TWI343917B - Therapeutic agents useful for treating pain - Google Patents
Therapeutic agents useful for treating pain Download PDFInfo
- Publication number
- TWI343917B TWI343917B TW092132303A TW92132303A TWI343917B TW I343917 B TWI343917 B TW I343917B TW 092132303 A TW092132303 A TW 092132303A TW 92132303 A TW92132303 A TW 92132303A TW I343917 B TWI343917 B TW I343917B
- Authority
- TW
- Taiwan
- Prior art keywords
- compound
- formula
- tetrazolyl
- another embodiment
- alkyl
- Prior art date
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Description
1343917 玖、發明說明: 本案主張2002年11月18曰申請之美國臨時專利申請案序 列編號60/427,381,2003年4月3日申請之美國臨時專利申請 案序列編號60/460,278,及2003年7月17日申請之美國臨時 專利申請案序列編號60/488,488之利益,各揭示全部併入本 文供參考。 【發明所屬之技術領域】 本發明係關於4-四唑基-4-苯基哌啶化合物,包含有效量 4-四唑基-4-苯基哌啶化合物之組合物,用於預防或治療動 物疼痛或腹瀉之方法’包含對於需要治療或預防之動物施 用有效量之4-四唑基-4-苯基喊啶化合物。 【先前技術】 疼痛為病人尋求醫學建議及治療之最普通之徵候。雖然 急性疼痛一般自我限制,但是慢性疼痛可能持續3個月或更 久而導致病人之人格,生活形式,能力,或生活品質顯著 改變(K.M. Foley,Pain, Cecil Textbook of Medicine 100-107, J.C. Bennett and F. Plum eds., 20th ed. 1996)。 疼痛在傳統上係以施用一種非類搗片(opioid)止痛劑,如 乙酿基水楊酸,三水楊酸膽驗鎂,乙酿胺盼(acetaminophen) ,異丁 苯丙酸(ibuprofen),苯氧苯丙酸(fenoprofen),二 轨辛納(difulusina)及甲氧萘丙酸(naproxen),或一種類搞片 止痛劑,如嗎啡,氫嗎啡_ (hydromorphone),美沙酮 (methadone),經甲左嗎喃(levorphanol),芬太尼(fentanyl), 氧可酮(oxycodone),及幾二氫嗎啡晒(oxymorphone)處理。 89531-960524.doc
Yaksh之美國專利第6,576,650 B1號,美國專利第 6,166,039號,及美國專利第5,849,761號,及Yaksh等人之美 國專利第6,573,282號述及1,4經取代之哌啶衍生物可用作 末稍活性之抗痛覺過敏(hyperalgesic)鸦片(opiates)。
Mogi等人之美國專利第6,362,203 B1號述及4-羥基-4-苯 基喊啶衍生物具有末梢止痛作用。
Carron等人之加拿大專利公開案第949560號述及具有取 代基在1及4位之味啶衍生物可用作止痛劑。
Dunn等人之國際公開案w〇 02/38185 A2述及1,4-經取代 之哌啶化合物可用作一種抗痛覺過敏鴉片。 國際公開案WO 01/70689 A1之摘要亦揭示具有取代基在 1及4位之哌啶衍生物可用作類鴉片δ受體激動劑。 傳統類鴉片止痛劑在通過血腦障壁時具有藥理學活性。 但是此血腦障壁之通過可導致不欲之中樞神經系統副作 用,如呼吸抑制,增加藥物耐受性,増加藥物依賴性,便 秘’及不欲之欣快症(eUph〇ria)。 仍需要可用於治療或預防疼痛或腹瀉及減少或避免一或 多種與傳統治療疼痛或腹瀉有關副作用之新穎藥物。 引據本文第2節中任何參考資料不被允許,該參考資料為 本案之先前技術。 【發明内容】 3.發明之摘要 本發明包括具有下式(Ia)之化合物: 89531-960524.doc 1343917 第092丨323〇3號專利申嗜亲 中文說明書替換頁⑼土 u月)
(la) 及其醫藥可接受鹽,其中:
Ar〗為(VC8環烷基,苯基,萘基,蒽基,菲基,或至7 負)雜芳基’各未經取代或經一或多個R2基取代;
Ai"2為表基,茶基,慈基,菲基,或(5至7員)雜芳基,各 未經取代或經一或多個r2基取代; G 為 _H,-L-(CH2)nC02R4,-L-(CH2)nR5,-(Cl_C5 伸垸 基)CO2R4,或-(Ci-C5 伸燒基)R5 ; L為-C(0)-,-S〇2-,或-SO-; 1^為-Η,-C(0)NH2,-C(0)NHOH,-C02R4,-CHO,-CN, -(CVC4 烷基),烷基),烷基)2,
(CH2), -或 R2及R3各獨立為-函素,_Ci_C3fe基’ -0(Ci_C3;fe基)’ -NHCCVCs 烷基),或-NCCVC^ 烷基)2; R4 為-Η,-CVC 丨。烷基,-CH^CKCVC^ 垸基),-C^NCCVC^ 烷基)2,或-CH^HiCVC*烷基); 89531-961130.doc 1343917
r -C(0)NH2’ -C(〇)NHOH,-S02NH2, 燒基)2,_s〇2NH(Ci-C4 第092132303號專利申請案 中文說明書替換頁(96年11月) R5為-NH2,-NHS02R4,_c -C(0)NH(Ci-C4烷基), 2,-H,-OH,-CN,- -<^3-(:8環垸基’ 烷基)’ -SC^Nei-C*烷基)2, 苯基’奈基,蒽基,菲基,或(5至7員)雜芳基,各未經取代 或經一或多個R2基取代; m為0至4之整數; η為1至4之整數; ρ為0或1, q為0至3之整數;及 r為1至6之整數。 本發明亦包括具有下式(Ib)之化合物:
及其醫藥可接受鹽,其中:
Ari為- C3-C8罐;基,苯基’茶基’慈基,菲基,或(5皇7 員)雜芳基’各未經取代或經一或多個r2基取代; Αι*2為苯基,莕基’蒽基,菲基,或(5至7員)雜芳基,各 未經取代或經一或多個R2基取代; G 為 Η,-L(CH2)nC(0)〇R4,-L(CH2)nR5,-(Cl_C5 伸烷 基)COOR4 ,或-((VC5伸烷基)R5 ; 89531-961130.doc ·9· 1343917 L為-C(O)-,-S02-,或-SO-; 1^為-H,-C(0)NH2,-C(0)NH0H,-C02R4,-CHO,-CN ’ -(CVC4烷基),-(:(0)ΝΗ((ν(:4烷基),烷基)2,
K
一 C-N, mz)r (CH2)
及R3各獨立為_素,-C丨-C3烷基,-0(Ci-C3烷基), -CH2N(C1-C4
-NHCCVCs 烷基),或烷基)2; R4 為-Η,-Ci-Cw烷基,-Ci^CKCi-CU 烷基), 烷基)2’ 或烷基); R5為-NH2,-NHS02R4,-C(〇)NH2,-C(0)NH0H,-S02NH2, -(^(CONHiC^-C^ 烷基),-C(0)N(Ci-C4 烷基)2,-S02NH(Ci-C4 燒基)’ -SCh^CVC^ 燒基)2, _h,-〇H,-CN,-C3-C8 環烷基, 苯基,莕基,蔥基,菲基,或-(_5至7_員)雜芳基,各未經 取代或經一或多個R_2基取代;
m為0至4之整數; η為1至4之整數; Ρ為0或1, q為0至3之整數;及 r為1至6之整數。 本發明亦包括具有下式(Ic)之化合物: 89531-960524.doc -10- 1343917 第092132303號專利申請案 中文說明書替換頁(96年11月) i 格充: l 2« ^ lL 0專1月;0
及其醫藥可接受鹽,其中: Αι*3為苯基,荅基,蒽基,菲基,或(5至7員)雜芳基,各 未經取代或經一或多個112基取代; G為-H,-L-(CH2)nC02R4,-L-(CH2)nR5 ’ _(Cl_C5伸烷基) COOR4,或-(CVCs伸烷基)R5; L為-C(0)-,-S02-,或-SO-; 1為-Η,-C(〇)NH2,-C(0)NH0H,-C02R4,-CHO,-CN, -(CVC4烷基),-c(o)nh(c〗-c4烷基),-c(o)N(c丨-C4烷基)2,
R2及R3各獨立為齒素,-CVC3烷基,-CKCVC3烷基),-NH (Ci-C〗板基),或-N(C,-C3垸基)2 ; R4 為-Η ’ -C丨-C〗。烷基,-Ci^CKCrC^ 烷基),-C^NiCrC* 烷基)2,或烷基); R5為-NH2,-NHS02R4,_c(〇)NH2,-C(0)NH0H,-S02NH2, -C^CONHCCVCU 烷基)’ 烷基)2,-S02NH(Ci-C4 89531-961130.doc -11 - 1343917
第092132303號專利申請案 中文說明書替換頁(96年11月) 2 ’ -H ’ -OH,-CN,-C3-C8環烷基, 烷基),-so2n(Ci-c4貌基)2, 菲基’或-(5-至7-員)雜芳基,各未經 苯基’蓁基,蔥基, 取代或經一或多個基取代; m為0至4之整數; η為1至4之整數; ρ為0或1, q為0至3之整數;及 r為1至6之整數。 本發明亦包括具有下式(Id)之化合物:
及其醫藥可接受鹽,其中:
Ar:3為苯基’莕基’惠基,菲基,或-(5-至7-員)雜芳基, 各未經取代或經一或多個R2基取代; G為-H ’ -L-(CH2)nC02R4,-L-(CH2)nR5,-(C丨-C5伸燒基) COOR4,或-(C〗-C5 伸烷基)R5; L為-C(0)-,-S02-,或-SO-; 1^為-Η,-C(0)NH2,-C(0)NHOH,-CO2R4,-CHO,-CN, -(CVC4 烷基)’ -C^CONHCCVC^ 烷基),烷基)2, 8953l.961130.doc -12- 1343917
(CH2)
R2及R3各獨立為由素,-C「C3烷基,-CKCt-C;烷基), -NH(C 丨-C3 烷基),或-^KCVC]烷基)2 ; R_4 為-Η ’ -Ci-Ci〇;fe 基 ’ -CH2〇(C!-C4fe 基),-CH2N(Ci-C4 烷基)2,或-CHzNf^Ci-C^烷基); R5為-NH2,-NHS02R4 ’ -C(0)NH2,-C(0)NH0H,-S02NH2, -CCCONHCCt-C*烷基),-〇(0)>1((:1-(:4烷基)2, -SOzNHCCVC^ 炊•基)’ -S〇2N(Ci-C4 坑基)2,-H’ -OH,-CN,-C^-Cg 環炫•基, 苯基,莕基,蒽基,菲基,或-(5-至7-員)雜芳基,各未經 取代或經一或多個R2基取代; m為0至4之整數: η為1至4之整數; ρ為0或1, q為0至3之整數;及 r為1至6之整數。 一種式(la),(lb) ’(Ic) ’(Id)之化合物或其醫藥可接受鹽 (各為一種「4-四唑基-4-苯基哌啶化合物」)可用於治療或 預防動物之疼痛或腹瀉。 本發明亦關於包含有效量一種4-四咬基-4-苯基喊咬化合 物及一種醫藥可接受載劑或賦形劑之組合物。本發明組合 物可用於治療或預防動物之疼痛或腹瀉。 89531-960524.doc -13- 1343917 本發明亦關於包含一個含有有效量一種4_四唑基__4•笨基 喊咬化合物之容器及使用其治療或預防疼痛或腹瀉之指示 之套組。 本發明另關於預防動物疼痛或腹瀉之方法,包含對於需 要之動物施用有效量之4-四唑基-4-苯基哌啶化合物。 本發明另關於治療動物疼痛或腹瀉之方法,包含對於需 要之動物施用有效量之4-四唑基-4-苯基喊啶化合物。 本發明另關於刺激一個細胞内類鴉片(〇pi〇id)受體功能
V 又万法,包含使一個可表現類鴉片受體之細胞接觸有效量 之4-四唑基_4_苯基哌啶化合物。 本發明另關於用於製備一種醫藥組合物之方法,包含混 合一種4-四唑基-4-苯基哌啶化合物及一種醫藥可接受載劑 或賦形劑之步驟。 1 本發明可由參考下列詳細說明及用以例示本發明之非限 制具體實施例之例示實例而更完全明瞭。
4.發明之詳細說明 4.1定義 上述所用術語具有下列意義: 「-CrC3烷基」意為具有1至3個碳原子之直鏈或分支鏈非 環狀烴鏈。代表性直鏈及分支鏈/广^烷基包括-甲基,乙 基,-正丙基,及異丙基。 「_Cl-C4烷基」意為具有1至4個碳原子之直鏈或分支鏈 環狀烴鏈。代表性直鏈_C^C4烷基包括_甲基,乙基,_ 丙基,及-正了基。代表性分支鏈_Ci_c4燒基包括異丙基 8953 l-960524.doc •14· 1343917 _第二丁基,-異丁基,及-第三丁基。 「-CU-C6烷基」意為具有1至6個碳原子之直鏈或分支鍵非 環狀烴鏈。代表性直鏈-Cl_C6烷基包括-曱基,-乙基,-正 丙基,-正丁基’-正戊基,及·正己基。代表性分支鏈 燒基包括-異丙基,-第二丁基,-異丁基,-第三丁基,異 戊基,-新戊基’ 1-甲基丁基,2-甲基丁基,3-曱基丁基, 1,1_二甲基丙基,1,2-二甲基丙基,1_甲基戊基,2_甲基戊 基,3-甲基戊基,4-甲基戊基,1-乙基丁基,2_乙基丁基,
3-乙基丁基,1,1-二甲基丁基,丨’2·二曱基丁基,13二甲 基丁基,2,2-二曱基丁基,2,3_二甲基丁基,及3,3二曱基 丁基。 -(C^C^)烷基」意為具有1至1〇個碳原子之直鏈或分支 鏈非環狀煙鏈。代表性直鏈_(Cl_Cl〇)烷基包括-甲基,_乙 基,-正丙基,·正丁基,-正戊基,_正己基,-正庚基,正 辛基,-正壬基’及-正癸基。代表性分支之·(CrCu)烷基包 括-異丙基’·第二丁基,-異丁基,_及第三丁基,_異戊基, -新戊基,1-甲基丁基,2-曱基丁基,3-甲基丁基,1,1_二甲 基丙基,1,2-二甲基丙基,卜甲基戊基,2_甲基戊基,3甲 基戊基’ 4-曱基戊基,丨_乙基丁基,2_乙基丁基,3_乙基丁 基,1,1-二甲基丁基,丨,2·二甲基丁基,13_二甲基丁基, 2,2-二甲基丁基,2,3-二甲基丁基,3,3_二甲基丁基,〗_甲 基己基,2-甲基己基,3_甲基己基,4_甲基己基,5甲基己 基,1,2-二甲基戊基,丨,3_二甲基戊基,二甲基己基, 1,3-二曱基己基,3,3-二甲基己基,1>2_二甲基庚基,丨,3_ 89531-960524.doc -15·
X X 1343917 f 092132303號專利命請案 0參〜〇日修 中文說明書替換頁(96年丨丨月)p ^ 二甲基庚基,及3,3-二甲基庚基。 -Ci-Cs伸烷基」意為具有1至5個碳原子之直鏈或分支鏈 非環狀二價烴。代表性直鏈-CVC5伸烷基為_ch2_, -(CH2)2·,_(CH2)3·,_(CH2)4_,及_(CH2)5…代表性分支之 -C2-C5伸烷基包括 ,·〇((:Η3)2·,_CH(CH3)CH2_, -CH2CH(CH3)- > -CH2C(CH3)2- . -C(CH3)2CH2- . -CH(CH3)CH (CH3)-,-CH2C(CH3)2CH2-’-(CH2)2C(CH3)2-,-(CH3)2(CH2)2C_ ,及-ch(ch3)ch2ch(ch3)_。 -C:3-C8環燒基」意為具有3至8個碳原子之飽和環狀烴e 代表性-C;j-C8環燒基為-環丙基,-環丁基,-環戊基,_環己 基,-環庚基,及-環辛基。 「-(5-至7-員)雜芳基」意為具有5至7員之芳族雜環,其 中環中至少一個碳原子以一個獨立選自氮,氧及硫之雜原 子替代。-(5-至7-員)雜芳基之環含有至少一個碳原子。代 表性-(5-至7-員)雜芳基包括吡啶基,吱喃基,硫苯基,咕 咯基’噚唑基,咪唑基,嘍唑基’異呤唑基,吡唑基,異 11塞吐基,塔17井基,哺淀基’峨P井基,P塞二吐基,及三喷基。 「鹵素」意為-F’ -Cl’ -Br’或·ι。 術語「動物」包括,但不限於’牛,猿,猴,黑獲獲, 狒狒,馬,缚羊,豬,難’火雞,鵪鶴’描,狗,小鼠(m〇use), 大鼠(rat),兔,天竺鼠,及人類。 本文中所用之術語「醫藥可接受鹽」為一種由酸及4•四 唑基-4-苯基哌啶化合物之驗氮基所形成之鹽。例示之鹽包 括,但不限於,硫酸鹽’檸檬酸鹽,醋酸鹽,草酸鹽,氣 89531-961130.doc •16· 1343917 化物,漠化物,碘化物,硝酸鹽,硫酸氩鹽,磷酸鹽,磷 酸氫鹽,異菸鹼酸鹽,乳酸鹽,水楊酸鹽,檸檬酸氫鹽, 酒石酸鹽’油酸鹽’丹寧酸鹽,泛酸鹽,酒石酸氫鹽,抗 壞血酸鹽’琥珀酸鹽,順丁婦二酸鹽,龍膽酸鹽,反丁烯 一酸鹽’葡萄庚酸鹽’葡糖二酸鹽(glucar〇nate),蔗糖鹽 (saccharate),甲酸鹽,苯甲酸鹽,麩胺酸鹽,甲磺酸鹽, 乙%奴鹽’苯績酸鹽,對-甲苯績酸鹽,及雙幾荅酸鹽 (pamoate)(即Μ·_亞甲基_雙_(2_羥基_2·莕酸鹽)。術語「醫 藥可接爻鹽」亦表示具有一個酸官能基,如叛酸官能基, 之4-四吐基_4_苯基旅啶化合物及一個醫藥可接受無機或有 機驗之鹽。例示之鹼包括,但不限於,鹼金屬如納,钟, 及麵之氫氧化物,鹼土金屬如鈣及鎂之氫氧化物;其他金 屬如銘及鋅之氫氧化物;及有機胺,如未經取代或經基取 代之一,二,或三烷基胺,二環己基胺;三丁基胺;吡啶; N甲基-N-乙基胺,二乙胺,二乙胺;一,二,或三_(2·乡Ίτι 基-低fe基胺),如一,二,或三-(2-經基乙基)胺,2·經基_ 第三丁基胺,或三-(羥基甲基)甲基胺,N,N-二-低烷基·Ν_(經 基低烷基)-胺,如Ν,Ν-二甲基-Ν-(2-羥基乙基)胺,或三·(2_ 經基乙基)胺;Ν-甲基-D-葡糖胺;及胺基酸,如精胺酸, 離胺酸,等。 術語「治療」疼痛或腹虞包括疼痛或腹丨寫之嚴重性減輕 或停止。在一個具體實施例中,「治療」包括抑制,例如減 少’疼痛或腹瀉之總體頻率。 術語「預防」疼痛或腹瀉包括避免疼痛或腹丨寫之發生。 89531-960524.doc 1343917 K-類轉 術語「類辑片(opioid)受體J意為類鴨片受體 片又體 類辑片受體,或〇RL-I受體。 術二有效量」用於4-四嗤基_4_苯基_化合物時意為 ,四唑基-4·苯基哌啶化合物可用於治療或預防—種動物疼 痛或腹瀉或刺激一個細胞内類鴉片受體功能之量。 術語「有效量」用於另一種治療劑時意為提供該治療劑 治療效果之量。 *當第-個基「經-或多個第二個基取代」時,一或多個 第一個基之氫原子以第二個基替代β 在-個具體實施例中,第—個基經多達三個第二個基取 代。 在另-個具體實施例中,第一個基經一或二個第二個基 取代。 在另一具體實施例中,第—個基僅經-個第二個基取代。 4-2 苯某哌啶化会^ 如上述’本發明包括具有下式(⑷之心四唆基_4·苯基味咬 化合物:
及其醫藥可接受鹽 其中 Art,Ar2 , ,g,m,P及 q 89531-960524.doc 1343917 第092132303號專利申請案 中文說明書替換頁(奶年!!月)丨以專曰卞爹上£: 如上述定義。 ^ 在一個具體實施例中,式叫之4四峻基冬苯基喊咬化合 物為G為-Η者。 在另-具體實施例中,式(Ia)之心四哇基_4_苯基喊淀化合 物為 G為-L-(CH2)nC〇2R4者。 在另一具體實施例中,式(⑷之4-四咬基-4-苯基喊咬化合 物為 G為-L-(CH2)nC〇2R4及 L為-C(0)_者。 在另具實施例中,式(la)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nC〇2R4及[為 _s〇2 或·s〇 者。 在另具Ba實施例中’式(la)之4-四唑基-4-苯基哌啶化合 物為 〇為·L-(CH2)nC〇2R4及 r4*h者。 在另一具體實施例中’式(1叻之4_四唑基·4·苯基哌啶化合 物為 G為-L-(CH2)nC〇2R4&R4為·Ci_Cig烷基者。 在另一具體實施例中,式(la)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nC〇2R4及尺4為 _CH2〇(Ci_C4烷基)者。 在另一具體實施例中,式(la)之4-四唑基-4-苯基哌啶化合 物為 G 為-L-(CH2)nC〇2R4 及 & 為 _CH2NH(Ci_C4 烷基)或 烷基)2者。 在另一具體實施例中,式(1&)之4_四唑基_4_苯基哌啶化合 物為G為-(CVCs伸烷基)c〇〇r4者。 在另具體實施例中,式(la)之4-四吐基-4-苯基味啶化合 物為G為-Ch2-C〇〇r4者。 在另一具體實施例中,式(1昀之4_四唑基·4_苯基哌啶化合 物為 G為-(CH2)2-CO〇R4者。 89531-961130.doc •19· f 092132303號專利申請案 …—. . 中又說明書替換頁(%年11月)心丨丨‘又 在另U施例中’式(la)之ίΓ四咬基-4-苯基喊咬化合 物為 G為-(CH2)3-C〇〇R4者。 在另一具體實施例中’式叫之4_四峻基_4_苯基㈣化合" 物為 G為-(Ch2VC00R4。 、 在另一具體實施例中,式Ua)之4-四吐基-4-苯基喊咬化合 物為 G為-(CH2)5-C〇〇r4者。 在另-具體實施例中’式(⑷之心四吐基_4_笨基略咬化合 物為 G為-L-(CH2)nR5&R5為·NHS〇2R4者。 在另〃sa實施例中,式(⑷之4_四峻基_4_苯基略咬化合參 物為 G 為-L-(CH2)nR5 及 R5g_s〇2NH2,_s〇2NH(Ci_C4 烷基卜 或-SC^NiCVC^烷基)2者。 在另一具體實施例中’式(la)之4-四唑基-4-笨基哌啶化合 物為 G為-L — (CH2)nR5及尺5為_>11^〇211者。 在另一具體實施例中’式(la)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nR5及 Lg_c(〇)·者。 在另一具體實施例中,式(1&)之4_四唑基_4_苯基哌啶化合 物為 G為-L_(CH2)nR5ms02或 _SQ_者。 ® 在另一具體實施例中,式(la)之4-四唑基-4-苯基哌啶化合 物為G為-(Ci-Cs伸燒基)r5者。 在另一具體實施例中,式(la)之4-四吐基-4-苯基喊咬化合, 物為G為-(:}42-115者。 在另一具體實施例中,式(la)之4-四峻基-4-苯基錢化合、 物為G為-(CH2)2-R5者。 % 在另-具體實施例中,式(1&)之4_四峻基_4_苯基略咬化合 89531-961130.doc 1343917
構充 第092132303號專利申請案 丨,------------ 中文說明書替換頁(96年11月)%年丨丨月^日 物為G為-——— 在另一具體實施例中,式(la)之4-四吐基-4-苯基喊啶化合 物為G為-(CH2)4-R5者。 在另一具體實施例中,式(la)之4-四吨基-4-苯基喊啶化合 物為G為-(CH2)5-R5者。 在另一具體實施例中,式(la)之4-四吐基-4-苯基喊咬化合 物為0為-((:1-(:5伸烷基)115及115為_(:(0)>^2,-(:(0如1^011, -C^CONI^CVC^ 烷基)’或-CCCONCCi-C^ 烷基)2 者。 在另一具體實施例中,式(la)之4-四唑基-4-苯基哌啶化合
物為 G 為-CH2-R5 及 R5 為-C(0)NH2,-C(0)NH0H,-C(0)NH (C「C4 燒基),或/(0)1^((^-04 垸基)2 者。 在另一具體實施例中,式(la)之4-四吐基-4-苯基喊咬化合 物為 G為-CH2C(0)N(CH3)2者。 在另一具體實施例中,式(la)之4-四唑基-4-苯基哌啶化合 物為 G為-(CH2)2-R5及 R5為-C(0)NH2,-C(0)NH0H,-C(0)NH (cvc4烷基)’或烷基)2者。 在另一具體實施例中,式(la)之4-四攻基-4-苯基喊咬化合
物為 G為-(CH2)3-R5及 R5為-C(0)NH2,-C(0)NH0H,-C(0)NH (CVC4 烷基),或-C^C^NCCrC^ 烷基)2者。 在另一具體實施例中’式(la)之4-四吐基-4-苯基旅啶化合 物為 G為-(CH2)4-R5及 R5為-C(0)NH2,-C(0)NH0H,-C(0)NH (CVC4 烷基),或-(:(0^((^-(:4 烷基)2 者。 在另一具體實施例中,式(la)之4-四吐基-4-苯基喊咳化合
物為 G為-(CH2)5-R5及 R5為-C(0)NH2,-C(0)NH0H,-C(0)NH 89531-961130.doc •21- (C,-C4燒基),或.c(〇)n(Ci_C4燒基者。 在另具實施例中’式(Ia)之4-四唑基_4·苯基哌啶化合 物為p為〇者。 在另—具體實施例中,式(Ia)之4_四♦基_4·苯基喊淀化合 物為P為1者。 在另一具體實施例中,式叫之4•四峻基·4·苯基㈣化合 物為Ρ為1及R3相接之碳原子呈(R)組態者。 在另具體實施例中’式(1&)之4_四峻基_4_苯基喊咬化合 物為p為1及R3相接之碳原子呈(s)_組態者。 在另一具體實施例中’式(1&)之4_四唑基_4苯基哌啶化合 物為p為1及R3為-CVC3烷基者》 在另一具體實施例中,式(la)之4-四唑基_4-苯基哌啶化合 物為p為1及R3為-CH3者。 在另一具體實施例中,式(la)之4-四唑基_4-苯基哌啶化合 物為p為1,R3為-C1-C3燒基’及I相接之碳原子呈(r)組態 者。 在另一具體實施例中,式(la)之4-四唑基-4-苯基哌淀化合 物為p為1 ’ R·3為-CH3 ’及&相接之碳原子呈(r)組態者。 在另一具體實施例中,式(la)之4-四唑基_4-苯基喊咬化合 物為ρ為1 ’ R3為-C1-C3燒基,及R_3相接之碳原子呈(s)組賤 者。 在另一具體實施例中’式(la)之4-四唑基_4-苯基喊咬化合 物為p為1,為-CH3,及R3相接之碳巧子呈(s)组態者。 在另一具體實施例中’式(la)之4·四唑基_4_苯基哌咬化合 89531-960524.doc -22- 物為q為0者。 〃也實施例中’式(Μ之4-四吨基-4-苯基旅淀化合 物為m為〇者。 备 在另一具體實施例中,、、 J中式(la)疋4-四唑基-4-苯基哌啶化合 # 物為m為1者。 在另一具體實施例φ,、、 中式(Ia)<4-四唑基-4-苯基哌啶化合 物為m為0及p為〇者。 在另一具體實施例φ,彳/τ、. J中式(Ia)<4-四唑基-4-苯基哌啶化合 物為m為1及p為〇者。 鲁 在另一具體實施例中’式(⑷之4-四峻基-4-苯基喊咬化合 物為m為0及q為〇者。 在另一具體實施例φ,、,< 肀式(Ia)<_4-四峻基_4_苯基喊啶化合 物為m為1及q為〇者。 在另'一具體實施例中,-Vwt、、/( ** J甲式(Ia)<4-四唑基-4-苯基哌啶化合 物為m為0,p為〇及q為〇者。 在另"具體實施例中,β、、/1 J甲式(Ia)<4-四唑基-4-苯基哌啶化合 物為m為1,p為0及q為〇者。 I· 在另一具體實施例中,式(⑷之4-四吐基-4-苯基喊唆化合 物為R_2為-Br’ -C1,者。 在另一具體實施例中,~WTa、>4 Λ ^ ^ J γ,式(la)之4-四唑基·4-苯基哌啶化合 . 物為R2為-CK-CVC3燒基)者。 在另一具體實施例中,e ^ ^ , ’· T 式(la)之4-四唾基-4-苯基喊唉化合 物為烷基者。 ° 、 在另-具體實施例中,式(Ia)之4·四吐基_4_苯基味咬化合' 89531-960524.doc -23· 1343917 物為112為-ΝΗ(-(ν(:3烷基)或-NGCrC;烷基)2者。 在另一具體實施例中’式(la)之4-四吨基-4-苯基p瓜淀化合 物為 R3為-Br,-Cl,-I,或-F者。 在另一具體實施例中’式(la)之4-四峻基-4-苯基喊啶化合 物為R3為-CK-CrCs烷基)者。 在另一具體實施例中’式(la)之4-四唑基-4-苯基哌啶化合 物為R3為-Ci-Cs燒·基者。 在另一具體實施例中,式(la)之4-四唑基-4-苯基哌啶化合 物為R3為-NH(-Ci-C3烧基)或燒•基)2者。 在另一具體實施例中’式(la)之4-四唑基-4-苯基哌啶化合 物為1^為1^者。 在另一具體實施例中,式(la)之4-四吐基-4-苯基味咬化合 物為心為-C(0)NH2,-C(0)NH0H,烷基),或 烷基)2 者。 在另一具體實施例中,式(la)之4_四唑基_4_苯基哌啶化合 物為 1^為-(:(0)>1((:113)2 者。 在另一具體實施例中,式(la)之4_四唑基_4苯基哌啶化合 物為 RA -(:(0)1^((^2(:113)2者。 在另一具體實施例中,式(1&)之4•四唑基_4_苯基哌啶化合 物為1^為-0:(〇)>111(:113者。 在另-具體實施例中,式(Ia)之4·四吐基_4_苯基旅咬化合 物為1^為-(:(0)1^((:112(:1^)者。 在另-具體實施例中,式叫之4_四峻基_4_苯基喊唆化合 物為R|為-COOR4者。 89531-960524.doc -24. 1343917 在另一具體實施例中,式(la)之4_四唑基_4·苯基哌啶化合 物為RiS-CHO者。 在另一具體實施例中,式(la)之4_四唑基_4_苯基哌啶化合 物為Ri為-01^者。 在另一具體實施例中,式(1&)之4_四唑基_4_苯基哌啶化合 物為烷基)者。 在另一具體實施例中,式(1勾之4_四唑基_4_苯基哌啶化合 物為R1為下列者
V
在另-具體實施例中,式(叫之4四吐基_4.苯基❹化合 物為AnS-C^-C8環烷基者。 在另-具體實施例中,式(Ia)之4_四♦基_4_苯基錢化合 物為Ang苯基, ’萘基,1基, 在另一具體實施例中, 物為八〇為-(5至7員)雜芳基者。 在另一具體實施例中,式n 恩基,或菲基者。 式(la)之4-四唑基-4-苯基哌啶化合 靠· 物為Ar〗經一或多個&基取代者 式(la)之4-四唑基-4-苯基哌啶化合 在另一具體實施例中,
在另一具體實施例中, 式(la)之4-四唑基-4-苯基哌啶化合 基,或菲基者。 式(la)之4-四唑基·4-苯基哌啶化合 89531-960524.doc •25· 1343917 物為Αι*2為-(5至7員)雜芳基者。 在另一具體實施例中,式(la)之4-四吐基-4-苯基喊咬化合 物為Ar2經一或多個R2基取代者。 4 在另一具體實施例中,式(la)之4-四也基-4-苯基I»瓜咬化合 、 物為八^及八!^為苯基者。 在另一具體實施例中,式(la)之4-四唑基-4-苯基哌啶化合 物為An環己基者。
在另一具體實施例中,式(la)之4-四嗤基-4-苯基喊咬化合 物為An為環己基及Ar2為苯基者。 在另一具體實施例中,式(la)之4-四吐基-4-苯基喊咬化合 物為G為Η及p為〇者。 在另一具體實施例中,式(la)之4-四吐基-4-苯基喊咬化合 物為G為Η及q為〇者。 在另一具體實施例中,式(la)之4-四吐基-4-苯基喊咬化合 物為G為11及111為〇者。 在另一具體實施例中’式(la)之4-四咬基-4-苯基p底咬化合 物為G為Η及m為1者。 在另一具體實施例中’式(la)之4-四吐基-4-苯基味咬化合 物為G為Η,及Ari&Ar2為苯基者。 在另一具體實施例中’式(la)之4-四咬基-4-苯基p底咬化合 物為G為Η,p為〇,及q為〇者。 在另一具體實施例中’式(1幻之4_四唑基_4·苯基哌啶化合 物為G為Η,p為〇,及爪為〇者。 在另一具體實施例中’式(la)之4-四唑基-4-苯基哌啶化合 89531-960524.doc • 26 - 1343917 物為G為Η,p為0,及Μ為1者。 在另一具體實施例中,式(la)之4-四唑基-4-苯基旅咬化合 物為G為Η,p為0,及八1^及Ar2為苯基者。 在另一具體實施例中,式(la)之4-四唑基-4-苯基喊咬化合 物為G為Η,p為0,q為0,及m為0者。 在另一具體實施例中’式(la)之4-四唑基-4-苯基喊咬化合 物為G為Η,p為0,q為0,及m為1者。 在另一具體實施例中,式(la)之4-四峻基-4-苯基喊咬化合 物為G為Η,p為0,q為0,及八1^及Ar2為苯基者。 在另一具體實施例中,式(la)之4-四唑基-4-苯基哌啶化合 物為G為Η,p為0,q為0,m為0,及八1^及Ar2為苯基者。 在另一具體實施例中,式(la)之4-四咬基-4-苯基旅淀化合 物為G為Η,p為0,q為0,m為1,及八1^及Ar2為苯基者。 例示之式(la)之4-四唑基-4-苯基哌啶化合物具有下列結 構:
及其醫藥可接受鹽, 其中0及1^如下: 89531-960524.doc -27- 1343917 化合物編號: G : Ri · AAA -H -H AAB -CH2C(0)NH2 -H AAC -CH2C(0)N(CH3)2 -H AAD -C(0)CH2NHS02CH3 -H AAE -(CH2)2C(0)NH2 -H AAF -(ch2)2c(o)n(ch3)2 -H AAG -c(o)(ch2)2nhso2ch3 -H AAH -ch2co2ch3 -H AAI -CH2C02CH2CH3 -H AAJ -(CH2)2C02CH3 -H AAK -(ch2)2co2ch2ch3 -H AAL -(CH2)3C02CH3 -H ΛΛΜ -(CH2)3C02CH2CH3 -H AAN -(CH2)4C02CH3 -H AAO -(ch2)4co2ch2ch3 -H AAP -ch2so2nh2 -H AAQ -ch2so2n(ch3)2 -H AAR -(ch2)2nhso2h -H AAS -(ch2)2nhso2ch3 -H AAT -H -C(0)NH2 AAU -CH2C(0)NH2 -C(0)NH2 AAV -ch2c(o)n(ch3)2 -C(0)NH2 AAW -ch2nhso2ch3 -C(0)NH2 AAX -(CH2)2C(0)NH2 -C(0)NH2 AAY -(ch2)2c(o)n(ch3)2 -C(0)NH2 89531-960524.doc -28 - 1343917 AAZ -(CH2)NHS02CH3 -C(0)NH2 ΑΒΑ -ch2co2ch3 -C(0)NH2 ABB -ch2co2ch2ch3 -C(0)NH2 ABC -(CH2)2C02CH3 -C(0)NH2 ABD -(CH2)2C02CH2CH3 -C(0)NH2 ABE -(CH2)3C02CH3 -C(0)NH2 ABF -(CH2)3C02CH2CH3 -C(0)NH2 ABG -(CH2)4C02CH3 -C(0)NH2 ABH -(ch2)4co2ch2ch3 -C(0)NH2 ABI -ch2so2nh2 -C(0)NH2 ABJ -ch2do2n(ch3)2 -C(0)NH2 ABK -(CH2)2NHS02H -C(0)NH2 ABL -(CH2)2NHS02CH3 -C(0)NH2 ABM -H -C02CH3 ABN -CH2C(0)NH2 -C02CH3 ABO -CH2C(0)N(CH3)2 -C02CH3 ABP -C(0)CH2NHS02CH3 -co2ch3 ABQ -(CH2)2C(0)NH2 -C02CH3 ABR -(ch2)2c(o)n(ch3)2 -C02CH3 ABS -c(o)(ch2)2nhso2ch3 -co2ch3 ABT -ch2co2ch3 -co2ch3 ABU -CH2C〇2CH2CH3 -C02CH3 ABV -(CH2)2C02CH3 -C02CH3 ABW -(CH2)2C02CH2CH3 -C02CH3 ABX -(CH2)3C02CH3 -C02CH3 ABY -(CH2)3C02CH2CH3 -co2ch3 89531-960524.doc •29- 1343917
ABZ -(CH2)4C02CH3 -C02CH3 ACA -(ch2)4co2ch2ch3 -C02CH3 ACB -CH2S02NH2 -co2ch3 ACC -ch2so2n(ch3)2 -C02CH3 ACD -(CH2)2NHS02H -C02CH3 ACE -(CH2)2NHS02CH3 -C02CH3 ACF -H -CHO ACG -CH2C(0)NH2 -CHO ACH -ch2c(o)n(ch3)2 -CHO ACI -C(0)CH2NHS02CH3 -CHO ACJ -(CH2)2C(0)NH2 -CHO ACK -(CH2)2C(0)N(CH3)2 -CHO ACL -c(o)(ch2)2nhso2ch3 -CHO ACM -ch2co2ch3 -CHO ACN -ch2co2ch2ch3 -CHO ACO -(ch2)2co2ch3 -CHO ACP -(ch2)2co2ch2ch3 -CHO ACQ -(CH2)3C02CH3 -CHO ACR -(CH2)3C02CH2CH3 -CHO ACS -(CH2)4C02CH3 -CHO ACT -(ch2)4co2ch2ch3 -CHO ACU -ch2so2nh2 -CHO ACV -CH2S02N(CH3)2 -CHO ACW -(CH2)2NHS02H -CHO ACX -(CH2)2NHS02CH3 -CHO ACY -H -CN 89531-960524.doc •30- 1343917 ACZ -CH2C(0)NH2 -CN ADA -CH2C(0)N(CH3)2 -CN ADB -C(0)CH2NHS02CH3 -CN ADC -(CH2)2C(0)NH2 -CN ADD -(CH2)2C(0)N(CH3)2 -CN ADE -C(0)(CH2)2NHS02CH3 -CN ADF -ch2co2ch3 -CN ADG -ch2co2ch2ch3 -CN ADH -(CH2)2C02CH3 -CN ADI -(ch2)2co2ch2ch3 -CN ADJ -(CH2)3C02CH3 -CN ADK -(ch2)3co2ch2ch3 -CN ADL -(ch2)4co2ch3 -CN ADM -(CH2)4C02CH2CH3 -CN ADN -ch2so2nh2 -CN ADO -ch2so2n(ch3)2 -CN ADP -(CH2)2NHS02H -CN ADQ -(ch2)2nhso2ch3 -CN ADR -H -ch3 ADS -CH2C(0)NH2 -ch3 ADT -CH2C(0)N(CH3)2 -ch3 ADU -C(0)CH2NHS02CH3 -ch3 ADV -(CH2)2C(0)NH2 -ch3 ADW -(CH2)2C(0)N(CH3)2 -ch3 ADX -C(0)(CH2)2NHS02CH3 -ch3 ADY -ch2co2ch3 -ch3 89531-960524.doc •31 - 1343917 ADZ -ch2co2ch2ch3 -ch3 AEA -(ch2)2co2ch3 -ch3 AEB -(CH2)2C02CH2CH3 -ch3 AEC -(CH2)3C02CH3 -ch3 AED -(CH2)3C02CH2CH3 -ch3 AEE -(CH2)4C02CH3 -ch3 AEF -(ch2)4co2ch2ch3 -ch3 AEG -ch2so2nh2 -ch3 AEH -ch2so2n(ch3)2 -ch3 AEI -(CH2)2NHS02H -ch3 AEJ -(CH2)2NHS02CH3 -ch3 AEK -H -C(0)NH(CH3) AEL -CH2C(0)NH2 -C(0)NH(CH3) AEM -CH2C(0)N(CH3)2 -C(0)NH(CH3) AEN -C(0)CH2NHS02CH3 -C(0)NH(CH3) AEO -(CH2)2C(0)NH2 -C(0)NH(CH3) AEP -(CH2)2C(0)N(CH3)2 -C(0)NH(CH3) AEQ -c(o)(ch2)2nhso2ch3 -C(0)NH(CH3) AER -ch2co2ch3 -C(0)NH(CH3) AES -ch2co2ch2ch3 -C(0)NH(CH3) AET -(ch2)2co2ch3 -C(0)NH(CH3) AEU -(ch2)2co2ch2ch3 -C(0)NH(CH3) AEV -(CH2)3C02CH3 -C(0)NH(CH3) AEW -(ch2)3co2ch2ch3 -C(0)NH(CH3) AEX -(CH2)4C02CH3 -C(0)NH(CH3) 89531-960524.doc -32- 1343917 ΑΕΥ •(CH2)4C02CH2CH3 -C(0)NH(CH3) ΑΕΖ -ch2so2nh2 -C(0)NH(CH3) AFA -CH2S〇2N(CH3)2 -C(0)NH(CH3) AFB -(CH2)2NHS02H -C(0)NH(CH3) AFC -(CH2)2NHS02CHj -C(0)NH(CH3) AFD -H -C(0)N(CH3)2 AFE -CH2C(0)NH2 •c(o)n(ch3)2 AFF -ch2c(o)n(ch3)2 -c(o)n(ch3)2 AFG -C(0)CH2NHS02CH3 -C(0)N(CH3)2 AFH -(CH2)2C(0)NH2 -C(0)N(CH3>2 AFI -(CH2)2C(0)N(CH3)2 -c(o)n(ch3)2 m AFJ -C(0)(CH2>2NHS02CH3 -C(0)N(CH3)2 I AFK -CH2C〇2CH3 -C(0)N(CH3)2 AFL -ch2co2ch2ch3 -C(0)N(CH3>2 AFM -(CH2)2C02CH3 -C(0)N(CH3)2 AFN -(CH2>2C02CH2CH3 -C(0)N(CH3)j AFO (CH2)3C〇2CH3 •c(o)n(ch3)2 AFP *(CH2)3C〇2CH2CH3 _c(o)n(ch3)2 AFQ *(CH2)4C02CH3 -C(0)N(CH3)2 AFR -(CH2)4C〇2CH2CH3 -C(0)N(CH3)2 AFS -ch2so2nh2 -C(0)N(CH3)2 i AFT -ch2so2n(ch3)2 -C(0)N(CH3)2 , AFU <CH2)2NHS〇2H -c(o)n(ch3)2 AFV •(ch2)2nhso2ch3 -C(0)N(CH3)2 AFW -H n厂飞 一C—bi CH3 AFX -CH2C(0)NH2 厂Λ —0一 N、/N - CH3 AFY -ch2c(o)n(ch3)2 ff厂λ u —C-N N-CH3 9. 89531-960524.doc -33 - 1343917 AFZ -C(0)CH2NHS02CH3 AGA -(CH2)2C(0)NH2 —C 一 \ AGB •(ch2)2c(o)n(ch3)2 0 ,^^ —C~N N-CH3 AGC -c(o)(ch2)2nhso2ch3 ?\ r~\ —C一 N 户 一 CH3 AGD -CH2C02CH3 i? /-Λ —C-Ni N-CH3 AGE -CH2C〇2CH2CH3 5?厂Λ —c-ri n-ch3 AGF -(CH2)2C02CH3 M厂飞 —C-N N-CH3 AGG -(CH2>2C02CH2CH3 S厂 —C-Ni N~CH3 AGH Kch2)3co2ch3 1? —ΰ一 Ν Ν—CH3 3 AGI -(ch2)3co2ch2ch3 —C-Ns>4~CH3 AGJ -(CH2)4C02CH3 Μ厂~\ —c—Ν N—CH3 AGK •(CH2)4COjCH2CH3 i?厂λ AGL -ch2so2nh2 ff厂λ —C-Nx jN-CH3 AGM •ch2so2n(ch3)2 S /^Λ — AGN •(CH2)2NHS02H π /~Λ —c~ti V1-CH3 89531-960524.doc -34- 1343917 AGO •(ch2)2nhso2ch3 —Lq_CH3 AGP -H AGQ -CH2C(0)NH2 一 L〇 AGR -ch2c(o)n(ch3)2 —c-^ AGS -C(0)CH2NHS02CH3 -L〇 AGT .(ch2)2c(o)nh2 一 L〇 AGU -(CH2)2C(0)N(CH3)2 -L〇 AGV -c(o)(ch2)2nhso2ch3 X〇 AGW -ch2co2ch3 —L〇 AGX -CH2C〇2CH2CH3 AGY -(CH2)2C〇2CH3 一 L〇 AGZ •(ch2)2co2ch2ch3 ~^~o AHA -(ch2)3co2ch3 o AHB -(CH2)3C〇2CH2CH3 』-〇 AHC -(CH2)4C〇2CH3 89531-960524.doc -35- 1343917 AHD -(CH2)4C〇2CH2CH3 -L〇 AHE -ch2so2nh2 /~Λ -c-\J AHF -CH2S02N(CH3)2 —L〇 AHG -(CH2)2NHS02H ft厂' 一 C一 N > AHH -(ch2)2nhso2ch3 AHI -H i? -c-fQ AHJ -CH2C(0)NH2 AHK -ch2c(o)n(ch3)2 i? AHL -C(0)CH2NHS02CH3 if /=5¾ -c-^Q AHM KCH2)2C(0)NH2 1? 一 c-hQ AHN •<CH2)2C(0)N(CHj)2 /==51 AHO -C(〇XCH2)2NHS〇2CH3 i? ~C~\J AHP -CH2C02CH3 1? ~C~\J AHQ -CH2C〇2CH2CH3 AHR -(CH2>2C〇2CH3 i? %· Ι· 89531-960524.doc -36- 1343917 AHS -(ch2)2co2ch2ch3 i? ΑΗΤ •(CH2)3C02CH3 -c-hQ AHU -(CH2)3C02CH2CH3 AHV -(CH2)4C〇2CH3 if -cQ AHW •(ch2)4co2ch2ch3 i? -c-rQ AHX -ch2so2nh2 1? -c_Cl AHY -CH2S02N(CH3)2 i? 一 c-rQ AHZ -(CH2)2NHS〇2H —c- "Q AIA -(ch2)2nhso2ch3 一 c-rQ AIB -H AIC -CH2C(0)NH2 4一 〇 AID -ch2c(o)n(ch3)2 AEE -C(0)CH2NHS〇2CH3 —C->^ AIF -(CH2)2C(0)NH2 — AIG -(ch2)2c(o)n(ch3)2 %· ι· 89531-960524.doc -37- 1343917
ΑΙΗ •c(o)(ch2)2nhso2ch3 ΑΠ -CH2C〇2CH3 AU -CH2C02CH2CH3 -LQ AIK -(CH2)2C02CH3 i?厂Λ -c-VJ5 AIL •(ch2)2co2ch2ch3 —Lq AIM -(CH2hC〇2CH3 —Lq AIN -(CH2)3C〇2CH2CH3 Xq AIO (CH2)4C02CH3 AIP •(CH2)4C〇2CH2CH3 —Lq A1Q -ch2so2nh2 —Lq AIR -CH2S〇2N(CH3)2 AIS •(CHANHSCbH — AIT -(CHzJzNHSOzCHj -L〇 AIU -(CH2)3NHS02H -H AIV -(CH2)3NHS02H -C(0)NH2 AIW -(CH2)3NHS02H -C02CH3 AJX -(CH2)3NHS02H -CHO AIY -(CH2)3NHS〇2H -CN 89531-960524.doc -38- ΑΙΖ -(CH2)3NHS02H -ch3 AJA -(CH2)3NHS02H •c(o)nhch3 AJB *(CH2)3NHS02H -C(0)N(CH3)2 AJC ~(CH2)3NHSOzH if厂λ —C-Ni )m-CH3 AJD *(CH2)3NHS02H 』-〇 AJE -(CH2)3NHS02H 1? 一 c-rQ AJF *<ch2)3nhso2h if 厂 一0一 N 0 本發明另包括具有下式(lb)之化合物:
1343917 及其醫藥可接受鹽,其中Ar〗,Ar2,Rrh,G ’ m,p及q 如上述定義。 在一個具體實施例中,式(lb)之4-四吐基-4-苯基喊啶化合 物為G為-H者。 在另一具體實施例中’式(lb)之4-四峻基-4-苯基喊啶化合 物為 G為-L-(CH2)nC(0)0R4者。 在另一具體實施例中,式(lb)之4-四也基-4-苯基喊峻化合 物為 G為-L-(CH2)nC(0)0R4及 L為-C(O)-者。 在另一具體實施例中,式(lb)之4-四吨基-4-苯基咬咬化合 89531-960524.άοο -39- 1343917 據充 f 092132303號專利申請案 中文說明書替換頁(%年11月)丨丨以- 物為 G為-L-(CH2)nC(0)OR4及 Li :—S02-或-SO-者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nC(0)〇R4&RAH者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nC(〇)〇R4&R4 _Cl_c1Q燒基者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 〇為 _L_(CH2)nC(0)〇R4&R44 烷基)者。 在另一具體實施例中,式(11))之4_四唑基_4_苯基哌啶化合 物為 G 為-L-(CH2)nC(〇)〇R4 及 r4 為 _CH2NH(Cl_c4 烷基)或 -CHal^CVC^烷基)2者。 在另一具體實施例中,式(115)之4_四唑基·4_苯基哌啶化合 物為G為-(C1-C5伸燒基)r5者。 在另一具體實施例中’式(lb)之4-四峻基-4_苯練咬化合 物為G為-CH2-R5者。 在另—具體實施例中,式(lb)之4-四峻基-4-苯基喊咬化合 物為G為-(CH2)2-R5者。 在另—具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為G為-(CH2)3-R5者。 另μ心實施例中’式(lb)之4-四唑基-4-苯基哌啶化合 物為G為-(CH2)4-r5者。 在另一具體實施例ψ,4 宁式(Ib)(4-四峻基-4-苯基旅咬化合 物為 G為-(CH2)5-R5·。 在另一具體實施例中々 ^ 4 Y式丨11^)之4-四唑基-4-苯基哌啶化合 物為G為-(Cl-C5伸虼基)c〇〇i者。 89531-961130.doc 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G為-(CH2)2-CO〇R4者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G為-(CH2)3-COOR4者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G為-(CH2)4-COOR4者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G為-(CH2)5-COOR4者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nR5及 R5為-NHS02R4者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G 為·L-(CH2)nR5 及 R5 為 _c(0)NH2 ’ -C(0)NHCH, -C(0)NH(Ci-C4 烷基),或_C(0)N(CrC4 烷基)2 者。 在另一具體實施例中’式(lb)之4-四唑基-4-苯基哌啶化合 物為 G 為-L-(CH2)nR5 及 R5S-S〇2NH2, -SC^NH^-C^ 烷基),
或-SG^NWi-Ci 烷基)2 者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nR5及 R5為 _NHS02H者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nR5及 L為-C(0)-者·> 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nR5及R5g_s〇2-或-SO-者。 在另一具體實施例中’式(lb)之4-四唑基-4-苯基哌啶化合 物為p為0者。 89531-960524.doc -41 · 1343917 在另-具體實施例中’式⑽之4_四吐基_4苯基旅咬化合 物為p為1者。 在另具體實施例中,式(Ib)之心四吨基ι苯基喊咬化合’ 物為ρ為1及R3相接之碳原子呈(⑴組態者。 . 在另-具體實施例中’式(叫之4_四吐基_4苯基喊唆化合 物為ρ為1及R3相接之碳原子呈(s)組態者。 在另-具體實施例中’式⑽之心四吐基_4苯基喊咬化合 物為p為1及R_3為烷基者。 在另-具體實施例中,式(Ib)之4_四吨基_4•苯基喊峻化合t籲 物為p為1及R3為-ch3者。 在另-具體實施例中’式(lb)之4_四吨基_4·苯基喊咬化合 物為p為1,R3為-Cl-C3烷基,及I相接之碳原子呈(R)組態 者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為p為1,R_3為-CH3,及&相接之碳原子呈(R)組態者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為P為1,R_3為-CrC3烷基,及R3相接之碳原子呈(s)組態 者0 在另一具體實施例中’式(lb)之4-四吐基-4-苯基味咬化合 物為p為1,&為-CH3 ’及I相接之碳原子呈(s)組態者。 在另一具體實施例中’式(lb)之4-四唑基-4-苯基哌啶化合 物為q為0者。 在另一具體實施例中’式(lb)之4-四唑基-4-苯基哌啶化合 物為m為〇者。 8953I-960524.doc -42- 1343917 在另一具體實施例中,式(lb)之4-四峻基-4-苯基喊啶化合 物為m為1者。 在另一具體實施例中,式(lb)之4-四峻基-4-苯基喊啶化合 物為m為0及p為〇者。 .. 在另一具體實施例中,式(lb)之4-四吐基-4-苯基喊啶化合 物為m為1及p為〇者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為m為0及q為〇者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合I· 物為m為1及q為〇者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為m為0,p為〇及q為〇者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為m為1,ρ為〇及q為0者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌咬化合 物為 R2 為-Br,-Cl,-I,或-F 者。 苯基味咬化合
在另一具體實施例中,式(lb)之4-四唑基-4-物為烷基)者。 在另一具體實施例中’式(lb)之4 -四峻基-4-苯基味淀化合 物為R2為-CVC3烷基者。 在另一具體實施例中,式(lb)之4 -四吐基-4-苯基I»瓜咬化合 物為R2為-NHGCVCs烷基)或-NGCi-C;烷基)2者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌咬化合 物為 R3 為-Br,-Cl,-I,或-F 者。 8953 l-960524.doc -43- 1343917 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為R3為-〇(-CrC3烷基)者。 在另一具體實施例中’式(lb)之4-四唑基-4-苯基哌啶化合 物為R3為-CrCs烷基者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為R3為-NHGCrCs烷基)或-NC-CVC^烷基)2者。 在另一具體實施例中,式(lb)之4-四吐基-4-苯基喊咬化合 物為1^為Η者。 在另一具體實施例中’式(lb)之4-四唑基-4-苯基哌啶化合t隹 物為 R〗為-C(0)NH2 ’ -C(0)NH0H,-CCCONi^CVC^ 烷基),或 -C^C^ISKCVC^ 烷基)2 者。 在另一具體實施例中,式(lb)之4 -四咬基-4-苯基喊淀化合 物為 Ι^Α-(:(0)Ν((:Η3)2者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為 RA-C(0)N(CH2CH3)2者。
在另一具體實施例中’式(lb)之4-四唑基-4-苯基哌啶化合 物為 r^-c(o)nhch3者。 在另一具體實施例中’式(lb)之4-四峻基-4-苯基喊咬化合 物為 Ι^&-<:(0)ΝΗ((:Η2(:Η3)者。 在另一具體實施例中’式(Ib)24_四唑基_4_苯基哌啶化合 物為11〗為-COOR4者。 在另一具體實施例中’式(113)之4_四唑基_4_苯基哌啶化合 物為1^為-CHO者。 在另具實施例中’式(lb)之4-四哇基-4-苯基喊咬化合 89531-960524.doc •44· 1343917 物為Rig-CN者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為Ri為- (C1-C4抗基)者。 在另一具體實施例中’式(lb)之4-四唑基-4-苯基哌啶化合 , 物為心為下列者
在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為Ar^-C3-C8環燒基者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為Αι^為笨基’茶基’慈基,或菲基者。 在另一具體實施例中,式(Ib)之4·四唑基_4_苯基哌啶化合 物為ΑΓι*-(5-至7-員)雜芳基者。
在另一具體實施例中,式(115)之4_四唑基_4_苯基哌啶化合 物為An經一或多個r2基取代者。 在另一具體實施例中,式(Ib)之4·四吐基_4苯基喊咬化合 物為At*2為苯基,莕基,蒽基,或菲基者。 在另-具體實施例中,式(1|3)之4_四也基·4苯基喊咬化合 物為Ah為-(5-至7-員)雜芳基者。 在另一具體實施例中,式⑽之4-四吨基-4-苯基喊唆化合 物為Ar2經一或多個r2基取代者。 〇 8953U960524.doc -45- 1343917 在另一具體實施例中,式(lb)之4-四座基-4-苯基喊啶化合 物為Ar!&Ar2為苯基者。 在另一具體實施例中,式(lb)之4-四咕基-4-苯基p底咬化合 物為ΑΓι環己基者。 在另一具體實施例中’式(lb)之4-四唑基-4-苯基哌啶化合 物為ΑΓι為環己基及Ar2為苯基者。 在另一具體實施例中,式(lb)之4-四也基-4-苯基喊咬化合 物為G為Η及p為0者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為G為Η及q為〇者。 在另一具體實施例中,式(lb)之4·四唑基-4-苯基哌啶化合 物為G為11及〇1為0者。 在另一具體實施例中,式(Ib)i4_四唑基_4_苯基哌啶化合 物為G為Η及m為1者。 在另一具體實施例中,式(Ib)之‘四唑基_4_苯基哌啶化合 物為G為Η,及Ari&Ar2為苯基者。 在另一具體實施例中,式(11))之4_四唑基_4苯基哌啶化合 物為G為Η,p為〇,及q為〇者。 在另一具體實施例中’式(Ib)之心四吨基-4苯基喊咬化合 物為G為Η,p為〇,及〇1為〇者。 在另一具體實施例中,式(lb)之4-四峻基-4-苯基喊唆化合 物為G為Η’ p為〇’及爪為!者。 在另一具體實施例中,式(lb)之4-四吐基-4-苯基喊唆化合 物為G為Η,p為〇,及Ari及Ar2為笨基者。 89531-960524.doc -46- 1343917 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為G為Η,p為0,q為0,及m為0者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為G為Η,ρ為0,q為0,及m為1者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為G為Η,ρ為0,q為0,及Ar!&Ar2為苯基者。 在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為G為Η,ρ為0,q為0,m為0,及Ar!及Ar2為苯基者。
在另一具體實施例中,式(lb)之4-四唑基-4-苯基哌啶化合 物為G為Η,ρ為0,q為0,m為1,及八1^及八4為苯基者。 例示之式(lb)之4-四唑基-4-苯基哌啶化合物具有下列結 構.
及其醫藥可接受鹽, 其中GgRi如下: 化合物編號: G : Ri ·· BAA -H -Η BAB -CH2C(0)NH2 -Η BAC -ch2c(o)n(ch3)2 -Η BAD -C(0)CH2NHS02CH3 -Η 89531-960524.doc -47- 1343917 BAE -(CH2)2C(0)NH2 -H BAF -(ch2)2c(o)n(ch3)2 -H BAG -C(0)(CH2)2NHS02CH3 -H BAH -ch2co2ch3 -H BAI -ch2co2ch2ch3 -H BAJ -(ch2)2co2ch3 -H BAK -(ch2)2co2ch2ch3 -H BAL -(ch2)3co2ch3 -H BAM -(ch2)3co2ch2ch3 -H BAN -(CH2)4C02CH3 -H BAO _(ch2)4co2ch2ch3 -H BAP -ch2so2nh2 -H BAQ -CH2S02N(CH3)2 -H BAR -(CH2)2NHS02H -H BAS -(CH2)2NHS02CH3 -H BAT -H -C(0)NH2 BAU -CH2C(0)NH2 -C(0)NH2 BAV -CH2C(0)N(CH3)2 -C(0)NH2 BAW -C(0)CH2NHS02CH3 -C(0)NH2 BAX -(CH2)2C(0)NH2 -C(0)NH2 BAY -(CH2)2C(0)N(CH3)2 -C(0)NH2 BAZ -c(o)(ch2)2nhso2ch3 -C(0)NH2 BBA -ch2co2ch3 -C(0)NH2 BBB -CH2C02CH2CH3 -C(0)NH2 BBC -(ch2)2co2ch3 -C(0)NH2 BBD -(CH2)2C02CH2CH3 -C(0)NH2 89531-960524.doc -48- 1343917 BBE -(CH2)3C02CH3 -C(0)NH2 BBF -(CH2)3C02CH2CH3 -C(0)NH2 BBG -(ch2)4co2ch3 -C(0)NH2 BBH -(ch2)4co2ch2ch3 -C(0)NH2 BBI -ch2so2nh2 -C(0)NH2 BBJ -ch2so2n(ch3)2 -C(0)NH2 BBK -(ch2)2nhso2h -C(0)NH2 BBL -(ch2)2nhso2ch3 -C(0)NH2 BBM -H -C02CH3 BBN -CH2C(0)NH2 -co2ch3 BBO -CH2C(0)N(CH3)2 -C02CH3 BBP -C(0)CH2NHS02CH3 -co2ch3 BBQ -(CH2)2C(0)NH2 -co2ch3 BBR -(ch2)2c(o)n(ch3)2 -co2ch3 BBS -c(o)(ch2)2nhso2ch3 -C02CH3 BBT -ch2co2ch3 -C02CH3 BBU -ch2co2ch2ch3 -C02CH3 BBV -(CH2)2C02CH3 -C02CH3 BBW -(CH2)2C02CH2CH3 -C02CH3 BBX -(ch2)3co2ch3 -co2ch3 BBY -(ch2)3co2ch2ch3 -C02CH3 BBZ -(CH2)4C02CH3 -co2ch3 BCA -(ch2)4co2ch2ch3 -co2ch3 BCB -ch2so2nh2 -C02CH3 BCC -ch2so2n(ch3)2 -C02CH3 BCD -(ch2)2nhso2h -co2ch3 -49- 89531-960524.doc 1343917
BCE -(ch2)2nhso2ch3 -C02CH3 BCF -H -CHO BCG -CH2C(0)NH2 -CHO BCH -CH2C(0)N(CH3)2 -CHO BCI -C(0)CH2NHS02CH3 -CHO BCJ -(CH2)2C(0)NH2 -CHO BCK -(CH2)2C(0)N(CH3)2 -CHO BCL -C(0)(CH2)2NHS02CH3 -CHO BCM -ch2co2ch3 -CHO BCN -CH2C02CH2CH3 -CHO BCO -(ch2)2co2ch3 -CHO BCP -(CH2)2C02CH2CH3 -CHO BCQ -(ch2)3co2ch3 -CHO BCR -(CH2)3C02CH2CH3 -CHO BCS -(ch2)4co2ch3 -CHO BCT -(ch2)4co2ch2ch3 -CHO BCU -ch2so2nh2 -CHO BCV -CH2S02N(CH3)2 -CHO BCW -(ch2)2nhso2h -CHO BCX -(CH2)2NHS〇2CH3 -CHO BCY -H -CN BCZ -CH2C(0)NH2 -CN BDA -CH2C(0)N(CH3)2 -CN BDB -C(0)CH2NHS02CH3 -CN BDC -(CH2)2C(0)NH2 -CN BDD -(CH2)2C(0)N(CH3)2 -CN 89531-960524.doc -50- 1343917 BDE -c(o)(ch2)2nhso2ch3 -CN BDF -ch2co2ch3 -CN BDG -CH2CO2CH2CH3 -CN BDH -(ch2)2co2ch3 -CN BDI -(ch2)2co2ch2ch3 -CN BDJ -(ch2)3co2ch3 -CN BDK -(ch2)3co2ch2ch3 -CN BDL -(ch2)4co2ch3 -CN BDM -(CH2)4C02CH2CH3 -CN BDN -ch2so2nh2 -CN BDO -CH2S02N(CH3)2 -CN BDP -(ch2)2nhso2h -CN BDQ -(ch2)2nhso2ch3 -CN BDR -H -ch3 BDS -CH2C(0)NH2 -ch3 BDT -CH2C(0)N(CH3)2 -ch3 BDU -C(0)CH2NHS02CH3 -ch3 BDV -(CH2)2C(0)NH2 -ch3 BDW -(CH2)2C(0)N(CH3)2 -ch3 BDX -c(o)(ch2)2nhso2ch3 -ch3 BDY -ch2co2ch3 -ch3 BDZ -ch2co2ch2ch3 -ch3 BEA -(CH2)2C02CH3 -ch3 BEB -(CH2)2C02CH2CH3 -ch3 BEC -(CH2)3C02CH3 -ch3 BED -(CH2)3C02CH2CH3 -ch3 89531-960524.doc 51 1343917 BEE -(ch2)4co2ch3 -ch3 BEF -(CH2)4C〇2CH2CH3 -ch3 BEG -ch2so2nh2 -ch3 BEH -ch2so2n(ch3)2 -ch3 BEI -(CH2)2NHS02H -ch3 BEJ -(CH2)2NHS02CH3 -ch3 BEK -H -C(0)NH(CH3) BEL -CH2C(0)NH2 -C(0)NH(CH3) BEM -CH2C(0)N(CH3)2 -C(0)NH(CH3) BEN -C(0)CH2NHS02CH3 -C(0)NH(CH3) BEO -(CH2)2C(0)NH2 -C(0)NH(CH3) BEP -(ch2)2c(o)n(ch3)2 -C(0)NH(CH3) BEQ -C(0)(CH2)2NHS02CH3 -C(0)NH(CH3) BER -ch2co2ch3 -C(0)NH(CH3) BES -ch2co2ch2ch3 -C(0)NH(CH3) BET -(ch2)2co2ch3 -C(0)NH(CH3) BEU -(ch2)2co2ch2ch3 -C(0)NH(CH3) BEV -(ch2)3co2ch3 -C(0)NH(CH3) BEW -(ch2)3co2ch2ch3 -C(0)NH(CH3) BEX -(CH2)4C02CH3 -C(0)NH(CH3) BEY -(CH2)4C02CH2CH3 -C(0)NH(CH3) BEZ -ch2so2nh2 -C(0)NH(CH3) BFA -ch2so2n(ch3)2 -C(0)NH(CH3) BFB -(CH2)2NHS02H -C(0)NH(CH3)
89531-960524.doc •52- 1343917
BFC BFD (CH2)2NHS02CH3 -C(0)NH(CH3)
H -C(0)N(CH3)2
BFE -CH2C(0)NH2 -C(0)N(CH3)2
BFF -CH2C(0)N(CH3)2 -C(0)N(CH,)2
BFG -C(0)CH2NHS02CH3 -c(o)n(ch3)2
BFH -(CH2)2C(0)NH2 -C(0)N(CH3)2
BFI -(CH2)2C(0)N(CH3)2 -C(0)N(CH3)2
BFJ -C(0)(CH2>2NHS02CH3 -c(o)n(ch3)2
BFK -CH2C02CH3 -C(0)N(CH3)2
BFL -CH2CO2CH2CH3 -C(0)N(CH3)2
BFM •(CH2>2C02CH3 -C(0)N(CH3)2
BFN -(CHz^CChCHzCHa •C(0)N(CH3)2
BFO -(CH2)3C〇2CH3 -C(0)N(CH3)2
BFP <CH2)3C〇2CH2CH3 -c(o)n(ch3)2
BFQ -(CH2)4C02CH3 -C(0)N(CH3)j
BFR -(CH2)4C〇2CH2CH3 -c(o)n(ch3)2
BFS -CH2SO2NH2 •C(0)N(CH3)2
BFT -CH2S〇2N(CH3)2 -C(0)N(CH3>2
BFU
-(CH2)2NHS02H -C(0)N(CH3)2
BFV -(CH2)2NHS02CH3 -c(o)n(ch3)2
BFW
-H -L〇ch3
BFX -CH2C(0)NH2 -C-N N-CH3
BFY •CH2C(0)N(CH3)2
〇 , II / -c一 N ,n-ch3
BFZ -C(0)CH2NHS02CH3 〇 >, —C—N N—CH3
BGA -(CH2)2C(0)NH2
I-CH3 89531-960524.doc -53- 1343917 BGB -(CH2)2C(0)N(CH3)2 if —C—乂 N~CH3 BGC -C(0)(CH2)2NHS02CH3 S厂λ u —C—N N一CH3 v_/ BGD .ch2co2ch3 0 f^, 一C—N N*"CH3 BGE -CH2CO2CH2CH3 —C—\ /N"^CH3 BGF -(ch2)2co2ch3 S厂λ —C—N N*CH3 \_/ BGG -(ch2)2co2ch2ch3 S厂Λ —C—吹严~CH3 BGH •(ch2)3co2ch3 1? —c-h/ n-ch3 BGI •(ch2)3co2ch2ch3 i?厂飞 —0 一乂 N—CH3 BGJ -(CH2)4C〇2CH3 ff厂Λ —C—N N—CH3 BGK -(CH2)4C02CH2CH3 !?厂λ —C 一吹户―CH3 BGL -CH2S〇2NH2 ί? —c-f/ n-ch3 BGM -CHzS〇2N(CH3)2 i? /~Λ —ό一 N N~CH3 \_y BGN -(CH2)2NHS02H η厂、 —c—isi Vj—CH3 BGO -(ch2)2nhso2ch3 i?厂飞 —C~N^ CH3 BGP -H 上0 89531-960524.doc -54- 1343917 BGQ -CH2C(0)NH2 —L〇 BGR -ch2c(o)n(ch3)2 BGS -C(0)CH2NHS02CH3 —L〇 BGT -(CH2)2C(0)NH2 —L〇 BGU -(CH2)2C(0)N(CH3)2 —L〇 BGV -C(0)(CH2)2NHS02CH3 —L〇 BGW -CH2C02CH3 -m) BGX -CH2C02CH2CH3 0 J^v BGY -(ch2)2co2ch3 0 J~v —ci-N^ ^ BGZ -(CH2>2C02CH2CH3 ΒΗΑ -(CH2)3C〇2CH3 -L〇 ΒΗΒ -(CH2)3C〇2CH2CH3 一L〇 BHC -(CH2)4C〇2CH3 -L〇 BHD -(ch2)4co2ch2ch3 —L〇 ΒΗΕ -ch2so2nh2 4-0 ι· 1· 89531-960524.doc •55- 1343917
BHF -ch2so2n(ch3)2 S厂 ~c-vy BHG •(ch2)2nhso2h -MZ) BHH -(CH2)2NHS〇2CH3 』〇 BHI •H i? ~C_^Q BHJ -CH2C(0)NH2 i? -c-hQ BHK. -CH2C(0)N(CH3)2 -c-rQ BHL -C(0)CH2NHS02CH3 i? -c 一 rQ BHM •(CH2>2C(0)NH2 n - BHN 1 -(CH2)2C(0)N(CH3)2 —Lq BHO -c(o)(ch2)2nhso2ch3 i? _c-rQ BHP -ck2co2ch3 ii -C-rQ BHQ -ch2co2ch2ch3 -C一 hQ BHR -iCH2)2C〇2CH3 i? -c-hQ BHS •(CH2)2C02CH2CH3 -c-rQ BHT •(ch2)3co2ch3 —c-^Q 89531-960524.doc -56- 1343917 BHU -(ch2)3co2ch2ch3 /^1 -C-fQ BHV •(CH2)4C〇aCH3 1? -cO BHW -(ch2)4co2ch2ch3 -c-rQ BHX -CH2SO2NH2 -c-hQ BHY -ch2so2n(ch3)2 i? /5¾ -c-rQ BHZ -<CH2)2NHSOjH 一 c-rQ BIA -(CH2>2NHS02CH3 if BIB -H ??厂、 —C-Νί ρ BIC -CH2C(0)NH2 BID -ch2c(o)n(ch3)2 -Lq> BIE -C(0)CH2NHS02CH3 M厂Λ 一 C 一乂 0 BIF •(ch2)2c(o)nh2 厂Ά BIG *(CH2)2C(0)N(CH3)2 BIH -c(o)(ch2)2nhso2ch3 i? —0—N 0 BII -CH2C02CH3 0 /. -ϊ~Νν_/ 89531-960524.doc -57- 1343917 BU -ch2co2ch2ch3 0 J, BIK -(ch2)2co2ch3 BIL •(CH2)2C02CH2CH3 0 t, BIM -(ch2)3co2ch3 —C~l^ BIN -(ch2)3co2ch2ch3 -L〇) BIO -(ch2)4co2ch3 —i BIP •(CH2)4C02CH2CH3 BIQ -ch2so2nh2 —c-n^ BIR •ch2so2n(ch3)2 —Lq BIS -(ch2)2nhso2h -Lq> BIT -(CH2)2NHS02CH3 η 1 —c-ri o J BIU -(CH2)3NHS〇2H •H BIV -(CH2)3NHS〇2H -C(0)NHi BIW >(CH2)3NHS02H -co2ch3 BIX -(CH2)3NHS02H -CHO BIY -(ch2)3nhso2h -CN BIZ -(ch2)3nhso2h -ch3 BJA -(CH2)3NHS02H -C(0)NHCHj BJB -(ch2)3nhso2h -C(0)N(CH3)2 89531-960524.doc -58- BJC -(CH2)3NHS02H 0 /~^ —C—N N~CH3 BJD -(CH2)3NHS02H —L〇 BJE -(CH2)3NHS02H ί? BJF -(CH2)3NHS02H 一c—isi 0 本發明另包括具有下式(Ic)之化合物:
1343917 及其醫藥可接受鹽’其中Ar3,R1-R3,G,m,p及q如上述 定義。 在一個具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 物為G為Η者。 在另一具體實施例中,式(Ic)之4-四竣基-4-苯基喊咬化合 物為 G為-L-(CH2)nC02R4者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nC02R4及 L為-C(O)-者。 在另一具體實施例中,式(Ic)之4-四峻基-4-苯基喊咬化合 物為 G為-L-(CH2)nC〇2R>4及 L為- S〇2-或- SO-者。 89531-960524.doc -59- 第092132303號專利申請案 L ff jL ί 中文說明書替換頁(96年11月)^卑,Μ日士涂 I_楫无: 在另一具體實施例中’式(Ic)之4·四唑基-4-苯基哌啶化合 物為G為-(CVCs伸烷基)R5者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 物為G為-CH2-R5者。 在另一具體實施例中’式(Ic)之4-四唑基-4·苯基哌啶化合 物為G為-(CH2)2-R5者。 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基哌啶化合 物為G為-(CH2)3-R5者。 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基哌啶化合 物為G為-(CH2)4-R5者》 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基哌啶化合 物為G為-(CH2)5-R5者。 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nC02R4及 R4為 Η 者。 在另一具體實施例中’式(Ic)之4-四峻基-4-苯基味啶化合 物為 G為-L-(CH2)nC〇2R4 及 Κ·4 為-Ci-Ciofe 基者。 在另一具體實施例中’式(Ic)之4·四唑基_4·苯基味啶化合 物為 G為-L-(CH2)nC02R4及 R4為-CHaCHCVC^烷基)者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 物為 G 為-L-(CH2)nC02R4 及 R4 為烷基)或 -ch2n (q-cu烷基)2者。 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基哌啶化合 物為G為-(Ci-Cs伸烷基)COOR4者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 89531-961130.doc •60· 1343917 物為G為-CH2-CO〇R4者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 物為 G為-(CH2)2-COOR4者。 在另一具體實施例中’式(Ic)之4-四咬基-4-苯基喊淀化合 物為 G為-(CH2)3-COOR4者。 在另一具體實施例中’式(Ic)之4-四峻基-4-苯基喊咬化合 物為 G為-(CH2)4-COOR4者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合
物為 G為-(CH2)5-COOR4者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nR5及 R5為 _NHS02R4者。 在另一具體實施例中’式(Ic)之4-四峻基-4-苯基喊咬化合 物為 G 為 _L-(CH2)nR5 及 R5 為 _c(〇)NH2 , _c(〇)NH〇H, -C^CONHCCi-C^烷基)’或烷基)2者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合
物為 G為-L-(CH2)nR5及R5為 _S〇2Nh2,_s〇2NH(Ci_C4烷基) 或- S〇2N(Ci-C4:fe 基)2 者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nR5及 R54-NHS02H者。 在另一具體實施例中’式(Ic)之4-四也基-4-苯基喊啶化合 物為 G為-L-(CH2)nR5及 L為-C(0)-者。 在另一具體實施例中’式(IC)之4-四吐基-4-苯基喊咬化合 物為 G為-L-(CH2)nR5&R5s _S〇2_或·80·者。 在另一具體實施例中,式(IC)之4-四唑基-4-苯基哌啶化合 89531-960524.doc •61 - 1343917 物為G為-(Ci-Cs次烷基)Rs者。 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基哌啶化合 物為p為0者》 · 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基哌啶化合 * 物為p為1者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 物為p為1及R_3相接之碳原子呈(r)_組態者。
在另一具體實施例中,式(Ic)之4-四吐基-4-苯基喊咬化合 物為p為1及R_3相接之碳原子呈〇組態者。 在另一具體實施例中,式(Ie)之4-四吨基-4-苯基喊啶化合 物為p為1及R3為-Ci-C〗坑基者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 物為p為1及R3為-(:113者。 在另一具體實施例中,式(Ic)之4-四岭基-4-苯基喊咬化合 物為p為1,R3為-C1-C3烷基,及&相接之碳原子呈(R)組態 者。 在另一具體實施例中,式(1〇)之4_四唑基苯基哌啶化合f修 物為p為1,R_3為-CH3,及I相接之碳原子呈(R)組態者。 在另一具體實施例中,式(1幻之4_四唑基_4苯基哌啶化合 物為p為1,R3為·Cl_C3烷基,及&相接之碳原子呈(s)組態♦ 者0 在另-具體實施例中,式⑽之心四吐基_4_苯基喊咬化合 物為p為1 ’ HCH3 ’及R3相接之碳原子呈⑻組態者。 在另具胆·實施例中,式(Ic)之4·四唑基_4-苯基哌啶化合 8953l-960524.doc •62- 1343917 物為q為〇者。 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基喊啶化合 物為m為〇者。 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基喊啶化合 物為m為1者。 在另一具體實施例中’式(Ic)之4-四哇基-4-苯基略咬化合 物為m為0及p為〇者。 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基哌啶化合
物為m為1及p為〇者 在另一具體實施例中’式(Ic)之4-四唑基-4-笨基哌啶化合 物為m為0及q為〇者。 在另一具體實施例中,式(1(;)之4_四唑基_4_苯基哌啶化合 物為m為1及q為〇者。 在另一具體實施例中,式(1(;)之4•四唑基_4_苯基哌啶化合 物為m為0 ’ p為〇及q為〇者。
在另一具體實施例中’式(Ie)之4·四4基·4·苯基錢化合 物為m為1,ρ為〇及q為〇者。 在另一具體實施例中,式(Ic)之4-四吐基-4-苯基喊咬化合
或-F者。 物為R2為-Br,-C1 在另-具體實施例中,式⑽之4_四< 基_4苯基㈣化+ 物為R2為-0(-C,-c3烷基)者。 在另具體實施例中,式(Ie)之4·四咬基·4·苯基喊唆化合 物為R2為-CVC:3燒基者。 在另一具體實施例中,式(Ic)之4-四吐基-4-苯基麵化合 89531-960524.doc •63- 1343917 物為R3為-NHGCVq烷基)或烷基)2者。 在另一具體實施例中,式(1勾之4_四唑基_4_苯基哌啶化合 物為 R3為-Br,-Cl,-I,或-F者。 在另一具體實施例中,式(1勹之4_四唑基_4_苯基哌啶化合 物為R3為-〇(-cvc3燒基)者。 在另一具體實施例中,式(1勾之4•四唑基_4•苯基哌啶化合 物為R3為-Ci-C3燒基者。
在另一具體實施例中,式(1(:)之4_四唑基_4_苯基哌啶化合 物為R3為-NHGC^Cs烷基)或烷基)2者。 在另一具體實施例中,式(1勹之4_四唑基·4_苯基哌啶化合 物為Ri為Η者。 在另一具體實施例中,式(Ic)之4-四峻基-4-苯基味咬化合 物為 RA-C(0)NH2,-C(0)NH0H,-C(0)NH(C丨-C4烷基),或 -C^C^ISKCVC^ 烷基)2 者。 在另一具體實施例中,式(Ic)之4-四吐基-4-苯基cr底啶化合 物為 Ri為-C(0)N(CH3)2者。
在另一具體實施例中,式(le)之4-四也基-4-苯基味啶化合 物為1^為-0:(〇)1^(〇^12(:113)2者》 在另一具體實施例中,式(Ic)之4-四也基-4-苯基味啶化合 物為 Ι^Λ-(:(0)ΝΗ(:Η3者。 在另一具體實施例中,式(Ic)之4-四吨基-4-苯基喊啶化合 物為 1^為-0:(〇)1^11(:112(:113 者。 在另一具體實施例中,式(1C)之4-四唑基-4-苯基哌啶化合 物為1^為-(:00114者。 89531-960524.doc -64 - 1343917 在另一具體實施例中,式(Ic)之4-四唆基-4-苯基α底咬化合 物為Ria-CHO者。 在另一具體實施例中,式(Ic)之4-四吐基-4-苯基>»底唆化合 物為!^為-CN者。 * 在另一具體實施例中,式(Ic)之4-四吐基-4·•苯基p展唆化合 物為Ri為-(C1-C4燒基)者。 在另一具體實施例中,式(Ic)之4-四峻基-4-苯基p瓜咬化合 物為1^為下列者 I·
在另一具體實施例中,式(1勾之4_四唑基_4_苯基哌啶化合 物為Ah為苯基,萘基,蒽基,或菲基者。 在另一具體實施例中,式(1勹之4四唑基_4_苯基哌啶化合
物為A1·3為-(5-至7-員)雜芳基者。 -四唑基-4-苯基哌啶化合 在另一具體實施例中,式(Ic)之4 物為Ar·3經一或多個I基取代者。 在另〃體實施例中,式(Ic)之4-四峻基-4-苯基喊啶化合 物為G為Η及p為〇者。 在另一具體實施例中,式(Ic)之4-四吐基-4-苯基喊咬化合 物為G為Η及q為〇者。 在另一具體實施例中,式⑽之4_四峻基_4_苯基❹化合 89531-960524.doc *65· 物為G為Η及m為0者。 在另一具體實施例中,式(1幻之4_四峻基_4_苯基喊啶化合 物為G為Η及m為1者。 在另一具體實施例中,式(Ic)之4-四峻基-4-苯基p底咬化合 物為G為Η,及Ar3為苯基者。 在另一具體實施例中,式(Ic)之4-四峻基苯基喊咬化合 物為G為Η,p為0,及q為〇者。 在另一具體實施例中,式(Ic)之4-四唑基_4·苯基哌啶化合 物為G為Η,p為0,及m為〇者。 在另一具體實施例中,式(Ic)之4-四吐基-4-苯基喊啶化合 物為G為Η,p為0,及m為1者。 在另一具體實施例中’式(Ic)之4-四峻基-4-苯基喊咬化合 物為G為Η ’ p為0 ’及At〗為苯基者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌啶化合 物為G為Η,p為0,q為0,及m為0者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌咬化合 物為G為Η,p為0,q為0,及m為1者。 在另一具體實施例中’式(Ic)之4-四唑基-4-苯基哌咬化合 物為G為Η,p為0’ q為0’及Ar3為苯基者。 在另一具體實施例中,式(Ic)之4-四唑基-4-苯基哌唆化合 物為G為Η’ p為0’ q為0,m為0,及Ar3為笨基者。 例示之式(Ic)之4-四唑基-4-苯基哌啶化合物具有下列結 構: 89531-960524.doc -66 - 1343917
其中如下: 化合物編號: G : Ri : CAA -H -H CAB -CH2C(0)NH2 -H CAC -ch2c(o)n(ch3)2 -H CAD -C(0)CH2NHS02CH3 -H CAE -(CH2)2C(0)NH2 -H CAF -(CH2)2C(0)N(CH3)2 -H CAG -c(o)(ch2)2nhso2ch3 -H CAH -ch2co2ch3 -H CAI -ch2co2ch2ch3 -H CAJ -(ch2)2co2ch3 - H CAK -(ch2)2co2ch2ch3 -H CAL -(ch2)3co2ch3 -H CAM -(ch2)3co2ch2ch3 -H CAN -(CH2)4C02CH3 -H CAO -(ch2)4co2ch2ch3 -H CAP -ch2so2nh2 -H CAQ -ch2so2n(ch3)2 -H CAR -(ch2)2nhso2h -H CAS -(ch2)2nhso2ch3 -H 89531-960524.doc •67- 1343917 CAT -H -C(0)NH2 CAU -CH2C(0)NH2 -C(0)NH2 CAV -ch2c(o)n(ch3)2 -c(o)nh2 CAW -C(0)CH2NHS02CH3 -C(0)NH2 CAX -(CH2)2C(0)NH2 -C(0)NH2 CAY -(CH2)2C(0)N(CH3)2 -C(0)NH2 CAZ -C(0)(CH2)2NHS02CH3 -C(0)NH2 CBA -CH2C02CH3 -C(0)NH2 CBB -CH2C02CH2CH3 -C(0)NH2 CBC -(ch2)2co2ch3 -C(0)NH2 CBD -(ch2)2co2ch2ch3 -C(0)NH2 CBE -(CH2)3C02CH3 -C(0)NH2 CBF -(ch2)3co2ch2ch3 -C(0)NH2 CBG -(CH2)4C02CH3 -C(0)NH2 CBH -(ch2)4co2ch2ch3 -C(0)NH2 CBI -ch2so2nh2 -C(0)NH2 CBJ -ch2so2n(ch3)2 -C(0)NH2 CBK -(CH2)2NHS02H -C(0)NH2 CBL -(ch2)2nhso2ch3 -C(0)NH2 CBM -H -co2ch3 CBN -CH2C(0)NH2 -C02CH3 CBO -CH2C(0)N(CH3)2 -co2ch3 CBP -C(0)CH2NHS02CH3 -co2ch3 CBQ -(CH2)2C(0)NH2 -C02CH3 CBR -(ch2)2c(o)n(ch3)2 -C02CH3 CBS -c(o)(ch2)2nhso2ch3 -C02CH3 89531-960524.doc -68- 1343917
CBT -CH2CO2CH3 -co2ch3 CBU -ch2co2ch2ch3 -C02CH3 CBV -(CH2)2C02CH3 -C02CH3 CBW -(CH2)2C02CH2CH3 -C02CH3 CBX -(ch2)3co2ch3 -C02CH3 CBY -(ch2)3co2ch2ch3 -C02CH3 CBZ -(ch2)4co2ch3 -C02CH3 CCA -(CH2)4C02CH2CH3 -C02CH3 CCB -ch2so2nh2 -C02CH3 CCC •ch2so2n(ch3)2 -C02CH3 CCD -(ch2)2nhso2h -C02CH3 CCE -(ch2)2nhso2ch3 -co2ch3 CCF -H -CHO CCG -CH2C(0)NH2 -CHO CCH -CH2C(0)N(CH3)2 -CHO CCI -C(0)CH2NHS02CH3 -CHO CCJ -(CH2)2C(0)NH2 -CHO CCK -(ch2)2c(o)n(ch3)2 -CHO CCL -c(o)(ch2)2nhso2ch3 -CHO CCM -ch2co2ch3 -CHO CCN -ch2co2ch2ch3 -CHO CCO -(ch2)2co2ch3 -CHO CCP -(ch2)2co2ch2ch3 -CHO CCQ -(CH2)3C02CH3 -CHO CCR -(CH2)3C02CH2CH3 -CHO CCS -(ch2)4co2ch3 -CHO 89531-960524.doc -69- 1343917 ,CCT -(CH2)4C02CH2CH3 -CHO ecu -ch2so2nh2 -CHO ccv -ch2so2n(ch3)2 -CHO ccw -(CH2)2NHS02H -CHO ccx -(ch2)2nhso2ch3 -CHO CCY -H -CN ccz -CH2C(0)NH2 -CN CDA -CH2C(0)N(CH3)2 -CN CDB -C(0)CH2NHS02CH3 -CN CDC -(CH2)2C(0)NH2 -CN CDD -(CH2)2C(0)N(CH3)2 -CN CDE -c(〇)(ch2)2nhso2ch3 -CN CDF -ch2co2ch3 -CN COG -ch2co2ch2ch3 -CN CDH -(CH2)2C02CH3 -CN CDI -(CH2)2C02CH2CH3 -CN CDJ -(ch2)3co2ch3 -CN CDK -(CH2)3C02CH2CH3 -CN CDL -(ch2)4co2ch3 -CN CDM -(CH2)4C02CH2CH3 -CN CDN -ch2so2nh2 -CN CDO -ch2so2n(ch3)2 -CN CDP -(CH2)2NHS02H -CN CDQ -(CH2)2NHS02CH3 -CN CDR -H -ch3 CDS -CH2C(0)NH2 -ch3 89531-960524.doc -70- 1343917 CDT -CH2C(0)N(CH3)2 -ch3 CDU -C(0)CH2NHS02CH3 -ch3 CDV -(CH2)2C(0)NH2 -ch3 CDW -(CH2)2C(0)N(CH3)2 -ch3 CDX -c(o)(ch2)2nhso2ch3 -ch3 CDY -ch2co2ch3 -ch3 CDZ -ch2co2ch2ch3 -ch3 CEA -(CH2)2C02CH3 -ch3 CEB -(CH2)2C02CH2CH3 -ch3 CEC -(ch2)3co2ch3 -ch3 CED -(CH2)3C02CH2CH3 -ch3 CEE -(CH2)4C02CH3 -ch3 CEF -(ch2)4co2ch2ch3 -ch3 CEG -ch2so2nh2 -ch3 CEH -ch2so2n(ch3)2 -ch3 CEI -(CH2)2NHS02H -ch3 CEJ -(CH2)2NHS02CH3 -ch3 CEK -H -C(0)NH(CH3) CEL -CH2C(0)NH2 -C(0)NH(CH3) CEM -CH2C(0)N(CH3)2 -C(0)NH(CH3) CEN -C(0)CH2NHS02CH3 -C(0)NH(CH3) CEO -(CH2)2C(0)NH2 -C(0)NH(CH3) CEP -(CH2)2C(0)N(CH3)2 -C(0)NH(CH3) CEQ -C(0)(CH2)2NHS02CH3 -C(0)NH(CH3) CER -ch2co2ch3 -C(0)NH(CH3) CES -ch2co2ch2ch3 -C(0)NH(CH3) 89531-960524.doc 1343917 CET -(CH2)2C02CH3 -C(0)NH(CH3) CEU -(CH2)2C02CH2CH3 -C(0)NH(CH3) CEV -(CH2)3C02CH3 -C(0)NH(CH3) CEW -(ch2)3co2ch2ch3 -C(0)NH(CH3) CEX -(CH2)4C02CH3 -C(0)NH(CH3) CEY -(ch2)4co2ch2ch3 -C(0)NH(CH3) CEZ -ch2so2nh2 -C(0)NH(CH3) CFA -ch2so2n(ch3)2 -C(0)NH(CH3) CFB -(CH2)2NHS02H -C(0)NH(CH3) CFC -(CH2)2NHS02CH3 -C(0)NH(CH3) CFD -H -C(0)N(CH3)2 CFE -CH2C(0)NH2 -C(0)N(CH3)2 CFF -ch2c(o)n(ch3)2 -C(0)N(CH3)2 CFG -C(0)CH2NHS02CH3 -c(〇)N(ch3)2 CFH -(CH2)2C(0)NH2 -C(0)N(CH3)2 CFI -(CH2)2C(0)N(CH3)2 -c(〇)N(ch3)2 CFJ -c(o)(ch2)2nhso2ch3 -c(〇)N(ch3)2 CFK -ch2co2ch3 -C(0)N(CH3)2 CFL -ch2co2ch2ch3 -C(0)N(CH3)2 CFM -(ch2)2co2ch3 -C(0)N(CH3)2 CFN -(CH2)2C02CH2CH3 -C(0)N(CH3)2 CFO -(ch2)3co2ch3 -c(o)n(ch3)2 CFP -(CH2)3C02CH2CH3 -C(0)N(CH3)2 CFQ -(CH2)4C02CH3 -C(0)N(CH3)2 CFR -(ch2)4co2ch2ch3 -C(0)N(CH3)2 CFS -ch2so2nh2 -C(0)N(CH3)2 89531-960524.doc -72- 1343917 CFT •ch2so2n(ch3)2 -c(o)n(ch3)2 CFU -(CH2)2NHS02H -C(0)N(CH3)2 CFV -(ch2)2nhso2ch3 -C(0)N(CH3)2 CFW -H ff厂λ —ΰ—乂 N—CH3 CFX •ch2c(o)nh2 Μ厂飞 —C一 Ν }j~CH3 CFY -CH2C(0)N(CH3)2 If / \ A —C一N、/N~~CH3 CFZ -C(0)CH2NHS〇2CH3 0倉~, 一C""N N—CH3 CGA -(CH2>2C(0)NH2 II / \ —C—isi N—CH3 CGB -(ch2)2c(o)n(ch3)2 11 /-λ —C_N、/N—CH3 CGC -C(0)(CH2)2NHS02CH3 5? /~λ —c-乂 n-ch3 CGD -CH2C02CH3 S —c-K n-ch3 CGE -CH2C〇2CH2CH3 f?厂 —ό 一吹 ΝΗΟΗβ CGF -(CH2)iC02CHj n厂Λ —C-nV4-CH3 CGG -(CH2)2C〇2CH2CH3 ί? —〇—(s/ N—CH3 CGH -(ch2)3co2ch3 Μ /~λ —0_Ν、/N—CH3 CGI -(ch2)3co2ch2ch3 II / \ —c-ri 户一ch3 CGJ -(ch2)4co2ch3 1? /^\ —c-Ν W-CH3 89531-960524.doc •73- 1343917 CGK -(ch2)4co2ch2ch3 —t〇-CH3 CGL .CH2SO2NH2 —Lq—CH3 CGM -ch2so2n(ch3)2 』_〇_CH3 CGN -(CH2)2NHS02H 0 身^ —N—CH3 CGO -(CH2>2NHS02CH3 _Lq_CH3 CGP -H 0 ,^v -“0 CGQ -CH2C(0)NH2 -L〇 CGR -CH2C(0)N(CH3)2 一 CGS -C(0)CH2NHS02CH3 CGT -(CH2)2C(0)NH2 CGU -(CH2)2C(0)N(CH3)2 0 >, -m) CGV •c(o)(ch2)2nhso2ch3 CGW -CH2C〇2CH3 CGX -ch2co2ch2ch3 丄〇 CGY -(ch2)2co2ch3 一 L〇 89531-960524.doc -74- 1343917
CGZ -(ch2)2co2ch2ch3 —C-N^ ^ CHA -(ch2)3co2ch3 i? /~\ CHB -(ch2)3co2ch2ch3 o ,, -K3 CHC -(ch2)4co2ch3 —L〇 CHD -(ch2)4co2ch2ch3 -KD CHE -CH2S〇2NH2 O J~, -KD CHF -CH2S02N(CH3)2 s厂' -CA_) CHG -iCH2)2NHS02H CHH •(ch2)2nhso2ch3 一 Lq CHI -H ?\ CHJ -CH2C(0)NH2 i? -c-rQ CHK -CH2C(0)N(CH3)2 i? /¾¾ -c-iQ CHL -C(0)CH2NHS02CH3 i? -c-rQ CHM <ch2)2c(o)nh2 ?\ /==5:1 -c-rQ CHN -(ch2)2c(o)n(ch3)2 1? /^1 _C*"Q -75- 89531-960524.doc 1343917 CHO -C(0)(CH2)2NHS02CH3 i? — CHP -CH2C〇2CH3 i? CHQ -ch2co2ch2ch3 ?\ - CHR -(ch2)2co2ch3 CHS -(ch2)2co2ch2ch3 5? CHT -(ch2)3co2ch3 Π /5¾] — CHU -(CH2)3C〇aCH2CH3 i? /5¾^ —C-N^J CHV -(CH2)4C〇2CH3 if —C-lQ CHW -(CH2)4C02CH2CH3 ~c_rCJ CHX -ch2so2nh2 -c-rQ CHY -CH2S02N(CH3)2 n — CHZ -(CH2)2NHS〇2H ~c_rQ CIA -(ch2)2nhso2ch3 il /^i —c-rQ cm -H -Lq〇 cic -CH2C(0)NH2 —Lq〇 -76- 89531-960524.doc 1343917 CID -CH2C(0)N(CHj)2 —CH^ CIE -C(0)CH2NHS02CH3 -Lq C1F -(CH2)2C(0)NH2 —c-r^ CIG .(CH2)2C(0)N(CH3)2 —Lq cm -c(o)(ch2)2nhso2ch3 cu -ch2co2ch3 cu -CH2C02CH2CH3 cnc •(ch2)2co2ch3 CIL -(ch2)2co2ch2ch3 J—0 CIM •(ch2)3co2ch3 -L〇> CIN -(ch2)3co2ch2ch3 CIO •(ch2)4co2ch3 -L〇) CIP •(CH2)4C02CH2CH3 — CIQ -ch2so2nh2 —c-l^ CtR •CH2S02N(CH3)2 0 /~v —c-t^y> 89531-960524.doc -77- 1343917 CIS -(CH2)2NHS02H n厂Λ —C-N p ατ -(ch2)2nhso2ch3 o ,~, CIU -(CH2)3NHS02H -H CIV -(ch2)3nhso2h -C(0)NH2 CIW -(CH2)3NHS02H -COiCHj CIX -(CH2)3NHS02H -CHO CIY (ch2)3nhso2h -CN CIZ -(CH2)3NHS02H -ch3 CJA -(CH2)3NHS02H -C(0)NHCH3 CJB -(CH2)3NHS02H -c(o)n(ch3>2 CJC -(ch2)3nhso2h u厂Λ —d—N N-CH3 v_y 3 CJD -(ch2)3nhso2h CJE -(CH2)3NHS02H 1? ~c_fQ CJF -(CH2)3NHS02H —C-t^ 本發明另包括具有下式(Id)之化合物:
(R2)q 及其醫藥可接受鹽,其中Ar3,,G,m,p及q如上述 -78 - 89531-960524.doc 1343917 弟092132303號專利申請案 t · — · 中文說明書替換頁(96年11月〕月押怜乇丨 定義。 I——— 在一個具體實施例中,式(1幻之4四唑基_4_苯基哌啶化合 物為G為η者。 在另—具體實施例中’式(Id)之4-四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nC〇2R4者。 在另一具體實施例中,式(Id)之4·四唑基-4-苯基哌啶化合 物為 G為-L-(CH2)nC02R4及 L為·(:(〇)·者。 在另一具體實施例中’式(1(1)之4_四唑基_4_苯基哌啶化合 物為 G為-L-(CH2)nC〇2R4及 l為 _S〇2_或 _SO_者。 在另一具體實施例中,式(1句之4_四唑基_4_苯基哌啶化合 物為 G為-L-(CH2)nC02R4及 r4*h者。 在另一具體實施例中,式(1(1)之4_四唑基_4_苯基哌啶化合 物為 G為-L-(CH2)nC02R4& r4為·Ci_Ci〇烷基者。 在另一具體實施例中’式(Id)之扣四唑基_4_苯基哌啶化合 物為 G為-L-(CH2)nC02R4及尺4為 _CH2〇(Ci_C4燒基)者。 在另一具體實施例中,式(1句之4_四唑基_4_苯基哌啶化合 物為 G 為-L-(CH2)nC02R4 及 r4 為 _CH2NH(Cl_c4 烷基)或 -ch2n (c,-c4烷基)2者。 在另一具體實施例中’式(Id)之4-四唑基-4-苯基哌啶化合 物為G為-(Ci-Cs伸燒基)c〇〇r4者。 在另一具體實施例中’式(Id)之4-四唑基-4-苯基哌啶化合 物為G為-CH2-CO〇R4者。 在另一具體實施例中’式(Id)之4-四唑基_4_苯基哌啶化合 , 物為 G為-(CH2)2-CO〇R4者。 8953K96M30.doc -79- 1343917 …v ϊ 092132303號專利申請案修β 中文說明書替換頁(96年u月)L 月 在另一具體實施例中,式(Id)之;:四唑基_4_苯基哌啶化合 物為 G為-(CH2)3-C〇〇R4者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌咬化合 物為 G為-(CH2)4-CO〇R4者。 在另一具體實施例中,式(Id)之4·四唑基_4_苯基哌啶化合 物為 G為-(CH2)5-CO〇R4者。 在另一具體實施例中’式(1幻之4_四唑基苯基哌啶化合 物為 G為 _L-(CH2)nR5及 R54_nhs〇2r4者。 在另一具體實施例中,式(1(1)之4_四唑基_4•苯基哌啶化合 物為 G 為-L-(CH2)nR5 及 r5 為 <(0"^ , _c(〇)NH〇H , C(0)NH (CVCU烷基)’或/⑴州⑷广山烷基)2者。 在另一具體實施例中,式(1(1)之4_四唑基_4_苯基哌啶化合 物為 G為-L-(CH2)nR5及心為 _s〇2NH2,_s〇2NH(Ci_C4烷基), 或-S02N((VC4 燒基)2 者。 在另一具體實施例中,式(1幻之4•四唑基_4苯基哌啶化合 物為 G為-L-(CH2)nRAnNHS〇2H者。 在另一具體實施例中’式(Id)之4-四唑基-4-苯基哌啶化合 物為G為-L-(CH2)nR5及[為^⑴)者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為G為·L-(CH2)nR5及尺5為_8〇2_或_s〇·者。 在另一具體實施例中’式(1旬之4•四唑基_4苯基哌啶化合 物為G為-(Ci-C5伸燒基)r5者。 在另一具體實施例中’式(Id)之4-四唑基-4-苯基哌啶化合 物為G為-CH2-R5者。 89531-961130.doc 在另—具體實施例中,式(Id)t4_四唑基_4_苯基哌啶化合 物為G為-(CH2)2-R5者。 在另—具體實施例中,式(id)<4_四唑基_4_苯基哌啶化合, 物為 G為-(CH2)3_R5 者。 · 在另—具體實施例中,式(1(〇之4_四唑基_4_苯基哌啶化合 物為G為-(CH2)4-R5者。 在另—具體實施例中,式(1句之4•四唑基_4_苯基哌啶化合 物為G為-(CH2)5-R5者。 在另-具體實施例中,式(Id)之心四4基_4_苯基派*化合免籲
物為p為〇者D 在另-具體實施例中,式(Id)之4_四咬基冬苯基喊咬化合 物為p為1者。 具體實施例中,式(1(1)之4_四唑基_4_苯基哌啶化合 在另 物為P為1及R3相接之碳原子呈(R)_組態者。 在另-具體實施例中,式⑽之心四吐基_4苯基喊咬化合 物為P為1及&相接之碳原子呈(s)組態者。 在另-具體實施例中,式(Id)之心四吐基心苯基喊嗓化合J· 物為p為1及R3為-C1-C3燒基者。 在另一具體實施财,式⑽之4-四咬基-4-苯基喊咬化合 物為ρ為1及R3為-CH〗者。 在另-具體實施例中,式⑽之心四吐基_4_苯基旅咬化合 物為p為1 ’ R3為_Cl_C3烷基,及I相接之碳原子呈(汉)組態 者。 在另一 具體實施例中,式⑽之‘四唑基苯基哌啶化合 89531-960524.doc 1343917 物為p為卜r3為偶,及_接之碳原予呈(r)組態者。 在另—具體實施例中’式⑽之4_四吐基_4•苯基喊咬化合 物為P為1 ’ R_3為-(^以基,及心相接之碳原子呈⑻組態-者0 .4 在另一具體實施例中,式⑽之心四峻基_心苯基錢化合 物為p為1 ’ R3為·CH3 ’及尺3相接之碳原子呈(S)組態者。 在另-具體實施例中,式⑽之4_四嗤基_4_苯基喊咬化合 物為q為0者。 在另-具體實施例中,式⑽之4_四峻基_4_苯基錢化合1· 物為m為〇者。 在另一具體實施例中,式(1句之4_四唑基_4_苯基哌啶化合 物為m為1者。 在另一具體實施例中,式(1(1)之4_四唑基_4_苯基哌啶化合 物為m為0及p為〇者。 在另一具體實施例中,式(1(〇之4_四唑基_4_苯基哌啶化合 物為Π1為1及p為〇者。 在另一具體實施例中,式(Id)之4_四唑基_4_苯基哌啶化合f參 物為m為0及q為〇者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為m為1及q為〇者》 « 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為m為0,p為0及q為〇者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為m為1,p為0及q為〇者。 89531-960524.doc -82- 1343917 在另一具體實施例中’式(Id)之4-四唑基-4-苯基哌啶化合 物為 R24-Br,-Cl,-I,或-F 者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為I^a-CK-CVC^烷基)者。 . 在另一具體實施例中’式(Id)之4-四唑基-4-苯基派啶化合 物為R2為-CVC3烷基者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為R2為-NH(-C〗-C3燒基)或-NGCi-Cs燒基)2者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為 R3A-Br,-Cl,-I,或-F 者。 在另一具體實施例中’式(Id)之4-四唑基-4-苯基旅啶化合 物為R3為-烷基)者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為R3為-CVC3烧·基者。
在另一具體實施例中,式(Id)之4-四吐基-4-苯基旅咬化合 物為R3為-NH(-Ci-C3燒基)或-NGC^C^燒基)2者。 在另一具體實施例中,式(Id)之4-四吐基-4-苯基旅咬化合 物為心為!!者。 在另一具體實施例中’式(Id)之4-四唑基-4-苯基哌啶化合 物為尺丨為-C(0)NH2 ’ -C(0)NH0H,烷基),或 -cccoisKCi-c^ 烷基)2 者。 在另一具體實施例中’式(Id)之4-四唑基-4-苯基哌啶化合 物為 RA-C(0)N(CH3)2者。 在另一具體實施例中,式(Id)之4-四吐基-4-苯基喊啶化合 89531-960524.doc • 83 - 1343917 物為 RiS-C^CONHCHs者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為 Κ,*-(:(0)ΝΗ(:Η2(:Η3者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為 者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為1^為-COOR4者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為Ri為-CHO者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為心為/]^者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為烷基)者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為1為下列者
^2)r (CH2) -技-或-[Ο3 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為Ar3為苯基,莕基,蒽基,或菲基者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為Ar3為-(5-至7-員)雜芳基者。 89531-960524.doc •84- 1343917 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為經一或多個R>2基取代者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為G為Η及p為0者。 ’ 在另一具體實施例中’式(Id)之4-四唑基-4-苯基哌啶化合 物為G為Η及q為0者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為G為Η及m為0者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合t修 物為G為Η及m為1者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為G為Η ’及為苯基者。 在另一具體實施例中,式(Id)之4-四唑基_4_苯基哌啶化合 物為G為Η,p為0,及q為〇者。 在另一具體實施例中,式(1(1)之4_四唑基_4_苯基哌啶化合 物為G為Η,p為0 ’及m為〇者。 在另一具體實施例中,式⑽之4_四吐基_4_苯基喊咬化合|鲁 物為G為Η,p為0,及m為1者。 在另-具體實施例中’式(1(1)之4•四吐基·4苯基喊咬化合 物為G為Η,ρ為〇,及αΓ3為苯基者。 在另一具體實施例中’式⑽之4-四吐基_4_苯基喊唉化合 物為G為Η,p為G,q為〇,及病Q者。 ’ 在另一具體實施例中,式(Id)之4-四也基-4-苯基派咬化合、 物為G為Η,p為〇 ’ q為〇,及_ i者。 . 8953l-960524.doc -85 · 1343917 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為G為Η,p為0,q為0,及Ar3為苯基者。 在另一具體實施例中,式(Id)之4-四唑基-4-苯基哌啶化合 物為G為Η,p為0,q為0,m為0,及Ar3為苯基者。 例示之式(Id)之4-四唑基-4-苯基哌啶化合物具有下列結 構.
及其醫藥可接受鹽, 其中G及Ri如下:
化合物編號: G : R,: DAA •H -H DAB -CH2C(0)NH2 -H DAC -CH2C(0)N(CH3)2 -H DAD -C(0)CH2NHS02CH3 -H DAE -(CH2)2C(0)NH2 -H DAF -(CH2)2C(0)N(CH3)2 -H DAG -c(o)(ch2)2nhso2ch3 -H DAH -ch2co2ch3 -H DAI -ch2co2ch2ch3 -H DAJ -(CH2)2C02CH3 -H DAK -(CH2)2C02CH2CH3 -H 89531-960524.doc -86- 1343917 DAL -(CH2)3C02CH3 -H DAM -(ch2)3co2ch2ch3 -H DAN -(CH2)4C02CH3 -H DAO -(ch2)4co2ch2ch3 -H DAP -ch2so2nh2 -H DAQ -ch2so2n(ch3)2 -H DAR -(ch2)2nhso2h -H DAS -(ch2)2nhso2ch3 -H DAT -H -C(0)NH2 DAU -CH2C(0)NH2 -C(0)NH2 DAV -CH2C(0)N(CH3)2 -C(0)NH2 DAW -C(0)CH2NHS02CH3 -C(0)NH2 DAX -(CH2)2C(0)NH2 -C(0)NH2 DAY -(CH2)2C(0)N(CH3)2 -C(0)NH2 DAZ -C(0)(CH2)2NHS02CH3 -C(0)NH2 DBA -ch2co2ch3 -C(0)NH2 DBB -ch2co2ch2ch3 -C(0)NH2 DBC -(CH2)2C02CH3 -C(0)NH2 DBD -(CH2)2C02CH2CH3 -C(0)NH2 DBE -(ch2)3co2ch3 -C(0)NH2 DBF -(ch2)3co2ch2ch3 -C(0)NH2 DBG -(CH2)4C02CH3 -C(0)NH2 DBH -(ch2)4co2ch2ch3 -C(0)NH2 DBI -ch2so2nh2 -C(0)NH2 DBJ -ch2so2n(ch3)2 -C(0)NH2 DBK -(ch2)2nhso2h -C(0)NH2 89531-960524.doc • 87- 1343917
DBL -(ch2)2nhso2ch3 -C(0)NH2 DBM -H -C02CH3 DBN -CH2C(0)NH2 -C02CH3 DBO -ch2c(o)n(ch3)2 -C02CH3 DBP -ch2nhso2ch3 -C02CH3 DBQ -(CH2)2C(0)NH2 -co2ch3 DBR -(CH2)2C(0)N(CH3)2 -C02CH3 DBS -(ch2)2nhso2ch3 -co2ch3 DBT -ch2co2ch3 -co2ch3 DBU -CH2C02CH2CH3 -C02CH3 DBV -(ch2)2co2ch3 -C02CH3 DBW -(ch2)2co2ch2ch3 -co2ch3 DBX -(CH2)3C02CH3 -C02CH3 DBY -(ch2)3co2ch2ch3 -C02CH3 DBZ -(CH2)4C02CH3 -C02CH3 DCA -(ch2)4co2ch2ch3 -C02CH3 DCB -ch2so2nh2 -C02CH3 DCC -ch2so2n(ch3)2 -C02CH3 DCD -(CH2)2NHS02H -C02CH3 DCE -(ch2)2nhso2ch3 -co2ch3 DCF -H -CHO DCG -CH2C(0)NH2 -CHO DCH -ch2c(o)n(ch3)2 -CHO DCI -C(0)CH2NHS02CH3 -CHO DCJ -(CH2)2C(0)NH2 -CHO DCK -(ch2)2c(o)n(ch3)2 -CHO 89531-960524.doc * 88 - 1343917
DCL -c(〇)(ch2)2nhso2ch3 -CHO DCM -ch2co2ch3 -CHO DCN -ch2co2ch2ch3 -CHO DCO -(ch2)2co2ch3 -CHO DCP -(CH2)2C02CH2CH3 -CHO DCQ -(CH2)3C02CH3 -CHO DCR -(CH2)3C02CH2CH3 -CHO DCS -(ch2)4co2ch3 -CHO DCT -(CH2)4C02CH2CH3 -CHO DCU -ch2so2nh2 -CHO DCV -ch2so2n(ch3)2 -CHO DCW -(CH2)2NHS02H -CHO DCX -(ch2)2nhso2ch3 -CHO DCY -H -CN DCZ -CH2C(0)NH2 -CN DDA -CH2C(0)N(CH3)2 -CN DDB -C(0)CH2NHS02CH3 -CN DDC -(CH2)2C(0)NH2 -CN DDD -(CH2)2C(0)N(CH3)2 -CN DDE -C(0)(CH2)2NHS02CH3 -CN DDF -ch2co2ch3 -CN DDG -ch2co2ch2ch3 -CN DDH -(CH2)2C02CH3 -CN DDI -(CH2)2C02CH2CH3 -CN DDJ -(CH2)3C02CH3 -CN DDK -(ch2)3co2ch2ch3 -CN 89531-960524.doc •89- 1343917 DDL -(CH2)4C02CH3 -CN DDM -(ch2)4co2ch2ch3 -CN DDN -ch2so2nh2 -CN DDO -ch2so2n(ch3)2 -CN DDP -(ch2)2nhso2h -CN DDQ -(ch2)2nhso2ch3 -CN DDR -H -ch3 DDS -CH2C(0)NH2 -ch3 DDT -ch2c(o)n(ch3)2 -ch3 DDU -C(0)CH2NHS02CH3 -ch3 DDV -(CH2)2C(0)NH2 -ch3 DDW -(CH2)2C(0)N(CH3)2 -ch3 DDX -c(o)(ch2)2nhso2ch3 -ch3 DDY -ch2co2ch3 -ch3 DDZ -CH2C02CH2CH3 -ch3 DEA -(ch2)2co2ch3 -ch3 DEB -(CH2)2C02CH2CH3 -ch3 DEC -(ch2)3co2ch3 -ch3 DED -(CH2)3C02CH2CH3 -ch3 DEE -(ch2)4co2ch3 -ch3 DEF -(ch2)4co2ch2ch3 -ch3 DEG -ch2so2nh2 -ch3 DEH -ch2so2n(ch3)2 -ch3 DEI -(CH2)2NHS02H -ch3 DEJ -(ch2)2nhso2ch3 -ch3 DEK -H -C(0)NH(CH3) 89531-960524.doc -90- 1343917 DEL -CH2C(0)NH2 -C(0)NH(CH3) DEM -CH2C(0)N(CH3)2 -C(0)NH(CH3) DEN -C(0)CH2NHS02CH3 -C(0)NH(CH3) DEO -(CH2)2C(0)NH2 -C(0)NH(CH3) DEP -(CH2)2C(0)N(CH3)2 -C(0)NH(CH3) DEQ -c(o)(ch2)2nhso2ch3 -C(0)NH(CH3) DER -ch2co2ch3 -C(0)NH(CH3) DES -ch2co2ch2ch3 -C(0)NH(CH3) DET -(CH2)2C02CH3 -C(0)NH(CH3) DEU -(CH2)2C02CH2CH3 -C(0)NH(CH3) DEV -(CH2)3C02CH3 -C(0)NH(CH3) DEW -(CH2)3C〇2CH2CH3 -C(0)NH(CH3) DEX -(CH2)4C02CH3 -C(0)NH(CH3) DEY -(ch2)4co2ch2ch3 -C(0)NH(CH3) DEZ -ch2so2nh2 -C(0)NH(CH3) DFA -ch2so2n(ch3)2 -C(0)NH(CH3) DFB -(CH2)2NHS02H -C(0)NH(CH3) DFC -(ch2)2nhso2ch3 -C(0)NH(CH3) DFD -H -C(0)N(CH3)2 DFE -CH2C(0)NH2 -c(o)n(ch3)2 DFF -CH2C(0)N(CH3)2 -c(o)n(ch3)2 DFG -C(0)CH2NHS02CH3 -C(0)N(CH3)2 DFH -(CH2)2C(0)NH2 -C(0)N(CH3)2 DFI -(CH2)2C(0)N(CH3)2 -c(o)n(ch3)2 DFJ -C(0)(CH2)2NHS02CH3 -c(o)n(ch3)2 89531-960524.doc •91 · 1343917 DFK -CH2CO2CH3 -c(o)n(ch3)2 DFL -CH2C02CH2CH3 -c(o)n(ch3)2 DFM -(CH2)2C〇2CH3 -C(0)N(CH3)2 DFN •(CH2)2C〇2CH2CH3 -C(0)N(CH3)2 DFO •<CH2)3C02CHj -C(0)N(CH3)2 DFP •(CH2)3C〇2CH2CH3 -C(0)N(CH3)2 DFQ -(ch2)4co2ch3 -C(0)N(CH3)2 DFR -(ch2)4co2ch2ch3 -C(0)N(CH3)2 DFS -CH2S02NH2 -C(0)N(CH3)2 DFT -CH2S02N(CH3)2 -c(o)n(ch3)2 DFU -(CH2)2NHS02H -c(o)n(ch3)2 DFV ~<ch2)2nhso2ch3 -C(0)N(CH3)2 DFW -H i? /~λ —0 一乂 N—CH3 DFX -CH2C(0)NH2 0 J, II / \ —0 一 N~"CH3 DFY -CH2C(0)N(CH3)j II —C—N DFZ -C(0)CH2NHS02CH3 —C~~N Vj—CH3 DGA -<CH2)2C(0)NH2 0 .. II / \ —C-N N-CH3 \_y 3 DGB -(CH2)2C(0)N(CH3)2 ff厂Λ -C-N Vj-CH3 DGC ,c(o)(ch2)2nhso2ch3 1? /~Λ -C-N N-CH3 w 3 DGD -ch2co2ch3 S厂Λ 一ΙΨ~CH3 \_y DGE .CH2C02CH2CH3 S —C—l·/ N—CH3 89531-960524.doc -92- 1343917
89531-960524.doc -93- 1343917
DGU -(ch2)2c(o)n(ch3)2 -t〇 1 DGV -C(0)(CH2)2NHS〇2CH3 — DGW -ch2co2ch3 - KD DGX -CH2CO2CH2CH3 -K3 DGY -(CH2)2C02CH3 DGZ -(ch2)2co2ch2ch3 —L〇 DHA -(ch2)3co2ch3 —L〇 DHB KCH2)3C02CH2CH3 —L〇 DHC -(ch2)4co2ch3 —L〇 DHD •(CH2)4C02CH2CH3 0 J^, —c-r/~\ ' ' DHE -ch2so2nh2 』-〇 { DHF -CH2S02N(CH3)2 —Lq DHG -(ch2)2nhso2h 0 / j-0 DHH -(ch2)2nhso2ch3 —L〇 DHI -H 8953N960524.doc .94- 1343917 1 DHJ -CH2C(0)NH2 1? DHK -ch2c(o)n(ch3)2 DHL -C(0)CH2NHS02CH3 M -c-rQ DHM -(CH2)2C(0)NH2 1? DHN -(CH2)2C(0)N(CH3)2 n ~C~\J DHO -c(o)(ch2)2nhso2ch3 -c 一 〇 DHP -ch2co2ch3 if DHQ -ch2co2ch2ch3 -ca5 DHR -(CH2)2C〇2CH3 i? -c-。 DHS -(CH2)2C02CH2CH3 -c-rQ DHT _(ch2)3co2ch3 DHU •<ch2)3co2ch2ch3 i? DHV -(CH2)4C〇2CH3 i? _C'^Q DHW -(ch2)4co2ch2ch3 i? —C-N^J DHX -CH2S02NH2 II —c-fQ ι·
89531-960524.doc -95- 1343917 DIIY _ch2so2n(ch3)2 il -cO DHZ -(CH2)2NHS02H D1A -(ch2)2nhso2ch3 n DIB -H —c-i^ DIC -CH2C(0)NH2 i?厂' —C~N 0 DID -ch2c(o)n(ch3)2 DIE -c(o)cii2nhso2ch3 ff厂*λ —c—hi 0 DIF -(CH2)2C(0)NH2 1? Α~Λ 一c—hi p DIG -(ch2)2c(o)n(ch3)2 厂飞 —c—乂 。 DIH •c(o)(ch2)2nhso2ch3 —Lq DII -CH2C02CH3 —Lq DU -ch2co2ch2ch3 DIK -(CH2)2C02CH3 —Lq DIL -(ch2)2co2ch2ch3 -trQo DIM -(CH2)3C〇2CH3 89531-960524.doc •96- 1343917
DIN -(ch2)3co2ch2ch3 〇 t~~V DIO -(ch2)4co2ch3 II /~λ —C-吹 0 DIP _(ch2)4co2ch2ch3 —c-l^~~ DIQ -ch2so2nh2 n厂飞 —c-吹 b DIR -ch2so2n(ch3)2 M厂 —C-hi 0 DIS -(CH2)2NHS〇2H i?厂 —c-^ b DIT -(CH2)2NHS02CH3 J-rQ DIU -(CH2)3NHS〇2H •H DIV -(CH2)3NHS02H -C(0)NH2 D1W -(ch2)3nhso2h -COjCHs D1X -(CH2)3NHS02H -CHO D1Y -(CH2)3NHS〇2H -CN DIZ -(CH2)3NHS02H •ch3 DJA -(CH2)jNHS02H •c(o)nhch3 DJB -(ch2)3nhs〇2h -C(0)N(CH3)2 DJC -(CH2)3NHS02H S厂~\ —C—N N—CH3 \_/ DJD -(CH2)3NHS〇2H —Lq DJE -(CH2)3NHS02H II -c-rQ DJF -(CH2)3NHS02H i? /~Λ —C—N O 89531-960524.doc -97- 1343917 4.3製造4-四唑基-4-笨基p底啶化合物之古法 本發明4-四峻基-4-苯基成咬化合物可使用習知有機合成 及下列例示方法製造: 概圖1顯示製造4-四唑基-4-苯基哌啶化合物之方法,其中 Ri為- C(0)NZ2,其中各Z為-(C1-C4燒基)或二個Z及相接之氣 原子一起形成N-(4-R_4)-N'-l-哌啡基,氮》元基,氮咀基,吡 洛淀基’ 11底淀基’高喊淀基’峨洛基,或嗎琳基。溴酸1使 用亞硫醯氣轉化為溴醯基氯2(J. S. Pizey,Synthetic Reactions L65 (1974))。溴醯基氯2與22价1反應,選擇性在 鹼如Na2C〇3存在下,獲得反應性中間物3,其以4_氰基-4_ 苯基哌啶處理(概圖10),獲得氰基苯基化合物5 ^氰基苯基 化合物5以MeJnN3或Me3SiN3及氧化錫處理(S. j.
Wittenberg et al.s J. Org. Chem. 58:4134-41 41 (1993)),獲得 4-四唑基-4-苯基哌啶化合物6,其中Rig_c(〇)Nz2&G& 化合物6與〇1-乂反應,其中Gl為上述定義之G,除氫外, X為一個離去基,如鹵素,三氟甲磺酸基,甲磺酸基,或 苯磺酸基,獲得4-四唑基-4·苯基哌啶化合物7及8之混 物。化合物7及8使用習知方式分離,如矽膠層析,高性能 液態層析,或再結晶。式G1_x之化合物可由商業上獲得, 或使用習知有機合成方法製造。 8953l-960524.doc •98- 1343917 概圖1 H02C-W-(CH2)m+i-Br SOCI2> 1 CI-C(0)™W—(CH2)m+rBr 2
Z2NH Ν32〇〇3 4 Na^CO^/DMF^
m,p,q,R2及R3如上述定義,-W為-◦(AhXAq)-或 -C(H)(Ar3)-。 概圖2顯示製造4-四唑基-4-苯基哌啶化合物之方法,其中 1^為-(:02«_4。溴醯基氣2(概圖1)與R4OH反應,選擇性在鹼 如吡啶,4-二甲基胺基吡啶,三乙胺,或亨利(Hunig)鹼存 在下,獲得溴酯9。溴酯9與4-氰基-4-苯基哌啶4反應(概圖 89531-960524.doc -99- 1343917 10),獲得氰基苯基化合物ίο,其以Me3SnN3或Me3SiN3及氧 化錫處理(S. J. Wittenberg et al.,J· Org. Chem. 58:4134-4141 (1993)),獲得4-四唑基-4-苯基哌啶化合物11,其中1為 R40C(0)-及G為-H。化合物11與01乂反應,其中〇丨及)(如上 述定義,獲得4-四唑基-4-苯基哌啶化合物12及13之混合 物。化合物12及13可使用上述習知方式分離。 概圖2 a—C(0 卜 W-(CH2)mH-Br R4〇HR4〇-C(0)--W-(CH2)m+r-Br 2 9
m,p,q,R2 及 R3 如上述定義,-W-為-C(Ari)(Ar2)_ 或 -100- 89531-960524.doc -C(H)(Ar3)-。 概圖3顯示製造4-四唑基-4-苯基哌啶化合物之方法,其中 Rl為-C(0)NH(Ci-C4烷基)。化合物11(概圖2)以一種鹼安定 性保護基如菜磺醯胺,環己基胺基甲酸酯,丨,丨_二甲基 -2,2,2-三氯乙基胺基甲酸酯,n_(1_乙氧基)乙基,或一個相 似保 s蔓基(參見 T. W. Greene et al.,Protective Groups in Organic Synthesis 615_63 1 (1999))保護,獲得經保護之化合 物14。化合物14使用氫氧化物鹼,選擇性在甲醇存在下水 解’在處理後獲得酸15,其使用(CV^Ni^醯胺化,獲得經 保護之化合物16。化合物16使用一種強酸去保護(Greene,pp 615-631)’獲得4 -四吐基-4 -苯基喊咬化合物17,其中1^為 燒基)及G為-H。化合物Η與反應,其中 如上述定義’獲得4-四唑基-4-苯基哌啶化合物18及 19之混合物。化合物18及19可使用上述習知方式分離。 89531-960524.doc 101 - 1343917 概圖3 Γ
(CVC4 烷基)νη2
Η
m,ρ,q,R2 及 如上述定義,-W-為-C(Ar!)(Ar2)-或 -C(H)(Ar3)-。 89531-960524.doc -102- 1343917 概圖4顯示製造4-四唑基-4-苯基哌啶化合物之方法,其中 Ri.-CCCONHOH。酸15(概圖3)以NH2OH處理,獲得經保護 之化合物20,其使用強酸去保護(Greene pp. 6 1 5-63 1),獲得 4-四唑基-4-苯基哌啶化合物21,其中Rig-C^CONHOH及G 為-H。化合物21與01-乂反應,其中如上述定義,獲 得4-四唑基-4-苯基哌啶化合物22及23之混合物。化合物22 及23可使用上述習知方式分離。 概圖4 H0NH-C(0)-W-(CH2)m+1- 20
15 NH?OH H0NH-C(0)-W-(CH2)m+1—N 21
n:Gi
89531-960524.doc -103- 1343917 m,ρ,q,R2及R3如上述定義,-W-為-CCAr^Ar〗)-或 -C(H)(Ar3)-。 概圖5顯示製造4-四唑基-4-苯基哌啶化合物之方法,其中 1^為-11。溴化物24以4-氰基-4-苯基哌啶4處理,獲得氰基苯 基中間物25,其與Me3SnN3或Me3SiN3及氧化錫處理(S. J. Wittenberg et al., J. Org. Chem. 5 8:41 39-4141 (1993)),獲得 4-四唑基-4-苯基哌啶化合物26,其中心及-G為-H。化合物 26與01-乂反應,其中G1&X如上述定義,獲得4-四唑基-4-苯基哌啶化合物27及28之混合物。化合物27及28可使用上 述習知方式分離。 概圖5 H-W-(CH2)m+1—Br 24
H-W-iCHzW^. 26
89531-960524.doc -104-
1343917 m,p,q,R2 及 R3 如上述定義,-W-為-(^(Ar^Ara)-或 -C(H)(Ar3)-。 概圖6顯示製造4-四唑基-4-苯基哌啶化合物之方法,其中 1^為-CHO。4-四唑基-4-苯基哌啶化合物27(概圖5)以強鹼如 NaNH2處理及以二甲基甲醯胺淬火(參見U_ T. Mueller Westerhoffet al.,Synlett 975 (1994)),處理後獲得經保護之 醛28。經保護之醛28去保護(Greene,ρρ· 615-631),獲得4-四唑基-4-苯基咮啶化合物29,其中1^為-CHO及-G為-Η。化 合物29與01-乂反應,其中如上述定義,獲得4-四唑基 -4-苯基哌啶化合物30及31之混合物*其可使用上述習知方 式分離。 概圖6
89531-960524.doc -105- 1343917
0HC-W-(CH2)m+1- 30
m,P,q,R2 及 R3 如上述定義 ’ _ w-為-C(Ari)(Ar2)-或 -C(H)(Ar3)-。 概圖7顯示製造4_四嗓基-4-苯基瓜淀化合物之方法,其中 Ri為(CVC4烷基)。化合物27(概圖5)以強鹼如NaNH2處理及 以(Ci-CU燒基)-X淬火’其中X如上述定義,獲得經保護之 化合物32。化合物32去保護(Greene,pp. 615-631),獲得4- 四唑基-4-苯基哌啶化合物33,其中心為⑷厂^烷基) Η。化合物33與01-又反應’其中如上述定義,獲得 四也基-4-苯基哌啶化合物34及35之混合物,其可使用上述 習知方式分離。 概圖7 27 NaNH2 ^
89531-960524.doc -106- 1343917 Η Λι
GvX +
m,ρ,q,R2 及 R3 如上述定義,-W-為-C(Ari)(Ar2)-或 -C(H)(Ar3)- 〇 is,_ β 概圖8顯示製造4-四唑基-4-苯基哌啶化合物之方法,其中 1^為-(:(0)1^112。經保護之酯14(概圖3)以NH3處理(參見Μ· B. Smith et al., March's Advanced Organic Chemistry: Reactions Mechanims,and Structure 5 10-5 11 (200 1)),獲得經保護之 胺36,其去保護(Greene,pp_ 615-631),獲得4-四唑基-4-苯 基哌啶化合物37,其中Ι^4-(:(0)ΝΗ2及-G為-H。化合物37 與01-又反應,其中G1&X如上述定義,獲得4-四唑基-4-苯 基哌啶化合物38及39之混合物,其可使用上述習知方式分 離。 89531-960524.doc •107- 1343917 概圖8 14 NH3 /
m,p,q,R2 及 R3 如上述定義,-W-為-C(Ari)(Ar2)-或 -C(H)(Ar3)- 〇 概圖9顯示製造4-四吐基-4-苯基喊咬化合物之方法,其中 心為-CN。4-四唑基-4-苯基哌啶化合物37(概圖8)以Ph3P及 CCU處理(W.J. Rogers,Synthesis 4J_ (1997)),獲得 4-四攻基 -4-苯基哌啶化合物40,其中RtS-CN及G為-Η。化合物40 與01-又反應,其中如上述定義,獲得4-四唑基-4-苯 89531-960524.doc -108- 1343917 基哌啶化合物41及42之混合物,其可使用上述習知方式分 離。 概圖9
-C(H)(Ar3)-。 概圖10顯示製造4-氰基-4-苯基哌啶4之方法。(R3)p取代 之胺基二醇43使用苯甲基氣44於NaHC03/H20中N-烷基 化,獲得N-苯甲基二醇45,其使用SOCl2氯化,獲得二氯化 物46。二氯化物46與去質子化(NaNH2於甲苯中)之苯甲基氰 化物47縮合,獲得苯甲基化合物48,其使用H2及Pd/C(95°/〇 EtOH)去苯甲基化,獲得4-氰基-4-苯基哌啶4。 89531-960524.doc -109- 1343917 概圖ίο
1. NaHC03 2. 苯甲基氣(44)
某些4-四唑基-4-苯基哌啶化合物可能具有不對稱中心, ‘ 因此以不同對映體及非對映體形式存在。4-四唑基-4-苯基 .. 哌啶化合物可呈光學異構物或非對映體形式。因此,本發 、 明包括4-四唑基-4-苯基哌啶化合物及其用途,如本文中所 - 89531-960524.doc -110- 述’呈光學異構物,非對映體,及其混合物,包括消旋混 合物之形式。 此外’某些4-四唑基-4-苯基哌啶化合物可以互變體存 在。例如,若G為Η,式1(a)及式1(b)之某些4-四唑基-4-苯基 . 哌哫化合物(例如結構ΑΑΤ及ΒΑΤ)及式1(c)及式1(d)之某些 4-四唾基-4-苯基哌啶化合物(例如結構cAT及DAT)相互為 互變體。本文中所述之各結構包括其所有互變體,各包括 在本發明中’不論是否特別揭示,及不論本文中所示之互 又體疋否表一種互變體相對於任何其他互變體為過量。因 此,本發明亦包括4_四唑基_4苯基喊啶化合物及其用途, 如本文中所述,呈互變體形式β 此外,4-四唑基·4_苯基哌啶化合物之一或多個氫,碳, 或其他原子可以氫,碳,或其他原子之一個同位素替代。 本發明所包括之化合物可用作代謝藥物動力學研究及結合 分析之研究及診斷工具。 4,4 峻基-4-笨基呔嗆化合物々法年同;令 根據本發明’ 4_四唑基-4-苯基哌啶化合物施用於一種動 物,在一個具體實施例中為喷乳類’在另一個具體實施例 中為人類,以治療或預防疼痛。4_四唑基苯基哌啶化合 物可用於治療或預防急性或慢性疼痛。例如,4四唑基· 苯基㈣化合物可用於,但不限於,治療或預防癌症疼痛, 中樞性疼痛,分娩痛’心肌梗塞痛,騰臟痛,結腸痛,手 術後疼痛,頭痛,肌肉痛,及與加護⑽咖〜⑽)有關之, 疼痛。 . 89531-960524.doc -111 - 1343917 4四唑基-4-苯基哌啶化合物亦可用於抑制,預防,或治 療與動物發炎或發炎疾病有關之疼痛。所抑制,治療,或 預防之疼痛可能與-種發炎疾病之發炎有關,其可能由於> 身體組織之發炎引起’其可能為—種局部發炎反應及/或一 * 種全身性發炎。例如,4·四♦基_4•苯基喊唆化合物可用以 抑制,治療,或預防與下列發炎疾病有關之疼痛,包括, 但不限於:器官移植排斥;器官移植所產生之再氧化傷害 (參見 Grupp et al. J, Mol. Cell Cardiol. 3 1:297 303 (1999)), 包括’但不限於,心,肺,肝,或腎之移植丨關節之慢性寒· 發炎疾病,包括關節炎,類風濕性關節炎,骨關節炎,及 與骨骼吸收增加有關之骨骼疾病;發炎性腸疾病,如迴腸 炎,消癌性結腸炎,貝瑞特氏(Barrett,s)徵候群,及克隆氏 (Crohn s)症,發炎性肺病,如氣喘,成人呼吸週迫徵候群,
及慢性阻塞性呼吸道疾病;眼睛之發炎疾病,包括角膜營 養不良’沙眼’墙尾絲蟲病’葡萄膜炎,交感性眼炎,及 眼内炎;齒齦慢性發炎疾病’包括齒齦炎及牙周病;肺結 核;麻風;腎之發炎疾病’包括尿毒症之併發症,腎絲球 腎炎’及腎變病;皮膚之發炎疾病,包括硬化性皮炎,牛 皮癖,及濕疹;中樞神經系統之發炎疾病,包括神經系統 之慢性髓鞘脫失疾病,多發性硬化,aidS有關之神經變性 及阿滋海默(Alzheimer’s)症’感染性腦膜炎,腦脊髓炎,巴 金森氏(Parkinson's)症,亨丁頓氏(Huntington's)症,肌萎缩 性側索硬化’及病毒或自體免疫性腦炎;自體免疫疾病, 包括第I型及第II型糖尿病;糖尿病併發症,包括,但不限 89531-960524.doc -112· 1343917 於,糖尿病性白内障,青光眼,視網膜病,腎病(如微鋁尿 症(microa丨uminuria)及進行糖尿病性腎病),多神經病單神 經病,自主神經病,腳壞疽,動脈粥瘤硬化性冠狀動脈疾 ‘ 病’末稍動脈疾病’非_ (nonketotic)高血糖滲透過速昏迷,. 腳潰瘍,關節問題’及皮膚或黏膜併發症(如感染,脛斑(shin spot) ’ 一種念珠菌感染,或糖尿病脂性漸進性壞死免疫 複合血管炎,全身性紅斑性狼瘡(SLE);心臟之發炎疾病, 如心肌病,絕血性心臟病高膽固醇血症,及動脈粥瘤硬化; 及各種其他可能具有顯著發炎之疾病,包括初期子癇,慢 性肝衰竭,腦及脊髓創傷,及癌症。4-四唑基_4-苯基哌啶 化合物亦可用於抑制,治療,或預防與發炎疾病有關之疼 痛,其可為例如身體之全身性發炎,例如革蘭陽性或革蘭 陰性休克’出血性或過敏性休克’或癌症化學治療對於原 發炎細胞動素(cytokines)反應所引發之休克,例如與原發炎 細胞動素有關之休克。該休克可能由例如癌症治療施用之 化學治療劑所引發》 在另一具體實施例中,4-四唑基-4-苯基哌啶化合物施用 於一種動物,在一個具體實施例中為一種哺乳類,在另一 具體實施例中為人類,用於治療或預防腹瀉 。4-四唑基-4- 苯基旅咬化合物可用於治療或預防急性或慢性腹瀉。例, 如’ 4-四吐基-4-苯基哌啶化合物可用於,但不限於,治療 :· 或預防一種病毒,例如,但不限於,諾瓦克(N〇rwalk)病毒, 似諾瓦克病毒’輪狀病毒’及巨細胞病毒,原生動物’例 如’但不限於’吉拉德氏菌(Girardia iamia),隱抱菌 89531-960524.doc •113· 1343917 (Crpytosporidium)及溶組織内阿米巴(Entamoeba histolytica);及細菌,包括,但不限於,金黃色葡萄球菌 (Stapylococcus aureus),蠛狀芽孢桿菌(Bacillus cereus),產 氣莢膜梭狀芽跑桿菌(Clostridium perfringens),腸毒性大腸 桿菌(E. coli),霍亂娘菌(Vibrio cholera),腸出血性大腸桿 菌(E. coli)0157: H5’ 副出血性旅菌(Vibrio parahaemolyticus) ,梭狀芽孢桿菌(Clostridium difficile),空腸彎曲桿菌
(Campylobacter jejuni),沙門氏菌(Salmonella),腸侵襲性大 腸桿菌(E. coli),產氣單抱菌(Aeromonas),鄰單胞菌 (Plesiomonas) ’ 結腸耶氏样菌(Yersinia enterocolitica),披衣 菌(Chlamydia),淋病雙球菌(Nisseria gonorrhoeae),及單核 球李斯特菌(Listeria monocytogenes)所引起之急性腹消。例 如,4-四唑基-4-苯基哌啶化合物可用於治療或預防慢性腹 瀉,包括’但不限於,滲透性腹瀉,分泌性腹瀉,或由一 種發炎症狀,吸收不良徵候群,運動性違常,及慢性感染 所造成者。 申請人相信 不像傳統類鴉片(opioid)激動劑及非類固
抗發炎劑,4-四唑基-4-苯基哌啶化合物不顯著通過血腦障 壁。因此,申請人相信有效量4·四唑基_4_苯基哌啶化合物 施用於一種動物產生較少副作用,包括呼吸抑制,不欲之 欣快,鎮靜,便秘,耐藥性增加,及藥物依賴性增加,其 可能由施用傳統類鴉片激動劑或非類醇抗發炎劑所產生。 在-個具體實施例中,有效量4_四吐基_4苯基味喊化合物 施用於一種動物不產生上述副作用。因此,在某些具體實 89531-960524.doc _ 114· 施例中,本發明方法包括治療或預防疼痛,減少或去除— 或多個上述副作用。 不欲為理論所限’相信4-四唑基-4-苯基哌啶化合物為激 動劑’可刺激一個類鴉片受體。 本發明亦關於刺激一個細胞内類鴉片受體功能之方法, 包括使一個可表現類鴉片受體之細胞接觸有效量之4_四唑 基-4-苯基哌啶化合物。該方法亦可用於刺激活體内在一 種動物中,在一個具體實施例中為人類,一個細胞内類鸦. 片受體之功能,由使一種動物中一個可表現類鴣片受體之 細胞接觸有效量之4-四唑基-4-苯基哌啶化合物β在一個具 體實施例中,該方法可用於治療或預防一種動物之疼痛或 腹瀉。腦组織,脊髓組織,免疫細胞,胃腸道細胞,及主 要傳入神經細胞為可表現類鸦片受體之組織及/或細胞之 實例。該方法在活體外可用於例如一個可選擇表現類鴉片 受體之細胞之分析。 4.4.1治療/預防性施用及本發明組合物 由於其活性,4-四唑基_4_苯基哌啶化合物可用於獸醫及 人類醫學。如上述,4-四唑基-4-笨基哌啶化合物可用於需 要之動物治療或預防疼痛或腹填。 當施用於一種動物時,4-四唑基_4-苯基哌啶化合物可作 為一種包含醫藥可接受載劑或賦形劑之醫藥組合物之一個 成份施用。本發明包含一種4_四唑基_4苯基哌啶化合物之 組合物在一個具體實施例中經口施用。本發明組合物亦可 以任何其他合宜途徑施用,例如由注入或團式(b〇lus)注 89531-960524.doc -115- 1343917 射’經由上皮或黏膜皮膚襯裡(例如口腔黏膜,直腸黏膜, 及腸黏膜等)吸收,且可與另一種治療劑—起施用。可以全 身或局部施用.各種輸送系統已知,例如包膠於脂小體,- 微粒子,微膠囊,膠囊等中,可用於施用4·四唑基_4_苯基 . 哌啶化合物。 施用方法包括,但不限於,經皮内,經肌肉内,經腹膜 内,經靜脈内,經皮下,經鼻内,經硬膜外,經口,經舌 下,經腦内,經陰道内,經皮,經直腸,由吸入,或局部, 特別是經耳’冑,眼,或皮膚。施用方式由醫生決定。在|籲 大部份情況,施用可造成4·四唑基·4_苯基哌啶化合物釋入 血流。 在特定具體實施例中,較佳局部施用4_四唑基_4_苯基哌 呢化合物。其可由例如’但不限於,外科手術期間局部注 入,局部施用,例如在外科手術後與傷口敷料結合,以注 射’以導管’以栓劑,或以植人,該植人物為—種多孔, 非多孔’或明膠材料’包括膜’如秒銘(sialasUc)膜,或纖 1· 亦可肺施用’例如由使用—個吸人器或霧化器,以— 種氣溶膠化劑調配’或在一種氟碳或合成之肺表面活性劑 中經由灌注。在某些具體實施例中’ 4-四吐基-4-苯基旅啶· 化口物可傳統黏合劑及賦形劑(如三酸甘油酯)調配呈栓劑。 在另一具體實施例中,4-四峻基-4-苯基㈣化合物可於·· 一種小囊’特別是脂小體中輸送(參見Langer,Science趣, 1527-1533 (1990)及Treat et al,u,酣s & 加仉咖打 · 89531-960524.doc • 116- 1343917
Infectious Disease and Cancer 317-327 and 353-365 (1989)) ° 在另一具體實施例中,4-四唑基-4-苯基哌啶化合物可以 一種控制釋放系統輸送(參見例如Goodson,in Medical Applications of Controlled Release,上述,vol· 2, ρρ· 115-138 (1984))。可使用 Langer,Science 249:1527-1533 (1990)之回
顧中所討論之其他控制釋放系統。在一個具體實施例中, 可使用一種系(Langer,Science 249: 1527-1533 (1990); Sefton, CRC Crit. Ref. Biomed. Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980);及 Saudek et al” N. Engl. J. Med. 321:574 (1989))。在另一具體實施例中,可使用聚合 物質(參見 Medical Application of Controlled Release (Langer and Wise eds., 1974); Controlled Drug Bioavailability, Drug Product Design and Performance (Smolen and Ball eds., 1984); Ranger and Peppas, J. Macromol. Sci. Rev. Macromol. Chem. 23:61 (1983); Levy et al.,Science 228:190 (1985); During et al., Ann. Neurol. 2_1:35 1 (1989);及 Howard et al., J. Neurosurg. 11:105 (1989))。在另一具體實施例中,一個控制釋放系統< 可放於接近4-四唑基-4-苯基哌啶化合物之目標,因此僅需 要一部份系統劑量。 本發明組合物可選擇性包含適量之一種醫藥可接受賦形 劑以提供適合施用於動物之形式。 該醫藥賦形劑可為液體,如水及油,包括石油,動物, 植物,或合成來源者,如花生油,大豆油,礦油,麻油等。 醫藥賦形劑可為食鹽水,金合歡膠,明膠,澱粉糊,滑石, 89531-960524.doc -117- 1343917 角蛋白’膠態以’脉等。此外,可使用輔助劑,安定劑, 增稠劑,潤滑劑,及著色劑。當施用於動物時,醫藥可接 又賦形劑可滅菌。當4_四吨基_4_苯基喊淀化合物經靜脈内 施用時’水為特別有用之賦形劑。食鹽水溶液及右旋糖水· 溶液及甘油溶液亦可用作液體賦形劑,特別用於注射溶 液7適a之醫藥賦形劑亦包括澱粉,葡萄糖,乳糖,蔗糖, 月膠麥芽’米,麵粉,白堊,碎膠,硬脂酸納,一硬脂 酸甘油酯,滑石,氯化鈉,乾燥脫脂牛奶,甘油,丙二醇, 水乙醇等。若需要,本發明組合物亦可含有少量潤濕劑象· 或乳化劑或pH緩衝劑。 適合4-四唑基_4-苯基哌啶化合物經靜脈内施用之醫藥可 接受載劑或賦形劑包括,但不限於,生理(約0.9%)食鹽水, 約25至約30%聚乙二醇("PEG")以食鹽水或水稀釋,及約2 至約3 0%經基丙基β_環糊精以水稀釋。 適合4-四唑基-4-苯基哌啶化合物經腹膜内施用之醫藥可 接受載劑或賦形劑包括,但不限於,生理(約0.9%)食鹽水, 約25至約30% PEG以食鹽水或水稀釋,約25至約3〇%丙二醇 (PG)以食鹽水或水稀釋,及約2至約3〇%經基丙基β_環糊精 以水稀釋。 適合4-四唑基-4-苯基哌啶化合物經皮下及經肌肉内施用 之醫藥可接受載劑或賦形劑包拾,但不限於,水,生理(約 0.9%)食鹽水,約25至約30% PEG以食鹽水或水稀釋,及約 2 5至約3 0 % P G以食鹽水或水稀釋。 適合4-四唑基-4-苯基哌啶化合物經口施用之醫藥可接受 89531-960524.doc -118· 1343917 載劑或賦形齊】包括,但不限於,水,生理(約〇 9%)食鹽水, 約25至約30%聚乙二醇PEG以食鹽水或水稀釋約2至約 30%羥基丙基β-環糊精以水稀釋,約25至約3〇% pG以食鹽· 水或水稀釋,及約i至約5%甲基纖維素以水稀釋。 . 適合4-四唑基-4-苯基哌啶化合物經腦室内及經椎管内施 用之醫藥可接受載劑或賦形劑包括,但不限於,生理(約 0.9%)食鹽水。 本發明組合物可呈溶液,懸浮液,乳液,錠,藥丸,顆 粒,膠囊,含有液體之膠囊,粉末,持續釋放調配物,检t籲 劑,氣膠,喷液,懸浮液,或任何其他適合使用之形式。 在一個具體實施例中,組合物呈膠囊形式(參見例如美國專 利5,698,155)。適合之醫藥賦形劑之其他實例述於 Remington's Pharmaceutical Sciences 1447-1676 (Alfonso R. Gennaro ed.,19th ed_ 1995),併入本文供參考。 在一個具體實施例中,4-四唑基苯基哌啶化合物係根 據適合經口施用於動物,特別是人類,之組合物之一般程 序調配。經口輸送之組合物可呈例如錠,含片(1〇zenges)籲 水或油性懸浮液,顆粒,粉末,乳液,膠囊,糖漿,或酏 劑之形式。經口施用之組合物可含有防腐劑,著色劑,及 一或多種劑,例如甜化劑,如果糖,阿斯巴甜(aspartame),. 或糖精,及周味劑,如薄荷,白珠樹(wintergreen)之油,或 櫻桃,以提供一種醫藥可口製劑。此外,若呈錠或藥丸形. η 式’組合物可Μ塗覆以延遲崩解及吸收於胃腸道,因而提 供持續作用一段延長期間。選擇性滲透膜包圍一種滲透活 •119- 89531-960524.doc 1343917 包=合物亦適合經口施用之-合物,些形式中, 環境液體為驅動化合物所吸收,其膨脹而經一 二?換樂劑或藥劑組合物。這些輸送形式可提供一種‘ 1輸送形式’相對於立即釋放調配物之穗狀. Ρ1 〇形式。亦可使用-種時間延遲物質,如一硬脂酸甘 /酿或硬脂酸甘油酿。口服組合物可包括標準賦形劑,如 甘露糖醇’乳糖’澱粉’硬脂酸鎮,糖精執,纖維素,及 碳酸鎂。在-個具體實施例中,賦形劑為醫藥級。 在另-具體實施例中,4·心基_4苯基錢化合物可調 配用於靜脈内施用。在一個具體實施例中,用於靜脈内施 用之組合物包含該化合物溶於滅菌之等張水性緩衝液中。 若需要’組合物亦可包括一種溶解劑。用於靜脈内施用之 組合物可選擇性包括一種局部麻醉劑,如利多卡因 (lignocaine),以減少注射部位之疼痛。一般而言各成份 係分開提供,或混合在一起呈單位劑形,例如呈乾燥之凍 乾知末或播水濃縮物於一個密封容器如安說或小藥囊 (sachette)中顯示活性劑之量。若4_四唑基_4苯基哌啶化合 物以注入施用,彼等可由一個含有滅菌醫藥級水或食鹽水 之注入瓶配藥。若4-四唑基·4·苯基哌啶化合物由注射施 用’可提供一安瓿注射用滅菌水或食鹽水以便在施用前可. 混合各成份。 4-四唑基-4-苯基哌啶化合物可以控制釋放方式或由熟習 技藝人士周知之輸送裝置施用。實例包括,但不限於,美 國專利 3,845,770 ; 3,916,899 ; 3,536,8〇9 ; 3,598,123 ; 89531-960524.doc -120- 1343917 4,008,719 ; 5,674,533 ; 5,059,595 ; 5,591,767 ; 5,120,548 ; 5’073,543 ; 5,639,476 ; 5,354,556 ;及 5,733,566 中所述者, 各併入本文供參考。該劑形可用於提供緩慢或控制釋放一 或多種活性成份’例如使用經基丙基曱基纖維素,其他聚 . 合物基質,凝膠,滲透膜,滲透系統,多層塗層,微粒子 脂小體,微小球,或其合併物,以提供所欲各種比例之釋 放情況。可輕易選擇熟習技藝人士已知之適合控制釋放調 配物,包括本文中所述者,與4_四唑基_4_苯基哌啶化合物 使用。因此,本發明包括適合口服施用之單一單位劑形, 例如,但不限於,適合控制釋放之錠,膠囊,凝膠膠囊 (gelcaps) ’ 及小膠囊(eaplets)。 控制釋放之醫藥組合物可具有改良非控制釋放者所達成 之藥物治療之普通目標。在一個具體實施例中,一種控制 釋放之組合物包含最少量之4-四唑基-4-苯基哌啶化合物以 在最少時間内治療或控制症狀。控制釋放組合物之優點包 括延長藥物之活性,減少施用頻率,及增加病人之順從性。 此外,控制釋放之組合物可有利地影響作關始之時間或|籲 其他特徵’如4’四吐基.4-苯基喊淀化合物之血液濃度,因 而減少副(例如不良)作用之發生。 在個具體實施例中,控制釋放之組合物最初可釋放一. S量4四唆基_4_苯基喊咬化合物以立即治療或預防疼痛或 腹瀉,並逐漸及繼續釋放其他量之4·四唑基-4-苯基哌啶化·、 合物以維持治療或預防作用之量經歷一段延長期間。為維 持此恆定4 m h4 ‘ -峻基-4-苯基喊咬化合物於體内,4-四吐 89531-960524.doc • 121 - 1343917 基_4·苯基喊啶化合物可以替代身體代謝及排泄4-四唑基 -4-苯基哌啶化合物之量之速率由劑量形式釋放。活性成份 之控制釋放可以各種情況刺激,包括,但不限於,pH之改 變’溫度之改變,酶之濃度或可利用性,水之濃度或可利 用性,或其他生理情況或化合物。 可有效治療或預防疼痛或腹瀉之4-四唑基-4-苯基哌啶化 合物之量可依引起疼痛之疾病或症狀之本質或嚴重性而 定,可由標準臨床技術決定。此外,可選擇性使用活體外
或活體内分析以協助鑑定最適有效劑量。所用之精確劑量 亦可依施用之途徑及疼痛或腹瀉之程度或嚴重性而定,應 根據醫生之判斷及各病人之情況由公開之臨床研究決定。 然而,適合之有效劑量範圍為約每4小時約1 〇微克至約2500 毫克’雖然典型約1〇〇毫克或以下。在一個具體實施例中, 有效劑量範圍為約每4小時約0,01毫克至約ι〇〇毫克4_四吨 基-4 -苯基β底喊化合物,在另 0.020毫克至約50毫克,在另 0.025毫克至約20毫克。本
一具體實施例中,約每4小時約 一具體實施例中’約每4小時約 文中所述之劑量為所施用之總 量;亦即’若施用多於一種4-四唑基-4-苯基哌啶化合物, 有效劑量為所施用之總量。 若一個可表現類鴉片受體之細胞在活體外與一種4-四吐 基-4-苯基哌啶化合物接觸,有效量範園典型為約〇 〇1毫克 至約1〇〇毫克/升’在一個具體實施例中為約01毫克至約5〇 毫克/升,在另一具體實施例中為約1亳克至約2〇毫克/升, 一種醫藥可接受載劑或賦形劑之溶液或懸浮液。 89531-960524.doc -122- 右個可表現類鴉片受體之細胞在活體内與一種4-四唑 基_4_苯基^化合物接觸,有效量範1S典型為約G.01毫克 至約100毫克’公斤體重/天’在-個具體實施例中為約0.1毫 克至約50¾克/公斤體重’天,在另一具體實施例中為約(毫 克至約20毫克/公斤體重/天。 ^ 4-四唑基_4_苯基哌啶化合物可在用於人類之前在活體外 或活體内分析其治療或預防疼痛或腹瀉之能力。可使用動 物模型系統以證明4_四唑基_4_苯基哌啶化合物之安全性或 功效。 本發明用於治療或預防動物疼痛或腹瀉之方法可另包含 對於該動物施用有效量之另一種治療劑。 本發明用於刺激一個細胞内類鴉片受體功能之方法可另 包ό使該細胞接觸有效量之另___種治療劑。 其他治療劑之實例包括,但不限於,一種類鴉片激動劑, 非類稿片止痛劑,非類固醇抗發炎劑,抗偏頭痛劑,CoxW 抑制劑’止吐劑’ β-腎上腺素激導性(adrenergic)阻斷劑, 抗痙攣劑,抗抑鬱劑,Ca2 +通道阻斷劑,抗癌劑,抗焦慮 劑,治療或預防上癮之劑,及其混合物。 其他治療劑之有效量為熟習技藝人士周知。然而,熟習 技藝人士可決定其他治療劑之最適有效量範圍。在本發明 之一個具體實施例中’若另一治療劑施用於一種動物,則 4-四唑基-4-苯基喊啶化合物之有效量低於未施用該另一治 療劑之有效量。在此情況,未受限於理論,相信4_四吐基 苯基哌啶化合物及其他治療劑係協同作用以治療或預防疼 89531-960524.doc • 123- 1343917
痛或腹瀉。 有用之類鴉片激動劑之實例包括,但不限於,阿芬坦尼 (alfentanil),晞丙苯喊淀(allylprodine),安那度 (alphaprodine),安尼樂利定(anileridine),苯甲基嗎啡 (benzylmorphine),貝紀查麥(bezitramide),布潘据啡 (buprenorphine),布脫芬語(butorphanol),氯硝胺咪 (clonirazene),可待因(codeine),二氫脫氧嗎啡(desomorphine) ,右旋嗎酿胺(dextromoramide),戴卓辛(dezocine),雙胺丙 酿胺(diampromide),二乙酿嗎啡 _ (diamorphone),二氫可待 因,二氩嗎讲,戴曼崎嗓(dimenoxadol),戴曼非坦据 (dimepheptanol),二甲基 p塞吩丁酿胺(dimethylthiambutene), 嗎苯丁 ^(dioxaphetyl butyrate),地 p比潘酮(dipipanone),伊 它卓辛(eptazocine),乙庚井(ethoheptazine),乙基甲基p塞吩 丁醯胺(ethylmethylthiambutene),乙基嗎啡,伊頓尼金 (etonitazene),芬太尼(fentanyl),海洛英(heroin),氫可待因 酮(hydrocodone),氫嗎啡酮(hydromorphone),經基 展替咬 (hydroxypethidine),異美沙酮(isomethadone),鲷經基喊替 咬(ketobemidone),幾曱左嗎喃(levorphanol),左苯醯甲嗎喃 (levophenacylmorphan),洛芬坦尼(lofentanil),喊替咬 (meperidine),美它金諾(meptazinol),間吐新(metazocine), 美沙酉同(methazone),甲氫嗎啡酮(metopon),嗎啡 (morphine),爷嗎啡十四酸酿(myrophine),環丁甲輕氮嗎啡 (nalbuphine),那碎因(narceine),二 If 酿嗎啡(nicomorphine) ,左旋3-輕嗎啡燒(norlevorphanol),去甲美沙酿| 89531-960524.doc -124- 1343917
(normethadone),稀丙嗎啡(nalorphine),去甲嗎啡 (normorphine),二苯〇底己酮(norpipanone),牙鳥片(opium),氧 可酮(oxycodone),#二氫嗎啡酮(oxymorphone),鴣片全驗 (papaveretum)’ 鎮痛新(pentazocine),非那多松(phenadoxone) ,經苯乙嗎喃(phenomorphan),那爾芬(phenazocine),苯丙 苯旅醋(phenoperidine),去痛定(piminodine),氰苯雙底醯胺 (piritramide),丙庚 11 井(proheptazine),二甲喊替咬(promedol) ,異丙11底替淀(properidine),丙p比胺(propiram),丙氧吩 (propoxyphene),卩塞味苯胺(sufentanil),痛立定(tilidine)’ 反 胺苯環醇(tramadol),其醫藥可接受鹽,及其混合物。 在某些具體實施例中,類鴉片激動劑係選自可待因,氫 嗎啡S同,氫可待因酮,氧可S同,二氫可待因,二氫嗎啡, 嗎啡,反胺苯環醇,羥二氫嗎啡,其醫藥可接受鹽,及其 混合物。 有用之非類鴉片止痛劑之實例包括非類固醇抗發炎劑, 如阿斯匹靈(aspirin),異丁苯丙酸(ibuprofen),二氣胺苯乙 酸(diclofenac),曱氧茶丙酸(naproxen),苯p号丙芬彳 (benoxaprofen),氟聯苯丙酸(flurbiprofen),苯氧苯丙酸 (fenoprofen),氟丁吩(flubufen),g同丙吩(ketoprofen),節酮 苯丙酸(indoprofen),p比丙芬(piroprofen),卡丙吩(carprofen) · ,p号普哨 (oxaprozin),丙嗎丙吩(pramoprofen),谬若丙吩 (muroprofen),三 p号丙吩(trioxaprofen),,塞丙吩(suprofen), 胺丙吩(aminoprofen),苯p塞丙酸(tiaprofenic acid),氟苯丙酸 (fluprofen),布可西酸(bucloxic acid),消炎痛(indomethacin) 89531-960524.doc -125- ,蘇靈大(sulindac),甲苯酿p比酸(tolmetin),氯苯酿二曱基p比 嘻乙酸(zomepirac),塞庚乙酸(tiopinac),疊氮叫丨酸 (zidometacin) ’ 乙醯美它辛(acemetacin),雙苯 p塞酸(fentiazac) « ,可利丹内(clidanac) ’奥斯賓内(oxpinac),甲滅酸(mefenamic acid),甲氯滅酸(meclofenamic acid),氟滅酸(flufenamic acid),氮氟滅酸(niflumic acid),鄰甲氣滅酸(tolfenamic acid),二氟苯水楊酸(diflurisal),氟苯乙醯水楊酸 (flufenisal),ρ比氧 p塞啡(piroxicam),《>塞氧 塞》^(sudoxicam), 異p号p塞醯胺(isoxicam),及其醫藥可接受鹽,及其混合物。 其他適合之非類鴉片止痛劑之實例包括下列非限制之化學 種類之止痛劑,退熱藥,非類固醇抗發炎藥;水楊酸衍生物, 包括阿斯匹靈(aspirin),水楊酸鈉,膽素三水楊酸鎂,水楊 醯水楊酸酯(salsalate),二氟苯水楊酸(diflunisal),水楊醯基 水楊酸,水楊酸偶氮續胺峨咬(sulfasalazine),及歐沙拉〃井 (olsalazin);對-胺基齡衍生物,包括乙酿胺齡·(acetaminophen) 及非那西汀(phenacetin);吲嗓及茚醋酸,包括消炎痛 (indomethacin),蘇靈大(suindac),及伊托杜拉克(etodolac);暴響 雜芳基醋酸,包括甲苯醯吡酸(tolmetin),二氣胺苯乙酸 (diclofenac),及克托羅拉克(ketorolac);鄰胺苯甲酸(滅酸鹽 (fenamates)),包括甲滅酸(mefenamic acid)及曱氣滅酸 . (meclofenamic acid);烯醇酸,包括p号 V»塞酿胺(oxicams),(口 比 氧p塞啡(piroxicam),坦4 »塞酿胺(tenoxicam)),及p比吐咬二酮 (苯基保泰松(phenylbutazone), 氧吩沙泰松 (oxyphenthartazone));及燒酉同,包括那布米嗣(nabumetone) ° 89531-960524.doc -126- 1343917 NSAIDs之車交詳細說明請參見Paul A. Insel, Analgesic Antipyretic and Antiinflammatory Agents and Drugs Employed in the Treatment of Gout, in Goodman & Gilman's The Pharmacological Basis of Therapeutics 617-57 (Perry B. Molinhoff and Raymond W. Ruddon eds., 9th ed 1996) and Glen R. Hanson, Anlgesic, Antipyretic and Anti Inflammatory Drugs in Remington: The Science and Practice of Pharmacy Vo 1 II 1196-1221 (A.R. Gennaro ed. 19th ed. 1995),其全部併 入本文供參考。適合之Cox-II抑制劑及5-脂肪氧化酶抑制劑 及其合併物述於美國專利6,136,839。Cox II抑制劑包括,但 不限於,若非考克斯(rofecoxib)及塞利考克斯(celecoxib)。 有用之抗偏頭痛劑之實例包括,但不限於,阿吡若哌 (alpiropride),二氫麥角胺,多拉西創(dolasetron),麥角柯 靈(ergocornine),麥角異柯靈(ergocorninine),麥角環肽 (ergocryptine),麥角,麥角胺,三氟甲地孕嗣(flumedroxone acetate),風那11 井(fonazine),李舍來德(lisuride),羅美立11 井 (lomerizine),二曱麥角新驗(methysergide),苯咬 11号庚胺 (oxetorone),苯 ρ塞咬(pizotyline),及其混合物。 其他治療劑亦可為一種止吐劑。有用之止吐劑包括,但 不限於,滅吐靈(metoclopromide),同喊立酬(domperidone), 甲喊氣丙哨·(prochloperazine),異丙?井(promethazine),氯丙 月井(chlorpromazine),三甲氧苯酿胺(trimethobenzamide),翁 丹西重(ondansetron),葛尼西重(granisetron),經口井 (hydroxyzine),乙酿基白胺酸(acetylleucine)—乙醇胺,苯p比 89531-960524.doc -127- 1343917 三吐(alizapride),氮雜西重(azasetron),苯<»奎縫胺 (benzquinamide),胺醇酷茶驗(bietanautine),漠普來 (bromopride),安其敏(buclizine),克雷伯普來(clebopride), 赛克利p井(cyclizine),氣茶驗苯海拉明(dimenhydrinate),二 苯喊淀丁醇(diphenidol),多拉西重(dolasetron),敏克靜 (meclizine),稀丁硫比妥(methallatal),甲項味丙畊 (metopimazine),庚苯 p比 _ (nabilone),氮經成丙井 (oxyperndyl),叶匕喊嗎 口井(pipamazine),·茨箸胺(scopolamine) ,舒必利(sulpiride),四氫大麻盼(tetrahydrocannabinol),硫 I9 乙旅丙 井(thiethylperazine),硫丙拉 0井(thioproperazine),脫 p比西重(tropisetron),及其混合物。 有用之β-腎上腺素激導性阻斷劑之實例包括,但不限 於,醋丁酿心安(acebutolol),缔丙心安(alprenolol),阿莫蘇 拉伯(amosulabol),阿若丁諾羅(arotinolol),胺酿心安 (atenolol),比方諾羅(befunolol) ’ 貝他索羅(betaxolol),比萬 脫洛(bevantolol),必索普洛(bisoprolol),吲苯酯心安 (bopindolol),布庫莫洛(bucumolol),丁嗅心安(bufetolol),鲁 布夫拉洛(bufuralol),丁苄腈心安(bunitrolol),氣甲苯心安 (bupranolol) ’ 丁酚胺(butidrine)鹽酸鹽,布脫非洛 (butofilolol),卡拉周洛(caraz〇l〇l),卡啼歐洛(carte〇i〇i),卡. 非地(carvedilol),二乙脲心安(celipr〇l〇i),西坦莫洛 (cetamolol),克羅蘭諾洛(ci〇ran〇l〇l),戴來法洛(diievai〇1), 伊潘諾洛(epanolol),伊士莫洛(esm〇l〇l),茚酚洛(indeno丨〇ι), 樂貝塔洛(labetalol),左旋邦諾洛(levobunolol),甲4哚心安 89531-960524.doc -128- (mepindolol),美替潘据洛(metipranolol),美多心安 (metoprolol),莫普洛(moprolol),那都落(nadolol),那多索 洛(nadoxolol),内必佛洛(nebivalol),硝苯心安(nifenalol), 尼帕地洛(nipradilol),心得平(oxprenolol),環戊丁心安 (penbutolol),⑷嗓心安(pindolol),心得寧(practolol),答心 定(pronethalol),答心安(propranolol),梭達羅(sotalol),績 爷心安(sulfinalol),環脈心安(talinolol),特它妥洛 (tertatolol),替利索洛(tilisolol),p塞嗎心安(timolol),甲苯心 安(toliprolol),及西苯諾洛(xibenolol)。 有用之抗痙攣劑之實例包括,但不限於,乙醯苯醯脲 (acetylpheneturide),丁 硫妥英(albutoin),締丙·^号嗣 (aloxidone),胺麵精(aminoglutethimide),4-胺基-3-經基丁 酸,苯乳酿胺(atrolactamide),;氯丙酿胺(beclamide),經乙 辛胺酿(buramate),溴化約,卡巴咪11井(carbamazepine),心若 麥德(cinromide),氯甲p塞嗤(clomethiazole),氯硝安定 (clonazepam),代西曼麥德(decimemide),二乙 11 号》井二嗣 (diethadione),二甲二酮(dimethadione),杜山尼重因 (doxenitroin),雙甲鍵苯比妥(eterobarb),乙 号二酮 (ethadione)’ 乙琥胺(ethosuximide),乙妥英(ethotoin),非巴 媚(felbamate),對氟苯乙ί風(fluoresone),加巴潘汀 (gabapentin),5-幾基色胺酸,拉莫崔禁(lamotrigine),漠化 鎂,硫酸鎂,3-曱基苯乙妥因(mephenytoin),甲基苯巴比妥 (mephobarbital),甲巴比妥(metharbital),1-甲基苯乙妥因 (methetoin),甲琥胺(methsuximide),5-甲基-5-(3-菲基)-乙内 89531-960524.doc -129- 1343917 酿月尿,3-甲基-5-苯基乙内酿脉,曱溴丙巴比妥(narcobarbital) ,硝基去氣安定(nimetazepam),蜗基安定(nitrazepam),氧酿 胺氮吁(oxcarbazepine),帕拉美#_(paramethadione),苯乙 醯脲(phenacemide),苯二乙巴比妥(phenetharbital),苯丁醯 脲(pheneturide),苯巴比妥(phenobarbital),苯琥胺 (phensuximide),苯甲巴比妥(phenylmethylbarbituric acid),
苯妥因(phenytoin),苯 p塞咪鈉(phethenylate sodium),溴化 钾,培加巴林(pregabaline),普里米酮(primidone),氟柳雙 胺(progabide),溴化鈉,茄(solanum)’溴化總,琥氯苯續胺 (suclofenide),歧口塞哨'(sulthiame),四氫菩妥因(tetrantoin), 替兒加拜(tiagabine),托比拉媚(topiramate),三甲雙酮 (trimethadione),丙戊酸(valproic acid),丙戊酿胺 (valpromide),維加巴春(vigabatrin),及卓尼沙麥 (zonisamide) 〇 有用之抗抑鬱劑之實例包括,但不限於,拜達林 (binedaline),醋胺苯号酮(caroxazone)’ 西塔洛盼(citalopram) ,(S)-西塔洛盼(citalopram),二甲占(dimethazan),苯雙胺咖1 «#驗(fencamine),喊咬基乙基< 11 朵(indalpine),因代爾口号p井 (indeloxazine)鹽酸鹽,甲苯号唆辛(nefopam),胺苯甲異p奎 (nomifensine),5-經色胺酸(oxitriptan),奥潑定(oxypertine), 氟苯喊苯醚(paroxetine),色茶林(sertraline),胺苯硫革酮 (thiazesim),氣喊三也酮(trazodone),苯酿甲节肼 (benmoxine),異丙克羅寨(iproclozide),異丙異於肼 (iproniazid),異吨耕(isocarboxazid),尼亞酿胺(nialamide), 89531-960524.doc -130- 1343917 2-月井辛坑(octamoxin),苯乙耕(phenelzine),可鐵寧(cotinine) ,環丙胺(rolicyprine),環丙胺(rolipram),麥普替林 (maprotiline),美差卜朵(metralindole),米安色潤(mianserin) ,米塔氮吁(mirtazepine),阿地那唑蘭(adinazolam),阿米替 林(amitriptyline),阿米替林氧化物(amitriptylinoxide),氯喊 氧萆(amoxapine),丁替林(butriptyline),氣丙咪嗅 (clomipramine),代美西替林(demexiptiline),去镫敏 (desipramine),二苯氮萆(dibenzepin),地美它克林 (dimetacrine)’ 二苯口塞庚英(dothiepin)’ 多慮平(doxepin), 氟 阿西哨"(fluac丨zine),丙咪唤(imipramine),丙味嗪Ν-氡化物, 胺丙Μ卜朵(iprindole),羅非帕明(lofepramine),四甲惠丙胺 (melitracen),二氫二甲基二苯并氮雜萆胺(metapramine),去 甲替林(nortriptyline),肋替林(noxiptilin),經乙旅萆 (opipramol),苯 口塞咬(pizotyline),丙 ρ比氮萆(propizepine), 普羅替林(protriptyline),峻核氮革(quinupramine),替安内;丁 (tianeptine),三甲丙咪嗔(trimipramine),阿爪芬尼 _ (adrafinil),苯乃靜(benactyzine),丁胺苯丙酮(bupropion)籲 丁醋苯胺(butacetin),二苯'»底咬二。号炫> (dioxadrol),杜洛西ί丁 (duloxetine),伊妥派利酿I (etoperidone),非巴班美 (febarbamate),非莫西汁(femoxetine),氯苯己二醇 (fenpentadiol),氟苯氧丙胺(fluoxetine),氟 β号胺 (fluvoxamine) » 血 p比哈紫質(hematoporphyrin),金絲桃素 (hypericin),苯基六氫ρ比症甲醇乙酸醋(levophacetoperane), 二甲基二苯氧基乙胺_ (medifoxamine),米那西盼 89531-960524.doc -131 - 1343917 (milnacipran),米那普林(minaprine),莫克羅貝麥 (moclobemide),内法吐酮(nefazodone),丙象苯嗎淋 (oxaflozane),节 p比酿 B底 p井(piberaline),苯洛戊炫· (prolintane),ρ比咬琥醇(pyrisuccideanol),瑞坦絲林 (ritanserin),羅西》5丨17朵(roxindole),氯化铷,舒必利 (sulpiride),坦多司必隆(tandospirone),胺苯^号也酮 (thozalinone),二苯甲氧胺(tofenacin),甲苯 号酮 (toloxatone),反苯環丙胺(tranylcypromine),L-色胺酸,范 拉法克辛(venlafaxine),乙氧苯氧甲嗎ρ林(viloxazine),及苯 p比浠胺(zimelidine)。 有用之Ca2+通道阻斷劑之實例包括,但不限於,貝皮地 (bepridil),克蘭提阿占(clentiazem),地提阿占(diltiazem), 潘地林(fendiline),甲洛潘米爾(gallopamil),米貝法地 (miberfradil) > 甲基 丁烯胺(prenylamine),西莫替地 (semotiadil),雙苯丁胺(terodiline),戊脈安(verapamil),安 洛地平(amolodipine),阿蘭尼地平(aranidipine),邦尼地平 (barnidipine),班尼地平(benidipine),西尼地平(cilnidipine) ,伊風尼地平(efonidipine),伊苟地平(elgodipine),非洛地 平(felodipine),衣雷地平(isradipine),拉西地平 (lacidipine),樂肯尼地平(lercanidipine),曼尼地平 (manidipine),硝 ρ比胺甲酉旨(nicardipine),利心平(nifedipine), 尼法地平(nilvadipine),尼莫地平(nimodipine),硝p比丁甲酉旨 (nisoldipine),硝ρ比乙甲酉旨(nitrendipine),肉桂苯p辰哨· (cinnarizine),氟苯桂啡(flunarizine),利多 井(lidoflazine) 89531-960524.doc -132- 4 41343917 ,洛美利_ (lomerizine),_爷環庚字(bencyclane),乙胺苯丙 酮(etafenone),范脫法龍(fantofarone),及雙環己乙喊淀 (perhexiline) 〇 有用之抗癌劑之實例包括,但不限於,阿西唯新 ‘ (acivicin),阿克拉露比新(aclarubicin),阿可達岭(acodazole) 鹽酸鹽,阿克羅寧(acronine),阿多戴來心(adozelesin),阿 代斯留金(aldesleukin),阿崔他命(altretamine),二黴素 (ambomycin),安美坦重(ametantrone)醋酸鹽,胺麵精 (aminoglutethimide),安沙克林(amsacrine),安那絲萆吐 t· (anastrozole),胺茴黴素(anthramycin) ’精胺酸酶,曲林菌 素(asperlin),胺基吱喃核糖基三p井酮(azacitidine),氮替喊 (azetepa),含氮黴素(azotomycin) ’ 貝替馬斯特(batimastat), 苯并代巴(benzodepa),必卡露它麥(bicalutamide),必山春 (bisantrene)鹽酸鹽,必斯那菲(bisnafide)二甲續酸鹽,比戴 來新(bizelesin),博萊徽素(bleomycin)硫酸鹽,伯立p奎那 (brequinar)納,伯 p比立明(bropirimine),白消安(busulfan) 放線菌素 C(cactinomycin),7β,17α-二甲筆酮(calusterone) 卡拉塞麥(caracemide),卡貝替莫(carbetimer),卡玻普拉丁 (carboplatin),卡氮芥(carmustine),卡露比新(carubicin)鹽 酸鹽,卡載來辛(carzelesin),西代芬苟(cedefingol),苯丁酸 氮芥(chlorambucil),西若來黴素(cirolemycin),順氯氣銘 (cisplatin),克雷錐拜(cladribine),克立絲那妥(crisnatol)甲 續酸鹽,環憐酷胺(cyclophosphamide),阿糖胞芬 (cytarabine),氮缔也胺(dacarbazine),達克黴素 89531-960524.doc -133 - 1343917
(dactinomycin),正定黴素(daunorubicin)鹽酸鹽,代西它拜 (decitabine),代索馬普拉汁(dexormaplatin),代查胍 (dezaguanine) ’代查鳥嘌呤(dezaguanine)甲績酸鹽,地阿紀 奎 S同(diaziquone),杜西它索(docetaxel),阿徽素 (doxorubicin),阿徽素鹽酸鹽,卓洛西芬(droloxifene),卓洛 西芬檸檬酸鹽,甲雄炫>8同(dromostanolone)丙酸鹽,偶氮徽 素(duazomycin),伊答崔沙(edatrexate),伊福尼辛 (eflornithine)鹽酸鹽,伊山米楚心(elsamitrucin),恩洛拉ί丁 (enloplatin),苯環丙块酿(enpromate),雙環氧ρ底淀 (epipropidine),艾ρ比露比斯(epirubicin)鹽酸鹽,耳布洛吐 (erbulozole),伊索必新(esorubicin)鹽酸鹽,雌二醇氮芬 (estramustine),轉二醇氮芥磷酸鈉,伊坦尼答嗅 (etanidazole),伊妥波塞(etoposide),伊妥波塞鱗酸鹽,氯 苯乙π密胺(etoprine),法卓吐(fadrozole)鹽酸鹽,法扎拉拜 (fazarabine),番瑞丁奈(fenretidine),乳嘗(floxuridine),氟 答拉拜(fludarabine)構酸鹽,氣尿η密咬(fluorouracil),氟西它 拜(flurocitabine),福斯 查嗣(fosquidone),福斯崔新 (fostriecin)納,間西它拜(gemcitabine),間西它拜鹽酸鹽, 趙基脲,伊答露比斯(idarubicin)鹽酸鹽,異環麟酸胺 (ifosamide),伊莫福心(ilmofosine),間白素11(包括重組間白 素II或rIL2),干擾素a-2a,干擾素a-2b,干擾素α-ηΐ,千擾 素α-η3,干擾素β-Ia,干擾素γ-Ib,伊普拉丁(iproplatin), 伊元雜它肯(irinotecan)鹽酸鹽,蘭芮歐太(lanreotide)醋酸 鹽,來卓也(letrozole),流普賴(leuprolide)酷酸鹽’利阿若 89531-960524.doc -134- 1343917 吨(liarozole)鹽酸鹽,洛美崔索(lometrexol)鈉,羅氮芥 (lomustine),羅索占重(losoxantrone)鹽酸鹽,美索普可 (masoprocol),美坦素(maytansine),甲基二氣乙基胺 (mechlorethamine)鹽酸鹽,甲地經孕酮(megestrol)醋酸鹽, 甲缔雌醇(melengestrol)醋酸鹽,梅爾法蘭(melphalan) ’曼語 甲瑞(menogaril),酸基嗓呤(mercaptopurine),胺甲蝶呤 (methotrexate),胺甲蝶呤納,美投普林(metoprine),米得派 (meturedepa),米替卩5丨嗓麥(mitindomide),麥投卡新
(mitocarin),麥投括明(mitocromin),麥投基林(mitogillin) 絲裂馬菌素(mitomalcin),絲裂徽素(mitomycin),麥投絲柏 (mitosper),麥投坦(mitotane),麥投山重(mitomantrone)鹽酸 鹽,徽齡酸(mycophenolicacid),諾可達唆(nocodazole),諾 加黴素(nogalamycin),歐馬普拉丁(ormaplatin),亞橫酿ν»比 淀(oxisuran),佩可利它塞(paclitaxel),p比甲斯帕加爾 (pegaspargase),佩里黴素(pelomycin),戊氮芥(pentamustine)
,匹來黴素(peplomycin)硫酸鹽,佩福斯酿胺(perfosamide), 11底酿溴燒(pipobroman),喊酿硫垸(piposulfan),p比若山重 (piroxantrone)鹽酸鹽,普利卡黴素(plicamycin),普洛美斯 坦(plomestane),波非莫(porfimer)鈉,波福黴素 (porfiromycin) > 松龍苯芥(prednimusine),甲基节肼 (procarbazine)鹽酸鹽,嘌呤徽素(puromycin),標呤黴素鹽 酸鹽’ p比攻吱喃菌素(pyrazofurin),異戊晞腺嘗(riboprine), 若葛來麥(rogletimide),沙芬苟(safingol),沙芬苟鹽酸鹽, 賽代芬(semustine),二甲二苯四氮晞(simtrazene),史巴福塞 89531-960524.doc -135- 1343917 (sprfosate)納,稀疏黴素(sparsomycin),螺旋鍺 (spirogermanium)鹽酸鹽,螺旋氮芬(spiromustine),螺旋普 拉丁(spiroplatin),鏈黑黴素(streptonigrin),鏈脉菌素 (streptozocin),沙洛芬勒(sulofenur),太利蘇黴素 (talisomycin),太可加蘭(tecogalan)納,吱氟尿》密淀(tegafur) ,太洛山重(teloxantrone)鹽酸鹽,探莫波芬(temoporfin), 鬼臼口塞吩嘗(teniposide),環氧三啡_ (teroxirone),睪内酿 (testolactone),硫咪嗓呤(thiamiprine),硫鳥嗓呤
(thioguanine),塞替喊(thiotepa),替阿唾吱林(tiazofurin) 替拉帕扎明(tirapazamine),妥瑞密芬(toremifene)檸檬酸 鹽,7-甲諾銅(tresolone)醋酸鹽,崔色利拜(triciribine)磷酸 鹽,三美崔塞(trimetrexate),三美崔塞葡糖醛酸鹽,崔普妥 林(triptorelin),土布洛峻(tubulozole)鹽酸鹽,尿喊咬氮芥 (mustard),尿燒亞胺(uredepa),維皮歐太(vapreotide),弗貼
波芬(vereporfin),長春驗(vinblastine)硫酸鹽,新長春驗 (vincristine)硫酸鹽,長春驗酿胺(vindesine),長春驗酿胺硫 酸鹽,文内p比淀(vinepidine)硫酸鹽,長春曱甘酿 (vinglycinate)硫酸鹽,環氧長春驗(vinleurosine)硫酸鹽,文 洛瑞拜(vinorelbine),酒石酸鹽,異長春驗(vinrosidine)硫酸 鹽,文处症(vinzolidine)硫酸鹽,吱若也(vorozole),詹尼普 拉丁(zeniplatin),新製癌菌素(zinostatin),紅比脑(zorubicin) 鹽酸鹽。 其他抗癌藥之實例包括,但不限於,20-表(epi)-l,25-二 羥基維生素D3 ; 5-乙块基尿嘧啶;阿比瑞特龍 89531-960524.doc -136- 1343917 (abiraterone);克拉露比新(clarubicin);臨氟文(acylfulvene) ;阿代西潘婼(adecypenol);阿多載來心(adozelesin);阿代 斯留金(aldesleukin); ALL-TK拮抗劑;阿崔他命(altretamine) :安巴氮芥 (ambamustine);安密多(amidox);安密福斯丁 (amifostine);胺基 4-戊納酸(aminolevulinic acid);安露比新 (amrubicin);安沙克林(amsacrine);安那圭賴(anagrelide); 安那絲卓吐(anastrozole);穿心蓮内醋(andrographolide);血 管形成抑制劑;拮抗劑D ;拮抗劑G ;安它瑞利(antarelix); 抗背部化(dorsalizing)形態發育蛋白質-1 ;抗雄性素,前列 I· 腺癌;抗動情素;抗腫瘤劑(antineoplaston);反義(antisene)
寡核苷酸;蚜可林(aphidicolin)甘胺酸鹽;程序性細胞死亡 (apoptosis)基因調節劑;程序性細胞死亡調節劑;無嗓呤酸 (apurinic acid) ; ara-CDP-DL-PTBA ;精胺酸去胺酶;阿蘇 拉克林(asulacrine);阿它美斯坦(atamestane);阿崔氮齐 (atrimustine);阿辛那思丁(axinastatin)l ;阿辛那思丁 2 ;阿 辛那思丁 3 ;阿扎西重(azasetron);阿扎土新(azatoxin);氮 酶胺酸(azatyrosine);蒙果赤徽素(baccatin)III衍生物;貝 諾(balanol);貝替馬斯特(batimastat); BCR/ABL 拮抗劑;苯 并綠素類(benzochlorins);苯甲酿基星狀抱子素 (staurosporine) ; β-内醯胺衍生物;β-阿來新(alethine) ; β-. 克蘭黴素(betaclamycin)B ;樺木酸(betulinic acid); bFGF 抑 制劑;必卡露它麥(bicalutamide);必山春(bisantrene);雙氮 口元精胺(bisaziridinylspermine);必斯那非(bisnafide);必斯 查丁(bistratene)A ;比載來新(bizelesin);布瑞福來 89531-960524.doc -137- (breflate);伯 p比立明(bropirimine);布多替坦(budotitane); 布塞翁寧(buthionine)沙風辛明(sulfoximine);卡西波垂 (calciotriol);卡福斯丁(calphostin)C;喜樹驗(camptothecin) 衍生物;金絲雀症(canarypox)IL-2;克派西它拜(capecitabine) ;羧醯胺-胺基-三唑;羧基醯胺基三唑;CaRest M3 ; CARN 700 ;軟骨衍生之抑制劑;卡載辛來(carzelesin);路蛋白 (casein)激酶抑制劑(ICOS);栗精胺(castanospermine);西克 羅平(cecropin)B ;西卓瑞利(cetrorelix);綠素類(chlorlns); 氯p奎π号琳(chloroquinoxaline)績醯胺;西卡普斯(cicaprose); 順式p比洛紫質(porphyrin);克雷錐拜(cladribine);克羅米芬 (clomifene)類似物;克霉嗅(clotrimazole);可利斯黴素 (collismycin)A ;可利斯黴素 B ;康卑史它丁(combretastatin) A4 ;康卑史它丁類似物;康那精寧(conagenin);昆貝西丁 (crambescidin)816 ;克絲那妥(crisnatol);隱藥素 (cryptophycin)8 ;隱蕩素A衍生物;庫瑞新(curacin)A ;環戊 燒砂p奎淋酮(thraquinones);環普拉炭(cycloplatam);塞佩黴 素(cypemycin);阿糖胞嘗(cytarabine)歐福斯費(ocfosfate); 細胞溶解因子;細胞抑制劑(cytostatin);大克利西媚 (dacliximab);代西它拜(decitabine);去氫代丹寧 (dehydrodidemnin)B ;代斯羅瑞林(deslorelin);地塞米松 (dexamethasone);代西福斯麥(dexifosfamide);代拉卓山 (dexrazoxane);代伏拉盼(dexverapamil);地阿紀,奎 _ (diaziquone);代丹寧(didemnin)B ;代多斯(didox);二乙基 去甲精胺(diethylnorspermine);二氫-5-氮雜胞苷;二氫紫杉 89531-960524.doc -138- 1343917 醇(taxol); 9-二号黴素;二苯基螺旋氮芥(spiromustine);多 西它索(docetaxel);二十二燒醇;多拉西重(dolasetron);多 西氟來定(doxifuridine);卓洛西芬(droloxfene);卓那拜諾 (dronabinol);雙卡黴素(duocarmycinSA);艾塞倫(ebselen); 伊可氮芥(ecomustine);伊代福新(edelfosine);伊錐可隆 (edrecolomab);伊福尼辛(efi〇rnithine);禮香烯(elemene);
安密貼佛(emitefur);艾吡露比新(epirubicin);伊普斯特來 (epristeride);雌二醇氮芥(estramustine)類似物;動情素激動 劑;動情素结抗劑;伊坦尼答吐(etanidazole);伊妥波塞 (etoposide)鱗酸鹽:伊克沾美坦(exemestane);法卓吐 (fadrozole);法扎拉拜(fazarabine);潘瑞丁奈(fenretinide); 非11瓜絲丁(Hlgrastim);芬那斯特來(finasteride);黃p比醇 (flavopiridol);福來遮拉斯丁(flezelatine);氟絲特龍 (fluasterone);氟答拉拜(fludarabine);氣當諾露新 (fluorodaunorunicin)鹽酸鹽;福芬尼美(forfl/ .limex);福美斯 坦(formestane);福斯崔新(fostriecin);福貼氮芬(fotemustine) ;德沙非林(texaphyrin)此;硝酸鎵;嘉洛西它拜< (galocitabine);甘尼瑞利(ganirelix);明膠酶抑制劑;間西 它拜(gemcitabine);麵胱甘肽抑制劑;黑沙泛(hepsulfam); 黑瑞古林(heregulin);六亞甲雙乙酿胺;金絲桃素(hypericin) ;伊班鐘酸(ibandronic acid);伊答露比新(idarubicin);伊多 西芬(idoxifene);伊爪曼同(idramantone);伊莫福心 (ilmofosine);伊洛馬斯它(ilomastat);咪处 t*丫咬酮 (imidazoacridones);伊米奎莫(imiquimod);免疫刺激肽;似 89531-960524.doc -139- 1343917 胰島素生長因子-1受體抑制劑;干擾素激動劑;干擾素; 間捱素;艾歐班官(iobenguane);換阿黴素(iododoxorubicin) ;4-伊波曼諾(4-ipomeanol);耳若普雷(iroplact);兒索葛拉 定(irsogladine);異苯格唑(isobengazole);異高哈里孔屯 (isohomohalicondrin)B ;伊塔西重(itasetron);家拉金諾 (jasplakinolide);卡哈拉來(kahalalide)F ;片螺素(lamellarin)· N三醋酸鹽;蘭芮歐太(lanreotide);林那黴素(leinamycin); 蘭諾葛拉丁(lenograstim);香益糖(lentinan)硫酸鹽;來投史 塔丁(leptolstatin);來卓哇(letrozole);白血病抑制劑因子; I· 白血球α干擾素;流普賴(ieuprplide)+動情素+黃體嗣;亮普 瑞林(leuprorelin);左旋四咪吨(levamisole);利阿若咬 (liarozole);線性聚胺類似物;親脂性雙醣肽;親脂性鉑化 合物;利索克林那麥(lissoclinamide)7 ;洛巴普拉丁 (lobaplatin);龍比立心(lombricine);洛美崔索(lometrexol); 龍尼答明(lonidamine);羅索占重(losoxantrone);羅法史塔 丁(lovastatin);洛索立拜(loxoribine);樂 土帖肯(lurtotecan) :德沙非林(texaphyrin)錄(lutetium);溶解非林(lysofylline) Π 溶解肽;美坦新(maitansine);甘露史塔丁(mannostatin)A; 馬林馬斯特(marimastat);美索普可(masoprocol);馬斯平 (maspin);馬崔溶素(matrilysin)抑制劑;基質金屬蛋白酶抑 制劑;曼諾曱瑞(menogaril);莫巴隆(merbarone);美特瑞林 (meterelin),甲硫胺酸酶,滅吐靈(metoclopramide) ; MIF抑 制劑;米非普斯酮(mifepristone);米貼福新(mi丨tefosine); 米梨莫斯丁(mirimostim);錯配雙股rnA ;麥托咕腙 89531-960524.doc -140· 1343917 (mitoguazone);麥托乳醇(mitolatol);絲裂黴素類似物;麥 托那菲(mitonafide);絲裂毒素(mitotoxin)纖維母細胞生長因 子沙波林(saporin);麥投山重(mitoxantrone);莫法若丁 (mofarotene);莫狐莫斯丁(molgramostim);單株抗體,人類 絨毛膜促性腺激素(gonadotrophin);單麟醯基脂質A+肌肉 細菌(myobacterium)細胞壁sk ;莫V»比丹末(mopidamol);多藥 物抗性基因抑制劑;以多腫瘤抑制劑-1為基本之治療;芥 子(mustard)抗癌劑;麥卡過氧化物(mycaperpxide)B ;多枝 桿菌細胞壁萃取物;麥利波龍(myriaporone) ; N-乙酿基地 那林(dinaline) ; N-經取代之苯甲醯胺;那法瑞林 (nafarelin);那圭史地(nagrestip);納洛 _ (naloxone)+戊咬 星(pentazocine);那帕文(napavin);那夫特平(naphterpin) 那投 p瓜斯丁(nartograstim);内答普拉丁(nedaplatin);内莫 露比新(nemorubicin);樂立鐘酸(neridronic acid);中性内肽 酶;尼露它麥(nilutamide);尼沙徽素(nisamycin);氧化氮 調節劑;硝基氧(nitroxide)抗氧化劑;尼出林(nitrullyn); 06-苯曱基鳥嗓呤;奥崔歐太(octrecotide);歐奇辛酮 (okicenone);寡核嘗酸;翁那普斯通(onapristone);翁丹西 重(ondansetron);歐瑞新(oracin); 口服細胞動素誘發劑; 歐馬普拉丁(ormaplatin);歐沙特龍(osateron) ; 17号利普拉丁 (oxaliplatin);号稍語黴素(oxaunomycin);佩可利它塞 (paclitaxel);佩可利它塞類似物;佩可利它塞衍生物;巴勞 胺(palauamine);十六基來周新(palmitoylrhizoxin);帕咪鐘 酸(pamidronic acid);班那希三醇(panaxytriol);潘諾米芬 89531-960524.doc • 141 - 1343917 (panomifene);副菌素(parabactin);佩栽利丁(pazelliptine); 口比甲斯帕加酶(pegaspargase);佩代辛(peldesine);戊聚糖聚 4 硫酸納;戊咪二氮箪(pentostatin);潘卓也(pentrozole);全 « 氟硼(perflubron);佩福斯臨胺(perfosfamide);紫蘇子(perilly) 醇;吩唤徽素(phenazinomycin);苯基錯酸酿;鱗酸酶抑制 劑;溶鏈菌素(picibanil);毛果芸香驗(pilocarpine)鹽酸鹽; 皮拉露比新(pirarubicin);皮里崔新(piritrexim);普來西丁 (placetin)A ;普來西丁 B ;纖維蛋白溶酶原(plasminogen)活 化劑抑制劑;鉑複合物;鉑化合物;鉑三胺複合物;波非 I· 莫(porfimer)鈉;波福黴素(porfiromycin);脫氫可的松 (prednisone);丙基雙丫咬酮(acridone);前列腺素J2 ;蛋白 松(proteasome)抑制劑;以蛋白質A為基礎之免疫調節劑;蛋 白質激酶C抑制劑;蛋白質激酶C抑制劑;微藻類 (microalgal);蛋白質酪胺酸麟酸酶抑制劑;嘌呤核苷磷醯 酶抑制劑;紫紅素(purpurine); ρ比吐并 p丫淀(pyrazoloacridine) ;吡醇羥乙酯化血紅素聚氧乙烯共軛物;raf拮抗劑;拉替 崔塞(raltitrexed);蘭莫西重(ramosetron) ; ras法呢基(farnesyl, 蛋白質轉移酶抑制劑;ras抑制劑;ras-GAP抑制劑;瑞胎里 丁(retelliptine);去甲基化;經乙二轉酸(etidronate)銖 Re 186 ;來周新(rhizoxin);核糖酶(ribozymes) ; RII視黃酿胺 (retinamide);若葛來麥(rogletimide);羅希土金(rohitukine); 羅抹太(romurtide);羅峻尼美(roquinimex);露比金農 (rubiginone)Bl ;露玻西(ruboxyl);沙芬苟(safingol) ; ·;山脫 平(saintopin) ; SarCNU ;沙可非妥(sarcophytol)A ;沙 p瓜莫斯 89531-960524.doc -142· 1343917
丁(sargramostim); Sdi 1擬似物;賽氮芥(semustine);衰老 (senescence)衍生之抑制劑1 ;有意義(sense)寡核苷酸;訊號 傳導抑制劑;訊號傳導調節劑;單鏈抗原結合蛋白質;希 峻佛蘭(sizoHran);索布唑占(sobuzoxane);硼卡它酸 (borocaptate)鈉;苯基醋酸鈉;索佛若(solverol);促生長因 子(somatomedin)結合蛋白質;索樂明(sonermin);史巴夫酸 (sparfosic acid);穗黴素(spicamycin)D ;螺旋氮芥 (spiromustine);脾潘丁(splenopentin);海綿史塔丁 (spongistatin)l ;鯊胺(squalamine);幹細胞抑制劑;幹細胞 分裂抑制劑;史替皮酿胺(stipiamide);史卓美來辛 (stromelysin)抑制劑;沙芬据辛(sulfinosine);超活性血管活 性腸肤结抗劑;舍拉地它(suradista);蘇拉明(suramin);八 氫啕畊三醇(swainsonine);合成之葡糖胺基聚糖(glycans); 塔利氮芥(tallimustine);阿莫西芬(tamoxifen)甲破化物 (methiodide);牛績氮芥(tauromustine);塔扎若丁(tazarotene) ;太可加蘭(tecogalan)納;吱氟尿墙淀(tegafur); ρ比喃錯碎 (tellurapyrylium);調節聚合酶(telomerase)抑制劑;探莫波 芬(temoporfin);探莫岭洛麥(temozolomide);鬼臼p塞吩嘗 (teniposide);四氯十氧化物(decaoxide);四嗅明(tetrazomine) ;莎利布拉史丁(thaliblastine);硫可瑞林(thiocoraline);血 小板生成素(thrombopoietin);血小板生成素擬似物;塞馬 費辛(thymalfasin);胸腺生成素(thymopoietin)受體激動劑; 胸腺三喃(thymotrinan);甲狀腺刺激荷爾蒙;乙基本紫紅素 (etiopurpurin)錫;替拉帕扎明(tirapazamine);二氣環戊二晞 89531-960524.doc -143- 1343917 鈥(titanocene);陶普生丁(topsentin);妥瑞密芬 (toremifene);全能(totipotent)幹細胞因子;轉譯抑制劑;全 反視黃酸(tretinoin);三乙酿基尿嘗;崔色利拜(triciribine); 三美崔塞(trimetrexate);崔普妥林(triptorelin);托皮西重 (tropisetron); 土若史特來(turosteride);酪胺酸激酶抑制劑; 太佛斯丁(tyrphostins) ; UBC抑制劑;攸班尼美斯 (ubenimex);泌尿生殖竇衍生之生長抑制因子;尿激酶受體 拮抗劑;法皮歐太(vapreotide);豆瘡素(vari〇iin)B;載體系 I· 藜蘆明 統’紅血球基因治療;弗刺瑞索(velares〇l) (veramine);弗定(verdine);弗貼波芬(verteporfin);文洛瑞 拜(vinorelbine);文沙丁(vinxaltine);維他新(vitaxin);佛若 唑(vorozole);詹諾特龍(zanoterone);詹尼普拉丁(zeniplatin) ;季拉斯扣(zilascorb);及新製癌菌素(zinostatin)史丁馬拉 莫(stimalamer)。
可用於治療或預防上瘾之治療劑包括,但不限於,美沙 酮(methadone),去參敏(desipramine),金剛燒1 胺(amantadine) ,氟苯氧丙胺(fluoxetine),布潘諾啡(buprenorphine),一種 鴆片激動劑,3 -苯氧基p比淀,或一種血清素拮抗劑。 有可用之抗焦慮劑之實例包括,但不限於,苯并二氮砰 如三咬安定(alprazolam),甲胺二氮萆(chlordiazepoxide), 氣硝安定(clonazepam),氯氮革(clorazepate),苯甲二氮萆 (diazepam),三氣甲安定(halazepam),氯經安定(lorazepam) ,去甲經基安定(oxazepam),及環丙安定(prazepam);非苯 并二氮吁劑,如布斯p比龍(buspirone);及鎮靜劑,如巴比土 89531-960524.doc • 144- 1343917 酸鹽(brdituates) 〇 有用之抗腹演劑之實例包括,但不限於,氣苯喊酿胺 (loperamide) ’具有阿托品之氰苯哌酯(diphen〇xyiate),可樂. 寧(clonidine) ’奥崔歐太(〇ctre〇tide),及消膽胺. (cholestyramine)。 一種4-四4基-4-苯基喊咬化合物及其他治療劑可加成作 用’或在一個具體實施例中協同作用。在一個具體實施例 中,一種4-四唑基-4-苯基哌啶化合物與另一種治療劑同時 施用;例如可施用一種包含有效量之一種4_四唑基_4_苯基|鲁 哌啶化合物,有效量之另一種治療劑之組合物。或者,一 種包含有效量之一種4-四纟基_4_苯基錢化合物之組合物 及-種包含有效量之另-種治療劑之不同組合物可同時施 用。在另一具體實施例中,有效量之一種4·四唑基苯基 喊咬化合物在有效量之另—種治療劑⑯用之前或之後施 用。在此具體實施例中’-種4_四峻基_4_苯基喊咬化合物 在另一種治療劑發揮治療作用時施用,或另一種治療劑在 4-四唑基-4-苯基哌啶化合物發揮預防或治療作用時施用, 用於治療或預防疼痛或腹瀉。 本發明之一種組合物係由一種包含混合一種4_四唑基_4_ 苯基哌啶化合物或其醫藥可接受鹽及一種醫藥可接受載劑· 或賦形劑之方法製備。混合可由使用;昆合一 及-種醫藥可接受載劑或域形劑之已知方法完;物二:).. 具體實施例中,製備組合物以使4_四吐基苯基㈣化合 物以有效量存在於組合物中。 89531-960524.doc •145· 1343917 4.4.2套組 本發明包括套組,其可使一種4-四也基-4-苯基喊淀化合 物施用於一種動物簡單化。 ‘ 本發明之一種典型套組包含一種4-四唑基-4-苯基哌啶化 . 合物之一個單位劑形。在一個具體實施例中,單位劑形為 一個容器,在一個具體實施例中為一個滅菌容器,含有有 效量之一種4-四唑基_4_苯基哌啶化合物及一種醫藥可接受 <載劑或賦形劑。套組可另包含一個標示或抑制之指示指 導使用4-四唑基_4_苯基哌啶化合物以治療或預防疼痛或腹|鲁 4。套組亦可另包含另一治療劑之單位劑形,例如,一個 谷器含有有效量之另一治療劑。在一個具體實施例中,套 組包含-個容器含有有效量之一種4_四吨基冬苯基喊咬化 合物及有效量之另一治療劑。其他治療劑之實例包括,但 不限於,上述所列者。 本發明 <套組可另包含一種可用於施用單位劑形之裝
置。該裝置之實例包括,但不限於,注射筒,滴袋,貼片, 灌腸袋,及吸入器。 下列實例係用於協助明瞭本發明,不應視為特定限制本 文中所述及主張之本發明。本發明之變異包括現在已 以後發展之所有相等物之取代,其應在熟習技藝人士之範 圍内,調配之改變岑音私β 、&, 、 飞實驗5又计 < 微小改變應視為在本發明 之範圍内。 【實施方式】 5.實m 89531-960524.doc -146· 1343917 實例1 -7係關於本發明4-四峻基-4-苯基喊喊化合物之合 成0
5.1 實例1 :化合物AAA之合成 概圖11
在(A)(3.0毫莫耳)及(B)(3.〇毫莫耳)於1〇毫升DMF中之溶 液内加入1.2當量DIEA。混合物在801攪拌過夜《反應混合 物冷卻’以醋酸乙酯稀釋,以水(2〇毫升χ2)洗。水層以醋酸 乙酯(25毫升)萃取一次。合併之有機相乾燥(Na2S〇4),溶劑 在旋轉蒸發器上移除。殘餘物以管柱層析(5% NEt3/250/〇 EtOAc/70%己捉)純化,獲得所欲產物(〇,呈無色固體。化 合物(C):產率85% ’純度(HPLC)>97%; ms: m/z381.3 ; 4 >JMR (CDC13):S 2.05-2.15 (m,4H),2.25-2.35 (m, 2H),2.4-2.5 (m, 4H), 2.95-3.05 (m, 2H), 4.0 (t, 1H), 7.1-7.4 (m, 11H))5 7.4-7_5 (m, 2H), 7.5-7.55 (m,2H)。 89531-960524.doc •147- 1343917 概圖12
在(C)(0.5毫莫耳)於10毫升甲苯中之溶液内加入2當量 Me3SiN3及0.1當量氧化二丁基錫。混合物在回流於氬氣壓下 攪拌24小時。LC/MS顯示反應完全。溶劑在真空中蒸發。 粗物質溶於CHCh中,加入裝有5克矽膠之管柱中。進行急 驟層析,以5% Et3N,25%醋酸乙酯,及70%己烷溶離,然 後以10% Et3N,40% EtOAc,5 0%己烷溶離。最後以2% ΝΗ3/Η20, 15%甲醇,及83% CH2C12溶離。獲得化合物 (AAA),呈固體。化合物(AAA):產率30% ;純度(HPLC) >97% ; MS : m/z 424.2 ; NMR (MeOD):8 2.3-2.5 (m, 4H), 2.8-3.1 (m, 6H), 3.4-3.5 (m, 2H), 3.9 (t, 1H), 7.1-7.3 (m, 15H)。 5.2實例2 :化合物ACY之合成 概圖13
89531-960524.doc -148- 1343917 在(0)(3.0¾莫耳)及(B)(3.0毫莫耳)於ι〇毫升DMF中之溶 液内加入1.2當量DIEA。混合物在80°C攪拌過夜。反應混合 物冷卻,以醋酸乙酯稀釋,以水(2〇毫升χ2)洗。水層以醋酸 乙酯(25毫升)萃取一次。合併之有機相乾燥(Na2S〇4),溶劑 在旋轉蒸發器上移除。殘餘物以管柱層析(5% NEt3/25% EtOAc/70%己烷)純化,獲得所欲產物(E),呈無色固體。化 合物(E):產率 80%,純度(HPLC)>97% ; MS : m/z 406.2 ;咕
NMR (CDC13):6 2.0-2.1 (m, 4H), 2.5-2.7 (m, 6H), 2.9-3.0 (m, 2H), 7.3-7.5 (m,15H)。 概圖14
在(E)(4.0毫莫耳)於1 5毫升對_二甲苯中之溶液内加入i」
當量Me3S11N3。混合物在回流於氬氣壓下撥掉36小時。反應 混合物冷卻,倒入150毫升1M NaOH中。乙醚(150毫升)加 入’此溶液在室溫攪拌1小時。各層分離,水層以乙醚(15〇 毫升xl)萃取。水層以醋酸/醋酸銨酸化至pH 6.3。固體過 濾,以水(100毫升)洗,以冷甲醇碾製,獲得產物,呈白色 固體。急驟層析以醋酸乙酯,然後以醋酸乙酯:甲醇(7〇 : 3〇)溶離,獲得化合物(ACY),呈白色固體。化合物(ACY) (5.0 克’ 11.14毫莫耳)懸浮於沸騰甲醇(200毫升)中並攪拌。胺 89531-960524.doc -149· 1343917 磺酸(1.08克,11.14毫莫耳)於熱水(5毫升)中加入以形成透 明溶液。其緩慢冷卻幾小時,然後過濾,獲得化合物(ACY) 之胺磺酸鹽(4.46克,73%),呈白色針狀。化合物(ACY)(胺 磺酸鹽):純度(HPLC) >97% ; MS : m/z 449.2 ; NMR (DMSO-d6):5 2.25-2.4 (m, 2H), 2.4-2.5 (m, 2H), 2.55-2.65 (m, 2H), 2.7-2.85 (m, 4H), 3.1-3.25 (m, 2H), 3.3-3.4 (bs, 2H), 7.2-7.3 (m,3H),7.3-7.4 (m,4H), 7.4-7.5 (m, 8H)。
在化合物(ACY)(0_45毫莫耳)於無水DMF中之溶液内加 入三乙胺(0.54毫莫耳),然後加入烷基化劑Br(CH2)2C(0)0 (CH2CH3)(0.54毫莫耳)。生成之混合物在80°C攪拌過夜。在 反應完全後,冷卻之混合物分配於醚及鹽水之間,有機相I 分離,乾燥(MgS04),溶劑在旋轉蒸發器上移除,獲得無色胃 至淡黃色膠。以醚/己烷或醚/醋酸乙酯(1 :卜1〇毫升)碾製, 由母液沉澱化合物(ADI)呈白色固體:產率:24% ;純度 (HPLC) >97% ; MS : m/z 549.3 (M+l) ; !H NMR (DMSO d6):5 2.2-2.6 (m, 6H), 2.7-2.9 (m, 4H), 3.05 (t, 3H), 3.2-3.4 (m, 4H), 3.95 (q,2H), 4.9 (t, 2H), 7.1-8.1 (m,17H)。 母液包括化合物(ADI)及化合物(BDI),其使用習知分離 方法分離。 89531-960524.doc •150- 1343917 5.4實例4 :化合物ADO及BDO之合成 概圖16
在化合物(ACY)(0.45毫莫耳)於無水DMF中之溶液内加 入三乙胺(0.54毫莫耳),然後加入烷基化劑(Br(CH2)2NHS02 CH3) (0.54毫莫耳)。生成之混合物在80°C攪拌過夜。在反 應完全後,冷卻之混合物分配於醚及鹽水之間,有機相分 離,乾燥(MgS04),溶劑在旋轉蒸發器上移除,獲得無色至 淡黃色膠。以醚/己烷或醚/醋酸乙酯(1 : 1,10毫升)碾製, 由母液沉澱化合物(ADQ)呈白色固體:產率:59% ;純度 (HPLC) >97%; MS: m/z 570.2 (M+l); lU NMR (CD3OD):6 2.1-2.3 (m, 6H), 2.6-2.7 (m, 2H), 2.75 (s, 3H), 2.85 (d, 4H), 3.25- 3.35 (m, 1H), 3.6 (t, 2H), 4.65 (t, 2H), 7.15-7.2 (m, 1H), 7.25- 7.35 (m, 6H),7.38-7.45 (m,8H)。 母液包括化合物(ADQ)及化合物(BDQ),其使用習知分離 方法分離。 5.5實例5 :化合物ACZ及BCZ之合成 概圖17
89531-960524.doc -151 - 1343917 在化合物(ACY)(0.78毫莫耳)於無水dmf(5毫升)中之溶 液内加入二乙胺(0.94毫莫耳),然後加入2_溴乙醯胺(〇 27毫 莫耳)。生成之混合物在80。(:攪拌過夜。在反應完全後,冷 卻之混合物分配於醚及鹽水之間,有機相分離,乾燥 * (MgSCU) ’溶劑在旋轉蒸發器上移除,獲得淡黃色膠。急驟 層析(Si〇2 ’醚:甲醇:氫氧化銨(1〇〇〇 : 4 :丨)),獲得化合 物(ACZ) ’呈白色固體(48%產率)。化合物(Acz):純度 >97%(HPLC) ; MS : m/z 506.2 (M+l) ; »H NMR (DMSO d6):5 1.8 (m, 2H), 2.2 (m, 4H), 2.6-2.8 (m, 6H), 5.35 (s, 2H), I· 7.0-7.5 (m,16H),7.7 (m,1H)。 進一步層析獲得化合物(BCZ)。 5.6實例6 :化合物AFD夕合成, 概圖18
4-溴-2,2-二苯基丁酸(化合物(F),23克,72毫莫耳)懸浮 於150毫升氣仿中,2〇毫升亞硫醯氯(27〇毫莫耳)逐滴加入。 在亞硫酿氣加入後,0.2毫升二甲基曱醯胺加入,生成之溶 液在回流加熱約4小時。然後反應混合物在減壓下濃縮,獲 得4-澳-2,2-二苯基丁醯基氣(化合物(G)),呈淡黃色油其 不進一步純化而用於下一步驟。 89531-960524.doc -152- 1343917 在100耄升飽和Na2C〇3水溶液中加入50毫升二甲胺於四 氫呋喃中之2M溶液。生成之溶液冷卻至〇〇c,如上述製備 之化合物(G)溶於1〇〇毫升甲苯中之溶液逐滴加入。生成之 混合物攪拌約12小時。反應混合物之有機層及水層分離, 水層以30毫升曱苯萃取,然後以1〇〇毫升氯仿萃取3次,有 機層合併。合併之有機萃取物以水(3〇毫升)洗,乾燥 (Κ/Ο3),溶劑在減壓下移除,獲得殘餘物,其由甲基異丁 基酮中結晶’獲得12克(53%產率)溴化二甲基(四氫_3,3_二
苯基-2-亞吱喃基)錄(化合物(H))。 概圖19
在化合物(H)(3.0毫莫耳)及(B)(3_0毫莫耳)於1〇毫升DMFf 中之溶液内加入3當量NazCO3。混合物在80°C攪拌3小時。 反應混合物冷卻,以醋酸乙酯稀釋,以水(20毫升x2)洗。水 層以醋酸乙酯(25毫升)萃取一次。合併之有機層乾燥 (NajO4) ’溶劑在旋轉蒸發器上移除。殘餘物以管柱層析 · (5% NEt3/25% EtOAc/70%己烷)純化,獲得產物化合物⑴,·, 呈無色結晶:(產率:81%);純度(HPLC) >97% ; MS : m/z 452.2 ; !H NMR (CDC13):6 2.0-2.1 (m> 4H), 2.2 (m, 2H), 2.3- 89531-960524.doc -153 - 1343917 2.4 (m, 5H), 2.4-2.5 (m, 2H), 2.9 (m, 2H), 3.0 (bs, 3H), 7.2- 7.3 (m, 3H), 7.3-7.5 (m,12H)。 概圖20
在化合物(1)(0.5毫莫耳)於i〇毫升曱苯中之溶液内加入2 I· 當量MesSiN3及0.1當量氧化二丁基錫。混合物在回流於氬氣 壓下攪拌24小時。LC/MS顯示反應完全。溶劑在減壓下蒸 發。粗產物溶於CHC13中,加入裝有5克矽膠之管柱中。進 行急驟層析’以5% Et3N,25%醋酸乙酯,及70%己烷溶離, 然後以10% Et3N,40% EtOAc,50%己烷溶離》最後以2% NH3/H20 ’ 15%甲醇,及83% CH2C12溶離。獲得化合物
(AFD),呈固體(產率 35%);純度 >97%(HPLC) ; MS : m/z 495.2 ; ]H NMR (DMSO d6):5 2.2 (bs, 3H), 2.3-2.4 (m, 2H), 2.5 (m, 3H), 2.6-2.7 (m, 2H)S 2.7-2.8 (m, 2H), 2.9 (bs, 3H), 3.3-3.4 (bs, 3H), 7.2-7.3 (m, 3H), 7.3-7.4 (m, 4H), 7.4-7.5 (m, 8H)。 5.7實例7 :化合物AFE及BFE之合成 概圖21 89531-960524.doc • 154· 1343917
在化合物(AFD)(0.40毫莫耳)於無水DMF中之溶液内加入 三乙胺(0.45毫莫耳),然後加入烷基化劑Br(CH2)2C(0)NH2 (〇·45毫莫耳)。生成之混合物在80°C攪拌過夜。在反應完全 後,冷卻之混合物倒入1M NaOH(150毫升)中,以醋酸乙酯 (2x100毫升)萃取。有機萃取物乾燥(MgS04),溶劑在旋轉 蒸發器上蒸發,獲得膠。殘餘物急驟層析(Si02,醚:曱醇: 氫氧化銨(200 : 10 : 1)),獲得化合物(AFE),呈無色膠:(產 率:69%);純度>97%(HPLC); MS: m/z 552.3 (M+l); iNMR (DMSO 4_6):δ 2.2-2.3 (br s,3H),2.35-3.0 (m,11H),3.3-3.4 (m, 4H),5.35 (s,2H),7.15-7.5 (m,16H),7.8 (br s,1H)。 進一步層析獲得化合物(BFE)。 5.8實例8 :化合物AFV及BFV之合成
r-J^
在化合物(AFD)(0.40毫莫耳)於無水DMF中之溶液内加入 三乙胺(0.45毫莫耳),然後加入烷基化劑Br(CH2)2NHS02CH3) (0.45毫莫耳)。生成之混合物在80°C攪拌過夜。在反應完全 後,冷卻之混合物倒入1M NaOH(150毫升)中,以醋酸乙酯 89531-960524.doc -155- 1343917
(2x100毫升)萃取。有機萃取物乾燥(MgS04),溶劑在旋轉 蒸發器上蒸發,獲得膠。殘餘物急驟層析(Si02,醚:甲醇: 氫氧化銨(200 : 10 : 1)),獲得化合物(AFV),呈無色膠:(產 率:26%);純度>97%(HPLC); MS: m/z 616.3 (M+l); WNMR (DMSO d6):5 2.1-2.2 (br s, 3H), 2.3-2.4 (m, 5H), 2.75 (s, 3H), 2.9-2.10 (br s, 3H), 3.3-3.4 (m, 6H), 3.5 (m, 3H), 4.65 (m, 2H), 7.15-7.5 (m, 16H)。 進一步層析獲得化合物(BFV)。
5.9會例22 : u-及ORL-1-受體結合親和力分拚 下列實例證明4-四吐基·4-苯基哌啶化合物結合於μ_及 ORL-1-受體,因此可用於治療或預防疼痛或腹瀉。 5.9.1材料及方法 ORL-1令體膜製備 所有試劑得自Sigma(St. Louis, ΜΟ),除非另外說明。表 現似人類類鵠片(opioid)(ORL-l)受體之重組HEK-293細胞
(Perkin Elmer, Boston,MA)之膜係由細胞溶於冰冷低張緩 衝液(2.5 1111^1^(212,5〇1111^[11£?£8,卩117.4)(1〇毫升/1〇公 分盤)中,然後以一種組織研磨器/鐵弗龍(tefl〇n)杵均質化 而製備。在4°C以30,000 X g離心收集膜,粒子再懸浮於低 張緩衝液中至最終濃度1-3毫克/毫升。蛋白質濃度係使用 BioRad(Hercules,CA)蛋白質分析試劑之牛血清白蛋白作為 標準而測定。等份ORL-1受體膜貯存在_8〇〇c。 μ-及ORL-1 -受體結合分拚程庠 ORL-1及μ受醴之放射配位體劑量置換結合分析係分別 89531-960524.doc -156- 1343917 使用 0.1 nM[3H]-致痛素(nociceptin)或 0.2 nM[3H]-二普諾芬 (diprenorphine)(NEN,Boston, ΜΑ)與 5-20 毫克膜蛋白質/井 於最終體積500毫升結合緩衝液(1〇 mM MgCl2,1 mM EDTA,5% DMSO,50 mM HEPES,pH 7.4)中。反應係在 增加濃度之未標示致痛素(American Peptide Company, Sunnyvale,CA)或納洛酮(naloxone)不存在或存在下分別對 於ORL-1及μ進行。所有反應係在96個深井聚丙烯板中在室 溫進行卜2小時。由使用一個96井組織收穫器(Brandel, Gaithersburg, MD),在0.5%聚乙烯亞胺中預先濡濕之96井 Unifilter GF/C過遽板(Packard, Meriden,CT)上迅速過滤,然 後以500微升冰冷結合緩衝液進行三次過濾清洗,而終止結 合反應。然後過濾板在50°C乾燥2-3小時。BetaScint閃爍混 合液(cocktail)(Wallac,Turku,Finland)加入(50 微升/井),各 板使用一個Packard Top-Count計數1分鐘/井。數據係使用 GraphPad PRISM v.3.0 (San Diego, CA)中一個位置競爭曲線 配合函數分析。 5.9.2 Li-夸贈Μ合數據 一般而言,Ki值愈低,則4-四峻基-4-苯基喊淀化合物治 療或預防疼痛或腹瀉愈有效。4-四唑基-4-苯基哌啶化合物 結合於μ-類鴉片受體之Ki(nM)典型為約300或以下。在一個 具體實施例中,4-四唑基-4-苯基哌啶化合物具有Ki(nM)約 100或以下。在另一具體實施例中,本發明之4-四唑基-4-苯基哌啶化合物具有Ki(nM)約10或以下。在另一具體實施 例中,4-四唑基-4-苯基哌啶化合物具有Ki(nM)約1或以下。 89531-960524.doc -157- 1343917 在另一具體實施例中,4_四唑基-4-苯基哌啶化合物具有 Ki(nM)約0.1或以下。化合物AFD,一個例示之4-四唑基_4_ 苯基哌啶化合物,結合於μ-類鴉片受體之Ki(nM)為3.2。 5.9.3 ORL-1-受體結合數攄 一般而言’ Ki值愈低’則4-四唑基-4-苯基哌啶化合物治 療或預防疼痛或腹瀉愈有效。4-四唑基-4-苯基喊啶化合物 對於ORL-1受體之Ki(nM)典型為約ι〇,〇〇〇或以下。在一個具 體實施例中,4-四唑基-4-苯基喊啶化合物具有κ丨(nM)約 2000或以下。在另一具體實施例中,4-四嗤基-4-苯基略淀 化合物具有Ki(nM)約1000或以下。在另一具體實施例中, 4-四吐基-4-苯基瓜淀化合物具有Ki(nM)約100或以下》在另 一具體實施例中’ 4-四唑基-4-苯基哌啶化合物具有Ki(nM) 約10或以下。 5.1〇免例23 :_μ-及ORL-1-類獍片夸醋之^8功能活性 下列實例證明4-四唑基-4-苯基旅啶化合物可刺激μ•及 ORL-1 -受體功能,因此可用於治療或預防疼痛或腹瀉。 5.10.1材料及古法 [35S]GTPyS功能分析係使用新鮮解凍之〇RL]或μ_受體 膜進行,如適合。分析反應係由下列試劑依序加入在冰上 之結合緩衝液(100 mM NaCl,10 mM MgCl2,20 mM HEPES, pH 7.4)(顯π最終濃度)中而製備;膜蛋白質(對於〇RL1受 體0.066毫克/毫升,對於μ_受體〇 〇26毫克/毫升),皂素 (saP〇nin)(l〇 毫克/毫升),gDP (3 mM),及[35s]GTPyS (〇2 nM; NEN)。所製備之膜溶液(19〇微升/井)移入外個淺井之 89531-960524.doc -158· 1343917
聚丙缔板中,其中含有激動劑致痛素(nociceptin)在二曱亞 砜("DMSO")中所製備之10微升20x濃縮原料溶液。各板在室 溫培育30分鐘並搖動。由使用一個96井組織收穫器(Brandel, Gaithersburg, MD)在 96 井 Unifilter GF/B 過滤板(Packard, Meriden, CT)上迅速過濾,然後以200微升冰冷結合緩衝液 (10 mM NaH2P04,10 mM Na2HP04,pH 7_4)進行三次過濾 清洗,而終止反應。然後過濾板在50 °C乾燥2-3小時。 BetaScint閃燦混合液(cocktail)(Wallac,Turku, Finland)加入 (50微升/井),各板使用一個Packard Top-Count計數1分鐘/ 井。數據係使用GraphPad PRISM v.3.0中S形劑量反應曲線 配合函數分析。 5.10.2 u-受體功能數據 μ GTP EC5Q為一種化合物對於μ受體提供50%最大反應之
濃度。4-四唑基-4-苯基哌啶化合物刺激μ類鴉片受體功能典 型具有μ GTP EC5。(ηΜ)約5000或以下。在一個具體實施例 中,4·四唑基-4-苯基哌啶化合物具有μ GTP EC5G (ηΜ)約 1000或以下。在另一具體實施例中,4-四唑基-4-苯基旅啶 化合物具有gGTPEC5〇(nM)約100或以下。在另一具體實施 例中,4-四唑基-4-苯基哌啶化合物具有μ GTP EC5Q (ηΜ)約 10或以下。在另一具體實施例中,4-四唑基-4-苯基哌啶化 合物具有μ GTP EC5Q (ηΜ)約1或以下。在另一具體實施例 中,4-四唑基-4-苯基哌啶化合物具有pGTPEC5〇(nM)約0.1 或以下。 μ GTP Emax%為一種化合物所激發之最大作用相對於[D- 89531-960524.doc -159- 1343917
Ala2,N-甲基-Phe4,Gly-〇15]-英克法林(enkephalin) ("DAMGO",一種標準μ激動劑)所激發之作用。一般而言, μ GTP Emax(%)值係測量一種化合物治療或預防疼痛或腹 瀉之功效。4-四唑基-4-苯基哌啶化合物典型具有μ GTP Emax(%)大於50%。在一個具體實施例中,4-四唑基-4-苯基 旅咬化合物具有μ GTP Emax(%)大於75%。在另一具體實施 例中4-四唑基-4-苯基哌啶化合物具有μ GTP Emax(°/〇)大於 88%。在另一具體實施例中,4-四唑基-4-苯基哌啶化合物 具有 μ GTP Emax(%)大於 100% 〇 5.10.3 ORL-1-受體功能數據 ORL-1 GTP EC5〇為一種化合物對於ORL-1受體提供50% 最大反應之濃度。4-四唑基-4-苯基旅啶化合物刺激〇RL-1 類鴉片受體功能典型具有ORL-1 GTP EC50 (nM)約10,000或 以下。在一個具體實施例中,4-四唑基-4-苯基哌啶化合物 具有ORL-1 GTP EC50 (nM)約1000或以下。在另一具體實施 例中’ 4-四唑基-4-苯基喊啶化合物具有ORL-1 GTP EC5〇 (nM)約100或以下。在另一具體實施例中,4-四峻基-4-苯基 哌啶化合物具有ORL-1 GTP EC50 (nM)約50或以下。在另一 具體實施例中,4-四哇基-4-苯基喊淀化合物具有〇RL-l GTP EC5〇 (nM)約 10或以下。 ORL-1 GTP Emax%為一種化合物所激發之最大作用相對 於致痛素(nociceptin)( —種標準ORL-1激動劑)所激發之作 用。一般而言,ORL-1 GTP Emax(%)值係測量一種化合物治 療或預防疼痛或腹瀉之功效。4-四唑基-4-苯基哌啶化合物 89531-960524.doc •160- 1343917 典型具有ORL-l GTPEmax(%)大於50%。在一個具體實施例 中,4-四唑基-4-苯基哌啶化合物具有ORL-1 GTP Emax(%) 大於75%。在另一具體實施例中4-四唑基-4-苯基哌啶化合 物具有ORL-l GTP Emax(%)大於88%。在另一具體實施例 中,4-四唑基-4-苯基哌啶化合物具有ORL-l GTP Emax(%) 大於100%。 本發明範圍不限於實例中所揭示之特定具體實施例,其 係用於例示本發明之一些方面,在功能上相等之任何具體 實施例係在本發明之範圍内。事實上,本發明之各種修飾, 除本文中已顯示及說明者,可為熟習技藝人士所明瞭,包 括在申請專利範圍内。 本文中引據許多參考資料,其全部揭示併入本文供參考。 89531-960524.doc -161 -
Claims (1)
1343917 修丨U
第092132303號專利申請案 中文申請專利範圍替換本(96年11月) 拾、申請專利範圍: 1. 一種下式(la)之化合物
或其醫藥可接受鹽,其中: G 為-H,-(CVCs 伸烷基)R5,-L(CH2)nC(0)0R4, -L-(CH2)nR5 或-((VCs 伸烷基)C02R4 ; L為-C(O)-,-S02-,或-SO-; RjgH,-C(0)NH2, -C^CONHCCVC^ 烷基),-CCCONCCVC^ 烷基)2, -C(0)NH0H,-C02R4, -CHO, -CN或-(CVCU烷基); R4 為-Η,-cvc,。烷基,-CHzNCCi-CU 烷基)2,或 -CHaN^CVC^烷基); R5 為-NH2,-NHS02R4,-C(0)NH2,-C(0)NH0H, -S02NH2,-C^CONHCC^-C^烷基),烷基)2, -S02NH(C丨-C4烷基),-S02N(C丨-C4烷基)2,-H,-OH,-CN ;及 n為1至4之整數。 2.根據申請專利範圍第1項之化合物或其醫藥可接受鹽,其 中 R丨為-C(0)NH2, -C^CONI^CVCU烷基),或-0:(0)1^((^-(:4 烷基)((^-(:4烷基)。 3-根據申請專利範圍第1項之化合物或其醫藥可接受鹽,其 中 1^為-((:0)1^((:113)2。 89531-961130.doc 1343917 4.根據申請專利範圍第1項之化合物或其醫藥可接受Μ,其 中心為-CN。 5·根據申請專利範圍第1項之化合物或其醫藥可接受睡,其 中 G為-(CH2)2NHS02H。 6.根據申請專利範圍第1項之化合物或其醫藥可接受鹽,其 中 G為-CH2C(0)NH2,-CH2C(0)NH(CrC4烷基),或·CH2c(〇) N(Ci-C4 奴基)(〇1-€4垸>基)。
7. 根據申請專利範圍第1項之化合物或其醫藥可接受缺,其 中 G為-CH2C(0)NH2。 8. 根據申請專利範圍第1項之化合物或其醫藥可接受雄,其 中 G為-(CH2)2C(0)OCH2CH3。 9. 根據申請專利範圍第1項之化合物或其醫藥可接受睡,其 中 G為-(CH2)4C(0)0CH2CH3。 10. 根據申請專利範圍第1項之化合物或其醫藥可接受跑,其 中G為
或其醫藥可接受鹽。 12. —種如下式之化合物, 89531-961130.doc 1343917
或其醫藥可接受鹽。 1 3 . —種如下式之化合物, 或其醫藥可接受鹽。 14. 一種如下式之化合物, 或其醫藥可接受鹽。 1 5 · —種如下式之化合物,
89531-961130.doc
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Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7202259B2 (en) * | 2002-11-18 | 2007-04-10 | Euro-Celtique S.A. | Therapeutic agents useful for treating pain |
EA009623B1 (ru) | 2003-04-30 | 2008-02-28 | Пэдью Фарма Л.П. | Устойчивая к манипуляциям дозировочная форма для трансдермального введения |
US8790689B2 (en) * | 2003-04-30 | 2014-07-29 | Purdue Pharma L.P. | Tamper resistant transdermal dosage form |
KR100886002B1 (ko) * | 2004-01-30 | 2009-03-03 | 유로-셀띠끄 소시에떼 아노님 | 4-테트라졸릴-4-페닐피페리딘 화합물의 제조방법 |
SE0401656D0 (sv) * | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | Chemical compounds |
UA91250C2 (en) * | 2005-11-21 | 2010-07-12 | Пердью Фарма Л.П. | 4-oxadiazolyl-piperidine compounds and use thereof |
US20080051380A1 (en) | 2006-08-25 | 2008-02-28 | Auerbach Alan H | Methods and compositions for treating cancer |
WO2011056561A1 (en) | 2009-10-27 | 2011-05-12 | Beth Israel Deaconess Medical Center | Methods and compositions for the generation and use of conformation-specific antibodies |
ME02367B (me) | 2010-09-21 | 2016-06-20 | Purdue Pharma Lp | Analozi buprenorfina kao agonisti i/ili antagonisti opioidnog receptora |
CN102648915B (zh) * | 2011-02-28 | 2015-04-15 | 鲁南制药集团股份有限公司 | 一种治疗或预防神经病理性疼痛的药物组合物 |
WO2012149334A2 (en) | 2011-04-27 | 2012-11-01 | Beth Israel Deaconess Medical Center, Inc. | Methods and compositions for the generation and use of conformation-specific antibodies |
EP2917182B1 (en) | 2012-11-09 | 2018-01-03 | Purdue Pharma LP | Benzomorphan analogs and the use thereof |
WO2014087226A1 (en) | 2012-12-07 | 2014-06-12 | Purdue Pharma L.P. | Buprenorphine analogs as opiod receptor modulators |
US8987287B2 (en) | 2012-12-14 | 2015-03-24 | Purdue Pharma L.P. | Spirocyclic morphinans and their use |
ES2631197T3 (es) | 2012-12-14 | 2017-08-29 | Purdue Pharma Lp | Análogos de piridonamorfinano y actividad biológica sobre los receptores opiodes |
EP2951160B1 (en) | 2013-01-31 | 2019-04-24 | Purdue Pharma LP | Benzomorphan analogs and the use thereof |
US8969358B2 (en) | 2013-03-15 | 2015-03-03 | Purdue Pharma L.P. | Buprenorphine analogs |
WO2015097548A1 (en) | 2013-12-26 | 2015-07-02 | Purdue Pharma L.P. | 7-beta-alkyl analogs of orvinols |
WO2015097545A1 (en) | 2013-12-26 | 2015-07-02 | Purdue Pharma L.P. | Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans |
US9994571B2 (en) | 2013-12-26 | 2018-06-12 | Purdue Pharma L.P. | 10-substituted morphinan hydantoins |
JP6353543B2 (ja) | 2013-12-26 | 2018-07-04 | パーデュー、ファーマ、リミテッド、パートナーシップ | 環縮小モルフィナン及びその使用 |
WO2015097546A1 (en) | 2013-12-26 | 2015-07-02 | Purdue Pharma L.P. | Propellane-based compounds and their use as opioid receptor modulators |
US10550088B2 (en) | 2013-12-27 | 2020-02-04 | Purdue Pharma L.P. | 6-substituted and 7-substituted morphinan analogs and the use thereof |
CA2950567A1 (en) | 2014-05-27 | 2015-12-03 | Purdue Pharma L.P. | Spirocyclic morphinans and use thereof |
US10202382B2 (en) | 2014-06-13 | 2019-02-12 | Purdue Pharma L.P. | Azamorphinan derivatives and use thereof |
MA41125A (fr) | 2014-12-05 | 2017-10-10 | Purdue Pharma Lp | Dérivés de 6.7-cyclomorphinane et leur utilisation |
AU2017238208B2 (en) | 2016-03-22 | 2022-01-06 | Regents Of The University Of Minnesota | Combination for treating pain |
KR20240115925A (ko) | 2016-07-29 | 2024-07-26 | 얀센 파마슈티카 엔브이 | 전립선암의 치료 방법 |
US10745402B2 (en) | 2017-01-02 | 2020-08-18 | Purdue Pharma L.P. | Morphinan derivatives and use thereof |
WO2022246298A1 (en) * | 2021-05-21 | 2022-11-24 | Whiteside Garth | Methods of treating interstitial cystitis/bladder pain syndrome |
WO2023250190A1 (en) * | 2022-06-24 | 2023-12-28 | Purdue Pharma L.P. | Methods of treating or preventing overactive bladder syndrome |
Family Cites Families (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3536809A (en) * | 1969-02-17 | 1970-10-27 | Alza Corp | Medication method |
US3598123A (en) * | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
US3598122A (en) * | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
BE775611A (fr) | 1970-11-24 | 1972-03-16 | Synthelabo | Derives de la (diphenyl-3,3 propyl-1)-1 piperidine, leur preparation etles medicaments qui en contiennent |
US4076717A (en) * | 1971-12-15 | 1978-02-28 | G. D. Searle & Co. | Derivatives of 1-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidine-4-carboxylic acid |
US3845770A (en) * | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
US3916899A (en) * | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
US4008719A (en) * | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
IE58110B1 (en) * | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
DK162087D0 (da) * | 1987-03-31 | 1987-03-31 | Ferrosan As | Piperidinforbindelser, deres fremstilling og anvendelse |
US4831192A (en) * | 1987-12-31 | 1989-05-16 | Boc, Inc. | Methods of preparing 4-heteropentacyclic-4-(N-phenyl)amido) piperidine derivatives and intermediate compounds |
US5073543A (en) * | 1988-07-21 | 1991-12-17 | G. D. Searle & Co. | Controlled release formulations of trophic factors in ganglioside-lipsome vehicle |
IT1229203B (it) * | 1989-03-22 | 1991-07-25 | Bioresearch Spa | Impiego di acido 5 metiltetraidrofolico, di acido 5 formiltetraidrofolico e dei loro sali farmaceuticamente accettabili per la preparazione di composizioni farmaceutiche in forma a rilascio controllato attive nella terapia dei disturbi mentali organici e composizioni farmaceutiche relative. |
US5120548A (en) * | 1989-11-07 | 1992-06-09 | Merck & Co., Inc. | Swelling modulated polymeric drug delivery device |
US5733566A (en) * | 1990-05-15 | 1998-03-31 | Alkermes Controlled Therapeutics Inc. Ii | Controlled release of antiparasitic agents in animals |
US5698155A (en) * | 1991-05-31 | 1997-12-16 | Gs Technologies, Inc. | Method for the manufacture of pharmaceutical cellulose capsules |
US5580578A (en) * | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
US5449989A (en) | 1992-07-31 | 1995-09-12 | Correa; Paulo N. | Energy conversion system |
US5606037A (en) | 1992-11-09 | 1997-02-25 | Biochem Pharma Inc. | Processes antineoplastic heteronaphthoquinones |
US5736523A (en) | 1992-11-09 | 1998-04-07 | Biochem Pharma Inc. | Antineoplastic heteronapthoquinones |
US5591767A (en) * | 1993-01-25 | 1997-01-07 | Pharmetrix Corporation | Liquid reservoir transdermal patch for the administration of ketorolac |
IT1270594B (it) * | 1994-07-07 | 1997-05-07 | Recordati Chem Pharm | Composizione farmaceutica a rilascio controllato di moguisteina in sospensione liquida |
US5849737A (en) | 1995-04-14 | 1998-12-15 | The Regents Of The University Of California | Compositions and methods for treating pain |
US6166085A (en) | 1995-04-14 | 2000-12-26 | The Regents Of The University Of California | Method of producing analgesia |
EP0833622B8 (en) * | 1995-06-12 | 2005-10-12 | G.D. Searle & Co. | Compositions comprising a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor |
US6573282B1 (en) | 1995-09-12 | 2003-06-03 | Adolor Corporation | Peripherally active anti-hyperalgesic opiates |
US5849761A (en) | 1995-09-12 | 1998-12-15 | Regents Of The University Of California | Peripherally active anti-hyperalgesic opiates |
WO1997024325A1 (en) | 1995-12-28 | 1997-07-10 | Takeda Chemical Industries, Ltd. | DIPHENYLMETHANE DERIVATIVES AS MIP-1α/RANTES RECEPTOR ANTAGONISTS |
US6221888B1 (en) | 1997-05-29 | 2001-04-24 | Merck & Co., Inc. | Sulfonamides as cell adhesion inhibitors |
EE03970B1 (et) * | 1997-06-10 | 2003-02-17 | Synthon B.V. | 4-fenüülpiperidiinühend, selle valmistamine ja kasutamine ning seda sisaldav ravim |
PL342818A1 (en) | 1998-03-06 | 2001-07-02 | Janssen Pharmaceutica Nv | Glycin transport inhibitors |
US6423519B1 (en) * | 1998-07-15 | 2002-07-23 | Gpc Biotech Inc. | Compositions and methods for inhibiting fungal growth |
US7217714B1 (en) | 1998-12-23 | 2007-05-15 | Agouron Pharmaceuticals, Inc. | CCR5 modulators |
PE20001420A1 (es) | 1998-12-23 | 2000-12-18 | Pfizer | Moduladores de ccr5 |
ATE278674T1 (de) | 1999-03-12 | 2004-10-15 | Boehringer Ingelheim Pharma | Heterocyklischer harnstoff und verwandte verbindungen als entzündungshemmende mittel |
EP1219294A4 (en) | 1999-09-20 | 2005-01-26 | ANTAGONISTS OF THE MELANIN CONCENTRATING HORMON | |
CA2324330A1 (en) | 1999-11-08 | 2001-05-08 | Ssp Co., Ltd. | 4-hydroxy-4-phenylpiperidine derivatives and pharmaceuticals containing the same |
ATE302770T1 (de) | 1999-12-06 | 2005-09-15 | Euro Celtique Sa | Benzimidazolverbindungen die nociceptinrezeptoraffinität haben |
JP2003518130A (ja) | 1999-12-22 | 2003-06-03 | メルク フロスト カナダ アンド カンパニー | 蛋白チロシンホスファターゼ1b(ptp−1b)阻害薬としてのホスホン酸誘導体 |
US6703525B2 (en) | 2000-02-16 | 2004-03-09 | Boehringer Ingelheim Pharmaceuticals, Inc. | Sulfonamide intermediates and methods of producing same |
US6608052B2 (en) | 2000-02-16 | 2003-08-19 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compounds useful as anti-inflammatory agents |
WO2001070689A1 (fr) * | 2000-03-24 | 2001-09-27 | Meiji Seika Kaisha, Ltd. | DERIVES DE LA DIPHENYLALKYLAMINE UTILES COMME AGONISTES DU RECEPTEUR DE L'OPIOIDE $g(d) |
US6544981B2 (en) | 2000-06-09 | 2003-04-08 | Bristol-Myers Squibb Company | Lactam inhibitors of factor Xa and method |
KR20030043970A (ko) | 2000-10-12 | 2003-06-02 | 에스에스 세야쿠 가부시키 가이샤 | 2,2-디페닐부탄아미드 유도체 및 이를 함유하는 의약 |
WO2002038185A2 (en) | 2000-11-13 | 2002-05-16 | Atrix Laboratories, Inc. | Injectable sustained release delivery system with loperamide |
US7202259B2 (en) * | 2002-11-18 | 2007-04-10 | Euro-Celtique S.A. | Therapeutic agents useful for treating pain |
KR100886002B1 (ko) * | 2004-01-30 | 2009-03-03 | 유로-셀띠끄 소시에떼 아노님 | 4-테트라졸릴-4-페닐피페리딘 화합물의 제조방법 |
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