RU2436768C2 - Глютаматы в качестве ингибиторов аггреканазы - Google Patents

Глютаматы в качестве ингибиторов аггреканазы Download PDF

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RU2436768C2
RU2436768C2 RU2007149182/04A RU2007149182A RU2436768C2 RU 2436768 C2 RU2436768 C2 RU 2436768C2 RU 2007149182/04 A RU2007149182/04 A RU 2007149182/04A RU 2007149182 A RU2007149182 A RU 2007149182A RU 2436768 C2 RU2436768 C2 RU 2436768C2
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glutamine
biphenyl
carbonyl
ylcarbonyl
dimethylethyl
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RU2007149182/04A
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RU2007149182A (ru
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Файк-Инг САМ (US)
Файк-Инг САМ
Дэвид Брайн ХАУ (US)
Дэвид Брайн ХАУ
Джошуа Джеймс САБАТИНИ (US)
Джошуа Джеймс Сабатини
Джейсон Шаойюн КСЯНГ (US)
Джейсон Шаойюн КСЯНГ
Эрик ФЕЙФАНТ (US)
Эрик ФЕЙФАНТ
Стив ЙикКай ТАМ (US)
Стив ЙикКай ТАМ
Джеральд Стэнли СКОТНИКИ (US)
Джеральд Стэнли СКОТНИКИ
Тарек Сахэйл МАНСУР (US)
Тарек Сахэйл МАНСУР
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Abstract

Настоящее изобретение относится к новым соединениям формулы (I) или к их фармацевтически приемлемым солям, обладающим способностью модулировать активность металлопротеиназы, представляющей собой металлопротеиназу матрикса или аггреканазу, к фармацевтической композиции на их основе и к способу лечения остеоартрита.
Figure 00000242
где W представляет собой -С(О)-; R1 представляет собой бифенил, возможно содержащий один или более заместителей R5 или R6; и если R1 содержит более одного заместителя R5 или R6, заместители могут быть как одинаковыми, так и различными; R2 представляет собой водород; R3 представляет собой -CO2H, -CONHOH, -CONHR7 или -COOR7; R4 представляет собой -CONR9R10; m равно 0. Значения заместителей R5-R7, R9, R10 такие, как указаны в формуле изобретения. 3 н. и 15 з. п. ф-лы, 6 табл., 2 ил.

Description

Текст описания приведен в факсимильном виде.
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Claims (18)

1. Соединение формулы (I)
Figure 00000237

или его фармацевтически приемлемая соль, где
W представляет собой -С(О)-;
R1 представляет собой бифенил, возможно содержащий один или более заместителей R5 или R6; и если R1 содержит более одного заместителя R5 или R6, заместители могут быть как одинаковыми, так и различными;
R2 представляет собой водород;
R3 представляет собой -CO2H, -CONHOH, -CONHR7 или -COOR7;
R4 представляет собой -CONR9R10;
R5 представляет собой (С6-С10)арил, -NHCO-(C6-C10)арил, -NHCO-гетероарил, где гетероарил, представляет собой 5-членное ароматическое гетероциклическое кольцо, содержащее один гетероатом, выбранный из кислорода, (С1-С6)алкил, -O-(С1-С6)алкил или -NНСО-(С1-С6)алкил, при этом каждый алкил, арил или гетероарил, возможно, содержит один или более заместителей R6, и если R5 содержит более одного заместителя R6, заместители могут быть как одинаковыми, так и различными;
R6 представляет собой водород, галоген, -ОН, -CO2R7, (С2-С6)алкинил, (С2-С6)алкенил, -O-(С1-С6)алкил-(С3-С6)циклоалкил, -O-(С1-С6)алкенил, -O-(С1-С6)арил, О-гетероарил, где гетероарил представляет собой 5-членное насыщенное гетероциклическое кольцо, содержащее 2 гетероатома, выбранных из кислорода, и указанное кольцо конденсировано с 6-членным ароматическим кольцом, -O-(С1-С6)алкил, содержащий в качестве заместителя (С6-С10)арил, причем каждый арил, возможно, содержит один или более заместителей R13;
R7 представляет собой водород или (С1-С6)алкил;
R9 представляет собой водород или (С1-С6)алкил, возможно содержащий один или более заместителей R12;
R10 представляет собой (С1-С6)алкил, возможно содержащий один или более заместителей R12;
R12 представляет собой (С6-С10)арил, возможно содержащий один или более заместителей R13, 5-членное насыщенное гетероциклическое кольцо, содержащее 2 гетероатома, выбранных из кислорода, где указанное кольцо конденсировано с 6-членным ароматическим кольцом;
R13 представляет собой галоген, -O-(С1-С6)алкил, -СO2Н, -ОН, -CF3, водород, (С1-С6)алкил, (С6-С10)арил, 5-6-членный гетероарил, содержащий 1 гетероатом, выбранный из азота и серы, (С2-С6)алкенил, (С2-С6)алкинил, (С3-С6)циклоалкил, содержащий в качестве заместителя -ОН; (С6-С10)арил, содержащий в качестве заместителя -NH2, или (С6-С10)арил, содержащий в качестве заместителя -O-(С1-С6)алкил;
m равно 0;
n равно 0-4; и
p равно 2.
2. Соединение или фармацевтически приемлемая соль соединения по п.1, отличающееся тем, что R3 представляет собой -СO2Н.
3. Соединение или фармацевтически приемлемая соль соединения по п.1, отличающееся тем, что соединение или фармацевтически приемлемая соль соединения представляет собой S-энантиомер относительно атома углерода, с которым связана группа R4.
4. Соединение по п.1 формулы (Iа)
Figure 00000238

или его фармацевтически приемлемая соль, где
R1, R2 и R4 определены в п.1.
5. Соединение по п.4 или его фармацевтически приемлемая соль, отличающееся тем, что
R4 представляет собой
Figure 00000239
6. Соединение по п.4 или его фармацевтически приемлемая соль, отличающееся тем, что
R4 представляет собой
Figure 00000240
7. Соединение по п.4 или его фармацевтически приемлемая соль, отличающееся тем, что
R4 представляет собой
Figure 00000241
8. Соединение по п.1, отличающееся тем, что R13 представляет собой галоген.
9. Соединение по п.1, отличающееся тем, что R5 представляет собой -(С1-С6)алкил.
10. Соединение по п.1, отличающееся тем, что R6 представляет собой водород.
11. Соединение по п.10, отличающееся тем, что R7 представляет собой водород.
12. Соединение по п.1, отличающееся тем, что
R4 представляет собой -CONR9R10;
R5 представляет собой -(С1-C6)алкил;
R6 представляет собой водород;
R7 представляет собой водород;
R12 представляет собой (С6-С10)арил;
R9 представляет собой водород и
R10 представляет собой (С1-С6)алкил, возможно замещенный одним или более из R12.
13. Соединение или его фармацевтически приемлемая соль по п.1, где соединение выбрано из следующих:
N1-бензил-N2-[(4'-этинил-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-фторбензил)-L-α-глютамин,
N1-бензил-N2-[(2',5'-диметил-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3,4-диметоксибензил)-L-α-глютамин,
N1-бензил-N2-[(3',5'-диметил-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N1-бензил-N2-[(4'-этил-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N1-бензил-N2-[(3'-этокси-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N1-бензил-N2-[(2'-этокси-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N1-бензил-N2-[(2',6'-диметил-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(4-метоксибензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-[2-(3,4-диметоксифенил)этил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-[2-(4-метоксифенил)этил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(1-нафтилметил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3-метилбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3-метоксибензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(2,4-дихлорбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-[2-(3-метоксифенил)этил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(2,4-диметоксибензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(2-метоксибензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3,4-дихлоробензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3,5-дифторбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N5-гидрокси-N1-[2-(3-метоксифенил)этил]-L-глютамамид,
N2-(1,1,-бифенил-4-илкарбонил)-N5-гидрокси-N1-(3,4,5-триметоксибензил)-L-глютамамид,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3,5-диметоксибензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3,5-диметоксибензил)-N5-гидрокси-L-глютамамид,
N1-бензил-N2-[(4'-винил-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3,4-диметилбензил)-L-α-глютамин,
N1-бензил-N2-[(4'-этокси-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N1-бензил-N2-[(4'-пропокси-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N1-бeнзил-N2-[(4'-бутокси-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N1-бензил-N2-{[4'-(циклобутилметокси)-1,1'-бифенил-4-ил]карбонил}-L-α-глютамин,
N1-бензил-N2-{[4'-(циклогексилметокси)-1,1'-бифенил-4-ил]карбонил}-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3,4-диметилбензил)-N5-гидрокси-L-глютамамид,
N2-{[4'-(ацетиламино)-1,1'-бифенил-4-ил]карбонил}-N1-бензил-L-α-глютамин,
N1-бензил-N2-{[4'-(2-фуроиламино)-1,1'-бифенил-4-ил]карбонил}-L-α-глютамин,
N1-бензил-N2-{4'-[(4-фторбензоил)амино]-1,1'-бифенил-4-ил}карбонил)-L-α-глютамин,
N2-{[4'-бифенил-4-ил]карбонил}-N1-бензил-L-α-глютамин,
N2-[(2,2'-диметил-1,1'-бифенил-4-ил)карбонил]-N1-(3-метоксибензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(2-фенилэтил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-[3-(трифторметил)бензил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-[2-трифторметил)бензил]-L-α-глютамин,
N1-бензил-N2-[(2-фтор-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3-фторбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3-фенилпропил)-L-α-глютамин,
N1-бензил-N2-(1,1'-бифенил-3-илкарбонил)-L-α-глютамин,
N1-бензил-N2-[(3-хлор-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N1-бензил-N2-[(2,6-диметокси-1,1'-бифенил-4-ил)карбонил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-[2-(3-хлорфенил)этил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(2-фторбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3,4-дифторбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(2-метилбензил)-L-α-глютамин,
N1-бензил-N2-({4'-[(метоксибензил)окси]-1,1'-бифенил-4-ил}карбонил)-L-α-глютамин,
N1-бензил-N2-({4'-[(3,5-диметоксибензил)окси]-1,1'-бифенил-4-ил}карбонил)-L-α-глютамин,
N1-бензил-N2-{[4'-(2-нафтилметокси)-1,1'-бифенил-4-ил]карбонил}-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(2,3-диметилбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(4-фенилбутил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(4-метилбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-[4-фтор-3-(трифторметил)бензил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3-йодбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3-винилбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-[2-(4-фторфенил)-1,1'-диметилэтил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(4-трет-бутилбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(4-йодбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(4-винилбензил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-[2-(4-бромфенил)этил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(2-бифенил-4-илэтил)-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-[2-(2'-этоксибифенил-4-ил)этил]-L-α-глютамин,
N2-(1,1'-бифенил-4-илкарбонил)-N1-(3,3'-дифенилпропил)-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[2-(4'-метоксибифенил-3-ил)этил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[2-(4'-метоксибифенил-4-ил)этил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[2-(3-бромфенил)этил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[2-(4-хлорфенил)-1,1-диметилэтил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-(1-метил-1-фенилэтил)-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[2-(4-фторфенил)этил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[2-(4-хлорфенил)этил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N1-бензил-N2-(1,1'-бифенил-4-илкарбонил)-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[(1S)-1-(4-фторфенил)этил]-L-α-глютамин,
трет-бутил N2-(бифенил-4-илкарбонил)-N1-(1-фенилэтил)-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[(1R)-1-(4-фторфенил)этил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[(1R)-1-фенилэтил]-L-α-глютамин,
N2-[(3'-этоксибифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-[(2,-этоксибифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-[(4'-метоксибифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-[(3'-этоксибифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
4'-{[((1S)-3-карбокси-1-{[(3,4,5-триметоксибензил)амино]карбонил}пропил)амино]карбонил}бифенил-3-карбоновая кислота,
N2-[(4'-этилбифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-[(3',4'-диметоксибифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-[(2',4'-диметоксибифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N-(3,4,5-триметоксибензил)-N2-[(3',4',5'-триметоксибифенил-4-ил)карбонил]-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-[(3-метоксибифенил-4-ил)карбонил]-L-α-глютамин,
N2-[(3',4'-диметоксибифенил-4-ил)карбонил]-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-[(2'-этоксибифенил-4-ил)карбонил]-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-[(3'-фтор-4'-метилбифенил-4-ил)карбонил]-L-α-глютамин,
N2-[(2',4'-диметоксибифенил-4-ил)карбонил]-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-[(3'-фтор-4'-метилбифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-({4'-[(3,5-диметоксибензил)окси]бифенил-4-ил}карбонил)-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N-метил-N-(2-фенилэтил)-L-α-глютамин,
N2-[(4'-втор-бутилбифенил-4-ил)карбонил]-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N-2-[(4'-изопропилбифенил-4-ил)карбонил]-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-(1,1:4',1''-терфенил-4-илкарбонил)-L-α-глютамин,
N2-({4'-[(3,5-диметоксибензил)окси]бифенил-4-ил}карбонил)-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-[(4'-гидроксибифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N-[2-(4-фторфенил)-1,1-диметилэтил]-N2-[(3'-метилбифенил-4-ил)карбонил]-L-α-глютамин,
N2-({4'-[(3,5-диметилбензил)окси]бифенил-4-ил}карбонил)-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-[(4'-{[3,5-бис(трифторметил)бензил]окси}бифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-[(3'-изопропилбифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-[(4'-изопропилбифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-[(3'-этоксибифенил-4-ил)карбонил]-N-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N-[2-(4-фторфенил)-1,1-диметилэтил]-N2-[(3'-метоксибифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-фторфенил)-1,1-диметилэтил]-N2-[(3'-изопропилбифенил-4-ил)карбонил]-L-α-глютамин,
N2-[(3'-фтор-4'-метилбифенил-4-ил)карбонил]-N-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N-[2-(4-фторфенил)-1,1-диметилэтил]-N2-[(4'-изобутилбифенил-4-ил)карбонил]-L-α-глютамин,
N2-1,1':4',1'-терфенил-4-илкарбонил)-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N-бензил-N2-{[3'-(гидроксиметил)бифенил-4-ил]карбонил}-L-α-глютамин,
N-бензил-N2-({4'-[(3-фторбензил)окси]бифенил-4-ил}карбонил)-L-α-глютамин,
N-бензил-N2-{[4'-(бензилокси)бифенил-4-ил]карбонил}-L-α-глютамин,
N-(3,4,5-триметоксибензил)-N2-[(2',4',6'-триметилбифенил-4-ил)карбонил]-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-({4'-[(3-метоксибензил)окси]бифенил-4-ил}карбонил)-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-[(4'-гидроксибифенил-4-ил)карбонил]-L-α-глютамин,
N-{1,1-диметил-2-фенилэтил)-N2-[(3'-этоксибифенил-4-ил)карбонил]-L-α-глютамин,
N2-({4'-[(3-метоксибензил)окси]бифенил-4-ил}карбонил)-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N-[2-(4-фторфенил)-1,1-диметилэтил]-N2-[(4'-гидроксибифенил-4-ил)карбонил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N-[2-(3,4-диметоксифенил)этил]-N-метил-L-α-глютамин,
N2-[(3'-гидроксибифенил-4-ил)карбонил]-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-{[4'-(гидроксиметил)бифенил-4-ил]карбонил}-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-[(4'-метилбифенил-4-ил)карбонил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-(4-фторфенил)-1,1-диметилэтил]-L-глютамамид,
N2-({4'-[(3-трет-бутилфенокси)метил]бифенил-4-ил}карбонил)-N-(1,1-димeтил-2-фeнилэтил)-L-α-глютамин,
N2-({4'-[(3,5-ди-трет-бутилфенокси)метил]бифенил-4-ил}карбонил)-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-({4'-[(3-этилфенокси)метил]бифенил-4-ил}карбонил)-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-({4'-[(3-метоксифенокси)метил]бифенил-4-ил}карбонил)-L-α-глютамин,
N-[2-(4-фторфенил)-1,1-диметилэтил]-N2-[(3'-гидроксибифенил-4-ил)карбонил]-L-α-глютамин,
N2-(бифенил-4-илкарбонил)-N1-[2-(4-фторфенил)-1,2-диметилэтил]-N5-гидрокси-L-глютамамид,
N2-[(3',4'-дифторбифенил-4-ил)карбонил]-N-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(3',4'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',4'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',5'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',6'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(3',5'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',3'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N2-[(3',4'-дифторбифенил-4-ил)карбонил]-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-[(3',5'-дифторбифенил-4-ил)карбонил]-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-{[4'-(гидроксиметил)бифенил-4-ил]карбонил}-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-{[4'-(бромметил)бифенил-4-ил]карбонил}-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-{[4'-(гидроксиметил)бифенил-4-ил]карбонил}-N-(3-метилбензил)-L-α-глютамин,
N2-{[3'-(гидроксиметил)бифенил-4-ил]карбонил}-N-(3-метилбензил)-L-α-глютамин,
N2-[(3'-хлор-4'-фторбифенил-4-ил)карбонил]-N-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N2-{[3'-(бромметил)бифенил-4-ил]карбонил}-N-(3-метилбензил)-L-α-глютамин,
N2-[(3'-хлорбифенил-4-ил)карбонил]-N-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N2-[(4'-хлорбифенил-4-ил)карбонил]-N-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N2-[(4'-фторбифенил-4-ил)карбонил]-N-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N2-[(3'-фторбифенил-4-ил)карбонил]-N-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N2-[(4'-хлорбифенил-4-ил)карбонил]-N-[2-(4-хлорфенил)-1,1-диметилэтил]-L-α-глютамин,
N2-[(3'-хлорбифенил-4-ил)карбонил]-N-[2-(4-хлорфенил)-1,1-диметилэтил]-L-α-глютамин,
N-(1,1-диметил-2-фенилэтил)-N2-[(4'-фторбифенил-4-ил)карбонил]-L-α-глютамин,
N2-[(4'-{[3,5-бис(трифторметил)фенокси]метил}бифенил-4-ил)карбонил]-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-({4'-[(1,3-бензодиоксол-5-илокси)метил]бифенил-4-ил}карбонил)-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-{[3'-(бензилокси)бифенил-4-ил]карбонил}-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-({3'-[(3,5-диметоксибензил)окси]бифенил-4-ил}карбонил)-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-({3'-[(3-метоксибензил)окси]бифенил-4-ил}карбонил)-N-(3,4,5-триметоксибензил)-L-α-глютамин,
N2-({4'-[(3,5-диметоксибензил)окси]бифенил-4-ил}карбонил)-N-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N-бензил-N2-{[4'-(бифенил-3-илметокси)бифенил-4-ил]карбонил}-L-α-глютамин,
N-бензил-N2-({4'-[(3'-метоксибифенил-3-ил)метокси]бифенил-4-ил}карбонил)-L-α-глютамин,
N2-({4'-[(3,5-диметоксифенокси)метил]бифенил-4-ил}карбонил)-N-(3-метилбензил)-L-α-глютамин,
N2-({3'-[(3,5-диметоксифенокси)метил]бифенил-4-ил}карбонил)-N-(3-метилбензил)-L-α-глютамин,
N2-[(3'-{[3,5-бис(трифторметил)фенокси]метил}бифенил-4-ил)карбонил]-N-(3-метилбензил)-L-α-глютамин,
N2-({3'-[(3-этилфенокси)метил]бифенил-4-ил}карбонил)-N-(3-метилбензил)-L-α-глютамин,
N-бензил-N2-{[4'-(бифенил-2-илметокси)бифенил-4-ил]карбонил}-L-α-глютамин и
N-бензил-N2-({4'-[(3'-метоксибифенил-2-ил)метокси]бифенил-4-ил}карбонил)-L-α-глютамин.
14. Соединение или фармацевтически приемлемая соль соединения по п.13, где соединение выбрано из следующих:
N2-(1,1'-бифенил-4-илкарбонил)-N1-[2-(4-фторфенил)1,1-диметилэтил]-L-α-глютамин,
N2-[(3',4'-дифторбифенил-4-ил)карбонил]-N-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(3',4'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',4'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',5'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',6'-дифторбифенил-4-ил)каpбoнил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[3',5'-дифторбифенил-4-ил)кapбoнил]-L-α-глютaмин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',3'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N2-[(3',4'-дифторбифенил-4-ил)карбонил]-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-[(3',5'-дифторбифенил-4-ил)карбонил]-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-{[4'-(гидроксиметил)бифенил-4-ил]карбонил}-N-(3,4,5-триметоксибензил)-L-α-глютамин.
15. Композиция для модулирования активности металлопротеиназы, представляющей собой металлопротеиназу матрикса или аггреканазу, содержащая эффективное количество соединения или фармацевтически приемлемой соли соединения по п.1, и фармацевтически приемлемый носитель.
16. Композиция по п.15, отличающаяся тем, что соединение или фармацевтически приемлемая соль соединения выбраны из следующих:
N2-(1,1'-бифенил-4-илкарбонил)-N1-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N2-[(3',4'-дифторбифенил-4-ил)карбонил]-N-[2-(4-фторфенил)-1,1-диметилэтил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(3',4'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',4'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',5'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',6'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(3',5'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N-[2-(4-хлорфенил)-1,1-диметилэтил]-N2-[(2',3'-дифторбифенил-4-ил)карбонил]-L-α-глютамин,
N2-[(3',4'-дифторбифенил-4-ил)карбонил]-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-[(3',5'-дифторбифенил-4-ил)карбонил]-N-(1,1-диметил-2-фенилэтил)-L-α-глютамин,
N2-{[4'-(гидроксиметил)бифенил-4-ил]карбонил}-N-(3,4,5-триметоксибензил)-L-α-глютамин.
17. Композиция по п.15, отличающаяся тем, что фармацевтически приемлемый носитель подходит для перорального введения, а композиция представлена в лекарственной форме для перорального введения.
18. Способ лечения остеоартрита, включающий введение эффективной дозы соединения по пп.1-14 или его фармацевтически приемлемой соли.
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Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1468102B1 (en) * 2002-01-22 2009-05-27 Biomatera Inc. Method of drying biodegradable polymers
US9492400B2 (en) * 2004-11-04 2016-11-15 Massachusetts Institute Of Technology Coated controlled release polymer particles as efficient oral delivery vehicles for biopharmaceuticals
JP2009505962A (ja) * 2005-07-29 2009-02-12 バイエル・ヘルスケア・エルエルシー 肥満を治療するためのビフェニルアミノ酸誘導体の製造および使用
KR20080058436A (ko) 2005-10-13 2008-06-25 와이어쓰 글루탐산 유도체의 제조 방법
US9267937B2 (en) 2005-12-15 2016-02-23 Massachusetts Institute Of Technology System for screening particles
US8623871B2 (en) 2006-01-25 2014-01-07 Synta Pharmaceuticals Corp. Substituted biaryl compounds for inflammation and immune-related uses
WO2008105773A2 (en) * 2006-03-31 2008-09-04 Massachusetts Institute Of Technology System for targeted delivery of therapeutic agents
US20110052697A1 (en) * 2006-05-17 2011-03-03 Gwangju Institute Of Science & Technology Aptamer-Directed Drug Delivery
PE20080312A1 (es) * 2006-06-02 2008-05-14 Wyeth Corp Metodos para preparar derivados de acido glutamico e intermediarios del mismo
US9381477B2 (en) * 2006-06-23 2016-07-05 Massachusetts Institute Of Technology Microfluidic synthesis of organic nanoparticles
WO2008019142A2 (en) * 2006-08-04 2008-02-14 Massachusetts Institute Of Technology Oligonucleotide systems for targeted intracellular delivery
EP2089012A2 (en) * 2006-11-09 2009-08-19 Wyeth Polymorphs of n²-(1,1'- biphenyl- 4-ylcarbonyl)-n¹-[2-(4-fluorophenyl)-1,1-dimethylethyl]-l-alpha -glutamine
US20100216886A1 (en) * 2006-11-09 2010-08-26 Wyeth Polymorphs of n2-(1,1'-biphenyl-4-ylcarbonyl)-n1-[2-(4-fluorophenyl)-1,1-dimethylethyl]-l-alpha-glutamine
US20100303723A1 (en) * 2006-11-20 2010-12-02 Massachusetts Institute Of Technology Drug delivery systems using fc fragments
US9217129B2 (en) 2007-02-09 2015-12-22 Massachusetts Institute Of Technology Oscillating cell culture bioreactor
EP2136788B1 (en) * 2007-03-30 2011-10-26 Bind Biosciences, Inc. Cancer cell targeting using nanoparticles
WO2008124639A2 (en) * 2007-04-04 2008-10-16 Massachusetts Institute Of Technology Poly (amino acid) targeting moieties
MX2010003642A (es) 2007-10-12 2010-08-09 Massachusetts Inst Technology Nanotecnologia de vacuna.
JP6363320B2 (ja) 2008-06-16 2018-07-25 ファイザー・インク 薬剤を装填したポリマーナノ粒子及びその製造方法と使用方法
WO2010005726A2 (en) * 2008-06-16 2010-01-14 Bind Biosciences Inc. Therapeutic polymeric nanoparticles with mtor inhibitors and methods of making and using same
EA020753B1 (ru) 2008-06-16 2015-01-30 Бинд Терапьютикс, Инк. Терапевтические полимерные наночастицы, содержащие алкалоиды vinca, и их применение
US8277812B2 (en) 2008-10-12 2012-10-02 Massachusetts Institute Of Technology Immunonanotherapeutics that provide IgG humoral response without T-cell antigen
US8591905B2 (en) 2008-10-12 2013-11-26 The Brigham And Women's Hospital, Inc. Nicotine immunonanotherapeutics
JP5584696B2 (ja) * 2008-11-17 2014-09-03 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 Ｍｍｐ−１３阻害剤として有用なヘテロアリールジアミド化合物
US8563041B2 (en) 2008-12-12 2013-10-22 Bind Therapeutics, Inc. Therapeutic particles suitable for parenteral administration and methods of making and using same
WO2010075072A2 (en) * 2008-12-15 2010-07-01 Bind Biosciences Long circulating nanoparticles for sustained release of therapeutic agents
TR201906255T4 (tr) 2009-12-11 2019-05-21 Pfizer Terapötik partiküllerin liyofilize edilmesine yönelik stabil formülasyonlar.
EP2515942B1 (en) 2009-12-15 2020-02-12 Pfizer Inc. Therapeutic polymeric nanoparticle compositions with high glass transition temperature or high molecular weight copolymers
EP2576536B1 (en) * 2010-06-01 2016-09-14 The University of Queensland Haematopoietic-prostaglandin d2 synthase inhibitors
AU2013315118B2 (en) 2012-09-17 2017-10-05 Pfizer Inc. Process for preparing therapeutic nanoparticles
AR092971A1 (es) * 2012-10-26 2015-05-06 Lilly Co Eli Inhibidores de agrecanasa
CA2900116C (en) * 2013-02-06 2021-08-10 Merck Patent Gmbh Substituted carboxylic acid derivatives as aggrecanase inhibitors for the treatment of osteoarthritis
GB201312311D0 (en) 2013-07-09 2013-08-21 Uni I Oslo Uses of enzyme inhibitors
WO2015075699A1 (en) 2013-11-25 2015-05-28 Sanofi Dotam derivatives for therapeutic use
EP3116547B1 (en) 2014-03-14 2019-06-05 Pfizer Inc Therapeutic nanoparticles comprising a therapeutic agent and methods of making and using same
EP3672939A1 (en) 2017-08-21 2020-07-01 Celgene Corporation Processes for preparation of (s)-tert-butyl 4,5-diamino-5-oxopentanoate
CN109516925B (zh) * 2018-10-31 2021-07-16 陕西慧康生物科技有限责任公司 一种谷氨酸-1-甲酯-5-叔丁酯的合成方法
CN109734660B (zh) * 2019-01-18 2020-07-28 西安交通大学 一种含有叔丁基取代的丝氨酸的类肽类化合物及其制备方法和应用
CN109824584B (zh) * 2019-01-18 2020-08-18 西安交通大学 一种含有叔亮氨酸的类肽类化合物及其制备方法和应用
CN109824581B (zh) * 2019-01-18 2020-08-18 西安交通大学 一种含有丙氨酸的类肽类化合物以及其制备方法和应用
CN109824582B (zh) * 2019-01-18 2020-06-19 西安交通大学 一种丙氨酸衍生物及其制备方法和应用
KR20230128503A (ko) * 2020-12-25 2023-09-05 (주)앰틱스바이오 신규한 아미노알칸산에 바이페닐기를 도입한 유도체 화합물 및 이를 포함하는 항염증용 조성물

Family Cites Families (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2440649A (en) 1948-04-27 Quinazoline
GB1108819A (en) * 1964-07-31 1968-04-03 Rotta Research Lab Derivatives of 2-acylaminobicarboxylic acids and method for preparing same
DE3332633A1 (de) 1983-09-09 1985-04-04 Luitpold-Werk Chemisch-pharmazeutische Fabrik GmbH & Co, 8000 München Substituierte carbonsaeurederivate, verfahren zu ihrer herstellung, und arzneimittel
IT1215169B (it) 1985-12-17 1990-01-31 Rotta Research Lab Derivati alchil ossigenati degli acidi glutammico ed aspartico ad attivita antagonista su polipeptidi bioattivi e procedimento per la loro preparazione
IT1217123B (it) 1987-02-05 1990-03-14 Rotta Research Lab Derivati otticamente attivi dell acido 5 pentilammino 5 oxo pentanoico r ad attivita antagonista della colecistochinina e procedimento per la loro preparazione
DE4102024A1 (de) 1991-01-24 1992-07-30 Thomae Gmbh Dr K Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
EP0673247A4 (en) 1992-12-01 1996-05-01 Merck & Co Inc FIBRINOGEN RECEPTOR ANTAGONISTS.
JPH06192199A (ja) 1992-12-25 1994-07-12 Mitsubishi Kasei Corp ケトン誘導体
US5563127A (en) 1993-03-24 1996-10-08 The Dupont Merck Pharmaceutical Company Boronic acid and ester inhibitors of thrombin
JPH09510442A (ja) 1994-03-11 1997-10-21 ファーマコペイア，インコーポレイテッド スルホンアミド誘導体及びそれらの使用
GB2292149A (en) 1994-08-09 1996-02-14 Ferring Res Ltd Peptide inhibitors of pro-interleukin-1beta converting enzyme
US6306840B1 (en) 1995-01-23 2001-10-23 Biogen, Inc. Cell adhesion inhibitors
CA2227466A1 (en) 1995-07-24 1997-02-06 Fujisawa Pharmaceutical Co., Ltd. Esters and amides as pla2 inhibitors
DE69637307T2 (de) 1995-11-28 2008-02-28 Cephalon, Inc. Aus d-aminosäuren abgeleitete cystein-und serinproteasehemmer
DE69833858T2 (de) 1997-07-08 2007-02-22 Ono Pharmaceutical Co. Ltd. Aminosäurederivate
JP4129069B2 (ja) 1997-09-16 2008-07-30 株式会社Ａｄｅｋａ アシル化ペプチド類の製造方法
JP4090541B2 (ja) 1997-10-15 2008-05-28 株式会社Ａｄｅｋａ アシル化ペプチド類の製造方法
AU3366899A (en) 1998-03-27 1999-10-18 Regents Of The University Of California, The Novel hiv integrase inhibitors and hiv therapy based on drug combinations including integrase inhibitors
TWI245035B (en) 1998-06-26 2005-12-11 Ono Pharmaceutical Co Amino acid derivatives and a pharmaceutical composition comprising the derivatives
US7157430B2 (en) 1998-10-22 2007-01-02 Idun Pharmaceuticals, Inc. (Substituted)acyl dipeptidyl inhibitors of the ICE/CED-3 family of cysteine proteases
US6242422B1 (en) 1998-10-22 2001-06-05 Idun Pharmacueticals, Inc. (Substituted)Acyl dipeptidyl inhibitors of the ice/ced-3 family of cysteine proteases
DE19851184A1 (de) 1998-11-06 2000-05-11 Aventis Pharma Gmbh N-Arylsulfonyl-aminosäure-omega-amide
AU4180900A (en) * 1999-04-02 2000-10-23 Du Pont Pharmaceuticals Company Novel amide derivatives as inhibitors of matrix metalloproteinases, tnf-alpha, and aggrecanase
ES2228527T5 (es) 1999-05-07 2013-05-23 Encysive Pharmaceuticals, Inc. Derivados del ácido propanoico que inhiben la unión de las integrinas a sus receptores
US6723711B2 (en) 1999-05-07 2004-04-20 Texas Biotechnology Corporation Propanoic acid derivatives that inhibit the binding of integrins to their receptors
EP1081137A1 (en) * 1999-08-12 2001-03-07 Pfizer Products Inc. Selective inhibitors of aggrecanase in osteoarthritis treatment
JP2003146905A (ja) * 1999-11-11 2003-05-21 Yamanouchi Pharmaceut Co Ltd アグリカナーゼ活性を有する新規な金属プロテアーゼ
CN1366518A (zh) 2000-04-25 2002-08-28 三星电子株式会社 作为基质金属蛋白酶抑制剂的联苯基丁酸衍生物
AU2001264595A1 (en) * 2000-05-19 2001-12-03 Guilford Pharmaceuticals Inc. Sulfonamide and carbamide derivatives of 6(5h)phenanthridinones and their uses
JP2002145849A (ja) 2000-11-10 2002-05-22 Kyorin Pharmaceut Co Ltd アルキニルアミノ酸誘導体及びその製造法
US20050049242A1 (en) 2000-12-21 2005-03-03 W. Edward Robinson Novel HIV integrase inhibitors and HIV therapy based on drug combinations including integrase inhibitors
WO2003093498A1 (en) 2002-04-29 2003-11-13 The Ohio State University Inhibition of protein tyrosine phosphatases and sh2 domains by a neutral phosphotyrosine mimetic
CA2490646A1 (en) * 2002-06-25 2003-12-31 Pharmacia Corporation Arylsulfonylhydroxamic acid and amide derivatives and their use as protease inhibitors
US20040229955A1 (en) * 2003-01-08 2004-11-18 Andersen Niels H. Antibacterial agents
JP2007502287A (ja) 2003-08-13 2007-02-08 アムジェン インコーポレイテッド メラニン凝集ホルモン受容体アンタゴニスト
US20070208166A1 (en) 2003-10-24 2007-09-06 Exelixis, Inc. Tao Kinase Modulators And Method Of Use
JP2007525406A (ja) 2003-12-04 2007-09-06 ワイス ビアリールスルホンアミドおよびその使用方法
CN1894206A (zh) * 2003-12-15 2007-01-10 日本烟草产业株式会社 N－取代的n－磺酰氨基环丙烷化合物和其药学应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Li Xun et al. Structure confirmation of L-iso-glutamine derivatives. Journal of Chemical Research, 2005, №2, с.94-95. F. Macovec et al. New glutamic and aspartic derivatives with potent CCK-antagonistic activity. Eur. J. Med. Chem.-Chim.Ther., 1986, т.21, №1, с.9-20. U. Kuefner et al. Carboxypeptidase-Mediated Release of Methotrexate from Methotrexate α-Peptides. Biochemistry, 1989, т.28, №5, с.2288-2297. W.E. Gaunt et al. CCLXIX. The Action of Phenyl Isocyanate on Insulin. II. Further Observation on the Chemistry of Insulin and its Phosphate-Lowering Power. The Biochemical Journal, 1936, том XXX, №10, с.1915-1926. D.L. Boger et al. Conformationally Restricted Analogues Designed for Selective Inhibition of GAR Tfase Versus Thymidylate Synthase or Dihydrofolate Reductase. Bioorganic & Medicinal Chemistry, 2000, т.8, с.5, с.1075-1086. I. Selmiciu, Zur Synthese der Nicotinoyl-p-aminobenzoyl-glutaminsaüre. Pharmazeutische Zentralhalle, 1951, т.90, №9, с.300-301. M. Bergmann et al. On Prote *

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