丙基磺醯基）六氫吡畊-1 -基]己 基]-2,5 -二氫-3-甲基-2,5 -二氧代- lH-p比咯-1-基]-2-(三 氟甲基）苯甲腈4- [2,5 -dihydro- 3- [6- [4-[[2- (2-methoxyethoxy) ethoxy] ethenyl] hexahydropyridin-1-yl] hexyl ] -4 -methyl-2,5-dioxo-lH-pyrrole-l-yl] -2- (trifluoromethyl) benzonitrile 4-[4-[6-[4-(cyclopropyl Sulfonyl) hexahydropyridine-1 -yl] hexyl] -2,5-dihydro-3-methyl-2,5-dioxo-lH-ppyrrol-1-yl] -2- ( Trifluoromethyl) benzonitrile 4-[2,5-二氫- 3-[6-[4-(2-甲氧基乙基）磺醯基]六氫吡 畊-1 -基]己基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[6-[4-[[2-(2 -甲氧基乙氧基）乙基]磺 醯基]六氫吡畊-1 -基]己基]-4 -甲基-2，5 -二氧代-1 Η -吡 咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[6-[4-[[2-[2-(2-甲氧基乙氧基）乙氧基] 乙基]磺醯基]六氫吡畊-1-基]己基]-4 -甲基-2,5-二氧 代-1 Η -吡咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基^3-二甲基六氫 -40- 2003011174- [2,5-dihydro- 3- [6- [4- (2-methoxyethyl) sulfofluorenyl] hexahydropyridine-1 -yl] hexyl] -4 -methyl-2, 5 -dioxo-1 hydrazone -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro- 3- [6- [4-[[2- ( 2-methoxyethoxy) ethyl] sulfofluorenyl] hexahydropyrimyl-1 -yl] hexyl] -4 -methyl-2,5-dioxo-1 fluorene -pyrrole-1-yl] 2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro- 3- [6- [4-[[2- [2- (2-methoxyethoxy) ethoxy) ] Ethyl] sulfofluorenyl] hexahydropyridin-1-yl] hexyl] -4 -methyl-2,5-dioxo-1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl ) Benzonitrile 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo- 111-pyrrole-3-yl] hexyl ^ 3-dimethylhexahydro-40- 200301117 吡畊-1 -磺醯胺 4-[3-[6-[4-[[4-(l，l-二甲基乙基）苯氧基]乙醯基]六氫 吡畊-1 -基]己基]-2，5 ·二氫-4 -甲基-2，5 -二氧代-1 Η -叶匕 咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-(苯基磺醯 基）六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三氟甲基） 苯甲腈Pycnogenol-1 -sulfamethoxamine 4- [3- [6- [4-[[4- (l, l-dimethylethyl) phenoxy] ethenyl] hexahydropyridine-1 -yl ] Hexyl] -2,5 · dihydro-4 -methyl-2,5 -dioxo-1 fluorene-leafyl-1-yl] -2- (trifluoromethyl) benzonitrile 4- [ 2,5-dihydro-3-methyl-2,5-dioxo-4- [6- [4- (phenylsulfonyl) hexahydropyridine-1 -yl] hexyl] -1 Η- Pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4-[2,5-二氫-3-甲基-4-[6-[4-(甲基磺醯基）六氫吡畊 -1-基]己基]-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[2,5-二氫-3-甲基-4-[6-[4-[(4 -甲基苯基）-磺醯基] 六氫说畊-1-基]己基]-2,5-二氧代-1Η- 口比咯-1-基]-2-(三氟甲基）苯甲腈4- [2,5-dihydro-3-methyl-4- [6- [4- (methylsulfonyl) hexahydropyridin-1-yl] hexyl] -2,5-dioxo- 1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4- [6- [4-[(4-methylbenzene ) -Sulfofluorenyl] hexahydrocyclo-1-yl] hexyl] -2,5-dioxo-1fluorene-pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile ^-[4-[[4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫 -4 -甲基-2，5 -二氧代-1 Η -吡咯-3 -基]己基]六氫吡畊-1 -基]績酿基]苯基]乙酸胺 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-[(苯基甲基） 磺醯基]六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三氟 甲基）苯甲腈 4-[3-[6-[4-[(4-氰基苯基）磺醯基]六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代- lH-p比咯-1-基]-2-(三 氟甲基）苯甲腈 4 - [ 2,5 --一 氣-3-甲基-4-[6-[4-[(奈-2 -基）績酿基]7Τ 風 叶匕'?井-1-基]己基]-2,5 --一氧代-1 Η - ρ比17各-1-基]-2-(二氣 -41 - 200301117^-[4-[[4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4 -methyl-2,5 -di Oxo-1 fluorene-pyrrole-3 -yl] hexyl] hexahydropyridine-1 -yl] pyrrolyl] phenyl] acetamide 4- [2,5-dihydro-3-methyl-2,5 -Dioxo-4- [6- [4-[(phenylmethyl) sulfofluorenyl] hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-1 -yl] -2-(tri Fluoromethyl) benzonitrile 4- [3- [6- [4-[(4-cyanophenyl) sulfonyl] hexahydropyridin-1-yl] hexyl] -2,5 -dihydro- 4-methyl-2,5-dioxo-lH-p than pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[2,5 --monogas-3-methyl- 4- [6- [4-[(Nana-2 -yl) pyridyl] 7T wind leaf dagger '? 1--1-yl] hexyl] -2,5 --- oxo-1 Η-ρ ratio 17 Each-1-yl) -2- (digas-41-200301117 甲基）苯甲腈 4 - [ 3 - [ 6 - [ 4 - [[ 5 -(二甲基胺基）莕-1 -基]磺醯基]六氫吡 畊-1-基]己基]-2,5-二氫-4-甲基-2,5-二氧代-1H -吡咯 -1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-[〇塞-2-基） 磺醯基]六氫说畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三氟 甲基）苯甲腈Methyl) benzonitrile 4-[3-[6-[4-[[5-(dimethylamino) fluoren-1 -yl] sulfofluorenyl] hexahydropyridin-1-yl] hexyl]- 2,5-dihydro-4-methyl-2,5-dioxo-1H -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro- 3-methyl-2,5-dioxo-4- [6- [4- [〇Se-2-yl) sulfofluorenyl] hexahydrocyclo-1 -yl] hexyl] -1 hydrazone -pyrrole- 1 -yl] -2-(trifluoromethyl) benzonitrile 4 - [ 3 - [ 6 - [4 -[(喳啉-8 -基）磺醯基]六氫吡畊-1 -基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4 - [ 3 - [ 6 - [ 4 - [(2 -氟苯基）磺醯基]六氫吡畊-1 -基]己 基]-2,5 -二氫-4-甲基-2,5-二氧代-111-吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[6-[4-[(2 -氯苯基）磺醯基]六氫吡畊-1-基]己 基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-1·基]-2-(三4-[3-[6-[4-[(Amorpholin-8-yl) sulfofluorenyl] hexahydropyridine-1 -yl] hexyl] -2,5 -dihydro-4-methyl-2, 5 -dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[6-[4-[(2-fluorophenyl) sulfonyl]] Hydropyridine-1 -yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-1-yl] -2- (trifluoromethyl) benzyl Nitrile 4- [3- [6- [4-[(2-chlorophenyl) sulfonamido] hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2, 5-dioxo-1'-pyrrole-1.yl] -2- (tri 氟甲基）苯甲腈 4-[3-[6-[4-[(2-氰基苯基）磺醯基]六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[3-[6-[4-[(3-氰基苯基）磺醯基]六氫吡畊-1-基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基-4-[6-[4-[[5-[2 -甲基- 5-(三氟甲 基）-2 Η -吡唑-3 -基]噻-2 -基]磺醯基]六氫吡畊-1 -基]己 -42- 200301117Fluoromethyl) benzonitrile 4- [3- [6- [4-[(2-cyanophenyl) sulfofluorenyl] hexahydropyridin-1-yl] hexyl] -2,5 -dihydro- 4-methyl-2,5-dioxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4-[(3-cyano Phenyl) sulfofluorenyl] hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1fluorene-pyrrole-1-yl] -2- (Trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4- [6- [4-[[5- [2-methyl-2- (trifluoromethyl) -2 hydrazone-pyrazole-3 -yl] thia-2-yl] sulfonyl] hexahydropyridine-1 -yl] hex-42- 200301117 基]-2，5 -二氧代-1 Η -说咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-[[1，2,3,4-四 氫-2 -(三氟乙醯基）異喹啉-7 -基]磺醯基]六氫吡畊-1 -基]己基]-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4 - [ 3 - [ 6 - [ 4 - [ 3，5 -二甲基異呤唑-4 -基]磺醯基]六氫吡 畊-1 -基]己基]-2，5 -二氫-4 -甲基-2，5 -二氧代-1 Η -吡咯 -1-基]-2-(三氟甲基）苯甲腈 4-[3-[6-[4-[(5 -氯-1，3-二甲基-1Η-说唑-4-基）磺醯基] 六氫吡畊-1-基]己基]-2,5-二氫-4-甲基-2,5-二氧代 -1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫-3-甲基- 4- [6-[4-[(1-甲基-1Η -咪唑-4-基） 磺醯基]六氫吡畊-1 -基]己基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈Group] -2,5 -dioxo-1 fluorene -single-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2, 5-dioxo-4- [6- [4-[[1,2,3,4-tetrahydro-2-(trifluoroethylfluorenyl) isoquinolin-7-yl] sulfonyl] hexahydro] Pyrene-1 -yl] hexyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[6-[4-[3,5 -dimethylisopropyl Pyrazol-4-yl] sulfofluorenyl] hexahydropyridine-1 -yl] hexyl] -2,5-dihydro-4 -methyl-2,5-dioxo-1 fluorene -pyrrole-1- Yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4-[(5-chloro-1,3-dimethyl-1fluorenyl-sazol-4-yl) sulfonyl [Yl] hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl ) Benzonitrile 4- [2,5-dihydro-3-methyl- 4- [6- [4-[(1-methyl-1Η-imidazol-4-yl) sulfonyl] hexahydropyracine -1 -yl] hexyl] -2,5 -dioxo-1 fluorene -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4-[6-[1-[4-氣基- 3- (二氣甲基）冬基]-2,5-« — 氣-4 -甲 基-2,5-二氧代-111-吡咯-3-基]己基]-?^-(1，1-二甲基乙 基）六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1Η-吡咯-3-基]己基]-Ν-苯基六氫吡畊 -1 -複龜胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1^1-说咯-3-基]己基]-〜（莕-1-基）六氫 吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]-.(莕-2-基）六氫 -43 - 2003011174- [6- [1- [4-Gasyl-3- (difluoromethyl) winteryl] -2,5- «— ga-4 -methyl-2,5-dioxo-111-pyrrole -3-yl] hexyl]-? ^-(1,1-dimethylethyl) hexahydropyridine-1 -carboxamidin 4- [6- [1- [4-cyano-3- (tri Fluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1'-pyrrole-3-yl] hexyl] -N-phenylhexahydropyridine-1- Dipyramidamine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 ^ 1-Sale-3-yl] hexyl]-~ (fluoren-1-yl) hexahydropyridine-1 -carboxamidin 4- [6- [1- [4-cyano-3- (trifluoro (Methyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl]-. (Fluoren-2-yl) hexahydro-43 -200301117 吡畊-1 -羧醯胺 N-(4-氰基苯基）-4-[6-[l-[4-氰基-3-(三氟甲基）苯 基]-2,5-二氫-4-甲基-2,5-二氧代-1H-吡咯-3-基]己基] 六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-叶!：咯-3-基]己基]*^-(1-甲基乙基） 六氫说p井-1 -竣S盛胺Pycnogenol-1 -carboxamide N- (4-cyanophenyl) -4- [6- [l- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-di Hydrogen-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] hexahydropyridine-1 -carboxamidin 4- [6- [1- [4-cyano-3 -(Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-leaf!: Role-3-yl] hexyl] * ^-(1- Methylethyl) Hexahydrogen p-well-1-Jun S Sheng Amine 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]^-[3-(三氟甲基） 苯基]六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]^-(2-氟苯基）六 氫吡畊-1 -羧醯胺 N-(2-氯苯基）-4-[6-[1-[4-氰基-3-(三氟甲基）苯 基]-2,5 -二氫-4-甲基-2,5-二氧代-1H -咐咯-3-基]己基]4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole- 3-yl] hexyl] ^-[3- (trifluoromethyl) phenyl] hexahydropyridine-1 -carboxamidin 4- [6- [1- [4-cyano-3- (trifluoromethyl) ) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl] ^-(2-fluorophenyl) hexahydropyridine- 1-Carboxamidamine N- (2-chlorophenyl) -4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4- Methyl-2,5-dioxo-1H -methyl-3-yl] hexyl] 六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-lH〃比咯-3-基]己基]-N-(2-甲氧基苯基） 六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-说咯-3-基]己基]-^^[2-(三氟甲基） 苯基]六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]-?^(2-甲基苯基） -44- 200301117 六氫ρ比呼-1 -竣st胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lHパ比咯-3-基]己基]-N-(3-氟苯基）六 氫吡畊-1 -羧醯胺 N-(3 -氯苯基）-4-[6-[1-[4-氰基-3-(三氟甲基）苯 基]-2,5 -二氫-4 -甲基-2,5-二氧代-1H -吡咯-3-基]己基] 六氫p比呼-1 -致S盛胺Hexahydropyridine-1 -carboxamide 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2, 5-dioxo-lH-pyrrole-3-yl] hexyl] -N- (2-methoxyphenyl) hexahydropyrimidine-1 -carboxamidin 4- [6- [1- [4- Cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-syl-3-yl] hexyl]-^^ [ 2- (trifluoromethyl) phenyl] hexahydropyridine-1 -carboxamide 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5 -Dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl]-? ^ (2-methylphenyl) -44- 200301117 hexahydroρ bihu-1- Junstamine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH Bipyrrol-3-yl] hexyl] -N- (3-fluorophenyl) hexahydropyridine-1 -carboxamidine N- (3-chlorophenyl) -4- [6- [1- [4 -Cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4 -methyl-2,5-dioxo-1H -pyrrole-3-yl] hexyl] hexahydro p ratio Hu-1-To S Sheng Amine 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111^比咯-3-基]己基]->^(3-甲氧基苯基） 六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]-?^(3-甲基苯基） 六氫吡畊-1 -羧醯胺4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111 ^ pyrro -3-yl] hexyl]-> ^ (3-methoxyphenyl) hexahydropyridine-1 -carboxamidine 4- [6- [1- [4-cyano-3- (trifluoromethyl) (Phenyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl]-? ^ (3-methylphenyl) hexahydropyridine Plow-1 -carboxamide 4-[6-[1-[4-氰基-3_(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lH-吡咯-3-基]己基]-N-(4-氟苯基）六 氫吡畊-1 -羧醯胺 N-(4-氯苯基）-4-[6-[1-[4-氰基-3-(三氟甲基）苯 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -吡咯-3-基]己基] 六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-lH-吡咯-3-基]己基]-N-(4-甲氧基苯基） 六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-11^-说咯-3-基]己基]-心（4-(三氟甲基） -45- 2003011174- [6- [1- [4-cyano-3_ (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-pyrrole-3 -Yl] hexyl] -N- (4-fluorophenyl) hexahydropyridine-1 -carboxamide N- (4-chlorophenyl) -4- [6- [1- [4-cyano-3 -(Trifluoromethyl) phenyl] -2,5 -dihydro-4-methyl-2,5 -dioxo-1H -pyrrole-3-yl] hexyl] hexahydropyridine-1 -carboxamidine Amine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-pyrrole -3-yl] hexyl] -N- (4-methoxyphenyl) hexahydropyridine-1 -carboxamidine 4- [6- [1- [4-cyano-3- (trifluoromethyl) ) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-11 ^ -sorrol-3-yl] hexyl] -heart (4- (trifluoromethyl) -45 -200301117 苯基）六氫17比呼-1 -竣S盔胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lHパ比咯-3-基]己基]-N-(4-甲基苯基） 六氫p比_ - 1 -幾酿胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-说咯-3-基]己基]->^(丙-2-烯基）六 氫吡畊-1 -羧醯胺Phenyl) hexahydro 17 bihu-1-Jun S helmet amine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4- Methyl-2,5-dioxo-lH-pyrrol-3-yl] hexyl] -N- (4-methylphenyl) hexahydro p ratio 1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-syl-2-yl] hexyl ]-> ^ (prop-2-enyl) hexahydropyridine-1 -carboxamide 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-1H-吡咯-3-基]己基]-N-環己基六氫吡 畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lH-吡咯-3-基]己基]-N-(苯基甲基）六 氫吡畊-1 -羧醯胺 N-(3-氰基苯基）-4-[6-[1-[4-氰基-3-(三氟甲基）苯 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1H -说咯-3-基]己基]4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1H-pyrrole- 3-yl] hexyl] -N-cyclohexylhexahydropyridine-1 -carboxamidin 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5 -Dihydro-4-methyl-2,5-dioxo-lH-pyrrole-3-yl] hexyl] -N- (phenylmethyl) hexahydropyrine-1 -carboxamide N- (3 -Cyanophenyl) -4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-di Oxo-1H-speaking 3-yl] hexyl] 六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-口比咯-3-基]己基]-N-(3,5-二甲氧基 苯基）六氫吡畊-1 -羧醯胺 4-[6-[1-[4 -夜基- 3- (二氣甲基）冬基]-2,5-« — 鼠-4 -甲 基-2,5-二氧代- ΙΗ-说咯-3-基]己基]-N-(3-(甲基硫烷 基）苯基）六氫说_ - 1 -複龜胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-说咯-3-基]己基]^-(4-苯氧基苯基） -46- 200301117Hexahydropyridine-1 -carboxamidine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2, 5-dioxo-1H-pyrrol-3-yl] hexyl] -N- (3,5-dimethoxyphenyl) hexahydropyramine-1 -carboxamide 4- [6- [1 -[4 -N-yl-3- (difluoromethyl) winteryl] -2,5- «—murine-4 -methyl-2,5-dioxo- 1Η-salyl-3-yl] hexyl ] -N- (3- (methylsulfanyl) phenyl) hexahydrogenation--1-Futanamine 4- [6- [1- [4-cyano-3- (trifluoromethyl) benzene Yl] -2,5-dihydro-4-methyl-2,5-dioxo-111-salyl-3-yl] hexyl] ^-(4-phenoxyphenyl) -46- 200301117 六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代- ΙΗ-说咯-3-基]己基]-N-[4-(甲基硫烷 基）苯基]六氫P比呼-1 -複gS胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111^比咯-3-基]己基]-1^[4-(1-甲基乙基） 苯基]六氫吡畊-1 -羧醯胺Hexahydropyridine-1 -carboxamidine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2, 5-dioxo-il-l-syl-3-yl] hexyl] -N- [4- (methylsulfanyl) phenyl] hexahydro P bihu-1-complex gS amine 4- [6- [ 1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111 ^ pyrrol-3-yl] hexyl ] -1 ^ [4- (1-methylethyl) phenyl] hexahydropyridine-1 -carboxamide 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-1H-吡咯-3-基]己基]-N-[4-(2-苯基乙基） 六氫4 p井-1 -幾SS胺 Ν-([1，Γ-聯苯基]-2-基）-4-[6-[1-[4-氰基-3-(三氟甲 基）苯基]-2,5-二氫-4-甲基-2,5-二氧代-1Η-吡咯-3-基] 己基]六氫吡畊-1 -羧醯胺4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1H-pyrrole- 3-yl] hexyl] -N- [4- (2-phenylethyl) hexahydro 4 p-well-1-several SS amine N-([1, Γ-biphenyl] -2-yl) -4 -[6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1Η-pyrrole-3 -Yl] hexyl] hexahydropyridine-1 -carboxamide 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]-^^[4-(苯基甲氧 基）苯基]六氫吡畊-1 -羧醯胺 Ν-(2-氰基苯基）-4-[6-[1-[4 -氰基-3-(三氟甲基）苯 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-3-基]己基] 六氫说畊-1 -叛醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1^1-吡咯-3-基]己基]-〜[2-(嘧-2-基）乙 基]六氫吡畊-1 -羧醯胺 (1R-反式）-4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基-2,5-二氧代-lH-说咯-3-基]己基]-N-(2-苯 -47- 20030111?4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole- 3-yl] hexyl]-^^ [4- (phenylmethoxy) phenyl] hexahydropyridine-1 -carboxamidine N- (2-cyanophenyl) -4- [6- [1 -[4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1Η-pyrrole-3-yl] hexyl] hexa HYDROGEN-1-Betamine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5 -Dioxo-1 ^ 1-pyrrole-3-yl] hexyl]-~ [2- (pyrim-2-yl) ethyl] hexahydropyrine-1 -carboxamide (1R-trans) -4 -[6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-speak- 3-yl] hexyl] -N- (2-benzene-47- 20030111? 基環丙基）六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-lH-吡咯-3-基]己基]-N-(2,6-二氟苯基） 六氫批_ - 1 -幾酿胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lH-吡咯-3-基]己基]-N-(2,6-二氯苯基） 六氫吡畊-1 -羧醯胺Cyclopropyl) hexahydropyridine-1 -carboxamidin 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4- Methyl-2,5-dioxo-lH-pyrrole-3-yl] hexyl] -N- (2,6-difluorophenyl) hexahydropyridine 1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-pyrrole-3-yl] hexyl] -N- (2,6-dichlorophenyl) hexahydropyrine-1 -carboxamide 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-说咯-3-基]己基]-]^(2,4-二甲氧基 苯基）六氫说p井-1 -叛S&胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]-.(2,5-二甲氧基 苯基）六氫？比p井-1 -複胺4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-speak -3-yl] hexyl]-] ^ (2,4-dimethoxyphenyl) hexahydrogen p-well-1 -amino S & amine 4- [6- [1- [4-cyano-3- (Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl]-. (2,5-dimethoxy Phenyl) hexahydro? Than p-1 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]-心（2,6-二甲氧基 苯基）六氫？比。井-1 -叛酿胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯-3-基]己基]-N-(三氯乙醯基） 六氫吡畊-1 -羧醯胺 (S)-4-[6-[l-[4-氰基- 3-(三氟甲基）苯基]-2,5-二氫-4-甲基-2,5-二氧代-lH-吡咯-3-基]己基]-N-(l-苯基乙基） 六氫说p井-1 -致酷胺 (R)-4-[6-[l-[4-氰基- 3-(三氟甲基）苯基]-2,5-二氫-4-甲基-2,5-二氧代-lH-说咯-3-基]己基]-N-[l-(莕-l-基） -48 - 2003011174- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole- 3-yl] hexyl] -heart (2,6-dimethoxyphenyl) hexahydro? ratio. Well-1-Beverage amine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-di Oxo-1H-pyrrole-3-yl] hexyl] -N- (trichloroethenyl) hexahydropyrimidine-1 -carboxamide (S) -4- [6- [l- [4-cyano -3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-pyrrole-3-yl] hexyl] -N- (l-benzene Ethyl) hexahydrogen p-well-1 -Crylamyl (R) -4- [6- [l- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-di Hydrogen-4-methyl-2,5-dioxo-lH-salrol-3-yl] hexyl] -N- [l- (fluoren-l-yl) -48-200301117 六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]->^(2,4,6-三氯苯 基）六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-口比咯-3-基]己基]-?^[2-(1-甲基乙基） 苯基]六氫吡畊· 1 -羧醯胺Hexahydropyridine-1 -carboxamidine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2, 5-dioxo-111-pyrrole-3-yl] hexyl]-> ^ (2,4,6-trichlorophenyl) hexahydropyrine-1 -carboxamide 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-methylpyrrol-3-yl] hexyl] -? ^ [2- (1-methylethyl) phenyl] hexahydropyrine · 1-carboxamide 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]-〜（3,5-二氯苯基） 六氫说p井-1 -竣Si胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯-3-基]己基]-N-(2,4,6-三甲基 苯基）六氫吡畊-1 -羧醯胺4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole- 3-yl] hexyl]-~ (3,5-dichlorophenyl) Hexahydrogen p-well-1-Jun Si amine 4- [6- [1- [4-cyano-3- (trifluoromethyl) ) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- (2,4,6-trimethylphenyl ) Hydroxypyrine-1 -carboxamide 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-1H-吡咯-3-基]己基]-N-[4-[(三氟甲基） 硫燒基]苯基]六氫p比啡-1 -複S盛胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-lH-吡咯-3-基]己基]-N-(2,4-二氯苯基） 甲基]六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯-3-基]己基]-N-[2-(甲基硫烷 基）苯基]六氫吡畊-1-羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-1H-吡咯-3-基]己基]-N-(2,6-二氯吡啶 -49- 2003011174- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl- 2,5-dioxo-1H-pyrrole- 3-yl] hexyl] -N- [4-[(trifluoromethyl) sulfanyl] phenyl] hexahydrop-biffin-1 -sulfaamine 4- [6- [1- [4-cyano 3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-pyrrole-3-yl] hexyl] -N- (2, 4-dichlorophenyl) methyl] hexahydropyridine-1 -carboxamide 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5- Dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- [2- (methylsulfanyl) phenyl] hexahydropyridine-1-carboxyl Amidine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H- Pyrrol-3-yl] hexyl] -N- (2,6-dichloropyridine-49- 200301117 -4 -基）六氫吡畊-1 -羧醯胺 (R)-4-[6-[l-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲基-2,5-二氧代-lHパ比咯-3-基]己基]-N-(l-苯基乙基） 六氫p比_ - 1 -竣酿胺-4 -yl) hexahydropyridine-1 -carboxamide (R) -4- [6- [l- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-di Hydrogen-4-methyl-2,5-dioxo-lH-pyrrol-3-yl] hexyl] -N- (l-phenylethyl) hexahydro p-ratio (S)_4-[6-[l-[4-氰基- 3-(三氟甲基）苯基卜2,5-二氫-4-甲基-2,5-二氧代-lH-吡咯-3-基]己基]-N-[l-甲基 -1 - [ 3 - (1 -甲基乙烯基）苯基]乙基]六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lH-吡咯-3-基]己基]-N-[l-甲基-l-[3-甲基乙烯基]苯基]乙基]六氫吡畊-l-羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]-心[2-(三氟甲氧 基）苯基]六氫吡畊-1 -羧醯胺 4-[6-[1-[4-篆基-3-(二氣甲基）冬基]-2,5 - —氮-4 -甲 基-2,5-二氧代-1H- 口比咯-3-基]己基]-N-(三環 [3.3.1.13.7]癸-1-基）六氫吡畊-1-羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-说咯-3-基]己基]-1^-[4-(二甲基胺 基）苯基]六氫p比畊-1 -致驢胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-1H-吡咯-3-基]己基]-N-[3-[(三氟甲基） 硫烷基]苯基]六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]->1-[(2-甲基苯基） -50- 200301117(S) _4- [6- [l- [4-cyano-3- (trifluoromethyl) phenylb, 2,5-dihydro-4-methyl-2,5-dioxo-lH- Pyrrole-3-yl] hexyl] -N- [l-methyl-1-[3-(1-methylvinyl) phenyl] ethyl] hexahydropyrine-1 -carboxamide 4- [6 -[1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-pyrrole-3-yl] Hexyl] -N- [l-methyl-l- [3-methylvinyl] phenyl] ethyl] hexahydropyridine-l-carboxamide 4- [6- [1- [4-cyano -3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl] -heart [2- (tri Fluoromethoxy) phenyl] hexahydropyridine-1 -carboxamidin 4- [6- [1- [4-fluorenyl-3- (difluoromethyl) dongyl] -2,5--nitrogen -4 -methyl-2,5-dioxo-1H-pyrrol-3-yl] hexyl] -N- (tricyclo [3.3.1.13.7] dec-1-yl) hexahydropyridine- 1-carboxyamidoamine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo -111-Hydroxy-3-yl] hexyl] -1 ^-[4- (dimethylamino) phenyl] hexahydropeptone-1 -Donylamine 4- [6- [1- [4 -Cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] hexyl] -N- [ 3-[(trifluoromethyl) sulfanyl ] Phenyl] hexahydropyridine-1 -carboxamidin 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl -2,5-dioxo-111-pyrrole-3-yl] hexyl]-> 1-[(2-methylphenyl) -50- 200301117 甲基]六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lH-说咯-3-基]己基]-N-[(3-甲基苯基） 甲基]六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lH-吡咯·3-基]己基]-N-[(4-甲基苯基） 甲基]六氫吡畊-1 ·羧醯胺Methyl] hexahydropyridine-1 -carboxamidine 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl -2,5-dioxo-lH-salrol-3-yl] hexyl] -N-[(3-methylphenyl) methyl] hexahydropyridine-1 -carboxamide 4- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole · 3-yl] hexyl ] -N-[(4-methylphenyl) methyl] hexahydropyrine-1 · Carboxamide 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lH-吡咯-3-基]己基]-N-[(4-甲氧基苯 基）甲基]六氫吡畊-1 -羧醯胺 4-[6-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]己基]~^-(1，1，3,3-四甲 基丁基）甲基]六氫吡畊-1 -羧醯胺 4-[3-[7-(4-乙醯基六氫吡畊-1-基）庚基]-2,5-二氫-4-甲基-2,5-二氧代-lH-吡咯-l-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[7-[4-(1-氧代丙基） 六氫吡畊-1-基]庚基]-1H-吡咯-1-基]-2-(三氟甲基）苯 甲腈 4 - [ 3 - [ 7 - (4 -(環丙基羰基）六氫吡畊-1 -基）庚基]-2，5 -二氫-4 -甲基-2,5-二氧代-1H -吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[2,5-二氫-3-[7-[4-(甲氧基乙醯基）六氫吡畊-1-基] 庚基]-4 -甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基） 苯甲月青 -51 - 2003011174- [6- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-pyrrole- 3-yl] hexyl] -N-[(4-methoxyphenyl) methyl] hexahydropyridine-1 -carboxamidin 4- [6- [1- [4-cyano-3- (tri Fluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl] ~ ^-(1,1,3,3- Tetramethylbutyl) methyl] hexahydropyridine-1 -carboxamide 4- [3- [7- (4-ethylamidohexahydropyridine-1-yl) heptyl] -2,5- Dihydro-4-methyl-2,5-dioxo-lH-pyrrole-l-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl -2,5-dioxo-4- [7- [4- (1-oxopropyl) hexahydropyridin-1-yl] heptyl] -1H-pyrrole-1-yl] -2- ( Trifluoromethyl) benzonitrile 4-[3-[7-(4- (cyclopropylcarbonyl) hexahydropyridine-1 -yl) heptyl] -2,5 -dihydro-4 -methyl- 2,5-dioxo-1H -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- [7- [4- (methoxy Ethylfluorenyl) hexahydropyridin-1-yl] heptyl] -4 -methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzyl Blue-51-200301117 4-[2,5 -二氫- 3- [7-[4-(3-甲氧基-1-氧代丙基）六氫吡 啩-1-基]庚基]-4-甲基-2,5-二氧代-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫-3-[7-[4-[(2-甲氧基乙氧基）乙醯基]六氫 吡畊-1 -基]庚基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 _ 基]-2-(三氟甲基）苯甲腈4- [2,5 -dihydro- 3- [7- [4- (3-methoxy-1-oxopropyl) hexahydropyridin-1-yl] heptyl] -4-methyl- 2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- [7- [4-[(2- Methoxyethoxy) ethenyl] hexahydropyridine-1 -yl] heptyl] -4 -methyl-2,5-dioxo-1 pyrene -pyrrole-1 —yl] -2- ( Trifluoromethyl) benzonitrile 4-[2,5 -二氫- 3-[7-[4-[[2-(2 -甲氧基乙氧基）乙氧基] 乙醯基]六氫吡畊-1-基]庚基]-4 -甲基-2,5-二氧代-ΙΗ-吡咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[2,5 -二氫-3-[7-[4-(2-甲氧基苯甲醯基）六氫吡畊 -1-基]庚基]-4 -甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-4-[7-[4-(甲基磺醯基）六氫吡畊 -1-基]庚基]-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲月膏4- [2,5 -dihydro- 3- [7- [4-[[2- (2-methoxyethoxy) ethoxy] ethenyl] hexahydropyridine-1-yl] heptane Yl] -4 -methyl-2,5-dioxo-l-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- [7 -[4- (2-methoxybenzylidene) hexahydropyridin-1-yl] heptyl] -4 -methyl-2,5-dioxo-1Η-pyrrole-1-yl]- 2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-4- [7- [4- (methylsulfonyl) hexahydropyridine-1-yl] Heptyl] -2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzyl cream 4-3-[7-[4-(乙基磺醯基）六氫吡畊-1-基]庚基]-2,5-二 氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯 甲腈 4-3-[7-[4-(環丙基磺醯基）六氫吡畊-1-基]庚基]-2,5-二氫-4 -甲基-2，5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲月膏 4-[2,5 -二氫- 3- [7-[4-(2 -甲氧基乙基）磺醯基]六氫吡 畊-1 -基]庚基]-4 -甲基-2，5 -二氧代-1 Η - 口比咯-1 -基]-2-(三氟甲基）苯甲腈 -52- 2003011174-3- [7- [4- (ethylsulfonyl) hexahydropyridin-1-yl] heptyl] -2,5-dihydro-4-methyl-2,5-dioxo- 1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-3- [7- [4- (cyclopropylsulfonyl) hexahydropyrine-1-yl] heptyl] -2,5-dihydro-4 -methyl-2,5-dioxo-1'-pyrrole-1-yl] -2- (trifluoromethyl) benzyl cream 4- [2,5 -di Hydrogen-3- [7- [4- (2-methoxyethyl) sulfonamido] hexahydropyridine-1 -yl] heptyl] -4 -methyl-2,5-dioxo-1 Hydrazone-bipyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile-52- 200301117 4-[2,5 -二氫-3-[7-[4-[[2-(2 -甲氧基乙氧基）乙基]磺 醯基]六氫吡畊-1-基]庚基]-4 -甲基- 2,5-二氧代-1Η-ρ比 咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[7-[4-[[2-[2-(2 -甲氧基乙氧基）乙氧基] 乙基]磺醯基]六氫吡畊-1-基]庚基]-4 -甲基-2,5-二氧 代-1H-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[7-[4-(苯基磺醯 基）六氫吡畊-1 -基]庚基]-1 Η -说咯-1 -基]-2 -(三氟甲基） 苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[7-[4-[(苯基甲基） 磺醯基]六氫吡畊-1 -基]庚基]-1 Η -吡咯-1 -基]-2 -(三氟 甲基）苯甲腈 4-[2,5 -二氫-3-甲基- 4- [7-[4-[(1-甲基-1Η -咪唑-4-基） 磺醯基]六氫吡畊-1-基]庚基]-2,5-二氧代-1Η-吨咯-1-基]-2-(三氟甲基）苯甲腈4- [2,5 -dihydro-3- [7- [4-[[2- (2-methoxyethoxy) ethyl] sulfofluorenyl] hexahydropyridin-1-yl] heptyl ] -4 -methyl-2,5-dioxo-1Η-ρbipyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- 3- [ 7- [4-[[2- [2- (2-methoxyethoxy) ethoxy] ethyl] sulfofluorenyl] hexahydropyridin-1-yl] heptyl] -4 -methyl -2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo Substituted for 4- [7- [4- (phenylsulfonyl) hexahydropyridine-1 -yl] heptyl] -1 fluorene -syl-1 -yl] -2-(trifluoromethyl) benzene Nitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [7- [4-[(phenylmethyl) sulfonamido] hexahydropyridine-1 -Yl] heptyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl- 4- [7- [4 -[(1-methyl-1fluorene-imidazol-4-yl) sulfofluorenyl] hexahydropyridine-1-yl] heptyl] -2,5-dioxo-1fluorene-tonyl-1-yl] -2- (trifluoromethyl) benzonitrile 4-[7-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-lH-吡咯-3-基]庚基]-N-(l-甲基乙基） 六氫说喷-1 -竣醯胺 4-[7-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基- 2,5-二氧代-1Η-吡咯-3-基]庚基]-Ν -乙基六氫吡畊 -1 -碳硫酿胺 4-[7-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 ·二氧代-1 Η -吡咯-3 -基]庚基]六氫吡畊-1 -羧酸 甲酉旨 -53 - 2003011174- [7- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-lH-pyrrole- 3-yl] heptyl] -N- (l-methylethyl) hexahydrocyclopentane-1 -endrimidine 4- [7- [1- [4-cyano-3- (trifluoromethyl) Phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-3-yl] heptyl] -N-ethylhexahydropyridine-1 -carbon sulfur Amine 4- [7- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5 · dioxo-1 Η- Pyrrole-3 -yl] heptyl] hexahydropyrine-1 -carboxylic acid formamidine -53-200301117 4-[7-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η - 口比咯-3 -基]庚基]六氫吡畊-1 -碳硫 酸S -甲酯 4-[7-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-说咯-3-基]庚基]-1>1-二甲基六氫 吡畊-1 -磺醯胺4- [7- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 Η-口Pyrrole-3 -yl] heptyl] hexahydropyrine-1 -Carbonsulfate S -methyl 4- [7- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2 , 5-dihydro-4-methyl-2,5-dioxo-111-salrol-3-yl] heptyl] -1 > 1-dimethylhexahydropyridine-1 -sulfamethoxamine 4-3-[8-(4 -乙媪基氮？比。井-1 -基）辛基]-2，5 --一氮-4 -甲基- 2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫-3 -甲基- 2,5-二氧代- 4-[8-(4-(1-氧代丙基） 六氫吡畊-1-基）辛基]-1Η-吡咯-1-基]-2-(三氟甲基）苯 甲腈 4-3-[8-[4-(環丙基羰基）六氫吡畊-1-基]辛基]-2,5 -二 氫-4-甲基-2，5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基）苯 甲月青4-3- [8- (4-Ethylfluorenyl nitrogen? Ratio. Well-1 -yl) octyl] -2,5 -monoazol-4-methyl-2,5-dioxo-1fluorene- Pyrrol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3 -methyl-2,5-dioxo- 4- [8- (4- ( 1-oxopropyl) hexahydropyridin-1-yl) octyl] -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-3- [8- [4- (Cyclopropylcarbonyl) hexahydropyridin-1-yl] octyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (Trifluoromethyl) benzazine 4-[2,5-二氫-3-[8-[4_(甲氧基乙醯基）六氫吡畊-1-基] 辛基]-4 -甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[2,5 -二氫- 3- [8-[4-(3 -甲氧基-乙氧基-1-氧代丙基） 六氫吡畊-1 -基]辛基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[8-[4-[(2 -甲氧基乙氧基）乙醯基]六氫 吡畊-1 -基]辛基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫-3-[8-[4-[[2-(2-甲氧基乙氧基）乙氧基] -54- 2003011174- [2,5-Dihydro-3- [8- [4_ (methoxyethenyl) hexahydropyridin-1-yl] octyl] -4 -methyl-2,5-dioxo -1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5 -dihydro- 3- [8- [4- (3-methoxy-ethoxy- 1-oxopropyl) hexahydropyridine-1 -yl] octyl] -4 -methyl-2,5-dioxo-1 hydrazone -pyrrole-1 -yl] -2- (trifluoromethyl ) Benzonitrile 4- [2,5-dihydro- 3- [8- [4-[(2-methoxyethoxy) ethenyl] hexahydropyridine-1 -yl] octyl]- 4-methyl-2,5-dioxo-1 fluorene-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- [8- [ 4-[[2- (2-methoxyethoxy) ethoxy] -54- 200301117 乙醯基]六氫吡畊-1 -基]辛基]-4 -甲基-2，5 -二氧代-ΙΗ-吡咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[2,5 -二氫-3-[8-[4-(2-甲氧基苯甲醯基）六氫吡畊 -1-基]辛基]-4 -甲基-2,5 -二氧代-1H -口比咯-1-基]-2-(三 氟甲基）苯甲腈 4 - [ 2，5 -二氫-3 -甲基-4 - [ 8 - [ 4 -(甲基磺醯基）六氫吡畊 -1-基]辛基]-4 -甲基-2,5 -二氧代-1H -吡咯-1-基]-2-(三 氟甲基）苯甲腈 4-3-[8-[4-(乙基磺醯基）六氫吡畊-1-基]辛基]·2,5 -二 氫-4-甲基-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯 甲腈 4 - 3 - [ 8 - [ 4 -(環丙基磺醯基）六氫吡畊-1 -基]辛基]-2，5 -二氫-4-甲基-2，5 -二氧代-1Η-吡咯-1-基]-2-(三氟甲基） 苯甲腈 4-[2,5-二氫- 3-[8-[4-(2 -甲氧基乙基）磺醯基]六氫吡 畊-1 -基]辛基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[2,5 -二氫-3-[8-[4-[[2-(2-甲氧基乙氧基）乙基]磺 醯基]六氫吡畊-1 -基]辛基]-4 -甲基-2，5 -二氧代-1 Η -吡 咯-1-基]-2-(三氟甲基）苯甲腈 4-[2,5-二氫- 3-[8-[4-[[2-[2-(2-甲氧基乙氧基）乙氧基] 乙基]磺醯基]六氫吡畊-1-基]辛基]-4 -甲基-2,5-二氧 代-1 Η - ρ比咯-1 -基]-2 -(三氟甲基）苯甲腈 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[8-[4-(苯基磺醯 -55- 20030111?Ethylfluorenyl] hexahydropyridine-1 -yl] octyl] -4 -methyl-2,5 -dioxo-l-pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5 -Dihydro-3- [8- [4- (2-methoxybenzylidene) hexahydropyridin-1-yl] octyl] -4 -methyl-2,5 -Dioxo-1H -Hippyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-[2,5-dihydro-3 -methyl-4-[8-[4- (Methylsulfonyl) hexahydropyridin-1-yl] octyl] -4 -methyl-2,5-dioxo-1H -pyrrole-1-yl] -2- (trifluoromethyl) Benzonitrile 4-3- [8- [4- (ethylsulfonyl) hexahydropyridin-1-yl] octyl] · 2,5-dihydro-4-methyl-2,5-di Oxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4-3-[8-[4-(cyclopropylsulfonyl) hexahydropyridine-1 -yl] Octyl] -2,5-dihydro-4-methyl-2,5-dioxo-1H-pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5 -Dihydro- 3- [8- [4- (2-methoxyethyl) sulfonamido] hexahydropyridine-1 -yl] octyl] -4 -methyl-2,5-dioxo -1 hydrazone -pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro-3- [8- [4-[[2- (2-methoxy Ethoxy) ethyl] sulfofluorenyl] hexahydropyridine-1 -yl] octyl] -4 -methyl -2,5 -dioxo-1 Η -pyrrole-1-yl] -2- (trifluoromethyl) benzonitrile 4- [2,5-dihydro- 3- [8- [4-[[ 2- [2- (2-methoxyethoxy) ethoxy] ethyl] sulfofluorenyl] hexahydropyridin-1-yl] octyl] -4 -methyl-2,5-dioxy Substitute -1 Η-ρ pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [2,5-dihydro-3-methyl-2,5-dioxo-4- [8- [4- (phenylsulfonium-55- 20030111? 基）六氫吡畊-1 -基]辛基]-1 Η -吡咯-1 -基]-2 -(三氟甲基） 苯甲月f 4-[2,5-二氫-3-甲基-2,5-二氧代-4-[8-[4-(苯基甲基） 磺醯基]六氫吡畊-1 -基]辛基]-1 Η -吡咯-1 -基]-2 -(三氟 甲基）苯甲腈) Hydroxypyridine-1 -yl] octyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzyl f 4- [2,5-dihydro-3-formyl -2,5-dioxo-4- [8- [4- (phenylmethyl) sulfofluorenyl] hexahydropyridine-1 -yl] octyl] -1 hydrazone -pyrrole-1 -yl] -2-(trifluoromethyl) benzonitrile 4-[2,5 -二氫-3-甲基- 4- [8-[4-[(1-甲基-1Η -咪唑-4-基） 磺醯基]六氫吡畊-1 -基]辛基]-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯甲腈 4-[8-[1-[4_氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]辛基]->1-(1-甲基乙基） 六氫吡畊-1 -羧醯胺 4-[8-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η -吡咯-3 -基]辛基]-Ν-乙基六氫吡畊 -1 -致硫酸胺4- [2,5 -dihydro-3-methyl- 4- [8- [4-[(1-methyl-1Η-imidazol-4-yl) sulfofluorenyl] hexahydropyridine-1 -yl ] Octyl] -2,5-dioxo-1 fluorene-pyrrole-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [8- [1- [4_cyano-3- (Trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] octyl]-> 1- (1-methyl Ethyl) hexahydropyridine-1 -carboxamidine 4- [8- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl -2,5 -dioxo-1 hydrazone -pyrrole-3 -yl] octyl] -N-ethylhexahydropyrine-1 -amine sulfate 4-[8-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η -吡咯-3 -基]辛基]六氫吡畊-1 -羧酸 甲酉旨 4-[8-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2，5 -二氧代-1 Η -吡咯-3 -基]辛基]六氫吡畊-1 -羰硫 酸S -甲酯 4-[8-[1-[4-氰基-3-(三氟甲基）苯基]-2,5-二氫-4-甲 基-2,5-二氧代-111-吡咯-3-基]辛基]->^，>^-二甲基六氫 吡畊-1 -磺醯胺 Ν-[4-[2,5-二氫- 3-[6-[4-(2 -甲氧基苯甲醯基）六氫吡 -56- 2003011174- [8- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-1 Η-pyrrole -3 -yl] octyl] hexahydropyridine-1 -carboxylic acid formamidine 4- [8- [1- [4-cyano-3- (trifluoromethyl) phenyl] -2,5- Dihydro-4-methyl-2,5-dioxo-1 fluorene-pyrrole-3 -yl] octyl] hexahydropyrine-1 -carbonylsulfate S -methyl 4- [8- [1- [ 4-cyano-3- (trifluoromethyl) phenyl] -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] octyl]-> ^, ≫ ^-dimethylhexahydropyridine-1 -sulfamethoxamine N- [4- [2,5-dihydro- 3- [6- [4- (2-methoxybenzidine Yl) hexahydropyridine-56- 200301117 畊-1 -基]己基]-4 -甲基-2，5 -二氧代-1 Η -吡咯-1 -基]-2-(三氟甲基）苯基]乙醯胺 Ν - [4 - [ 3 - [ 6 - [ 4 -(環丁基羰基）六氫吡畊-1 -基]己 基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三 氟甲基）苯基]乙醯胺Geng-1 -yl] hexyl] -4 -methyl-2,5-dioxo-1 fluorene -pyrrole-1 -yl] -2- (trifluoromethyl) phenyl] acetamidinamine N-[4 -[3-[6-[4- (Cyclobutylcarbonyl) hexahydropyridine-1 -yl] hexyl] -2,5 -dihydro-4-methyl-2,5 -dioxo-1Η- Pyrrol-1-yl] -2- (trifluoromethyl) phenyl] acetamidamine ^^-[4-[2,5-二氫-3-甲基-2,5-二氧代-4-[6-[4-[〇塞-2-基）-羰基]六氫吡畊-1 -基]己基]-1 Η -吡咯-1 -基]-2 -(三 氟甲基）苯基]乙醯胺 Ν-[4-[3-[6-[4-[4-(二甲基胺基）苯甲醯基]六氫吡畊 - 1-基]己基]-2,5 -二氫-4-甲基-2,5 -二氧代-1Η -吡咯-1-基]-2-(三氟甲基）苯基]乙醯胺 N-[4-[3-[6-(4-乙醯基六氫吡畊-l-基）己基]-2,5-二氫 -4 -甲基-2,5-二氧代-1Η -吡咯-1·基]-2-(三氟甲基）苯基] 乙醯胺^^-[4- [2,5-Dihydro-3-methyl-2,5-dioxo-4- [6- [4- [〇 塞 -2-yl) -carbonyl] hexahydropyridine -1 -yl] hexyl] -1 fluorene -pyrrole-1 -yl] -2-(trifluoromethyl) phenyl] acetamidamine N- [4- [3- [6- [4- [4- ( Dimethylamino) benzylidene] hexahydropyridine-1-yl] hexyl] -2,5-dihydro-4-methyl-2,5-dioxo-1fluorene-pyrrole-1-yl ] -2- (trifluoromethyl) phenyl] acetamidamine N- [4- [3- [6- [4-ethylfluorenylhexahydropyridine-l-yl) hexyl] -2,5-di Hydrogen-4 -methyl-2,5-dioxo-1Η-pyrrole-1 · yl] -2- (trifluoromethyl) phenyl] acetamidine Ν-[4-[2,5-二氫-3-甲基-4-[6-[4-(甲基磺醯基）六氫吡 畊-1-基]己基]-2,5-二氧代-1Η-吡咯-1-基]-2-(三氟甲 基）苯基]乙醯胺 N-[4-[3-[6-[4-[(2，l，3-苯并嘍二唑-4 -基）磺醯基]六 氫吡畊-1-基]己基]-2,5 -二氫-4 -甲基-2,5 -二氧代-1Η-吡咯-1-基]-2-(三氟甲基）苯基]乙醯胺 4-[6-[1-[4-(乙醯基胺基）-3-(三氟甲基）苯基]-2,5-二 氫-4 -甲基-2，5 -二氧代-1 Η -吡咯-3 -基]己基]-Ν -(吡啶 -4 -基）六氫吡畊-1 -羧醯胺 3-[6-[4-(環丁基羰基）六氫吡畊-1-基]己基]-4 -甲基 -57- 200301117Ν- [4- [2,5-dihydro-3-methyl-4- [6- [4- (methylsulfonyl) hexahydropyridin-1-yl] hexyl] -2,5-di Oxo-1Η-pyrrole-1-yl] -2- (trifluoromethyl) phenyl] ethanamine N- [4- [3- [6- [4-[(2, l, 3-benzo Oxadiazol-4-yl) sulfofluorenyl] hexahydropyridin-1-yl] hexyl] -2,5-dihydro-4 -methyl-2,5-dioxo-1pyridine-1-pyrrole-1- Yl] -2- (trifluoromethyl) phenyl] ethanamine 4- [6- [1- [4- (ethylamidoamino) -3- (trifluoromethyl) phenyl] -2, 5-dihydro-4 -methyl-2,5 -dioxo-1 fluorene -pyrrole-3 -yl] hexyl] -N-(pyridin-4 -yl) hexahydropyridine-1 -carboxamide 3 -[6- [4- (cyclobutylcarbonyl) hexahydropyridin-1-yl] hexyl] -4 -methyl-57- 200301117 -1 - [ 4 -硝基-3 -(三氟甲基）苯基]-1 Η - 口比咯-2，5 -二酮 3-[6-[4-[4-(二甲基胺基）苯甲醯基]六氫吡畊-1-基] 己基]-4 -甲基-1-[4-硝基- 3- (三氟甲基）苯基]-1Η -吡咯 _ 2，5 -二酮-1-[4 -Nitro-3-(trifluoromethyl) phenyl] -1 hydrazone-orbital-2,5-dione 3- [6- [4- [4- (dimethylamine (Benzyl) benzyl] hexahydropyridin-1-yl] hexyl] -4 -methyl-1- [4-nitro-3-(trifluoromethyl) phenyl] -1Η -pyrrole-2, 5-dione 3 - [ 6 - ( 4 -乙醯基六氫吡畊-1 -基）己基]-4 -甲基-1 - [ 4 -硝 基- 3- (三氟甲基）苯基]-1Η -口比咯-2,5-二酮 3 -甲基-4 - [ 6 - [ 4 -(甲基磺醯基）六氫吡啩-1 -基]己 基]-1 - [ 4 -硝基-3 -(三氟甲基）苯基]-1 Η -说咯-2，5 -二酮 3-[6-[4-[(2，1，3-苯并噻二唑-4-基）磺醯基]六氫吡畊 -1-基]己基]-心甲基-1-[4-硝基-3-(三氟甲基）苯 基]-1 Η -吡咯-2，5 -二酮3-[6-(4-Acetylhexahydropyridine-1 -yl) hexyl] -4 -methyl-1-[4-nitro-3-(trifluoromethyl) phenyl] -1Η- MK-2,5-dione 3-methyl-4-[6-[4-(methylsulfonyl) hexahydropyridine-1 -yl] hexyl] -1-[4 -nitro- 3-(trifluoromethyl) phenyl] -1 hydrazone -shall-2,5-dione 3- [6- [4-[(2,1,3-benzothiadiazol-4-yl) Sulfonyl] hexahydropyridine-1-yl] hexyl] -cardiomethyl-1- [4-nitro-3- (trifluoromethyl) phenyl] -1 hydrazone-pyrrole-2,5-di ketone 1-[3,4-雙（三氟甲基）苯基]-3-[6-[4-(2 -甲氧基苯甲醯 基）六氫吡畊-1 -基]己基]-4 -甲基-1 Η -吡咯-2，5 -二酮 3-[6-(4-乙醯基六氫吡啩-1-基）己基]-1-[3,4-雙（三氟 甲基）苯基]-4 -甲基-1 Η -吡咯-2，5 -二酮 1-[3,4-雙（三氟甲基）苯基]-3-[6-[4-(環丁基羰基）六 氫吡畊-1 -基]己基]-4 -甲基-1 Η -吡咯-2，5 -二酮 1-[3,4-雙（三氟甲基）苯基]-3 -甲基-4-[6-[4-[〇塞-2-基） 羰基]-六氫吡畊-1 -基]己基]-1 Η -吡咯-2，5 -二酮 1-[3,4-雙（三氟甲基）苯基]-3-[6-[4-[4-(二甲基胺基） 苯甲醯基]六氫吡畊-1-基]己基]-4 -甲基-1Η-说咯-2,5-二酮 1-[3,4-雙（三氟甲基）苯基]-3 -甲基-4-[6-[4-(甲基磺 醯基）六氫吡畊-1 -基]己基]-1 Η -吡咯-2，5 -二酮 -58- 2003011171- [3,4-bis (trifluoromethyl) phenyl] -3- [6- [4- (2-methoxybenzylidene) hexahydropyridine-1 -yl] hexyl] -4 -Methyl-1 fluorene-pyrrole-2,5-dione 3- [6- (4-ethylfluorenylhexahydropyridin-1-yl) hexyl] -1- [3,4-bis (trifluoromethyl) ) Phenyl] -4-methyl-1 fluorene-pyrrole-2,5-dione 1- [3,4-bis (trifluoromethyl) phenyl] -3- [6- [4- (cyclo Butylcarbonyl) hexahydropyridine-1 -yl] hexyl] -4 -methyl-1 fluorene -pyrrole-2,5-dione 1- [3,4-bis (trifluoromethyl) phenyl]- 3 -methyl-4- [6- [4- [〇Se-2-yl) carbonyl] -hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-2,5-dione 1- [ 3,4-bis (trifluoromethyl) phenyl] -3- [6- [4- [4- (dimethylamino) benzamidine] hexahydropyridine-1-yl] hexyl]- 4-methyl-1H-sulphone-2,5-dione 1- [3,4-bis (trifluoromethyl) phenyl] -3 -methyl-4- [6- [4- (methyl Sulfonyl) hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-2,5-dione-58- 200301117 3 - [ 6 - [ 4 - [ ( 2，1，3 -苯并噻二唑-4 -基）磺醯基]六氫吡畊 -1-基]己基]-l-[3,4-雙（三氟甲基）苯基]-4 -甲基-1H-吡 咯-2，5 -二酮 1-[3 -氟-4-(三氟甲基）苯基]-3-[6-[4-(2 -甲氧基苯甲 醯基）六氫吡畊-1 -基]己基]-1 Η -吡咯-2，5 -二酮 3-[6-[4-(環丁基羰基）六氫吡畊-1-基]己基]-1-[3-氟 -4-(三氟甲基）苯基]-4 -甲基-1Η -吡咯-2,5 -二酮 1-[3-氟- 4-(三氟甲基）苯基]-3-甲基-4-[6-[4-(噻-2-基）· 羰基]六氫吡畊-1 -基]己基]-1 Η -吡咯-2，5 -二酮 3-[6-[4-[4-(二甲基胺基）苯甲醯基]六氫吡畊-1-基] 己基]-氟-4-(三氟甲基）苯基]-4-甲基-1Η-4咯 -2，5 -二酮3-[6-[4-[(2,1,3-Benzothiadiazol-4 -yl) sulfofluorenyl] hexahydropyridin-1-yl] hexyl] -l- [3,4-bis (Trifluoromethyl) phenyl] -4-methyl-1H-pyrrole-2,5-dione 1- [3-fluoro-4- (trifluoromethyl) phenyl] -3- [6- [ 4- (2-methoxybenzylidene) hexahydropyridine-1 -yl] hexyl] -1 hydrazone -pyrrole-2,5-dione 3- [6- [4- (cyclobutylcarbonyl) Hexahydropyridin-1-yl] hexyl] -1- [3-fluoro-4- (trifluoromethyl) phenyl] -4-methyl-1Η-pyrrole-2,5-dione 1- [3 -Fluoro 4- (trifluoromethyl) phenyl] -3-methyl-4- [6- [4- (thia-2-yl) · carbonyl] hexahydropyridine-1 -yl] hexyl]- 1 hydrazone -pyrrole-2,5 -dione 3- [6- [4- [4- (dimethylamino) benzylidene] hexahydropyridine-1-yl] hexyl] -fluoro-4- (Trifluoromethyl) phenyl] -4-methyl-1Η-4role-2,5-dione 3-[6-[4-乙醯基六氫吡畊-1-基]己基]-1-[3 -氟- 4- (三 氟曱基）苯基]-4 -甲基-1Η -吡咯-2,5 -二酮 1-[3-氟- 4-(三氟甲基）苯基]-3-甲基-4-[6-[4-(甲基磺 醯基）-六氫吡畊-1 -基]己基]-1 Η -批咯-2，5 -二酮 3-[6-[4-[(2，1，3-苯并嘧二唑-4-基）磺醯基]六氫吡畊 -1-基]己基]-1-[3 -氟-4-(三氟甲基）苯基]-4 -甲基-1Η-叶匕嘻-2，5 -二酮 3-[4-(4-乙醯基六氫吡畊-1-基）丁基]-1-(1，3-二氫-1-氧代異苯并呋喃-5 -基）-4 -甲基-1 Η -吡咯-2，5 -二酮 1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-3-甲基 -4 - [ 4 - [ 4 - ( 1 -氧代丙基）-六氫吡畊-1 -基]丁基]-1 Η -吡咯 -2，5 -二酮 -59- 2003011173- [6- [4-Acetylhexahydropyridin-1-yl] hexyl] -1- [3-fluoro-4 (trifluorofluorenyl) phenyl] -4 -methyl-1fluorene -pyrrole -2,5-dione 1- [3-Fluoro 4- (trifluoromethyl) phenyl] -3-methyl-4- [6- [4- (methylsulfonyl) -hexahydropyridine Plow-1 -yl] hexyl] -1 hydrazone -pyrrol-2,5-dione 3- [6- [4-[(2,1,3-benzopyridazol-4-yl) sulfonyl ] Hexahydropyrine-1-yl] hexyl] -1- [3-fluoro-4- (trifluoromethyl) phenyl] -4 -methyl-1fluorene-leaf dioxin-2,5 -dione 3 -[4- (4-Ethylhexylpyridin-1-yl) butyl] -1- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -4 -methyl -1 fluorene-pyrrole-2,5-dione 1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -3-methyl-4-[4-[4- (1-oxopropyl) -hexahydropyridine-1-yl] butyl] -1 hydrazone-pyrrole-2,5-dione-59- 200301117 1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-3-[4-[4-[(2-甲 氧基乙氧基）-乙醯基]六氫吡畊-1-基]丁基]-4 -甲基 -1 Η -吡咯-2，5 -二酮1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -3- [4- [4-[(2-methoxyethoxy) -ethenyl] hexahydro Pyrhen-1-yl] butyl] -4-methyl-1 fluorene-pyrrole-2,5-dione 1-(1，3 -二氯-1-氧代異苯并咬喃-5 -基）-3-[4-[4-[[2_ (2 -甲氧基乙氧基）乙氧基]-乙醯基]六氫吡畊-1-基]丁 基]_ 4 -甲基-1 Η -吡咯-2，5 -二酮 1-(1,3 -二氫-1-氧代異苯并呋喃-5 -基）-3-甲基 -4 - [ 4 - [ 4 -(甲基磺醯基）-六氫吡畊-1 -基]丁基]-1 Η -吡咯 -2，5 -二酮 4-[4-[1-(1，3 -二氮-1-氧代異冬并咬喃-5 -基）-2,5-«— 氫-4-甲基- 2,5-二氧代-lH-吡咯-3-基]丁基]-N-乙基六 氫吡畊-1 -碳硫醯胺 4-[4-[1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-2,5-二 氫-4-甲基-2,5-二氧代-111-吡咯-3-基]丁基]->^丙基六 氫吡畊-1 -後硫醯胺1- (1,3-dichloro-1-oxoisobenzoan-5-yl) -3- [4- [4-[[2_ (2-methoxyethoxy) ethoxy] -Ethylfluorenyl] hexahydropyridin-1-yl] butyl] -4 -methyl-1 fluorene -pyrrole-2,5-dione 1- (1,3-dihydro-1-oxoisobenzene Benzofuran-5 -yl) -3-methyl-4-[4-[4-(methylsulfonyl) -hexahydropyridine-1 -yl] butyl] -1 fluorene -pyrrole-2,5 -Diketone 4- [4- [1- (1,3 -diaza-1-oxoisodongol-5-yl) -2,5-«— hydro-4-methyl-2,5 -Dioxo-lH-pyrrole-3-yl] butyl] -N-ethylhexahydropyracin-1 -carbothioamide 4- [4- [1- (1,3-dihydro-1- Oxo-isobenzofuran-5-yl) -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] butyl]-> ^ propylhexa Hydropyrin-1 4-[4-[1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-2,5-二 氫-4 -甲基-2,5-二氧代-lH-吡咯-3-基]丁基]-N-(丙-2-烯基）六氫吡畊-l-碳硫醯胺 3-[5-(4-乙醯基六氫吡畊-1-基）戊基]-1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-4 -甲基- lH-p比咯- 2,5-二酮 1-(1,3 -二氫-1-氧代異苯并呋喃-5-基）-3-甲基 一 4 - [ 5 - [ 4 - ( 1 -氧代丙基）-六氫吡畊-1 -基]戊基]-1 Η - Ρ比咯 -2，5 -二酮 1-(1,3-二氫-1-氧代異苯并呋喃-5-基）-3-[5-[4-[(2-甲 -60- 2003011174- [4- [1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -2,5-dihydro-4 -methyl-2,5-dioxo- lH-pyrrole-3-yl] butyl] -N- (prop-2-enyl) hexahydropyridine-l-carbothiomamine 3- [5- (4-ethylpyridylhexahydropyridine-1 -Yl) pentyl] -1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -4 -methyl-lH-p-pyrrole-2,5-dione 1- (1,3 -Dihydro-1-oxoisobenzofuran-5-yl) -3-methyl- 4-[5-[4-(1 -oxopropyl) -hexahydropyracine-1 -Yl] pentyl] -1 fluorene-P-pyrrole-2,5-dione 1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -3- [5- [ 4-[(2-A-60- 200301117 氧基乙氧基）-乙醯基]六氫吡畊-1-基]戊基]-4 -甲基 -1 H j比咯-2，5 -二酮 1-(1,3 -二氫-1-氧代異苯并呋喃-5 -基）-3-[5-[4-[[2-(2 -甲氧基乙氧基）乙氧基]-乙醯基]六氫吡畊-1-基]戊 基]_ 4 -甲基-1 Η -吡咯-2，5 -二酮 1-(1,3-二氫-1-氧代異苯并呋喃-5 -基）-3-甲基 _ 4 - [ 5 - [ 4 -(甲基磺醯基）-六氫吡畊-1 -基]戊基]-1 Η -吡咯Ethoxyethoxy) -ethenyl] hexahydropyridin-1-yl] pentyl] -4 -methyl-1H jpyrole-2,5-dione 1- (1,3-dihydro -1-oxoisobenzofuran-5 -yl) -3- [5- [4-[[2- (2-methoxyethoxy) ethoxy] -acetamidinyl] hexahydropyridine -1-yl] pentyl] _4-methyl-1 fluorene-pyrrole-2,5-dione 1- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -3 -Methyl_ 4-[5-[4-(methylsulfonyl) -hexahydropyridine-1 -yl] pentyl] -1 fluorene -pyrrole 3 - [5-[4-(環丙基磺醯基）六氫吡畊-1-基]戊 基]-1-(1，3 -二氮-1-氧代異冬并咬喃-5 -基）-4 -甲基-1Η_ 叶匕ρ各-2，5 -二酮 1-(1,3 -二氣-1-氧代異冬并咬喃-5 -基）-3-[5-[4-[[2_ [2-(2 -甲氧基乙氧基）乙氧基]乙基]磺醯基]六氫吡畊 -1 -基]戊基]-4 -甲基-1 Η -吡咯-2，5 -二酮3-[5- [4- (Cyclopropylsulfonyl) hexahydropyridin-1-yl] pentyl] -1- (1,3 -diaza-1-oxoisodongol-5 -Yl) -4 -methyl-1Η_ leaf dagger each -2,5 -dione 1- (1,3 -digas-1-oxoisodong and sulfan-5 -yl) -3- [5 -[4-[[2_ [2- (2-methoxyethoxy) ethoxy] ethyl] sulfonyl] hexahydropyrimyl-1 -yl] pentyl] -4 -methyl-1 Η -Pyrrole-2,5-dione 4-[5-[1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-2,5-二 氫-4-甲基-2,5-二氧代-11^吡咯-3-基]戊基]-1^-乙基六 氫吡畊-1 -碳硫醯胺 4-[5-[1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-2,5-二 氫-4-甲基-2,5-二氧代-111-吡咯-3-基]戊基]-?^丙基六 氫吡畊-1 -碳硫醯胺 4-[5-[1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-2,5-二 氫-4 -甲基-2,5-二氧代-lH-吡咯-3-基]戊基]-N-(丙-2-晞基）六氫吡畊-l-碳硫醯胺 1-(1，3 -二氫-1-氧代異苯并呋喃-5-基）-3-[6-[4-(2 -甲 -61 - 2003011174- [5- [1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -2,5-dihydro-4-methyl-2,5-dioxo- 11 ^ pyrrole-3-yl] pentyl] -1 ^ -ethylhexahydropyridine-1 -carbothioamide 4- [5- [1- (1,3-dihydro-1-oxoisobenzene) Benzofuran-5-yl) -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] pentyl]-? Propylhexahydropyrrol-1 -Carbothioamide 4- [5- [1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -2,5-dihydro-4 -methyl-2,5 -Dioxo-lH-pyrrole-3-yl] pentyl] -N- (prop-2-fluorenyl) hexahydropyridine-l-carboxamidine 1- (1,3-dihydro-1- Oxo-isobenzofuran-5-yl) -3- [6- [4- (2-methyl-61-200301117 氧基苯甲醯基）六氫吡畊-1-基]己基卜4-甲基- ΙΗ-说咯 -2，5 -二酮 3 —[6-[4-(環丁基碳基）六氫吡畊-1-基]己基]-l-(l，3-二氫-l-氧代異苯并呋喃-5-基）-4-甲基-lH-吨咯-2,5-二酮 1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-3-甲基 • 4 - [ 6 - [ 4 -[(噻-2 -基）羰基]六氫吡畊-1 -基]己基]-1 Η -吡 咯-2，5 -二酮 1-(1，3 -二氮-1-氧代異冬并咬喃-5-基）-3-[6-[4-[4-(<一 甲基胺基）-苯甲醯基]六氫吡畊-1-基]己基]-4 -甲基 -1 Η -吡咯-2，5 -二酮 3- [6-(4-乙醯基六氫吡畊-1-基）己基]-1-(1，3-二氫-1-氧代異苯并呋喃-5 -基）-4 -甲基-1 Η - ρ比咯-2，5 -二酮 4- [4-[1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-2,5-二 氫-4-甲基-2,5-二氧代-111-吡咯-3-基]己基]*^3-二甲 基六氫吡畊-1 -磺醯胺 1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-3-甲基 _ 4 - [ 6 - [ 4 -(甲基磺醯基）-六氫吡畊-1 -基]己基]-1 Η -吡咯 -2，5 -二酮 3 - [ 6 - [ 4 - [(2，1，3 -苯并嘧二唑-4 -基）磺醯基]六氫吡畊 -1-基]己基]-1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-4-甲基-1 Η -吡咯-2，5 -二酮 1-(1,3-二氫-1-氧代異苯并呋喃-5-基）-3-[6-[4-(乙基 磺醯基）六氫吡畊-1 -基]己基]-4 -甲基-1 Η - ρ比咯-2，5 -二 -62- 20030111?Oxybenzyl) hexahydropyrimidin-1-yl] hexyl 4-methyl-1, -dioxo-2,5-dione 3 — [6- [4- (cyclobutylcarbonyl) hexa Pyridin-1-yl] hexyl] -l- (l, 3-dihydro-l-oxoisobenzofuran-5-yl) -4-methyl-lH-tonrole-2,5-di Ketone 1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -3-methyl • 4-[6-[4-[(thia-2-yl) carbonyl] hexahydro] Pycnogenol-1 -yl] hexyl] -1 hydrazone -pyrrole-2,5-dione 1- (1,3-diazol-1-oxoisodongol-5-yl) -3- [6 -[4- [4-(< monomethylamino) -benzylidene] hexahydropyridine-1-yl] hexyl] -4 -methyl-1 hydrazone -pyrrole-2,5-dione 3- [6- (4-Ethylhexylpyridin-1-yl) hexyl] -1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -4-methyl -1 Η-ρ-pyrrole-2,5-dione 4- [4- [1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -2,5-di Hydroxy-4-methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl] * ^ 3-dimethylhexahydropyrrolene-1 -sulfamidamine 1- (1,3-di Hydrogen-1-oxoisobenzofuran-5-yl) -3-methyl_ 4-[6-[4-(methylsulfonyl) -hexahydropyridine-1 -yl] hexyl] -1 Η -pyrrole-2,5 -dione 3-[6- [4-[(2,1,3-benzopyrimidazol-4-yl) sulfofluorenyl] hexahydropyridin-1-yl] hexyl] -1- (1,3-dihydro-1-oxy Isobenzofuran-5-yl) -4-methyl-1 fluorene-pyrrole-2,5-dione 1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -3- [6- [4- (Ethylsulfonyl) hexahydropyridine-1 -yl] hexyl] -4 -methyl-1 Η-ρbiro-2,5 -di-62- 20030111? 酮 4-[6-[l-(l，3 -二氫-1-氧代異苯并呋喃-5 -基）-2,5 -二 氫-4-甲基-2,5-二氧代-111-吡咯-3-基]己基]^-乙基六 氫吡畊-1 -碳硫醯胺 4-[6-[1-(1，3 -二氮-1-氧代異冬并咬喃-5 -基）-2,5->— 氫-4-甲基-2,5-二氧代-11吡咯-3-基]己基]*^-丙基六 氫吡畊-1 -碳硫醯胺 4-[6-[1-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-2,5 -二 氫-4-甲基-2,5-二氧代-11^-吡咯-3-基]己基]->^(丙-2-晞基）六氫吡畊-1 -碳硫醯胺 4-[6-[1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-2,5-二 氫-4 -甲基-2,5-二氧代-111-吡咯-3-基]己基]-〜（苯基 甲基）六氫吡畊-1 -碳硫醯胺 4-[6-[1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-2,5-二 氫-4 -甲基-2,5-二氧代-111-吡咯-3-基]己基]-?^[(4-甲 基苯基）甲基]六氫吡畊-1 -碳硫醯胺 N-[(4-氯苯基）甲基]-4-[6-[l-(l，3-二氫-1-氧代異苯 并呋喃-5 -基）-2，5 -二氫-4 -甲基-2，5 -二氧代-1 Η -吡咯 -3 -基]己基]六氫吡畊-1 -碳硫醯胺 4-[6-[1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-2,5-二 氫-4-甲基-2,5-二氧代-1^1-吡咯-3-基]己基]-]^-苯基六 氫吡畊-1 -碳硫醯胺 4-[6-[1-(1，3-二氫-1-氧代異苯并呋喃-5-基）-2,5-二 氫-4-甲基-2,5-二氧代-111-吡咯-3-基]己基]->^(2,6-二 -63- 200301117Ketone 4- [6- [l- (l, 3-dihydro-1-oxoisobenzofuran-5 -yl) -2,5-dihydro-4-methyl-2,5-dioxo -111-pyrrole-3-yl] hexyl] ^-ethylhexahydropyridine-1 -carbothioamide 4- [6- [1- (1,3 -diazine-1-oxoiso Winter) Alan-5 -yl) -2,5- > —hydro-4-methyl-2,5-dioxo-11pyrrole-3-yl] hexyl] * ^-propylhexahydropyridine-1- Carbothioamide 4- [6- [1- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -2,5-dihydro-4-methyl-2,5- Dioxo-11 ^ -pyrrole-3-yl] hexyl]-> ^ (propyl-2-amidino) hexahydropyridine-1 -carbothioamide 4- [6- [1- (1,3 -Dihydro-1-oxoisobenzofuran-5-yl) -2,5-dihydro-4 -methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl]-~ (Phenylmethyl) hexahydropyridine-1 -carbothioamide 4- [6- [1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -2,5 -Dihydro-4 -methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl]-? ^ [(4-methylphenyl) methyl] hexahydropyridine-1 -carbon Thiamine N-[(4-chlorophenyl) methyl] -4- [6- [l- (l, 3-dihydro-1-oxoisobenzofuran-5 -yl) -2,5 -Dihydro-4 -methyl-2,5 -dioxo-1 Η -pyrrole-3 -yl] hexyl] hexahydropyridine-1 -carbon Thiamidine 4- [6- [1- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -2,5-dihydro-4-methyl-2,5-di Oxo-1 ^ 1-pyrrole-3-yl] hexyl]-] ^-phenylhexahydropyridine-1 -carbothioamide 4- [6- [1- (1,3-dihydro-1- Oxo-isobenzofuran-5-yl) -2,5-dihydro-4-methyl-2,5-dioxo-111-pyrrole-3-yl] hexyl]-> ^ (2,6 -Two-63- 200301117 甲基苯基）六氫吡畊-1 -碳硫醯胺 3-[6-[4-(2 -甲氧基苯甲醯基）六氫吡畊-1-基]己基]-4-甲基_1-(4 -甲基-1-氧代-1Η-2,3-苯并吟畊-6-基）-1Η-吡 咯-2，5 -二酮 3 _ [6-[4-(環丁基羰基）六氫吡畊-1-基]己基]-4 -甲基 -1 - (4 -甲基-1 -氧代-1 Η - 2，3 -苯并崎畊-6 -基）-1 Η -说咯 -2，5 -二酮(Methylphenyl) hexahydropyridine-1 -carbothioxamine 3- [6- [4- (2-methoxybenzylidene) hexahydropyridine-1-yl] hexyl] -4-methyl 1- (4-methyl-1-oxo-1'-2,3-benzyl-6-yl) -1'-pyrrole-2,5-dione 3 _ [6- [4- ( Cyclobutylcarbonyl) hexahydropyridin-1-yl] hexyl] -4 -methyl-1-(4-methyl-1 -oxo-1 fluorene -2,3 -benzozaki-6 -yl ) -1 Η -speak slightly -2,5 -dione 3-甲基-1-(4-甲基-1-氧代-1Η·2,3-苯并嘮畊-6-基 ） _ 4 - [ 6 - [ 4 - [(嘧 - 2 - 基） 羰基] 六 氫吡畊 - 1 - 基] 己基] - 1 Η - 叶匕嘻-2，5 -二酮 3-[6-[4-[4-(二甲基胺基）苯甲醯基]六氫吡畊-1-基] 己基]_4_甲基-1-(4 -甲基-1-氧代-1Η-2,3-苯并呤畊-6-基）-1 Η -吡咯-2，5 ·二酮 3-[6-(4-乙醯基六氫吡畊-1-基）己基]-4 -甲基-1-(4 -甲 基-1 -氧代-1 Η - 2，3 -苯并崎畊-6 -基）-1 Η -吡咯-2，5 -二酮3-methyl-1- (4-methyl-1-oxo-1Η · 2,3-benzopyrene-6-yl) _ 4-[6-[4-[(pyrimidin-2-yl) Carbonyl] hexahydropyridine-1 -yl] hexyl]-1 Η-dagger -2,5 -dione 3- [6- [4- [4- (dimethylamino) benzyl] Hexahydropyridine-1-yl] hexyl] _4-methyl-1- (4-methyl-1-oxo-1fluorene-2,3-benzopyridine-6-yl) -1 pyrene-pyrrole- 2,5 · diketone 3- [6- (4-ethylfluorenylhexahydropyridin-1-yl) hexyl] -4 -methyl-1- (4-methyl-1 -oxo-1 Η- 2,3-Benzobenzozine-6-yl) -1 pyrene-pyrrole-2,5-dione 3-甲基-1-(4-甲基-1-氧代-1Η-2,3-苯并呤畊-6-基）-4 - [ 6 - [ 4 -(甲基磺醯基）六氫吡畊-1 -基]己基]-1 Η -吡 咯-2，5 -二酮 1-(2,3 -二氫-1-氧代-1Η -茚-5-基）-3-[6-[4-(2 -甲氧基 苯甲醯基）六氫吡畊-1 -基]己基]-4 -甲基-1 Η -吡咯-2，5 -二酮 3-[6-[4-(環丁基羰基）六氫吡畊-1-基]己基]-1-(2,3-二氫-1 -氧代-1 Η -茚-5 -基）-4 -甲基-1 Η -外匕咯-2，5 -二酮 1-(2,3 -二氫-1-氧代-1Η -茚-5 -基）-3 -甲基-4-[6-[4- -64- 2003011173-methyl-1- (4-methyl-1-oxo-1'-2,3-benzopyridin-6-yl) -4-[6-[4-(methylsulfonyl) hexa Hydropyridine-1 -yl] hexyl] -1 Η -pyrrole-2,5-dione 1- (2,3-dihydro-1-oxo-1Η-inden-5-yl) -3- [6 -[4- (2-methoxybenzylidene) hexahydropyridine-1 -yl] hexyl] -4 -methyl-1 hydrazone -pyrrole-2,5-dione 3- [6- [4 -(Cyclobutylcarbonyl) hexahydropyridin-1-yl] hexyl] -1- (2,3-dihydro-1 -oxo-1 fluorene-inden-5 -yl) -4 -methyl-1 Η -Exo-2,5 -dione 1- (2,3 -dihydro-1-oxo-1 Η -inden-5 -yl) -3 -methyl-4- [6- [4-- 64- 200301117 [(噻-2 -基）羰基]六氫吡畊-1 -基]己基]-1 Η -说咯-2，5 -二 酮 1-(2,3 -二氫-1-氧代-1Η -茚-5-基）-3-[6-[4-[4-(二甲基 胺基）苯甲醯基]六氫吡畊-1-基]己基]-4-甲基- ΙΗ-说咯 -2，5 -二酮 3- [6-(4 -乙醯基六氫吡畊-1-基）己基]-l-(2,3-二氫-l-氧代-lH-茚-5-基）-4-甲基-lH-叶l:咯-2,5-二酮[(Thi-2-yl) carbonyl] hexahydropyridine-1 -yl] hexyl] -1 Η -Sale-2,5-dione 1- (2,3-dihydro-1-oxo-1Η -Inden-5-yl) -3- [6- [4- [4- (dimethylamino) benzylidene] hexahydropyridin-1-yl] hexyl] -4-methyl- 1Η- Say -2,5 -dione 3- [6- (4-Ethylhexylpyridin-1-yl) hexyl] -l- (2,3-dihydro-l-oxo-lH-indene -5-yl) -4-methyl-lH-leaf l: role-2,5-dione 1-(2,3 -二氫-1-氧代-1Η -茚-5-基）-3 -甲基-4- [6-[4-(甲 基磺醯基）六氫吡畊-1 -基]己基]-1 Η -吡咯-2，5 -二酮 3 - [ 6 - [ 4 - [(2，1，3 -苯并噻二唑-4 -基）磺醯基]六氫吡畊 -1-基]己基]-1-(2，3 -二氫-1-氧代-1Η -雖-5-基）-4 -甲基 -1 Η -说咯-2，5 -二酮 4- [3-[2-(4-乙醯基六氫吡畊-1-基）乙基]-4,4-二甲基 -5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯甲腈1- (2,3 -dihydro-1-oxo-1'-inden-5-yl) -3 -methyl-4- [6- [4- (methylsulfonyl) hexahydropyroxy-1 -Yl] hexyl] -1 Η -pyrrole-2,5 -dione 3-[6-[4-[(2,1,3-benzobenzodiazol-4 -yl) sulfonyl] hexahydropyridine] Phen-1-yl] hexyl] -1- (2,3-dihydro-1-oxo-1Η-though-5-yl) -4-methyl-1Η-speaking-2,5-dione 4- [3- [2- (4-Ethylhexylpyridin-1-yl) ethyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl ] -2-(trifluoromethyl) benzonitrile 4-[4,4·二甲基-5-氧代- 3- [2-[4-(1-氧代丙基）六氫吡 畊-1 -基]乙基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯甲 腈 4-[4,4-二甲基- 3- [2-[4-(2 -甲基-1-氧代丙基）六氫吡 畊-1 -基]乙基]-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲 基）苯甲腈 4-[4,4 - 一 甲基-5-氧代- 3- [2-[4-(1-氧代丁基）ττ 鼠口比 畊-1 -基]乙基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯甲 腈 4-[3-[2-[4-(環丙基羰基）六氫吡畊-1-基]乙基]-4，4- -65- 2003011174- [4,4 · dimethyl-5-oxo- 3- [2- [4- (1-oxopropyl) hexahydropyrine-1 -yl] ethyl] -2 -thioximidazole Pyridin-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl-3-[2- [4- (2-methyl-1-oxopropyl) Hexahydropyrimyl-1 -yl] ethyl] -5 -oxo-2 -thiooximidazol-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4,4 -monomethyl -Yl-5-oxo-3-[2- [4- (1-oxobutyl) ττ rat mouth pike-1 -yl] ethyl] -2 -thioximidazol-1 -yl] -2 -(Trifluoromethyl) benzonitrile 4- [3- [2- [4- (cyclopropylcarbonyl) hexahydropyridine-1-yl] ethyl] -4,4- -65- 200301117 二甲基_ 5 -氧代-2 -硫乳味σ坐淀-1-基]-2-(二氣甲基）丰 甲月f 4-[3-[2-[4-(環丁基羰基）六氫吡畊-1-基]乙基]-4,4-二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯 甲腈 4-[4,4-二甲基-5-氧代- 3- [2-[4-[(噻-2-基）乙醯基]六 氫吡畊-1-基]乙基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）Dimethyl_ 5 -oxo-2 -sulfur milky flavor σ sitting lake-1-yl] -2- (digas methyl) fungazol f 4- [3- [2- [4- (cyclobutyl (Carbonyl) hexahydropyridin-1-yl] ethyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzyl Nitrile 4- [4,4-dimethyl-5-oxo- 3- [2- [4-[(thia-2-yl) ethylfluorenyl] hexahydropyridin-1-yl] ethyl]- 2-thiooximidazol-1-yl] -2- (trifluoromethyl) 苯甲月青 4-[4,4-二甲基-5-氧代- 3- [2-[4-[(噻-2 -基）羰基]六氫 吡畊-1-基]乙基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲腈 4-[4,4-二甲基-5-氧代-3- [2-[4-[(吡啶-4 -基）羰基]六 氮p比17并-1 -基]乙基]-2 -硫氧味唆淀-1-基]-2-(二氣甲基） 苯甲月tBenzylpyrene 4- [4,4-dimethyl-5-oxo-3- [2- [4-[(thia-2-yl) carbonyl] hexahydropyridin-1-yl] ethyl] 2-thiothioimidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [2- [4-[( Pyridine-4 -yl) carbonyl] hexazine p ratio 17 acyl-1 -yl] ethyl] -2 -thiooxy misodian-1-yl] -2- (difluoromethyl) benzyl t 4-[4,4-二甲基- 3-[2-[4-(甲基磺醯基）六氫吡畊-1-基] 乙基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[2-[4-(乙基磺醯基）六氫吡畊-1-基]乙基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲腈 4-[4,4-二甲基-5-氧代-3-[2-[4-(丙基磺醯基）六氫吡 畊-1-基]乙基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[4,4-二甲基-5-氧代-3-[2-[4-(苯基磺醯基）六氫吡 -66- 2003011174- [4,4-dimethyl- 3- [2- [4- (methylsulfonyl) hexahydropyridin-1-yl] ethyl] -5-oxo-2-thiooximidazole -1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [2- [4- (ethylsulfonyl) hexahydropyridin-1-yl] ethyl] -4, 4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo- 3- [2- [4- (propylsulfonyl) hexahydropyridin-1-yl] ethyl] -2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzyl Nitrile 4- [4,4-dimethyl-5-oxo-3- [2- [4- (phenylsulfonyl) hexahydropyridine-66- 200301117 畊-1-基]乙基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[2-[4-[(4-氰基苯基）磺醯基]六氫吡畊-1-基]乙 基卜4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈Phen-1-yl] ethyl] -2-thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [2- [4-[(4-cyano Phenyl) sulfonyl] hexahydropyridin-1-yl] ethylbuthyl-4,4-dimethyl-5 -oxo-2 -thioximimidazol-1 -yl] -2-(trifluoromethyl Base) benzonitrile 4-[2-[3-[4-氰基-3-(三氟甲基）苯基]磺醯基]-5,5-二 甲基-4-氧代-2-硫氧咪峻淀-1-基]乙基]-N -乙基六氫叶匕 畊-1 -碳硫醯胺 4-[2-[3-[4-氰基-3-(三氟甲基）苯基]磺醯基]-5,5-二 甲基-4 -氧代-2-硫氧咪峻淀-1-基]乙基]-N -丙基六氫叶匕 畊-1 -碳硫醯胺 4-[2-[3-[4-氰基-3-(三氟甲基）苯基]磺醯基]-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]乙基]-N-(丙-2-烯基） 六氫吡畊-1 -碳硫醯胺4- [2- [3- [4-cyano-3- (trifluoromethyl) phenyl] sulfofluorenyl] -5,5-dimethyl-4-oxo-2-thioxanthene -1-yl] ethyl] -N-ethylhexahydropyridine-1 -carbothioamide 4- [2- [3- [4-cyano-3- (trifluoromethyl) phenyl] Sulfofluorenyl] -5,5-dimethyl-4 -oxo-2-thioxoamido-1-yl] ethyl] -N-propylhexahydropyridine-1 -carboxamidine 4- [2- [3- [4-cyano-3- (trifluoromethyl) phenyl] sulfonyl] -5,5-dimethyl-4-oxo-2-thiooximidazolidine- 1-yl] ethyl] -N- (prop-2-enyl) hexahydropyridine-1 -carbothioamide 4-[2-[3-[4-氰基-3-(三氟甲基）苯基]磺醯基]-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]乙基]六氫吡畊-1-碳 硫酸S -甲酯 4-[2-[3-[4-氰基-3-(三氟甲基）苯基]磺醯基]-5,5-二 甲基-4 -氧代-2 -硫氧咪哇淀-1 -基]乙基]六氫p比_ -1 -碳 硫酸S -乙酯 4-[3-[3-[4-(2-甲氧基苯甲醯基）六氫吡畊-1-基]丙 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟 甲基）苯甲腈 4-[3-[3-(4-乙醯基六氫吡畊-1-基）丙基]-4,4-二甲基 -67· 2003011174- [2- [3- [4-cyano-3- (trifluoromethyl) phenyl] sulfonyl] -5,5-dimethyl-4-oxo-2-thiooximidazolidine- 1-yl] ethyl] hexahydropyridine-1-carbon sulfate S-methyl 4- [2- [3- [4-cyano-3- (trifluoromethyl) phenyl] sulfonyl]- 5,5-dimethyl-4 -oxo-2 -thioxomidazoline-1 -yl] ethyl] hexahydro p ratio -1 -carbon sulfate S -ethyl 4- [3- [3- [4- (2-methoxybenzylidene) hexahydropyridin-1-yl] propyl] -4,4-dimethyl-5-oxo-2-thioximidazol-1-yl ] -2- (trifluoromethyl) benzonitrile 4- [3- [3- [4- (Ethylhexylpyridin-1-yl) propyl] -4,4-dimethyl-67 · 200301117 -5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4-[4,4-二甲基-5-氧代- 3- [3-[4-(l-氧代丙基）六氫吡 口井-1 -基]-丙基]-2 -硫氧k味σ全淀-1 -基]-2 -(二氣甲基）冬 甲月青 4-[4,4-二甲基- 3- [3-[4-(2 -甲基-1-氧代丙基）六氫吡 畊-1 -基]丙基]-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲 基）苯甲腈 4-[4,4-二甲基-5-氧代- 3-[3-[4-(1-氧代丁基）六氫吡 畊-1-基]丙基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[3-[4-(環丙基談基）六氫ρ比哨-1-基]丙基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲腈 4-[3-[3-[4-(環丁基羰基）六氫吡畊-1-基]丙基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲月青 4-[4,4-二甲基-5-氧代-3- [3-[4-(嘧-2-基）乙醯基]六 氫吡畊-1 -基]丙基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基） 苯甲腈 4-[4,4-二甲基-5-氧代-3-[3-[4-(噻-2-基）羰基]六氫 吡畊-1-基]丙基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 曱月膏 4-[4,4-二甲基-5-氧代-3-[3-[4-(吡啶-4-基）羰基]六 氫吡畊-1 -基]丙基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基） -68- 200301117-5-oxo-2-thiooxyimidazolidin-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- 3- [3- [4- (l-oxopropyl) hexahydropyranowell-1 -yl] -propyl] -2 -thiooxy k odor sakayodo-1 -yl] -2-(digas methyl) dong Methylpyrene 4- [4,4-dimethyl- 3- [3- [4- (2-methyl-1-oxopropyl) hexahydropyrine-1 -yl] propyl] -5- Oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3-[3- [4- (1-oxobutyl) hexahydropyridine-1-yl] propyl] -2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [ 3- [4- (Cyclopropylalkynyl) hexahydro-r [rho] -1-yl] propyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [3- [4- (cyclobutylcarbonyl) hexahydropyrine-1-yl] propyl] -4,4-dimethyl- 5-oxo-2-thiooxyimidazolidine-1-yl] -2- (trifluoromethyl) benzylazine 4- [4,4-dimethyl-5-oxo-3- [3- [4- (pyrim-2-yl) ethenyl] hexahydropyridine-1 -yl] propyl] -2-thiothioimidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [3- [4- (thia-2-yl) carbonyl] hexahydropyridine-1-yl ] Propyl] -2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzene hydrazone cream 4- [4,4-dimethyl-5-oxo-3- [3- [4- (pyridin-4-yl) carbonyl] hexahydropyridine-1 -yl] propyl] -2-thiothioimidazol-1-yl] -2-(trifluoromethyl) -68- 200301117 苯甲月膏 4-[3-[3-[4-(3 -甲氧基-1-氧代丙基）六氫吡畊-1-基]丙 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4-[3-[3-[4-[(2 -甲氧基乙氧基）乙醯基]六氫吡畊-1-基] 丙基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三 氟甲基）苯甲腈Benzyl month cream 4- [3- [3- [4- (3-methoxy-1-oxopropyl) hexahydropyrine-1-yl] propyl] -4,4-dimethyl- 5-oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [3- [3- [4-[(2-methoxyethoxy) Ethylfluorenyl] hexahydropyridine-1-yl] propyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) Benzonitrile 4-[3-[3-[4-[[2-(2 -甲氧基乙氧基）乙氧基]乙醯基]六 氫吡畊-1-基]丙基]_ 4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 4-[4,4-二甲基-3-[3-[4-(甲基磺醯基）六氫吡畊-1-基] 丙基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4 - [ 3 - [ 3 - [ 4 -(乙基磺醯基）六氫吡畊-1 -基]丙基]-4，4 -二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯4- [3- [3- [4-[[2- (2-methoxyethoxy) ethoxy] ethenyl] hexahydropyridin-1-yl] propyl] _ 4,4- Dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-3- [3- [4 -(Methylsulfonyl) hexahydropyridin-1-yl] propyl] -5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4 -[3-[3-[4-(Ethylsulfonyl) hexahydropyridine-1 -yl] propyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine- 1-yl] -2- (trifluoromethyl) benzene 甲月青 4-[4,4-二甲基-5 -氧代-3-[3-[4-(丙基磺醯基）六氫吡 畊-1-基]丙基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[4,4-二甲基-5-氧代-3-[3-[4-(苯基磺醯基）六氫吡 畊-1-基]丙基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[3-[4-[(4 -氰基苯基）磺醯基]六氫吡畊-1-基]丙 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 -69- 200301117Methylpyrene 4- [4,4-dimethyl-5 -oxo-3- [3- [4- (propylsulfonyl) hexahydropyridin-1-yl] propyl] -2-sulfide Oximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [3- [4- (phenylsulfonyl ) Hydroxypyrine-1-yl] propyl] -2-thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [3- [4-[( 4-cyanophenyl) sulfofluorenyl] hexahydropyridin-1-yl] propyl] -4,4-dimethyl-5 -oxo-2 -thioximimidazol-1 -yl] -2 -(Trifluoro-69- 200301117 甲基）苯甲腈 4-[3-[3-[4 -氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l基]丙基]-N-乙基六氫吡畊-l-碳 硫醯胺 4-[3-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]丙基]-N-丙基六氫吡畊-l-碳 硫醯胺Methyl) benzonitrile 4- [3- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thioximidazole Pyridyl-l-yl] propyl] -N-ethylhexahydropyridine-l-carboxamidine 4- [3- [3- [4-cyano-3- (trifluoromethyl) phenyl]- 5,5-dimethyl-4-oxo-2-thiooximidazolidine-l-yl] propyl] -N-propylhexahydropyridine-l-carboxamidine 4-[3-[3-[4-氰基- 3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]丙基]-N-(丙-2-晞基）六氫吡 畊-1 -碳硫醯胺 4-[3-[3-[4 -氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪σ坐淀-l-基]丙基]六氫p比p井-l-破硫酸S-甲酉旨 4-[3-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪σ坐淀-l-基]丙基]六氫p比p井-l-破硫酸S-4- [3- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazol-l-yl] Propyl] -N- (prop-2-fluorenyl) hexahydropyridine-1 -carbothioamide 4- [3- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-Dimethyl-4-oxo-2-thiooxyimidoσ-l-yl-propyl] propyl] hexahydro p ratio p-well-l-sulfuric acid S-formyl 4- [3 -[3- [4-Cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thioxomidazolyl-l-yl] propyl ] Hexane p ratio p well-l-broken sulfuric acid S- 乙酉旨 4-[3-[4-[4-(2 -甲氧基苯甲醯基）六氫吡畊-1-基]丁 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4-[3-[4-(4-乙醯基六氫吡畊-1-基）丁基]-4,4-二甲基 -5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4-[4,4-二甲基-5-氧代- 3- [3-[4-(l-氧代丙基）六氫吡 畊-1-基]丁基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 -70- 20030111?Acetyl 4- [3- [4- [4- (2-methoxybenzylidene) hexahydropyridin-1-yl] butyl] -4,4-dimethyl-5 -oxo- 2-thiothioimidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4- [3- [4- (4-ethylfluorenylhexahydropyridin-1-yl) butyl]- 4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo -3- [3- [4- (l-oxopropyl) hexahydropyridin-1-yl] butyl] -2-thiooximidazol-1-yl] -2- (trifluoromethyl ) Benzonitrile-70- 20030111? 4-[4,4-二甲基-3-[4-[4-(2 -甲基-1-氧代丙基）六氫吡 口井-1-基]丁基]-5 -氧代-2-硫氧1味哇淀-1-基]-2-(二氣甲 基）苯甲腈 4-[4,4-二甲基-5-氧代- 3- [3-[4-(l-氧代丁基）六氫吡 畊-1-基]丁基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈4- [4,4-dimethyl-3- [4- [4- (2- (methyl-1-oxopropyl) hexahydropyrano-1-yl] butyl] -5-oxo -2-thiooxy 1 misawadien-1-yl] -2- (digasmethyl) benzonitrile 4- [4,4-dimethyl-5-oxo- 3- [3- [4- (l-oxobutyl) hexahydropyridin-1-yl] butyl] -2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4_[3-[4-[4_(環丙基羰基）六氫吡畊-1-基]丁基]_4,4_ 二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲腈 4-[3-[4-[4-(環丁基羰基）六氫吡畊-1-基]丁基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲腈 4-[4,4·二甲基-5-氧代-3- [4-[4-[〇塞-2-基）乙醯基]六 氫吡畊-1-基]丁基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基） 苯甲月青4_ [3- [4- [4_ (Cyclopropylcarbonyl) hexahydropyridin-1-yl] butyl] _4,4_dimethyl-5-oxo-2-thiooximidazol-1-yl] 2- (trifluoromethyl) benzonitrile 4- [3- [4- [4- (cyclobutylcarbonyl) hexahydropyrine-1-yl] butyl] -4,4-dimethyl- 5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4 · dimethyl-5-oxo-3- [4- [ 4- [〇Se-2-yl) ethenyl] hexahydropyridin-1-yl] butyl] -2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzyl green 4-[3-[4-[4_(3 -甲氧基-1-氧代丙基）六氫吡畊-1-基]丁 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4-[3-[4-[4-[(2 -甲氧基乙氧基）乙醯基]六氫吡畊-1-基] 丁基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 _基]-2 -(三 氟甲基）苯甲腈 4-[3-[4-[4-[[2-(2 -甲氧基乙氧基）乙氧基]乙醯基]六 氫叶I： 11井-1 -基]丁基]-4,4 -二甲基-5 -氧代-2 -硫氧咪哇淀 -1-基]-2-(三氟甲基）苯甲腈 -71 - 2003011174- [3- [4- [4_ (3-methoxy-1-oxopropyl) hexahydropyrine-1-yl] butyl] -4,4-dimethyl-5 -oxo- 2-thiothioimidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4- [3- [4- [4-[(2-methoxyethoxy) ethenyl] hexa] Hydropyrin-1-yl] butyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [3- [4- [4-[[2- (2-methoxyethoxy) ethoxy] ethenyl] hexahydro leaf I: 11 well-1 -yl] butyl] -4,4 -Dimethyl-5 -oxo-2 -thioxanmidone-1-yl] -2- (trifluoromethyl) benzonitrile-71-200301117 4 - [ 3 - [ 4 - [ 4 - [ ( 1，3 -二甲基-1 Η -吡唑-5 -基）羰基]六氫吡 畊-1 -基]丁基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[4-[4-[(呋喃-3 -基）羰基]六氫吡畊-1-基]丁 基]_ 4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4 - [ 3 - [ 4 - [ 4 - [( 2，5 -二甲基呋喃-3 -基）羰基]六氫吡畊 -1 -基]丁基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-卜 基]-2-(三氟甲基）苯甲腈 4-[3-[4-[4-[(異哼唑-5-基）羰基]六氫吡畊-1-基]丁 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4-[4,4-二甲基- 3-[4-[4-[(5 -甲基異呤唑-3-基）羰基] 六氫吡畊-1 -基]丁基]-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[4,4-二甲基-5-氧代-3-[4-[4-( 口塞-3 -基）羰基]六氫 吡畊-1 -基]丁基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯 甲月青 4-[4,4-二甲基- 3-[4-[4-[(4 -甲基-1，2,3-噻二唑-4-基） 羰基]六氫吡畊-1 -基]丁基]-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[4-[4-[(呋喃-2 -基）羰基]六氫吡畊-1-基]丁 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 -72- 2003011174-[3-[4-[4-[(1, 3 -Dimethyl-1 fluorene-pyrazol-5 -yl) carbonyl] hexahydropyridine-1 -yl] butyl] -4,4- Dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4-[(furan-3 -yl ) Carbonyl] hexahydropyridin-1-yl] butyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzene Carbonitrile 4-[3-[4-[4-[(2,5-dimethylfuran-3 -yl) carbonyl] hexahydropyridine-1 -yl] butyl] -4,4-dimethyl -5 -oxo-2 -thioximidazolidine-butyl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4-[(isohumazol-5-yl) carbonyl ] Hexahydropyrim-1-yl] butyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl- 3- [4- [4-[(5-methylisopurazol-3-yl) carbonyl] hexahydropyridine-1 -yl] butyl] -5- Oxo-2 -thiothioimidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [4- [4- (Moxa-3 -yl) carbonyl] hexahydropyridine-1 -yl] butyl] -2-thiothioimidazol-1-yl] -2-(trifluoromethyl) benzylazine 4- [ 4,4-dimethyl- 3- [4- [4-[(4 -Methyl-1,2,3-thiadiazol-4-yl) carbonyl] hexahydropyridine-1 -yl] butyl] -5 -oxo-2 -thioximimidazol-1 -yl]- 2- (trifluoromethyl) benzonitrile 4- [3- [4- [4-[(furan-2-yl) carbonyl] hexahydropyridine-1-yl] butyl] -4,4-di Methyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile-72- 200301117 4-[4,4-二甲基-5-氧代- 3-[4-[4-(噻-2 -基）羰基]六氫 吡畊-1-基]丁基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲月f 4-[4,4-二甲基-5-氧代-3-[4-[4-(吡啶-4-基）羰基]六 鼠p比呼-1_基]丁基]-2 -硫氧味σ坐淀-1-基]-2-(二氣甲基） 苯甲腈4- [4,4-dimethyl-5-oxo- 3- [4- [4- (thia-2 -yl) carbonyl] hexahydropyridine-1-yl] butyl] -2-thiooxy Imidazol-1-yl] -2- (trifluoromethyl) benzyl f 4- [4,4-dimethyl-5-oxo-3- [4- [4- (pyridin-4-yl ) Carbonyl] hexamidine pbihexyl-1-yl] butyl] -2-thiothio sigma azeo-1-yl] -2- (difluoromethyl) benzonitrile 4-[4,4-二甲基-3- [4-[4-(甲基磺醯基）六氫吡畊-1-基] 丁基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4 - [ 3 - [ 4 - [ 4 -(乙基磺醯基）六氫吡畊-1 -基]丁基]-4，4 -二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲月膏 4-[4,4-二甲基-5 -氧代-3- [4-[4-(丙基磺醯基）六氫吡 畊-1-基]丁基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈4- [4,4-dimethyl-3- [4- [4- (methylsulfonyl) hexahydropyridine-1-yl] butyl] -5-oxo-2-thiooximidazole -1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[4-[4-(ethylsulfonyl) hexahydropyridine-1 -yl] butyl] -4, 4-Dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzyl cream 4- [4,4-dimethyl-5 -oxo -3- [4- [4- (propylsulfonyl) hexahydropyridine-1-yl] butyl] -2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzene Nitrile 4-[4,4-二甲基-5-氧代-3-[4-[4-(苯基磺醯基）六氫吡 畊-1-基]丁基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[4-[4-[(4-氰基苯基）磺醯基]六氫吡畊-1·基]丁 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4-[4,4-二甲基- 3- [4-[4-[(1-甲基-1Η -咪唑-4-基）磺醯 基]7Τ鼠0比啡-1-基]丁基]-5 -氧代-2 -硫氧味σ坐咬-1 _ 基]-2-(三氟甲基）苯甲腈 -73 - 2003011174- [4,4-dimethyl-5-oxo-3- [4- [4- (phenylsulfonyl) hexahydropyridine-1-yl] butyl] -2-thiooximidazole -1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [4-[(4-cyanophenyl) sulfonyl] hexahydropyridine-1 · yl] Butyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl -3- [4- [4-[(1-methyl-1Η-imidazol-4-yl) sulfofluorenyl] 7T mouse 0bimorph-1-yl] butyl] -5 -oxo-2 -sulfur Oxygen sigma sitting bite -1 _yl] -2- (trifluoromethyl) benzonitrile-73-200301117 4-[3-[4-[4-[(3,5-二甲基異呤唑-4-基）磺醯基]六氫吡 畊-1 -基]丁基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[4-[3-[4 -氰基-3-(三氟甲基）苯基]-5,5·二甲基-4-氧代-2-硫氧咪σ坐淀-l-基]丁基]-N-乙基六氫p比tr井-l-碳 硫醯胺4- [3- [4- [4-[(3,5-dimethylisopurazol-4-yl) sulfofluorenyl] hexahydropyridine-1 -yl] butyl] -4,4-di Methyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [4- [3- [4 -cyano-3- (trifluoro (Methyl) phenyl] -5,5 · dimethyl-4-oxo-2-thioxomidazolyl-l-yl] butyl] -N-ethylhexahydrop ratio tr-l-l- Carbamide 4-[4-[3-[4-氣基-3-(二氣甲基）冬基]-5,5-^ — 甲基-4-氧代-2-硫氧咪唑啶-1-基]丁基]-N -丙基六氫吡畊-1-碳 硫醯胺 4-[4-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]丁基]-N-(丙-2-晞基）六氫吡 畊-1 -碳硫醯胺 4-[4-[3-[4-氰基- 3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]丁基]六氫吡畊-l-碳硫酸S-甲酉旨4- [4- [3- [4-Gas-3- (diaminomethyl) hexyl] -5,5- ^ —methyl-4-oxo-2-thioximidazol-1-yl ] Butyl] -N-propylhexahydropyridine-1-carboxamidine 4- [4- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5- Dimethyl-4-oxo-2-thiooximidazolidine-l-yl] butyl] -N- (prop-2-amidino) hexahydropyrimidine-1 -carbothioamide 4- [4- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazolidine-l-yl] butyl] hexahydro Pycnogenol-l-Carbon Sulphate 4-[4-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l_基]丁基]六氫吡畊-l-碳硫酸S-乙酉旨 4-[3-[5-(4-乙醯基六氫吡畊-1-基）戊基]-4,4-二甲基 -5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯甲腈 4-[4,4-二甲基-5-氧代- 3-[5-[4-(l-氧代丙基）六氫吡 畊-1 -基]戊基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯甲 腈 4-[4,4-二甲基- 3-[5-[4-(2 -甲基-1-氧代丙基）六氫吡 -74- 2003011174- [4- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazol-l-yl] Butyl] hexahydropyridine-l-carbosulfate S-acetamidine -5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3-[5- [4- (l-oxopropyl) hexahydropyridine-1 -yl] pentyl] -2-thiothioimidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4- [ 4,4-dimethyl- 3- [5- [4- (2-methyl-1-oxopropyl) hexahydropyridine-74- 200301117 畊-1 -基]戊基]-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲 基）苯甲腈 4-[4,4-二甲基-5-氧代- 3- [5-[4-(l-氧代丁基）六氫吡 畊-1-基]戊基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4 - [ 3 - [ 5 - [ 4 -(環丙基羰基）六氫吡畊-1 -基]戊基]-4，4 -二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯Geng-1 -yl] pentyl] -5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5 -Oxo- 3- [5- [4- (l-oxobutyl) hexahydropyridin-1-yl] pentyl] -2-thiooximidazol-1-yl] -2- (trifluoro Methyl) benzonitrile 4-[3-[5-[4- (Cyclopropylcarbonyl) hexahydropyridine-1 -yl] pentyl] -4,4-dimethyl-5-oxo-2 -Thiothioimidazol-1-yl] -2- (trifluoromethyl) benzene 4-[3-[5-[4-(環丁基羰基）六氫吡畊-1-基]戊基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲腈 4-[4,4-二甲基-5-氧代-3-[5-[4-[(嘧-2-基）乙醯基]六 氫吡畊-1 ·基]戊基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基） 苯曱腈4- [3- [5- [4- (Cyclobutylcarbonyl) hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine- 1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [5- [4-[(pyrim-2-yl) acetamidine [Hydroxy] pyrazine-1 -yl] pentyl] -2 -thiothioimidazol-1 -yl] -2-(trifluoromethyl) benzoxonitrile 4 - [ 3 - [ 5 - [ 4 - (3 -甲氧基-1 -氧代丙基）六氫吡畊-1 -基]戊 基]-4，4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟 甲基）苯甲腈 4-[3-[5-[4-[(2 -甲氧基乙氧基）乙醯基]六氫吡4-1-基] 戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三 氟甲基）苯甲腈 4-[3-[5-[4-[[2-(2 -甲氧基乙氧基）乙氧基]乙醯基]六 氫吡畊-1 -基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 4 - [ 3 - [ 5 - [ 4 - [(1，3 -二甲基-1 Η - p比唑-5 -基）羰基]六氫吡 -75 - 20030111?4-[3-[5-[4-(3-methoxy-1 -oxopropyl) hexahydropyridine-1 -yl] pentyl] -4,4-dimethyl-5-oxo 2-thiothioimidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4-[(2-methoxyethoxy) ethenyl] Hexahydropyridin 4-yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4 -[3- [5- [4-[[2- (2-methoxyethoxy) ethoxy] ethenyl] hexahydropyridine-1 -yl] pentyl] -4,4-di Methyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[5-[4-[(1,3 -dimethyl -1 hydrazone-p-pyrazole-5 -yl) carbonyl] hexahydropyridine-75-20030111? 畊-1 -基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4 - [ 3 - [ 5 - [ 4 -[(呋喃-3 -基）羰基]六氫吡畊-1 -基]戊 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈Geng-1 -yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3 -[5-[4-((furan-3 -yl) carbonyl] hexahydropyridine-1 -yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine- 1 -yl] -2-(trifluoromethyl) benzonitrile 4 - [ 3 - [ 5 - [ 4 - [(2，5 -二甲基呋喃-3 -基）羰基]六氫吡畊 -1 -基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4 - [ 3 - [ 5 - [ 4 -[(異呤唑-5 -基）羰基]六氫吡畊-1 -基]戊 基]_4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟 甲基）苯甲腈 4-[4,4-二甲基-3-[5-[4-[(5 -甲基異吟唑-3-基）羰基] 六氫吡畊-1 -基]戊基]-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈4-[3-[5-[4-[(2,5-Dimethylfuran-3 -yl) carbonyl] hexahydropyridine-1 -yl] pentyl] -4,4-dimethyl-5 -Oxo-2 -thioximidazolidine-1 -yl] -2- (trifluoromethyl) benzonitrile 4-[3-[5-[4-[(isopurazol-5 -yl) carbonyl]] Hexahydropyrimyl-1 -yl] pentyl] _4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-3- [5- [4-[(5-methylisoindazol-3-yl) carbonyl] hexahydropyridine-1 -yl] pentyl] -5 -oxo -2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[4,4-二甲基-5-氧代-3- [5-[4-(噻-3 -基）羰基]六氫 吡畊-1 -基]戊基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯 甲腈 4-[4,4-二甲基- 3- [5-[4-[(4 -甲基-1，2,3-噻二唑-4-基） 談基]六氫p比呼-1 -基]戊基]-5 -氧代-2 -硫氧咪峻淀-1 -基]-2-(三氟甲基）苯甲腈 4-[4,4-二甲基-5-氧代-3- [5-[4-(嘧-2 -基）羰基]六氫 吡畊-1 -基]戊基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯 甲腈 4-[4,4-二甲基-5-氧代-3- [5-[4-(吡啶-4-基）羰基]六 -76-4- [4,4-dimethyl-5-oxo-3- [5- [4- (thia-3 -yl) carbonyl] hexahydropyridine-1 -yl] pentyl] -2 -thiooxy Imidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl-3-[5- [4-[(4 -methyl-1,2,3 -Thiadiazol-4-yl) Tanyl] hexahydro pbihu-1 -yl] pentyl] -5 -oxo-2 -thioxomidol-1 -yl] -2- (trifluoromethyl Benzoylnitrile 4- [4,4-dimethyl-5-oxo-3- [5- [4- (pyrimin-2-yl) carbonyl] hexahydropyridine-1 -yl] pentyl] -2 -thioximidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [5- [4- (pyridine -4-yl) carbonyl] hexa-76- 氮p比p井-1 -基]戊基]-2 -硫氧味峻咬-1-基]-2-(二氣甲基） 苯甲月青 4-[4,4-二甲基-3-[5-[4-(甲基磺醯基）六氫吡畊-1-基] 戊基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4 - [ 3 - [ 5 - [ 4 -(乙基磺醯基）六氫吡畊-1 -基]戊基]-4，4 -二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲腈 4-[4,4-二甲基-5-氧代-3- [5-[4-(丙基磺醯基）六氫吡 畊-1-基]戊基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 月青 4-[4,4-二甲基-5-氧代-3- [5-[4-(苯基磺醯基）六氫吡 畊-1-基]戊基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[5-[4-[(4-氰基苯基）磺醯基]六氫吡畊-1-基]戊 基]-4，4 - «一甲基-5 -氧代-2 -硫乳味σ坐淀-1 -基]-2 -(二氣 甲基）苯甲腈 4-[3-[5-[4-[(2-甲氧基乙氧基）磺醯基]六氫吡畊-1-基] 戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三 氟甲基）苯甲腈 4-[3-[5-[4-[[2-(2-甲氧基乙氧基）乙基]磺醯基]六氫 吡畊-1 -基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[5-[4-[[2-[2-(2 -甲氧基乙氧基）乙氧基]乙基]磺 遞 醯基]六氫吡畊-1 -基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧 咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4 - [ 4，4 -二甲基-3 - [ 5 - [ 4 - [( 1 -甲基-1 Η -咪唑-4 -基）磺醯 基]六氫吡畊-1 -基]戊基]-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4 - [ 3 - [ 5 - [ 4 - [( 3，5 -二甲基異呤唑-4 -基）磺醯基]六氫吡 畊-1 -基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[5-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪σ坐咬-l-基]戊基]-N-乙基六氫tI比t7井-l-後 硫醯胺 4-[5-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧味σ坐症-l-基]戊基]-N-丙基六氫tI比tr井-l-碳 硫醯胺 4-[5-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2 -硫氧咪吐淀-1 -基]戊基]-Ν -(丙-2 -婦基）六氫ρ比 畊-1 -碳硫醯胺 4-[5-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]戊基]六氫吡畊-l-碳硫酸S-甲醋 4-[5·[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]戊基]六氫吡畊-l-碳硫酸S-乙酉旨 4-[4,4-二甲基- 3-[6-(4-甲基六氫吡畊-1-基）己基]-5- 20030111?Nitrogen p ratio p-well-1 -yl] pentyl] -2 -thioxol 1 -yl] -2- (digas methyl) benzazine 4- [4,4-dimethyl- 3- [5- [4- (methylsulfonyl) hexahydropyridin-1-yl] pentyl] -5-oxo-2-thiooximidazol-1-yl] -2- (trifluoro Methyl) benzonitrile 4-[3-[5-[4- (Ethylsulfonyl) hexahydropyridine-1 -yl] pentyl] -4,4-dimethyl-5-oxo- 2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [5- [4- (propyl Sulfonyl) hexahydropyridin-1-yl] pentyl] -2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzazine 4- [4,4-dimethyl Yl-5-oxo-3- [5- [4- (phenylsulfonyl) hexahydropyridin-1-yl] pentyl] -2-thiooximidazol-1-yl] -2- ( Trifluoromethyl) benzonitrile 4- [3- [5- [4-[(4-cyanophenyl) sulfonyl] hexahydropyridin-1-yl] pentyl] -4,4-« Monomethyl-5 -oxo-2 -sulfur milky taste σ sitting lake-1 -yl] -2-(digas methyl) benzonitrile 4- [3- [5- [4-[(2-methyl Ethoxyethoxy) sulfofluorenyl] hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2- (Trifluoromethyl) benzonitrile 4- [3- [5- [4-[[2- (2-methoxyethyl (Oxy) ethyl] sulfofluorenyl] hexahydropyridine-1 -yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximimidazol-1 -yl] -2- (Trifluoromethyl) benzonitrile 4- [3- [5- [4-[[2- [2- [2- (2-methoxyethoxy) ethoxy] ethyl] sulfonyl]] Hydropyrine-1 -yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-Dimethyl-3-[5-[4-[(1 -Methyl-1 fluorenyl-imidazol-4-yl) sulfofluorenyl] hexahydropyridine-1 -yl] pentyl]- 5 -oxo-2 -thioximidazolidine-1 -yl] -2- (trifluoromethyl) benzonitrile 4-[3-[5-[4-[(3,5- dimethylisopurin Azole-4 -yl) sulfofluorenyl] hexahydropyridine-1 -yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine 1 -yl] -2- (Trifluoromethyl) benzonitrile 4- [5- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2- Thioimide σ sitting bite-l-yl] pentyl] -N-ethylhexahydro tI ratio t7 well-l-post-thiamine 4- [5- [3- [4-cyano-3- (tri Fluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooxy sigma sigma-l-yl] pentyl] -N-propylhexahydrotI than tr-l-l -Carbothioamide 4- [5- [3- [4-cyano-3- (trifluoro (Methyl) phenyl] -5,5-dimethyl-4-oxo-2 -thioxomethotine-1 -yl] pentyl] -N-(propan-2-yl) hexahydroρ ratio Phen-1 -carbothioamide 4- [5- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-sulfide Oximidazol-l-yl] pentyl] hexahydropyridine-l-carbon sulfate S-methyl acetate 4- [5 · [3- [4-cyano-3- (trifluoromethyl) phenyl]- 5,5-dimethyl-4-oxo-2-thiooximidazolidine-l-yl] pentyl] hexahydropyridine-l-carbon sulfate S-acetamidine 4- [4,4-dimethyl -3- [6- (4-methylhexahydropyridin-1-yl) hexyl] -5- 20030111? 氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4-[4,4-二甲基-3-[6-[4-(l-甲基乙基）六氫吡畊-1-基] 己基]-5 -氧代-2 -硫氧咪吐淀-1 -基]-2 -(三氟甲基）苯甲 腈 4-3-[6-[4-(2 -甲氧基苯甲醯基）六氫吡畊-1-基]己 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈Oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-3- [6- [4- (l-methyl (Ethyl) hexahydropyridine-1-yl] hexyl] -5 -oxo-2 -thioxomethotine-1 -yl] -2-(trifluoromethyl) benzonitrile 4-3- [6 -[4- (2-methoxybenzylidene) hexahydropyridin-1-yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl ] -2-(trifluoromethyl) benzonitrile 4-[3-[6-(4-乙醯基六氫吡畊-1-基）己基]-4,4-二甲基 -5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4-[4,4-二甲基-5-氧代- 3- [6-[4-(l-氧代丙基）六氫吡 畊-1-基]己基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[4,4-二甲基- 3- [6-[4_(2 -甲基-1·氧代丙基）六氫吡 畊-1 -基]己基]-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲 基）苯甲腈4- [3- [6- (4-Ethylhexylpyridin-1-yl) hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo- 3- [6- [4- (l-oxopropyl) hexahydropyracine-1 -Yl] hexyl] -2-thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl- 3- [6- [4_ (2- Methyl-1 · oxopropyl) hexahydropyridine-1 -yl] hexyl] -5 -oxo-2 -thioximimidazol-1 -yl] -2-(trifluoromethyl) benzonitrile 4-[4,4-二甲基-5-氧代- 3- [6-[4-(l-氧代丁基）六氫吡 畊-1-基]己基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[6-[4-(環丙基羰基）六氫吡畊-1-基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲月青 4_[3-[6-[4-(環丁基羰基）六氫吡畊-1-基]己基]-4,4-二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯 甲月青 -79- 2003011174- [4,4-Dimethyl-5-oxo- 3- [6- [4- (l-oxobutyl) hexahydropyrine-1-yl] hexyl] -2-thiooximidazole -1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4- (cyclopropylcarbonyl) hexahydropyridin-1-yl] hexyl] -4,4- Dimethyl-5-oxo-2-thioximidazolidine-1-yl] -2- (trifluoromethyl) benzylazine 4_ [3- [6- [4- (cyclobutylcarbonyl) hexa Hydropyrine-1-yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzidine-79 -200301117 4-[3-[6-[4-(3 -甲氧基-1-氧代丙基）六氫吡畊-1-基]己 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4-[3-[6-[4-[(2 -甲氧基乙氧基）乙醯基]六氫吡畊-1-基] 己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三 氟甲基）苯甲腈4- [3- [6- [4- (3-methoxy-1-oxopropyl) hexahydropyrine-1-yl] hexyl] -4,4-dimethyl-5 -oxo- 2-thiothioimidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4- [3- [6- [4-[(2-methoxyethoxy) ethenyl]] Hydropyrin-1-yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4-[3-[6-[4-[[2-(2 -甲氧基乙氧基）乙氧基]乙醯基]六 氫吡畊-1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶 基]_2-(三氟甲基）苯甲腈 4-[4,4-二甲基-5-氧代- 3- [6-[4-[(噻-2-基）乙醯基]六 氫吡畊-1-基]己基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基） 苯甲腈 4-[3-[6-[4-[(呋喃-3 -基）羰基]六氫吡畊-1-基]己 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈4- [3- [6- [4-[[2- (2-methoxyethoxy) ethoxy] ethenyl] hexahydropyridine-1 -yl] hexyl] -4,4-di Methyl-5 -oxo-2 -thioximidazolidinyl] _2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3-[6- [4 -[(Thia-2-yl) ethylfluorenyl] hexahydropyridin-1-yl] hexyl] -2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4-[(furan-3 -yl) carbonyl] hexahydropyridin-1-yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazole -1 -yl] -2-(trifluoromethyl) benzonitrile 4-[4,4-二甲基-5-氧代-3-[6-[4-(噻-2-基）羰基]六氫 吡畊-1 -基]己基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯 甲腈 4-[4,4-二甲基-5-氧代-3-[6-[4-(吡啶-4-基）羰基]六 氫吡畊-1-基]己基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基） 苯甲腈 4-[4,4-二甲基-3- [6-[4-(甲基磺醯基）六氫吡畊-1-基] 己基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 -80- 2003011174- [4,4-dimethyl-5-oxo-3- [6- [4- (thia-2-yl) carbonyl] hexahydropyridine-1 -yl] hexyl] -2-thiothioimidazole Pyridin-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [6- [4- (pyridin-4-yl) carbonyl ] Hexahydropyridin-1-yl] hexyl] -2-thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-3- [ 6- [4- (methylsulfonyl) hexahydropyridin-1-yl] hexyl] -5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzene Nitrile-80- 200301117 4-[3-[6-[4-(乙基磺醯基）六氫吡畊-1-基]己基]-4,4-二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯 甲月青 4 - [ 4，4 -二甲基-5 -氧代-3 - [ 6 - [ 4 -(丙基績酿基）六氫叶匕 p井-1-基]己基]-2 -硫氧i味峻淀·〗-基]-2-(二氣甲基）冬甲 腈4- [3- [6- [4- (ethylsulfonyl) hexahydropyridin-1-yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine- 1 -yl] -2-(trifluoromethyl) benzylazine 4-[4,4-dimethyl-5 -oxo-3-[6-[4-(propyl phenyl methyl) hexahydro] Leaf d-p-well-1-yl] hexyl] -2 -thiooxyi odor Jundian ·〗 -based] -2- (digas methyl) orthocarbonitrile 4-[4,4-二甲基-5-氧代-3- [6-[4-(苯基磺醯基）六氫吡 畊-1-基]己基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[6-[4-[(4-氰基苯基）磺醯基]六氫吡畊-1-基]己 基]-4，4 -二甲基-5 -氧代-2 -硫氧味吐淀-1-基]-2-(二氣 甲基）苯甲腈 4-[6-[3-[4 -氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪σ坐症-l-基]己基]-N-乙基六氫ΐ7比ί7井-l-碳 硫醯胺4- [4,4-dimethyl-5-oxo-3- [6- [4- (phenylsulfonyl) hexahydropyridin-1-yl] hexyl] -2-thiooximidazole- 1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4-[(4-cyanophenyl) sulfonamido] hexahydropyridin-1-yl] hexyl ] -4,4 -Dimethyl-5 -oxo-2 -thioxotriol-1-yl] -2- (digasmethyl) benzonitrile 4- [6- [3- [4- Cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thioxoamido sigma-l-yl] hexyl] -N-ethylhexahydro ΐ7 than ί7-l-Carbothioamide 4-[6-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唾咬-l-基]己基]-N-丙基六氫外kϊί井-l-石炭 硫醯胺 4-[6-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]己基]-N-(丙-2-烯基）六氫吡 ρ井-1 -碳硫臨胺 4-[6-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪嗤淀-l-基]己基]六氫ίτ比ϊί井-l-碳硫酸S-甲醋 -81 - 2003011174- [6- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thioximimidazoline-l-yl ] Hexyl] -N-propylhexahydroxide-l-carbothioanine 4- [6- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5- Dimethyl-4-oxo-2-thiooximidazolidine-l-yl] hexyl] -N- (prop-2-enyl) hexahydropyridine-well-1 -Carbothiophenamine 4- [6- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thioxamidino-l-yl] hexyl] hexahydro ίτ 比 ϊί Well-l-Carbon Sulphate-81-200301117 4-[6-[3-[4 -氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]己基]六氫吡畊-l-碳硫酸S-乙酉旨 4-[4,4-二甲基- 3- [7-(4 -甲基六氫吡畊-1-基）庚基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4-[3-[7-(4-乙醯基六氫吡畊-1-基）庚基]-4,4-二甲基 -5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4 - [ 4，4 -二甲基-3 - [ 7 - [ 4 -(甲基磺醯基）六氫吡畊-1 -基] 庚基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[4,4-二甲基- 3- [8-[4-(2 -甲基-1-氧代丙基）六氫吡 畊-1-基]辛基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲 基）苯甲腈 4 - [ 3 - [ 8 - [ 4 -(環丙基羰基）六氫吡畊-1 -基]辛基]-4，4 -二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲腈 4-[3-[8-[4-(環丁基羰基）六氫吡畊-1-基]辛基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯 甲腈 4-[4,4-二甲基-5-氧代-3- [8-[4-(嘧-2 -基）羰基]六氫 吡畊-1 -基]辛基]-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯 甲腈 4-[4,4-二甲基-5-氧代-3- [8-[4-(吡啶-4-基）羰基]六 氫吡畊-1 -基]辛基]-2 -硫氧咪唑啶-1 -基]_ 2 -(三氟甲基） -82- 2003011174- [6- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazol-l-yl] Hexyl] hexahydropyridine-l-carbosulfate S-ethylsulfonyl 4- [4,4-dimethyl-3 3- [7- (4-methylhexahydropyridine-1-yl) heptyl] -5 -Oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [7- (4-ethylamidinohexahydropyridine-1-yl) Heptyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[4,4-dimethyl -3-[7-[4-(Methylsulfonyl) hexahydropyridine-1 -yl] heptyl] -5-oxo-2-thiooximidazol-1-yl] -2- (tri Fluoromethyl) benzonitrile 4- [4,4-dimethyl- 3- [8- [4- (2-methyl-1-oxopropyl) hexahydropyridine-1-yl] octyl ] -5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[8-[4-(cyclopropylcarbonyl) hexahydropyridine Geng-1 -yl] octyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3 -[8- [4- (Cyclobutylcarbonyl) hexahydropyridin-1-yl] octyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [ 8- [4- (pyrim-2-yl) carbonyl] hexahydropyridine-1 -yl] octyl] -2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [8- [4- (pyridin-4-yl) carbonyl] hexahydropyridine-1 -yl] octyl] -2 -thiooxy Imidazolidine-1 -yl] _ 2-(trifluoromethyl) -82- 200301117 苯甲腈 4-[4,4-二甲基- 3- [8-[4-(甲基磺醯基）六氫吡畊-1-基] 辛基]-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[4,4-二甲基-5-氧代-3- [8-[4-(丙基磺醯基）六氫吡 畊-1-基]辛基]-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲 腈Benzonitrile 4- [4,4-dimethyl- 3- [8- [4- (methylsulfonyl) hexahydropyridine-1-yl] octyl] -5-oxo-2-sulfide Oximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-3- [8- [4- (propylsulfonyl ) Hydroxypyrine-1-yl] octyl] -2-thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[4,4-二甲基- 3- [8-[4-[(l-甲基乙基）磺醯基]六氫吡 畊-1 -基]辛基]-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲 基）苯甲腈 4 - [ 3 - [ 8 - [ 4 - [(2 -甲氧基乙氧基）磺醯基]六氫吡畊-1 -基] 辛基]-4，4 --一甲基-5 -氧代-2 -硫氧味哇咬-1 -基]-2 -(二 氟曱基）苯甲腈4- [4,4-dimethyl- 3- [8- [4-[(l-methylethyl) sulfonamido] hexahydropyridine-1 -yl] octyl] -5 -oxo- 2-thiothioimidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4-[3-[8-[4-[(2-methoxyethoxy) sulfonyl]] Hydropyridine-1 -yl] octyl] -4,4 -monomethyl-5 -oxo-2 -thiooxy scented bite-1 -yl] -2-(difluorofluorenyl) benzonitrile 4-[3-[8-[4-[(4-氰基苯基）磺醯基]六氫吡畊-1-基]辛 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4-[8-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-输氧咪σ全淀-l-基]辛基]-N-丙基六氫p比ϊ7井-l-碳 硫醯胺 4-[8-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]辛基^N-(丙-2-烯基）六氫吡 畊-1 -碳硫醯胺 4-[8-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧^代-2 -硫氧味。坐淀-1 -基]辛基]7T鼠？比p井-1 -碳^硫酸S_ -83 - 2003011174- [3- [8- [4-[(4-cyanophenyl) sulfonamido] hexahydropyridin-1-yl] octyl] -4,4-dimethyl-5 -oxo- 2-thiothioimidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4- [8- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5 , 5-Dimethyl-4-oxo-2-oxyimide sigma yodo-l-yl] octyl] -N-propylhexahydro p ratio ϊ7-well-l-carbothioamide 4- [8- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazolidine-l-yl] octyl ^ N- (Prop-2-enyl) hexahydropyridine-1 -carbothioamide 4- [8- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-di Methyl-4-oxo-2-oxothioate. Sitting Lake-1 -yl] octyl] 7T mouse? Than p-well-1 -Carbosulfuric acid S_ -83-200301117 甲酉旨 3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 -1 _[ 3 - [ 4 -[(魂-2 -基）羰基]六氫吡畊-1 -基]丙基]-2 -硫氧 味峻淀-4 -嗣 3- [1，3-二氮-1-氧代異麥并咬喃-5-基]-1-[3-[4-[4-(·— 甲基胺基）苯甲醯基]六氫吡畊-1-基]丙基]-5,5-二甲基 -2 -硫氧咪σ坐淀-4 -酮Formazan purpose 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-1 _ [3-[4-[(soul-2 -yl ) Carbonyl] hexahydropyridine-1 -yl] propyl] -2 -thioxotripine-4 -fluorene 3- [1,3-diaza-1-oxoisomai and sulfan-5-yl ] -1- [3- [4- [4- (· (methylamino) benzyl)] hexahydropyridine-1-yl] propyl] -5,5-dimethyl-2 -sulfur Oxamizo Ν-[(4-氯苯基）甲基]-4-[3-[3-(1，3-二氫-1-氧代異苯 并吱喃-5 -基）-5，5 -二甲基-2 -硫氧咪咬淀-1 -基]丙基]六 氫吡畊-1 -碳硫醯胺 4- [3-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4 -氧代-2 -硫氧咪峡咬-1 -基]丙基]六氫ρ比p井-1 -石炭 硫酸S -乙酯 4 - [ 3 - [ 3 - ( 1，3 -二氫-1 -氧代異苯并呋喃-5 -基）-5，5 -二 甲基-4-氧代-2-硫氧咪唑啶-1-基]丙基]-Ν，Ν-二乙基六Ν-[(4-chlorophenyl) methyl] -4- [3- [3- (1,3-dihydro-1-oxoisobenzoan-5-yl) -5,5-di Methyl-2 -thioxantheline-1 -yl] propyl] hexahydropyridine-1 -carbothioamide 4- [3- [3- (1,3-dihydro-1-oxoiso Benzofuran-5 -yl) -5,5 -dimethyl-4 -oxo-2 -thioxosulfan-1 -yl] propyl] hexahydroρ ratio p-well-1 -carbosulfuric acid S- Ethyl ester 4-[3-[3-(1,3-dihydro-1 -oxoisobenzofuran-5 -yl) -5,5-dimethyl-4-oxo-2-thiooximidazole Pyridin-1-yl] propyl] -N, N-diethylhexa 氫吡畊-1 -羧酸醯胺 3-(1,3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 _1_[4-[4-[〇塞-2-基）羰基]六氫吡畊-1-基]丁基]-2-硫氧 味峻淀-4 -酉同 3-(1,3-二氫-1-氧代異苯并呋喃-5-基）-1-[4-[4-(2 -甲 氧基苯甲醯基）六氫吡畊-1-基]丁基]-5,5-二甲基-2-硫 氧味吐咬-4 -酉同 3-(1,3-二氫-1-氧代異苯并呋喃-5-基）-1-[4-[4-[4-(二 甲基胺基）苯甲醯基]六氫吡畊-1-基]丁基]-5,5-二甲基 -84- 200301117Pyridoxine-1 -carboxamide 3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl_1_ [4- [4- [ 〇Se-2-yl) carbonyl] hexahydropyridine-1-yl] butyl] -2-thioxotripine-4 -pyridine 3- (1,3-dihydro-1-oxoisobenzene Benzofuran-5-yl) -1- [4- [4- (2- (methoxymethoxybenzyl) hexahydropyridin-1-yl] butyl] -5,5-dimethyl-2- Sulfur odor bite-4 -pyridine with 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -1- [4- [4- [4- (dimethylamine ) Benzyl)] hexahydropyridin-1-yl] butyl] -5,5-dimethyl-84- 200301117 -2 -硫氧咪吐淀-4 -酮 1 _[ 4 - [ 4 - [ 2，1，3 -苯并噻二唑-4 -基]磺醯基]六氫吡畊 -1-基]丁基]-3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5，5 -二甲基-2 -硫氧咪唑啶-4 -酮 N-(2,6-二氯吡啶-4-基）-4-[4-[3-(1，3-二氫-1-氧代異 苯并呋喃-5 -基）-5，5 -二甲基-2 -硫氧咪唑啶-1 -基]丁基] 六氫p比啡-1 -複酸酿胺-2-Thioxetamine-4 -one-1 _ [4-[4-[2,1,3 -benzothiadiazole-4 -yl] sulfofluorenyl] hexahydropyridine-1-yl] Butyl] -3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-2-thiothioimidazolidine-4-one N- (2 , 6-dichloropyridin-4-yl) -4- [4- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl- 2-thiothioimidazol-l-yl] butyl] hexahydrop-biffin-1 4-[4-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4 -氧代-2 -硫氧咪唑啶-1 -基]丁基]六氫吡畊-1 -碳 硫酸S -甲酯 4-[4-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]丁基]六氫吡畊-1-碳 硫酸S -乙酯4- [4- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4 -oxo-2 -thiooximidazolidine- 1-yl] butyl] hexahydropyridine-1 -carbon sulfate S -methyl ester 4- [4- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl)- 5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] butyl] hexahydropyridine-1-carbon sulfate S-ethyl ester 3-(1，3-二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 -l-[5-[4-(2 -甲基-1-氧代丙基）六氫吡畊-1-基]戊基]-2-硫氧味峻淀-4 -酉同 3 - (1，3 -二氫-1 -氧代異苯并呋喃-5 -基）-5，5 -二甲基 -1 - [ 5 - [ 4 -[(嘧-2 -基）乙醯基]六氫吡畊-1 -基]戊基]-2 -硫 氧味σ坐淀-4 -酉同 3 - (1，3 -二氫-1 -氧代異苯并呋喃-5 -基）-5，5 -二甲基 -1-[5-[4-[(噻-2-基）羰基]六氫吡畊-1-基]戊基]-2-硫氧 味吐淀-4 -酉同 3-(1,3-二氫-1-氧代異苯并呋喃-5-基）-1-[5-[4 -乙基 磺醯基]六氫吡畊-1-基]戊基]-5,5-二甲基-2-硫氧咪唑 -85- 2003011173- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-1- [5- [4- (2-methyl-1-oxo (Propyl) hexahydropyridin-1-yl] pentyl] -2-thioxotripine-4 -pyridine 3-(1,3-dihydro-1 -oxoisobenzofuran-5 -yl ) -5,5 -Dimethyl-1-[5-[4-[(Pyrimidin-2-yl) ethenyl] hexahydropyridine-1 -yl] pentyl] -2 -thiooxygen σ sitting Yodo-4 -pyridine with 3-(1,3-dihydro-1 -oxoisobenzofuran-5 -yl) -5,5-dimethyl-1- [5- [4-[(thio- 2-yl) carbonyl] hexahydropyridine-1-yl] pentyl] -2-thiooxytitu-4 -pyridine 3- (1,3-dihydro-1-oxoisobenzofuran- 5-yl) -1- [5- [4-Ethylsulfonyl] hexahydropyridin-1-yl] pentyl] -5,5-dimethyl-2-thioximidazole-85- 200301117 咬-4 -酮 4-[[4-[5-[3-(l，3 -二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基-4 -氧代-2 -硫氧咪唑啶-1 -基]戊基]六氫吡畊-1 -基]磺醯基]苯甲腈 4-[5-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4 -氧代-2 -硫氧咪唑啶-1 -基]戊基]六氫吡畊-1 -碳 硫酸S -乙酯Bite-4 -one 4-[[4- [5- [3- (l, 3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4 -oxo -2 -thioximidazolidine-1 -yl] pentyl] hexahydropyridine-1 -yl] sulfofluorenyl] benzonitrile 4- [5- [3- (1,3-dihydro-1- Oxo-isobenzofuran-5 -yl) -5,5-dimethyl-4 -oxo-2 -thioximidazolidine-1 -yl] pentyl] hexahydropyridine-1 -carbon sulfate S- Ethyl ester 3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-1-[6-[4-(2 -甲 氧基苯甲醯基）六氫吡畊-1-基]己基]-5，5-二甲基-2-硫 氧味峻淀-4 -酮 3-(1，3 -二氮-1-氧代異豕并咬喃-5-基）-1-[6-[4-[4-(^— 甲基胺基）苯甲醯基]六氫吡畊-1-基]己基]-5, 5-二甲基 -2 -硫氧味σ坐淀-4 -酮3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -1- [6- [4- (2-methoxybenzylhydratino) hexahydropyrine-1- [Hexyl] hexyl] -5,5-dimethyl-2-thiooxojun-do-4 -one 3- (1,3 -diaza-1-oxoisofluorenyl and sulfan-5-yl) -1 -[6- [4- [4-(^-methylamino) benzamidine] hexahydropyridin-1-yl] hexyl] -5, 5-dimethyl-2 -thiooxy sigma Yodo-4 -one 3-[[4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基-4 -氧代-2 -硫氧咪峻淀-1 -基]己基]六氫叶I： ρ井-1 -基]羰基]苯甲腈 1-[6-(4-乙醯基六氫吡畊-1-基）己基]-3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基-2-硫氧咪唑啶- 4- 酮 3-(1,3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 -1-[6-[4-(1-氧代丙基）六氫吡畊-1-基]己基]-2-硫氧咪 峻淀-4 -商同 3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 -1-[6-[4-(2 -甲基-1-氧代丙基）六氫吡畊-1-基]己基]-2- -86- 2003011173-[[4- [6- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4 -oxo-2 -sulfur Imidamido-1 -yl] hexyl] hexahydro leaf I: ρ well-1 -yl] carbonyl] benzonitrile 1- [6- (4-ethylfluorenylhexahydropyridin-1-yl) hexyl] -3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-2-thiooximidazolidine 4-one 3- (1,3- Dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-1- [6- [4- (1-oxopropyl) hexahydropyridine-1-yl] Hexyl] -2-thiooxyimidose-4 -Shangtong 3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-1- [ 6- [4- (2-methyl-1-oxopropyl) hexahydropyrine-1-yl] hexyl] -2- -86- 200301117 硫氧味峻咬-4 -酮 3-(1,3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1 - [ 6 - [ 4 - ( 1 -氧代丁基）六氫吡畊-1 -基]己基]-2 -硫氧咪 吐淀-4 - Ϊ同 1 [4-(環丙基羰基）六氫吡畊-1-基]己基]-3-( 1，3- 二氫-1 -氧代異苯并呋喃-5 -基）-5，5 -二甲基-2 -硫氧咪 哇啶-4 -酮Sulfur odor bite-4 -one 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-1-[6-[4-( 1-oxobutyl) hexahydropyridine-1 -yl] hexyl] -2 -thioxomidol-4-hydrazone with 1 [4- (cyclopropylcarbonyl) hexahydropyridine-1-yl] Hexyl] -3- (1,3-dihydro-1 -oxoisobenzofuran-5 -yl) -5,5 -dimethyl-2 -thiooximidin-4 -one 1_ [6-[4-(環丁基羰基）六氫吡畊-1-基]己基]-3-( 1,3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基-2-硫氧咪 峻淀-4 -酉同 3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 —1 - [ 6 - [ 4 -[(吡啶-4 -基）羰基]六氫吡畊-1 -基]己基]-2 -硫 氧味峻淀-4 -酮1_ [6- [4- (Cyclobutylcarbonyl) hexahydropyridin-1-yl] hexyl] -3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5 , 5-Dimethyl-2-thioxanmidol-4 -pyridine 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl —1-[6-[4-[(Pyridin-4 -yl) carbonyl] hexahydropyridine-1 -yl] hexyl] -2 -thiooxytimonol-4 -one 3 - (1，3 -二氫-1 -氧代異苯并呋喃-5 -基）-5，5 -二甲基 -l-[6-[4-[(噻-2-基）羰基]六氫吡畊-1-基]己基]-2-硫氧 味唆淀-4 -酉同 3-(1，3 -二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1 - [ 6 - [ 4 -[(嘧-2 -基）乙醯基]六氫吡畊-1 -基]己基]-2 -硫 氧咪唾咬-4 -酮 3-(1，3-二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 -1-[6-[4-(甲基磺醯基）六氫吡畊-1-基]己基]-2-硫氧咪 吨咬-4 -酉同 3-(1,3-二氫-1-氧代異苯并呋喃-5-基）-1-[6-[4-(乙基 磺醯基）六氫吡畊-1 -基]己基]-5，5 -二甲基-2 -硫氧咪唑 -87 - 2003011173-(1,3-dihydro-1 -oxoisobenzofuran-5 -yl) -5,5-dimethyl-1-[6- [4-[(thia-2-yl) carbonyl] Hexahydropyridin-1-yl] hexyl] -2-thiooxymisosulfonate-4 -pyridine 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5, 5-dimethyl-1-[6-[4-[(pyrimidin-2-yl) ethenyl] hexahydropyridine-1 -yl] hexyl] -2 -thioxanthelin-4 -one-3 -(1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-1- [6- [4- (methylsulfonyl) hexahydropyridine -1-yl] hexyl] -2-thioxanthene, 4-tetrahydropyridine, 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -1- [6- [ 4- (ethylsulfonyl) hexahydropyridine-1 -yl] hexyl] -5,5-dimethyl-2 -thioximidazole-87-200301117 淀-4 -酉同 3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 _ 1 _ [ 6 - [ 4 -(丙基磺醯基）六氫吡畊-1 -基]己基]-2 -硫氧咪 吐淀-4 -酮 3-(1,3 -二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1 - [ 6 - [ 4 -(苯基磺醯基）六氫吡呼-1 -基]己基]-2 -硫氧咪 嗤淀-4 -酮Yodo-4 -pyridine with 3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl_ 1 _ [6-[4-(propylsulfonate Fluorenyl) hexahydropyridine-1 -yl] hexyl] -2 -thioxomidol-4 -one 3- (1,3 -dihydro-1-oxoisobenzofuran-5-yl)- 5,5-Dimethyl-1-[6-[4-(phenylsulfonyl) hexahydropyridine-1 -yl] hexyl] -2 -thioximidate-4 -one 4-[[4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基-4 -氧代-2 -硫氧咪唑啶-1 -基]己基]六氫吡畊-1 -基]磺醯基]苯甲腈4-[[4- [6- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4 -oxo-2 -sulfur Oximidazol-1 -yl] hexyl] hexahydropyridine-1 -yl] sulfofluorenyl] benzonitrile 1-[6-[4-[(2，1，3-苯并噻二唑-4-基）磺醯基]六氫吡畊 -1-基]己基]-3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5，5 -二甲基-2 -硫氧咪唑啶-4 -酮 4-[6-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4 -氧代-2 -硫氧咪唑啶-1 -基]己基]-N - [ 3 -(甲基硫 燒基）苯基]六氫说_ - 1 -複酸酸胺 4-[6-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4-氧代-2-硫氧咪唑啶-1-基]己基]-N-(3-氟苯基） 六氫4 - 1 -致酸酿胺 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]己基]-N-(4-氟苯基） 六氫说。井-1 -複酸酿胺 4-[6-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]己基]-乙基六氫吡 -88- 200301117 畊-1 _碳硫醯胺 4-[6-[3-(l，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4 -氧代-2 -硫氧咪σ坐淀-1 -基]己基]-N -丙基六氫叶匕 ρ井-1 -峡硫S盛胺 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5 -二 甲基-4-氧代-2-硫氧咪唑啶-卜基]己基]-Ν-(丙-2-烯基） 六氫吡畊-1 -碳硫醯胺1- [6- [4-[(2,1,3-benzothiadiazol-4-yl) sulfofluorenyl] hexahydropyridin-1-yl] hexyl] -3- (1,3-di Hydrogen-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-2-thiothioimidazolidine-4 -one 4- [6- [3- (1,3-dihydro- 1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-4 -oxo-2 -thioximidazolidine-1 -yl] hexyl] -N-[3-(methylsulfur Alkyl) phenyl] hexahydrogen _-1 -fatty acid amine 4- [6- [3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5 -Dimethyl-4-oxo-2-thiooximidazol-1-yl] hexyl] -N- (3-fluorophenyl) hexahydro 4-1 -acid-producing amine 4- [6- [3 -(1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] hexyl]- N- (4-fluorophenyl) hexahydro said. Well-1-double acid amine 4- [6- [3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-4-oxo 2-thiothioimidazol-1-yl] hexyl] -ethylhexahydropyridine-88- 200301117 Geng-1 _Carbothioamide 4- [6- [3- (l, 3-dihydro-1- Oxo-isobenzofuran-5 -yl) -5,5-dimethyl-4 -oxo-2 -thiooxyimide σ sitting lake-1 -yl] hexyl] -N -propylhexahydro leaf Well-1 -Sulfur S, Amine 4- [6- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo 2-thiothioimidazolidine-butyl] hexyl] -N- (prop-2-enyl) hexahydropyridine-1 -carboxamidine 4-[6-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4-氧代-2-硫氧咪唑啶-1-基]己基]-Ν-苯基六氫吡 畊-1 -碳硫醯胺 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]己基]-Ν-(苯基甲基） 六氮Ρ比？井-1 -碳硫S盔yfe*4- [6- [3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-4-oxo-2-thiooximidazolidine- 1-yl] hexyl] -N-phenylhexahydropyridine-1 -carbothioamide 4- [6- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl ) -5,5-Dimethyl-4-oxo-2-thiooximidazol-1-yl] hexyl] -N- (phenylmethyl) Hexa nitrogen P ratio? Well-1-Carbon-Sulfur S Helmet 4-[6-[3-(l，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4 -氧代-2 -硫氧咪峻淀-1 -基]己基]六氫叶I: p井-1 -碳 硫酸S -曱酯 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4 -氧代-2 -硫氧咪哇淀· 1 -基]己基]六氫说_ -1 -石炭 硫酸S -乙酯 4-[6-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]己基]-N，N-二乙基六 氫吡畊-1 -羧酸醯胺 3-(1,3 -二氫-1-氧代異苯并呋喃-5-基）-1-[7-[4-(2 -二 甲氧基苯甲醯基）六氫吡畊-1-基]庚基]-5, 5-二甲基-2- -89- 2003011174- [6- [3- (l, 3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4 -oxo-2 -thioxanthemidate -1 -yl] hexyl] hexahydro leaf I: p well-1 -Carbon sulfate S -fluorenyl ester 4- [6- [3- (1,3-dihydro-1-oxoisobenzofuran-5- ) -5,5-dimethyl-4 -oxo-2 -thioxomidazoline · 1 -yl] hexyl] hexahydrogenation _ 1 -Carbon sulfate S -ethyl ester 4- [6- [3 -(1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] hexyl]- N, N-diethylhexahydropyroxy-1 -carboxamide 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -1- [7- [4- (2-Dimethoxybenzylidene) hexahydropyridin-1-yl] heptyl] -5, 5-dimethyl-2- -89- 200301117 硫氧咪峻咬-4 -酮 1-[7-(4-乙醯基六氫吡畊-1-基）庚基]-3-(1，3-二氫-1-氧代異夺并咬喃-5-基）-5, 5 - —甲基-2-硫氧味峻淀-4 _ 酮 3-(1，3-二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 _ 1 - [ 7 - [ 4 - ( 1 -氧代丙基）六氫吡畊-1 -基]庚基]-2 -硫氧咪 峻淀-4 -酉同 3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 -l-[7-[4-(2 -甲基-1-氧代丙基）六氫吡畊-1-基]庚基]-2-硫氧咪唑啶-4 -酮 3-(1，3 -二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 氧代丁基）六氫吡畊-1-基]庚基]-2-硫氧咪 。坐淀-4 -嗣 1 - [ 7 - [ 4 -(環丙基羰基）六氫吡畊-1 -基]庚基]-3 - (1，3 -二氫-1 -氧代異苯并呋喃-5 -基）-5，5 -二甲基-2 -硫氧咪 峻淀-4 -酉同 1-[7-[4-(環丁基羰基）六氫吡畊-1-基]庚基]-3-(1,3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基-2-硫氧咪 峻淀-4 -酉同 3-(1，3 -二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 [(噻-2-基）羰基]六氫吡畊-1-基]庚基]-2-硫氧 味σ坐咬-4 -酉同 3-(1,3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 一 1 _[ 7 - [4- [ (4 - 2 -基）乙醯基]六氫吡畊-1 -基]庚基]-2 -硫 -90- 200301117Thiothiophene bite-4 -one 1- [7- (4-ethylfluorenylhexahydropyridin-1-yl) heptyl] -3- (1,3-dihydro-1-oxoisodepletion Sulfan-5-yl) -5, 5--methyl-2-thiooxyamijun-4-ketone 3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl_ 1-[7-[4-(1 -oxopropyl) hexahydropyridine-1 -yl] heptyl] -2 -thioxomidazoline-4- 3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-1- [7- [4- (2-methyl-1-oxo Propyl) hexahydropyridin-1-yl] heptyl] -2-thioximidazolidine-4-one 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl)- 5,5-dimethyloxobutyl) hexahydropyridin-1-yl] heptyl] -2-thioxenimide. Zyodo-4 -fluorene1-[7-[4- (cyclopropylcarbonyl) hexahydropyridine-1 -yl] heptyl] -3-(1,3-dihydro-1 -oxoisobenzo Furan-5 -yl) -5,5 -dimethyl-2 -thioxanmidol-4 -pyridine 1- [7- [4- (cyclobutylcarbonyl) hexahydropyridine-1-yl] Heptyl] -3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-2-thioxoamido-4 -pyridine 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl [(thia-2-yl) carbonyl] hexahydropyridin-1-yl] heptyl ] -2-thiooxy odor σ sitting bite -4-pyridine with 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-1 1 _ [ 7-[4- [(4-2 -yl) ethenyl] hexahydropyridine-1 -yl] heptyl] -2 -sulfur-90- 200301117 氧咪吐淀-4 -酮 3-(1，3 -二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1 _[ 7 - [ 4 -(甲基磺醯基）六氫吡畊-1 -基]庚基]-2 -硫氧咪 峻淀-4 -酉同 3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-1-[7-[4-(乙基 磺醯基）六氫吡畊-1 -基]庚基]-5，5 -二甲基-2 -硫氧咪唑 淀-4 -酉同Oxamidine-4 -one 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-1 _ [7-[4-( Sulfofluorenyl) hexahydropyridine-1 -yl] heptyl] -2 -thioxoamido-4 -pyridine 3- (1,3-dihydro-1-oxoisobenzofuran-5 -Yl) -1- [7- [4- (ethylsulfonyl) hexahydropyridine-1 -yl] heptyl] -5,5 -dimethyl-2 -thioximidazole-4 -fluorene with 3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 -1 _[ 7 - [ 4 -(丙基磺醯基）六氫吡畊-1 -基]庚基]-2 -硫氧咪 哇咬-4 -酉同 3-(1,3 -二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1-[7-[4-(苯基磺醯基）六氫吡畊-1-基]庚基]-2-硫氧咪 。圭淀-4 -酮3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-1 _ [7-[4-(propylsulfonyl) hexahydropyridine Geng-1 -yl] heptyl] -2 -thioxoamiwa-4 -pyridine 3- (1,3 -dihydro-1-oxoisobenzofuran-5-yl) -5,5- Dimethyl-1- [7- [4- (phenylsulfonyl) hexahydropyridin-1-yl] heptyl] -2-thioxol. Guiyodo-4 -one 4-[7-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]庚基]-N -乙基六氫吡 畊-1 -碳硫醯胺 4-[7-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4 -氧代-2 -硫氧咪σ坐淀-1 -基]庚基]-N -丙基六氫叶匕 呼-1 -碳^硫酿胺 4-[7-[3-(1，3-二氫-1-氧代異苯并呋喃-5_基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]庚基]-Ν-(丙-2-烯基） 六氫吡畊-1 -碳硫醯胺 4-[7-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4-氧代-2-硫氧咪唑啶-1-基]庚基]六氫吡畊-1-碳 -91 - 2003011174- [7- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazolidine- 1-yl] heptyl] -N-ethylhexahydropyridine-1 -carbothioamide 4- [7- [3- (1,3-dihydro-1-oxoisobenzofuran-5- ) -5,5-dimethyl-4 -oxo-2 -thioxoamido σ sitting lake-1 -yl] heptyl] -N -propyl hexahydropyridine-1 -Carbosulfanamine 4- [7- [3- (1,3-dihydro-1-oxoisobenzofuran-5_yl) -5,5-dimethyl-4-oxo-2-thiooximidazolidine- 1-yl] heptyl] -N- (prop-2-enyl) hexahydropyridine-1 -carbothioamide 4- [7- [3- (1,3-dihydro-1-oxoiso Benzofuran-5 -yl) -5,5 -dimethyl-4-oxo-2-thiooximidazol-1-yl] heptyl] hexahydropyridine-1-carbon-91-200301117 硫酸s -甲酯 4-[7-[3-(l，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 曱基-4-氧代-2-硫氧咪唑啶-1-基]庚基]六氫吡畊-1-碳 硫酸S -乙酯 3-(1，3 -二氨-1-氧代異麥并咬喃-5-基）-1-[8-[4-(2-«一 甲氧基苯甲醯基）六氫吡畊-1-基]辛基]-5,5-二甲基- 2-硫氧味。坐淀-4 - Ϊ同S-methyl sulfate 4- [7- [3- (l, 3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-difluorenyl-4-oxo-2- Thioximidazol-1-yl] heptyl] hexahydropyridine-1-carbon sulfate S-ethyl 3- (1,3-diamino-1-oxoisomai and sulfan-5-yl)- 1- [8- [4- (2-methoxymonomethoxybenzyl) hexahydropyridine-1-yl] octyl] -5,5-dimethyl-2-thioxine. Zuodian-4 3-(1,3 -二鼠-1-乳代異冬并咬喃-5-基）-1-[8-[4-[4-(>— 甲基胺基）苯甲醯基]六氫吡畊-1-基]辛基]-5,5-二甲基 -2 -硫氧味峻淀-4 -酉同 1-[8-(4-乙醯基六氫吡畊-1-基）辛基]-3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基-2-硫氧咪唑啶-4- 酮3- (1,3 -dimur-1-lactoisodonganyl-5-yl) -1- [8- [4- [4-(> -methylamino) benzyl] Hexahydropyridin-1-yl] octyl] -5,5-dimethyl-2 -thiooxytaste Junyodo-4 -pyridine 1- [8- (4-ethylpyridylhexahydropyridine-1 -Yl) octyl] -3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-2-thiooximidazolidine-4-one 3-(1，3 -二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -l-[8-[4-(l-氧代丙基）六氫吡畊-1-基]辛基]-2-硫氧咪 吐淀-4 -酉同 1-[8-[4-(環丙基羰基）六氫吡畊-1-基]辛基]-3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基-2-硫氧咪 17坐淀-4 -酮 1-[8-[4-(環丁基羰基）六氫吡畊-1-基]辛基]-3-(1，3-二氫-1 -氧代異苯并呋喃-5 -基）-5，5 -二甲基-2 -硫氧咪 。坐淀-4 -酮 3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 -l_[8-[4-[(噻-2-基）羰基]六氫吡畊-1-基]辛基]-2-硫氧 -92- 2003011173- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-l- [8- [4- (l-oxopropyl) hexahydro Pyridin-1-yl] octyl] -2-thioxomethotine-4 -pyridine 1- [8- [4- (cyclopropylcarbonyl) hexahydropyridin-1-yl] octyl]- 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-2-thioxanimide 17-azide-4 -one 1- [8- [ 4- (cyclobutylcarbonyl) hexahydropyridin-1-yl] octyl] -3- (1,3-dihydro-1 -oxoisobenzofuran-5 -yl) -5,5-di Methyl-2-Thioxan. Zyodo-4 -one 3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-l_ [8- [4-[(thio-2 -Yl) carbonyl] hexahydropyridin-1-yl] octyl] -2-thiooxy-92- 200301117 咪峻症-4 -酮 3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1 _[ 8 - [ 4 -[(噻-2 -基）乙醯基]六氫吡畊-1 -基]辛基]-2 -硫 氧咪峻淀-4 -酮 3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1 _[ 8 - [ 4 -[(说啶-4 -基）羰基]六氫吡畊-1 -基]辛基]-2 -硫 氧咪嗤啶-4 -酮Mycosis-4 -one 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-1 _ [8-[4-[(thia -2 -yl) ethynyl] hexahydropyridine-1 -yl] octyl] -2 -thioxomidazine-4 -one 3- (1,3-dihydro-1-oxoisobenzo) Furan-5-yl) -5,5-dimethyl-1 _ [8-[4-[(Said pyridin-4 -yl) carbonyl] hexahydropyridine-1 -yl] octyl] -2 -sulfur Imipramine-4 -one 3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1 - [ 8 - [ 4 -(曱基磺醯基）六氫吡畊-1 -基]辛基]-2 -硫氧咪 咬淀-4 -酉同 3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-1-[8-[4-(乙基 磺醯基）六氫吡畊-1 -基]辛基]-5，5 -二甲基-2 -硫氧咪唑 淀-4 -酉同3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-1-[8-[4-(fluorenylsulfonyl) hexahydropyridine Geng-1 -yl] octyl] -2 -thioxantheline -4 -pyridine 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -1- [8 -[4- (ethylsulfonyl) hexahydropyrimyl-1 -yl] octyl] -5,5 -dimethyl-2 -thioximidazole-4 -pyridine 3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -1 - [ 8 - [ 4 -(丙基磺醯基）六氫吡畊-1 -基]辛基]-2 -硫氧咪 峻淀-4 -酮 3-(1，3 -二氫-1-氧代異苯并呋喃-5-基）-5,5-二甲基 -l-[8-[4-[(2,2,2-三氟乙基）磺醯基]六氫吡畊-1-基]辛 基]-2 -硫氧味吐淀-4 -酉同 3- (1，3-二氫-1-氧代異苯并呋喃-5 -基）-5,5-二甲基 -1-[8-[4-(苯基磺醯基）六氫吡畊-1-基]辛基]-2-硫氧咪 。坐咬-4 -酮 4- [8-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4 -氧代-2 -硫氧味σ坐淀-1 -基]辛基]-N-[3-(甲基硫 -93 - 2003011173- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-1-[8-[4-(propylsulfonyl) hexahydropyridine Geng-1 -yl] octyl] -2 -thioxanmidol-4 -one 3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-di Methyl-l- [8- [4-[(2,2,2-trifluoroethyl) sulfofluorenyl] hexahydropyridin-1-yl] octyl] -2 -thiooxytituline-4 -Pyrene 3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-1- [8- [4- (phenylsulfonyl) Hexahydropyridin-1-yl] octyl] -2-thioxetrimidine. Seated bite-4 -one 4- [8- [3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-4 -oxo-2 -Sulfur odor σ sitting lake-1 -yl] octyl] -N- [3- (methylsulfide-93-200301117 烷基）苯基]六氫吡畊-1 -羧酸醯胺 4-[8-[3-(1，3 -二氫-1-氧代異苯并呋喃-5-基）-5,5 -二 甲基-4-氧代-2-硫氧咪唑啶-1-基]辛基]-N-(3-氟苯基） 六氫说4 -1 -複酸si胺 4-[8-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4-氧代-2-硫氧咪唑啶-1-基]辛基]-N -乙基六氫吡 畊-1 -碳硫醯胺 4-[8-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4 -氧代-2 -硫氧咪唑啶-1 -基]辛基]-N -丙基六氫吡 畊-1 -碳硫醯胺 4-[8-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]辛基]-N-(丙-2-晞基） 六氫吡畊-1 -碳硫醯胺 4-[8-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4-氧代-2-硫氧咪唑啶-1-基]辛基]-N-(苯基甲基） 穴鼠卩比17井-1 -碳硫酸胺 4-[8-[3-(1，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4-氧代-2-硫氧咪唑啶-1-基]辛基]-N-苯基六氫吡 畊-1 -碳硫醯胺 4-[8-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4 -氧代-2 -硫氧咪σ圭淀-1 -基]辛基]六氫p比ρ井-1 -碳 硫酸S -甲酯 4-[8-[3-(1，3-二氫-1-氧代異苯并呋喃-5-基）-5,5-二 甲基-4 -氧代-2 -硫氧咪唑啶-1 -基]辛基]六氫吡畊-1 -碳 -94- 200301117Alkyl) phenyl] hexahydropyridine-1 -carboxylic acid amine 4- [8- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5 -Dimethyl-4-oxo-2-thiooximidazol-1-yl] octyl] -N- (3-fluorophenyl) hexahydrogen 4-1-double acid siamine 4- [8- [3- (1,3-Dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] octane Phenyl] -N-ethylhexahydropyridine-1 -carbothioamide 4- [8- [3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5, 5 -dimethyl-4 -oxo-2 -thioximidazolidine-1 -yl] octyl] -N -propylhexahydropyridine-1 -carbothioxamine 4- [8- [3- ( 1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2-thiooximidazol-1-yl] octyl] -N -(Propyl-2-amidino) hexahydropyridine-1 -carbothioamide 4- [8- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl)- 5,5-Dimethyl-4-oxo-2-thiooximidazol-1-yl] octyl] -N- (phenylmethyl) hamster mole ratio 17-well-1 -Carbonamine sulfate 4- [8- [3- (1,3-dihydro-1-oxoisobenzofuran-5 -yl) -5,5-dimethyl-4-oxo-2-thiooximidazolidine-1- Yl] octyl] -N-phenylhexahydropyridine-1 -carbothioamide 4- [8- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4 -oxo-2 -thioxoimide σ-Guyodo-1 -yl ] Octyl] hexahydro p ratio ρ well-1 -Carbon sulfate S -methyl ester 4- [8- [3- (1,3-dihydro-1-oxoisobenzofuran-5-yl) -5 , 5-dimethyl-4 -oxo-2 -thioximidazolidine-1 -yl] octyl] hexahydropyridine-1 -carbon-94- 200301117 硫酸s -乙酯 4-[8-[3-(l，3 -二氫-1-氧代異苯并呋喃-5 -基）-5,5 -二 甲基-4-氧代-2-硫氧咪唑啶-1-基]辛基]-N，N-二乙基六 氫吡畊-1 -羧酸醯胺 6-[4,4-二甲基-5 -氧代-3-[5-[4-(甲基磺醯基）六氫吡 畊-1 -基]戊基]-2 -硫氧咪唑啶-1 -基]-4 -甲基-1 Η - 2，3 -苯 并17号畊-1 -酮S-ethyl sulfate 4- [8- [3- (l, 3-dihydro-1-oxoisobenzofuran-5-yl) -5,5-dimethyl-4-oxo-2- Thioximidazol-1-yl] octyl] -N, N-diethylhexahydropyridine-1 -carboxamide-6- [4,4-dimethyl-5 -oxo-3- [ 5- [4- (methylsulfonamido) hexahydropyridine-1 -yl] pentyl] -2 -thiothioimidazol-1-yl] -4 -methyl-1 pyrene -2,3-benzene And No. 17 plough-1 6 - [ 4，4 -二甲基-5 -氧代-3 - [ 6 - [ 4 -(甲基磺醯基）六氫吡 畊-1 -基]戊基]-2 -硫氧咪唑啶-1 -基]-4 -甲基-1 Η - 2，3 -苯 并崎畊—1 _酮 1-[6-(4_乙醯基六氫吡畊-1-基）己基]-3-(2,3-二氫-；l-氧代-lH-茚-5-基）-5,5-二甲基-2-硫氧咪唑啶-4-酮 3-(2,3-二氫-1-氧代-1Η-茚-5-基）-5,5-二甲基 -1-[6-[4-(2 -甲基-1-氧代丙基）六氫吡畊-1-基]己基]-2-硫氧味峻淀-4 -酉同6-[4,4-Dimethyl-5 -oxo-3-[6-[4-(methylsulfonyl) hexahydropyridine-1 -yl] pentyl] -2 -thioximidazole -1 -yl] -4 -methyl-1 hydrazone -2,3 -benzozakigen-1 _one 1- [6- (4_ethylfluorenylhexahydropyrine-1-yl) hexyl] -3 -(2,3-dihydro-; l-oxo-lH-inden-5-yl) -5,5-dimethyl-2-thioximidazolidine-4-one 3- (2,3-di Hydro-1-oxo-1fluorene-inden-5-yl) -5,5-dimethyl-1- [6- [4- (2-methyl-1-oxopropyl) hexahydropyridine- 1-yl] hexyl] -2-thiooxytaste Junyodo-4 -same 3-(2,3-二氫-1-氧代-1Η·茚-5-基）-5,5-二甲基 _1_[6-[4-[(嘧-2-基）羰基]六氫吡畊-1-基]己基]-2-硫氧 咪唑啶-4 -酮 3-(2,3-二氫-1-氧代-1Η-茚-5-基）-5,5-二甲基 -1-[6-[4-[(吡啶-4-基）羰基]六氫吡畊-1-基]己基卜2-硫 氧咪哇咬-4 -酮 3-(2,3-二氫-1-氧代-1Η-菲-5-基）-5,5-二甲基 -1-[6-[4-(甲基磺醯基）六氫吡畊-1-基]己基]-2-硫氧咪 峻淀-4 -酮 -95 - 2003011173- (2,3-dihydro-1-oxo-1fluorene · inden-5-yl) -5,5-dimethyl_1_ [6- [4-[(pyrim-2-yl) carbonyl] hexa Pyridin-1-yl] hexyl] -2-thiooximidazolidine-4 -one 3- (2,3-dihydro-1-oxo-1fluoren-inden-5-yl) -5,5-di Methyl-1- [6- [4-[(pyridin-4-yl) carbonyl] hexahydropyridine-1-yl] hexylb 2-thioxomidazole-4 -one 3- (2,3- Dihydro-1-oxo-1'-phenanthrene-5-yl) -5,5-dimethyl-1- [6- [4- (methylsulfonyl) hexahydropyridin-1-yl] hexyl ] -2-Thioximidate-4 -one-95-200301117 3- (2，3-二氫-1-氧代-1H-茚-5-基）-5，5-二甲基 _ 1 _[ 6 - [ 4 -(丙基磺醯基）六氫吡畊-1 -基]己基]-2 -硫氧咪 哇咬-4 -嗣 4- [6-[3-(2,3-二氫-1-氧代-1H-茚-5 -基）-5,5-二甲基 -4 -氧代-2 -硫氧咪哇淀-1 -基]己基]-N -乙基六氫p比喷 -1 - 硫酸胺 4-[6-[3-(2,3 -二氫-1-氧代-1H -茚-5 -基）-5,5-二甲基 -4 -氧代-2 -硫氧咪哇淀-1 -基]己基]六氫p比呼-1 -碳硫酸 S -曱酉旨。 9 .如申請專利範圍第1項之化合物，即， 4-[3-[3-[4-[(2 -甲氧基乙基）磺醯基]六氫吡畊-1-基] 丙基]-4,4-二甲基-5 -氧代-2-硫氧咪唑啶-1-基]-2-(三 氟甲基）苯甲腈 4-[4-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]丁基]六氫吡畊-l-碳腈 !^1_4-[3-[4-[(211，53)-4-乙醯基-2,5-二甲基六氫吡畊 -1 -基]丁基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[4-(4-乙醯基六氫-1H-1，4-二氮呼-1-基）丁 基]-4,4-二甲基-5 -氧代-2-硫氧咪唑啶-1-基]-2-(三氟 甲基）苯甲腈 rel-4-[3-[4-[(2R，5S)-2,5-二甲基- 4-(2 -甲基-1-氧代丙 基）六氫吡畊-1-基]丁基]-4,4-二甲基-5-氧代-2-硫氧咪 唑啶-1-基]-2-(三氟甲基）苯甲腈 -96- 20030111?3- (2,3-dihydro-1-oxo-1H-inden-5-yl) -5,5-dimethyl_ 1 _ [6-[4-(propylsulfonyl) hexahydropyridine Geng-1 -yl] hexyl] -2 -thioxomidazine-4-嗣 4- [6- [3- (2,3-dihydro-1-oxo-1H-inden-5 -yl)- 5,5-Dimethyl-4 -oxo-2 -thioxomidazoline-1 -yl] hexyl] -N -ethylhexahydrop ratio spray-1-amine sulfate 4- [6- [3- (2,3 -dihydro-1-oxo-1H-inden-5 -yl) -5,5-dimethyl-4 -oxo-2 -thioximidolide-1 -yl] hexyl] hexa Hydrogen p is more than 1-carbosulfuric acid S-intention. 9. The compound according to item 1 of the scope of patent application, that is, 4- [3- [3- [4-[(2-methoxyethyl) sulfonyl] hexahydropyridine-1-yl] propyl ] -4,4-dimethyl-5 -oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4- [3- [4-cyano 3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazolidine-l-yl] butyl] hexahydropyridine-l-carbonitrile ! ^ 1_4- [3- [4-[(211,53) -4-Ethyl-2,5-dimethylhexahydropyridine-1 -yl] butyl] -4,4-dimethyl -5 -oxo-2 -thioximidazolidine-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- (4-ethylfluorenylhexahydro-1H-1, 4-diazol-1-yl) butyl] -4,4-dimethyl-5 -oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile rel-4- [3- [4-[(2R, 5S) -2,5-dimethyl-4- (2-methyl-1-oxopropyl) hexahydropyrine-1-yl] butyl Group] -4,4-dimethyl-5-oxo-2-thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile-96- 20030111? 4-[3-[3-[4-(2 -羥基-2-甲基-1-氧代丙基）六氫吡畊-1-基]丁基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[4-[3-[4-(2,2-二甲基-1-氧代丙基）六氫吡畊-1-基] 丁基]4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 rel-4-[3-[4-[(2R，5S)-4-(2,2-二甲基-1-氧代丙基）-2,5 -二甲基六氫吡畊-1 -基]丁基]-4，4 -二甲基-5 -氧代-2 -硫 氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4-[3-[4-(4-(2,2-二甲基-1-氧代丙基）六氫-1H-1，4 -二 氮呼-1-基）丁基]-4，4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 rel-4-[3-[4-[(2R，5S)-4-(環丙基羰基）-2,5-二甲基六 氫吡畊-1 -基]丁基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 4-[3-[4-(甲氧基乙醯基）六氫吡畊-1-基]丁基]-4,4-二 甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯甲 腈 4-[3-[4-[六氫-4-(3-甲氧基-1-氧代丙基）-1Η-1，4 -二 氮呼-1-基]丁基]-4，4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4-[4,4-二甲基-5-氧代-2-硫氧- 3-[4·[4-(三氟乙醯基） 六氫吡畊-1 - 丁基]咪唑啶-1 -基]-2 -(三氟甲基）苯甲腈 4-[3-[4-[六氫- 4- (三氟乙醯基）-1Η-1，4-二氮呼-1-基] -97- 2003011174- [3- [3- [4- (2-hydroxy-2-methyl-1-oxopropyl) hexahydropyrine-1-yl] butyl] -4,4-dimethyl-5 -Oxo-2 -thioximidazolidine-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [4- [3- [4- (2,2-dimethyl-1-oxo Propyl) hexahydropyrine-1-yl] butyl] 4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzene Nitrile rel-4- [3- [4-[(2R, 5S) -4- (2,2-dimethyl-1-oxopropyl) -2,5-dimethylhexahydropyridine- 1-yl] butyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [ 4- (4- (2,2-Dimethyl-1-oxopropyl) hexahydro-1H-1,4-diazahu-1-yl) butyl] -4,4-dimethyl- 5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile rel-4- [3- [4-[(2R, 5S) -4- (cyclopropane Carbonyl) -2,5-dimethylhexahydropyridine-1 -yl] butyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2 -(Trifluoromethyl) benzonitrile 4- [3- [4- (methoxyethylfluorenyl) hexahydropyridine-1-yl] butyl] -4,4-dimethyl-5 -oxo -2 -thiothioimidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4- [3- [4- [hexahydro-4- (3-methoxy Yl-1-oxopropyl) -1Η-1,4-diazeth-1-yl] butyl] -4,4-dimethyl-5-oxo-2-thiooximidazolidine-1- Phenyl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-2-thiooxy- 3- [4 · [4- (trifluoroacetamido) Hexahydropyridine-1 -butyl] imidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [3- [4- [hexahydro- 4- (trifluoroacetamidyl) -1Η-1,4-diazeth-1-yl] -97- 200301117 丁基]-4，4 -二甲基-5 -氧代-2 -硫氧咪峻淀-1 -基]-2 -(三 氟甲基）苯甲腈 4-[3-[4-[4-[(呋喃-2-基）羰基]六氫-1H-1，4 -二氮呼-1-基]丁基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈Butyl] -4,4-dimethyl-5 -oxo-2 -thioxanmidone-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [3- [4- [ 4-[(furan-2-yl) carbonyl] hexahydro-1H-1,4-diazol-1-yl] butyl] -4,4-dimethyl-5 -oxo-2 -thiooxy Imidazolidine-1 -yl] -2- (trifluoromethyl) benzonitrile 4-[3-[4-[六氫-4-[(嘍-2 -基）羰基]-1H-1，4-二氮呼-1-基]丁基]-4，4 -二甲基· 5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 rel-4-[4,4-二甲基-3-[4-[(2R，5S)-2,5-二甲基-4-(甲基 磺醯基）六氫吡畊-1 -基]丁基]-5 -氧代-2 -硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 4-[3-[4-[六氫- 4- (甲基磺醯基）-1Η-1，4 -二氮呼-1-基] 丁基]_ 4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三 氟甲基）苯甲腈4- [3- [4- [hexahydro-4-[(fluoren-2-yl) carbonyl] -1H-1,4-diazol-1-yl] butyl] -4,4-dimethyl 5 -oxo-2 -thioximidazolidine-1-yl] -2- (trifluoromethyl) benzonitrile rel-4- [4,4-dimethyl-3- [4-[(2R , 5S) -2,5-Dimethyl-4- (methylsulfonyl) hexahydropyridine-1 -yl] butyl] -5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [4- [hexahydro- 4- (methylsulfonyl) -1, -1,4-diazol-1-yl] butyl ] _ 4,4-Dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2-(trifluoromethyl) benzonitrile 4-[3-[4-[4-[(2 -甲氧基乙基）磺醯基]六氫吡畊-1-基] 丁基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三 氟甲基）苯甲腈 4-[4-[3-[4-夜基-3-(二氣甲基）苯基]-5,5-二甲基-4-氧代-2 -硫氧咪唑啶-1 -基]丁基]六氫-1 Η - 1，4 -二氮呼 -1 -基-羰硫酸S -甲酯 4-[4-[3-[4-氰基-3-(三氟甲基）苯基]-5,5·二甲基-4-氧代-2-硫氧咪唑啶-l-基]丁基]六氫吡畊-l-磺醯胺 Ν，Ν-二甲酯 4 - [3-[ 5-[4_ (2 -甲氧基苯甲醯基）六氫吡畊-1-基]戊 -98- 2003011174- [3- [4- [4-[(2-methoxyethyl) sulfonamido] hexahydropyridin-1-yl] butyl] -4,4-dimethyl-5 -oxo -2 -thioximidazol-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [4- [3- [4-nightyl-3- (diaminomethyl) phenyl]- 5,5-dimethyl-4-oxo-2 -thioximidazolidine-1 -yl] butyl] hexahydro-1 hydrazone -1,4 -diazepine-1 -yl-carbonylsulfate S -formyl Ester 4- [4- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5 · dimethyl-4-oxo-2-thiooximidazol-l-yl ] Butyl] hexahydropyridine-l-sulfamethoxamine N, N-dimethyl ester 4-[3- [5- [4_ (2-methoxybenzylidene) hexahydropyridine-1-yl ] Pent-98- 200301117 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟 甲基）苯甲腈 4-[5-[3-[4 -氰基- 3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]戊基]六氫吡畊-l-碳腈 ^1-4-[3-[5-[(211，63)-4-乙醯基-2,6-二甲基六氫吡畊 -1 -基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈Yl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [5- [3- [4- Cyano 3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazolidine-l-yl] pentyl] hexahydropyridine-l-carbon Nitrile ^ 1-4- [3- [5-[(211,63) -4-Ethylfluorenyl-2,6-dimethylhexahydropyridine-1 -yl] pentyl] -4,4-di Methyl-5 -oxo-2 -thioximidazolidine 1 -yl] -2- (trifluoromethyl) benzonitrile 4-[3-[5-(4-乙醯基六氫-1H-1，4-二氮呼-1-基）戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟 甲基）苯甲腈 4-[3-[5-[六氫-4-(2 -甲基-1-氧代丙基）-1Η-1,4-二氮 呼-1 -基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈4- [3- [5- (4-Acetylhexahydro-1H-1,4-diazol-1-yl) pentyl] -4,4-dimethyl-5-oxo-2- Thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [hexahydro-4- (2-methyl-1-oxopropyl) -1Η -1,4-Diazepine-1 -yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximimidazol-1 -yl] -2- (trifluoromethyl) Benzonitrile 4-[3-[5-[4-(2 -羥基-2-甲基-1-氧代丙基）六氫吡畊-1-基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[5-[4-(2,2-二甲基-1-氧代丙基）六氫吡畊-1-基] 戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三 氟甲基）苯甲腈 4-[3-[5-[4-(2,2-二甲基-1-氧代丙基）六氫-1H-1，4 -二 氮呼-1 -基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[5-[4-(甲氧基乙醯基）六氫吡畊-1-基]戊 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟 -99- 2003011174- [3- [5- [4- (2-hydroxy-2-methyl-1-oxopropyl) hexahydropyrine-1-yl] pentyl] -4,4-dimethyl-5 -Oxo-2 -thioximidazolidine-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4- (2,2-dimethyl-1-oxo Propyl) hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) Benzonitrile 4- [3- [5- [4- (2,2-dimethyl-1-oxopropyl) hexahydro-1H-1,4-diazahu-1 -yl] pentyl] -4,4-Dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4- (methyl Oxyethenyl) hexahydropyridin-1-yl] pentyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoro- 99- 200301117 甲基）苯甲腈 4-[4,4-二甲基-5-氧代-2-硫氧- 3- [5-[4-(三氟乙醯基） 六氫吡畊-1-基]戊基]咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[3-[5-[4-[(呋喃-3-基）羰基]六氫-111-1，4-二氮呼-1-基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈Methyl) benzonitrile 4- [4,4-dimethyl-5-oxo-2-thiooxy- 3- [5- [4- (trifluoroethylfluorenyl) hexahydropyridine-1-yl ] Pentyl] imidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4-[(furan-3-yl) carbonyl] hexahydro-111-1 , 4-Diazetidin-1-yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2- (trifluoromethyl) benzyl Nitrile 4-[3-[5-[六氫-4-[(噻-3-基）羰基]-1H-1，4-二氮呼-1-基]戊基]_ 4，4 -二甲基-5 -氧代-2 -硫氧味σ坐淀-1 · 基]-2-(三氟甲基）苯甲腈 4-[3-[5-[4-[(呋喃-2-基）羰基]六氫-1Η-1，4-二氮呼-1-基]戊基]-4,4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈4- [3- [5- [hexahydro-4-[(thia-3-yl) carbonyl] -1H-1,4-diazeth-1-yl] pentyl] -4,4-dimethyl -5 -oxo-2 -thiooxy odor σ sitting lake-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [3- [5- [4-[(furan-2-yl) Carbonyl] hexahydro-1Η-1,4-diazeth-1-yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2- (Trifluoromethyl) benzonitrile 4-[3-[5-[六氫-4-[(噻-2 -基）羰基]-1Η-1，4-二氮呼-1-基]戊基]-4，4 -.一甲基-5 -氧代-2 -硫氧味σ坐淀-1 * 基]-2-(三氟甲基）苯甲腈 rel-4-[3-[5-[(2R，6S)-2,6-二甲基-4-(甲基磺醯基）六 氫说畊-1 -基]戊基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶 -1-基]-2-(二氣甲基）苯甲猜 4-[3-[5-[六氫- 4-(甲基磺醯基）-1Η-1，4-二氮呼-1-基] 戊基]-4，4 -—甲基-5 -氧代-2 -硫氧味吐咬-1 -基]-2 -(二 氣甲基）苯甲月青 4-[5-[3-[4-氰基- 3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]戊基]六氫-lH-l，4-二氮呼 -100- 2003011174- [3- [5- [hexahydro-4-[(thia-2-yl) carbonyl] -1Η-1,4-diazeth-1-yl] pentyl] -4,4 -.monomethyl -5 -oxo-2 -thiooxy odor σ sitting lake -1 * yl] -2- (trifluoromethyl) benzonitrile rel-4- [3- [5-[(2R, 6S) -2 , 6-Dimethyl-4- (methylsulfonyl) hexahydrocyclo-1 -yl] pentyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -Yl] -2- (difluoromethyl) benzyl 4- [3- [5- [hexahydro- 4- (methylsulfonyl) -1, -1,4-diazepine-1-yl ] Amyl] -4,4 -methyl-5 -oxo-2 -thiooxy odor bite-1 -yl] -2-(digasmethyl) benzazine 4- [5- [3 -[4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazolidine-l-yl] pentyl] hexahydro-1H -l, 4-diazepine-100- 200301117 -1 -基·羰硫酸s -甲酯 4-[5-[3-[4 -氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪峻咬-l-基]戊基]六氫p比ϊ7井-l-績ϊi胺 N，N-二甲酯 4-[6-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪σ坐淀-l-基]己基]六氫p比ϊT井-l-碳腈-1 -yl carbonyl sulfate s -methyl ester 4- [5- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo- 2-thioxanthine-l-yl] pentyl] hexahydro p ratio ϊ7-l-ji amine N, N-dimethyl ester 4- [6- [3- [4-cyano-3- (Trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thioxoimide σ sitting-l-yl] hexyl] hexahydro p ratio T well-l-carbonitrile ^1-4-[3-[6-[(211，53)-4-乙醯基-2,5-二甲基六氫吡畊 -1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 1^1-4-[3-[6-[(211，63)-4-乙醯基-2,6-二甲基六氫吡畊 -1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 rel-4-[3-[6-[(2R，5S)-2,5-二甲基- 4-(2 -甲基-1-氧代丙 基）六氫吡畊-1 -基]己基]-4，4 -二曱基-5 -氧代-2 -硫氧咪 唑啶-1-基]-2-(三氟甲基）苯甲腈^ 1-4- [3- [6-[(211,53) -4-Ethyl-2,5-dimethylhexahydropyridine-1 -yl] hexyl] -4,4-dimethyl -5 -oxo-2 -thioximidazolidine-1 -yl] -2- (trifluoromethyl) benzonitrile 1 ^ 1-4- [3- [6-[(211,63) -4- Ethyl-2,6-dimethylhexahydropyridine-1 -yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximimidazol-1 -yl] -2- (Trifluoromethyl) benzonitrile rel-4- [3- [6-[(2R, 5S) -2,5-dimethyl-4- (2-methyl-1-oxopropyl) hexa Hydropyridine-1 -yl] hexyl] -4,4-difluorenyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[6-[六氫-4-(2 -甲基-1-氧代丙基）-1Η-1，4 -二氮 呼-1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[6-[4-(2-羥基-2-甲基-1-氧代丙基）六氫吡畊-1-基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[6-[4-(2,2-二甲基-1-氧代丙基）六氫吡畊-1-基] 己基]-4，4 -—甲基-5 -氧代-2 -硫氧i味σ坐淀-1 -基]-2 -(二 氟甲基）苯甲腈 -101 - 2003011174- [3- [6- [hexahydro-4- (2-methyl-1-oxopropyl) -1Η-1,4-diazahu-1 -yl] hexyl] -4,4 -di Methyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4- (2-hydroxy-2-methyl Yl-1-oxopropyl) hexahydropyridin-1-yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (tri Fluoromethyl) benzonitrile 4- [3- [6- [4- (2,2-dimethyl-1-oxopropyl) hexahydropyrine-1-yl] hexyl] -4,4- —Methyl-5 -oxo-2 -thiooxyi odor σ sitting lake-1 -yl] -2-(difluoromethyl) benzonitrile -101-200301117 rel-4-[3-[6-[(2R，5S)-4-(2,2-二甲基-1-氧代丙基）-2,5 -二甲基六氫吡畊-1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫 氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 rel-4-[3-[6-[(2R，6S)-4-(2,2-二甲基-1-氧代丙基）-2,6 -二甲基六氫吡畊-1 -基]己基]-4，4 -二甲基-5 ·氧代-2 -硫 氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 rel-4-[3-[6-[(2R，5S)-4-(環丙基羰基）-2,5-二甲基六 氫吡畊-1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 4-[3-[6-[4-(甲氧基乙醯基）六氫吡畊-1-基]己 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈rel-4- [3- [6-[(2R, 5S) -4- (2,2-dimethyl-1-oxopropyl) -2,5-dimethylhexahydropyridine-1- Yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile rel-4- [3- [6 -[(2R, 6S) -4- (2,2-dimethyl-1-oxopropyl) -2,6-dimethylhexahydropyridine-1 -yl] hexyl] -4,4- Dimethyl-5 · oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile rel-4- [3- [6-[(2R, 5S) -4 -(Cyclopropylcarbonyl) -2,5-dimethylhexahydropyridine-1 -yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl ] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [4- (methoxyethylfluorenyl) hexahydropyridin-1-yl] hexyl] -4,4-dimethyl -5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile rel-4-[3-[6-[(2R，5S)-4-(3-甲氧基-1-氧代丙基）-2,5-二甲基六氫吡畊-1-基]己基]-4,4-二甲基-5-氧代-2-硫 氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4-[3-[6-[六氫-4-(3-甲氧基-1-氧代丙基）-1Η-1，4-二 氮呼-1-基]己基]-4，4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4-[4,4-二甲基-5-氧代-2-硫氧-3_[6-[4-(三氟乙醯基） 六氫吡畊-1-基]己基]咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 rel-4-[3-[6-[(2R，5S)-2,5-二甲基-4-(三氟乙醯基）六 氫吡畊-1-基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 -102- 20030111?rel-4- [3- [6-[(2R, 5S) -4- (3-methoxy-1-oxopropyl) -2,5-dimethylhexahydropyridine-1-yl] Hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [hexahydro -4- (3-methoxy-1-oxopropyl) -1Η-1,4-diazol-1-yl] hexyl] -4,4-dimethyl-5-oxo-2- Thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-2-thiooxy-3_ [6- [4- ( Trifluoroacetamido) hexahydropyridin-1-yl] hexyl] imidazol-1-yl] -2- (trifluoromethyl) benzonitrile rel-4- [3- [6-[(2R, 5S) -2,5-dimethyl-4- (trifluoroethylfluorenyl) hexahydropyridine-1-yl] hexyl] -4,4-dimethyl-5-oxo-2-thiooximidazole Pyridin-1-yl] -2- (trifluoromethyl) benzonitrile-102- 20030111? ^1-4-[3-[6-[(211，53)-4-[(呋喃-3-基）羰基]-2,5-二甲 基六氫吡畊-1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪 唑啶-1-基]-2-(三氟甲基）苯甲腈 以1-4-[3-[6-[(211，53)-4-[(異吟唑-5-基）羰基]-2,5-二 甲基六氫毗畊-1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧 咪唑啶-1-基]-2-(三氟甲基）苯甲腈 1^1-4-[3-[6_[(211，53)-4-[(呋喃-2-基）羰基]-2,5-二甲 基六氫吡畊-1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪 唑啶-1-基]-2-(三氟甲基）苯甲腈 4-[3-[6-[4-[(呋喃-2-基）羰基]六氫-1H-1，4-二氮呼-1-基]己基]-4，4 -二f7基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈^ 1-4- [3- [6-[(211,53) -4-[(furan-3-yl) carbonyl] -2,5-dimethylhexahydropyridine-1 -yl] hexyl]- 4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile to 1-4- [3- [6-[(211 , 53) -4-[(Isinazol-5-yl) carbonyl] -2,5-dimethylhexahydropyridine-1 -yl] hexyl] -4,4-dimethyl-5 -oxo -2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 1 ^ 1-4- [3- [6 _ [(211,53) -4-[(furan-2- Yl) carbonyl] -2,5-dimethylhexahydropyridine-1 -yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2 -(Trifluoromethyl) benzonitrile 4- [3- [6- [4-[(furan-2-yl) carbonyl] hexahydro-1H-1,4-diazol-1-yl] hexyl] -4,4 -di-f7yl-5 -oxo-2 -thioximidazolidine-1 -yl] -2- (trifluoromethyl) benzonitrile rel-4-[3-[6-[(2R，5S)-2,5·二甲基-4-[(噻-2-基）羰基] 六氫吡畊-1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑 啶-1-基]-2-(三氟甲基）苯甲腈 4-[3-[6-[六氫-4-[(噻-2-基）羰基]-1H-1，4-二氮呼-1-基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 rel-4-[3-[6-[(2R，5S)-2,5-二甲基-4-(甲基磺醯基）六 氫吡畊-1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 rel-4-[3-[6-[(2R，6S)-2,6-二甲基-4-(甲基磺醯基）六 氫吡嗜-1-基]己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 -103 - 200301117rel-4- [3- [6-[(2R, 5S) -2,5 · dimethyl-4-[(thia-2-yl) carbonyl] hexahydropyridine-1 -yl] hexyl] -4 , 4-Dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [6- [hexahydro-4- [ (Thi-2-yl) carbonyl] -1H-1,4-diazeth-1-yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl ] -2- (trifluoromethyl) benzonitrile rel-4- [3- [6-[(2R, 5S) -2,5-dimethyl-4- (methylsulfonyl) hexahydropyridine Geng-1 -yl] hexyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile rel-4- [ 3- [6-[(2R, 6S) -2,6-dimethyl-4- (methylsulfonyl) hexahydropyridin-1-yl] hexyl] -4,4-dimethyl-5 -Oxo-2-thioxazomidazol-1-yl] -2- (trifluoromethyl) benzonitrile-103-200301117 4-[3-[6-[六氫- 4- (甲基磺醯基）-1Η-1，4-二氮呼-1-基] 己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三 氟甲基）苯甲腈4- [3- [6- [hexahydro- 4- (methylsulfonyl) -1′-1,4-diazol-1-yl] hexyl] -4,4-dimethyl-5 -oxy -2 -thiothioimidazol-1 -yl] -2-(trifluoromethyl) benzonitrile rel-4-[3-[6-[(2R，5S)-4-(乙基磺醯基）-2,5 -二甲’基六 氫吡畊-1 -基]己基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 4-[4,4-二曱基- 3- [6-[4-[(l-甲基乙基）磺醯基]六氫吡 畊-1 -基]己基]-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲 基）苯甲腈 4-[3-[6-[4-[(2 -甲氧基乙基）磺醯基]六氫吡畊-1-基] 己基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三 氟甲基）苯甲腈 4-[6-[3-[4-氰基- 3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]己基]六氫-lH-l，4-二氮呼 -1 -基-羰硫酸S -甲酯rel-4- [3- [6-[(2R, 5S) -4- (ethylsulfonyl) -2,5-dimethyl'ylhexahydropyrimyl-1 -yl] hexyl] -4,4 -Dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-diamidino- 3- [6- [ 4-[(l-methylethyl) sulfofluorenyl] hexahydropyridine-1 -yl] hexyl] -5 -oxo-2 -thioximimidazol-1 -yl] -2-(trifluoromethyl ) Benzonitrile 4- [3- [6- [4-[(2-methoxyethyl) sulfonyl] hexahydropyridin-1-yl] hexyl] -4,4-dimethyl- 5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [6- [3- [4-cyano-3- (trifluoromethyl) Phenyl] -5,5-dimethyl-4-oxo-2-thioximidazolidine-l-yl] hexyl] hexahydro-1H-l, 4-diazepine-1 -yl-carbonylsulfate S -Methyl ester 4-[7-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]庚基]六氫吡畊-l-碳腈 1^1-4-[3-[7-[(211，63)-4-乙醯基-2,6-二甲基六氫吡畊 -1 -基]庚基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4 - [ 3 - [ 7 - [ 4 - (2 -羥基-2 _甲基-1 -氧代丙基）六氫吡畊-1 -基]庚基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈 4-[3-[7-[4-(2,2-二甲基-1-氧代丙基）六氫吡畊-1-基] -104- 2003011174- [7- [3- [4-cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazol-l-yl] Heptyl] hexahydropyridine-l-carbonitrile 1 ^ 1-4- [3- [7-[(211,63) -4-ethenyl-2,6-dimethylhexahydropyridine-1 -Yl] heptyl] -4,4-dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[7 -[4-(2-hydroxy-2 -methyl-1 -oxopropyl) hexahydropyridine-1 -yl] heptyl] -4,4-dimethyl-5 -oxo-2 -sulfur Oximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [3- [7- [4- (2,2-dimethyl-1-oxopropyl) hexahydropyridine Plough-1-based] -104- 200301117 庚基]_ 4，4 -二甲基-5 -氧代-2 -硫氧味坐淀-1-基]-2-(二 氟甲基）苯甲腈Heptyl] _ 4,4-dimethyl-5 -oxo-2 -thiooxyzine-1-yl] -2- (difluoromethyl) benzonitrile rel-4-[3-[7-[(2R，6S)-4-(2,2-二甲基-1-氧代丙 基）-2,6-二甲基六氫吡畊-1-基]庚基]-4,4-二甲基-5-氧 代-2 -硫氧咪唑啶-1 -基]-2 -(三氟甲基）苯甲腈 4-[3-[7-[4-(甲氧基乙醯基）六氫吡畊-1-基]庚 基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4-[4,4-二甲基-5-氧代-2-硫氧-3-[7-[4-(三氟乙醯基） 六氫吡畊-1-基]庚基]咪唑啶-1-基]-2-(三氟甲基）苯甲 腈rel-4- [3- [7-[(2R, 6S) -4- (2,2-dimethyl-1-oxopropyl) -2,6-dimethylhexahydropyrine-1- Yl] heptyl] -4,4-dimethyl-5-oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [3- [7- [4- (methoxyethylfluorenyl) hexahydropyridin-1-yl] heptyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2 -(Trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-2-thiooxy-3- [7- [4- (trifluoroethylfluorenyl) hexahydropyridine -1-yl] heptyl] imidazol-1-yl] -2- (trifluoromethyl) benzonitrile rel-4-[3-[7-[(2R，6S)-2,6-二甲基-4-(三氟乙醯基）六 氫吡畊-1 -基]庚基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 rel-4-[3-[7-[(2R，6S)-2,6-二甲基-4-(甲基磺醯基）六 氫吡畊-1 -基]庚基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶 -1-基]-2-(三氟甲基）苯甲腈 4 - [ 3 - [ 7 - [ 4 - [(2 -甲氧基乙基）磺醯基]六氫吡畊-1 -基] 庚基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三 氟甲基）苯甲腈 4-[8-[3-[4 -氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]辛基]六氫吡畊-l-碳腈 !^1-4-[3-[8-[(211，63)-4-乙醯基-2,6-二甲基六氫吡畊 -1-基]辛基]-4,4-<一甲基-5 -氧代-2 -硫氧味17全淀-1 _ -105 - 200301117 基]-2-(三氟甲基）苯甲腈 4-[3-[8-[4-(2 -羥基-2-甲基-1-氧代丙基）六氫吡畊-1-基]辛基]-4，4 -二甲基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2-(三氟甲基）苯甲腈rel-4- [3- [7-[(2R, 6S) -2,6-dimethyl-4- (trifluoroethylfluorenyl) hexahydropyridine-1 -yl] heptyl] -4,4 -Dimethyl-5 -oxo-2 -thioximidazol-1-yl] -2- (trifluoromethyl) benzonitrile rel-4- [3- [7-[(2R, 6S)- 2,6-dimethyl-4- (methylsulfonamido) hexahydropyridine-1 -yl] heptyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine- 1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[7-[4-[(2-methoxyethyl) sulfonamido] hexahydropyridine-1 -yl] Heptyl] -4,4-dimethyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2-(trifluoromethyl) benzonitrile 4- [8- [3- [4 -Cyano-3- (trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooximidazolidine-l-yl] octyl] hexahydropyridine-l- Carbonitrile! ^ 1-4- [3- [8-[(211,63) -4-Ethyl-2,6-dimethylhexahydropyrimidin-1-yl] octyl] -4,4 -< monomethyl-5 -oxo-2 -thiooxy odor 17 full lake -1--105-200301117 radical] -2- (trifluoromethyl) benzonitrile 4- [3- [8- [ 4- (2-hydroxy-2-methyl-1-oxopropyl) hexahydropyridin-1-yl] octyl] -4,4-dimethyl-5 -oxo-2 -thioximidazole Pyridin-1 -yl] -2- (trifluoromethyl) benzonitrile rel-4-[3-[8-[(2R，6S)-4-(2,2-二甲基-1-氧代丙 基）-2,6-二甲基六氫吡畊-1-基]辛基]-4,4-二甲基-5-氧 代-2-硫氧咪唑啶-1-基]-2-(三氟甲基）苯甲腈 4_[3-[8-[4-(甲氧基乙醯基）六氫吡畊-1-基]辛 基]-4，4 -二曱基-5 -氧代-2 -硫氧咪唑啶-1 -基]-2 -(三氟 甲基）苯甲腈 4-[4,4-二甲基-5-氧代-2-硫氧-3- [8-[4-(三氟乙醯基） 六氫吡畊-1-基]辛基]咪唑啶-1-基]-2-(三氟甲基）苯甲 腈rel-4- [3- [8-[(2R, 6S) -4- (2,2-dimethyl-1-oxopropyl) -2,6-dimethylhexahydropyrine-1- Yl] octyl] -4,4-dimethyl-5-oxo-2-thiooximidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4_ [3- [8- [ 4- (methoxyethylfluorenyl) hexahydropyridin-1-yl] octyl] -4,4-difluorenyl-5 -oxo-2 -thioximidazolidine-1 -yl] -2- (Trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-2-thiooxy-3- [8- [4- (trifluoroacetamidyl) hexahydropyridine- 1-yl] octyl] imidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4-[3-[8-[4-(甲氧基乙醯基）六氫吡畊-1-基]辛 基]-4,4-二甲基-5-氧代-2-硫氧咪唑啶-1-基]-2-(三氟 甲基）苯甲腈 4-[4,4-二甲基-5-氧代-2-硫氧-3- [8-[4-(三氟乙醯基） 六氫吡畊-1-基]辛基]咪唑啶-1-基]-2-(三氟甲基）苯甲 腈 4-[8-[3-[4-氰基-3-(三氟甲基）苯基]-5,5-二甲基-4-氧代-2-硫氧咪唑啶-l-基]辛基]六氫吡畊-l-磺醯胺 N，N-二甲酯 10. —種製造如申請專利範圍第1項之通式I化合物的方法 ，其中 -106- 20030111?4- [3- [8- [4- (methoxyethylfluorenyl) hexahydropyridin-1-yl] octyl] -4,4-dimethyl-5-oxo-2-thiooximidazole Pyridin-1-yl] -2- (trifluoromethyl) benzonitrile 4- [4,4-dimethyl-5-oxo-2-thiooxy-3- [8- [4- (trifluoro Acetyl) hexahydropyridin-1-yl] octyl] imidazol-1-yl] -2- (trifluoromethyl) benzonitrile 4- [8- [3- [4-cyano-3 -(Trifluoromethyl) phenyl] -5,5-dimethyl-4-oxo-2-thiooxyimidazolidine-l-yl] octyl] hexahydropyridine-l-sulfonamide N, N-dimethyl ester 10. —A method for manufacturing a compound of the general formula I as described in item 1 of the patent application range, wherein -106- 20030111? 在鹼存在下，通式VIII化合物Compound of general formula VIII in the presence of a base VIII 其中A，B，η，i，j，R及Rf具有如申請專利範圍第1項 中通式I所示的意義，與以下試劑之一反應VIII in which A, B, η, i, j, R and Rf have the meanings represented by the general formula I in item 1 of the scope of patent application, and react with one of the following reagents Z--N—0 Z-N==S Z—COC1 Z—S02C1 ZO—COC1 ZS—COC1 ZZ，N—COC1Z--N—0 Z-N == S Z—COC1 Z—S02C1 ZO—COC1 ZS—COC1 ZZ, N—COC1 其中Z與Zf具有如申請專利範圍第1項所示的意義， 或 在鹼存在下，下式化合物 V-W-(CH2)n —— I VII 與下式產物反應Among them, Z and Zf have the meanings as shown in item 1 of the scope of patent application, or in the presence of a base, a compound of the formula V-W- (CH2) n —— I VII reacts with a product of the formula -107- 200301117-107- 200301117 其中i，j，Y，Z，Z’，R及R’具有如申請專利範圍第1 項中通式I所示的意義，然後視需要轉化成藥理上可相 容鹽。 11. 一種通式VIII的中間產物Among them, i, j, Y, Z, Z ', R, and R' have the meanings represented by the general formula I in item 1 of the scope of the patent application, and then are converted into pharmacologically compatible salts as required. 11. An intermediate product of general formula VIII VIIIVIII 其中 V表示通式II的經取代芳香族基，Where V represents a substituted aromatic group of the general formula II, 其中among them A 表示乙酿基、乙酿基胺基、氨基、梢基、三氣甲基 或鹵素（氟、氯）， B 表示氫原子、鹵素（氟、氯）或三氟甲基，或 A與B—起表示键結至芳香族環的式III或IV的環狀基， 其中E表示亞甲基或氧原子，A represents ethyl alcohol, ethyl amino, amino, tertiary, trimethyl or halogen (fluorine, chlorine), B represents hydrogen atom, halogen (fluorine, chlorine) or trifluoromethyl, or A and B — A cyclic group of formula III or IV bonded to an aromatic ring, wherein E represents a methylene or oxygen atom, -108 - 200301117-108-200301117 w表示式v的雜環化合物，w represents a heterocyclic compound of formula v, 其中 T表示碳，雙鍵呈現在Q與T之間，Q意指=C(CH3)-基而U 意指氧， η可假定為整數值1，2，3，4，5，6，7或8之一， i與j，互相獨立表示1與2之值，其中i+j可假設為2或3之 值， R與Rf，互相獨立可為氫原子或甲基。 12. —種通式VIII的中間產物Where T represents carbon, double bonds appear between Q and T, Q means = C (CH3) -group and U means oxygen, η can be assumed to be an integer value of 1, 2, 3, 4, 5, 6, 7 Or one of 8, i and j, independently represent the values of 1 and 2, where i + j can be assumed to be the value of 2 or 3, and R and Rf, independently of each other, can be a hydrogen atom or a methyl group. 12. — Intermediate products of general formula VIII 其中 V表示通式II的經取代芳香族基， 200301117Where V represents a substituted aromatic group of the general formula II, 200301117 A與B—起表示鍵結至芳香族環的式III或IV的環狀基， 其中E表示亞甲基或氧原子，A and B together represent a cyclic group of formula III or IV bonded to an aromatic ring, where E represents a methylene or oxygen atom, IV W表示式V的雜環化合物，IV W represents a heterocyclic compound of formula V, 其中 T表示氮，單鍵呈現在Q與T之間，Q意指-C(CH3)2-基而 U意指硫，Where T represents nitrogen, a single bond appears between Q and T, Q means -C (CH3) 2- and U means sulfur, η可假定為整數值2，3，4，5，6,7或8之一， i與j互相獨立表示1與2之值，其中i+j可假設為2或3之 值， R與R’互相獨立可為氫原子或甲基。 13. —種通式VII的中間產物 V-W-(CH2)n —— I VII 其中V，W，A，B，T，Q，U，η，i，j，R及R’具有如申請 專利範圍第10項所示的意義。 14. 一種通式VII的中間產物 V-W-(CH2)n---I VII -110- 200301117η can be assumed to be one of the integer values 2, 3, 4, 5, 6, 7, or 8. i and j are independent of each other to represent the values of 1 and 2, where i + j can be assumed to be the value of 2 or 3. R and R 'Independent of each other may be a hydrogen atom or a methyl group. 13. — An intermediate product VW- (CH2) n of general formula VII —— I VII where V, W, A, B, T, Q, U, η, i, j, R and R ′ have the same scope as the patent application The meaning shown in item 10. 14. An intermediate product of general formula VII V-W- (CH2) n --- I VII -110- 200301117 其中乂，界，八，8，丁，（^，1；，11，卜」’，11及11，具有如申請 專利範圍第11項所示的意義。 15. 一種醫藥組合物，其含有至少一種如申請專利範圍第1 至9項中任一項之通式I化合物，以及醫藥上可相容佐藥 與賦形藥。 16. —種如申請專利範圍第1至9項中任一項之通式I化合物 用於製造藥劑之用途。Among them, Jie, Jie, Jie, Jie, Jie, Jie, Jie, Jie, Jie, Jie, 11 and 11 have the meanings as shown in item 11 of the scope of patent application. 15. A pharmaceutical composition comprising A compound of the general formula I as described in any one of claims 1 to 9 and a pharmaceutically compatible adjuvant and excipient. 16. —A kind of as claimed in any one of claims 1 to 9 Use of a compound of formula I for the manufacture of a medicament. 17. 如申請專利範圍第16項之通式I化合物之用途，其用於 製造藥劑供治療可藉抑制及/或去安定雄性激素受體影 響的腫瘤疾病。 18. 如申請專利範圍第16項之用途，用於製造治療攝護腺 癌的藥劑。 19. 如申請專利範圍第16項之用途，用於製造治療良性攝 護腺增生、雄性激素禿髮、多毛症及雄性激素依附的 痤疫的藥劑。17. The use of a compound of formula I as claimed in claim 16 for the manufacture of a medicament for the treatment of tumor diseases which can be affected by the inhibition and / or destabilization of androgen receptors. 18. The use of item 16 in the scope of patent application for the manufacture of a medicament for the treatment of prostate cancer. 19. The use of item 16 in the scope of patent application is for the manufacture of a medicament for the treatment of benign prostatic hyperplasia, androgenetic alopecia, hirsutism and androgen-dependent acne. -111 - 200301117 陸、（一）、本案指定代表圖為：第_圖 (二）、本代表圖之元件代表符號簡單說明：-111-200301117 Lu, (1), the designated representative of this case is: Figure _ (2), the component representative symbols of this representative map are simply explained: 柒、本案若有化學式時，請揭示最能顯示發明特徵的化學式： V—W-(CH2)n—柒 If there is a chemical formula in this case, please disclose the chemical formula that can best show the characteristics of the invention: V—W- (CH2) n—
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