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    Novel carboxylic acids, benzoyl phenyl alkanoic acids and use thereof
    1.
    发明授权
    Novel carboxylic acids, benzoyl phenyl alkanoic acids and use thereof 失效
    新型羧酸，苯甲酰基苯基链烷酸及其应用

    公开(公告)号：US4337353A

    公开(公告)日：1982-06-29

    申请号：US875323

    申请日：1978-02-06

    申请人： Andre Allais ,  Francois Clemence ,  Jean Meier ,  Roger Deraedt

    发明人： Andre Allais ,  Francois Clemence ,  Jean Meier ,  Roger Deraedt

    IPC分类号： C07C59/76 ,  C07C45/41 ,  C07C51/00 ,  C07C51/08 ,  C07C51/09 ,  C07C59/84 ,  C07C59/88 ,  C07C59/90 ,  C07C67/00

    CPC分类号： C07C59/90 ,  C07C45/41 ,  C07C59/84 ,  C07C59/88

    摘要： Novel carboxylic acids of the formula ##STR1## wherein Z is an aliphatic hydrocarbon chain selected from the group consisting of --(CH.sub.2).sub.n -- and --CH.dbd.CH--(CH.sub.2).sub.n-2 -- where the double bond may be at any point in the chain, n is an integer from 5 to 10 and X, X.sub.1, X.sub.2 and X.sub.3 are individually selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 5 carbon atoms, alkylthio of 1 to 5 carbon atoms, CF.sub.3 --, CF.sub.3 O-- and CF.sub.3 S-- and their non-toxic, pharmaceutically acceptable organic and inorganic salts and esters having analgesic and anti-inflammatory activity and their preparation.

    摘要翻译： 式（Ⅰ）的新型羧酸，其中Z是选自 - （CH 2）n - 和-CH = CH-（CH 2）n-2-的脂族烃链，其中双键可以是任何 n为5至10的整数，X，X 1，X 2和X 3分别选自氢，卤素，1至5个碳原子的烷基，1至5个碳原子的烷氧基，烷硫基 1至5个碳原子，CF 3 - ，CF 3 O-和CF 3 S-及其无毒的药学上可接受的有镇痛和抗炎活性的有机和无机盐和酯及其制备。

    Benzoxazine-4-one intermediates
    2.
    发明授权
    Benzoxazine-4-one intermediates 失效
    苯并恶嗪-4-酮中间体

    公开(公告)号：US4518775A

    公开(公告)日：1985-05-21

    申请号：US495475

    申请日：1983-05-17

    申请人： Andre Allais ,  Francois Clemence ,  Roger Deraedt ,  Odile Lemartret

    发明人： Andre Allais ,  Francois Clemence ,  Roger Deraedt ,  Odile Lemartret

    IPC分类号： A61K31/47 ,  A61P25/04 ,  A61P29/00 ,  C07C237/04 ,  C07C237/22 ,  C07D215/56 ,  C07D233/88 ,  C07D263/48 ,  C07D265/16 ,  C07D265/22 ,  C07D277/20 ,  C07D277/46 ,  C07D277/82 ,  C07D401/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

    CPC分类号： C07D265/22 ,  C07D215/56 ,  C07D233/88 ,  C07D263/48 ,  C07D277/46

    摘要： Novel compounds of the formula ##STR1## wherein X is in the 5,6,7 or 8 position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, CF.sub.3 O--, CF.sub.3 S-- and CF.sub.3 -, R.sub.1 ' is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 ' is selected from the group consisting of hydrogen or an optionally unsaturated ring able to contain one or more heteroatoms of the group consisting of --S--, --O-- and --N-- optionally substituted with one or more members of the group consisting of (a) halogens, (b) alkyl of 1 to 4 carbon atoms optionally substituted with NH.sub.2, --NHAlK or --N--(AlK).sub.2 and AlK is alkyl of 1 to 3 carbon atoms, (c) phenyl, (d) alkoxy of 1 to 4 carbon atoms, (e) --OH, (f) --CF.sub.3 and (g) --NO.sub.2 or R.sub.1 ' and R.sub.2 ' together with the nitrogen atom to which they are attached form an optionally unsaturated ring, the said ring then being connected to the nitrogen atom by a double bond, R.sub.3 is selected from the group consisting of hydrogen, halogen and alkyl of 1 to 4 carbon atoms, R.sub.4 is selected from the group consisting of hydrogen and halogen, R.sub.5 is a halogen with the proviso that R.sub.3, R.sub.4 and R.sub.5 can not all be fluorine and R.sub.6 is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms and an acyl of an organic carboxylic acid of 2 to 8 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts and their salts with non-toxic, pharmaceutically acceptable bases having a remarkable analgesic activity, a very weak anti-inflammatory activity and a good tolerance by the gastrointestinal system and their preparation and their intermediates.

    摘要翻译： 新颖的式（Ⅰ）化合物，其中X为5,6,7或8位，选自氢，卤素，1至5个碳原子的烷基，1至4个碳原子的烷氧基 ，CF 3 O-，CF 3 S-和CF 3 - ，R''选自氢和1至4个碳原子的烷基，R 2'选自氢或任选不饱和的环，其能够含有一个或多个 任选被一个或多个由（a）卤素，（b）任选被NH 2取代的1至4个碳原子的烷基取代的-S-，-O-和 - NHAlK或-N-（AlK）2，AlK是1至3个碳原子的烷基，（c）苯基，（d）1-4个碳原子的烷氧基，（e）-OH，（f）-CF3和（g ）-NO 2或R 1'和R 2'与它们所连接的氮原子一起形成任选的不饱和环，然后所述环通过双键与氮原子连接，R 3选自C 存在氢，卤素和1至4个碳原子的烷基，R4选自氢和卤素，R5是卤素，条件是R3，R4和R5不能全部是氟，R6选自 由氢，1-8个碳原子的烷基和2至8个碳原子的有机羧酸的酰基及其无毒的药学上可接受的酸加成盐和它们的盐与无毒的药学上可接受的碱组成的组，其具有 显着的止痛活性，非常弱的抗炎活性和良好的耐胃肠系统及其制备及其中间体。

    2-Trifluoromethyl-3-quinoline carboxamides, analgesic and anti-inflammatory compositions and methods employing them
    3.
    发明授权
    2-Trifluoromethyl-3-quinoline carboxamides, analgesic and anti-inflammatory compositions and methods employing them 失效
    2-三氟甲基-3-喹啉羧酰胺，止痛剂和抗炎组合物和使用它们的方法

    公开(公告)号：US4299831A

    公开(公告)日：1981-11-10

    申请号：US097711

    申请日：1979-11-27

    申请人： Francois Clemence ,  Roger Deraedt ,  Andre Allais ,  Odile Le Martret

    发明人： Francois Clemence ,  Roger Deraedt ,  Andre Allais ,  Odile Le Martret

    IPC分类号： C07D413/12 ,  A61K31/47 ,  A61K31/505 ,  A61P25/04 ,  A61P29/00 ,  C07D215/56 ,  C07D401/12 ,  C07D417/12

    CPC分类号： C07D215/56

    摘要： Novel 3-quinoline carboxamides of the formula ##STR1## wherein X' is in the 5,6,7 or 8-position and is selected from the group consisting of hydrogen, halogen, straight or branched alkyl and alkoxy of 1 to 5 carbon atoms, --CF.sub.3, --SCF.sub.3 and --OCF.sub.3, R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 ' is selected from the group consisting of thiazolyl, 4,5-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl and tetrazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl optionally substituted with at least one member of the group consisting of alkyl and alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --NO.sub.2 and halogen and their non-toxic, pharmaceutically acceptable acid addition salts having analgesic and anti-inflammatory activity and novel intermediates and process for their preparation.

    摘要翻译： 具有式“IMAGE”I'的新型3-喹啉甲酰胺，其中X'为5,6,7或8-位，并且选自氢，卤素，直链或支链烷基和烷氧基，为1至5 碳原子，-CF 3，-SCF 3和-OCF 3，R 1选自氢和1至4个碳原子的烷基，R 2'选自噻唑基，4,5-二氢噻唑基，吡啶基，恶唑基 ，异恶唑基，咪唑基，嘧啶基和四唑基，其全部任选被1至4个碳原子的烷基取代，并且任选被至少一个由1至4个碳原子的烷基和烷氧基取代的基团，-CF 3，-NO 2和 卤素及其无毒，药学上可接受的具有镇痛和抗炎活性的酸加成盐和新型中间体及其制备方法。

    (4-Phenyl-piperazino alkyl)-3-benzoyl-benzene alkanoates
    4.
    发明授权
    (4-Phenyl-piperazino alkyl)-3-benzoyl-benzene alkanoates 失效
    （4-苯基 - 哌嗪基烷基）-3-苯甲酰基 - 苯基链烷酸酯

    公开(公告)号：US4147790A

    公开(公告)日：1979-04-03

    申请号：US869361

    申请日：1978-01-13

    申请人： Andre Allais ,  Francois Clemence ,  Roger Deraedt

    发明人： Andre Allais ,  Francois Clemence ,  Roger Deraedt

    IPC分类号： C07D295/02 ,  A61K31/495 ,  A61P25/04 ,  A61P25/06 ,  C07D295/088 ,  C07D295/14

    CPC分类号： C07D295/088

    摘要： Benzophenones of the formula ##STR1## wherein X.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 5 carbon atoms, X.sub.2 is selected from the group consisting of hydrogen, halogen and alkoxy of 1 to 5 carbon atoms, m is a whole number from 1 to 10, n is a whole number from 2 to 5 and Y is in the 2,3 or 4-position and is selected from the group consisting of hydrogen, halogen, CF.sub.3 --, CF.sub.3 O--, CF.sub.3 S--, alkyl of 1 to 8 carbon atoms and alkoxy of 1 to 8 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts having analgesic activity and their preparation.

    摘要翻译： 其中X 1选自氢和1至5个碳原子的烷基，X 2选自氢，卤素和1至5个碳原子的烷氧基， m为1〜10的整数，n为2〜5的整数，Y为2,3或4位，选自氢，卤素，CF 3 - ，CF 3 O-，CF 3 S - ，1〜8个碳原子的烷基和1〜8个碳原子的烷氧基，以及它们具有止痛活性的无毒，药学上可接受的酸加成盐及其制备方法。

    Quinoline-3-carboxamides
    5.
    发明授权
    Quinoline-3-carboxamides 失效
    喹啉-3-甲酰胺

    公开(公告)号：US4107310A

    公开(公告)日：1978-08-15

    申请号：US766487

    申请日：1977-02-07

    申请人： Andre Allais ,  Francois Clemence ,  Roger Deraedt ,  Odile Le Martret

    发明人： Andre Allais ,  Francois Clemence ,  Roger Deraedt ,  Odile Le Martret

    IPC分类号： C07D215/06 ,  A61K31/47 ,  A61K31/495 ,  A61K31/54 ,  A61P25/04 ,  C07D215/54 ,  C07D215/56 ,  C07D401/12 ,  C07D417/12 ,  C07F3/02 ,  C07D215/20

    CPC分类号： C07D215/56 ,  C07F3/02

    摘要： Novel quinoline-3-carboxamides of the formula ##STR1## wherein R.sub.1 is in the 5,6,7 or 8-position and is selected from the group consisting of hydrogen, halogen, --CF.sub.3, --OCF.sub.3, --SCF.sub.3, straight chain alkyl of 1 to 4 carbon atoms, branched alkyl of 3 to 5 carbon atoms and alkoxy of 1 to 4 carbon atoms, R.sub.2 is selected from the group consisting of hydrogen and methyl, R.sub.3 is selected from the group consisting of thiazolyl, 4,5-dihydrothiazolyl, pyridinyl, oxazolyl and imidazolyl and R.sub.4 is selected from the group consisting of hydrogen, hydroxyl, alkyl of 1 to 4 carbon atoms, phenyl and benzyl with the proviso that when R.sub.1 is in the 7 or 8-position and is halogen, --CH.sub.3, --OCF.sub.3 or --SCF.sub.3 and R.sub.4 is hydrogen, R.sub.3 is not thiazolyl, pyridinyl or oxazolyl and the non-toxic, pharmaceutically acceptable acid addition salts when R.sub.3 is imidazolyl or 4,5-dihydrothiazolyl having analgesic activity and their preparation and novel intermediates therefore.

    摘要翻译： 式（Ⅰ）的新型喹啉-3-甲酰胺其中R 1为5,6,7或8位且选自氢，卤素，-CF 3，-OCF 3，-SCF 3，直链 1至4个碳原子的烷基，3至5个碳原子的支链烷基和1至4个碳原子的烷氧基，R2选自氢和甲基，R3选自噻唑基，4,5 - 二氢噻唑基，吡啶基，恶唑基和咪唑基，R4选自氢，羟基，1至4个碳原子的烷基，苯基和苄基，条件是当R1为7或8位且为卤素时， -CH 3，-OCF 3或-SCF 3和R 4为氢，R 3不是噻唑基，吡啶基或恶唑基，当R 3为具有镇痛作用的咪唑基或4,5-二氢噻唑并且其制备和新颖的无毒的药学上可接受的酸加成盐 因此中间体。

    Analgesic 4-hydroxy-3-quinolinecarboxamides
    7.
    发明授权
    Analgesic 4-hydroxy-3-quinolinecarboxamides 失效
    止痛4-羟基-3-喹啉甲酰胺

    公开(公告)号：US4397856A

    公开(公告)日：1983-08-09

    申请号：US262952

    申请日：1981-05-12

    申请人： Andre Allais ,  Francois Clemence ,  Roger Deraedt ,  Odile Lemartret

    发明人： Andre Allais ,  Francois Clemence ,  Roger Deraedt ,  Odile Lemartret

    IPC分类号： A61K31/47 ,  A61P25/04 ,  A61P29/00 ,  C07C237/04 ,  C07C237/22 ,  C07D215/56 ,  C07D233/88 ,  C07D263/48 ,  C07D265/16 ,  C07D265/22 ,  C07D277/20 ,  C07D277/46 ,  C07D277/82 ,  C07D401/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

    CPC分类号： C07D265/22 ,  C07D215/56 ,  C07D233/88 ,  C07D263/48 ,  C07D277/46

    摘要： Novel compounds of the formula ##STR1## wherein X is in the 5,6,7 or 8 position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, CF.sub.3 O--, CF.sub.3 S-- and CF.sub.3 --, R.sub.1 ' is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 ' is selected from the group consisting of hydrogen or an optionally unsaturated ring able to contain one or more heteroatoms of the group consisting of --S--, --O-- and --N-- optionally substituted with one or more members of the group consisting of (a) halogens, (b) alkyl of 1 to 4 carbon atoms optionally substituted with NH.sub.2, --NHAlK or --N---(AlK).sub.2 and AlK is alkyl of 1 to 3 carbon atoms, (c) phenyl, (d) alkoxy of 1 to 4 carbon atoms, (e) --OH, (f) --CF.sub.3 and (g) --NO.sub.2 or R.sub.1 ' together with the nitrogen atom to which they are attached form an optionally unsaturated ring, the said ring then being connected to the nitrogen atom by a double bond, R.sub.3 is selected from the group consisting of hydrogen, halogen and alkyl of 1 to 4 carbon atoms, R.sub.4 is selected from the group consisting of hydrogen and halogen, R.sub.5 is a halogen with the proviso that R.sub.3, R.sub.4 and R.sub.5 can not all be fluorine and R.sub.6 is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms and an acyl of an organic carboxylic acid of 2 to 8 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts and their salts with non-toxic, pharmaceutically acceptable bases having a remarkable analgesic activity, a very weak anti-inflammatory activity and a good tolerance by the gastrointestinal system and their preparation and their intermediates.

    摘要翻译： 新颖的式（Ⅰ）化合物，其中X为5,6,7或8位，选自氢，卤素，1至5个碳原子的烷基，1至4个碳原子的烷氧基 ，CF 3 O-，CF 3 S-和CF 3 - ，R''选自氢和1至4个碳原子的烷基，R 2'选自氢或任选不饱和的环，其能够含有一个或多个 任选被一个或多个由（a）卤素，（b）任选被NH 2取代的1至4个碳原子的烷基取代的-S-，-O-和 - NHAlK或-N - （AlK）2，AlK是1至3个碳原子的烷基，（c）苯基，（d）1-4个碳原子的烷氧基，（e）-OH，（f）-CF3和（ g）-NO 2或R 1'与它们所连接的氮原子一起形成任选的不饱和环，然后所述环通过双键与氮原子连接，R 3选自组 氢，卤素和1至4个碳原子的烷基，R4选自氢和卤素，R5是卤素，条件是R3，R4和R5不能全部是氟，R6选自 由氢，1-8个碳原子的烷基和2至8个碳原子的有机羧酸的酰基及其无毒的药学上可接受的酸加成盐和它们的盐与无毒的药学上可接受的碱组成的组，其具有 显着的止痛活性，非常弱的抗炎活性和良好的耐胃肠系统及其制备及其中间体。

    Esters of indole-1-acetic acid and analgesic use thereof
    8.
    发明授权
    Esters of indole-1-acetic acid and analgesic use thereof 失效
    吲哚-1-乙酸的酯及其止痛用途

    公开(公告)号：US4233312A

    公开(公告)日：1980-11-11

    申请号：US904328

    申请日：1978-05-09

    申请人： Andre Allais ,  Jean Meier ,  Roger Deraedt

    发明人： Andre Allais ,  Jean Meier ,  Roger Deraedt

    IPC分类号： C07D209/12 ,  A61K31/40 ,  C07D209/20

    CPC分类号： C07D209/12 ,  Y10S514/971

    摘要： Novel indoles of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of hydrogen, halogen, --CF.sub.3, alkyl of 1 to 8 carbon atoms and alkoxy of 1 to 8 carbon atoms, R.sub.2 is in the 2, 3 or 4 position and is selected from the group consisting of halogen, --CF.sub.3 and alkyl, alkoxy and alkylthio of 1 to 8 carbon atoms, A is selected from the group consisting of branched alkylene of 3 to 5 carbon atoms and --(CH.sub.2).sub.n -- and n is a number of 2 to 5 and R.sub.3 and R.sub.4 are alkyl of 1 to 8 carbon atoms or taken together with the nitrogen atom form a heterocyclic ring selected from the group consisting of piperidinyl, pyrrolidinyl, morpholinyl, piperazinyl and N-alkyl piperazinyl with 1 to 4 alkyl carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts having analgesic activity and their preparation.

    摘要翻译： 其中R 1选自氢，卤素，-CF 3，1至8个碳原子的烷基和1至8个碳原子的烷氧基的新颖的吲哚，其中R2是2,3或4个 位置，并且选自卤素，-CF 3和具有1至8个碳原子的烷基，烷氧基和烷硫基，A选自3至5个碳原子的支链亚烷基和 - （CH 2）n - 和 n是2至5的数，R3和R4是1至8个碳原子的烷基或与氮原子一起形成选自哌啶基，吡咯烷基，吗啉基，哌嗪基和N-烷基哌嗪基的杂环， 1至4个烷基碳原子及其无毒的药学上可接受的具有止痛活性的酸加成盐及其制备。

    Indoles
    9.
    发明授权
    Indoles 失效
    吲哚

    公开(公告)号：US4105777A

    公开(公告)日：1978-08-08

    申请号：US758633

    申请日：1977-01-12

    申请人： Andre Allais ,  Jean Meier ,  Roger Deraedt

    发明人： Andre Allais ,  Jean Meier ,  Roger Deraedt

    IPC分类号： A61K31/403 ,  A61K31/404 ,  A61K31/405 ,  A61K31/535 ,  A61P25/04 ,  A61P25/06 ,  C07D209/12 ,  A61K31/40 ,  C07D209/20

    CPC分类号： C07D209/12

    摘要： Indoles of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of hydrogen, halogen, --CF.sub.3, alkyl of 1 to 8 carbon atoms and alkoxy of 1 to 8 carbon atoms, R.sub.2 is in the 2,3 or 4 position and is selected from the group consisting of halogen, --CF.sub.3 and alkyl, alkoxy and alkylthio of 1 to 8 carbon atoms, A is selected from the group consisting of branched alkylene of 3 to 5 carbon atoms and --(CH.sub.2).sub.n -- and n is a number of 2 to 5 and R.sub.3 and R.sub.4 are alkyl of 1 to 8 carbon atoms or taken together with the nitrogen atom form a heterocyclic ring selected from the group consisting of piperidinyl, pyrrolidinyl, morpholinyl, piperazinyl and N-alkyl piperazinyl with 1 to 4 alkyl carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts having analgesic activity and their preparation.

    摘要翻译： 式I的吲唑，其中R 1选自氢，卤素，-CF 3，1至8个碳原子的烷基和1至8个碳原子的烷氧基，R 2为2,3或4位 并且选自卤素，-CF 3和具有1至8个碳原子的烷基，烷氧基和烷硫基，A选自3至5个碳原子的支链亚烷基和 - （CH 2）n和n 是2至5的数，R3和R4是1至8个碳原子的烷基或与氮原子一起形成选自哌啶基，吡咯烷基，吗啉基，哌嗪基和N-烷基哌嗪基的杂环，其中1 至4个烷基碳原子及其无毒的药学上可接受的具有止痛活性的酸加成盐及其制备。

    Novel-3-(4-quinolylamino)-2-thiophene-carboxylates
    10.
    发明授权
    Novel-3-(4-quinolylamino)-2-thiophene-carboxylates 失效
    新型3-（4-喹啉基氨基）-2-噻吩 - 羧酸酯

    公开(公告)号：US4093724A

    公开(公告)日：1978-06-06

    申请号：US770304

    申请日：1977-02-22

    申请人： Andre Allais ,  Jean Meier ,  Roger Deraedt

    发明人： Andre Allais ,  Jean Meier ,  Roger Deraedt

    IPC分类号： C07D409/12 ,  A61K31/47 ,  A61K31/495 ,  C07D20060101 ,  C07D215/42 ,  C07D215/46 ,  C07D295/08 ,  C07D295/10 ,  C07D295/14 ,  C07D333/32 ,  C07D333/38 ,  C07D401/14 ,  C07D409/14

    CPC分类号： C07D401/12

    摘要： Novel 3-(4-quinolylamino)-2-thiophene-carboxylates of the formula ##STR1## wherein X is in the 6, 7 or 8-position and is selected from the group consisting of hydrogen, halogen, --CF.sub.3 and alkyl and alkoxy of 1 to 8 carbon atoms, n is 2, 3, 4 or 5, Y is in the 2, 3 or 4-position and is selected from the group consisting of hydrogen, halogen, --CF.sub.3 and alkyl and alkoxy of 1 to 8 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts having analgesic activity and process and intermediates for their preparation.

    摘要翻译： 式（VI）的新型3-（4-喹啉基氨基）-2-噻吩 - 羧酸酯，其中X为6,7或8-位，并且选自氢，卤素，-CF 3和烷基，和 1至8个碳原子的烷氧基，n为2,3,4或5，Y为2,3或4位，并且选自氢，卤素，-CF 3和1至 8个碳原子及其无毒的药学上可接受的具有镇痛活性的酸加成盐及其制备方法和中间体。