JP2016507504A - ジアゾールアミド - Google Patents
ジアゾールアミド Download PDFInfo
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- JP2016507504A JP2016507504A JP2015549830A JP2015549830A JP2016507504A JP 2016507504 A JP2016507504 A JP 2016507504A JP 2015549830 A JP2015549830 A JP 2015549830A JP 2015549830 A JP2015549830 A JP 2015549830A JP 2016507504 A JP2016507504 A JP 2016507504A
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
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Abstract
Description
本出願は、2012年11月21日に出願された米国特許仮出願第61/745,444号に対する優先権の利益を主張し、それは参照により全体が本明細書に組込まれる。
該当事項なし
各Aは、N及びCHから成る群から独立して選択され;
X及びZは、
(i)単環式又は縮合二環式アリール及びヘテロアリール(ここで前記へテロアリール基はN、O及びSから選択された1〜4個のヘテロ原子を環員として有する);
(ii)シクロアルカン及びヘテロシクロアルカンから成る群から選択された、単環式の4、5、6又は7員の環(ここで前記へテロシクロアルカン環はN、O及びSから選択された1〜3個のヘテロ原子を環員として有する)から成る群からそれぞれ独立して選択され、
ここで(i)及び(ii)における各環は、ハロゲン、CN、C1-8アルキル、C3-8シクロアルキル、C2-8アルケニル、C2-8アルキニル、C1-8ハロアルキル、C1-8ヒドロキシアルキル、−ORa、−CO2Ra、−SO2Ra、−NRaRb、−CONRaRb、アリール、5−又は6−員のヘテロアリール、及び3−、4−、5−又は6−員のヘテロシクロアルカンから選択された1〜5個の置換基により任意に置換され、ここでヘテロアリール及びヘテロシクロアルカン環の環頂点として存在するヘテロ原子はN、O及びSから選択され、そして前記置換基中のアルキル、シクロアルキル、アリール、ヘテロアリール及びヘテロシクロアルカン部分は任意にはさらに、1〜3個のRaにより置換され;そして任意には、隣接する環頂点上の2個の置換基は、C、O、N及びSから選択された環頂点を有する、飽和、不飽和又は芳香族である追加の5又は6員環を形成するために連結され;
R3は、H、ハロゲン、CN、C1-8アルキル、C3-8シクロアルキル、C2-8アルケニル、C2-8アルキニル、C1-8ハロアルキル、C1-8ヒドロキシアルキル、−ORa、−CO2Ra、−NRaRb、−CONRaRb、アリール、5−又は6−員のヘテロアリール、及び3−、4−、5−又は6−員のヘテロシクロアルカンから成る群から選択されたメンバーであり、ここでヘテロアリール及びヘテロシクロアルカン環の環頂点として存在するヘテロ原子はN、O及びSから選択され、そしてR3のアルキル、シクロアルキル、アリール、ヘテロアリール及びヘテロシクロアルカン部分は任意にはさらに、1〜3個のRaにより置換され;
R4は、H、−ORa、及び−ORa又は−NRaRbにより任意に置換されたC1-8アルキルから成る群から選択されたメンバーであり;又はR4はXと結合されて、二環式の縮合環系を形成し;
各Ra及びRbは、水素、ヒドロキシル、ハロゲン、シアノ、C1-8アルキル、C1-8アルコキシ、C1-8ハロアルキル、C3-6シクロアルキル、C3-6シクロアルキルアルキル、アミノ、C1-8アルキルアミノ、ジC1-8アルキルアミノ、カルボキサミド、カルボキシC1-4アルキルエステル、カルボン酸、及び−SO2−C1-8アルキルら成る群から独立して選択される。
用語「アルキル」(alkyl)とは、それ自体で又は別の置換基の一部として、特にことわらない限り、指定される炭素原子を有する直鎖又は分岐鎖の炭化水素基を意味する(すなわち、C1-8は、1〜8個の炭素を意味する)。アルキル基の例としては、メチル、エチル、n-プロピル、イソプロピル、n−ブチル、t-ブチル、イソブチル、sec−ブチル、n-ペンチル、n−ヘキシル、n-ヘプチル、n-オクチル、及び同様のものを挙げることができる。用語「アルケニル」(alkenyl)とは、1又は2以上の二重結合を有する不飽和アルキル基を言及する。同様に、用語「アルキニル」(alkynyl)とは、1又は2以上の三重結合を有する不飽和アルキル基を言及する。そのような不飽和アルキル基の例としては、ビニル、2−プロペニル、クロチル、2−イソペンテニル、2−(ブタジエニル)、2、4−ペンタジエニル、3−(1、4−ペンタジエニル)、エチニル、1− 及び 3−プロピニル、3−ブチニル、及び高級同族体及び異性体を挙げることができる。用語「シクロアルキル」(cycloalkyl)とは、示される数の環原子(例えば、C3-6シクロアルキル)を有し、そして十分に飽和されているか、又は環頂点間にわずか1つの二重結合を有する炭化水素環を言及する。「シクロアルキル」はまた、二環式及び多環式炭化水素環、例えばビシクロ[2.2.1]ヘプタン、ビシクロ[2.2.2]オクタン、等を意味する。用語「ヘテロシクロアルカン」(heterocycloalkane)又は「ヘテロシクロアルキル」(heterocycloalkyl)とは、N、O及びSから選択された1〜5個のヘテロ原子を含むシクロアルキル基を言及し、ここで窒素及び硫黄原子は任意には酸化され、そして窒素原子は任意には、四級化される。ヘテロシクロアルカンは、単環式、二環式又は多環式環系であり得る。ヘテロシクロアルカン基の非制限的例としては、ピロリジン、イミダゾリジン、ピラゾリジン、ブチロラクタム、バレロラクタム、イミダゾリジノン、ヒダントイン、ジオキソラン、フタルイミド、ピペリジン、1,4 - ジオキサン、モルホリン、チオモルホリン、チオモルホリン-S-オキシド、チオモルホリン-S、S-オキシド、ピペラジン、ピラン、ピリドン、3 - ピロリン、チオピラン、ピロン、テトラヒドロフラン、テトラヒドロチオフェン、キヌクリジン、及び同様のものを挙げることができる。ヘテロシクロアルカン基は、環炭素又はヘテロ原子を介して分子の残部に結合され得る。
本発明は、式Iの化合物がCCR1受容体の有能なアンタゴニストとして作用する発見に由来する。化合物は、インビボ抗炎症活性を有し、そして卓越した薬物動態学的特性を有する。従って、本明細書に提供される化合物は、医薬組成物、CCR1介在性疾患の治療方法において、及び競争的CCR1アンタゴニストの同定のためのアッセイにおける対照として有用である。
1つの態様によれば、本発明は、下記式I:
各Aは、N及びCHから成る群から独立して選択され;
X及びZは、
(i)単環式又は縮合二環式アリール及びヘテロアリール(ここで前記へテロアリール基はN、O及びSから選択された1〜4個のヘテロ原子を環員として有する);
(ii)シクロアルカン及びヘテロシクロアルカンから成る群から選択された、単環式の4、5、6又は7員の環(ここで前記へテロシクロアルカン環はN、O及びSから選択された1〜3個のヘテロ原子を環員として有する)から成る群からそれぞれ独立して選択され、
ここで(i)及び(ii)における各環は、ハロゲン、CN、C1-8アルキル、C3-8シクロアルキル、C2-8アルケニル、C2-8アルキニル、C1-8ハロアルキル、C1-8ヒドロキシアルキル、−ORa、−CO2Ra、−SO2Ra、−NRaRb、−CONRaRb、アリール、5−又は6−員のヘテロアリール、及び3−、4−、5−又は6−員のヘテロシクロアルカンから選択された1〜5個の置換基により任意に置換され、ここでヘテロアリール及びヘテロシクロアルカン環の環頂点として存在するヘテロ原子はN、O及びSから選択され、そして前記置換基中のアルキル、シクロアルキル、アリール、ヘテロアリール及びヘテロシクロアルカン部分は任意にはさらに、1〜3個のRaにより置換され;そして任意には、隣接する環頂点上の2個の置換基は、C、O、N及びSから選択された環頂点を有する、飽和、不飽和又は芳香族である追加の5又は6員環を形成するために連結され;
R3は、H、ハロゲン、CN、C1-8アルキル、C3-8シクロアルキル、C2-8アルケニル、C2-8アルキニル、C1-8ハロアルキル、C1-8ヒドロキシアルキル、−ORa、−CO2Ra、−NRaRb、−CONRaRb、アリール、5−又は6−員のヘテロアリール、及び3−、4−、5−又は6−員のヘテロシクロアルカンから成る群から選択されたメンバーであり、ここでヘテロアリール及びヘテロシクロアルカン環の環頂点として存在するヘテロ原子はN、O及びSから選択され、そしてR3のアルキル、シクロアルキル、アリール、ヘテロアリール及びヘテロシクロアルカン部分は任意にはさらに、1〜3個のRaにより置換され;
R4は、H、−ORa、及び−ORa又は−NRaRbにより任意に置換されたC1-8アルキルから成る群から選択されたメンバーであり;又はR4はXと結合されて、二環式の縮合環系を形成し;
各Ra及びRbは、水素、ヒドロキシル、ハロゲン、シアノ、C1-8アルキル、C1-8アルコキシ、C1-8ハロアルキル、C3-6シクロアルキル、C3-6シクロアルキルアルキル、アミノ、C1-8アルキルアミノ、ジC1-8アルキルアミノ、カルボキサミド、カルボキシC1-4アルキルエステル、カルボン酸、及び−SO2−C1-8アルキルら成る群から独立して選択される。
以下の実施例中のスキームは、本発明の特定の化合物にアクセスするために追跡することができる特定の合成経路を提供する。他の経路、又は下記に提供される経路の変更は、当業者には容易に明らかであり、そして本発明の範囲内であろう。
上記に提供される化合物の他に、ヒト及び動物においてCCR1活性を調節するための組成物は典型的には、医薬的担体又は希釈剤を含むであろう。
さらなる別の態様によれば、本発明は、治療的有効量の上記式Iの化合物を、CCR1−介在性状態又は疾患を有する対象に投与することにより、そのような疾患又は状態を治療する方法を提供する。「対象」(subject)とは、動物、例えば哺乳類、例えば霊長類(例えば、ヒト)、ウシ、ヒツジ、ヤギ、ウマ、イヌ、ネコ、ウサギ、ラット、マウス及び同様のもの(但し、それらだけには限定されない)を包含することが、本明細書においては、定義される。
次の実施例は、本発明を例示するために提供されるが、しかし本発明の範囲を制限するものではない。
この実施例は、本発明の目的の化合物に関連する生物学的活性の評価を例示する。
材料及び方法
A.細胞
1.CCR1発現細胞
a)THP−1細胞
走化性アッセイを、走化性緩衝液(ハンクス液(HBSS)及び1%FBS)を用いて、96ウェル走化性チャンバー(Neuroprobe; Gaithersburg, MD)における5μmの細孔ポリカーボネート製のポリビニルピロリドン被覆されたフィルターを用いて実施した。CCR1ケモカインリガンド(すなわち、MIP-1α、CCL15/Leukotactin; R&D Systems; Minneapolis, MN)を、CCR1介在性移行の化合物介在性阻害を評価するために使用する。他のケモカイン(すなわち、SDF-1α; R&D Systems; Minneapolis, MN)を、特異的対照として使用する。下部チャンバーを、29μlのケモカイン(すなわち、0.1nMのCCL15/ロイコタクチン)及び種々の量の化合物により充填し;上部チャンバーは、100,000個のTHP−1又は単球細胞を20μlで含んだ。チャンバーを、37℃で1〜2時間インキュベートし、そして下部チャンバー中の細胞の数を、ウェル当たり5つの高倍率フィールドにおける直接的細胞計数により、又はCyQuantアッセイ(Molecular Probes)、すなわち核酸含量及び顕微鏡観察を測定する蛍光色素法のいずれかにより定量する。
ケモカインの主要機能の1つは、ケモカイン受容体−発現細胞、例えば白血球細胞の移行を介在するそれらの能力である。目的の化合物が、CCR1特異的結合及びシグナル伝達(少なくとも、カルシウム移動アッセイにより決定されるような)のみならず、また、CCR1介在性移行を阻害したことを確認するために、走化性アッセイを使用した。単球及び新たに単離された単球に類似するTHP−1骨髄単球性白血病細胞を、CCR1ケモカインリガンド(すなわち、MIP−1α、CCL15/ロイコタクチン)による化学誘引のための標的として使用した。細胞を、マイクロウェル移行チャンバーの上部区画に配置し、そしてMIP−1α(又は他の有能なCCR1ケモカインリガンド)及び上昇する濃度の目的の化合物を、下部チャンバーに充填した。阻害剤の不在下で、細胞はケモカインアゴニストに応答して下部チャンバーに移行し;化合物がCCR1機能を阻害する場合、細胞の大部分は上部チャンバーに残るだろう。CCR1に対する目的の親和性の化合物を確認するために、及びCCR1介在性細胞移行を阻害するその能力を確かめるために、阻害活性を、この走化性アッセイにおいて1×10-10〜1×10-4Mの範囲の化合物濃度にわたって滴定した。このアッセイにおいては、化合物の量が変更され;ところが細胞数及びケモカインアゴニスト濃度は一定に維持された。走化性チャンバーが37℃で1〜2時間インキュベートされた後、下部チャンバー内の応答細胞を、CyQuant assay (Molecular Probes)による標識、核酸含量を測定する蛍光色素法、及びSpectrafluor Plus (Tecan)による測定により定量化した。GraphPad, Inc. (San Diego, Ca)からのコンピュータープログラムPrismを用いて、IC50値を計算した。IC50値は、CCR1に応答する細胞の数を、50%阻害するために必要とされるそれらの化合物濃度である。
a)破壊的関節炎症のウサギモデル
ウサギLPS研究を、Podolinら、J. Immunol. 169(11):6435-6444 (2002)に記載のようにして、実質的に実施した。雌のニュージーランドウサギ(約2kg)を、LPS(10ng)により、両膝の関節内を処理した。目的の化合物、例えば1.016(1%メトセルで処方された)又はビヒクル(1%メトセル)を、2度(関節内LPS注入の2時間前、及び関節LPS注入の4時間後)、5ml/kgの用量体積で経口投与した。LPS注入の16時間後、膝を洗浄し、そして細胞計算を行った。治療の有益な効果を、膝関節の炎症滑液にリクルートされる炎症性細胞の数の低下により決定した。目的の化合物による治療は、リクルートされた炎症性細胞の有意な低下をもたらした。
17日の進行性II型コラーゲン関節炎研究を行い、関節炎誘発された臨床学的足首の腫脹に対する目的の化合物の効果を評価する。ラットコラーゲン関節炎は、多数の抗−関節炎剤の前臨床試験のために広く使用されて来た多発性関節炎の実験モデルである(Trenthamら、J. Exp. Med. 146(3):857-868 (1977), Bendeleら、Toxicologic Pathol. 27:134-142 (1999), Bendeleら、Arthritis Rheum. 42:498-506 (1999)を参照のこと)。このモデルの特徴は、堅固で容易に測定できる多関節炎症、パンヌス形成に関連する顕著な軟骨破壊、及び軽度〜中程度の骨吸収及び骨膜骨増殖の信頼できる発症及び進行である。
本発明の化合物を、オキサゾロンにより誘発された皮膚遅延型過敏症のマウスモデルにおいて評価することができる。手短に言及すれば、生後8〜10週のBALB/cマウスを、エタノールに溶解されたオキサゾロンの1%溶液により、0日でそれらの毛剃りされた腹部に局部的に感作する。感作後6日目に、マウスを、ビヒクル、又は上昇する用量の本発明の化合物により、右耳上にエタノール中、オキサゾロンの0.5%溶液による局部投与の直前及び4時間後、経口投与する。次の日(7日目)、耳の厚さを、ノギス測定を用いて測定する。化合物により処置された動物は、ビヒクル処置された対象に比較して、有意に低められた耳腫脹を有し、このことは、オキサゾロン誘発された皮膚過敏症における化合物介在低下を示す。
本発明の化合物を、アレルギー性喘息のマウスモデルにおいて評価することができる。喘息を、生後8〜10週のBALB/cマウスにおいて、0日及び10日目、アラムアジュバント中、OVAによりマウスを感作することにより誘発する。20日目、マウスを、PBS中、OVAにより鼻腔内投与し、気道炎症を誘発する。マウスグループを、20日目に開始し、そして23日目まで続いて、ビヒクル、又は上昇する用量の本発明の化合物により処置する。動物を、気管支肺胞洗浄液(BAL)中の細胞浸潤物について、鼻腔内OVA投与の23日後、分析する。ビヒクル処置されたマウスに対する、BAL白血球数の有意な低下が、化合物がこのモデルにおいて効果的であることを示唆する。
この実施例は、全身性エリテマトーデス(SLE)の治療のためのCCR1アンタゴニストの有効性を評価するための手順を記載する。雌NZB/W FIマウスは、タンパク尿、血清自己抗体、糸球体腎炎及び結果的に死亡により特徴づけられる、生後6カ月の時点で開始するSLE様病理を自発的に進行せしめる。グループ当たり20匹のマウスを含む、3種のシリーズのNZB/W FIマウスグループを、次の通りにCCR1アンタゴニストの有効性について試験する:1つのシリーズのマウスはさらに、離乳後すぐに、及びその後、種々の投与スケジュールでリン酸緩衝生理食塩水(PBS)及びTween0.5%を、i.p.受容する。第2シリーズは、離乳後すぐに、及びその後の異なった投与スケジュールで、腹腔内、静脈内、皮下、筋肉内、経口、又は何れか他の投与モードを通して与えられる異なった用量のCCR1アンタゴニストを受けるマウスのグループから成る。正の対照として作用する第三シリーズのマウスは、離乳後すぐに、及びその後の異なったの投与スケジュールで、与えられる抗−IL10抗体により処理されるグループから成る。疾患の進行を、最終的な死亡率、腎組織学、血清自己抗体レベル及びタンパク質尿の面でモニターする。
この実施例は、悪性腫瘍の治療のためのCCR1アンタゴニストの有効性を評価するための手順を記載する。正常マウス株は、種々の十分に特徴づけられているマウス腫瘍系、例えばOVAによるワクチン接種に続いての腫瘍特異的抗原応答の評価を容易にするために、OVAによりトランスフェクトされたマウス胸腺腫EL4により移植され得る。それらの腫瘍モデルの何れかからの3種のシリーズのマウスグループを、次の通りに、CCR1アンタゴニスト有効性について試験する:1つのシリーズのマウスはさらに、腫瘍移植後すぐに、及びその後、種々の投与スケジュールでPBS及びTween0.5%を、i.p.受容する。第2シリーズは、腫瘍移植後すぐに、及びその後の異なったの投与スケジュールで、腹腔内、静脈内、皮下、筋肉内、経口、又は何れか他の投与モードを通して与えられる異なった用量のCCR1アンタゴニストを受けるマウスのグループから成る。正の対照として作用する第三シリーズのマウスは、腫瘍移植後すぐに、及びその後の異なったの投与スケジュールで、i.p.下で与えられる抗−IL4抗体、抗−IFNg 抗体、 IL4又は TNFにより処理されるグループから成る。効率は、退行に対する腫瘍増殖を通してモニターされる。OVAトランスフェクトされたEL4胸腺腫モデルの場合、細胞溶解性OVA特異的応答が、インビトロでOVAにより、排出するリンパ節細胞を刺激し、そして72時間での抗原特異的細胞毒性を測定することにより、測定され得る。
この実施例は、乾癬におけるCCR1アンタゴニストの有効性を評価するための手順を記載する。乾癬の齧歯類モデルは、免疫不全受容体CB.17scid/scidマウス中に、BALB/cマウスの脾臓から得られた精製T細胞集団(CD45Rbhi T細胞とも称する)を、静脈内トランスファーすることにより得られる。マウスは、その移行後8週までに、耳、足及び尾にヒト乾癬の徴候に類似する、発赤、腫張及び皮膚病変の徴候を発症する。グループ当たり10〜15匹のCB.17scid/scidマウスを含む3種のシリーズのマウスグループは、精製CD45Rbhi T細胞を注射される。1つのシリーズのマウスは、さらに、最初の細胞トランスファーで、及びその後の異なった投与スケジュールで、リン酸緩衝生理食塩水(PBS)及びTween0.5%を、i.p.下で受ける。第2シリーズは、初期細胞トランスファー後すぐに、及びその後の異なったの投与スケジュールで、腹腔内、静脈内、皮下、筋肉内、経口、又は何れか他の投与モードを通して与えられる異なった用量のCCR1アンタゴニストを受けるマウスのグループから成る。正の対照として作用する第三シリーズのマウスは、初期細胞トランスファー後すぐに、及びその後の異なったの投与スケジュールで、IL−12、IL−4、IFNg又はTNF、 又はサイトカインIL−10の何れかに対する抗体により処理されるグループから成る。動物は、細胞トランスファー後3ヶ月間、乾癬様病変の進行についてモニターされた。
P−糖タンパク質遺伝子を欠いているMDR1a−ノックアウトマウスが、特定病原体を含まない条件下で大腸炎を自発的に発症する。それらの動物における病理は、ヒトにおける潰瘍性大腸炎に類似するTh1型T細胞−介在性炎症として特徴づけられてきた。疾患は通常、生後、約8〜10週で発症し始める。しかしながら、疾患が出現する年齢及び究極な浸透レベルは、多くの場合、異なった動物施設間で相当に変化する。MDR1a−ノックアウトマウスを用いる研究においては、CCR1アンタゴニストが、投与時間に依存して、予防的に又は治療的に評価され得る。雌マウス(n=34)は、有効用量で、皮下方法で毎日、必要に応じて、目的の化合物を投与される。この研究は、IBD関連の成長遅延、及び肛門排出及び刺激の評点について評価される。肛門排出及び刺激を減じるか、又はIBD関連の成長遅延を阻害する化合物が、この適応症における化合物の有効性を示している。
マウスRENCA腫瘍モデルは、特に肺への自発的転移を参照して、成人腎細胞癌の進行を模倣し、そして固形腫瘍についてのモデルとして役立つ。生後6〜8週の雌のBalb/cマウスが、約5×105個のRENCA細胞(マウス腎腺細胞;ATCCカタログ番号CRL−2947)により、腎被膜下で接種され、そして腎腫瘍増殖が22日間にわたって観察され、そして肺転移が早くも15日目に観察される。動物は、ビヒクル又は本発明の化合物は、一次増殖に対する効果をモニターするために腫瘍移植の時点から、又は転移に対する化合物の効果をモニターするために、後の時点(例えば、7日目)で、毎日皮下投与される。一次腫瘍領域を、機械式キャリパーを用いて、週2度、測定する。腫瘍体積は、式v=pab2/6(ここで、aは最長径であり、そしてbは、aに対して垂直な次に長い直径である)により計算される。転移腫瘍体積又は発生率の低下は、この適応症における化合物の有効性を示している。
腹膜中に3%チオグリコレートを導入することにより腹膜炎症を誘発する方法は、当技術分野において知られている。チオグリコレートの導入に続いて、主にCCR1担持好中球の部位への免疫細胞の急速な流入が、24時間で局所的炎症をもたらす。腹腔滲出物をサンプリングし、そして細胞数及び組成が、チオグリコレート誘発の前、その間、又はその後、投与される目的の化合物の抗炎症性質を決定するために評価され得る。
Claims (28)
- 下記構造(I):
各Aは、N及びCHから成る群から独立して選択され;
X及びZは、
(i)単環式又は縮合二環式アリール及びヘテロアリール(ここで前記へテロアリール基はN、O及びSから選択される1〜4個のヘテロ原子を環員として有する);
(ii)シクロアルカン及びヘテロシクロアルカンから成る群から選択される、単環式の4、5、6又は7員の環(ここで前記へテロシクロアルカン環はN、O及びSから選択される1〜3個のヘテロ原子を環員として有する)から成る群からそれぞれ独立して選択され、
ここで(i)及び(ii)における各環は、ハロゲン、CN、C1-8アルキル、C3-8シクロアルキル、C2-8アルケニル、C2-8アルキニル、C1-8ハロアルキル、C1-8ヒドロキシアルキル、−ORa、−CO2Ra、−SO2Ra、−NRaRb、−CONRaRb、アリール、5−又は6−員のヘテロアリール、及び3−、4−、5−又は6−員のヘテロシクロアルカンから選択される1〜5個の置換基で任意に置換され、ここでヘテロアリール及びヘテロシクロアルカン環の環頂点として存在するヘテロ原子は、N、O及びSから選択され、そして前記置換基中のアルキル、シクロアルキル、アリール、ヘテロアリール及びヘテロシクロアルカン部分は任意にはさらに、1〜3個のRaで置換され;そして任意には、隣接する環頂点上の2個の置換基は連結され、C、O、N及びSから選択される環頂点を有する、飽和、不飽和又は芳香族である追加の5又は6員環を形成し;
R3は、H、ハロゲン、CN、C1-8アルキル、C3-8シクロアルキル、C2-8アルケニル、C2-8アルキニル、C1-8ハロアルキル、C1-8ヒドロキシアルキル、−ORa、−CO2Ra、−NRaRb、−CONRaRb、アリール、5−又は6−員のヘテロアリール、及び3−、4−、5−又は6−員のヘテロシクロアルカンから成る群から選択されるメンバーであり、ここでヘテロアリール及びヘテロシクロアルカン環の環頂点として存在するヘテロ原子はN、O及びSから選択され、そしてR3のアルキル、シクロアルキル、アリール、ヘテロアリール及びヘテロシクロアルカン部分は任意にはさらに、1〜3個のRaで置換され;
R4は、H、−ORa、及び−ORa又は−NRaRbで任意に置換されたC1-8アルキルから成る群から選択されるメンバーであり;又はXと結合されて、二環式の縮合環系を形成し;
各Ra及びRbは、水素、ヒドロキシル、ハロゲン、シアノ、C1-8アルキル、C1-8アルコキシ、C1-8ハロアルキル、C3-6シクロアルキル、C3-6シクロアルキルアルキル、アミノ、C1-8アルキルアミノ、ジC1-8アルキルアミノ、カルボキサミド、カルボキシC1-4アルキルエステル、カルボン酸、及び−SO2−C1-8アルキルから成る群から独立して選択される]
により表される化合物、その任意の塩、溶媒和物、水和物、N−酸化物又は回転異性体。 - 下記構造:
A1は、N又はC(R5)であり;
A2は、N又はC(R7)であり;
R5、R6、R7及びR8は、H、ハロゲン、CN、C1-8アルキル、C3-8シクロアルキル、C2-8アルケニル、C2-8アルキニル、C1-8ハロアルキル、C1-8ヒドロキシアルキル、−ORa、−CO2Ra、−NRaRb、−CONRaRb、アリール、5−又は6−員のヘテロアリール、及び3−、4−、5−又は6−員のヘテロシクロアルカンから成る群からそれぞれ独立して選択され、ここでヘテロアリール及びヘテロシクロアルカン環の環頂点として存在するヘテロ原子はN、O及びSから選択され、そしてR5、R6、R7及びR8のアルキル、シクロアルキル、アリール、ヘテロアリール及びヘテロシクロアルカン部分は任意にはさらに、1〜3個のRaで置換され;そして任意には、R4及びR5、R4及びR8又はR5、R6、R7及びR8の隣接するメンバーは連結され、C、O、N及びSから選択される環頂点を有する、飽和、不飽和又は芳香族である追加の5又は6員環を形成する]
により表される、請求項1に記載の化合物、その医薬的に許容できる塩、水和物、溶媒和物、回転異性体又はN−酸化物。 - R8がH以外である、請求項2に記載の化合物。
- 下記構造:
R1及びR2は、H、ハロゲン、CN、C1-8アルキル、C3-8シクロアルキル、C2-8アルケニル、C2-8アルキニル、C1-8ハロアルキル、C1-8ヒドロキシアルキル、−ORa、−CO2Ra、−SO2Ra、−NRaRb、−CONRaRb、及び3−、4−、5−又は6−員のヘテロシクロアルカンから成る群からそれぞれ独立して選択され、ここでヘテロシクロアルカン環の環頂点として存在するヘテロ原子はN、O及びSから選択され、そしてR1及びR2のアルキル、シクロアルキル、及びヘテロシクロアルカン部分は任意にはさらに、1〜3個のRaで置換される]
により表される、請求項2に記載の化合物。 - 各R1及びR2が、H、ハロゲン、CN、C1-8アルキル、C1-8ハロアルキル、−CO2Ra及び−SO2Raから成る群から独立して選択される、請求項4に記載の化合物。
- 下記構造:
- R4がCH3である、請求項6に記載の化合物。
- N、A1及びA2を環頂点として有する環部分が、下記構造:
- N、A1及びA2を環頂点として有する環部分が、下記構造;
R1及びR2は、H、ハロゲン、CN、C1-8アルキル、C3-8シクロアルキル、C2-8アルケニル、C2-8アルキニル、C1-8ハロアルキル、C1-8ヒドロキシアルキル、−ORa、−CO2Ra、−SO2Ra、−NRaRb、−CONRaRb、及び3−、4−、5−又は6−員のヘテロシクロアルカンから成る群からそれぞれ独立して選択され、ここでヘテロシクロアルカン環の環頂点として存在するヘテロ原子はN、O及びSから選択され、そしてここでR1及びR2のアルキル、シクロアルキル、及びヘテロシクロアルカン部分は任意にはさらに、1〜3個のRaで置換され;そして
R7は、H又はClであり、そしてR8は、1又は2個のRaで任意に置換されるC1-8アルキルである]
から成る群から選択される、請求項4に記載の化合物。 - 下記構造:
により表される、請求項7に記載の化合物。 - 下記構造:
- 下記構造:
- 下記構造:
- 下記構造:
により表される、請求項4に記載の化合物。 - 下記構造:
により表される、請求項7に記載の化合物。 - 下記構造:
- 下記構造:
- 下記構造:
- R3がC1-8アルキルである、請求項1〜14、16、17又は18のいずれか一項に記載の化合物。
- 請求項1に記載の化合物、及び医薬的に許容できる賦形剤又は担体を含む医薬組成物。
- 請求項2に記載の化合物、及び医薬的に許容できる賦形剤又は担体を含む医薬組成物。
- 治療的有効量の請求項2に記載の化合物を、それを必要とする対象に投与することを含む、CCR1介在性疾患又は状態の処置方法。
- 前記CCR1介在性疾患又は状態が、炎症状態である、請求項22に記載の方法。
- 前記CCR1介在性疾患又は状態が、免疫調節障害である、請求項22に記載の方法。
- 前記CCR1介在性疾患又は状態が、移植拒絶、皮膚炎、湿疹、蕁麻疹、血管炎、炎症性腸疾患、食物アレルギー、喘息、アルツハイマー病、パーキンソン病、乾癬、エリテマトーデス、脳卒中、再狭窄及び脳脊髄炎から成る群から選択される、請求項22に記載の方法。
- 前記CCR1介在性疾患又は状態が、関節リウマチ、多発性硬化症、変形性関節症、多発性骨髄腫及び骨粗鬆症から成る群から選択される、請求項22に記載の方法。
- 前記投与が、経口、非経口、直腸、経皮、舌下、鼻内又は局所である、請求項22に記載の方法。
- 前記化合物が、抗炎症剤、鎮痛剤、抗増殖剤、代謝阻害剤、白血球遊走阻害剤又は免疫調節剤と組み合わせて投与される、請求項22に記載の方法。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011520806A (ja) * | 2008-05-06 | 2011-07-21 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ccr1アンタゴニストとしてのピラゾール化合物 |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2012100A (en) * | 1931-12-17 | 1935-08-20 | Edwin Pierce Weber | Liquid fuel burner |
US4166452A (en) | 1976-05-03 | 1979-09-04 | Generales Constantine D J Jr | Apparatus for testing human responses to stimuli |
US4256108A (en) | 1977-04-07 | 1981-03-17 | Alza Corporation | Microporous-semipermeable laminated osmotic system |
US4265874A (en) | 1980-04-25 | 1981-05-05 | Alza Corporation | Method of delivering drug with aid of effervescent activity generated in environment of use |
LU86084A1 (fr) | 1985-09-20 | 1987-04-02 | Faco Sa | Apparei de massage electrique |
US5102417A (en) | 1985-11-07 | 1992-04-07 | Expandable Grafts Partnership | Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft |
US4800882A (en) | 1987-03-13 | 1989-01-31 | Cook Incorporated | Endovascular stent and delivery system |
US4886062A (en) | 1987-10-19 | 1989-12-12 | Medtronic, Inc. | Intravascular radially expandable stent and method of implant |
WO1990013332A1 (en) | 1989-05-11 | 1990-11-15 | Cedars-Sinai Medical Center | Stent with sustained drug delivery |
DE69110787T2 (de) | 1990-02-28 | 1996-04-04 | Medtronic Inc | Intraluminale prothese mit wirkstoffeluierung. |
US5429634A (en) | 1993-09-09 | 1995-07-04 | Pdt Systems | Biogenic implant for drug delivery and method |
US5419760A (en) | 1993-01-08 | 1995-05-30 | Pdt Systems, Inc. | Medicament dispensing stent for prevention of restenosis of a blood vessel |
US6774278B1 (en) | 1995-06-07 | 2004-08-10 | Cook Incorporated | Coated implantable medical device |
DE19539091A1 (de) * | 1995-10-20 | 1997-04-24 | Thomae Gmbh Dr K | 5-gliedrige Heterocyclen, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zur ihrer Herstellung |
CA2229617A1 (en) * | 1995-10-20 | 1997-05-01 | Dr. Karl Thomae Gmbh | 5-membered heterocycles, medicaments containing these compounds, their use and processes for their preparation |
US5833651A (en) | 1996-11-08 | 1998-11-10 | Medtronic, Inc. | Therapeutic intraluminal stents |
US6294192B1 (en) | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
US6756385B2 (en) * | 2000-07-31 | 2004-06-29 | Pfizer Inc. | Imidazole derivatives |
GT200100147A (es) * | 2000-07-31 | 2002-06-25 | Derivados de imidazol | |
US20040043904A1 (en) * | 2000-09-22 | 2004-03-04 | Hiroshi Yamaguchi | N-(4-pyrazolyl) amide derivatives, chemicals for agricultural and horticultural use, and usage of the same |
US6770729B2 (en) | 2002-09-30 | 2004-08-03 | Medtronic Minimed, Inc. | Polymer compositions containing bioactive agents and methods for their use |
WO2004098528A2 (en) | 2003-05-01 | 2004-11-18 | Bristol-Myers Squibb Company | Pyrazole-amine compounds useful as kinase inhibitors |
WO2006125190A1 (en) | 2005-05-19 | 2006-11-23 | Cv Therapeutics, Inc. | A1 adenosine receptor agonists |
EP2079728B1 (en) * | 2006-10-10 | 2013-09-25 | Amgen Inc. | N-aryl pyrazole compounds for use against diabetes |
EP3184527B1 (en) * | 2007-06-22 | 2020-01-29 | Eli Lilly and Company | 2,6-dioxo,-2,3-dihydro-1h-purine compounds useful for treating disorders related to the activity of the trpa1 channel |
WO2009140519A1 (en) * | 2008-05-14 | 2009-11-19 | Hydra Biosciences, Inc. | Compounds and compositions for treating chemical warfare agent-induced injuries |
US20110230497A1 (en) * | 2008-11-07 | 2011-09-22 | H. Lundbeck A/S | Biologically active amides |
GB0915892D0 (en) * | 2009-09-10 | 2009-10-14 | Smithkline Beecham Corp | Compounds |
MX2015007051A (es) * | 2012-12-07 | 2016-01-12 | Chemocentryx Inc | Diazol lactamas. |
AU2013364038B2 (en) | 2012-12-21 | 2018-04-05 | Chemocentryx, Inc. | Diazole amides |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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